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Abstract A straightforward nebulized spray system is designed to explore the hydrogenation of carbon dioxide (CO2) within water microdroplets surrounded by different gases such as carbon dioxide, nitrogen, oxygen, and compressed air. The collected droplets are analyzed using water‐suppressed nuclear magnetic resonance (NMR). Formate anion (HCOO−), acetate anion (CH3COO−), ethylene glycol (HOCH2CH2OH), and methane (CH4) are detected when water is nebulized. This pattern persisted when the water is saturated with CO2, indicating that CO2 in the nebulizing gas triggers the formation of these small organics. In a pure CO2 atmosphere, the formate anion concentration is determined to be ≈70 µm, referenced to dimethyl sulfoxide, which has been introduced as an internal standard in the collected water droplets. This study highlights the power of water microdroplets to initiate unexpected chemistry for the transformation of CO2 to small organic compounds.

Abstract Various erythropoietic abnormalities are highly prevalent among patients with pulmonary arterial hypertension (PAH) and associated with worse disease severity. Given the poorly understood yet important roles of dysregulated erythropoiesis and iron metabolism in PAH, we sought to further characterize the hematologic and iron profiles in PAH and their relationship to PAH severity. We recruited 67 patients with PAH and 13 healthy controls. Hemodynamics attained within 1 year of blood sample collection were available for 36 patients. Multiple hematologic, iron, and inflammatory parameters were evaluated for their association with hemodynamics. The subset with hemodynamic data consisted of 29 females (81%). The most common etiologies were idiopathic PAH (47%) and connective tissue disease‐related PAH (33%). 19 (53%) had functional class 3 or 4 symptomatology, and 12 (33%) were on triple pulmonary vasodilator therapy. Immature reticulocyte fraction (IRF) had significant positive correlations with mean pulmonary artery (PA) pressure (mPAP) (0.59, p

Abstract Rhizobia diversity in the rhizosphere is one of the key promoters of biological nitrogen fixation between host legumes and microsymbionts, although related complex interaction may depend on various factors. This research was intended to assess the abundance of indigenous rhizobia isolates under various soil conditions, as well as their effectiveness to nodulate legumes such as soybeans. Factors such as soil properties and legume species influence the volume and symbiotic effectiveness of native rhizobia to nodulate crop legumes. To investigate the abundance of rhizobia isolates, legume crops were uprooted to obtain nodules for most probable number (MPN) determination of rhizobia isolates, and soybean (Glycine max.) was used to verify the presence of suitable and efficient rhizobia strains for nitrogen fixation. Soil samples were obtained from the holes out of which nodules were collected, and the laboratory analysis included pH, Mg, K, available P, organic C, Ca, and N to establish the correlation between the soil status and number of rhizobia isolates' cells. Significant variations (p‐value

Abstract Introduction Carers of people with mental illness may face distinct challenges, including navigating fragmented health and social services during discharge from mental health hospitals. Currently, limited examples of interventions that support carers of people with mental illness in improving patient safety during transitions of care exist. We aimed to identify problems and solutions to inform future carer‐led discharge interventions, which is imperative for ensuring patient safety and the well‐being of carers. Methods The nominal group technique was used which combines both qualitative and quantitative data collection methods in four distinct phases: (1) problem identification, (2) solution generation, (3) decision making and (4) prioritisation. The aim was to combine expertise from different stakeholder groups (patients, carers and academics with expertise in primary/secondary care, social care or public health) to identify problems and generate solutions. Results Twenty‐eight participants generated potential solutions that were grouped into four themes. The most acceptable solution for each was as follows: (1) ‘Carer Involvement and Improving Carer Experience’ a dedicated family liaison worker, (2) ‘Patient Wellness and Education’ adapting and implementing existing approaches to help implement the patient care plan, (3) ‘Carer Wellness and Education’ peer/social support interventions for carers and (4) ‘Policy and System Improvements’ understanding the co‐ordination of care. Conclusion The stakeholder group concurred that the transition from mental health hospitals to the community is a distressing period, where patients and carers are particularly vulnerable to safety and well‐being risks. We identified numerous feasible/acceptable solutions to enable carers to improve patient safety and maintain their own mental wellbeing. Patient and Public Contribution Patient and public contributors were represented in the workshop and the focus of the workshop was to identify the problems they faced and co‐design potential solutions. Patient and public contributors were involved in the funding application and study design.

Abstract Introduction Stakeholder engagement remains scarce in basic brain research. However, it can greatly improve the relevance of investigations and accelerate the translation of study findings to policy. The Lifebrain consortium investigated risk and protective factors influencing brain health using cognition, lifestyle and imaging data from European cohorts. Stakeholder activities of Lifebrain—organized in a separate work package—included organizing stakeholder events, investigating public perceptions of brain health and dissemination. Here, we describe the experiences of researchers and stakeholders regarding stakeholder engagement in the Lifebrain project. Methods Stakeholder engagement in Lifebrain was evaluated through surveys among researchers and stakeholders and stakeholders' feedback at stakeholder events through evaluation forms. Survey data were analysed using a simple content analysis approach, and results from evaluation forms were summarized after reviewing the frequency of responses. Results Consortium researchers and stakeholders experienced the engagement activities as meaningful and relevant. Researchers highlighted that it made the research and research processes more visible and contributed to new networks, optimized data collection on brain health perceptions and the production of papers and provided insights into stakeholder views. Stakeholders found research activities conducted in the stakeholder engagement work package to be within their field of interest and research results relevant to their work. Researchers identified barriers to stakeholder engagement, including lack of time, difficulties in identifying relevant stakeholders, and challenges in communicating complex scientific issues in lay language and maintaining relationships with stakeholders over time. Stakeholders identified barriers such as lack of budget, limited resources in their organization, time constraints and insufficient communication between researchers and stakeholders. Conclusion Stakeholder engagement in basic brain research can greatly benefit researchers and stakeholders alike. Its success is conditional on dedicated human and financial resources, clear communication, transparent mutual expectations and clear roles and responsibilities. Public Contribution Patient organizations, research networks, policymakers and members of the general public were involved in engagement and research activities throughout the project duration.

Abstract INTRODUCTION We evaluated the accuracy of remote and in‐person digital tests to distinguish between older adults with and without AD pathological change and used the Montreal Cognitive Assessment (MoCA) as a comparison test. METHODS Participants were 69 cognitively normal older adults with known beta‐amyloid (Aβ) PET status. Participants completed smartphone‐based assessments 3×/day for 8 days, followed by TabCAT tasks, DCTclock™, and MoCA at an in‐person study visit. We calculated the area under the curve (AUC) to compare task accuracies to distinguish Aβ status. RESULTS Average performance on the episodic memory (Prices) smartphone task showed the highest accuracy (AUC = 0.77) to distinguish Aβ status. On in‐person measures, accuracy to distinguish Aβ status was greatest for the TabCAT Favorites task (AUC = 0.76), relative to the DCTclockTM (AUC = 0.73) and MoCA (AUC = 0.74). DISCUSSION Although further validation is needed, our results suggest that several digital assessments may be suitable for more widespread cognitive screening application.

Abstract INTRODUCTION We used cultural neuropsychology‐informed procedures to derive and validate harmonized scores representing memory and language across population‐based studies in the United States and Mexico. METHODS Data were from the Health and Retirement Study Harmonized Cognitive Assessment Protocol (HRS‐HCAP) and the Mexican Health and Aging Study (MHAS) Ancillary Study on Cognitive Aging (Mex‐Cog). We statistically co‐calibrated memory and language domains and performed differential item functioning (DIF) analysis using a cultural neuropsychological approach. We examined relationships among harmonized scores, age, and education. RESULTS We included 3170 participants from the HRS‐HCAP (Mage = 76.6 [standard deviation (SD): 7.5], 60% female) and 2042 participants from the Mex‐Cog (Mage = 68.1 [SD: 9.0], 59% female). Five of seven memory items and one of twelve language items demonstrated DIF by study. Harmonized memory and language scores showed expected associations with age and education. DISCUSSION A cultural neuropsychological approach to harmonization facilitates the generation of harmonized measures of memory and language function in cross‐national studies. HIGHLIGHTS We harmonized memory and language scores across studies in the United States and Mexico. A cultural neuropsychological approach to data harmonization was used. Harmonized scores showed minimal measurement differences between cohorts. Future work can use these harmonized scores for cross‐national studies of Alzheimer's disease and related dementias.

Abstract Introduction Research focusing on cognitive aging and dementia is a global endeavor. However, cross‐national differences in cognition are embedded in other sociocultural differences, precluding direct comparisons of test scores. Such comparisons can be facilitated by co‐calibration using item response theory (IRT). The goal of this study was to explore, using simulation, the necessary conditions for accurate harmonization of cognitive data. Method Neuropsychological test scores from the US Health and Retirement Study (HRS) and the Mexican Health and Aging Study (MHAS) were subjected to IRT analysis to estimate item parameters and sample means and standard deviations. These estimates were used to generate simulated item response patterns under 10 scenarios that adjusted the quality and quantity of linking items used in harmonization. IRT‐derived factor scores were compared to the known population values to assess bias, efficiency, accuracy, and reliability of the harmonized data. Results The current configuration of HRS and MHAS data was not suitable for harmonization, as poor linking item quality led to large bias in both cohorts. Scenarios with more numerous and higher quality linking items led to less biased and more accurate harmonization. Discussion Linking items must possess low measurement error across the range of latent ability for co‐calibration to be successful. HIGHLIGHTS We developed a statistical simulation platform to evaluate the degree to which cross‐sample harmonization accuracy varies as a function of the quality and quantity of linking items. Two large studies of aging—one in Mexico and one in the United States—use three common items to measure cognition. These three common items have weak correspondence with the ability being measured and are all low in difficulty. Harmonized scores derived from the three common linking items will provide biased and inaccurate estimates of cognitive ability. Harmonization accuracy is greatest when linking items vary in difficulty and are strongly related to the ability being measured.

Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC/BPS. One family has a previously reported SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier‐White disease. Two private heterozygous variants are identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (likely pathogenic)), indicative of Hailey‐Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare ATP2C1 variants in the IC/BPS cases versus a control cohort (p = 0.03, OR = 6.76), though does not survive Bonferroni correction. The data suggest that some individuals with IC/BPS may have unrecognized Mendelian syndromes. Comprehensive phenotyping and genotyping aid in understanding the range of diagnoses in the population‐based IC/BPS cohort. Conversely, ATP2C1, ATP2A2, and SIX5 may be candidate genes for IC/BPS. Further evaluation with larger numbers is needed. Genetically screening individuals with IC/BPS may help diagnose and treat this painful disorder due to its heterogeneous nature.

Aberrant kinase signaling that involves platelet‐derived growth factor receptor (PDGFR) α/β, colony stimulating factor 1 receptor (CSF1R), and stem cell factor receptor (c‐KIT) pathways may be responsible for vascular remodeling in pulmonary arterial hypertension. Targeting these specific pathways may potentially reverse the pathological inflammation, cellular proliferation, and fibrosis associated with pulmonary arterial hypertension progression. Seralutinib (formerly known as GB002) is a novel, potent, clinical stage inhibitor of PDGFRα/β, CSF1R, and c‐KIT delivered via inhalation that is being developed for patients with pulmonary arterial hypertension. Here, we report on an ongoing Phase 2 randomized, double‐blind, placebo‐controlled trial (NCT04456998) evaluating the efficacy and safety of seralutinib in subjects with World Health Organization Group 1 Pulmonary Hypertension who are classified as Functional Class II or III. A total of 80 subjects will be enrolled and randomized to receive either study drug or placebo for 24 weeks followed by an optional 72‐week open‐label extension study. The primary endpoint is the change from baseline to Week 24 in pulmonary vascular resistance by right heart catheterization. The secondary endpoint is the change in distance from baseline to Week 24 achieved in the 6‐min walk test. A computerized tomography sub‐study will examine the effect of seralutinib on pulmonary vascular remodelling. A separate heart rate monitoring sub‐study will examine the effect of seralutinib on cardiac effort during the 6‐min walk test.

Abstract The Pulmonary Arterial Hypertension‐Quality Enhancement Research Initiative Extension Program was designed to support physicians’ adherence to pulmonary arterial hypertension (PAH) guidelines. Guidelines were followed in >95% of patients with functional class (FC) II/III, but for only 28.6% of FC IV patients (Month 36). Low adherence was driven by FC IV patients’ preference to avoid parenteral treatment.

Abstract The pathobiology of in situ pulmonary thrombosis in acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection is incompletely characterized. In human pulmonary artery endothelial cells (HPAECs), hypoxia increases neural precursor cell expressed, developmentally downregulated 9 (NEDD9) and induces expression of a prothrombotic NEDD9 peptide (N9P) on the extracellular plasma membrane surface. We hypothesized that the SARS‐CoV‐2–ARDS pathophenotype involves increased pulmonary endothelial N9P. Paraffin‐embedded autopsy lung specimens were acquired from patients with SARS‐CoV‐2–​​​​​​ARDS (n = 13), ARDS from other causes (n = 10), and organ donor controls (n = 5). Immunofluorescence characterized the expression of N9P, fibrin, and transcription factor 12 (TCF12), a putative binding target of SARS‐CoV‐2 and known transcriptional regulator of NEDD9. We performed RNA‐sequencing on normal HPAECs treated with normoxia or hypoxia (0.2% O2) for 24 h. Immunoprecipitation‐liquid chromatography‐mass spectrometry (IP‐LC‐MS) profiled protein–protein interactions involving N9P relevant to thrombus stabilization. Hypoxia increased TCF12 messenger RNA significantly compared to normoxia in HPAECs in vitro (+1.19‐fold, p = 0.001; false discovery rate = 0.005), and pulmonary endothelial TCF12 expression was increased threefold in SARS‐CoV‐2–ARDS versus donor control lungs (p

Abstract Introduction The Role of Inflammation after Surgery for Elders study correlates novel inflammatory markers measured in blood, cerebrospinal fluid (CSF) assays, and [11C]‐PBR28 positron‐emission tomography imaging. Methods This study involved a prospective cohort design with patients who underwent elective hip and knee arthroplasty under spinal anesthesia. Sixty‐five adults participated with their family members. Inflammatory biomarker assays were measured preoperatively on day 1 and postoperatively at one month. Results On average, participants were 75 years old, and 72% were female. 54% underwent total knee arthroplasty, and 46% underwent total hip arthroplasty. The mean Modified Mini‐Mental State (3MS) Examination score was 89.3; four patients (6%) scored ≤77 points. Plasma assays were completed in 63 (97%) participants, cerebrospinal fluid assays in 61 (94%), and PET imaging in 44 (68%). Discussion This complex study presents an innovative effort to correlate peripheral and central inflammatory biomarkers before and after major surgery in older adults. Strengths include collecting concurrent blood, cerebrospinal fluid, and positron‐emission tomography with detailed clinical characterization of delirium, cognition, and functional status.

Abstract Introduction An increasing number of studies are using magnetoencephalography (MEG) to study dementia. Here we define a common methodological framework for MEG resting‐state acquisition and analysis to facilitate the pooling of data from different sites. Methods Two groups of patients with mild cognitive impairment (MCI, n = 84) and healthy controls (n = 84) were combined from three sites, and site and group differences inspected in terms of power spectra and functional connectivity. Classification accuracy for MCI versus controls was compared across three different types of MEG analyses, and compared with classification based on structural MRI. Results The spectral analyses confirmed frequency‐specific differences in patients with MCI, both in power and connectivity patterns, with highest classification accuracy from connectivity. Critically, site acquisition differences did not dominate the results. Discussion This work provides detailed protocols and analyses that are sensitive to cognitive impairment, and that will enable standardized data sharing to facilitate large‐scale collaborative projects.

The association of autoimmune disease (AI) with transplant-free survival in the setting of severe Group 3 pulmonary hypertension and extensive pulmonary fibrosis remains unclear. We report cases of severe pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg and right ventricular dysfunction) and extensive pulmonary fibrosis after pulmonary arterial hypertension-specific therapy. We used multivariate regression to determine the clinical variables associated with transplant-free survival. Of 286 screened patients, 55 demonstrated severe pulmonary hypertension and extensive pulmonary fibrosis and were treated with parenteral prostacyclin therapy. The (+)AI subgroup (n = 34), when compared to the (–)AI subgroup (n = 21), was more likely to be female (77% versus 19%) and younger (58.7 ± 12.1 versus 66.0 ± 10.7 years), and revealed lower forced vital capacity (absolute) (1.9 ± 0.7 versus 2.9 ± 1.1 L), higher D L CO (% predicted) (31.1 ± 15.2 versus 23.2 ± 8.0), and increased unadjusted transplant-free survival (1 year (84.6 ± 6.3% versus 45 ± 11.1%)), 3 years (71 ± 8.2% versus 28.6 ± 11.9%), and 5 years (47.6 ± 9.6% versus 6.4 ± 8.2%); (p = 0.01)). Transplant-free survival was unchanged after adjusting for age and gender. The pulmonary hemodynamic profiles improved after parenteral prostacyclin therapy, independent of AI status. The baseline variables associated with mortality included age at pulmonary hypertension diagnosis (heart rate (HR) 1.23 (confidence interval (CI) 1.03–1.47); p = 0.02) and presence of AI (HR 0.26 (confidence interval (CI) 0.10–0.70); p

Case. A 13-year-old skeletally immature female presenting with an anterior cruciate ligament (ACL) rupture after a noncontact injury was treated with an intraepiphyseal ACL reconstruction. Flexible instrumentation was utilized to drill a femoral tunnel with an anatomic starting point, with a trajectory that curved inferolaterally away from the physis. At three years postoperatively, she had returned to her preinjury functioning and did not display any lower limb length growth abnormalities. Conclusions. The novel application of curved guides and flexible instruments, with intraoperative fluoroscopy, facilitated growth plate avoidance and a successful outcome of ACL reconstruction in a skeletally immature patient.

Abstract Introduction The interaction between delirium and dementia is complex. We examined if Alzheimer's disease (AD) biomarkers in patients without clinical dementia are associated with increased risk of postoperative delirium, and whether AD biomarkers demonstrate a graded association with delirium severity. Methods Participants (n = 59) were free of clinical dementia, age ≥70 years, and scheduled for elective total knee or hip arthroplasties. Cerebrospinal fluid (CSF) was collected at the time of induction for spinal anesthesia. CSF AD biomarkers were measured by enzyme‐linked immunosorbent assay (ELISA) (ADX/Euroimmun); cut points for amyloid, tau, and neurodegeneration (ATN) biomarker status were A = amyloid beta (Aβ)42 80 pg/mL; and N = t‐tau >700 pg/mL. Confusion Assessment Method (CAM) and CAM‐Severity (CAM‐S) were rated daily post‐operatively for delirium and delirium severity, respectively. Results Aβ42, tau, and p‐tau mean pg/mL (SD) were 361.5 (326.1), 618.3 (237.1), and 97.1 (66.1), respectively, for those with delirium, and 550.4 (291.6), 518.3 (213.5), and 54.6 (34.5), respectively, for those without delirium. Thirteen participants (22%) were ATN positive. Delirium severity by peak CAM‐S [mean difference (95% confidence interval)] was 1.48 points higher (0.29‐2.67), P = 0.02 among the ATN positive. Delirium in the ATN‐positive group trended toward but did not reach statistical significance (23% vs. 7%, p = 0.10). Peak CAM‐S [mean (SD)] in the delirium group was 7 (2.8) compared to no delirium group 2.5 (1.3), but when groups were further classified by ATN status, an incremental effect on delirium severity was observed, such that patients who were both ATN and delirium negative had the lowest mean (SD) peak CAM‐S scores of 2.5 (1.3) points, whereas those who were ATN and delirium positive had CAM‐S scores of 8.7 (2.3) points; other groups (either ATN or delirium positive) had intermediate CAM‐S scores. Discussion The presence of AD biomarkers adds important information in predicting delirium severity. Future studies are needed to confirm this relationship and to better understand the role of AD biomarkers, even in pre‐clinical phase, in delirium.

Abstract Introduction Our goal was to determine if features of surgical patients, easily obtained from the medical chart or brief interview, could be used to predict those likely to experience more rapid cognitive decline following surgery. Methods We analyzed data from an observational study of 560 older adults (≥70 years) without dementia undergoing major elective non‐cardiac surgery. Cognitive decline was measured using change in a global composite over 2 to 36 months following surgery. Predictive features were identified as variables readily obtained from chart review or a brief patient assessment. We developed predictive models for cognitive decline (slope) and predicting dichotomized cognitive decline at a clinically determined cut. Results In a hold‐out testing set, the regularized regression predictive model achieved a root mean squared error (RMSE) of 0.146 and a model r‐square (R2) of .31. Prediction of “rapid” decliners as a group achieved an area under the curve (AUC) of .75. Conclusion Some of our models could predict persons with increased risk for accelerated cognitive decline with greater accuracy than relying upon chance, and this result might be useful for stratification of surgical patients for inclusion in future clinical trials.

Abstract Introduction Composite scores may be useful to summarize overall language or visuospatial functioning in studies of older adults. Methods We used item response theory to derive composite measures for language (ADNI‐Lan) and visuospatial functioning (ADNI‐VS) from the cognitive battery administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We evaluated the scores among groups of people with normal cognition, mild cognitive impairment (MCI), and Alzheimer's disease (AD) in terms of responsiveness to change, association with imaging findings, and ability to differentiate between MCI participants who progressed to AD dementia and those who did not progress. Results ADNI‐Lan and ADNI‐VS were able to detect change over time and predict conversion from MCI to AD. They were associated with most of the pre‐specified magnetic resonance imaging measures. ADNI‐Lan had strong associations with a cerebrospinal fluid biomarker pattern. Discussion ADNI‐Lan and ADNI‐VS may be useful composites for language and visuospatial functioning in ADNI.

Abstract Introduction The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for Alzheimer's disease (AD), accelerated cognitive aging, and hippocampal atrophy, but its influence on the association between hippocampus atrophy and episodic‐memory decline in non‐demented individuals remains unclear. Methods We analyzed longitudinal (two to six observations) magnetic resonance imaging (MRI)–derived hippocampal volumes and episodic memory from 748 individuals (55 to 90 years at baseline, 50% female) from the European Lifebrain consortium. Results The change‐change association for hippocampal volume and memory was significant only in ε4 carriers (N = 173, r = 0.21, P = .007; non‐carriers: N = 467, r = 0.073, P = .117). The linear relationship was significantly steeper for the carriers [t(629) = 2.4, P = .013]. A similar trend toward a stronger change‐change relation for carriers was seen in a subsample with more than two assessments. Discussion These findings provide evidence for a difference in hippocampus‐memory association between ε4 carriers and non‐carriers, thus highlighting how genetic factors modulate the translation of the AD‐related pathophysiological cascade into cognitive deficits.

Abstract Introduction Understanding the associations among depression, subjective cognitive decline, and prodromal Alzheimer's disease (AD) has important implications for both depression and dementia screening in older adults. The Geriatric Depression Scale (GDS) is a depression screening tool for older adults that queries memory concerns. To determine whether depression symptoms on the GDS (15‐item version), including self‐reported memory problems, differ by levels of brain amyloid beta (Aβ), a pathological hallmark of early stage AD, we investigated potential measurement bias with regard to Aβ level. We also examined measurement bias attributable to level of cognitive functioning and sex as positive controls. Methods We examined 3961 cognitively normal older adults from the A4/LEARN Study. We used the MIMIC (multiple indicators, multiple causes) approach to detect measurement bias. Results We found measurement bias with small‐to‐moderate range effect sizes in several GDS‐15 items with respect to Aβ level, cognitive functioning, and sex. There was negligible impact of measurement bias attributable to Aβ level on overall depressive symptom level. Discussion GDS‐15 item responses are sensitive to Aβ burden, cognitive functioning, and sex over and above what would be expected given the effect of those factors on depressive symptom severity overall. However, these direct effects for GDS item measurement bias are of small magnitude and do not appreciably impact the validity of inferences about depression based on the GDS‐15.

Abstract Background Practice effects (PEs) are improvements in performance after repeated exposure to test materials, and typically viewed as a source of bias in repeated cognitive assessments. We aimed to determine whether characterizing PEs could also provide a useful marker of early cognitive decline. Methods We conducted a systematic review of the literature, searching PsycInfo (Ebsco) and PubMed databases for articles studying PEs in aging and dementia populations. Articles published between 1920 and 2019 were included. Result We identified 259 articles, of which 27 studied PEs as markers of cognitive performance. These studies consistently showed that smaller, less‐robust PEs were associated with current diagnostic status and/or future cognitive decline. In addition, lower PEs were associated with Alzheimer's disease risk factors and neurodegeneration biomarkers. Conclusion PEs provide a potentially useful marker of cognitive decline, and could prove valuable as part of a cost‐effective strategy to select individuals who are at‐risk for dementia for future interventions.

Background Whether racial and neighborhood characteristics are associated with bystander cardiopulmonary resuscitation (BCPR) in pediatric out‐of‐hospital cardiac arrest (OHCA) is unknown. Methods and Results An analysis was conducted of CARES (Cardiac Arrest Registry to Enhance Survival) for pediatric nontraumatic OHCAs from 2013 to 2017. An index (range, 0–4) was created for each arrest based on neighborhood characteristics associated with low BCPR (>80% black; >10% unemployment;

Glenoid labrum articular disruption (GLAD) lesions are an uncommon concomitant injury associated with labral tears, occurring in 1.5-2.9% of cases. In previous reported cases, the articular lesion is debrided during repair of the labral injury, which may predispose patients to osteoarthritis, a longitudinal complication seen in articular debridement of the hip. We report the case of a 15-year-old healthy adolescent male swimmer who sustained a labral injury with a concomitant GLAD lesion. During operative management, three Polyetheretherketone (PEEK) SutureTaks were placed on the glenoid. #2 FiberWire was used to imbricate capsular tissue, passed beneath the labrum, and was then subsequently advanced through the fibrous rim of the displaced cartilage flap/GLAD lesion at the site of each suture anchor. This construct restored tension to the anterior band of the inferior glenohumeral ligament, recreated the anteroinferior labral bumper, and effectively reduced the cartilage flap/GLAD lesion to the anterior inferior glenoid. By six months postoperatively, the patient demonstrated near-normal function with full range of motion and evidence of a stable construct on MRI. Unlike previously described cases, this is the first report of a hybrid technique that simultaneously performed a primary repair of both labral and articular injuries without the use of additional implants for the articular lesion. Primary repair of the labral and articular lesions should provide longitudinal benefit to the patient by reducing the risk of developing glenohumeral osteoarthritis.

Abstract Introduction With expansion of clinical trials to individuals across the spectrum of Alzheimer disease (AD) from preclinical to symptomatic phases, it is increasingly important to quantify AD severity using methods that capture underlying pathophysiology. Methods We derived an AD severity measure based on biomarkers from brain imaging, neuropathology, and cognitive testing using latent variable modeling. We used data from ADNI‐1 (N = 822) and applied findings to BIOCARD study (N = 349). We evaluated criterion validity for distinguishing diagnostic groups and construct validity by evaluating rates of change in AD severity. Results The AD severity factor cross‐sectionally distinguishes cognitively normal participants from MCI (AUC = 0.87) and AD dementia (AUC = 0.94). Among ADNI MCI subjects, worsening scores predict faster progression to AD dementia (HR = 1.17; 95% CI, 1.13–1.22). In ADNI and BIOCARD, the pace of change in AD severity is steepest among progressors, with persisting differences by baseline diagnosis. Discussion Our content‐valid latent variable measurement model is a reasonable approach for grading AD severity across a broad spectrum beginning at preclinical stages of AD.

BackgroundCoronary atherosclerosis raises the risk of acute myocardial infarction (AMI), and is usually included in AMI risk‐adjustment models. Percutaneous coronary intervention (PCI) does not cause atherosclerosis, but may contribute to the notation of atherosclerosis in administrative claims. We investigated how adjustment for atherosclerosis affects rankings of hospitals that perform PCI. Methods and ResultsThis was a retrospective cohort study of 414 715 Medicare beneficiaries hospitalized for AMI between 2009 and 2011. The outcome was 30‐day mortality. Regression models determined the association between patient characteristics and mortality. Rankings of the 100 largest PCI and non‐PCI hospitals were assessed with and without atherosclerosis adjustment. Patients admitted to PCI hospitals or receiving interventional cardiology more frequently had an atherosclerosis diagnosis. In adjustment models, atherosclerosis was associated, implausibly, with a 42% reduction in odds of mortality (odds ratio=0.58, P

Objective. Peripheral sensory neuropathy (PSN) is among microvascular complications of diabetes that make patients prone to ulceration and amputation. Arterial stiffness is a predictor of cardiovascular diseases and microvascular complications associated with diabetes. We investigated the association between PSN and arterial stiffness, measured as aortic pulse wave velocity (PWVao) and cardio-ankle vascular index (CAVI). Method. In a case-control design, arterial stiffness was measured in 240 diabetes patients and 110 nondiabetic control. Large-fibre nerve function was assessed by vibration perception threshold (VPT) using a neurothesiometer. PSN was defined as the VPT > 97.5th percentile from age- and gender-adjusted models in nondiabetic controls. Results. The overall prevalence of PSN was 16.6% in the entire study participants. Compared to non-PSN participants, PSN patients had higher levels of PWVao (9.5 ± 1.7 versus 8.7 ± 1.2 m/s, p=0.016) and CAVI (8.4 ± 1.3 versus 7.6 ± 1.1, p=0.001). In multiple regression models, VPT was associated with PWVao (β=0.14, p=0.025) and CAVI (β=0.12, p=0.04). PSN patients had increased odds of CAVI (OR = 1.51 (1.02–2.4), p=0.043), but not PWVao (OR = 1.25 (0.91–1.71), p=0.173). Conclusion. PWVao and CAVI were associated with VPT and PSN in diabetes patients in Ghana. Patients having PSN have increased odds of CAVI, independent of other conventional risk factors.

We investigated the risk of death in relation to the apolipoprotein ε4 allele and evaluated how it interacts with education in 504 elderly adults (mean age 73 years, 65.3% women) who were enrolled in 1993 into the New Mexico Aging Process Study. During 9 years of follow-up, apolipoprotein ε2 appeared to be associated with a lower risk for all-cause mortality (hazard ratio (HR) = 0.73, 95% confidence interval (CI): 0.30–1.71) compared to apolipoprotein ε3 carriers in models adjusted for age, sociodemographic variables, medical conditions, adiposity, and lifestyle factors. The apolipoprotein ε4 allele conferred almost a threefold elevated risk of mortality (HR = 2.76, CI: 1.42–5.37). An interaction between education and apolipoprotein e4 (p=0.027) was observed with the HR of mortality among e4 carriers compared to noncarriers being 1.59 (0.64–3.96) for those with ≥college education; 6.66 (1.90–23.4) for those with some college or trade; and 14.1 (3.03–65.6) for participants with ≤high school education. No significant interaction was identified between apolipoprotein E genotype and cognitive function for mortality risk. These findings suggest that genetic (apolipoprotein ε4) and environmental (education) factors act interactively to influences survival in the elderly with higher education attenuating the adverse effect of apolipoprotein ε4 on mortality.

BACKGROUND: Objective monitoring of the severity of inflammation in patients with inflammatory bowel disease (IBD) is an essential part of disease management. However, repeat endoscopy to define extent and severity of inflammation is not practical. Fecal calprotectin (FC) is a biomarker that can be used as a surrogate test to distinguish inflammatory from noninflammatory gastrointestinal disease.

BACKGROUND: Adherence to maintenance medication regimens in inflammatory bowel disease patients has traditionally been poor. Although infliximab has demonstrated efficacy in inducing and maintaining disease remission, adherence to regularly scheduled infliximab infusions is required to maintain therapeutic trough drug levels and prevent the development of anti-infliximab antibodies.

BACKGROUND: Women with inflammatory bowel disease (IBD) may choose to remain childless due to a lack of IBD-specific reproductive knowledge.

Background. Biologic agents targeting tumor necrosis factor alpha are effective in the management of ulcerative colitis (UC), but their use is often postponed until after failure of other treatment modalities. Objectives. We aim to determine if earlier treatment with infliximab or adalimumab alters clinical and surgical outcomes in UC patients. Methods. A retrospective cohort study was conducted evaluating UC outpatients treated with infliximab or adalimumab from 2003 to 2014. Patients were stratified by time to first anti-TNF exposure; early initiation was defined as starting treatment within three years of diagnosis. Primary outcomes were colectomy, UC-related hospitalization, and clinical secondary loss of response. Kaplan-Meier analysis was used to assess time to the primary outcomes. Results. 115 patients were included (78 infliximab, 37 adalimumab). Median follow-up was 175.6 weeks (IQR 72.4–228.4 weeks). Fifty-seven (49.6%) patients received early anti-TNF therapy; median time to treatment in this group was 38.1 (23.3–91.0) weeks compared to 414.0 (254.0–561.3) weeks in the late initiator cohort (p

In assessing the potential collateral effects of bomb attacks on tanks of stored liquids, it is useful to separate the liquid that is aerosolized as an escaping cloud from that which remains inside the tank or rapidly falls to the nearby ground. One relationship currently in use partitions the two categories using a linear model of aerosolized fraction versus fragment energy deposited per unit mass of liquid which is based on calculations and a few test data points. Since this model is incorporated in popular programs used by an expanding number of first responders to assess potential hazards, there is a need for high-confidence test data across the parameter space of interest to improve and/or validate the model. Such a series of tests was conducted during November of 2008 in which 7.57-liter (ℓ) sized cans of water were impacted with fragments of known mass using scored cased explosive charges. Impact velocities were measured, and the remaining water in the can and on the nearby ground platform was collected and weighed. The missing water was assumed to be aerosolized. This new data establishes an S-curve as a more accurate relationship between aerosolized fraction (AF) and the fragment energy deposited per unit mass of liquid in the container.

The Canadian Digestive Health Foundation initiated a scientific program to assess the incidence, prevalence, mortality and economic impact of digestive disorders across Canada in 2009. The current article presents the updated findings from the study concerning irritable bowel syndrome.

BACKGROUND: A population-based database of inflammatory bowel disease (IBD) patients is invaluable to explore and monitor the epidemiology and outcome of the disease. In this context, an accurate and validated population-based case definition for IBD becomes critical for researchers and health care providers.

The majority of patients diagnosed with Crohn’s disease eventually require surgical intervention. Unfortunately, postsurgical remission tends to be short lived; a significant number of patients experience clinical relapse and many require additional operations. The pathogenesis of this postoperative recurrence is poorly understood and, currently, there are no reliable tools to predict when and in whom the disease will recur. Furthermore, the postoperative prophylaxis profiles of available Crohn’s disease therapeutic agents such as 5-aminosalicylates, immunomodulators, steroids and probiotics have been disappointing. Recently, the combination of antibiotics and azathioprine in selected high-risk patients has demonstrated some potential for benefit. The goal of the present article is to provide a coherent summary of previous and new research to guide clinicians in managing the challenging and complex problem of postoperative Crohn’s disease recurrence.

BACKGROUND: The optimal topical anesthesia regimen for unsedated transnasal endoscopy is unknown. The addition of a nasal decongestant, such as xylometazoline (X), to a topical anesthestic may improve patient comfort.

BACKGROUND: Guidelines regarding the use of infliximab in Crohn’s disease were previously published by the Canadian Association of Gastroenterology in 2004. However, recent clinical findings and drug developments warrant a review and update of these guidelines.

Crohn’s disease (CD) is an idiopathic inflammatory bowel disease and has no known cure. CD symptoms are treated using an array of medicines, including biological agents such as infliximab. However, infliximab therapy is expensive; therefore, identifying variables that can help predict response to infliximab is worthwhile. The present article reviews the impact of tobacco smoking on the efficacy of infliximab in CD. Earlier studies have speculated that smoking has a negative effect on the response to infliximab in CD, but the current literature is largely unable to identify a significant relationship between the two. Although smoking is known to have a negative effect on the course of CD, as well as other organ systems, presently, a CD patient’s smoking status should not influence treatment decisions regarding infliximab therapy.

BACKGROUND: Infliximab’s efficacy in the induction and maintenance of remission in luminal Crohn’s disease has been confirmed by randomized, controlled trials. Less clearly described are long-term outcomes in the clinical practice setting since the establishment of regularly scheduled, every eight-week maintenance infliximab infusions. Existing reports describing clinical practice outcomes are limited by short durations of follow-up or by the use of episodic dosing, or focus on safety data rather than clinical outcomes.

Intramural hematoma of the gastrointestinal tract is an uncommon occurrence, with the majority being localized to the esophagus or duodenum. Hematoma of the gastric wall is very rare, and has been described most commonly in association with coagulopathy, peptic ulcer disease, trauma, and amyloid-associated microaneurysms. A case of massive gastric intramural hematoma, secondary to anticoagulation therapy, and a gastric ulcer that was successfully managed with conservative therapy, is presented. A literature review of previously reported cases of gastric hematoma is also provided.

Infliximab is a chimeric, monoclonal anti-tumour necrosis factor-alpha antibody. It has been previously demonstrated to be an effective treatment for patients with Crohn’s disease who do not achieve the desired response with conventional treatments. Although the etiology of ulcerative colitis (UC) differs from that of Crohn’s disease, randomized controlled trials have demonstrated that infliximab is also beneficial for the treatment of moderate to severe UC in patients who are either intolerant of or refractory to immunosuppressant agents or steroids, or those who are steroid-dependent. A review of the literature is followed by practical recommendations regarding infliximab that address the needs of clinicians and UC patients. Where there is a lack of evidence-based information, the expert panel provides its combined opinion derived from the members’ clinical experiences.

Crohn’s disease and ulcerative colitis are both idiopathic inflammatory bowel diseases (IBDs) that affect 0.5% of Canadians. As yet, there is no known cure for either disease, and symptoms are treated with an array of medicines. The objective of the present review was to present the role of exercise and its impact on all facets of IBD. Exercise has been speculated to be protective against the onset of IBD, but the literature is inconsistent and weak. Preliminary studies reveal that exercise training may be beneficial to reduce stress and symptoms of IBD. Current research also recommends exercise to help counteract some IBD-specific complications by improving bone mineral density, immunological response, psychological health, weight loss and stress management ability. However, the literature advises that some patients with IBD may have limitations to the amount and intensity of exercise that they can perform. In summary, exercise may be beneficial to IBD patients, but further research is required to make a convincing conclusion regarding its role in the management of IBD and to help establish exercise regimens that can account for each IBD patient’s unique presentation.

BACKGROUND: Alkaline sphingomyelinase, an enzyme found exclusively in bile and the intestinal brush border, hydrolyzes sphingomyelin into ceramide, sphingosine and sphingosine-1-phosphate, thereby inducing epithelial apoptosis. Reduced levels of alkaline sphingomyelinase have been found in premalignant and malignant intestinal epithelia and in ulcerative colitis tissue. Probiotic bacteria can be a source of sphingomyelinase.

The Canadian North Helicobacter pylori (CANHelp) working group is a team composed of investigators, health officials and community leaders from Alberta and the Northwest Territories. The group’s initial goals are to investigate the impact of H pylori infection on Canada’s Arctic communities; subsequent goals include identifying treatment strategies that are effective in this region and developing recommendations for health policy aimed at management of H pylori infection. The team’s investigations have begun with the Aklavik H pylori Project in the Aboriginal community of Aklavik, Northwest Territories.

BACKGROUND: Unsedated transnasal gastroscopy is a technique with unverified clinical advantages.

Objective: To develop an efficient method for evaluating cell surface hydrophobicity and to apply the method to demonstrate the effects of fungal growth conditions on cell surface properties.

Objective: To develop an efficient method for evaluating cell surface hydrophobicity and to apply the method to demonstrate the effects of fungal growth conditions on cell surface properties.

BACKGROUND: Patients with inflammatory bowel disease (IBD) suffer physical dysfunction and impaired quality of life (QOL), and need frequent health care. They often lack knowledge about their disease and desire more education. Educational interventions for other chronic diseases have demonstrated reduced health care use and increased knowledge, medication adherence and QOL.