Stimulus Avoidance Assessment: A Systematic Literature Review.

Board certified behavior analysts are ethically required to first address destructive behavior using reinforcement-based and other less intrusive procedures before considering the use of restrictive or punishment-based procedures (ethics standard 2.15; Behavior Analyst Certification Board, 2020). However, the inclusion of punishment in reinforcement-based treatments may be warranted in some cases of severe forms of destructive behavior that poses risk of harm to the client or others. In these cases, behavior analysts are required to base the selection of treatment components on empirical assessment results (ethics standard 2.14; Behavior Analyst Certification Board, 2020). One such preintervention assessment is the stimulus avoidance assessment (SAA), which allows clinicians to identify a procedure that is likely to function as a punisher. Since the inception of this assessment approach, no studies have conducted a systematic literature review of published SAA cases. These data may be pertinent to examine the efficacy, generality, and best practices for the SAA. The current review sought to address this gap by synthesizing findings from peer-reviewed published literature including (1) the phenomenology and epidemiology of the population partaking in the SAA; (2) procedural variations of the SAA across studies (e.g., number of series, session length); (3) important quality indicators of the SAA (i.e., procedural integrity, social validity); and (4) how the SAA informed final treatment efficacy. We discuss findings in the context of the clinical use of the SAA and suggest several avenues for future research.

Reversal of C9orf72 mutation-induced transcriptional dysregulation and pathology in cultured human neurons by allele-specific excision.

Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus. We generated five different genomic excisions at the C9orf72 locus in a patient-derived induced pluripotent stem cell (iPSC) line and a non-diseased wild-type (WT) line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 frontotemporal dementia/amyotrophic lateral sclerosis in motor neurons differentiated from these lines. Comparing the excisions in these isogenic series removed the confounding effects of different genomic backgrounds and allowed us to probe the effects of specific genomic changes. A coding single nucleotide polymorphism in the patient cell line allowed us to distinguish transcripts from the normal vs. mutant allele. Using digital droplet PCR (ddPCR), we determined that transcription from the mutant allele is upregulated at least 10-fold, and that sense transcription is independently regulated from each allele. Surprisingly, excision of the WT allele increased pathologic dipeptide repeat poly-GP expression from the mutant allele. Importantly, a single allele was sufficient to supply a normal amount of protein, suggesting that the C9orf72 gene is haplo-sufficient in induced motor neurons. Excision of the mutant repeat expansion reverted all pathology (RNA abnormalities, dipeptide repeat production, and TDP-43 pathology) and improved electrophysiological function, whereas silencing sense expression did not eliminate all dipeptide repeat proteins, presumably because of the antisense expression. These data increase our understanding of C9orf72 gene regulation and inform gene therapy approaches, including antisense oligonucleotides (ASOs) and CRISPR gene editing.

Logistic burdens of cancer care: A qualitative study.

Cancer treatment often creates logistic conflicts with everyday life priorities; however, these challenges and how they are subjectively experienced have been largely unaddressed in cancer care. Our goal was to describe time and logistic requirements of cancer care and whether and how they interfered with daily life and well-being. We conducted interviews with 20 adults receiving cancer-directed treatment at a single academic cancer center. We focused on participants' perception of the time, effort, and energy-intensiveness of cancer care activities, organization of care requirements, and preferences in how to manage the logistic burdens of their cancer care. Participant interview transcripts were analyzed using an inductive thematic analysis approach. Burdens related to travel, appointment schedules, healthcare system navigation, and consequences for relationships had roots both at the system-level (e.g. labs that were chronically delayed, protocol-centered rather than patient-centered bureaucratic requirements) and in individual circumstances (e.g. greater stressors among those working and/or have young children versus those who are retired) that determined subjective burdensomeness, which was highest among patients who experienced multiple sources of burdens simultaneously. Our study illustrates how objective burdens of cancer care translate into subjective burden depending on patient circumstances, emphasizing that to study burdens of care, an exclusive focus on objective measures does not capture the complexity of these issues. The complex interplay between healthcare system factors and individual circumstances points to clinical opportunities, for example helping patients to find ways to meet work and childcare requirements while receiving care.

Treatment response biomarkers: working towards personalised radiotherapy for lung cancer.

Due to major advances in the field of radiation oncology, patients with lung cancer (LC) can now receive technically individualised radiotherapy treatments. However, in the era of precision oncology, radiotherapy-based treatment selection needs to be improved as many patients do not benefit or are not offered optimum therapies. Cost-effective robust biomarkers can address this knowledge gap and lead to individuals being offered more bespoke treatments leading to improved outcome. This narrative review discusses some of the current achievements and challenges in the realisation of personalised radiotherapy delivery in patients with LC.

Retrospective consecutive controlled case series of outcomes for functional analyses of severe destructive behavior.

Functional analysis methods allow clinicians to determine the variable(s) that maintain destructive behavior. Previous reviews of functional analysis outcomes have included large samples of published and unpublished data sets (i.e., clinical samples). The purpose of this review was to conduct a large retrospective consecutive controlled case series of clinical functional analyses. We sought to identify the prevalence of differentiation, procedural modifications for undifferentiated and differentiated cases, and identified function(s) of destructive behavior. In addition, we extended the existing literature by determining whether functional analysis differentiation and function varied when single or multiple behavior topographies were consequated in the functional analysis. We discuss our findings considering previously published functional analysis reviews, provide avenues for future research, and offer suggestions for clinical practice.

Prospective evaluation of acute neurological events after paediatric cardiac surgery.

OBJECTIVES: Children with CHD are at heightened risk of neurodevelopmental problems; however, the contribution of acute neurological events specifically linked to the perioperative period is unclear. AIMS: This secondary analysis aimed to quantify the incidence of acute neurological events in a UK paediatric cardiac surgery population, identify risk factors, and assess how acute neurological events impacted the early post-operative pathway. METHODS: Post-operative data were collected prospectively on 3090 consecutive cardiac surgeries between October 2015 and June 2017 in 5 centres. The primary outcome of analysis was acute neurological event, with secondary outcomes of 6-month survival and post-operative length of stay. Patient and procedure-related variables were described, and risk factors were statistically explored with logistic regression. RESULTS: Incidence of acute neurological events after paediatric cardiac surgery in our population occurred in 66 of 3090 (2.1%) consecutive cardiac operations. 52 events occurred with other morbidities including renal failure (21), re-operation (20), cardiac arrest (20), and extracorporeal life support (18). Independent risk factors for occurrence of acute neurological events were CHD complexity 1.9 (1.1-3.2), p = 0.025, longer operation times 2.7 (1.6-4.8), p < 0.0001, and urgent surgery 3.4 (1.8-6.3), p < 0.0001. Unadjusted comparison found that acute neurological event was linked to prolonged post-operative hospital stay (median 35 versus 9 days) and poorer 6-month survival (OR 13.0, 95% CI 7.2-23.8). CONCLUSION: Ascertainment of acute neurological events relates to local measurement policies and was rare in our population. The occurrence of acute neurological events remains a suitable post-operative metric to follow for quality assurance purposes.

Whole systems approaches to diet and healthy weight: A scoping review of reviews.

BACKGROUND: Obesity is a global epidemic affecting all age groups, populations, and income levels across continents, though is known to disproportionately affect socioeconomically disadvantaged populations. The causes of obesity are complex, informed by diet and weight practices, but shaped by social, commercial, and environmental factors and government policy. Consequently, a Whole System Approach (WSA)-which considers the many causes of obesity and shifts the focus away from individuals as points of intervention and puts an emphasis on understanding and improving the system in which people live-is required. This scoping review of reviews aims to: determine how WSAs to diet and healthy weight have been implemented and evaluated nationally and internationally; to determine what models or theories have been used to implement WSAs; describe how WSAs have been evaluated; determine if WSAs are effective; and to identify the contribution of the public and/or service users in the development of WSAs. METHOD: Systematic searches were carried out using CINAHL, Scopus, PsycINFO (ProQuest), the Cochrane Library, and MEDLINE. Included review papers were those that focused on the application of a whole system approach to diet and/or healthy weight, and/or reported the theory/model used to implement or simulate this approach. Databases were searched from 1995 to March 2022 using a combination of text and Medical Subject Headings (MeSH terms). In addition, reference sections of identified articles were examined for additional relevant articles. Covidence software was used to screen titles and abstracts from the electronic databases and resolve conflicts. RESULTS: A total of 20,308 articles were initially retrieved; after duplicate removal 7,690 unique title and abstracts were reviewed, and 110 articles were selected for full text review. On completion of full text review, 8 review articles were included for data extraction. These included: one umbrella review, four systematic reviews, a rapid review, and two literature reviews (one of which was on strategic reports written for government and public health policy). Evaluations of WSA were mainly process evaluations although health outcomes were assessed in some studies. Several conceptual frameworks or mathematical modelling approaches have been applied to WSAs for diet, healthy weight, and obesity to inform their planning or delivery, and to understand/map the associated systems. Common mathematical approaches include agent based or System Dynamic Modelling. Underlying both conceptual and mathematical models is an understanding how the elements of the complex systems impact each other to affect diet, healthy weight, and obesity. WSA implementations have reported some success in positively impacting health outcomes including reducing Body Mass Index, reducing sugary food intake, and increasing physical activity. Public and user involvement in WSA was not widely reported. CONCLUSION: The application of WSA to diet and healthy weight shows promise, yet the research is lagging behind their implementation. Further robust evidence for using WSA to address diet and healthy weight are required, including incorporating process and outcome evaluations (perhaps using established approaches such as Systems Dynamic Modelling). Furthermore, the analysis of epidemiological data alongside longitudinal process and outcome evaluation regarding the implementation of a WSA is required.

Contrasting somatic mutation patterns in aging human neurons and oligodendrocytes.

Characterizing somatic mutations in the brain is important for disentangling the complex mechanisms of aging, yet little is known about mutational patterns in different brain cell types. Here, we performed whole-genome sequencing (WGS) of 86 single oligodendrocytes, 20 mixed glia, and 56 single neurons from neurotypical individuals spanning 0.4-104 years of age and identified >92,000 somatic single-nucleotide variants (sSNVs) and small insertions/deletions (indels). Although both cell types accumulate somatic mutations linearly with age, oligodendrocytes accumulated sSNVs 81% faster than neurons and indels 28% slower than neurons. Correlation of mutations with single-nucleus RNA profiles and chromatin accessibility from the same brains revealed that oligodendrocyte mutations are enriched in inactive genomic regions and are distributed across the genome similarly to mutations in brain cancers. In contrast, neuronal mutations are enriched in open, transcriptionally active chromatin. These stark differences suggest an assortment of active mutagenic processes in oligodendrocytes and neurons.

Recommendations for accelerating open preprint peer review to improve the culture of science.

Peer review is an important part of the scientific process, but traditional peer review at journals is coming under increased scrutiny for its inefficiency and lack of transparency. As preprints become more widely used and accepted, they raise the possibility of rethinking the peer-review process. Preprints are enabling new forms of peer review that have the potential to be more thorough, inclusive, and collegial than traditional journal peer review, and to thus fundamentally shift the culture of peer review toward constructive collaboration. In this Consensus View, we make a call to action to stakeholders in the community to accelerate the growing momentum of preprint sharing and provide recommendations to empower researchers to provide open and constructive peer review for preprints.

Implementation of depression management by ambulatory care pharmacists in the primary care setting.

BACKGROUND: In the United States, depression is one of the most common mental health disorders. Ambulatory care pharmacists play a critical role in assisting with medication and dosage selection, identifying and managing drug interactions and adverse effects, and increasing medication adherence. Existing data on depression management by ambulatory care pharmacists trained in primary care is limited and outdated. OBJECTIVES: This study provides insight into current practices for depression management by primary care pharmacy specialists within an academic health center and how pharmacist interventions may impact functional outcomes of depression. METHODS: This single-center, retrospective study analyzed 27 patients with a primary care physician within the health system who were seen by an ambulatory care pharmacist for depression. Subjects were excluded if they were under 18 years old, pregnant, or had a diagnosis of bipolar disorder, schizophrenia, schizoaffective disorder, or dementia. The primary outcome was characterization of pharmacist interventions for treatment of depression. Secondary outcomes included change in depressive symptoms, as measured by the patient health questionnaire (PHQ), characterization of adverse effects correlated with medications for depression, and utilization of pharmacogenomics testing and results. RESULTS: Of 27 patients seen by a pharmacist for depression management, 38 total interventions were made, with an average of 1.77 interventions per patient. The most common intervention was new medication initiation (32%). Average PHQ-9 scores dropped from 14.9 to 7.3 twelve weeks following the initial pharmacist visit. Only 6 patients reported adverse effects to a current antidepressant during their visit with the pharmacist, and only 2 of these cases warranted a change in therapy. Ten patients obtained pharmacogenomic testing with pharmacist facilitation. CONCLUSION: Pharmacists in the primary care setting are positioned to be an additional resource for depression management and can offer a wide variety of interventions to improve patient health.

Metastatic gastric adenocarcinoma to the cutaneous neck and chest wall.

This case describes an atypical cutaneous presentation of metastatic gastric carcinoma in a patient initially presenting with dysphagia and a sclerotic red plaque overlying the anterior neck and chest. Skin biopsy revealed metastatic adenocarcinoma from the upper gastrointestinal tract. Esophagogastroduodenoscopy revealed stage IV metastatic gastric adenocarcinoma. Treatment with chemotherapy was initiated.

Updated Recommendations for Reinforcement Schedule Thinning following Functional Communication Training.

Schedule thinning is a necessary treatment procedure following the acquisition of a communication response during functional communication training. In this article, we update and extend the Hagopian et al. Behavior Analysis in Practice, 4, 4-16, (2011) review and recommendations on schedule-thinning procedures following functional communication training. Since their publication, substantial research has been published on the efficacy, efficiency, and social validity of schedule-thinning methods. We provide updated recommendations for schedule thinning based on contemporary literature that has been published since 2011, as well as discuss key areas for future research.

The Impact of Morbidities Following Pediatric Cardiac Surgery on Family Functioning and Parent Quality of Life.

We previously selected and defined nine important post-operative morbidities linked to paediatric cardiac surgery, and prospectively measured their incidence following 3090 consecutive operations. Our aim was to study the impact of these morbidities on family functioning and parental quality of life over 6 months in a subset of cases. As part of a prospective case matched study in five of the ten children's cardiac centers in the UK, we compared outcomes for parents of children who had a 'single morbidity', 'multiple morbidities', 'extracorporeal life support (ECLS)' or 'no morbidity'. Outcomes were evaluated using the PedsQL Family impact module (FIM) at 6 weeks and 6 months post-surgery. Outcomes were modelled using mixed effects regression, with adjustment for case mix and clustering within centers. We recruited 340 patients with morbidity (60% of eligible patients) and 326 with no morbidity over 21 months. In comparison to the reference group of 'no morbidity', after adjustment for case mix, at 6 weeks parent health-related quality of life (HRQoL) and total FIM sores were lower (worse) only for ECLS (p < 0.005), although a higher proportion of parents in both the ECLS and multi-morbidity groups had low/very low scores (p < .05). At 6 months, parent outcomes had improved for all groups but parent HRQoL and total score for ECLS remained lower than the 'no morbidity' group (p < .05) and a higher proportion of families had low or very low scores in the ECLS (70%) group (p < .01). Post-operative morbidities impact parent HRQoL and aspects of family functioning early after surgery, with this impact lessening by 6 months. Families of children who experience post-operative morbidities should be offered timely psychological support.

Abortion training in U.S. obstetrics and gynecology residency programs in a post-Dobbs era.

OBJECTIVES: The Accreditation Council for Graduate Medical Education requires all obstetrics and gynecology residents have access to abortion training. The impact of Dobbs on training remains unknown. We aimed to describe residency programs affected by abortion bans and those lacking abortion training despite permissive state policies. We considered demographic data to understand the impacts on residents under-represented in medicine. STUDY DESIGN: We used residency databases and websites to abstract data. We identified programs offering routine abortion training as either those with Ryan Programs or those with website or email acknowledgment of training. We defined states with abortion bans as those with either complete or 6-week bans as of December 2022. We used χ2 and Student's t tests in descriptive analyses and performed a logistic regression to adjust for demographic and program-specific variables. RESULTS: Of 286 residency programs included, 140 (49%) offered routine abortion training prior to Dobbs. As of December 2022, 19 of these (14%) had lost the ability to provide routine in-state abortion training. Of 223 residency programs in states with legal abortion, 102 (46%) programs lacked routine abortion training. These sites were more likely to be community or community-university programs, with graduates more likely to practice as generalists. Resident race/ethnicity did not differ between residents in states with legal abortion vs abortion bans. CONCLUSIONS: Nearly half of obstetrics and gynecology residency programs in states with legal abortion do not appear to provide routine abortion training. Further work is needed to understand this paucity of training and maximize access in legislatively permissible environments. IMPLICATIONS: Following Dobbs, 14% of residency programs lost in-state abortion training. Notably, in states with legal abortion, 46% of programs lack routine abortion training despite permissive legislation. This presents a window of opportunity for expansion of abortion training, particularly at community and community-university hybrid residency sites.

A Calvarial Defect Model to Investigate the Osteogenic Potential of Umbilical Cord Stem Cells in Bone Regeneration.

BACKGROUND: The standard graft material for alveolar cleft repair (ACR) is autogenous iliac crest. A promising alternative potential graft adjunct-newborn human umbilical cord mesenchymal stem cells (h-UCMSCs)-has yet to be explored in vivo. Their capacity for self-renewal, multipotent differentiation, and proliferation allows h-UCMSCs to be harnessed for regenerative medicine. This study sought to evaluate the efficacy of using tissue-derived h-UCMSCs and their osteogenic capabilities to improve ACR in a murine model. METHODS: Foxn1 mice were separated into three groups with the following calvarial defects: no treatment (empty defect; n = 6), poly(D,L-lactide-co-glycolide) (PLGA) scaffold ( n = 6), or h-UCMSCs with PLGA ( n = 4). Bilateral 2-mm-diameter parietal bone critical-sized defects were created using a dental drill. Microcomputed tomography (microCT) imaging was performed 1, 2, 3, and 4 weeks postoperatively. The mice were euthanized 4 weeks postoperatively for RNAScope, immunohistochemical, and histological analysis. RESULTS: No mice experienced complications during the follow-up period. MicroCT imaging and histological analysis demonstrated that the no-treatment and PLGA-only defects remained patent without significant defect size differences across groups. In contrast, the h-UCMSCs with PLGA group had significantly greater bone fill on microCT and histological analysis. CONCLUSIONS: This study demonstrates a successful calvarial defect model for the investigation of h-UCMSC-mediated osteogenesis and bone repair. Evidence reveals that PLGA alone has neither short-term effects on bone formation nor any unwanted side effects, making it an attractive scaffold. Further investigation using h-UCMSCs with PLGA in larger animals is warranted to advance future translation to patients requiring ACR. CLINICAL RELEVANCE STATEMENT: The authors' results demonstrate a successful murine calvarial defect model for the investigation of h-UCMSC-mediated osteogenesis and bone repair, and they provide preliminary evidence for the safe and efficacious use of this graft adjunct in alveolar cleft repair.

ICTV Virus Taxonomy Profile: Discoviridae 2023.

Discoviridae is a family of negative-sense RNA viruses with genomes of 6.2-9.7 kb that have been associated with fungi and stramenopiles. The discovirid genome consists of three monocistronic RNA segments with open reading frames (ORFs) that encode a nucleoprotein (NP), a nonstructural protein (Ns), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Discoviridae, which is available at ictv.global/report/discoviridae.

ICTV Virus Taxonomy Profile: Leishbuviridae 2023.

Leishbuviridae is a family of negative-sense RNA viruses with genomes of about 8.0 kb that have been found in protists. The leishbuvirid genome consists of three monocistronic RNA segments with open reading frames (ORFs) that encode a nucleoprotein (NP), a glycoprotein (GP), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Leishbuviridae, which is available at ictv.global/report/leishbuviridae.

ICTV Virus Taxonomy Profile: Mypoviridae 2023.

Mypoviridae is a family of negative-sense RNA viruses with genomes of about 16.0 kb that have been found in myriapods. The mypovirid genome consists of three monocistronic RNA segments that encode a nucleoprotein (NP), a glycoprotein (GP), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Mypoviridae, which is available at: ictv.global/report/mypoviridae.

ICTV Virus Taxonomy Profile: Tulasviridae 2023.

Tulasviridae is a family of ambisense RNA viruses with genomes of about 12.2 kb that have been found in fungi. The tulasvirid genome is nonsegmented and contains three open reading frames (ORFs) that encode a nucleoprotein (NP), a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain, and a protein of unknown function (X). This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Tulasviridae, which is available at ictv.global/report/tulasviridae.