Designing a Workplace-Based Learning Environment for Learning Health Promotion: A Design-Based Research.

Introduction: The healthcare landscape has a growing emphasis on health promotion (HP), which makes HP important in the training of future physicians. This study employed design-based research to develop a clerkship focused on HP and to outline design principles for shaping workplace learning environments to promote HP learning. Methods: We evaluated a nursing-home clerkship designed at Radboud University Medical Center in the Netherlands, and refined it over three rounds. Data collection involved individual and group interviews with students and supervisors, as well as observations during clerkship-related meetings and activities. These interactions also facilitated the exchange of perspectives between participants and generation of new design ideas, fostering co-creation of the clerkship design. Data were analyzed through iterative thematic inquiry to inform new design choices and develop design principles. Results: Evolved clerkship designs included an app for capturing practice experiences to discuss in relation to students' professional roles, loosening the strict assessment structure, and collaborative creation of a practice assignment about 'Positive Health'. We constructed four design principles, including: to question and discuss students' professional identity, provide concrete and meaningful assignments, aim for a peer-learner role for supervisors, and foster co-creation of the workplace learning environment. Discussion: Our design principles support the design of workplace-based learning for HP, a subject that is novel within healthcare practice. We find that co-creation of workplace-based learning, which requires embracing uncertainty, is pivotal in this context, for students, practitioners, and educational institutions.

Generation of two induced pluripotent stem cell lines (HIMRi006-A and HIMRi007-A) from Pompe patients with infantile and late disease onset.

Here we present the generation of HIMRi006-A and HIMRi007-A Pompe disease (PD) patient derived human induced pluripotent stem cell (hiPSC) lines. HIMRi006-A represents an infantile onset disease (IOPD) phenotype caused by a homozygous c.307 T > G mutation in the GAA gene. HIMRi007-A is characterized by heterozygous mutations c.-32-13 T > G/c.1716C > G and is associated with an adult onset of disease symptoms (LOPD). Both lines are generated via lentiviral expression of OCT4, SOX2, KLF4, and c-MYC. The lines display a typical embryonic stem cell morphology, express pluripotency markers, retain a normal karyotype (46, XX/XY) and have the differentiation capacity in all three germ layers. Altogether, both lines provide a resource tool to the community for future in depth molecular studies of PD pathomechanism.

Coronary calcifications as assessed on routine non-gated chest CT; a gatekeeper to tailor downstream additional imaging in patients with stable chest pain.

Background and aims: Currently applied methods for risk-assessment in coronary artery disease (CAD) often overestimate patients' risk for obstructive CAD. To enhance risk estimation, assessment of coronary artery calcium (CAC) can be applied. In 10 % of patients presenting with stable chest pain a previous non-gated computed tomography (CT) has been performed, suitable for CAC-assessment. This study is the first to investigate the clinical utility of CAC-assessment on non-gated CT for risk-assessment of obstructive CAD in symptomatic patients. Methods: For this analysis, all patients referred for coronary computed tomography angiography (CCTA), in whom a previous non-gated chest CT was performed were included. The extent of CAC was assessed on chest CT and ordinally scored. CAD was assessed on CCTA and obstructive CAD defined as stenosis of ≥70 %. Patients were stratified according to CAC-severity and percentages of patients with obstructive CAD were compared between the CAC groups. Results: In total, 170 patients of 32-88 years were included and 35 % were male. The percentage of obstructive CAD between the CAC groups differed significantly (p < 0.01). A calcium score of 0 ruled out obstructive CAD irrespective of sex, pre-test probability, type of complaints and number of risk factors with a 100 % certainty. Furthermore, a mild CAC score ruled out obstructive CAD in patients with low - intermediate PTP or non-anginal complaints with 100 % certainty. Conclusion: When available, CAC on non-gated chest CT can accurately rule out obstructive CAD and can therefore function as a radiation-free and cost-free gatekeeper for additional imaging in patients presenting with stable chest pain.

Hippocampus, amygdala, and insula activation in response to romantic relationship dissolution stimuli: A case-case-control fMRI study on emerging adult students.

BACKGROUND: Romantic relationship dissolutions (RRDs) are associated with posttraumatic stress symptoms (PTSS). Functional magnetic resonance imaging in RRD studies indicate overlapping neural activation similar to posttraumatic stress disorder. These studies combine real and hypothetical rejection, and lack contextual information and control and/or comparison groups exposed to non-RRD or DSM-5 defined traumatic events. AIM: We investigated blood oxygen level dependent (BOLD) activation in the hippocampus, amygdala, and insula of participants with RRDs compared with other traumatic or non-trauma stressors. METHODS: Emerging adults (mean age = 21.54 years; female = 74.7 %) who experienced an RRD (n = 36), DSM-5 defined trauma (physical and/or sexual assault: n = 15), or a non-RRD or DSM-5 stressor (n = 28) completed PTSS, depression, childhood trauma, lifetime trauma exposure, and attachment measures. We used a general and customised version of the International Affective Picture System to investigate responses to index-trauma-related stimuli. We used mixed linear models to assess between-group differences, and ANOVAs and Spearman's correlations to analyse factors associated with BOLD activation. RESULTS: BOLD activity increased between index-trauma stimuli as compared to neutral stimuli in the hippocampus and amygdala, with no significant difference between the DSM-5 Trauma and RRD groups. Childhood adversity, sexual orientation, and attachment style were associated with BOLD activation changes. Breakup characteristics (e.g., initiator status) were associated with increased BOLD activation in the hippocampus and amygdala, in the RRD group. CONCLUSION: RRDs should be considered as potentially traumatic events. Breakup characteristics are risk factors for experiencing RRDs as traumatic. LIMITATION: Future studies should consider more diverse representation across sex, ethnicity, and sexual orientation.

Coronary artery calcium assessment on non-gated chest CT to optimize pre-operative cardiac screening in liver transplantation.

BACKGROUND: Guidelines recommend standard pre-operative cardiac screening in all liver transplantation (LT) recipients, despite the relatively low prevalence of obstructive coronary artery disease. Most LT recipients often have non-gated computed tomography (CT) performed of the chest and abdomen. This study evaluated the ability of coronary artery calcification (CAC) assessment on consecutively available scans, to identify a selection of low-risk patients, in whom further cardiac imaging can be safely withheld. METHODS: LT recipients with prior non-gated CT chest-abdomen were included. CAC was visually scored on a semi-quantitative ordinal scale. Stress myocardial perfusion, coronary CT angiography (CCTA) and invasive coronary angiography (ICA) were used as golden standard. The sensitivity and specificity of CAC to exclude and predict obstructive CAD were assessed. In addition, peri- and postoperative mortality and cardiac events were analyzed. RESULTS: 149 LT recipients (ranged 31-71 years) were included. In 75% of patients, no CAC and mild CAC could rule out obstructive CAD on CCTA and ICA with 100% certainty. The threshold of mild CAC had a sensitivity of 100% for both CCTA and ICA and a specificity of 91% and 68%, respectively. None of the patients with no or mild calcifications experienced peri- and post-operative cardiac events or died of cardiac causes. CONCLUSION: Visual evaluation of CAC on prior non-gated CT can accurately and safely exclude obstructive CAD in LT recipients. Incorporation of these already available data can optimize cardiac screening, by safely withholding or correctly allocating dedicated cardiac imaging in LT recipients. Thereby, reducing patients' test burden and save health care expenses.

Prenatal alcohol exposure and white matter microstructural changes across the first 6-7 years of life: A longitudinal diffusion tensor imaging study of a South African birth cohort.

Prenatal alcohol exposure (PAE) can affect brain development in early life, but few studies have investigated the effects of PAE on trajectories of white matter tract maturation in young children. Here we used diffusion weighted imaging (DWI) repeated over three time points, to measure the effects of PAE on patterns of white matter microstructural development during the pre-school years. Participants were drawn from the Drakenstein Child Health Study (DCHS), an ongoing birth cohort study conducted in a peri-urban community in the Western Cape, South Africa. A total of 342 scans acquired from 237 children as neonates (N = 82 scans: 30 PAE; 52 controls) and at ages 2-3 (N = 121 scans: 27 PAE; 94 controls) and 6-7 years (N = 139 scans: 45 PAE; 94 controls) were included. Maternal alcohol use during pregnancy and other antenatal covariates were collected from 28 to 32 weeks' gestation. Linear mixed effects models with restricted maxium likelihood to accommodate missing data were implemented to investigate the effects of PAE on fractional anisotropy (FA) and mean diffusivity (MD) in specific white matter tracts over time, while adjusting for child sex and maternal education. We found significant PAE-by-time effects on trajectories of FA development in the left superior cerebellar peduncle (SCP-L: p = 0.001; survived FDR correction) and right superior longitudinal fasciculus (SLF-R: p = 0.046), suggesting altered white matter development among children with PAE. Compared with controls, children with PAE demonstrated a more rapid change in FA in these tracts from the neonatal period to 2-3 years of age, followed by a more tapered trajectory for the period from 2-3 to 6-7 years of age, with these trajectories differing from unexposed control children. Given their supporting roles in various aspects of neurocognitive functioning (i.e., motor regulation, learning, memory, language), altered patterns of maturation in the SCP and SLF may contribute to a spectrum of physical, social, emotional, and cognitive difficulties often experienced by children with PAE. This study highlights the value of repeated early imaging in longitudinal studies of PAE, and focus for early childhood as a critical window of potential susceptibility as well as an opportunity for early intervention.

Generation of two hiPSCs lines of two patients carrying truncating mutations in the dimerization domain of filamin C.

Here we introduce the human induced pluripotent stem cell lines (hiPSCs), HIMRi004-A and HIMRi005-A from dermal fibroblasts of a 48-year-old female (HIMRi004-A) carrying missense mutation that translate to the first described filamin C isoform p.W2710X and from a 56-year-old female (HIMRi005-A) carrying a recently described mutation in the same domain p.Y2704X. Both lines are generated via lentiviral expression of OCT4, SOX2, KLF4 and c-MYC. The lines display a typical embryonic stem cell-like morphology, express pluripotency markers, retain a normal karyotype (46, XX) and have the differentiation capacity in all three germ layers. The two lines can be used to elucidate the pathomechanisms of FLNC myofibrillar myopathies and to develop novel therapeutic options.

The Clear Value of Coronary Artery Calcification Evaluation on Non-Gated Chest Computed Tomography for Cardiac Risk Stratification.

To enhance risk stratification in patients suspected of coronary artery disease, the assessment of coronary artery calcium (CAC) could be incorporated, especially when CAC can be readily assessed on previously performed non-gated chest computed tomography (CT). Guidelines recommend reporting on patients' extent of CAC on these non-cardiac directed exams and various studies have shown the diagnostic and prognostic value. However, this method is still little applied, and no current consensus exists in clinical practice. This review aims to point out the clinical utility of different kinds of CAC assessment on non-gated CTs. It demonstrates that these scans indeed represent a merely untapped and underestimated resource for risk stratification in patients with stable chest pain or an increased risk of cardiovascular events. To our knowledge, this is the first review to describe the clinical utility of different kinds of visual CAC evaluation on non-gated unenhanced chest CT. Various methods of CAC assessment on non-gated CT are discussed and compared in terms of diagnostic and prognostic value. Furthermore, the application of these non-gated CT scans in the general practice of cardiology is discussed. The clinical utility of coronary calcium assessed on non-gated chest CT, according to the current literature, is evident. This resource of information for cardiac risk stratification needs no specific requirements for scan protocol, and is radiation-free and cost-free. However, some gaps in research remain. In conclusion, the integration of CAC on non-gated chest CT in general cardiology should be promoted and research on this method should be encouraged.

Validity of the ACS NSQIP surgical risk calculator as a tool to predict postoperative outcomes in subacute orthopedic trauma diagnoses.

Purpose: This retrospective study aimed to validate the ACS NSQIP Surgical Risk Calculator (SCR) to predict 30-day postoperative outcomes in patients with one of the following subacute orthopedic trauma diagnoses; multiple rib fractures, pelvic ring/acetabular fracture, or unilateral femoral fracture. Methods: Data of patients with these diagnoses treated between January 1, 2015 and September 19, 2020 were extracted from the patients' medical files. Diagnostic performance, discrimination, calibration, and accuracy of the ACS NSQIP SRC to predict specific outcomes developing within 30 days after surgery was determined. Results: The total cohort of the three diagnoses consisted of 435 patients. ACS NSQIP SRC underestimated the risk for serious complications, especially in patients with multiple rib fractures (8.3% predicted vs 17.2% observed) or pelvic ring/acetabular fracture (6.1% vs 19.8%). Underestimation was more pronounced for the composite outcome 'any complication'. Sensitivity ranged from 16.7% to 100% and specificity from 41.1% to 97.1%. Specificity exceeded sensitivity for pelvic ring/acetabular and femoral fractures. Discrimination was good for predicting death (femoral fracture), fair for readmission (femoral fracture), serious complication (multiple rib fractures), and any complication (multiple rib fractures), but poor in all other outcomes and diagnoses. Calibration and accuracy were adequate for all three diagnoses (p-value for Hosmer-Lemeshow test >0.05 and Brier scores <0.25). Conclusion: Performance of the ACS NSQIP SRC in the studied cohort was variable for all three diagnoses. Although it underestimated the risk of most outcomes, calibration and accuracy seemed generally adequate. For most outcomes, adequate diagnostic performance and discrimination could not be confirmed.

Evaluation of Clinical Applicability of Coronary Artery Calcium Assessment on Non-Gated Chest Computed Tomography, Compared With the Classic Agatston Score on Cardiac Computed Tomography.

Given current pretest probability (PTP) estimations tend to overestimate patients' risk for obstructive coronary artery disease, evaluation of patients' coronary artery calcium (CAC) is more precise. The value of CAC assessment with the Agatston score on cardiac computed tomography (CT) for risk estimation has been well indicated in patients with stable chest pain. CAC can be equally well assessed on routine non-gated chest CT, which is often available. This study aims to determine the clinical applicability of CAC assessment on non-gated CT in patients with stable chest pain compared with the classic Agatston score on gated CT. Consecutive patients referred for evaluation of the Agatston score, who had a previously performed non-gated chest CT for evaluation of noncardiac diseases, were included. CAC on non-gated CT was ordinally scored. Subsequently, patients were stratified according to CAC severity and PTP. The agreement and correlation between the classic Agatston score and CAC on non-gated CT were evaluated. The discriminative power for risk reclassification of both CAC assessment methods was assessed. Invasive coronary angiography was used as the gold standard, when available. A total of 140 patients aged between 30 and 88 years were included. The agreement between ordinally scored CAC and the Agatston score was excellent (κ = 0.82) and the correlation strong (r = 0.94). Most patients (80%) with an intermediate PTP had no or mild CAC on non-gated CT. They were reclassified at low risk with 100% accuracy compared with invasive coronary angiography. Similarly, 86% of patients had an Agatston score <300. These patients were reclassified with 98% accuracy. In patients with high PTP, the accuracy remained substantial and comparable, 94% and 89%, respectively. In conclusion, we believe this is the first study to assess the clinical applicability of CAC on non-gated CT in patients with stable chest pain, compared with the classic Agatston score. The agreement between methods was excellent and the correlation strong. Furthermore, CAC assessment on non-gated CT could reclassify patients' risk for obstructive coronary artery disease as accurately as could the classic Agatston score.

Generation of two human iPSC lines (HIMRi002-A and HIMRi003-A) derived from Caveolinopathy patients with rippling muscle disease.

Here we introduce the human induced pluripotent stem cell lines (hiPSCs), HIMRi002-A and HIMRi003-A, generated from cultured dermal fibroblasts of 61-year-old (HIMRi002-A) and 38-year-old (HIMRi003-A) female patients, carrying a known heterozygous pathogenic variant (p.A46T) in the Caveolin 3 (CAV3) gene, via lentiviral expression of OCT4, SOX2, KLF4 and c-MYC. HIMRi002-A and HIMRi003-A display typical embryonic stem cell-like morphology, carry the p.A46T CAV3 gene mutation, express several pluripotent stem cell markers, retain normal karyotype (46, XX) and can differentiate in all three germ layers. We postulate that the HIMRi002-A and HIMRi003-A iPSC lines can be used for the characterization of CAV3-associated pathomechanisms and for developing new therapeutic options.

Generation of a human iPSC line (HIMRi001-A) from a patient with filaminopathy.

Here we introduce the human induced pluripotent stem cell (hiPSC) line HIMRi001-A generated from cultured dermal fibroblasts of a 60-year-old male patient with a myofibrillar myopathy, carrying a heterozygous c.4984C > T [p.Q1662X] mutation in the filamin C (FLNC)-gene, via lentiviral expression of OCT4, SOX2, KLF4 and c-MYC. HIMRi001-A displays typical embryonic stem cell-like morphology, carries the c.4984C > T FLNC gene mutation, expressed several pluripotent stem cell makers, retained normal karyotype (46, XY) and holds the potential to differentiate in all three germ layers. We postulate that HIMRi001-A can be used for the elucidation of FLNC-associated pathomechanisms and for developing new therapeutic options.

Re-Exploring the Anthracycline Chemical Space for Better Anti-Cancer Compounds.

The anthracycline anti-cancer drugs are intensely used in the clinic to treat a wide variety of cancers. They generate DNA double strand breaks, but recently the induction of chromatin damage was introduced as another major determinant of anti-cancer activity. The combination of these two events results in their reported side effects. While our knowledge on the structure-activity relationship of anthracyclines has improved, many structural variations remain poorly explored. Therefore, we here report on the preparation of a diverse set of anthracyclines with variations within the sugar moiety, amine alkylation pattern, saccharide chain and aglycone. We assessed the cytotoxicity in vitro in relevant human cancer cell lines, and the capacity to induce DNA- and chromatin damage. This coherent set of data allowed us to deduce a few guidelines on anthracycline design, as well as discover novel, highly potent anthracyclines that may be better tolerated by patients.

Proactively Adjusting Stopping: Response Inhibition is Faster when Stopping Occurs Frequently.

People are able to stop actions before they are executed, and proactively slow down the speed of going in line with their expectations of needing to stop. Such slowing generally increases the probability that stopping will be successful. Surprisingly though, no study has clearly demonstrated that the speed of stopping (measured as the stop-signal reaction time, SSRT) is reduced by such proactive adjustments. In addition to a number of studies showing non-significant effects, the only study that initially had observed a clear effect in this direction found that it was artifactually driven by a confounding variable (specifically, by context-independence violations, which jeopardize the validity of the SSRT estimation). Here, we tested in two well-powered and well-controlled experiments whether the SSRT is shorter when stopping is anticipated. In each experiment, we used a Stop-Signal Task, in which the stop-trial frequency was either high (50%) or low (20%). Our results robustly show that the SSRT was shorter when stop signals were more anticipated (i.e., in the high-frequent condition) while carefully controlling for context-independence violations. Hence, our study is first to demonstrate a clear proactive benefit on the speed of stopping, in line with an ability to emphasize going or stopping, by trading off the speed of both.

Meningococcal ACWY conjugate vaccine immunogenicity and safety in adolescents with juvenile idiopathic arthritis and inflammatory bowel disease: A prospective observational cohort study.

BACKGROUND: Immunogenicity to meningococcal serogroup ACWY (MenACWY) conjugate vaccine has not been studied in immunocompromised minors with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD). We determined immunogenicity of a MenACWY-TT vaccine in JIA and IBD patients at adolescent age and compared results to data from aged-matched healthy controls (HCs). METHODS: We performed a prospective observational cohort study in JIA and IBD patients (14-18 years old), who received a MenACWY vaccination during a nationwide catch-up campaign (2018-2019) in the Netherlands. Primary aim was to compare MenACWY polysaccharide-specific serum IgG geometric mean concentrations (GMCs) in patients with HCs and secondary between patients with or without anti-TNF therapy. GMCs were determined before and 3-6, 12, and 24 months postvaccination and compared with data from HCs at baseline and 12 months postvaccination. Serum bactericidal antibody (SBA) titers were determined in a subset of patients at 12 months postvaccination. RESULTS: We included 226 JIA and IBD patients (66 % and 34 % respectively). GMCs were lower for MenA and MenW (GMC ratio 0·24 [0·17-0·34] and 0·16 [0·10-0·26] respectively, p < 0·01) in patients compared to HCs at 12 months postvaccination. Anti-TNF users had lower MenACWY GMCs postvaccination compared with those without anti-TNF (p < 0·01). The proportion protected (SBA ≥ 8) for MenW was reduced in anti-TNF users (76 % versus 92 % in non-anti-TNF and 100 % in HCs, p < 0.01). CONCLUSION: The MenACWY conjugate vaccine was immunogenic in the vast majority of JIA and IBD patients at adolescent age, but seroprotection was lower in patients using anti-TNF agents. Therefore, an extra booster MenACWY vaccination should be considered.

Implementing a newly prescribed cardiovascular medicine in daily routine: The patient perspective at readmission to primary care.

BACKGROUND: Readmission to primary care is challenging for patients due to involvement of multiple healthcare providers across different settings and implementing new medicines into their daily routine. Elucidating patients' needs is crucial to tailor counseling support. OBJECTIVE: To explore the patient perspectives on implementing a newly prescribed cardiovascular medicine into their daily routine at readmission to primary care. METHODS: A qualitative study was performed within the outpatient pharmacy. Adult patients who were prescribed a new cardiovascular medicine by their treating hospital physician at hospital discharge or during an outpatient clinic visit were eligible to participate. Purposive sampling was applied to equally distribute adherence-influencing factors. Patients were interviewed by telephone and inclusion continued until theoretical data saturation. An adapted Greenhalgh framework for implementation research was used for a thematic content analysis by conceptualizing the new medicine as an innovation that requires implementation by a patient (adopter). RESULTS: Data saturation was reached at 44 patients of which 19 discontinued their new medicine at the time of the interview. Reasons for discontinuing included: side-effects, insufficient efficacy or negligence. Patients considered a lack of basic knowledge on their newly prescribed cardiovascular medicine as a major barrier for adopting it into their daily routine. They were in need of information on risks and benefits of their new medicine. A noticeable effect and tailored counseling facilitated patients in taking their medicine as prescribed. Patients mentioned personalized organizing tools and routinization of medication intake as important success factors for addressing their practical challenges with their new medicine. CONCLUSIONS: By applying the adapted Greenhalgh framework, this study provided a unique and structured insight in patients' barriers and facilitators that could influence their ability to implement a new cardiovascular medicine at readmission to primary care. This knowledge enables pharmacists to tailor their patient support and provide individualized patient counseling.

A developmental delay linked missense mutation in Kalirin-7 disrupts protein function and neuronal morphology.

The Rac1 guanine exchange factor Kalirin-7 is a key regulator of dendritic spine morphology, LTP and dendritic arborization. Kalirin-7 dysfunction and genetic variation has been extensively linked to various neurodevelopmental and neurodegenerative disorders. Here we characterize a Kalirin-7 missense mutation, glu1577lys (E1577K), identified in a patient with severe developmental delay. The E1577K point mutation is located within the catalytic domain of Kalirin-7, and results in a robust reduction in Kalirin-7 Rac1 Guanosine exchange factor activity. In contrast to wild type Kalirin-7, the E1577K mutant failed to drive dendritic arborization, spine density, NMDAr targeting to, and activity within, spines. Together these results indicate that reduced Rac1-GEF activity as result of E1577K mutation impairs neuroarchitecture, connectivity and NMDAr activity, and is a likely contributor to impaired neurodevelopment in a patient with developmental delay.

A Network of Serum Proteins Predict the Need for Systemic Immunomodulatory Therapy at Diagnosis in Noninfectious Uveitis.

Purpose: Early identification of patients with noninfectious uveitis requiring steroid-sparing immunomodulatory therapy (IMT) is currently lacking in objective molecular biomarkers. We evaluated the proteomic signature of patients at the onset of disease and associated proteomic clusters with the need for IMT during the course of the disease. Design: Multicenter cohort study. Participants: Two hundred thirty treatment-free patients with active noninfectious uveitis. Methods: We used aptamer-based proteomics (n = 1305 proteins) and a bioinformatic pipeline as a molecular stratification tool to define the serum protein network of a Dutch discovery cohort (n = 78) of patients and healthy control participants and independently validated our results in another Dutch cohort (n = 111) and a United States cohort (n = 67). Multivariate Cox analysis was used to assess the relationship between the protein network and IMT use. Main Outcome Measures: Serum protein levels and use of IMT. Results: Network-based analyses revealed a tightly coexpressed serum cluster (n = 85 proteins) whose concentration was consistently low in healthy control participants (n = 26), but varied among patients with noninfectious uveitis (n = 52). Patients with high levels of the serum cluster at disease onset showed a significantly increased need for IMT during follow-up, independent of anatomic location of uveitis (hazard ratio, 3.42; 95% confidence interval, 1.22-9.5; P = 0.019). The enrichment of neutrophil-associated proteins in the protein cluster led to our finding that the neutrophil count could serve as a clinical proxy for this proteomic signature (correlation: r = 0.57, P = 0.006). In an independent Dutch cohort (n = 111), we confirmed that patients with relatively high neutrophil count at diagnosis (> 5.2 × 109/L) had a significantly increased chance of requiring IMT during follow-up (hazard ratio, 3.2; 95% confidence interval, 1.5-6.8; P = 0.002). We validated these findings in a third cohort of 67 United States patients. Conclusions: A serum protein signature correlating with neutrophil levels was highly predictive for IMT use in noninfectious uveitis. We developed a routinely available tool that may serve as a novel objective biomarker to aid in clinical decision-making for noninfectious uveitis.

Formation and relaxation of K-2 and K-2V double-core-hole states in n-butane.

Using a magnetic bottle multi-electron time-of-flight spectrometer in combination with synchrotron radiation, double-core-hole pre-edge and continuum states involving the K-shell of the carbon atoms in n-butane (n-C4H10) have been identified, where the ejected core electron(s) and the emitted Auger electrons from the decay of such states have been detected in coincidence. An assignment of the main observed spectral features is based on the results of multi-configurational self-consistent field (MCSCF) calculations for the excitation energies and static exchange (STEX) calculations for energies and intensities. MCSCF results have been analyzed in terms of static and dynamic electron relaxation as well as electron correlation contributions to double-core-hole state ionization potentials. The analysis of applicability of the STEX method, which implements the one-particle picture toward the complete basis set limit, is motivated by the fact that it scales well toward large species. We find that combining the MCSCF and STEX techniques is a viable approach to analyze double-core-hole spectra.