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1.
J Community Psychol ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38843405

ABSTRACT

Research has linked broad societal changes related to the COVID-19 pandemic and poorer mental health in young people. There remains a pressing need for studies examining the factors that are associated with better mental health and well-being. The current study addresses this gap using a community-based survey called the Waterloo Region Youth Impact Survey. It was designed in partnership with local youth and the Canadian Index of Well-Being in accordance with United Nations International Children's Emergency Fund guidelines. Using a convenience sampling methodology, this survey was developed to explore the domains, rates, and correlates of well-being and mental health among youth during the pandemic (N = 297). Confirmatory factor analysis was used to identify dimensions related to children's social environment (friends, school, family), sense of belonging, mental health, and well-being. Subsequently, a mediation model was tested. The relationship between children's environments and mental health and well-being operated via perceived sense of belonging. Findings shed light on patterns of youth mental health and well-being during the pandemic, illustrating the role of belonging as a promotive factor with public health relevance.

2.
Article in English | MEDLINE | ID: mdl-38886184

ABSTRACT

BACKGROUND: Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring. OBJECTIVES: We conducted a Follow-Up Study of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with two objectives. First, we determined if women who enrolled at the Utah site (N = 1001) of the EAGeR trial (2007-2011, N = 1228) could successfully be contacted and agree to complete an online questionnaire on their reproductive, cardio-metabolic, and offspring respiratory health 9-14 years after original enrollment. Second, we evaluated if maternal exposure to low-dose aspirin (LDA) during pregnancy was associated with maternal cardio-metabolic health and offspring respiratory health. METHODS: The original EAGeR study population included women, 18-40 years of age, who had 1-2 prior pregnancy losses, and who were trying to become pregnant. At follow-up (2020-2021), participants from the Utah cohort completed a 13-item online questionnaire on reproductive and cardio-metabolic health, and those who had a live birth during EAGeR additionally completed a 7-item questionnaire on the index child's respiratory health. Primary maternal outcomes included hypertension and hypercholesterolemia; primary offspring outcomes included wheezing and asthma. RESULTS: Sixty-eight percent (n = 678) of participants enrolled in the follow-up study, with 10% and 15% reporting maternal hypertension and hypercholesterolemia, respectively; and 18% and 10% reporting offspring wheezing and asthma. We found no association between maternal LDA exposure and hypertension (risk difference [RD] -0.001, 95% confidence interval [CI] -0.05, 0.04) or hypercholesterolemia (RD -0.01, 95% CI -0.06, 0.05) at 9-14 years follow-up. Maternal LDA exposure was not associated with offspring wheezing (RD -0.002, 95% CI -0.08, 0.08) or asthma (RD 0.13, 95% CI 0.11, 0.37) at follow-up. Findings remained robust after considering potential confounding and selection bias. CONCLUSIONS: We observed no association between LDA exposure during pregnancy and maternal cardiometabolic or offspring respiratory health.

3.
Chiropr Man Therap ; 32(1): 23, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38909258

ABSTRACT

BACKGROUND: Radiography is commonly used in the assessment of spinal disorders, despite a lack of high-quality evidence demonstrating improved clinical outcomes or additional benefit to the patient. There is disagreement amongst chiropractors regarding the appropriate use of radiography for clinical management. This study aims to qualitatively explore chiropractors' perceptions on the use of spinal radiographs in clinical practice with respect to how they determine when to order radiographs; and how they use radiographs to inform clinical management. METHODS: Online qualitative semi-structured interviews were conducted with 17 Australian chiropractors who currently manage patients with spinal disorders. Convienence, snowball, and purposive sampling strategies were used to ensure an appropriate breadth and depth of participant characterisitcs and beliefs. Interview data were recorded, transcribed and analysed using framework analysis. RESULTS: Three themes were developed to describe how chiropractors determined when to order radiographs. These themes included specific findings from the clinical encounter that may inform clinical management, their perceptions of radiation risk, and the influence of clinical experience/intuition. Three themes and four subthemes were developed for how chiropractors use radiographs to inform their management. These themes explored the use of radiography for the application of chiropractic technique, as well as the role of radiographs in predicting patient prognosis, and as an educational tool to provide reassurance. CONCLUSION: Australian chiropractors' decision-making around spinal radiography is diverse and can be influenced by a number of clinical and external factors. Previously unexplored uses of spinal radiography in clinical practice were highlighted. Some chiropractors reported potential benefits of radiography that are currently not supported by research evidence. Future research should address how radiographic findings are reported to patients with spinal disorders and how this could be optimised to improve patient outcomes.


Subject(s)
Chiropractic , Qualitative Research , Radiography , Humans , Female , Male , Australia , Adult , Middle Aged , Attitude of Health Personnel , Spinal Diseases/diagnostic imaging , Spine/diagnostic imaging
4.
ACS Chem Neurosci ; 15(12): 2396-2407, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38847395

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra, resulting in motor dysfunction. Current treatments are primarily centered around enhancing dopamine signaling or providing dopamine replacement therapy and face limitations such as reduced efficacy over time and adverse side effects. To address these challenges, we identified selective dopamine receptor subtype 4 (D4R) antagonists not previously reported as potential adjuvants for PD management. In this study, a library screening and artificial neural network quantitative structure-activity relationship (QSAR) modeling with experimentally driven library design resulted in a class of spirocyclic compounds to identify candidate D4R antagonists. However, developing selective D4R antagonists suitable for clinical translation remains a challenge.


Subject(s)
Computer-Aided Design , Quantitative Structure-Activity Relationship , Humans , Receptors, Dopamine D4/antagonists & inhibitors , Receptors, Dopamine D4/metabolism , Spiro Compounds/pharmacology , Spiro Compounds/chemistry , Dopamine Antagonists/pharmacology , Neural Networks, Computer , Parkinson Disease/drug therapy , Animals , Drug Design
5.
J Affect Disord ; 358: 487-499, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38705527

ABSTRACT

BACKGROUND: Glaucoma, a progressive neurodegenerative disorder leading to irreversible blindness, is associated with heightened rates of generalized anxiety and depression. This study aims to comprehensively investigate brain morphological changes in glaucoma patients, extending beyond visual processing areas, and explores overlaps with morphological alterations observed in anxiety and depression. METHODS: A comparative meta-analysis was conducted, using case-control studies of brain structural integrity in glaucoma patients. We aimed to identify regions with gray matter volume (GMV) changes, examine their role within distinct large-scale networks, and assess overlap with alterations in generalized anxiety disorder (GAD) and major depressive disorder (MDD). RESULTS: Glaucoma patients exhibited significant GMV reductions in visual processing regions (lingual gyrus, thalamus). Notably, volumetric reductions extended beyond visual systems, encompassing the left putamen and insula. Behavioral and functional network decoding revealed distinct large-scale networks, implicating visual, motivational, and affective domains. The insular region, linked to pain and affective processes, displayed reductions overlapping with alterations observed in GAD. LIMITATIONS: While the study identified significant morphological alterations, the number of studies from both the glaucoma and GAD cohorts remains limited due to the lack of independent studies meeting our inclusion criteria. CONCLUSION: The study proposes a tripartite brain model for glaucoma, with visual processing changes related to the lingual gyrus and additional alterations in the putamen and insular regions tied to emotional or motivational functions. These neuroanatomical changes extend beyond the visual system, implying broader implications for brain structure and potential pathological developments, providing insights into the overall neurological consequences of glaucoma.


Subject(s)
Anxiety Disorders , Depressive Disorder, Major , Glaucoma , Gray Matter , Humans , Glaucoma/pathology , Glaucoma/physiopathology , Gray Matter/pathology , Gray Matter/diagnostic imaging , Anxiety Disorders/pathology , Anxiety Disorders/diagnostic imaging , Depressive Disorder, Major/pathology , Depressive Disorder, Major/diagnostic imaging , Magnetic Resonance Imaging , Brain/pathology , Brain/diagnostic imaging , Emotional Regulation/physiology , Case-Control Studies , Putamen/pathology , Putamen/diagnostic imaging
6.
Phys Rev E ; 109(4-2): 045108, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38755946

ABSTRACT

Even when the partial differential equation underlying a physical process can be evolved forward in time, the retrospective (backward in time) inverse problem often has its own challenges and applications. Direct adjoint looping (DAL) is the defacto approach for solving retrospective inverse problems, but it has not been applied to deterministic retrospective Navier-Stokes inverse problems in 2D or 3D. In this paper, we demonstrate that DAL is ill-suited for solving retrospective 2D Navier-Stokes inverse problems. Alongside DAL, we study two other iterative methods: simple backward integration (SBI) and the quasireversible method (QRM). As far as we know, our iterative SBI approach is novel, while iterative QRM has previously been used. Using these three iterative methods, we solve two retrospective inverse problems: 1D Korteweg-de Vries-Burgers (decaying nonlinear wave) and 2D Navier-Stokes (unstratified Kelvin-Helmholtz vortex). In both cases, SBI and QRM reproduce the target final states more accurately and in fewer iterations than DAL. We attribute this performance gap to additional terms present in SBI and QRM's respective backward integrations which are absent in DAL.

7.
Nature ; 629(8013): 769-772, 2024 May.
Article in English | MEDLINE | ID: mdl-38778233

ABSTRACT

The magnetic dynamo cycle of the Sun features a distinct pattern: a propagating region of sunspot emergence appears around 30° latitude and vanishes near the equator every 11 years (ref. 1). Moreover, longitudinal flows called torsional oscillations closely shadow sunspot migration, undoubtedly sharing a common cause2. Contrary to theories suggesting deep origins of these phenomena, helioseismology pinpoints low-latitude torsional oscillations to the outer 5-10% of the Sun, the near-surface shear layer3,4. Within this zone, inwardly increasing differential rotation coupled with a poloidal magnetic field strongly implicates the magneto-rotational instability5,6, prominent in accretion-disk theory and observed in laboratory experiments7. Together, these two facts prompt the general question: whether the solar dynamo is possibly a near-surface instability. Here we report strong affirmative evidence in stark contrast to traditional models8 focusing on the deeper tachocline. Simple analytic estimates show that the near-surface magneto-rotational instability better explains the spatiotemporal scales of the torsional oscillations and inferred subsurface magnetic field amplitudes9. State-of-the-art numerical simulations corroborate these estimates and reproduce hemispherical magnetic current helicity laws10. The dynamo resulting from a well-understood near-surface phenomenon improves prospects for accurate predictions of full magnetic cycles and space weather, affecting the electromagnetic infrastructure of Earth.

8.
Chiropr Man Therap ; 32(1): 18, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802926

ABSTRACT

Scope of practice has been defined as the activities that an individual health care practitioner is allowed to undertake within a specific profession. The chiropractic profession in Australia does not currently have a documented scope of practice. Informed discussions around scope of practice are hampered by a paucity of literature in this area. Acknowledging this void in the literature, we chose to investigate the factors that influence scope of practice of the chiropractic profession. A knowledge of the factors will facilitate discussion on the topic and help the profession to work towards establishing a scope of practice.Aim The aim of this study was to identify the factors that influence scope of practice of chiropractic in Australia from the perspective of 4 stakeholder groups within the profession.Methods This study employed semi-structured, online-interviews. Open-ended questions, guided by a flexible interview protocol, and augmented by supplemental questions, probes and comments, were used to gather data on the research question. Data were analysed using reflexive thematic analysis.Results Six factors that influenced scope of practice of chiropractic were identified in this study: education, evidence (research-derived and practice-based), political influence, community expectations, entrepreneurial business models, and geographical location.Conclusion Knowledge of the factors that influence scope of practice of chiropractic in Australia is important for establishing a scope of practice for the profession. This knowledge is also of value to a range of stakeholders including patients, health care providers (within and outside the profession), professional associations, and policymakers.


Subject(s)
Chiropractic , Scope of Practice , Humans , Australia , Qualitative Research , Attitude of Health Personnel
9.
Article in English | MEDLINE | ID: mdl-38697259

ABSTRACT

OBJECTIVE: To compare demographic characteristics of women with and without a diagnosis of endometriosis. DESIGN: Data were collected from the National Survey of Family Growth-a publicly available survey designed and administered by the Centers for Disease Control, which uses a nationally-representative sample of the United States population. Univariate data were reported as survey-weighted percentages and means and were analyzed using chi-square, t tests, and logistic regression. Analyses accounted for complex survey design. SETTING: United States. PARTICIPANTS: Interviews were conducted with 6141 female respondents, aged 15 to 50, between 2017 and 2019. INTERVENTIONS: Data were collected through in-person interviews. RESULTS: Nationally, 5.7% reported a diagnosis of endometriosis (95% CI 4.6-6.9%). Those with endometriosis were older, with a mean age of 39 (95% CI 38.1-39.9), compared to 31.7 (95% CI 31.2-32.2) among those without (p <.0005). Endometriosis diagnosis was significantly associated with race. Compared to non-Hispanic White women, Hispanic women had an adjusted odds ratio (aOR) of 0.37 (95% CI 0.21-0.65) for diagnosis of endometriosis, and non-Hispanic Black women had an aOR of 0.54 (95% CI 0.35-0.84). We also observed a difference in diagnosis by health insurance: compared to those with private insurance or Medi-Gap coverage, those with Medicare or military insurance had an aOR for endometriosis diagnosis of 2.49 (95% CI 1.36-4.55). Finally, compared to those with less than a high school education, those who had completed high school or greater had an aOR for endometriosis diagnosis of 2.84 (95% CI 1.15-6.99). CONCLUSION: These disparities in endometriosis diagnosis suggest that intersecting barriers may preclude certain groups from accessing timely endometriosis diagnosis and management. Further studies are warranted to explore these hypothesis-generating data and to identify and address specific barriers to equitable endometriosis diagnosis and management.

10.
BMJ Open ; 14(4): e069236, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38626980

ABSTRACT

OBJECTIVES: The study aims to investigate the perceptions of patients with thyroid cancer on the potential impact of diagnosis and treatment delays during the COVID-19 pandemic. DESIGN: This study involved qualitative semi-structured telephone interviews. The interviews were transcribed verbatim, analysed using the thematic framework analysis method and reported using the Consolidated Criteria for Reporting Qualitative Research. SETTING: Participants in the study were treated and/or managed at hospital sites across New South Wales and Victoria, Australia. PARTICIPANTS: 17 patients with thyroid cancer were interviewed and included in the analysis (14 females and 3 males). RESULTS: The delays experienced by patients ranged from <3 months to >12 months. The patients reported about delays to diagnostic tests, delays to surgery and radioactive iodine treatment, perceived disease progression and, for some, the financial burden of choosing to go through private treatment to minimise the delay. Most patients also reported not wanting to experience delays any longer than they did, due to unease and anxiety. CONCLUSIONS: This study highlights an increased psychological burden in patients with thyroid cancer who experienced delayed diagnosis and/or treatment during COVID-19. The impacts experienced by patients during this time may be similar in the case of other unexpected delays and highlight the need for regular clinical review during delays to diagnosis or treatment.


Subject(s)
COVID-19 , Thyroid Neoplasms , Male , Female , Humans , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/therapy , Delayed Diagnosis , Iodine Radioisotopes , Pandemics , Victoria , Qualitative Research , COVID-19 Testing
11.
Article in English | MEDLINE | ID: mdl-38652504

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Pharmacogenetic testing can identify patients who may benefit from personalized drug treatment. However, clinical uptake of pharmacogenetic testing has been limited. Clinical practice guidelines recommend biomarker tests that the guideline authors deem to have demonstrated clinical utility, meaning that testing improves treatment outcomes. The objective of this narrative review is to describe the current status of pharmacogenetic testing recommendations within clinical practice guidelines in the US. SUMMARY: Guidelines were reviewed for pharmacogenetic testing recommendations for 21 gene-drug pairs that have well-established drug response associations and all of which are categorized as clinically actionable by the Clinical Pharmacogenetics Implementation Consortium. The degree of consistency within and between organizations in pharmacogenetic testing recommendations was assessed. Relatively few clinical practice guidelines that provide a pharmacogenetic testing recommendation were identified. Testing recommendations for HLA-B*57:01 before initiation of abacavir and G6PD before initiation of rasburicase, both of which are included in drug labeling, were mostly consistent across guidelines. Gene-drug pairs with at least one clinical practice guideline recommending testing or stating that testing could be considered included CYP2C19-clopidogrel, CYP2D6-codeine, CYP2D6-tramadol, CYP2B6-efavirenz, TPMT-thiopurines, and NUDT15-thiopurines. Testing recommendations for the same gene-drug pair were often inconsistent between organizations and sometimes inconsistent between different guidelines from the same organization. CONCLUSION: A standardized approach to evaluating the evidence of clinical utility for pharmacogenetic testing may increase the inclusion and consistency of pharmacogenetic testing recommendations in clinical practice guidelines, which could benefit patients and society by increasing clinical use of pharmacogenetic testing.

12.
World J Surg ; 48(5): 1037-1044, 2024 05.
Article in English | MEDLINE | ID: mdl-38497974

ABSTRACT

BACKGROUND: American Indian and Alaska Native (AIAN) health issues are understudied despite documentation of lower-than-average life expectancy. Urgent surgery is associated with higher rates of postsurgical complications and postoperative death. We assess whether American Indian and Alaska Native (AIAN) patients in Washington State are at greater risk of requiring urgent rather than elective surgery compared with non-Hispanic Whites (NHW). METHODS: We accessed data for the period 2009-2014 from the Washington State Comprehensive Hospital Abstract Reporting System (CHARS) database, which captures all statewide hospital admissions, to examine three common surgeries that are performed both urgently and electively: hip replacements, aortic valve replacements, and spinal fusions. We extracted patient race, age, insurance status, comorbidity, admission type, and procedures performed. We then constructed multivariable logistic regression models to identify factors associated with use of urgent surgical care. RESULTS: AIAN patients had lower mean age at surgery for all three surgeries compared with NHW patients. AIAN patients were at higher risk for urgent surgery for hip replacements (OR = 1.49, 95% CI 1.19-1.88), spinal fusions (OR = 1.39, 95% CI 1.04-1.87), and aortic valve replacements (OR = 2.06, 95% CI 1.12-3.80). CONCLUSION: AIAN patients were more likely to undergo urgent hip replacement, spinal fusion, and aortic valve replacement than NHW patients. AIAN patients underwent urgent surgery at younger ages. Medicaid insurance conferred higher risks for urgent surgery across all surgeries studied. Further research is warranted to more clearly identify the factors contributing to disparities among AIAN patients undergoing urgent surgery.


Subject(s)
Elective Surgical Procedures , Healthcare Disparities , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Arthroplasty, Replacement, Hip/statistics & numerical data , Elective Surgical Procedures/statistics & numerical data , Healthcare Disparities/statistics & numerical data , Healthcare Disparities/ethnology , Heart Valve Prosthesis Implantation/statistics & numerical data , Retrospective Studies , Spinal Fusion/statistics & numerical data , Washington , American Indian or Alaska Native/statistics & numerical data
13.
BMC Med Educ ; 24(1): 136, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38347486

ABSTRACT

BACKGROUND: The management of low back pain (LBP) is highly variable and patients often receive management that is not recommended and/or miss out on recommended care. Clinician knowledge and behaviours are strongly influenced by entry-level clinical training and are commonly cited as barriers to implementing evidence-based management. Currently there are no internationally recognised curriculum standards for the teaching of LBP content to ensure graduating clinicians have the appropriate knowledge and competencies to assess and manage LBP. We formed an international interdisciplinary working group to develop curriculum content standards for the teaching of LBP in entry-level clinical training programs. METHODS: The working group included representatives from 11 countries: 18 academics and clinicians from healthcare professions who deal with the management of LBP (medicine, physiotherapy, chiropractic, osteopathy, pharmacology, and psychology), seven professional organisation representatives (medicine, physiotherapy, chiropractic, spine societies), and one healthcare consumer. A literature review was performed, including database and hand searches of guidelines and accreditation, curricula, and other policy documents, to identify gaps in current LBP teaching and recommended entry-level knowledge and competencies. The steering group (authors) drafted the initial LBP Curriculum Content Standards (LBP-CCS), which were discussed and modified through two review rounds with the working group. RESULTS: Sixty-two documents informed the draft standards. The final LBP-CCS consisted of four broad topics covering the epidemiology, biopsychosocial contributors, assessment, and management of LBP. For each topic, key knowledge and competencies to be achieved by the end of entry-level clinical training were described. CONCLUSION: We have developed the LBP-CCS in consultation with an interdisciplinary, international working group. These standards can be used to inform or benchmark the content of curricula related to LBP in new or existing entry-level clinical training programs.


Subject(s)
Low Back Pain , Humans , Low Back Pain/therapy , Curriculum , Delivery of Health Care , Health Personnel
14.
Br J Gen Pract ; 74(744): e489-e497, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38164550

ABSTRACT

BACKGROUND: Online consultation systems (OCSs) allow patients to contact their healthcare teams online. Since 2020 they have been rapidly rolled out in primary care following policy initiatives and the COVID-19 pandemic. In-depth research of patients' experiences using OCSs is lacking. AIM: Explore patients' experiences of using an OCS. DESIGN AND SETTING: Qualitative study in English GP practices using the Patchs OCS (www.Patchs.ai) from March 2020 to July 2022. METHOD: Thematic analysis of 25 patient interviews and 21 467 written comments from 11 851 patients who used the OCS from nine and 240 GP practices, respectively. RESULTS: Patients cited benefits of using the OCS as speed, flexibility, and efficiency. Nevertheless, some patients desired a return to traditional consultation methods. GP practices often did not clearly advertise the OCS or use it as patients expected, which caused frustration. Patients reported advantages of having a written record of consultations and the opportunity to communicate detailed queries in free text. Views differed on how the OCS influenced clinical safety and discussions of sensitive topics. Patients who struggled to communicate in traditional consultations often preferred using the OCS, and male patients reported being more likely to use it. CONCLUSION: Globally, this is the largest in-depth study of patient experiences of an OCS. It contributes new knowledge that the patient experience of using OCSs can be influenced by previously unreported patient characteristics and the conditions they consult about. Further, it contributes recommendations on the design and implementation of the OCS in practice.


Subject(s)
COVID-19 , Primary Health Care , Qualitative Research , Remote Consultation , SARS-CoV-2 , Humans , COVID-19/epidemiology , Male , Female , England , Middle Aged , Adult , Patient Satisfaction , Physician-Patient Relations , Pandemics , Aged , General Practice
15.
Contraception ; 132: 110362, 2024 04.
Article in English | MEDLINE | ID: mdl-38190866

ABSTRACT

OBJECTIVE: To evaluate expulsion rates in the first 3 years of an academic postplacental levonorgestrel intrauterine device (LNG-IUD) insertion program. STUDY DESIGN: Retrospective case series, January 2016 to December 2018. We measured LNG-IUD expulsion rates by 12 weeks postpartum. RESULTS: Of 235 LNG-IUD insertions, in years 1, 2, and 3, expulsion rates were 11/39 (28%), 9/94 (10%), and 15/102 (15%) (p = 0.03). After vaginal delivery, manual insertion was associated with a higher expulsion rate than ring-forceps (10/28 [36%] vs 17/105 [16%], p = 0.04). CONCLUSIONS: LNG-IUD expulsion rates decreased after program year 1, suggesting program maturity may be associated with a lower expulsion risk.


Subject(s)
Internship and Residency , Intrauterine Devices , Female , Humans , Levonorgestrel , Retrospective Studies , Intrauterine Device Expulsion
16.
J Chem Theory Comput ; 20(3): 1434-1447, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38215214

ABSTRACT

Protein thermodynamics is intimately tied to biological function and can enable processes such as signal transduction, enzyme catalysis, and molecular recognition. The relative free energies of conformations that contribute to these functional equilibria evolved for the physiology of the organism. Despite the importance of these equilibria for understanding biological function and developing treatments for disease, computational and experimental methods capable of quantifying the energetic determinants of these equilibria are limited to systems of modest size. Recently, it has been demonstrated that the artificial intelligence system AlphaFold2 can be manipulated to produce structurally valid protein conformational ensembles. Here, we extend these studies and explore the extent to which AlphaFold2 contact distance distributions can approximate projections of the conformational Boltzmann distributions. For this purpose, we examine the joint probability distributions of inter-residue contact distances along functionally relevant collective variables of several protein systems. Our studies suggest that AlphaFold2 normalized contact distance distributions can correlate with conformation probabilities obtained with other methods but that they suffer from peak broadening. We also find that the AlphaFold2 contact distance distributions can be sensitive to point mutations. Overall, we anticipate that our findings will be valuable as the community seeks to model the thermodynamics of conformational changes in large biomolecular systems.


Subject(s)
Artificial Intelligence , Molecular Dynamics Simulation , Proteins/chemistry , Protein Conformation , Thermodynamics
17.
Nature ; 625(7994): 259-263, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38200302

ABSTRACT

To run large-scale algorithms on a quantum computer, error-correcting codes must be able to perform a fundamental set of operations, called logic gates, while isolating the encoded information from noise1-8. We can complete a universal set of logic gates by producing special resources called magic states9-11. It is therefore important to produce high-fidelity magic states to conduct algorithms while introducing a minimal amount of noise to the computation. Here we propose and implement a scheme to prepare a magic state on a superconducting qubit array using error correction. We find that our scheme produces better magic states than those that can be prepared using the individual qubits of the device. This demonstrates a fundamental principle of fault-tolerant quantum computing12, namely, that we can use error correction to improve the quality of logic gates with noisy qubits. Moreover, we show that the yield of magic states can be increased using adaptive circuits, in which the circuit elements are changed depending on the outcome of mid-circuit measurements. This demonstrates an essential capability needed for many error-correction subroutines. We believe that our prototype will be invaluable in the future as it can reduce the number of physical qubits needed to produce high-fidelity magic states in large-scale quantum-computing architectures.

18.
J Multimorb Comorb ; 14: 26335565231220202, 2024.
Article in English | MEDLINE | ID: mdl-38223165

ABSTRACT

Introduction: Long-term conditions are a major burden on health systems. One way to facilitate more research and better clinical care among patients with long-term conditions is to collect accurate data on their daily symptoms (patient-generated health data) using wearable technologies. Whilst evidence is growing for the use of wearable technologies in single conditions, there is less evidence of the utility of frequent symptom tracking in those who have more than one condition. Aims: To explore patient views of the acceptability of collecting daily patient-generated health data for three months using a smartwatch app. Methods: Watch Your Steps was a longitudinal study which recruited 53 patients to track over 20 symptoms per day for a 90-day period using a study app on smartwatches. Semi-structured interviews were conducted with a sub-sample of 20 participants to explore their experience of engaging with the app. Results: In a population of older people with multimorbidity, patients were willing and able to engage with a patient-generated health data app on a smartwatch. It was suggested that to maintain engagement over a longer period, more 'real-time' feedback from the app should be available. Participants did not seem to consider the management of more than one condition to be a factor in either engagement or use of the app, but the presence of severe or chronic pain was at times a barrier. Conclusion: This study has provided preliminary evidence that multimorbidity was not a major barrier to engagement with patient-generated health data via a smartwatch symptom tracking app.

19.
Stud Health Technol Inform ; 310: 1026-1030, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38269970

ABSTRACT

Clinical prediction models are increasingly used across healthcare to support clinical decision making. Existing methods and models are time-invariant and thus ignore the changes in populations and healthcare practice that occur over time. We aimed to compare the performance of time-invariant with time-variant models in UK National Adult Cardiac Surgery Audit data from Manchester University NHS Foundation Trust between 2009 and 2019. Data from 2009-2011 were used for initial model fitting, and data from 2012-2019 for validation and updating. We fitted four models to the data: a time-invariant logistic regression model (not updated), a logistic model which was updated every year and validated it in each subsequent year, a logistic regression model where the intercept is a function of calendar time (not updated), and a continually updating Bayesian logistic model which was updated with each new observation and continuously validated. We report predictive performance over the complete validation cohort and for each year in the validation data. Over the complete validation data, the Bayesian model had the best predictive performance.


Subject(s)
Cardiac Surgical Procedures , Models, Statistical , Adult , Humans , Bayes Theorem , Prognosis , Clinical Decision-Making
20.
Cereb Cortex ; 34(1)2024 01 14.
Article in English | MEDLINE | ID: mdl-37943770

ABSTRACT

Empathic function, which is primarily manifested by facial imitation, is believed to play a pivotal role in interpersonal emotion regulation for mood reinstatement. To explore this association and its neural substrates, we performed a questionnaire survey (study l) to identify the relationship between empathy and interpersonal emotion regulation; and a task-mode fMRI study (study 2) to explore how facial imitation, as a fundamental component of empathic processes, promotes the interpersonal emotion regulation effect. Study 1 showed that affective empathy was positively correlated with interpersonal emotion regulation. Study 2 showed smaller negative emotions in facial imitation interpersonal emotion regulation (subjects imitated experimenter's smile while followed the interpersonal emotion regulation guidance) than in normal interpersonal emotion regulation (subjects followed the interpersonal emotion regulation guidance) and Watch conditions. Mirror neural system (e.g. inferior frontal gyrus and inferior parietal lobe) and empathy network exhibited greater activations in facial imitation interpersonal emotion regulation compared with normal interpersonal emotion regulation condition. Moreover, facial imitation interpersonal emotion regulation compared with normal interpersonal emotion regulation exhibited increased functional coupling from mirror neural system to empathic and affective networks during interpersonal emotion regulation. Furthermore, the connectivity of the right orbital inferior frontal gyrus-rolandic operculum lobe mediated the association between the accuracy of facial imitation and the interpersonal emotion regulation effect. These results show that the interpersonal emotion regulation effect can be enhanced by the target's facial imitation through increased functional coupling from mirror neural system to empathic and affective neural networks.


Subject(s)
Emotional Regulation , Humans , Brain Mapping/methods , Imitative Behavior/physiology , Magnetic Resonance Imaging/methods , Empathy , Functional Neuroimaging , Emotions/physiology , Facial Expression
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