A validated heart-specific model for splice-disrupting variants in childhood heart disease.

BACKGROUND: Congenital heart disease (CHD) is the most common congenital anomaly. Almost 90% of isolated cases have an unexplained genetic etiology after clinical testing. Non-canonical splice variants that disrupt mRNA splicing through the loss or creation of exon boundaries are not routinely captured and/or evaluated by standard clinical genetic tests. Recent computational algorithms such as SpliceAI have shown an ability to predict such variants, but are not specific to cardiac-expressed genes and transcriptional isoforms. METHODS: We used genome sequencing (GS) (n = 1101 CHD probands) and myocardial RNA-Sequencing (RNA-Seq) (n = 154 CHD and n = 43 cardiomyopathy probands) to identify and validate splice disrupting variants, and to develop a heart-specific model for canonical and non-canonical splice variants that can be applied to patients with CHD and cardiomyopathy. Two thousand five hundred seventy GS samples from the Medical Genome Reference Bank were analyzed as healthy controls. RESULTS: Of 8583 rare DNA splice-disrupting variants initially identified using SpliceAI, 100 were associated with altered splice junctions in the corresponding patient myocardium affecting 95 genes. Using strength of myocardial gene expression and genome-wide DNA variant features that were confirmed to affect splicing in myocardial RNA, we trained a machine learning model for predicting cardiac-specific splice-disrupting variants (AUC 0.86 on internal validation). In a validation set of 48 CHD probands, the cardiac-specific model outperformed a SpliceAI model alone (AUC 0.94 vs 0.67 respectively). Application of this model to an additional 947 CHD probands with only GS data identified 1% patients with canonical and 11% patients with non-canonical splice-disrupting variants in CHD genes. Forty-nine percent of predicted splice-disrupting variants were intronic and > 10 bp from existing splice junctions. The burden of high-confidence splice-disrupting variants in CHD genes was 1.28-fold higher in CHD cases compared with healthy controls. CONCLUSIONS: A new cardiac-specific in silico model was developed using complementary GS and RNA-Seq data that improved genetic yield by identifying a significant burden of non-canonical splice variants associated with CHD that would not be detectable through panel or exome sequencing.

High Physiological 18 F-FDG Uptake in Normal Pituitary Gland on Digital PET Scanner.

Purpose Recently developed digital positron emission tomography/computed tomography (PET/CT) scanners (digital PET [dPET]) have given new dimensions to molecular imaging. dPET scanner has very high sensitivity, spatial resolution, and image contrast that leads to increased uptake of signal in small-volume structures like pituitary gland (PG) making them visible on PET/CT scan even in absence of any pathology. Adequate knowledge of physiological fluoro-2 deoxy D glucose uptake in PG is required in interpretation of dPET for correct diagnosis and reducing unnecessary additional imaging. The aim of this study is to evaluate the frequency of physiological PG uptake on dPET. Material and Methods Eighty-eight subjects (mean age, 54.44 ± 14.18 years; range, 26-84 years; 63 females and 25 males) with normal PG on magnetic resonance imaging brain and imaged within 6 months on dPET were included in this research study. Out of 88 patients, 20 control subjects (mean age, 58.15 ± 11.08 years: 15 females and 5 males) underwent PET/CT on conventional PET. All images were acquired with similar and standard acquisition protocol and reconstruction done with Time of flight with Point spread function. PG uptake was compared visually and quantitatively. Results PG uptake was seen in 43 patients (48.8%). Out of 43 patients, 31 (72%) showed low uptake, 11 (26%) showed intermediate grade of uptake, and 1 patient (2%) showed intermediate-to-high uptake and was categorized as high-grade uptake. In the control group of 20 patients, 3 (15%) showed low uptake, while none of them showed intermediate or high uptake. Conclusion Physiological PG uptake is commonly seen on dPET. Low-to-intermediate grade of PG uptake on dPET in an asymptomatic patient is physiological and does not require further evaluation and should be reported with caution.

Molecular imaging with 68Ga-PSMA PET/CT in high grade glioma: A biomarker for tumour neo-angiogenesis.

There are several promising radiotracers used for both staging and restaging of primary and recurrent brain tumours based on various mechanisms of tracer localization in tumour cells. 68Ga-PSMA PET has extremely low background uptake in normal brain tissue and consequently high tumour-to-brain ratio making it a promising imaging radiotracer for gliomas. 68Ga-PSMA demonstrates utility in evaluating high grade glioma during both initial workup or when suspecting recurrence. Herein the authors evaluate the role of this imaging modality and the potential future it holds in the management of high grade gliomas.

Unusual Soft Tissue Uptake of Tc-99m MDP in Radiation-induced Sarcoma: Diagnostic Conundrum.

Tc-99m methylene diphosphonate (MDP) is a bone imaging agent used for skeletal staging, but it can also be localized in extraosseous calcifying lesions. We report a case of an 84-year-old woman with breast carcinoma who underwent surgery followed by radiotherapy 10 years ago and now presented with a right axillary mass referred for Tc-99m MDP to exclude bone metastasis. Tc-99m MDP shows intense tracer uptake in the right thoracic region corresponding to the site of calcified soft tissue mass in the right lateral chest wall. Subsequent ultrasonography revealed an ill-defined lesion containing coarse calcifications. Biopsy showed radiation-induced sarcoma. Extra osseous Tc-99m MDP uptake may provide important diagnostic information that may alter patient management.

Super Mario sign at somatostatin receptor PET/CT.

68Ga-DOTA NOC PET-CT imaging has been shown to have high accuracy for the evaluation of neuroendocrine tumours. We present the case of a 59-year-old male with well differentiated gastric neuroendocrine tumour (grade II) treated with surgery. 68Ga-DOTA NOC PET/CT was performed to rule out metastasis. 68Ga-DOTA NOC showed physiological uptake in the bilateral adrenal and horseshoe kidney appearing as the famous character Super Mario. There is no evidence of any abnormal somatostatin avid lesion.

Technological Advances in SPECT and SPECT/CT Imaging.

Single photon emission tomography/computed tomography (SPECT/CT) is a mature imaging technology with a dynamic role in the diagnosis and monitoring of a wide array of diseases. This paper reviews the technological advances, clinical impact, and future directions of SPECT and SPECT/CT imaging. The focus of this review is on signal amplifier devices, detector materials, camera head and collimator designs, image reconstruction techniques, and quantitative methods. Bulky photomultiplier tubes (PMTs) are being replaced by position-sensitive PMTs (PSPMTs), avalanche photodiodes (APDs), and silicon PMs to achieve higher detection efficiency and improved energy resolution and spatial resolution. Most recently, new SPECT cameras have been designed for cardiac imaging. The new design involves using specialised collimators in conjunction with conventional sodium iodide detectors (NaI(Tl)) or an L-shaped camera head, which utilises semiconductor detector materials such as CdZnTe (CZT: cadmium-zinc-telluride). The clinical benefits of the new design include shorter scanning times, improved image quality, enhanced patient comfort, reduced claustrophobic effects, and decreased overall size, particularly in specialised clinical centres. These noticeable improvements are also attributed to the implementation of resolution-recovery iterative reconstructions. Immense efforts have been made to establish SPECT and SPECT/CT imaging as quantitative tools by incorporating camera-specific modelling. Moreover, this review includes clinical examples in oncology, neurology, cardiology, musculoskeletal, and infection, demonstrating the impact of these advancements on clinical practice in radiology and molecular imaging departments.

Enhancing precision in bone metastasis diagnosis for lobular breast cancer: reassessing the role of 18F-FDG PET/CT.

PURPOSE: Detection of osseous metastases by imaging can be challenging in patients with invasive lobular breast cancer (ILC). ILC may demonstrate low metabolic rate due to lower tumor cell density, decreased proliferation rate, diffuse infiltration of surrounding tissue, and low level of GLUT-1 expression. The aim of this study is to assess the diagnostic accuracy of 18F-FDG PET/CT in identifying bone metastases in ILC patients. MATERIAL AND METHODS: Out of 52 individuals diagnosed with lobular breast cancer and underwent 18F-FDG PET/CT for evaluation of metastases, 21 patients were included in our study population after applying inclusion and exclusion criteria. The radiological and clinical follow-up of at least 6 months served as the reference standard comparator. RESULTS: Bone metastases were confirmed in six patients. 18F-FDG PET/CT was true positive in two and false negative in four patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18F-FDG PET/CT were 33.33, 93.33, 66.67, 77.78, and 76.19%, respectively (95% confidence interval). The tendency of ILC osseous metastases to be more sclerotic explains the low diagnostic accuracy of 18F-FDG PET/CT in detection of bone metastases, making it a less suited method of evaluation. CONCLUSION: The results of the present study indicate that 18F-FDG PET/CT has a low diagnostic accuracy in detecting bone metastases in lobular breast cancer and, by inference, new functional modalities can be explored in these patients. The findings contribute valuable insights to optimize the integration of molecular imaging into the diagnostic algorithm for this specific breast cancer subtype.

Nicotine prevalence among youth of rural Jaipur, Rajasthan.

Background: Children are more sensitive to tobacco advertisements than adults. The World Health Organization (WHO) reported that tobacco use has doubled in the past four decades particularly among the youth. Smoking among teenagers is an issue that affects countries worldwide. Objective: This study identified the prevalence of tobacco consumption among youth of rural Jaipur. We also studied, their age of initiation of tobacco and their correlation with the income and occupation of parents. Method: Community based cross-sectional type of study was conducted on youth of 15-24 years of age in 30 clusters in the Vatika, Jaipur. Cluster sampling technique was adopted. A semi-structured pretested and predesigned questionnaire was used for data collection. The inter-personal communication technique was used maintaining full confidentiality. All the results were transferred onto Microsoft excel sheet and evaluated statistically. Results: Out of 420 youths, 79.0% youths consumes nicotine in any form. More male subjects (90.9%) consume nicotine than females (62.8%) highly significantly. 33.1% youths started nicotine consumption <12 years. Youths from more income family(63.6%), illiterate father (76.2%), illiterate mother (74.4%), father having farming as occupation (67.2%), consumes more nicotine. more (88.6%) of youths consume nicotine with their friends. 58.1% parents oppose their children. Conclusion: The prevalence of nicotine intake was higher in boys than girls and majority of them consumes nicotine in any form gutka or beedi-cigarette. The reasons for such high dependence of nicotine according to the youth were lack of knowledge of the ill effects of nicotine intake and peer pressure. However, majority of the youth did not want to quit nicotine consumption.

The role of 18F-FDG PET/CT in Neurolymphomatosis: A Comprehensive Imaging Approach.

Neurolymphomatosis (NL) is an uncommon and rare neurologic disorder characterised by extranodal lymphoma, where the tumour cells invade the cranial nerves, nerve plexus, nerve root, spinal nerve roots, trunk nerves or peripheral nerves. MRI is the modality of choice, but is often challenging in detection of early recurrence, assessing residual disease and response evaluation. 18FFDG PET/CT has superior diagnostic performance compared with body CT in the evaluation of NL. 18F-FDG PET-CT is helpful in evaluation of disease extent and potential to guide biopsy. 18F-FDG PETCT is a highly sensitive technique for early localisation of NL than MRI or CT alone. Besides diagnostic and prognostic value in NL, it might be very helpful in response assessment.

Anti-programmed-death-receptor-1 (PD-1) antibody (Pembrolizumab) induced pancreatitis diagnosed on 18F-FDG PET/CT.

Immunotherapy related adverse events are commonly seen with immune check point inhibitors therapy. We report the case of a 40-year-old female diagnosed with stage IVB endometroid grade III endometrial cancer, on pembrolizumab immunotherapy, an anti-programmed-death-receptor-1 (PD-1) antibody. Patient was referred for 18F-FDG PET/CT for restaging. 18F-FDG PET/CT demonstrated diffuse increased FDG uptake throughout the body of the pancreas associated with fat stranding in the peripancreatic region, suggestive of pembrolizumab-induced pancreatitis. The diagnosis was confirmed by elevated amylase and lipase levels. immune-related adverse events (irAE) are frequently identified on 18F-FDG PET-CT, which may lead to early diagnosis, close clinical follow-up, and appropriate clinical management of immune-related adverse events.

Ozanimod in Patients With Moderate to Severe Ulcerative Colitis Naive to Advanced Therapies.

BACKGROUND & AIMS: The pivotal phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod in patients with moderately to severely active ulcerative colitis. This analysis assessed ozanimod during TN and the ongoing open-label extension (OLE) in patients with active disease who were naive to advanced therapies (ATs). METHODS: TN was a randomized, double-blind, placebo-controlled trial consisting of 10-week induction period and 42-week maintenance period. Eligible patients could enter the OLE. Symptomatic efficacy was evaluated from induction through the OLE. Clinical, endoscopic, and mucosal outcomes were evaluated at the end of induction (Week [W] 10) and maintenance (W52) and at predefined OLE timepoints (OLE W46 and W94). Safety during TN was reported. RESULTS: This analysis included 616 AT-naive patients. Numerically greater proportions of patients receiving ozanimod than placebo achieved symptomatic response (39% vs 29%, 95% confidence interval, -0.1 to 18.8) by W2, with significant differences (56% vs 39%, 95% confidence interval, 6.3-26.3) achieved by W4. Patients receiving ozanimod showed significant improvements across efficacy outcomes versus placebo at W10 and W52 (P < .05, all endpoints). In patients on continuous ozanimod who entered the OLE in clinical response at W52, 91% maintained clinical response through OLE W94, and 74% achieved endoscopic improvement and 57% achieved mucosal healing at OLE W94. In ozanimod-treated patients without clinical response by W10 who received extended induction in the OLE, 62% achieved symptomatic response by OLE W10. Safety outcomes in AT-naive patients were consistent with the total TN population. CONCLUSIONS: Ozanimod is an effective, durable, and well-tolerated oral therapy for AT-naive ulcerative colitis patients. CLINICALTRIALS: gov, numbers NCT02435992 and NCT02531126.

Links between parental monitoring and parent-adolescent conflict: A multimodal test of bidirectional relations.

During adolescence, youth increase in both independence and conflict with parents. Parents vary in how much they know about their adolescents' whereabouts and activities and how they acquire this information (i.e., the sources of what parents know). We probed how parental knowledge of adolescents' whereabouts and activities-and their information sources-relates to (a) domains of parent-adolescent conflict (fighting about, or having different beliefs about, daily life topics) and (b) parent and adolescent attachment-related behavior during a conflict discussion task. Using the Actor-Partner Interdependence Model, we tested links between parental knowledge and its sources and conflict processes. Eighty-seven adolescents (Mage = 15.18; 55% female) and parents completed surveys about parental knowledge and its sources (i.e., parental solicitation of adolescents' activities, adolescent disclosure to parents about their activities) and separate interviews on conflict domains. A subset of parent-adolescent dyads (n = 65) interacted for 5 min about an adolescent-identified conflict topic. Different beliefs about daily life topics related to parental knowledge: parents' reports of greater different beliefs about daily life topics predicted less knowledge of adolescents' activities/whereabouts, solicitation, and disclosure, for both parent and adolescent reports of these domains. For adolescents, greater different beliefs related to less solicitation and disclosure. Only adolescent reports of parental knowledge, solicitation, and disclosure predicted attachment-related behaviors both dyad members displayed during the conflict discussion task. Findings reveal links between parental knowledge of adolescents' activities and conflict processes and demonstrate dyadic interdependence between parental knowledge of adolescents' activities and conflict processes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Emulgel: A Cutting Edge Approach for Topical Drug Delivery System.

Emulgel is considered an advanced leading form of topical drug delivery system. It possesses the quality of a dual control drug mechanism for drug release as it holds the properties of both gel as well as emulsion. Emulgel is capable of overcoming the problems of the conventional route of topical drug delivery, like low spreadability and stickiness with the delivery of hydrophobic drugs, enhanced bioavailability at the local site of action, no greasy texture, and ensuring patient compliance. An emulsion is used either w/o or o/w, and the drug can be incorporated into the suitable phase of the emulsion. After that, the emulsion is incorporated into the gel phase. Several factors like oil phase, gelling agent, and emulsifier can affect the efficacy and stability. This advancement is beneficial not only for dermatology but also for cosmetology as well. Currently, emulgel-based formulations are used for the delivery of anti-inflammatory, analgesic, anti-acne, and antifungal drugs with a wide array of exploration.

The Great Imitator: Pulmonary Paraganglioma Mimicking Pulmonary Metastasis of Breast Cancer on 18 F-FDG PET/CT.

ABSTRACT: Primary pulmonary paragangliomas are rare neuroendocrine tumors and are often discovered incidentally as nonfunctioning masses. We report a case of 58-year-old woman recently diagnosed with multifocal right breast cancer and suspicious right axillary lymph nodes. 18 F-FDG PET/CT showed a well-defined marginated lesion in the lower lobe of the right lung with intense FDG uptake. Findings were suspicious for pulmonary metastases. CT-guided biopsy results were consistent with a paraganglioma. Paragangliomas can mimic metastases, especially if they are large or have a high degree of FDG uptake, and careful evaluation of imaging features and clinical findings can help differentiate these entities. Most of the time biopsy is necessary to confirm the diagnosis.

Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension.

BACKGROUNDS AND AIMS: This interim analysis from the True North open-label extension [OLE] study examines efficacy and safety of approximately 3 years of continuous ozanimod treatment in patients with moderately to severely active ulcerative colitis. METHODS: Clinical responders after 52 weeks of ozanimod during the phase 3 True North study, who continued treatment in the OLE, were evaluated. Efficacy, including endoscopic and histological endpoints, was assessed during the OLE for approximately 2 additional years through OLE Week 94, using observed case [OC] and nonresponder imputation [NRI] analyses. Adverse events were monitored from True North baseline through OLE data cutoff and expressed as exposure-adjusted incidence rates. RESULTS: This analysis included 131 patients; 54% had achieved corticosteroid-free remission at True North Week 52. In OC analyses, clinical response, clinical remission, and corticosteroid-free remission were achieved by 91.4%, 69.1%, and 67.9% of patients, respectively, at OLE Week 94 [146 weeks of total treatment]. Similarly, endoscopic improvement, histological remission, and mucosal healing were achieved by 73.3%, 67.3%, and 56.3% of patients, respectively, at OLE Week 94. Efficacy rates were lower using NRI analyses, but maintenance of efficacy was demonstrated through OLE Week 94. No new safety signals emerged from this analysis. Serious infections, malignancy, cardiovascular events, and hepatic events occurred infrequently. CONCLUSIONS: Among patients who achieved clinical response after 1 year of ozanimod treatment during True North, a high percentage sustained clinical and mucosal efficacy over 2 additional years in the OLE. No new safety signals were observed with long-term ozanimod use.

Calcaneus metastasis: a rare presentation of poorly differentiated thyroid cancer.

Summary: A 60-year-old woman presented to our clinic with an acute onset 3 months history of right ankle pain. The patient had a history of poorly differentiated thyroid cancer, which was treated with total thyroidectomy, left lateral neck dissection levels II-V and central neck dissection levels VI-VII followed by postoperative I-131 radioactive iodine (131I) ablation therapy 3.7 GBq 6 months ago. The post-131I WBS showed residual iodine-avid thyroid tissue with no other iodine-avid disease or metastasis. SPECT/CT of the neck and chest showed nonavid bilateral pulmonary nodules, discrete nodal masses in mediastinum and nonavid bone lesions. FDG-PET CT scan showed FDG-avid mediastinal lymph nodes (LN), innumerable non-FDG-avid subcentimetric pulmonary nodules and few FDG-avid lytic lesions in the skeleton. X-ray and MRI of the right ankle showed a well-marginated lytic lesion in the posterior body of calcaneus and 5 × 6 cm soft tissue mass lesion, respectively. The histopathology of the calcaneus mass confirmed a positive immunostaining for thyroid origin which includes thyroglobulin and TTF-1 with PAX-8. Endobronchial mediastinal and bronchial LN biopsy confirmed thyroid cancer metastasis. Gene mutation showed HRAS and GNA13 with a high tumor mutational burden. We describe a rare case of poorly differentiated thyroid cancer in a patient who presented with right ankle pain; we confirmed the cause to be a calcaneus metastasis from the thyroid cancer, with calcaneus being an extremely rare site for bone metastases. Gene mutations points toward treatment with immune checkpoint inhibitors. Learning points: Poorly differentiated thyroid carcinoma (PDTC) usually metastasizes to lung and bone but can rarely occur in the calcaneus. Patients with distant metastases have significantly worse long-term prognosis. Radiotherapy is effective in reducing the metastatic pains as well as reducing the size of the metastasis. PAX-8 staining can be used to differentiate thyroid carcinomas from lung adenocarcinomas. The importance of searching for gene mutations to decide the treatment of PDTC.

Cardiovascular Safety of Ozanimod in Patients With Ulcerative Colitis: True North and Open-Label Extension Analyses.

BACKGROUND & AIMS: Evaluating cardiovascular safety of sphingosine 1-phosphate (S1P) receptor modulators is warranted due to S1P receptor expression on cardiomyocytes and vascular endothelial cells. This analysis reports the cardiovascular safety of ozanimod, an S1P receptor modulator, in patients with moderately to severely active ulcerative colitis from the phase 3 True North (TN) and open-label extension (OLE). METHODS: All patients who received ozanimod in TN (n = 796) and all eligible TN patients who entered the OLE (n = 823) were included. Cardiovascular-related adverse events were evaluated in patients with up to 146 weeks of ozanimod exposure (2219 patient-years), which included 52 weeks during TN. RESULTS: On TN day 1, first-dose ozanimod resulted in a 0.2 beats per minute mean decrease in heart rate from pretreatment to hour 6; 2 patients experienced bradycardia, which resolved without treatment modification. Mean systolic and diastolic blood pressure increases of 5.1 and 2.2 mm Hg, respectively, were observed at TN week 52. No second-degree Mobitz type II atrioventricular block events were reported; 1 third-degree atrioventricular block unrelated to ozanimod occurred in the OLE. Cardiac and vascular treatment-emergent adverse events were infrequent (3.8% [31 of 823] and 8.5% [70 of 823]); no ozanimod-related cardiovascular deaths occurred. The incidences of deep-vein thrombosis (0.2%; 2 of 823), pulmonary embolism (0.2%; 2 of 823), and ischemic stroke (0.4%; 3 of 823) in the OLE were low. CONCLUSIONS: No new cardiovascular safety signals were identified, consistent with findings from previous ozanimod studies. There were few major adverse cardiovascular events or thromboembolic events, which were unrelated or unlikely related to ozanimod. Ozanimod has a well-tolerated cardiovascular safety profile when prescribed in accordance with the label. Clinical trial registry website and trial numbers: ClinicalTrials.gov numbers: NCT02435992 and NCT02531126.

Guiding Principles to Address the Impact of Algorithm Bias on Racial and Ethnic Disparities in Health and Health Care.

Importance: Health care algorithms are used for diagnosis, treatment, prognosis, risk stratification, and allocation of resources. Bias in the development and use of algorithms can lead to worse outcomes for racial and ethnic minoritized groups and other historically marginalized populations such as individuals with lower income. Objective: To provide a conceptual framework and guiding principles for mitigating and preventing bias in health care algorithms to promote health and health care equity. Evidence Review: The Agency for Healthcare Research and Quality and the National Institute for Minority Health and Health Disparities convened a diverse panel of experts to review evidence, hear from stakeholders, and receive community feedback. Findings: The panel developed a conceptual framework to apply guiding principles across an algorithm's life cycle, centering health and health care equity for patients and communities as the goal, within the wider context of structural racism and discrimination. Multiple stakeholders can mitigate and prevent bias at each phase of the algorithm life cycle, including problem formulation (phase 1); data selection, assessment, and management (phase 2); algorithm development, training, and validation (phase 3); deployment and integration of algorithms in intended settings (phase 4); and algorithm monitoring, maintenance, updating, or deimplementation (phase 5). Five principles should guide these efforts: (1) promote health and health care equity during all phases of the health care algorithm life cycle; (2) ensure health care algorithms and their use are transparent and explainable; (3) authentically engage patients and communities during all phases of the health care algorithm life cycle and earn trustworthiness; (4) explicitly identify health care algorithmic fairness issues and trade-offs; and (5) establish accountability for equity and fairness in outcomes from health care algorithms. Conclusions and Relevance: Multiple stakeholders must partner to create systems, processes, regulations, incentives, standards, and policies to mitigate and prevent algorithmic bias. Reforms should implement guiding principles that support promotion of health and health care equity in all phases of the algorithm life cycle as well as transparency and explainability, authentic community engagement and ethical partnerships, explicit identification of fairness issues and trade-offs, and accountability for equity and fairness.

Development and Validation of the Adaptive Schema Questionnaire.

Background: Schemas help with the organization and interpretation of information. Adaptive schemas indicate positive predisposing thinking patterns in an individual. This study aimed to develop a psychometrically robust tool to assess adaptive schema in a nonclinical sample. Method: This research comprises two independent studies. Study I was multiphased. In Phase I (n = 70), 36 open-ended items were generated following the Young schema therapy model and qualitatively analyzed. This facilitated the generation of 144 items in Phase II (n = 152) which were evaluated for content validity and subjected to rigorous item analysis. Exploratory factor analysis was performed in Phase III (n = 751). Confirmatory factor analysis was conducted in Study II (n = 244). Results: Exploratory factor analysis resulted in a six-factor solution comprising 25 items. These factors correspond to the six adaptive themes, namely, adequate, secured, self-reliant/autonomous, resistant, successful, and self-assured. The newly developed Adaptive Schema Questionnaire demonstrated adequate reliability (α = 0.86). Significant correlations between the obtained factors and Early Maladaptive Schemas, depression, big five personality factors, and positive and negative effects established the concurrent validity. Confirmatory factor analysis indicated acceptable goodness of fit for the obtained model. Conclusion: The developed Adaptive Schema Questionnaire is a reliable and valid instrument with promising utility in psychotherapy and research context.