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Explaining the flaws in human random generation as local sampling with momentum
In many tasks, human behavior is far noisier than is optimal. Yet when asked to behave randomly, people are typically too predictable. We argue that these apparently contrasting observations have the same origin: the operation of a general-purpose local sampling algorithm for probabilistic inference. This account makes distinctive predictions regarding random sequence generation, not predicted by previous accounts—which suggests that randomness is produced by inhibition of habitual behavior, striving for unpredictability. We verify these predictions in two experiments: people show the same deviations from randomness when randomly generating from non-uniform or recently-learned distributions. In addition, our data show a novel signature behavior, that people’s sequences have too few changes of trajectory, which argues against the specific local sampling algorithms that have been proposed in past work with other tasks. Using computational modeling, we show that local sampling where direction is maintained across trials best explains our data, which suggests it may be used in other tasks too. While local sampling has previously explained why people are unpredictable in standard cognitive tasks, here it also explains why human random sequences are not unpredictable enough
International short‐term placements in health professions education : a meta‐narrative review
Introduction: In order to be prepared for professional practice in a globalised world, health professions students need to be equipped with a new set of knowledge, skills and attitudes. Experiential learning gained during an international placement has been considered as a powerful strategy for facilitating the acquisition of global health competencies. The aim of this review was to synthesise the diverse body of empirical research examining the process and outcomes of international short‐term placements in health professions education. Methods: A systematic review was conducted using a meta‐narrative methodology. Six electronic databases were searched between September 2016 and June 2022: Medline, Embase, CINAHL, PsycINFO, Education Research Complete and Web of Knowledge. Studies were included if they reported on international placements undertaken by undergraduate health professions students in socio‐economically contrasting settings. Included studies were first considered within their research tradition before comparing and contrasting findings between different research traditions. Results: This review included 243 papers from 12 research traditions, which were distinguished by health profession and paradigmatic approach. Empirical findings were considered in four broad themes: learner, educational intervention, institutional context and wider context. Most studies provided evidence on the learner, with findings indicating a positive impact of international placements on personal and professional development. The development of cultural competency has been more focus in research in nursing and allied health than in medicine. Whereas earlier research has focussed on the experience and outcomes for the learner, more recent studies have become more concerned with relationships between various stakeholder groups. Only few studies have looked at strategies to enhance the educational process. Conclusion: The consideration of empirical work from different perspectives provides novel understandings of what research has achieved and what needs further investigation. Future studies should pay more attention to the complex nature of the educational process in international placements
Systematic KMTNet Planetary Anomaly Search. X. Complete Sample of 2017 Prime-field Planets
We complete the analysis of planetary candidates found by the KMT AnomalyFinder for the 2017 prime fields that cover ∼13 deg2. We report three unambiguous planets: OGLE-2017-BLG-0640, OGLE-2017-BLG-1275, and OGLE-2017-BLG-1237. The first two of these were not previously identified, while the last was not previously published due to technical complications induced by a nearby variable. We further report that a fourth anomalous event, the previously recognized OGLE-2017-BLG-1777, is very likely to be planetary, although its light curve requires unusually complex modeling because the lens and source both have orbiting companions. One of the three unambiguous planets, OGLE-2017-BLG-1275, is the first AnomalyFinder discovery that has a Spitzer microlens parallax measurement, π E ≃ 0.045 ± 0.015, implying that this planetary system almost certainly lies in the Galactic bulge. In the order listed, the four planetary events have planet-host mass ratios q and normalized projected separations s of (logq, s)=(−2.31, 0.61) , (−2.06, 0.63/1.09), (−2.10, 1.04), and (−2.86, 0.72). Combined with previously published events, the 2017 prime fields contain 11 unambiguous planets with well-measured q and one very likely candidate, of which three are AnomalyFinder discoveries. In addition to these 12, there are three other unambiguous planets with large uncertainties in q
Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC)
Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter‐defibrillators and long‐term mechanical support. For others, more evidence is still needed before large‐scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device‐provided therapy and also device‐guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care
Grey wolf optimizer based deep learning mechanism for music composition with data analysis
Music composition using artificial intelligence has gained increasing research attention recently. However, existing methods often generate music that needs more coherence and authenticity. This paper proposes an evolutionary computation-based deep learning approach for music composition with data analysis. Specifically, we utilize long short-term memory (LSTM) networks for generating melodic sequences and adopt a grey wolf optimizer to optimize LSTM hyperparameters. The training data is first converted to musical instrument digital interface (MIDI) format for data analysis, and melody lines are extracted using a similarity matrix method. The MIDI data is then encoded for input into the LSTM networks. The generated music is evaluated using objective metrics like mean squared error and subjective methods, including surveys of music professionals. Comparisons made to benchmark algorithms like generative adversarial networks demonstrate the advantages of our approach in accurately capturing tone, rhythm, artistic conception, and other attributes of high-quality music. The proposed mechanism provides a practical framework for AI-based music generation while ensuring authenticity
Are better AI algorithms for breast cancer detection also better at predicting risk? A paired case–control study
Background: There is increasing evidence that artificial intelligence (AI) breast cancer risk evaluation tools using digital mammograms are highly informative for 1–6 years following a negative screening examination. We hypothesized that algorithms that have previously been shown to work well for cancer detection will also work well for risk assessment and that performance of algorithms for detection and risk assessment is correlated. Methods: To evaluate our hypothesis, we designed a case-control study using paired mammograms at diagnosis and at the previous screening visit. The study included n = 3386 women from the OPTIMAM registry, that includes mammograms from women diagnosed with breast cancer in the English breast screening program 2010–2019. Cases were diagnosed with invasive breast cancer or ductal carcinoma in situ at screening and were selected if they had a mammogram available at the screening examination that led to detection, and a paired mammogram at their previous screening visit 3y prior to detection when no cancer was detected. Controls without cancer were matched 1:1 to cases based on age (year), screening site, and mammography machine type. Risk assessment was conducted using a deep-learning model designed for breast cancer risk assessment (Mirai), and three open-source deep-learning algorithms designed for breast cancer detection. Discrimination was assessed using a matched area under the curve (AUC) statistic. Results: Overall performance using the paired mammograms followed the same order by algorithm for risk assessment (AUC range 0.59–0.67) and detection (AUC 0.81–0.89), with Mirai performing best for both. There was also a correlation in performance for risk and detection within algorithms by cancer size, with much greater accuracy for large cancers (30 mm+, detection AUC: 0.88–0.92; risk AUC: 0.64–0.74) than smaller cancers (0 to < 10 mm, detection AUC: 0.73–0.86, risk AUC: 0.54–0.64). Mirai was relatively strong for risk assessment of smaller cancers (0 to < 10 mm, risk, Mirai AUC: 0.64 (95% CI 0.57 to 0.70); other algorithms AUC 0.54–0.56). Conclusions: Improvements in risk assessment could stem from enhancing cancer detection capabilities of smaller cancers. Other state-of-the-art AI detection algorithms with high performance for smaller cancers might achieve relatively high performance for risk assessment
Untangling free carrier and exciton dynamics in layered hybrid perovskites using ultrafast optical and terahertz spectroscopy
Layered hybrid perovskites (LPKs) are promising as alternatives or additives to 3D metal halide perovskites for optoelectronic applications including photovoltaic cells, LEDs and lasers due to their increased stability. However, high exciton binding energies in these materials mean that excitons are the majority species under the operating conditions of many devices. Although the efficiency of devices that incorporate LPKs has been increasing, much is still unknown about the interplay of excitons and free charge-carriers in these materials, which is vital information for understanding how optoelectronic properties dictate device efficiency. In this work, we employ optical pump/THz probe spectroscopy (OPTP) and visible transient absorption spectroscopy (TAS) to analyse the optoelectronic properties and charge-carrier dynamics of phenylethylammonium lead iodide (PEA)2PbI4. By combining these techniques, we are able to disentangle the contributions from excitons and free charge-carriers. We observe fast cooling of free charge-carriers and exciton formation on a timescale of ∼400 fs followed by slower bimolecular recombination of residual free charge-carriers with a rate constant k 2 ∼ 109 cm3s−1. Excitons recombine via two monomolecular processes with lifetimes t 1 ∼ 11 ps and t2 ∼ 83 ps. Furthermore, we detect signatures of exciton–phonon coupling in the transient absorption kinetic traces. These findings provide new insight into the interplay between free charge-carriers and excitons as well as a possible mechanism to further understand the charge-carrier dynamics in LPKs
In silico and in vitro mapping of receptor-type Protein Tyrosine Phosphatase Receptor Type D in health and disease : implications for asprosin signalling in endometrial cancer and neuroblastoma
Simple Summary: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) plays a role in cell proliferation, differentiation, oncogenic transformation, and brain development and serves as an orexigenic asprosin receptor. This study investigates the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated by obesity. Using a tissue microarray, abundant PTPRD expression in low- and high-grade EC tumours is noted. Using liquid biopsies from EC patients, we show the expression of PTPRD in peripheral leukocytes. Moreover, asprosin treatment upregulates the expression of PTPRD in syncytialised placental cells in vitro, but not in EC cell lines. Collectively, our data suggest that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Abstract: Background: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) is involved in the regulation of cell growth, differentiation, and oncogenic transformation, as well as in brain development. PTPRD also mediates the effects of asprosin, which is a glucogenic hormone/adipokine derived following the cleavage of the C-terminal of fibrillin 1. Since the asprosin circulating levels are elevated in certain cancers, research is now focused on the potential role of this adipokine and its receptors in cancer. As such, in this study, we investigated the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). Methods: An array of in silico tools, in vitro models, tissue microarrays (TMAs), and liquid biopsies were employed to determine the gene and protein expression of PTPRD in healthy tissues/organs and in patients with EC and GBM. Results: PTPRD exhibits high expression in the occipital lobe, parietal lobe, globus pallidus, ventral thalamus, and white matter, whereas in the human placenta, it is primarily localised around the tertiary villi. PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated with obesity, whilst it is also expressed in the peripheral leukocytes. The EC TMAs revealed abundant PTPRD expression in both low- and high-grade tumours. Asprosin treatment upregulated the expression of PTPRD only in syncytialised placental cells. Conclusions: Our data indicate that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Future studies are needed to explore the potential molecular mechanisms/signalling pathways that link PTPRD and asprosin in cancer
A label-free strategy for immobilization of GPCRs using site-specific encoded non-natural amino acids to develop a selectively chromatographic approach for pursuing potential ligands binding to 5-hydroxytryptamine 1A receptor
G protein-coupled receptors (GPCRs) are one of the most prominent targets for drug discovery. Immobilizing GPCRs has proven to be an effective strategy for expanding the utility of GPCRs into nonbiological contexts. However, traditional strategies of immobilizing GPCRs have been severely challenged due to the loss of receptor function. Here, we reported a novel and general approach to realize the label-free and site-selective immobilization of 5-hydroxytryptamine 1A receptor (5-HT1AR) and the application in developing a chromatographic method with improved specificity for pursuing 5-HT1AR ligands from natural products. This method involved the use of a clickable non-natural amino acid, O-allyl-L-tyrosine (O-ALTyr) to immobilize the receptor onto thiol-functionalized silica gels through a 'thiol-ene' click chemistry, which allowed us to avoid the purification step and directly immobilize 5-HT1AR on silica gels. The immobilized receptor was characterized using immunofluorescence assay, and receptor-ligand interaction analysis was conducted through frontal analysis. To test the feasibility of the immobilized 5-HT1ARO-ALTyr in complex matrices, bioactive compounds in Ziziphi Spinosae Semen (ZSS) were screened and their interaction with the receptor was assessed using zonal elution. Our findings indicated that immobilizing the receptor through nnAAs effectively minimizes the chromatographic peak tailing and broadening of specific ligands, leading to a significant improvement in chromatographic performance. The association constants of the three ligands to 5-HT1AR were approximately one order of magnitude greater than those of Halo-tag attachment. These results demonstrated that the immobilized 5-HT1AR exhibits high specificity and the ability to recognize receptor ligands from complex matrices. This allowed us to identify magnoflorine (Mag) as a potential ligand of 5-HT1AR from ZSS extract. In vivo assay also proved that Mag presented a promising anxiolytic effect by promoting the expression of 5-HT1AR in mice brain. The above findings pointed to the fact that the immobilized 5-HT1AR affinity chromatographic strategy relying on the site-specific encoded non-natural amino acid is a powerful alternative for precisely determining the drug-protein interaction and discovering the specific ligand of GPCRs from complex matrixes
Diabetic retinopathy and quality of life : a systematic review and meta-analysis
ImportanceThe association between diabetic retinopathy (DR) and quality of life (QoL) has not been thoroughly investigated.ObjectiveTo investigate the association between DR and both vision-related QoL (VRQoL) and general health-related QoL (HRQoL).Data SourcesMEDLINE, EBSCO, Embase, and Web of Science were searched from their inception to April 2022.Study SelectionStudies included adults with DR and a measure of QoL.Data Extraction and SynthesisPreferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Two assumption-free meta-analyses were conducted. Analysis 1 included studies with participants without DR as the referent group to which QoL scores of participants with DR, grouped according to DR severity, were compared. Analysis 2 included all studies with participants with DR and a measure of QoL. QoL scores were pooled within categories of DR severity, and comparisons were made between these categories.Main Outcome and MeasuresQoL measured using HRQoL and VRQoL scales.ResultsA total of 93 articles were included: 79 in the meta-analyses and 14 in the narrative results. VRQoL was recorded in 54 studies, HRQoL in 26, and both in 13 studies. The most commonly used scales were the National Eye Institute 25-item Visual Function Questionnaire (VFQ-25) (n = 49) for VRQoL and the Short Form (SF) Health Survey (n = 18) for HRQoL. Thirty-five studies reported VFQ-25 composite scores. Analysis 1 consisted of 8 studies including 1138 participants with DR and 347 participants without DR. Compared with participants without DR, the composite VFQ-25 score was 3.8 (95% CI, 1.0-6.7) points lower in those with non–vision-threatening DR (NVTDR), 12.5 (95% CI, 8.5-16.5) lower in those with any DR, and 25.1 (95% CI, 22.8-27.2) lower in VTDR (P &amp;lt; .001 for trend). Analysis 2 consisted of 35 studies including 6351 participants with DR. The pooled mean VFQ-25 composite score was 91.8 (95% CI, 91.0-92.7) for participants with NVTDR, 77.6 (95% CI, 76.9-78.3) for any DR, and 73.2 (95% CI, 72.6-73.7) for VTDR (P &amp;lt; .001 for trend). HRQoL scores had weak or no associations with NVTDR and strong associations with VTDR.Conclusions and RelevanceThis study found that VRQoL declined with the presence and severity of DR. Interventions to reduce progression of DR at both early and more advanced stages could improve VRQoL