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1.
bioRxiv ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38798471

ABSTRACT

There is now increasing recognition of the important role of androgen receptor (AR) in modulating immune function. To gain a comprehensive understanding of the effects of AR activity on cancer immunity, we employed a computational approach to profile AR activity in 33 human tumor types using RNA-Seq datasets from The Cancer Genome Atlas. Our pan-cancer analysis revealed that the genes most negatively correlated with AR activity across cancers are involved in active immune system processes. Importantly, we observed a significant negative correlation between AR activity and IFNγ pathway activity at the pan-cancer level. Indeed, using a matched biopsy dataset from subjects with prostate cancer before and after AR-targeted treatment, we verified that inhibiting AR enriches immune cell abundances and is associated with higher IFNγ pathway activity. Furthermore, by analyzing immunotherapy datasets in multiple cancers, our results demonstrate that low AR activity was significantly associated with a favorable response to immunotherapy. Together, our data provide a comprehensive assessment of the relationship between AR signaling and tumor immunity.

2.
Article in English | MEDLINE | ID: mdl-38605573

ABSTRACT

BACKGROUND: Several studies have demonstrated that females have a higher risk of arrhythmia recurrence after pulmonary vein (PV) isolation for atrial fibrillation (AF). There are limited data on sex-based differences in PV reconnection rates at repeat ablation. We aimed to investigate sex-based differences in electrophysiological findings and atrial arrhythmia recurrence after repeat AF ablation METHODS: We conducted a retrospective study of 161 consecutive patients (32% female, age 65 ± 10 years) who underwent repeat AF ablation after index PV isolation between 2010 and 2022. Demographics, procedural characteristics and follow-up data were collected. Recurrent atrial tachycardia (AT)/AF was defined as any atrial arrhythmia ≥30 s in duration. RESULTS: Compared to males, females tended to be older and had a significantly higher prevalence of prior valve surgery (10 vs. 2%; P = .03). At repeat ablation, PV reconnection was found in 119 (74%) patients. Males were more likely to have PV reconnection at repeat ablation compared to females (81 vs. 59%; P = .004). Excluding repeat PV isolation, there were no significant differences in adjunctive ablation strategies performed at repeat ablation between females and males. During follow-up, there were no significant differences in freedom from AT/AF recurrence between females and males after repeat ablation (63 vs. 59% at 2 years, respectively; P = .48). CONCLUSIONS: After initial PV isolation, significantly fewer females have evidence of PV reconnection at the time of repeat ablation for recurrent AF. Despite this difference, long-term freedom from AT/AF was similar between females and males after repeat ablation.

3.
J Adolesc ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38570320

ABSTRACT

INTRODUCTION: Social media has become a ubiquitous part of everyday life; however, evidence suggests patterns of social media use can affect sleep health in children and adolescents. This study aimed to examine the associations of intense and problematic social media use (SMU) with sleep-onset difficulties in adolescence. METHODS: We analysed data from 212,613 adolescents aged 11-15 years (51.1% girls) from 40 European and North American countries that participated in the 2017/2018 Health Behaviour in School-aged Children survey. Intense SMU assessed how often respondents had online contact through social media, and problematic SMU was assessed by symptoms of addiction to social media. Sleep-onset difficulties were assessed using a self-reported item. Multilevel mixed-effects logistic regression was used to obtain the estimates. RESULTS: Sleep-onset difficulties were more common among girls than boys (27.1% vs 20.8%). Intense SMU was significantly associated with sleep-onset difficulties in boys in 17 countries and in girls in 25 countries, while problematic SMU was significantly associated in most of the participating countries. Overall, exposure to problematic SMU alone was highly associated with sleep-onset difficulties both in girls (OR 2.20, 2.04-2.38) and boys (OR 1.88, 1.73-2.04), while the association estimates for intense SMU were smaller and comparable across gender (Girls: OR 1.27, 1.23-1.31; Boys: OR 1.22, 1.18-1.27). Sensitivity analyses supported the above findings. CONCLUSIONS: Intense and/or problematic SMU were associated with sleep-onset difficulties across gender with associations being higher for problematic compared to intense SMU. Prospective research with objective measures is needed to understand the causal mechanisms underlying these relationships.

7.
Curr Top Med Chem ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38551050

ABSTRACT

BACKGROUND: Immunomodulation is the modification of immune responses to control disease progression. While the synthetic immunomodulators have proven efficacy, they are coupled with toxicity and other adverse effects, and hence, the efforts were to identify natural phytochemicals with immunomodulatory potential. OBJECTIVE: The objective of this study is to understand the immunomodulatory properties of various phytochemicals and investigate them in Echinacea species extracts using an in silico approach. METHODOLOGY: Several scientific database repositories were searched using different keywords: "Phytochemicals," "Alkaloids," "Polyphenols," "Flavonoids," "Lectins," "Glycosides," "Tannins," "Terpenoids," "Sterols," "Immunomodulators," and "Human Immune System" without any language restriction. Additionally, the study specifically investigated the immunomodulatory properties of Echinacea species extracts using gene expression analysis of GSE12259 from NCBI-GEO through the Bioconductor package GEOquery and limma. RESULTS: A total of 182 studies were comprehensively analyzed to understand immunomodulatory phytochemicals. The in silico analysis highlighted key biological processes (positive regulation of cytokine production, response to tumor necrosis factor) and molecular functions (cytokine receptor binding, receptor-ligand activity, and cytokine activity) among Echinacea species extracts contributing to immune responses. Further, it also indicated the association of various metabolic pathways, i.e., pathways in cancer, cytokine-cytokine receptor interaction, NF-kappa B, PI3K-Akt, TNF, MAPK, and NOD-like receptor signaling pathways, with immune responses. The study revealed various hub targets, including CCL20, CCL4, GCH1, SLC7A11, SOD2, EPB41L3, TNFAIP6, GCLM, EGR1, and FOS. CONCLUSION: The present study presents a cumulative picture of phytochemicals with therapeutic benefits. Additionally, the study also reported a few novel genes and pathways in Echinacea extracts by re-analyzing GSE 12259, indicating its anti-inflammatory, anti-viral, and immunomodulatory properties.

8.
Acta Psychol (Amst) ; 245: 104231, 2024 May.
Article in English | MEDLINE | ID: mdl-38531269

ABSTRACT

In the recent years, there has been a rising interest among luxury brands to be environmentally responsible and promote employee discretionary behaviour. However, the underlying mechanisms that explain why, when, and how employees demonstrate discretionary environmental attitudes and behaviour in luxury contexts are not well-known. To accelerate this discourse; the current study examines the impact of environmental corporate social responsibility (CSR) on employees' organizational citizenship behaviour towards environment. Drawing insights from social cognitive theory, this study empirically validates a conceptual model through the data collected from 406 employees of luxury hotels and analysed using structural equation modelling. The results confirm the significant effect of environmental CSR on employees' organizational citizenship behaviour towards environment. The results also reveal that employee environmental commitment and green work engagement partially mediate the proposed relationship. Moreover, contrary to expectations, gender did not moderate the influence of environmental CSR on employee environmental commitment and employee green work engagement, whereas the relationship between environmental CSR and organizational citizenship behaviour towards environment was stronger for males than females. We argue that creative environmental CSR assignments in luxury hotel chains help employees develop engagement, identification, and commitment with the environmental strategy of the hotels towards solving grave environmental problems that modern societies are grappling with.


Subject(s)
Citizenship , Psychological Theory , Female , Male , Humans , Empirical Research
9.
PLoS One ; 19(3): e0299932, 2024.
Article in English | MEDLINE | ID: mdl-38507433

ABSTRACT

Hypertension is a widely prevalent disease and uncontrolled hypertension predisposes affected individuals to severe adverse effects. Though the importance of controlling hypertension is clear, the multitude of therapeutic regimens and patient factors that affect the success of blood pressure control makes it difficult to predict the likelihood to predict whether a patient's blood pressure will be controlled. This project endeavors to investigate whether machine learning can accurately predict the control of a patient's hypertension within 12 months of a clinical encounter. To build the machine learning model, a retrospective review of the electronic medical records of 350,008 patients 18 years of age and older between January 1, 2015 and June 1, 2022 was performed to form model training and testing cohorts. The data included in the model included medication combinations, patient laboratory values, vital sign measurements, comorbidities, healthcare encounters, and demographic information. The mean age of the patient population was 65.6 years with 161,283 (46.1%) men and 275,001 (78.6%) white. A sliding time window of data was used to both prohibit data leakage from training sets to test sets and to maximize model performance. This sliding window resulted in using the study data to create 287 predictive models each using 2 years of training data and one week of testing data for a total study duration of five and a half years. Model performance was combined across all models. The primary outcome, prediction of blood pressure control within 12 months demonstrated an area under the curve of 0.76 (95% confidence interval; 0.75-0.76), sensitivity of 61.52% (61.0-62.03%), specificity of 75.69% (75.25-76.13%), positive predictive value of 67.75% (67.51-67.99%), and negative predictive value of 70.49% (70.32-70.66%). An AUC of 0.756 is considered to be moderately good for machine learning models. While the accuracy of this model is promising, it is impossible to state with certainty the clinical relevancy of any clinical support ML model without deploying it in a clinical setting and studying its impact on health outcomes. By also incorporating uncertainty analysis for every prediction, the authors believe that this approach offers the best-known solution to predicting hypertension control and that machine learning may be able to improve the accuracy of hypertension control predictions using patient information already available in the electronic health record. This method can serve as a foundation with further research to strengthen the model accuracy and to help determine clinical relevance.


Subject(s)
Hypertension , Machine Learning , Male , Humans , Adolescent , Adult , Aged , Female , Retrospective Studies , Predictive Value of Tests , Comorbidity , Hypertension/diagnosis , Hypertension/drug therapy
10.
J Conserv Dent Endod ; 27(1): 29-35, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38389734

ABSTRACT

Aim: The study aimed to assess the remineralizing potential of four different commercially available agents using a Scanning Electron Microscope (SEM), energy dispersive X-ray (EDX) analysis, and Vickers Microhardness (VMH) Test. Materials and Methods: Forty-four specimens (n = 11 per group) were prepared from extracted teeth. A window of 6 mm × 4 mm was made on all the specimens that represented three zones, namely, sound enamel, demineralized enamel, and remineralized enamel. The zone for demineralized enamel was subjected to four different remineralizing agents; casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF), tricalcium phosphate fluoride (TCP-F), calcium sucrose phosphate (CSP), and self-assembling peptide (P11-4). Remineralization (REM) was assessed using VMH; the structural changes were assessed using SEM that was analyzed using EDX analysis. The specimens were subjected to a newer regimen of demineralization. One-way ANOVA followed by post hoc Tukey test was used with a level of significance at P ≤ 0.05. Results: There were no significant differences in VMH between the groups for sound enamel (P = 0.472) and demineralized enamel (P = 0.116). VMH was statistically significantly more for P11-4 and the least for CPP-ACPF (P = 0.011). A post hoc analysis revealed higher VMH for P11-4 compared to CPP-ACPF (P = 0.014) and TCP-F (P = 0.035). SEM showed a homogeneous layer of minerals for all groups except CPP-ACPF. TCP-F reported a higher degree of REM, followed by P11-4 as assessed using EDX analysis. Conclusion: Self-assembling peptide (P11-4) exhibited a higher degree of REM than other remineralizing agents followed by CSP.

11.
Mov Disord ; 39(3): 546-559, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38173297

ABSTRACT

BACKGROUND: Dementia is common in Parkinson's disease (PD), but there is wide variation in its timing. A critical gap in PD research is the lack of quantifiable markers of progression, and methods to identify early stages of dementia. Atrophy-based magnetic resonance imaging (MRI) has limited sensitivity in detecting or tracking changes relating to PD dementia, but quantitative susceptibility mapping (QSM), sensitive to brain tissue iron, shows potential for these purposes. OBJECTIVE: The objective of the paper is to study, for the first time, the longitudinal relationship between cognition and QSM in PD in detail. METHODS: We present a longitudinal study of clinical severity in PD using QSM, including 59 PD patients (without dementia at study onset), and 22 controls over 3 years. RESULTS: In PD, increased baseline susceptibility in the right temporal cortex, nucleus basalis of Meynert, and putamen was associated with greater cognitive severity after 3 years; and increased baseline susceptibility in basal ganglia, substantia nigra, red nucleus, insular cortex, and dentate nucleus was associated with greater motor severity after 3 years. Increased follow-up susceptibility in these regions was associated with increased follow-up cognitive and motor severity, with further involvement of hippocampus relating to cognitive severity. However, there were no consistent increases in susceptibility over 3 years. CONCLUSIONS: Our study suggests that QSM may predict changes in cognitive severity many months prior to overt cognitive involvement in PD. However, we did not find robust longitudinal changes in QSM over the course of the study. Additional tissue metrics may be required together with QSM for it to monitor progression in clinical practice and therapeutic trials. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Subject(s)
Alzheimer Disease , Parkinson Disease , Humans , Parkinson Disease/diagnostic imaging , Parkinson Disease/pathology , Longitudinal Studies , Basal Ganglia/pathology , Substantia Nigra/pathology , Magnetic Resonance Imaging/methods
12.
Nat Commun ; 15(1): 630, 2024 Jan 20.
Article in English | MEDLINE | ID: mdl-38245544

ABSTRACT

The fragile nature of quantum circuits is a major bottleneck to scalable quantum applications. Operating at cryogenic temperatures, quantum circuits are highly vulnerable to amplifier backaction and external noise. Non-reciprocal microwave devices such as circulators and isolators are used for this purpose. These devices have a considerable footprint in cryostats, limiting the scalability of quantum circuits. As a proof-of-concept, here we report a compact microwave diode architecture, which exploits the non-linearity of a superconducting flux qubit. At the qubit degeneracy point we experimentally demonstrate a significant difference between the power levels transmitted in opposite directions. The observations align with the proposed theoretical model. At - 99 dBm input power, and near the qubit-resonator avoided crossing region, we report the transmission rectification ratio exceeding 90% for a 50 MHz wide frequency range from 6.81 GHz to 6.86 GHz, and over 60% for the 250 MHz range from 6.67 GHz to 6.91 GHz. The presented architecture is compact, and easily scalable towards multiple readout channels, potentially opening up diverse opportunities in quantum information, microwave read-out and optomechanics.

13.
Plant Sci ; 340: 111972, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38176527

ABSTRACT

Little is known about the molecular basis of host defense in resistant wild species Zingiber zerumbet (L.) Smith against the soil-borne, necrotrophic oomycete pathogen Pythium myriotylum Drechsler, which causes the devastating soft rot disease in the spice crop ginger (Zingiber officinale Roscoe). We investigated the pattern of host defense between Z. zerumbet and ginger in response to P. myriotylum inoculation. Analysis of gene expression microarray data revealed enrichment of phenylpropanoid biosynthetic genes, particularly lignin biosynthesis genes, in pathogen-inoculated Z. zerumbet compared to ginger. RT-qPCR analysis showed the robust activation of phenylpropanoid biosynthesis genes in Z. zerumbet, including the core genes PAL, C4H, 4CL, and the monolignol biosynthesis and polymerization genes such as CCR, CAD, C3H, CCoAOMT, F5H, COMT, and LAC. Additionally, Z. zerumbet exhibited the accumulation of the phenolic acids including p-coumaric acid, sinapic acid, and ferulic acid that are characteristic of the cell walls of commelinoid monocots like Zingiberaceae and are involved in cell wall strengthening by cross linking with lignin. Z. zerumbet also had higher total lignin and total phenolics content compared to pathogen-inoculated ginger. Phloroglucinol staining revealed the enhanced fortification of cell walls in Z. zerumbet, specifically in xylem vessels and surrounding cells. The trypan blue staining indicated inhibition of pathogen growth in Z. zerumbet at the first leaf whorl, while ginger showed complete colonization of the pith within 36 h post inoculation (hpi). Accumulation of salicylic acid (SA) and induction of SA regulator NPR1 and the signaling marker PR1 were observed in Z. zerumbet. Silencing of PAL in Z. zerumbet through VIGS suppressed downstream genes, leading to reduced phenylpropanoid accumulation and SA level, resulting in the susceptibility of plants to P. myriotylum. These findings highlight the essential role of PAL-dependent mechanisms in resistance against P. myriotylum in Z. zerumbet. Moreover, our results suggest an unconventional role for SA in mediating host resistance against a necrotroph. Targeting the phenylpropanoid pathway could be a promising strategy for the effective management of P. myriotylum in ginger.


Subject(s)
Pythium , Zingiber officinale , Zingiberaceae , Pythium/genetics , Phenylalanine Ammonia-Lyase/genetics , Phenylalanine Ammonia-Lyase/pharmacology , Lignin , Salicylic Acid/pharmacology , Zingiberaceae/genetics
14.
J Oral Pathol Med ; 53(1): 53-60, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38081145

ABSTRACT

INTRODUCTION: A major pitfall of many of the established oral epithelial dysplasia (OED) grading criteria is their lack of reproducibility and accuracy to predict malignant transformation. The main objective of this study was to determine whether calibration of practicing oral pathologists on OED grading could improve the reproducibility of the WHO 2017 and the binary OED grading systems. METHODS: A nationwide online exercise was carried out to determine the influence of calibration on the reproducibility of the WHO 2017 and the binary OED grading systems. RESULTS: A significant improvement was observed in the inter-observer agreement for the WHO 2017 OED grading system (K 0.196 vs. 0.448; Kw 0.357 vs. 0.562) after the calibration exercise. The significant difference (p = 0.027) in the level of agreement between those with five or more years and less than 5 years of experience was no more observed (p = 0.426) after the calibration exercise. The percent agreement for binary grading was significantly higher (91.8%) for buccal mucosal lesions as compared to lesions on the tongue after the calibration exercise. CONCLUSION: This study validates the significance of calibration in improving the reproducibility of OED grading. The nationwide exercise resulted in a statistically significant improvement in the inter-observer agreement for the WHO 2017 OED grading system among a large number of oral pathologists. It is highly recommended that similar exercises should be organized periodically by professional bodies responsible for continuing education among oral pathologists to improve the reliability of OED grading for optimal treatment of oral potentially malignant disorders.


Subject(s)
Mouth Neoplasms , Precancerous Conditions , Humans , Reproducibility of Results , Mouth Neoplasms/pathology , Mouth Mucosa/pathology , Malaysia , Calibration , Precancerous Conditions/pathology , Hyperplasia/pathology , Organic Chemicals
15.
JACC Clin Electrophysiol ; 10(2): 235-248, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38069971

ABSTRACT

BACKGROUND: Limited data exist about the origins and mechanisms of atypical atrial flutter that occurs in the absence of prior ablation or surgery. OBJECTIVES: The aims of this study were to report a large cohort of patients who presented for catheter ablation of de novo atypical flutters, to identify the most common locations and mechanisms of arrhythmia, and to describe outcomes after ablation. METHODS: Demographic, electrophysiological, and outcome data were collected for patients who underwent ablation of de novo atypical flutter. RESULTS: The mechanisms of 85 atypical flutters were identified in 62 patients and localized to the left atrium (LA) in 58 and right atrium (RA) in 27. In the LA, mechanisms were classified as macro-re-entry in 29 (50%) and localized re-entry in 29 (50%), whereas in the RA, mechanisms were macro-re-entry in 8 (30%) and localized re-entry in 19 (70%) (proportion of localized re-entry in the LA vs. RA, P = 0.08). Nine patients had both localized and macro-re-entrant atypical flutters. In the LA, localized re-entry was commonly found in the anterior LA, followed by the pulmonary veins and septum. In the RA, localized re-entry was found at various sites, including the lateral or posterior RA, septum, and coronary sinus ostium. During 39.4 months (Q1-Q3: 18.2-65.8 months) of follow-up, atrial arrhythmias occurred in 66% of patients after a single ablation and in 50% after >1 ablation. Among patients who underwent repeat ablation, compared with the index arrhythmia, different tachycardia circuits or arrhythmias were documented in 13 of 18 cases (72%). CONCLUSIONS: Atypical atrial flutters in patients without prior surgery or complex ablation are often due to localized re-entry (approximately 50% in the LA and a higher frequency in the RA). Other atrial tachycardias commonly occur during long-term follow-up following ablation, suggesting progressive atrial myopathy in these patients.


Subject(s)
Atrial Flutter , Catheter Ablation , Tachycardia, Supraventricular , Humans , Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/surgery , Arrhythmias, Cardiac/etiology , Atrial Flutter/epidemiology , Atrial Flutter/surgery , Tachycardia , Heart Atria/surgery , Catheter Ablation/adverse effects
16.
Nat Hum Behav ; 8(1): 82-99, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37957284

ABSTRACT

The influence of electronic screens on the health of children and adolescents and their education is not well understood. In this prospectively registered umbrella review (PROSPERO identifier CRD42017076051 ), we harmonized effects from 102 meta-analyses (2,451 primary studies; 1,937,501 participants) of screen time and outcomes. In total, 43 effects from 32 meta-analyses met our criteria for statistical certainty. Meta-analyses of associations between screen use and outcomes showed small-to-moderate effects (range: r = -0.14 to 0.33). In education, results were mixed; for example, screen use was negatively associated with literacy (r = -0.14, 95% confidence interval (CI) = -0.20 to -0.09, P ≤ 0.001, k = 38, N = 18,318), but this effect was positive when parents watched with their children (r = 0.15, 95% CI = 0.02 to 0.28, P = 0.028, k = 12, N = 6,083). In health, we found evidence for several small negative associations; for example, social media was associated with depression (r = 0.12, 95% CI = 0.05 to 0.19, P ≤ 0.001, k = 12, N = 93,740). Limitations of our review include the limited number of studies for each outcome, medium-to-high risk of bias in 95 out of 102 included meta-analyses and high heterogeneity (17 out of 22 in education and 20 out of 21 in health with I2 > 50%). We recommend that caregivers and policymakers carefully weigh the evidence for potential harms and benefits of specific types of screen use.


Subject(s)
Parents , Child , Humans , Adolescent , Bias , Risk Assessment
17.
JACC Clin Electrophysiol ; 10(2): 379-401, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38127010

ABSTRACT

Most forms of sustained ventricular tachycardia (VT) are caused by re-entry, resulting from altered myocardial conduction and refractoriness secondary to underlying structural heart disease. In contrast, VT caused by triggered activity (TA) is unrelated to an abnormal structural substrate and is often caused by molecular defects affecting ion channel function or regulation of intracellular calcium cycling. This review summarizes the cellular and molecular bases underlying TA and exemplifies their clinical relevance with selective representative scenarios. The underlying basis of TA caused by delayed afterdepolarizations is related to sarcoplasmic reticulum calcium overload, calcium waves, and diastolic sarcoplasmic reticulum calcium leak. Clinical examples of TA caused by delayed afterdepolarizations include sustained right and left ventricular outflow tract tachycardia and catecholaminergic polymorphic VT. The other form of afterpotentials, early afterdepolarizations, are systolic events and inscribe early afterdepolarizations during phase 2 or phase 3 of the action potential. The fundamental defect is a decrease in repolarization reserve with associated increases in late plateau inward currents. Malignant ventricular arrhythmias in the long QT syndromes are initiated by early afterdepolarization-mediated TA. An understanding of the molecular and cellular bases of these arrhythmias has resulted in generally effective pharmacologic-based therapies, but these are nonspecific agents that have off-target effects. Therapeutic efficacy may need to be augmented with an implantable defibrillator. Next-generation therapies will include novel agents that rescue arrhythmogenic abnormalities in cellular signaling pathways and gene therapy approaches that transfer or edit pathogenic gene variants or silence mutant messenger ribonucleic acid.


Subject(s)
Calcium , Tachycardia, Ventricular , Humans , Calcium/metabolism , Calcium/therapeutic use , Arrhythmias, Cardiac , Heart , Myocardium/pathology
18.
J Pediatr Orthop ; 44(3): e303-e309, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38145392

ABSTRACT

BACKGROUND: Analysis of industry payments to pediatric orthopaedic surgeons last occurred in 2017. We investigated payments to pediatric orthopaedic surgeons from 2015 to 2021 to understand surgeon characteristics associated with increased industry payments. METHODS: Open Payments Database datasets from 2015 to 2021 were queried for nonresearch payments to pediatric orthopaedic surgeons. Annual aggregates and subcategories were recorded. For surgeons receiving payments in 2021, the Hirsch index (h-index), gender, and US census division were found using the Scopus database, Open Payments Database, and online hospital profiles, respectively. χ 2 , Fisher exact, Mann-Whitney U , and t tests were used to compare surgeons in the top 25%, 10%, and 5% payment percentiles to the bottom 75%, 90%, and 95%, respectively. RESULTS: Payments rose 125% from 2015 to 2021. Education, royalties, and faculty/speaker increased most, while travel/lodging, honoraria, charitable contributions, and ownership interest decreased. Only royalties increased from 2019 to 2021. In 2021, of 419 pediatric orthopaedic surgeons receiving industry payments, men received greater median aggregate payments than women ($379.03 vs. $186.96, P =0.047). There were no differences in gender proportions between the top 75% and bottom 25% ( P =0.054), top 10% and bottom 90% ( P =0.235), and top 5% and bottom 95% ( P =0.280) earning comparison groups. The h-index was weakly positively correlated with industry payments ( rs =0.203, P <0.001). Mean h-indices in the 75th ( P <0.001, 95% CI: 2.62-7.65), 90th ( P =0.001, 95% CI: 3.28-13.03), and 95th ( P =0.005, 95% CI: 4.25-21.11) percentiles were significantly higher. Proportions of surgeons from the Middle Atlantic and West South Central in the 90th ( P =0.025) and 95th percentiles ( P =0.033), respectively, were significantly lower compared to all other regions. A higher proportion of surgeons from the Pacific were placed in the 90th ( P =0.004) and 95th ( P =0.024) percentiles. CONCLUSIONS: Industry payments to pediatric orthopaedic surgeons rose from 2015 to 2021. Most categories fell from 2019 to 2021, which may be related to the SARS-CoV-19 pandemic. In 2021, though gender was not related to aggregate payment percentile, location in select US census divisions and h-index was. LEVEL OF EVIDENCE: Level II-Retrospective study.


Subject(s)
Orthopedic Surgeons , Orthopedics , Surgeons , Male , Humans , Female , Child , United States , Retrospective Studies , Industry , Databases, Factual , Conflict of Interest
20.
Nat Commun ; 14(1): 7924, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38040683

ABSTRACT

The Josephson junction is a building block of quantum circuits. Its behavior, well understood when treated as an isolated entity, is strongly affected by coupling to an electromagnetic environment. In 1983, Schmid predicted that a Josephson junction shunted by a resistance exceeding the resistance quantum RQ = h/4e2 ≈ 6.45 kΩ for Cooper pairs would become insulating since the phase fluctuations would destroy the coherent Josephson coupling. However, recent microwave measurements have questioned this interpretation. Here, we insert a small Josephson junction in a Johnson-Nyquist-type setup where it is driven by weak current noise arising from thermal fluctuations. Our heat probe minimally perturbs the junction's equilibrium, shedding light on features not visible in charge transport. We find that the Josephson critical current completely vanishes in DC charge transport measurement, and the junction demonstrates Coulomb blockade in agreement with the theory. Surprisingly, thermal transport measurements show that the Josephson junction acts as an inductor at high frequencies, unambiguously demonstrating that a supercurrent survives despite the Coulomb blockade observed in DC measurements.

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