Direct Training to Increase Inter-rater Agreement between an Observer’s and Teachers’ Self-Report Ratings of Treatment Integrity

Measuring an implementer’s treatment integrity, specifically an implementer’s adherence to steps of an intervention, can be done via direct (e.g., observation) or indirect (e.g., self-report) methods of assessment. Direct observation is a widely used and accepted method of data collection in research due to its technical adequacy. However, direct observation is resource intensive, often making it impractical outside of research. Self-report measures of adherence can be less resource intensive and are commonly used in school settings, yet results from previous research indicate that implementers frequently overestimate their adherence when using self-report measures. To address this issue, results from research that build support for teacher self-report as a reliable method of treatment integrity assessment are needed. As such, the objective of the current study was to improve inter-rater agreement (IRA) between teachers’ adherence self-report ratings and ratings provided by an observer. The student investigator (i.e., primary observer) observed instructional practice during baseline. Then, after a brief indirect training on the intervention, the primary observer and teachers rated teacher adherence to an explicit instruction intervention. When it was determined that the teachers’ adherence ratings did not adequately agree with the observer’s, teachers were staggered into a phase in which they received direct training on the intervention steps to assess if a change in IRA occurred. Results indicate that after direct intervention training, IRA between the primary observer and teachers improved

The impact of conceptual structures on transaction and enterprise architecture practices

This research hypothesises is Conceptual Structures using the Resource Event Agent (REA) ontology adds value when defining a Transaction Oriented Architecture (TOA) for Enterprise Systems. Enterprise Systems drive global economic growth through well-designed implementations that provide organisations with multiple benefits, including streamlined business processes, increased efficiencies, improved productivity and decreased costs. Conversely, poorly implemented Enterprise Systems can lead to poor operating results. Most Enterprise Systems still use traditional methods of storing economic data mirroring the double-entry bookkeeping system, which can cause several problems, including data loss and repetition. Enterprise Systems must capture transaction data in a format available to multiple business processes to fulfil their goals. This thesis provides an overview of the currently available frameworks for Enterprise Architecture design. It details the problems that are observed and experienced during the completion of real-world Enterprise System development projects. The basis of the Transaction Concept is then presented as the general solution, leading to a TOA for Enterprise Systems. The Transaction Pyramid describes TOA through three layers of transactions: Enterprise, Business, and Database. The Design Science Research Methodology (DSRM) is used as the primary research methodology to provide a framework to this research. Together with the secondary research method of Action Research to provide a more granular basis for DSRM Step 3 : "Design and development", which required multiple minor iterations of the cyclical process of Action Research to produce the required artefacts. The case study approach is used also as a secondary research method for empirical inquiry and investigation required for DSRM step 4: "Demonstration". A Knowledge Management System is defined to validate TOA, and artefacts are implemented for an Automated REA (AREA) based on Protégé Frames to underpin TOA as a Proof of Concept. AREA provides a fully- edged, TOA design tool for Enterprise Architecture using the REA ontology. AREA's Knowledge Repository uses Conceptual Structures through a) the ISO Common Logic standard's Conceptual Graph Interchange Format (CGIF) to store and transmit the TOA using an REA ontology, and b) Formal Concept Analysis (FCA) for validation. AREA is then demonstrated and evaluated using two industrial case studies as exemplars. These Findings support the research's hypothesis and its contribution to knowledge

A scoping review of therapeutic mentoring for youth mental health

IntroductionTherapeutic mentoring, which leverages paraprofessional care, is a potential way to scale access to care to address the youth mental health crisis. This scoping review synthesizes the current state of research on self-designated therapeutic mentoring programs for youth mental health.MethodA systematic search was conducted across four databases using the term “therapeutic mento*” and related keywords, taking a label-first approach to describe the available literature. Inclusion criteria were peer-reviewed articles about research on therapeutic mentoring in the US, written in English. Data were extracted on study characteristics, intervention details, mentor background, and outcomes.ResultsEighteen empirical articles were identified, published between 2003 and 2024. Most studies focused on at-risk youth from diverse backgrounds. Therapeutic mentoring programming varied, although most (N = 13) studies examined the Campus Connections program. Mentors were typically trained paraprofessionals or undergraduate students supervised by clinical professionals. Only two randomized controlled trials were found, both of the Campus Connections program.DiscussionThe review revealed a lack of rigorous experimental studies on therapeutic mentoring efficacy, as defined by studies that use the term therapeutic mentoring. While some studies showed promising effects, more research is needed to establish the definition of therapeutic mentoring and whether it is an acceptable and effective intervention for youth mental health.ConclusionA clear definition of therapeutic mentoring is needed to advance the field and facilitate systematic evaluation of its effectiveness in supporting youth mental health. Future research should prioritize developing program models that align with diverse youth's cultural values, conducting randomized controlled trials, examining program components, and developing standardized measures for assessing therapeutic mentoring outcomes

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

PsAID12 provisionally endorsed at OMERACT 2018 as core outcome measure to assess psoriatic arthritis-specific health-related quality of life in clinical trials

Objective The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) psoriatic arthritis (PsA) working group is developing a Core Outcome Measurement Set for PsA clinical trials [randomized controlled trials (RCT) and longitudinal observational studies (LOS)] using the OMERACT Filter 2.1 instrument selection algorithm. Our objective was to assess the Psoriatic Arthritis Impact of Disease questionnaire (PsAID12) for the measurement of the core domain PsA-specific health-related quality of life (HRQOL). Methods PsAID12 measurement property evidence gathered in a systematic literature review, and additional analyses conducted in LOS, were used to inform a consensus process. Analyses that had not been published were independently reviewed by the OMERACT technical advisory group. Data and process were presented, discussed in breakout groups, and voted on at the OMERACT conference (Terrigal, Australia, May 2018). Results PsAID12 fulfilled the green (good to go) OMERACT standards for domain match, feasibility, reliability, and construct/longitudinal construct validity. Discrimination and thresholds of meaning were amber (caution but good enough to go forward). The overall working group recommendation was amber/provisional endorsement of PsAID12 for measuring PsA-specific HRQOL in RCT and LOS. Of 96 participants who voted at the PsA OMERACT workshop, 87.5% (84) voted “yes” to endorse this recommendation; 14 of the 96 were patient research partners (PRP) and 93% of them (13) voted “yes”; 82 participants were not PRP and 87% of them (71) voted “yes.” Conclusion At OMERACT 2018, PsAID12 was the first patient-reported outcome measure provisionally endorsed as a core outcome measure for disease-specific HRQOL in PsA clinical trials. PsAID12 discrimination and improvement thresholds will be studied in future RCT

Population genomic analysis of bacterial pathogen niche adaptation

Globally disseminated bacterial pathogens frequently cause epidemics that are of major importance in public health. Of particular significance is the capacity for some of these bacteria to switch into a new environment leading to the emergence of pathogenic clones. Understanding the evolution and epidemiology of such pathogens is essential for designing rational ways for prevention, diagnosis and treatment of the diseases they cause. Whole-genome sequencing of multiple isolates facilitating comparative genomics and phylogenomic analyses provides high-resolution insights, which are revolutionizing our understanding of infectious diseases. In this thesis, a range of population genomic analyses are employed to study the molecular mechanisms and the evolutionary dynamics of bacterial pathogen niche adaptation, specifically between humans, animals and the environment. A large-scale population genomic approach was used to provide a global perspective of the host-switching events that have defined the evolution of Staphylococcus aureus in the context of its host-species. To investigate the genetic basis of host-adaptation, we performed genome-wide association analysis, revealing an array of accessory genes linked to S. aureus host-specificity. In addition, positive selection analysis identified biological pathways encoded in the core genome that are under diversifying selection in different host-species, suggesting a role in host-adaptation. These findings provide a high-resolution view of the evolutionary landscape of a model multi-host pathogen and its capacity to undergo changes in host ecology by genetic adaptation. To further explore S. aureus host-adaptive evolution, we examined the population dynamics of this pathogen after a simulated host-switch event. S. aureus strains of human origin were used to infect the mammary glands of sheep, and bacteria were passaged in multiple animals to simulate onward transmission events. Comparative genomics of passaged isolates allowed us to characterize the genetic changes acquired during the early stages of evolution in a novel host-species. Co-infection experiments using progenitor and passaged strains indicated that accumulated mutations contributed to enhanced fitness, indicating adaptation. Within-host population genomic analysis revealed the existence of population bottlenecks associated with transmission and establishment of infection in new hosts. Computational simulations of evolving genomes under regular bottlenecks supported that the fitness gain of beneficial mutations is high enough to overcome genetic drift and sweep through the population. Overall, these data provide new information relating to the critical early events associated with adaptation to novel host-species. Finally, population genomics was used to study the total diversity of Legionella longbeachae from patient and environmental sources and to investigate the epidemiology of a L. longbeachae outbreak in Scotland. We analysed the genomes of isolates from a cluster of legionellosis cases linked to commercial growing media in Scotland and of non-outbreak-associated strains from this and other countries. Extensive genetic diversity across the L. longbeachae species was identified, associated with intraspecies and interspecies gene flow, and a wide geographic distribution of closely related genotypes. Of note, a highly diverse pool of L. longbeachae genotypes within compost samples that precluded the genetic establishment of an infection source was observed. These data represent a view of the genomic diversity of this pathogen that will inform strategies for investigating future outbreaks. Overall, our findings demonstrate the application of population genomics to understand the molecular mechanisms and the evolutionary dynamics of bacterial adaptation to different ecological niches, and provide new insights relevant to other major bacterial pathogens with the capacity to spread between environments

ABCA7 frameshift deletion associated with Alzheimer disease in African Americans

Objective: To identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD. Methods: Custom capture sequencing was performed on ∼150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; replication n = 1,749) and whole exome sequencing of Caribbean Hispanic (CH) AD families. Results: A 44-base pair deletion (rs142076058) was identified in all 77 risk genotype carriers, which shows that the deletion is in high linkage disequilibrium with the risk allele. The deletion was assessed in a large data set (531 cases and 527 controls) and, after adjustments for age, sex, and APOE status, was significantly associated with disease (p = 0.0002, odds ratio [OR] = 2.13 [95% confidence interval (CI): 1.42–3.20]). An independent data set replicated the association (447 cases and 880 controls, p = 0.0117, OR = 1.65 [95% CI: 1.12–2.44]), and joint analysis increased the significance (p = 1.414 × 10−5, OR = 1.81 [95% CI: 1.38–2.37]). The deletion is common in AA cases (15.2%) and AA controls (9.74%), but in only 0.12% of our non-Hispanic white cohort. Whole exome sequencing of multiplex, CH families identified the deletion cosegregating with disease in a large sibship. The deleted allele produces a stable, detectable RNA strand and is predicted to result in a frameshift mutation (p.Arg578Alafs) that could interfere with protein function. Conclusions: This common ABCA7 deletion could represent an ethnic-specific pathogenic alteration in AD

Amyloid-β predominant Alzheimer’s disease neuropathologic change

Different subsets of Alzheimer's disease neuropathologic change (ADNC), including the intriguing set of individuals with severe/widespread amyloid-β (Aβ) plaques but no/mild tau tangles [Aβ-predominant (AP)-ADNC], may have distinct genetic and clinical features. Analysing National Alzheimer's Coordinating Center data, we stratified 1187 participants into AP-ADNC (n = 95), low Braak primary age-related tauopathy (PART; n = 185), typical-ADNC (n = 832) and high-Braak PART (n = 75). AP-ADNC differed in some clinical features and genetic polymorphisms in the APOE, SNX1, WNT3/MAPT and IGH genes. We conclude that AP-ADNC differs from classical ADNC with implications for in vivo studies