Evaluation of an Online CBT Program for Bulimia Nervosa: A Randomised Controlled Trial of Pure vs. Clinician-Supported Self-Help

Cognitive behaviour therapy (CBT) is the treatment with the strongest evidence base for bulimia nervosa (BN); however, the reality remains that majority of individuals with the illness do not seek or access treatment. Innovative, low-resource delivery methods are needed to disseminate evidencebased treatments and overcome barriers to care. Online interventions offer promise as a costefficient and scalable alternative to therapist-led treatments, yet suboptimal rates of retention and adherence threaten their real-world applicability. The overarching aim of the present thesis was to evaluate a newly developed, online self- help treatment for BN, titled Binge Eating eTherapy (BEeT). A secondary aim was to investigate the aspects related the design and delivery of the digital intervention which are responsible for maximising treatment adherence and outcome. The findings are discussed in terms of the capacity for clinically meaningful change to be achieved in both clinician-supported and self-guided settings, the implications this may hold for future implementation of online interventions within the healthcare system, and the meaningful contribution this thesis provides to theoretical and empirical frameworks of digital intervention delivery

Differential expression of stem cell-like proteins in normal, hyperplastic and dysplastic oral epithelium

Objective The identification of stem cells (SC) remains challenging. In the human oral mucosal epithelium, these cells are believed to be in the basal layer (stem cell niche), but their exact location is unclear. The aim of this study was to examine the dysplastic oral epithelium for these SC-like proteins in order to assess their diagnostic value as biomarkers complementing the histological grading of dysplasia. Material and Methods Thirty oral epithelial dysplasia (OED), 25 oral lichen planus (OLP), 10 oral hyperkeratosis and 5 normal oral epithelium (OE) were immunohistochemically examined for four SC markers [integrin β1, neuron-glial-2 (NG2), notch 1 (N1) and keratin 15 (K15)]. Results Three of four SC markers were heterogeneously detected in all samples. K15 overexpression in the lower two-thirds of severe OED suggests an expanded SC niche. Integrin β1 distribution pattern was not measurably different between OEDs and control. NG2 was almost negative to absent in all samples examined. N1 expression was weak and highly variable in normal and dysplastic epithelium, making it an unreliable epithelial stem cell marker. Conclusions Present findings suggest that these markers were unable to identify individual epithelial stem cells. Instead, subpopulations of cells, most probably stem cells and transit amplifying cells with stem cell-like properties were identified in the dysplastic oral epithelium. The characteristic expressions of K15 might be of diagnostic value for oral dysplasia and should be investigated further

Solving the unsolved genetic epilepsies:Current and future perspectives

Many patients with epilepsy undergo exome or genome sequencing as part of a diagnostic workup; however, many remain genetically unsolved. There are various factors that account for negative results in exome/genome sequencing for patients with epilepsy: (1) the underlying cause is not genetic; (2) there is a complex polygenic explanation; (3) the illness is monogenic but the causative gene remains to be linked to a human disorder; (4) family segregation with reduced penetrance; (5) somatic mosaicism or the complexity of, for example, a structural rearrangement; or (6) limited knowledge or diagnostic tools that hinder the proper classification of a variant, resulting in its designation as a variant of unknown significance. The objective of this review is to outline some of the diagnostic options that lie beyond the exome/genome, and that might become clinically relevant within the foreseeable future. These options include: (1) re-analysis of older exome/genome data as knowledge increases or symptoms change; (2) looking for somatic mosaicism or long-read sequencing to detect low-complexity repeat variants or specific structural variants missed by traditional exome/genome sequencing; (3) exploration of the non-coding genome including disruption of topologically associated domains, long range non-coding RNA, or other regulatory elements; and finally (4) transcriptomics, DNA methylation signatures, and metabolomics as complementary diagnostic methods that may be used in the assessment of variants of unknown significance. Some of these tools are currently not integrated into standard diagnostic workup. However, it is reasonable to expect that they will become increasingly available and improve current diagnostic capabilities, thereby enabling precision diagnosis in patients who are currently undiagnosed.</p

Laser ablation strontium isotopes and spatial assignment show seasonal mobility in red deer (Cervus elaphus) at Lazaret Cave, France (MIS 6)

Funding statement This research is part of the collective research project named “Paleoecology of the Lazaret cave: human-environment interactions on the coast of the meridional Alps during the late Middle Pleistocene (MIS6)”, granted by the DRAC PACA (French Ministry of Culture). SB thanks QUADRAT DTP NERC (NE/S007377/1) studentship for stipend support. KB and MLC thank the Leverhulme Trust (RPG-2017-410 and PLP-2019-284) for support during the production of this paper.Peer reviewedPublisher PD

The acceptability, feasibility, and preliminary efficacy of a supported online self-help treatment program for binge-eating disorder

IntroductionStudies in transdiagnostic eating disorder (ED) samples suggest supported online self-help programs (eTherapies) are effective and may improve access to treatment; however, their evaluation in those with binge-eating disorder (BED) is limited. Given BED’s high prevalence and low levels of treatment uptake, further eTherapy evaluation is needed to broaden access to effective, evidence-based treatment options. The aim of this study was to investigate the acceptability, feasibility, and preliminary efficacy of a supported eTherapy for those with BED or subthreshold BED, and to examine symptom change across the duration of therapy.MethodNineteen women with BED completed a supported, 10-session Cognitive Behavioural Therapy-based eTherapy in an uncontrolled, pre-post, and 3 months follow up intervention study. Key outcomes were assessed by the Eating Disorder Examination Questionnaire (EDE-Q): objective binge episode (OBE) frequency and ED psychopathology. Feasibility was evaluated via program adherence and dropout, whilst acceptability was assessed through participant feedback post-treatment. Weekly symptom change (ED psychopathology) during treatment was assessed by the Eating Disorder Examination - Questionnaire Short (EDE-QS).ResultsGeneralised estimating equations showed statistically and clinically significant reductions in OBEs and ED psychopathology (large effects) post-treatment, with these decreases maintained at follow up. Across weekly assessment, a marked slowing in the rate of change in ED psychopathology was observed after four sessions of the program. Program feasibility was high (i.e., 84% of content completed), as was program acceptability (i.e., 93% of participants expressed high levels of satisfaction).DiscussionThese results support the acceptability, feasibility, and preliminary efficacy of a supported eTherapy program for those with BED and suggest the variability of symptom change across the duration of therapy. Future research should further investigate findings in an adequately powered randomised controlled trial

Synthesis, X-ray structure, Hirshfeld surface analysis and antimicrobial assessment of tetranuclear s-triazine hydrazine Schiff base ligand

Funding: The Deputyship for Research and Innovation, “Ministry of Education”, King Saud University (IFKSUOR3-188-3), Saudi Arabia.The unexpected tetranuclear [Cu4(DPPT)2Cl6] complex was obtained by self-assembly of CuCl2.2H2O and (E)-2,4-di(piperidin-1-yl)-6-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)-1,3,5-triazine, ( HDPPT ) in ethanol. In this tetranuclear [Cu4(DPPT)2Cl6] complex, the organic ligand acts as mononegative chelate bridging two crystallographically independent Cu(II) sites. The DPPT− anion acts as a bidentate ligand with respect to Cu(1), while it is a tridentate for Cu(2). The Cu(1)N2Cl3 and Cu(2)N3Cl spheres have square pyramidal and square planar coordination geometries with some distortion, respectively. Two of the chloride ions coordinating the Cu(1) are bridging between two crystallographically related Cu(1) sites connecting two [Cu2(DPPT)Cl3] units together, leading to the tetranuclear formula [Cu4(DPPT)2Cl6]. The packing of the [Cu4(DPPT)2Cl6] complex is dominated by C-H…Cl contacts, leading to one-dimensional hydrogen-bond polymeric structure. According to Hirshfeld surface analysis of molecular packing, the non-covalent interactions H…H, Cl…H, Cl…C, C…H, and N…H are the most significant. Their percentages are 52.8, 19.0, 3.2, 7.7, and 9.7%, respectively. Antimicrobial assessment showed good antifungal activity of the Cu(II) complex against A. fumigatus and C. albicans compared to Ketoconazole as positive control. Moreover, the [Cu4(DPPT)2Cl6] complex has higher activity against Gram-positive bacteria than Gentamycin as positive control. The opposite was observed when testing the tetranuclear [Cu4(DPPT)2Cl6] complex against the Gram-negative bacteria.Publisher PDFPeer reviewe

Patient/Family Education for Newly Diagnosed Pediatric Oncology Patients

There is a paucity of data to support evidence-based practices in the provision of patient/family education in the context of a new childhood cancer diagnosis. Since the majority of children with cancer are treated on pediatric oncology clinical trials, lack of effective patient/family education has the potential to negatively affect both patient and clinical trial outcomes. The Children’s Oncology Group Nursing Discipline convened an interprofessional expert panel from within and beyond pediatric oncology to review available and emerging evidence and develop expert consensus recommendations regarding harmonization of patient/family education practices for newly diagnosed pediatric oncology patients across institutions. Five broad principles, with associated recommendations, were identified by the panel, including recognition that (1) in pediatric oncology, patient/family education is family-centered; (2) a diagnosis of childhood cancer is overwhelming and the family needs time to process the diagnosis and develop a plan for managing ongoing life demands before they can successfully learn to care for the child; (3) patient/family education should be an interprofessional endeavor with 3 key areas of focus: (a) diagnosis/treatment, (b) psychosocial coping, and (c) care of the child; (4) patient/family education should occur across the continuum of care; and (5) a supportive environment is necessary to optimize learning. Dissemination and implementation of these recommendations will set the stage for future studies that aim to develop evidence to inform best practices, and ultimately to establish the standard of care for effective patient/family education in pediatric oncology

Phoenix: A CubeSat Mission to Study the Impact of Urban Heat Islands Within the U.S.

Phoenix is a student-led CubeSat mission, developed at Arizona State University (ASU), to study the effects of Urban Heat Islands in several U.S. cities through infrared remote sensing and educate students on space mission design. The spacecraft is designed using commercial off-the-shelf components (COTS) and several custom support boards developed by the student team. As such, the student team was responsible for the design, test, and validation of the spacecraft to demonstrate the capability of using COTS hardware to conduct high-fidelity science. This paper details the mission’s concept of operations, as well as the spacecraft and ground system design that was developed to complete the mission objective. In addition, it details the mission’s current status now that Phoenix has entered the operations phase, along with resources which have proved beneficial to the team while working with the spacecraft in orbit

Confirmation and expansion of the phenotype of the TCEAL1-related neurodevelopmental disorder

Numerous contiguous gene deletion syndromes causing neurodevelopmental disorders have previously been defined using cytogenetics for which only in the current genomic era the disease-causing genes have become elucidated. One such example is deletion at Xq22.2, previously associated with a neurodevelopmental disorder which has more recently been found to be caused by de novo loss-of-function variants in TCEAL1. So far, a single study reported six unrelated individuals with this monogenetic disorder, presenting with syndromic features including developmental delay especially affecting expressive speech, intellectual disability, autistic-like behaviors, hypotonia, gait abnormalities and mild facial dysmorphism, in addition to ocular, gastrointestinal, and immunologic abnormalities. Here we report on four previously undescribed individuals, including two adults, with de novo truncating variants in TCEAL1, identified through trio exome or genome sequencing, further delineating the phenotype of the TCEAL1-related disorder. Whereas overall we identify similar features compared to the original report, we also highlight features in our adult individuals including hyperphagia, obesity, and endocrine abnormalities including hyperinsulinemia, hyperandrogenemia, and polycystic ovarian syndrome. X chromosome inactivation and RNA-seq studies further provide functional insights in the molecular mechanisms. Together this report expands the phenotypic and molecular spectrum of the TCEAL1-related disorder which will be useful for counseling of newly identified individuals and their families.</p

Confirmation and expansion of the phenotype of the TCEAL1-related neurodevelopmental disorder

Numerous contiguous gene deletion syndromes causing neurodevelopmental disorders have previously been defined using cytogenetics for which only in the current genomic era the disease-causing genes have become elucidated. One such example is deletion at Xq22.2, previously associated with a neurodevelopmental disorder which has more recently been found to be caused by de novo loss-of-function variants in TCEAL1. So far, a single study reported six unrelated individuals with this monogenetic disorder, presenting with syndromic features including developmental delay especially affecting expressive speech, intellectual disability, autistic-like behaviors, hypotonia, gait abnormalities and mild facial dysmorphism, in addition to ocular, gastrointestinal, and immunologic abnormalities. Here we report on four previously undescribed individuals, including two adults, with de novo truncating variants in TCEAL1, identified through trio exome or genome sequencing, further delineating the phenotype of the TCEAL1-related disorder. Whereas overall we identify similar features compared to the original report, we also highlight features in our adult individuals including hyperphagia, obesity, and endocrine abnormalities including hyperinsulinemia, hyperandrogenemia, and polycystic ovarian syndrome. X chromosome inactivation and RNA-seq studies further provide functional insights in the molecular mechanisms. Together this report expands the phenotypic and molecular spectrum of the TCEAL1-related disorder which will be useful for counseling of newly identified individuals and their families.</p