Formal Treatment Research Articles

Caregivers’ socio-cultural influences on health-seeking behavior for their wasted children among forcibly displaced Myanmar Nationals and their nearest host communities

IntroductionA total of 19% of forcibly displaced Myanmar Nationals (FDMNs) Bangladesh fall within the age range of under five years old, while an average of 1% exhibit severe malnutrition. Cox’s Bazar is the closest host community for FDMNs, with similar traditional culture and religion and shared linguistic, ethnic, and cultural ties.MethodsA qualitative study was conducted to investigate the impact of socio-cultural factors on the healthcare-seeking behavior of caregivers of critically malnourished children in FDMN camps and neighboring host communities.ResultsThe utilization of informal healthcare by caregivers in both populations can be attributed to cultural attitudes, taboos, and peer pressure. The healthcare by practices in the FDMN camps and host towns were primarily affected by household responsibilities, familial assistance in accessing medical services, decisions made by husbands or mothers-in-law, and the availability and accessibility of healthcare facilities. Certain features were identified that prompt caregivers to seek formal treatment in both groups. The efficacy of the treatment was a primary consideration. In instances where conventional remedies and informal treatments proved ineffective in restoring the health of children, others who were invested in their well-being, such as family members and neighbors, advised caretakers to pursue professional medical care.DiscussionEnhanced caregiver awareness of severe wasting, enhanced healthcare accessibility, and increased community volunteer engagement have the potential to facilitate early identification of severely wasted children and mitigate delays in treatment.

Precision Lineage Deconvolution in Mixed Phenotype Acute Leukemia Using Cite-Seq Derived Hematopoietic Stages Identifies Lineage Dynamics Associated with Treatment Response

Introduction: Mixed phenotype Acute Leukemia (MPAL) is challenging due to ambiguous biology and lack of formal therapeutic guidelines. Although MPAL itself is rare, mixed phenotype lineage expression in secondary AML (sAML-MP) occurs with greater frequency and is associated with poor clinical outcomes. Multimodal single cell sequencing with cellular indexing of transcriptomes and epitopes (CITE-seq) offers more precise lineage characterization and assessment of lineage dynamics. Here we demonstrate a novel, unbiased approach to quantitative multistage hematopoietic lineage assessment in MPAL and sAML-MP using CITE-seq data. In addition, we demonstrate that this approach can be translated from single cell to bulk analysis. Methods: Sample preparation: Four MPAL and 6 sAML-MP samples displaying T-cell and myeloid subsets were identified and flow sorted into T and myeloid subgroups. RNA-seq was performed on each subset and analyzed using DESeq2. ComBat was used for batch correction when integrating with disparate data sources. Single cell lineage deconvolution: CITE-seq samples were processed using Seurat. A single cell deconvolution library was constructed using previously published hematopoietic stage clustering and labeling, and applied to CITE-seq data from five MPAL samples in the same dataset. Deconvolution algorithm parameters were optimized through a bootstrapping approach on in-silico sample mixtures. Bulk and translated lineage deconvolution: Bulk lineage deconvolution was performed using a published library of 13 stages of hematopoiesis derived from healthy donors.This was applied to bulk RNA-seq data from a cohort of published MPAL samples as well as the 6 sAML-MP and 4 MPAL samples described above. A pseudobulk was created for each CITE-seq lineage stage. Bulk lineage deconvolution was then re-run on the MPAL and sAML-MP samples using this library. Clinical Outcomes: A Wilcoxon signed-rank test was used to analyze differences among deconvolution-derived patient clusters, including response to induction therapy, specific gene mutations, and likelihood of transplant. Results: Lineage evolution with treatment: Deconvolution was applied on 17,848 MPAL cells and 35,038 control PBMC/BMMC cells. Antibody Derived Tag (ADT) features were consistent with lineage deconvolution stage assignments. CD38 was negatively correlated with HSC (-0.34, p < 0.001) and LMPP (-0.18, p < 0.001) while CD34 was positively correlated with both HSC (0.11, p < 0.001) and LMPP (0.27, p < 0.001) stages. MPAL 5 in particular was assessed at diagnosis and at two later time points. Unsupervised hierarchical clustering of all timepoints resulted in 10 clusters ( Figure A). The diagnostic time point was largely contained in clusters 4 (LMPP character, N = 1545 cells, 37.13%) and 9 (HSC character, N = 756 cells, 18.16%). The majority of both relapse timepoints were within cluster 4, with 76.77% (N=357 cells) of T1 and 73.92% (N=1100 cells) of T2 located in it. Bulk Unsupervised Analysis: Unsupervised analysis of sorted MPAL (N = 8), sorted AML-MP (N = 12), and unsorted MPAL (N = 24) bulk samples resulted in six distinct clusters, each with a distinct lineage signature ( Figure B). Some were enriched for more differentiated stages such as monocyte or GMP (clusters 6, 5), while others were enriched earlier stages such as LMPP (cluster 2). Secondary AML-MP samples were notably enriched in cluster 4. We found significant associations between lineage clusters and mutations in RUNX1 (p < 0.01), FLT3 (p = 0.004). Clinical Outcomes: Bulk RNA deconvolution cluster was significantly associated with complete remission (p = 0.0009). On average, individuals with an incomplete/no response to induction chemotherapy had a higher NK signature (p = 0.001), while individuals assigned to transplant had decreased LMPP character (p = 0.0495). Among the single-cell stages, decreased CLP 2 levels were associated with a poor response (p = 0.0224) while CMP / LMPP (p = 0.040) and CD4 N2 (p = 0.022) levels were decreased in patients who were able to undergo HSCT. Conclusions: Precise identification of lineage signatures in mixed phenotype leukemias shows promise in identifying clinically meaningful biological subsets of these diseases. Prospective analysis of lineage-derived biomarkers should be performed to undertake identification of formal risk stratification and treatment schemas.

Treatments and Outcomes of Lymphoma-Associated Hyperinflammation- a Report from the HLH in Adults Working Group for the Histiocyte Society

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome. Lymphoma is the most common cause of HLH in adults. Previous studies have indicated poor patient outcomes in lymphoma-associated HLH. The recently introduced optimized HLH inflammatory (OHI) index has improved prognostication and identification of the hyper-inflammatory phenotype of lymphoma; however, more comprehensive information on treatments and outcomes in a large cohort in the contemporary era is necessary. Our study aimed to investigate the clinical features, treatments, and outcomes of lymphoma-associated HLH through a multi-national effort by the HLH in Adults Working Group of the Histiocyte Society (NCT05898477). Methods: We conducted a multicenter, retrospective study evaluating patients diagnosed with lymphoma and hyperinflammation, defined by fulfilling 5/8 HLH diagnostic criteria or the OHI index from 2003-2022. Clinical characteristics were summarized using median and interquartile ranges (IQR). Survival analysis employed Kaplan-Meier curves and the log-rank test, considering HLH diagnosis as the zero time-point. Results: The analysis encompassed 181 patients with lymphoma: 55% had B-cell non-Hodgkin lymphoma (NHL), 35% had natural killer (NK) cell or T-cell lymphoma, and 10% had classical Hodgkin lymphoma. 35% of patients were from China, 21% from the USA, 17% from Israel, 16% from Europe, and 11% from Japan. Of the entire cohort, 157 (87%) patients met the HLH-2004 criteria, and 153 (83%) met the OHI index; The median age at HLH diagnosis was 60 years (IQR, 45-68), and 59% were males. 50% of patients presented with HLH before/at the time of lymphoma diagnosis (median time to lymphoma diagnosis 9 days), while 50% developed HLH after the initial lymphoma diagnosis (median time to HLH diagnosis 181 days). The median values of hemoglobin, absolute neutrophil count (ANC), and platelet count at HLH diagnosis were 8.6 g/dL, 2.1 K/microL, and 54.7 K/microL, respectively. The median values of triglycerides and fibrinogen were 241 mg/dL and 250 mg/dL, respectively. Interestingly, the median values for ANC, triglycerides, and fibrinogen fell outside the HLH-2004 diagnostic threshold. The median and interquartile ranges for ferritin and sCD25 (sIL-2r) were 3017 ng/mL (1337-8958) and 14098 U/mL (7894-39916), respectively. 48% of physicians altered their initial treatment approach due to the HLH diagnosis. Of these instances, 48% were treated with dexamethasone and etoposide outside of a formal treatment protocol, 11% with the HLH-94/2004 protocol, 24% with DEP regimen (liposomal doxorubicin, etoposide, and methylprednisolone), and 4% with DEP and ruxolitinib. Dexamethasone alone was used in 15% of the patients, while another 4% were treated with anakinra +/- steroids. After a median follow-up duration of 2.1y (range, 0.005-6.1), the median overall survival was 0.58 years. 46% of the patients died from multi-organ dysfunction/HLH, 17% from single-organ dysfunction, 16% from infection or septic shock, and 8% from bleeding. The risk of mortality among T-cell or NK cell lymphoma was higher than B-cell lymphoma (HR 1.7, 95% CI 1.16-2.61, Figure 1A). Finally, patients positive for the OHI index alone at diagnosis had a higher mortality risk (Figure 1B) compared to those positive for both the OHI index and HLH-2004 (HR 2.5; CI 1.26 - 4.8) or those positive for HLH-2004 alone (HR 3.72; CI- 1.62-8.58). Conclusions: Preliminary findings from this large multi-institutional study show that the overall survival for patients with lymphoma and HLH remains poor despite the institution of HLH-specific therapies. In nearly half of the cases, the physicians altered lymphoma treatment to control HLH, primarily through dexamethasone and etoposide-based or DEP regimens. Although B-cell lymphoma was our cohort's most common cause of HLH, overall survival was worse among those with T-cell or NK cell lymphoma, suggesting that the underlying lymphoma type might drive the prognosis even in cases with hyperinflammation. The most common causes of death included multi-organ dysfunction and infection. The OHI index-positive patients experienced higher mortality risk than those meeting the HLH-2004 criteria. The study is ongoing, and we plan to present data on the differential effects of treatment regimens at the meeting.

A UK national study of prevalence and correlates of adopting or not adopting a recovery identity among individuals who have overcome a drug or alcohol problem

BackgroundThe concept of recovery has increasingly become an organizing paradigm in the addiction field in the past 20 years, but definitions of the term vary amongst interested groups (e.g. researchers, clinicians, policy makers or people with lived experience). Although professional groups have started to form a consensus, people with lived experience of alcohol or drug (AOD) problems use the term in a different way, leading to confusion in policy making in the UK. Greater knowledge about the prevalence and correlates of adopting a recovery identity amongst those who have overcome an AOD problem would inform clinical, public health, and policy communication efforts.MethodsWe conducted a cross-sectional nationally representative survey of individuals resolving a significant AOD problem (n = 1,373). Weighted analyses estimated prevalence and tested correlates of label adoption. Qualitative analyses summarized reasons for adopting or not adopting a recovery identity.ResultsThe proportion of individuals currently identifying as being in recovery was 52.4%, never in recovery 28.6%, and no longer in recovery 19.0%. Predictors of identifying as being in recovery included current abstinence from AOD, formal treatment, recovery support service or mutual-help participation, and history of being diagnosed with AOD or other psychiatric disorders. Qualitative analyses found themes around not adopting a recovery identity related to low AOD problem severity, viewing the problem as resolved, or having little difficulty in stopping.ConclusionsDespite increasing use of the recovery label and concept in clinical and policy contexts, many resolving AOD problems do not identify in this manner. These are most likely to be individuals with less significant histories of impairment secondary to AOD and who have not engaged with formal or informal treatment systems. The understanding of the term recovery in this UK population did not completely align with abstinence from alcohol or drugs.

6 The Role of CPAP Treatment on Associations Between Obstructive Sleep Apnea and Cognition Among Black and White Older Adults

Objective:Obstructive sleep apnea (OSA) may be a modifiable risk factor for late-life cognitive impairment. We previously demonstrated that non-Hispanic Black older adults are less likely to be diagnosed with OSA despite having equal or greater health risk for OSA compared to non-Hispanic White older adults, and this disparity in diagnosis was strongest among individuals with lower education. Here, we aimed to determine 1) whether there are racial differences in continuous positive airway pressure (CPAP) treatment, 2) how CPAP treatment may influence OSA-cognition associations, and 3) whether CPAP differentially influences OSA-cognition associations across racial groups.Participants and Methods:Cross-sectional data were obtained from 424 socioeconomically diverse community-dwelling adults ages 55-83 (63.4±3.2 years, 41.7% male, 53.5% Black) from the Michigan Cognitive Aging Project. Physician-diagnosed OSA and current CPAP use were self-reported. Global cognition was operationalized as a composite of five factor scores derived from a comprehensive neuropsychological battery. Racial group differences were investigated with chi-square and Fisher’s exact tests with statistical significance set at the .05 level. Associations between OSA and cognition (adjusted for age, gender, race, and years of education) were investigated with linear regressions. Subsequent models isolated effects of uncontrolled OSA by excluding individuals using CPAP. Racial differences in OSA-cognition associations were investigated with race-stratified models.Results:Fewer Black participants (9.2%) reported diagnosed OSA compared to White participants (12.3%; x2 (1, N=424) =5.314, p=.021, cp=.112). In the whole sample, 47.3% of participants with diagnosed OSA reported CPAP use, and this proportion did not differ across race (x2 [1, N=86] =.048, p=.826). In the whole sample, OSA diagnosis was only associated with cognition when CPAP users were excluded (excluding CPAP users: ß=-.085, SE=.037, p=.024; including CPAP users: ß=-.067, SE=.036, p=.062). In race-stratified models, diagnosed OSA was only associated with cognition among Black participants, and this association was stronger when CPAP users were excluded (excluding CPAP users: ß=-.142, SE=.060, p=.018; including CPAP users: ß=-.126, SE=.058, p=.030). Diagnosed OSA was not associated with cognition among White participants, irrespective of whether CPAP users were included (excluding CPAP users: ß=-.084,SE=.068, p=.215; including CPAP users: ß=-.056, SE=.064, p=.378).Conclusions:Our findings support CPAP treatment as a potential intervention to mitigate late-life cognitive impairment among those with OSA. Despite being less likely to receive a diagnosis of OSA, Black older adults were equally likely to engage in CPAP treatment as White older adults when diagnosed. The detrimental impact of OSA on cognition may be more salient among Black older adults, which may reflect racial disparities in cardiovascular risk and/or resources that promote cognitive reserve. However, CPAP appears to be an effective treatment to reduce OSA-related cognitive impairment for Black older adults, highlighting the critical importance of diagnosis and treatment in this group. Intervention efforts that abate racial inequalities in access to quality healthcare in order to facilitate acquisition of a formal OSA diagnosis and CPAP treatment may help to reduce preventable cognitive health disparities among older adults.

Register-based observational study of associations between inflammatory remission, formal treatment targets and the use of disease-modifying antirheumatic drugs among patients with early rheumatoid arthritis

ObjectiveTo assess associations between inflammatory remission, formal treatment targets and the likelihood of starting a new disease-modifying antirheumatic drug (DMARD), among patients with early rheumatoid arthritis (RA).MethodsPatients newly diagnosed with...

Mental Health Self-Tracking Preferences of Young Adults With Depression and Anxiety Not Engaged in Treatment: Qualitative Analysis.

Despite the high prevalence of anxiety and depression among young adults, many do not seek formal treatment. Some may turn to digital mental health tools for support instead, including to self-track moods, behaviors, and other variables related to mental health. Researchers have sought to understand processes and motivations involved in self-tracking, but few have considered the specific needs and preferences of young adults who are not engaged in treatment and who seek to use self-tracking to support mental health. This study seeks to assess the types of experiences young adults not engaged in treatment have had with digital self-tracking for mood and other mental health data and to assess how young adults not seeking treatment want to engage in self-tracking to support their mental health. We conducted 2 online asynchronous discussion groups with 50 young adults aged 18 years to 25 years who were not engaged in treatment. Participants were recruited after indicating moderate to severe symptoms of depression or anxiety on screening surveys hosted on the website of Mental Health America. Participants who enrolled in the study responded anonymously to discussion prompts on a message board, as well as to each other's responses, and 3 coders performed a thematic analysis of their responses. Participants had mixed experiences with self-tracking in the past, including disliking when tracking highlighted unwanted behaviors and discontinuing tracking for a variety of reasons. They had more positive past experiences tracking behaviors and tasks they wanted to increase, using open-ended journaling, and with gamified elements to increase motivation. Participants highlighted several design considerations they wanted self-tracking tools to address, including building self-understanding; organization, reminders, and structure; and simplifying the self-tracking experience. Participants wanted self-tracking to help them identify their feelings and how their feelings related to other variables like sleep, exercise, and events in their lives. Participants also highlighted self-tracking as useful for motivating and supporting basic activities and tasks of daily living during periods of feeling overwhelmed or low mood and providing a sense of accomplishment and stability. Although self-tracking can be burdensome, participants were interested and provided suggestions for simplifying the process. These young adults not engaged in treatment reported interest in using self-tracking to build self-understanding as a goal in and of itself or as a first step in contemplating and preparing for behavior change or treatment-seeking. Alexithymia, amotivation, and feeling overwhelmed may serve both as barriers to self-tracking and opportunities for self-tracking to help.

Application of ideological and political education and mental health education in patients with mild anxiety

BackgroundAccording to the severity of the illness, anxiety can be divided into mild anxiety, moderate anxiety and severe anxiety. When anxiety attacks, patients will be accompanied by mental symptoms such as rising anxiety and restlessness, as well as physical symptoms such as tremor, sweating and nausea. Targeted at college students with mild anxiety disorder, the study combined ideological and political education with mental health education to intervene their treatment.Subjects and MethodsThe study divided 100 college students with mild anxiety disorders in a university into an experimental group and a control group, in which the experimental group was 50 students who received the intervention treatment of ideological and political education combined with mental health education, and the control group was 50 students who did not receive formal treatment. The study utilized the Hamilton Anxiety Measurement Scale (HAMA) to conduct measurements, and finally compared HAMA scores of the two groups after 8 weeks of treatment. The HAMA scores of these two groups were compared.ResultsThe study utilized SPSS23.0 statistical software to analyze the data. The HAMA score of the experimental group after 8 weeks was (8.96±0.59) and that of the control group after 8 weeks was (17.46±3.46), which was better than that of the control group, and there was a significant difference in the comparison of the groups (P<0.05).ConclusionsIdeological and political education combined with mental health education has a significant effect on the intervention of students with mild anxiety disorders, and has certain application value.Acknowledgement2016 Sichuan Provincial Department of Education Humanities and Social Sciences General Project (No.16SB0299); General project of Suining Social Science Federation in 2022 (No.SN22YB020); Key project of Suining Education and Sports Bureau in 2021 (No. 21SNJTG002).

Autonomy Without Borders? Understanding the Impact of Undocumented Residence Status on Healthcare Relationships in Belgium

Access to public healthcare services for Belgium’s undocumented migrants is regulated through a parallel, administrative procedure within the legal framework of Urgent Medical Aid. This imposes several constraints on their access to healthcare services. Drawing on empirical-ethical methodologies, we show how this procedure impacts on the relationship between patients with undocumented status and healthcare workers. We use the concept of relational autonomy to show how the imposed legal constraints reduce the formal treatment options available to healthcare workers, but simultaneously lead to informal care practices, and how the latter increase the discretionary power of the healthcare workers. We argue that in this context, provision becomes unpredictable and arbitrary, with undocumented migrants tending to value strong personal relations with one particular, trusted healthcare worker. Although this leads to increased dependence, it also increases patients’ options and autonomy by providing access to wider professional networks attached to that healthcare worker.

A Formal Treatment of Expressiveness and Relevanceof Digital Evidence

Digital investigations are largely concerned with reconstructing past events based on traces in digital systems. Given their importance, many concepts have been established to describe their quality—most of them concerned with procedural aspects, i.e., authenticity and integrity, for example. Besides that, there exist principal concepts that have been overlooked in the past: Two of those criteria are relevance and expressiveness of digital evidence. Unlike others, those are directly concerned with reaching the investigative goal. Therefore, we approach these two overlooked concepts of digital evidence by giving formal definitions. To illustrate the usefulness, we present two applications: First, we demonstrate that the notions of expressiveness and completeness can be used to guide investigations by presenting the Facet-oriented Criminalistic Cycle as a thinking model, which extends the well-established criminalistic cycle. Second, we put the concepts into practice by calculating the expressiveness of facets from a state machine representation of a digital system utilizing temporal logic and a model checker. Furthermore, we sketch out the implications of this improved way of defining relevance and expressiveness. Accordingly, this article aims to improve the understanding of these critical aspects of the overall investigative process.

Place and place names: a unified model.

The goal of this paper is to offer a unified account of Place as a central theoretical notion across different disciplines. We show that while psychology, geography and other sciences have been converging to a unified view of this notion, linguistics still offers a fragmented perspective. Consequently, place names lack a full-fledged analysis that connects this category to the psychological concept of place. We propose to overcome this impasse by introducing a multi-modal Discourse Representation Theory (DRT) account of place as a conceptual construct and place concepts as specific instances of this construct. We show that current variants of DRT permit us to model place names and their senses, i.e., the meaning(s) that individuals associate with Sydney. We then model non-linguistic place concepts, i.e., the mental representation(s) that individuals can have of the city carrying this name. We present a model of the relation between linguistic meaning and conceptual content via the notion of anchoring relations applied to place. We pair this formal treatment with a morpho-syntactic account of place names building on current generative syntax treatments of proper names. Once we have a morpho-syntactic and semantic model of place names, we use a frame semantics treatment to account for lexical relations among place names. We test the overarching model on a set of recalcitrant problems afflicting current linguistic and multi-disciplinary treatments of place. These are the grammatical complexity and lexical content of place names, place concepts and their networks, and inter-subjective, communicative models of place in discourse. By solving these problems, our account integrates several frameworks (DRT, conceptual analysis, generative syntax, frame semantics) and connects several disciplines (linguistics, psychology, geographic information science, communication models) via a novel, multi-modal account of place. We conclude by discussing the theoretical and empirical import of these results.

Similarity-based reasoning in conceptual spaces.

Whereas the validity of deductive inferences can be characterized in terms of their logical form, this is not true for all inferences that appear pre-theoretically valid. Nonetheless, philosophers have argued that at least some of those inferences-sometimes called "similarity-based inferences" -can be given a formal treatment with the help of similarity spaces, which are mathematical spaces purporting to represent human similarity judgments. In these inferences, we conclude that a given property pertains to a category of items on the grounds that the same property pertains to a similar category of items. We look at a specific proposal according to which the strength of such inferences is a function of the distance, as measured in the appropriate similarity space, between the category referenced in the premise and the category referenced in the conclusion. We report the outcomes of three studies that all support the said proposal.

Evaluating a Smartphone App (MeT4VeT) to Support the Mental Health of UK Armed Forces Veterans: Feasibility Randomized Controlled Trial.

Previous research demonstrates that less than 50% of military veterans experiencing mental health difficulties seek formal support. Veterans often struggle to identify problems as mental health difficulties. In addition, they may fail to recognize the need for support before reaching a crisis point and face difficulties navigating care pathways to access support. A feasibility trial was conducted to assess a novel digital smartphone app (Mental Health Toolkit for Veterans Project [MeT4VeT]) for UK Armed Forces (UKAF) veterans experiencing mental health difficulties. The trial aimed to explore the feasibility and acceptability of trial procedures for a later randomized controlled trial (RCT) and to assess the acceptability of the MeT4VeT app. Participants were recruited at UK military medical centers, by advertising on social media, and through veteran third-sector organizations between February and November 2021, and assessed for eligibility (male, owned a smartphone, served at least 2 years in the UKAF, left the UKAF within the last 2 years, not undertaking formal mental health treatment). Eligible participants were assigned, on a 1:1 ratio, to either the intervention group (full app) or a control group (noninteractive app with signposting information). Three key objectives were determined a priori to assess the practicality of running an RCT including an assessment of recruitment and retention, evaluation of the technical app delivery and measurement processes, and acceptability and usability of the intervention. In total, 791 individuals completed the participant information sheet, of which 261 (33%) were ineligible, 377 (48%) declined or were unable to be contacted for consent, and 103 (13%) did not download the app or complete the baseline measures. Of this, 50 participants completed baseline measures and were randomly assigned to the intervention group (n=24) or the control group (n=26). The trial was effective at enabling both the technical delivery of the intervention and collection of outcome measures, with improvements in mental health demonstrated for the intervention group from baseline to the 3-month follow-up. Recruitment and retention challenges were highlighted with only 50 out of the 530 eligible participants enrolled in the trial. The acceptability and usability of the MeT4VeT app were generally supported, and it was reported to be a useful, accessible way for veterans to monitor and manage their mental health. The results highlighted that further work is needed to refine recruitment processes and maintain engagement with the app. Following this, an RCT can be considered to robustly assess the ability of the app to positively affect mental health outcomes indicated within this trial. ClinicalTrials.gov NCT05993676; https://clinicaltrials.gov/ct2/show/NCT05993676.

Automation of Strategic Data Prioritization in System Model Calibration: Sensor Placement

Model calibration is challenging for large-scale system models with a great number of variables. Existing approaches to partitioning system models and prioritizing data acquisition rely on heuristics rather than formal treatments. The sensor placement problem in physical dynamic systems points to a promising avenue for formalizing data acquisition priorities, which addresses the following question for system models: With the model at hand and pre-existing data availability on a subset of model variables, what are the (next) k model variables that would bring the largest utility to model calibration, once their data are acquired? In this study, we formalize this problem as a combinatorial optimization and adapt two solutions, the information-entropy approach and the miss-probability approach, from physical dynamic systems to system models in management sciences. Next, based on the idea of the data availability partition, we develop a third solution. The new approach can be understood from the entropy perspective and is embedded in the theoretical framework for the evaluation of side information. Our solution applies to system models of all topologies: analytical results of the optimal placement are derived for binary/multinary trees; for general (directed) tree structures, an algorithm to determine the optimal placement is devised, whose complexity is upper-bounded by [Formula: see text] for an n-variable system; for arbitrary model topologies with the presence of loops, sequential-optimal and simulated-annealing schemes are formulated. Three approaches are compared on a validating example; our solution outperforms the two alternatives. Application on a multicompartment system demonstrates the toolkit’s practical use. History: Accepted by Pascal Van Hentenryck, Area Editor for Computational Modeling: Methods & Analysis. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0128 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0128 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .

Software/Code for "Automation of Strategic Data Prioritization in System Model Calibration: Sensor Placement"

Model calibration is challenging for large-scale system models with a great number of variables. Existing approaches to partitioning system models and prioritizing data acquisition rely on heuristics rather than formal treatments. The sensor placement problem in physical dynamic systems points to a promising avenue for formalizing data acquisition priorities, which addresses the following question for system models: With the model at hand and pre-existing data availability on a subset of model variables, what are the (next) k model variables that would bring the largest utility to model cali-bration, once their data are acquired? In this study, we formalize this problem as a com-binatorial optimization and adapt two solutions, the information-entropy approach and the miss-probability approach, from physical dynamic systems to system models in management sciences. Next, based on the idea of the data availability partition, we develop a third solution. The new approach can be understood from the entropy per-spective and is embedded in the theoretical framework for the evaluation of side infor-mation. Our solution applies to system models of all topologies: analytical results of the optimal placement are derived for binary/multinary trees; for general (directed) tree structures, an algorithm to determine the optimal placement is devised, whose complex-ity is upper-bounded by O(nlog2(n))for an n-variable system; for arbitrary model topolo-gies with the presence of loops, sequential-optimal and simulated-annealing schemes are formulated. Three approaches are compared on a validating example; our solution outperforms the two alternatives. Application on a multicompartment system demon-strates the toolkit’s practical use.

The Designed VR Game “Weirdno” on Emotional Regulations and Reality Connections

Visual reality (VR) plays a huge role in mental issue prevention and therapy by providing an immersive experience and distracting patients’ attention from the pain. However, since researchers mainly focus on clinical psychotherapy, VR products are more inclined to formal medical treatment rather than recreational programs. To create a project that is both playable and helpful in improving players' mental health, a game called Weirdno is developed in this article. Weirdno achieves the purpose of making players feel the targeted emotions through the special plot design and immersive experience from the first-person perspective. The fantasy art style and scene design allow players to hover on the edge of reality and virtuality, stimulating a more realistic feel. The open-world mode and interactive design would also increase the playability of the game based on improving players’ emotional management.

“It’s called homophobia baby” exploring LGBTQ + substance use and treatment experiences in the UK

Introduction Gender and sexual minority/minoritized groups are at a higher risk of substance misuse and related harm compared to the rest of the population. However, limited research has focused on understanding the extent of these issues and the support needs of all minoritized groups within the LGBTQ + population. Methods This qualitative cross-sectional survey sought to explore LGBTQ + individuals’ perspectives on substance use and treatment experiences. Researchers used a manual thematic analysis approach to thoroughly study the data, examining each part closely to uncover themes and patterns. Co-produced with stakeholders and developed with input from LGBTQ + individuals with lived experience, the survey included 38 participants across the UK. Results Cannabis (83% n = 20), ecstasy (68% n = 15), and cocaine (67% n = 16) were commonly used substances, while some participants (19% n = 6) reported consuming high levels of alcohol. Many respondents highlighted the role of “stigma” and peer pressure within the LGBTQ + communities as a motivator for substance use. Participants expressed a preference for informal support due to fears of “discrimination” from formal treatment services. Conclusions The study underscores the need for research inclusive of all LGBTQ + groups and highlights the importance of tailored interventions that address the diverse needs of LGBTQ + individuals. Further exploration of peer-led interventions is necessary to assess their effectiveness. The findings emphasize the necessity of person-centered treatment approaches that recognize the heterogeneity of service users.

An Overview of Emerging Trends and Technologies in Ulcerative Colitis


 This report provides an overview of the evolving therapeutic landscape for moderate to severe ulcerative colitis (UC), including recent changes to clinical practice guidelines, key trends in therapeutic strategies, and new or emerging treatment options, with a focus on biologics and small-molecule therapies.
 Recent guidelines on the medical management of patients with UC include those of the American Gastroenterological Association (AGA), American College of Gastroenterology (ACG), and European Crohn’s and Colitis Organisation (ECCO), which were published in 2019, 2020, and 2022, respectively. These guidelines provide an accurate reflection of how clinical practice has changed to incorporate newer therapies that have entered the market and newer evidence that has been published since the release of the Canadian guidelines in 2015. The ACG, AGA, and ECCO guidelines all recommend use of a tumour necrosis factor (TNF) antagonist, vedolizumab, or tofacitinib for induction of remission in patients with moderate to severe UC; the AGA and ECCO guidelines also recommend ustekinumab as an option and recommend vedolizumab over adalimumab, whereas the AGA guidelines recommend early use of biologic drugs over a step-up approach after failure of 5-aminosalicylates.
 Two important trends in therapeutic strategies for UC include changes in the use and definition of treatment targets and recommendations regarding therapeutic drug monitoring (TDM).
 
 The 2021 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) guidelines provide contemporary consensus recommendations for using new and updated targets throughout an individualized treatment timeline in patients with inflammatory bowel disease (IBD). Although histologic remission is not considered a formal UC treatment target in STRIDE-II, it is acknowledged as an adjunctive measure to endoscopic remission to represent a deeper level of healing and is the focus of many current studies.
 The use of TDM emerged from challenges associated with the use of older biologics (primarily TNF antagonists), which posed difficulties related to immunogenicity and dosing. The relevance of TDM for newer biologics with different mechanisms of action, reduced immunogenicity, and fixed dosing (e.g., vedolizumab and ustekinumab) is a topic of ongoing debate. Although AGA guidelines on TDM in IBD and expert consensus statements support the use of reactive TDM for patients with UC who lose response to a TNF antagonist, evidence gaps remain regarding appropriate use of proactive TDM, utility of TDM for small molecules and biologics outside of the TNF antagonist class, and consistent target concentration thresholds to guide dose changes.
 
 
 There is a substantial pipeline of new and emerging drugs for the treatment of adults with moderate to severe UC, with many in phase IIb or III of clinical development; several notable trends of emerging pharmacotherapies exist, including an increasing number of Janus kinase inhibitors, several therapies with biologic targets that are new in UC (e.g., interleukin-23 antibodies, TNF-like ligand 1A inhibitors), an increasing number of oral therapies, and the first combination of 2 biologic therapies in UC.
 The Canadian health care system should be prepared to adapt to the rapidly evolving treatment landscape and potential clinical practice changes in moderate to severe UC. Drugs with new mechanisms of action in the treatment area and the new paradigm of combination therapy with multiple biologics of different classes may lead to improved patient outcomes but can also further complicate the treatment decision-making process. Therefore, it is important for health care providers to stay up to date on new and upcoming treatment options, which may require educational initiatives for both providers and patients as well as updates to the Canadian treatment guidelines. Overall, potential changes on the horizon may have substantial implications for the health care system given the prevalence of UC in Canada, the costs of advanced therapies, and the increasing number of available treatment options.

A clinical decision support system to predict the efficacy for EGFR-TKIs based on artificial neural network.

The efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) was affected by numerous factors. In the study, we developed and validated an artificial neural network (ANN) system based on clinical characteristics and next-generation sequencing (NGS) to support clinical decisions. A multicenter retrospective non-interventional study was conducted. 240 patients from three hospitals with advanced non-small cell lung cancer (NSCLC) and EGFR mutation were tested by NGS before the first treatment. All patients received formal EGFR-TKIs treatment. Five different models were individually trained to predict the efficacy of EGFR-TKIs based on one medical center with 188 patients. Two independent cohorts from other medical centers were collected for external validation. Compared with logistic regression, four machine learning methods showed better predicting abilities for EGFR-TKIs. The inclusion of NGS tests improved the predictive power of models. ANN performed best on the dataset with mutations TP53, RB1, PIK3CA, EGFR mutation sites, and tumor mutation burden (TMB). The prediction accuracy, recall and AUC were 0.82, 0.82, and 0.82, respectively in our final model. In the external validation set, ANN still showed good performance and differentiated patients with poor outcomes. Finally, a clinical decision support software based on ANN was developed and provided a visualization interface for clinicians. This study provides an approach to assess the efficacy of NSCLC patients with first-line EGFR-TKI treatment. Software is developed to support clinical decisions.

Impact of Low Birth Weight on the Prevalence and Economic Burden of Common Childhood Illnesses Among Under-Five Children in India: Findings From Nationally Representative Surveys.

Background Common childhood illnesses such as diarrhea, fever, and acute respiratory infection impose substantial health burdensamong under-five children, and Low Birth Weight (LBW) has been associated with an increased prevalence of these illnesses. However, the impact of LBW on healthcare utilization and the economic burden of these illnesses remains understudied. Aim To assess the impact of LBW on the prevalence, healthcare utilization, and Out of Pocket Expenditure (OOPE) for outpatient (OP) treatment of selected Common Childhood Illnesses(CCHI) among under-five children in India. Methodology This study utilized data from two nationally representative surveys conducted in India; National Family Health Survey (NFHS-5) (2019-2021) and the National Sample Survey Organization (NSSO) 75th Round Schedule Social Consumption: Health (2017-2018). Data from the NFHS-5 was analyzed to assess the impact of LBW on the prevalence of selected CCHI and healthcare utilization. Comparison of OOPE for OP treatment of selected CCHI between LBW and Normal Birth Weight (NBW) children done using the median OOPE for OP visits of CCHI estimated from the NSSO data. Results The two-week prevalence of selected CCHI among LBW and NBW children was found to be 20.0% (95% CI19.6 -20.4) and 18.0% (95% CI 17.8 -18.2), respectively. There was no significant difference between LBW and NBW children on healthcare utilization for the treatment of CCHI; both groups had a similar proportion (around 70%) of formal medical treatment utilization for CCHI. The median OOPE spending for OP visits per episode of CCHI was comparable between LBW and NBW children. However, families of LBW children had higher annual OOPE spending for OP visits related to CCHI, with projected estimates of INR 1,446 ($19.56) for LBW children and INR 1,271 ($17.2) for NBW children. Conclusion LBW was associated with a higher prevalence of CCHI. Even though healthcare utilization was similar among LBW and NBW children, a higher prevalence of CCHI among LBW children led to higher OOPE. LBW children have approximately 13% higher annual OOPE spending for the OP visits related to selectedCCHI compared to NBW children.