Three-Dimensional Engineered Bone from Bone Marrow Stromal Cells and Their Autogenous Extracellular Matrix

Most bone tissue engineering research uses porous three-dimensional (3D) scaffolds for cell seeding. In this work, scaffold-less 3D bone-like tissues were engineered from rat bone marrow stromal cells (BMSCs) and their autogenous extracellular matrix (ECM). The BMSCs were cultured on a 2D substrate in medium that induced osteogenic differentiation. After reaching confluence and producing a sufficient amount of their own ECM, the cells contracted their tissue monolayer around two constraint points, forming scaffold-less cylindrical engineered bone-like constructs (EBCs). The EBCs exhibited alizarin red staining for mineralization and alkaline phosphatase activity and contained type I collagen. The EBCs developed a periosteum characterized by fibroblasts and unmineralized collagen on the periphery of the construct. Tensile tests revealed that the EBCs in culture had a tangent modulus of 7.5+/-0.5MPa at 7 days post-3D construct formation and 29+/-9MPa at 6 weeks after construct formation. Implantation of the EBCs into rats 7 days after construct formation resulted in further bone development and vascularization. Tissue explants collected at 4 weeks contained all three cell types found in native bone: osteoblasts, osteocytes, and osteoclasts. The resulting engineered tissues are the first 3D bone tissues developed without the use of exogenous scaffolding.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78137/1/ten.tea.2007.0140.pd

A systematic digital approach to implementation and dissemination of eating disorders interventions to large populations identified through online screening: Implications for post-traumatic stress

Background: We describe an approach to implementation and dissemination that focuses on changing outcomes variables within a large, defined population and attempts to provide cost-effective opportunities and resources-which might include the provision of both digital and traditional interventions-to address individual needs and interests. We present a case example of how aspects of this model are being applied to increase reach, engagement and outcomes for individuals who complete a national eating disorders screen, and are likely to have an eating disorder but who are not in treatment. We then describe how this model can apply to post-traumatic stress (PTS) and conclude with a discussion of limitations and issues with the model. Methods: The National Eating Disorders Association (NEDA) provides online screening for eating disorders. Results: From February 2017 through March 2018, over 200,000 individuals completed the NEDA screen. Of these, 96% screened positive or at risk for an eating disorder, and most of those who screened positive for a clinical/subclinical eating disorder were not currently in treatment. Less than 10% engaged in self-help or guided self-help online digital program, or expressed interest in calling a helpline for referral to treatment. Conclusions: A systematic digital approach to implementation and dissemination has the potential to increase the number of individuals who benefit from interventions in defined populations. Uptake rates need to be improved

Attenuated Expression of DFFB is a Hallmark of Oligodendrogliomas with 1p-Allelic Loss

Allelic loss of chromosome 1p is frequently observed in oligodendroglioma. We screened 177 oligodendroglial tumors for 1p deletions and found 6 tumors with localized 1p36 deletions. Several apoptosis regulation genes have been mapped to this region, including Tumor Protein 73 (p73), DNA Fragmentation Factor subunits alpha (DFFA) and beta (DFFB), and Tumor Necrosis Factor Receptor Superfamily Members 9 and 25 (TNFRSF9, TNFRSF25). We compared expression levels of these 5 genes in pairs of 1p-loss and 1p-intact tumors using quantitative reverse-transcriptase PCR (QRTPCR) to test if 1p deletions had an effect on expression. Only the DFFB gene demonstrated decreased expression in all tumor pairs tested. Mutational analysis did not reveal DFFB mutations in 12 tested samples. However, it is possible that DFFB haploinsufficiency from 1p allelic loss is a contributing factor in oligodendroglioma development

A framework for applying natural language processing in digital health interventions

BACKGROUND: Digital health interventions (DHIs) are poised to reduce target symptoms in a scalable, affordable, and empirically supported way. DHIs that involve coaching or clinical support often collect text data from 2 sources: (1) open correspondence between users and the trained practitioners supporting them through a messaging system and (2) text data recorded during the intervention by users, such as diary entries. Natural language processing (NLP) offers methods for analyzing text, augmenting the understanding of intervention effects, and informing therapeutic decision making. OBJECTIVE: This study aimed to present a technical framework that supports the automated analysis of both types of text data often present in DHIs. This framework generates text features and helps to build statistical models to predict target variables, including user engagement, symptom change, and therapeutic outcomes. METHODS: We first discussed various NLP techniques and demonstrated how they are implemented in the presented framework. We then applied the framework in a case study of the Healthy Body Image Program, a Web-based intervention trial for eating disorders (EDs). A total of 372 participants who screened positive for an ED received a DHI aimed at reducing ED psychopathology (including binge eating and purging behaviors) and improving body image. These users generated 37,228 intervention text snippets and exchanged 4285 user-coach messages, which were analyzed using the proposed model. RESULTS: We applied the framework to predict binge eating behavior, resulting in an area under the curve between 0.57 (when applied to new users) and 0.72 (when applied to new symptom reports of known users). In addition, initial evidence indicated that specific text features predicted the therapeutic outcome of reducing ED symptoms. CONCLUSIONS: The case study demonstrates the usefulness of a structured approach to text data analytics. NLP techniques improve the prediction of symptom changes in DHIs. We present a technical framework that can be easily applied in other clinical trials and clinical presentations and encourage other groups to apply the framework in similar contexts

Information theoretic evaluation of a noiseband-based cochlear implant simulator

Noise-band vocoders are often used to simulate the signal processing algorithms used in cochlear implants (CIs), producing acoustic stimuli that may be presented to normal hearing (NH) subjects. Such evaluations may obviate the heterogeneity of CI user populations, achieving greater experimental control than when testing on CI subjects. However, it remains an open question whether advancements in algorithms developed on NH subjects using a simulator will necessarily improve performance in CI users. This study assessed the similarity in vowel identification of CI subjects and NH subjects using an 8-channel noise-band vocoder simulator configured to match input and output frequencies or to mimic output after a basalward shift of input frequencies. Under each stimulus condition, NH subjects performed the task both with and without feedback/training. Similarity of NH subjects to CI users was evaluated using correct identification rates and information theoretic approaches. Feedback/training produced higher rates of correct identification, as expected, but also resulted in error patterns that were closer to those of the CI users. Further evaluation remains necessary to determine how patterns of confusion at the token level are affected by the various parameters in CI simulators, providing insight into how a true CI simulation may be developed to facilitate more rapid prototyping and testing of novel CI signal processing and electrical stimulation strategies

Training, supervision, and experience of coaches offering digital guided self-help for mental health concerns

Accessible, low-cost intervention options are necessary to address the rise in mental health problems among college students. Digital guided self-help, or coached, programs have been developed to provide such services, with many commercially available. As such, there are a large and growing number of individuals coaching these programs. However, an unmet need is to evaluate and assess best practices for training and supervising individuals in these positions. To this end, we describe how we recruited, trained, and supervised coaches as part of a large randomized controlled trial using a widely available digital commercial platform. Coaches were trained to provide digital guided self-help for depression, anxiety, and/or eating disorders for college students. Coaches initially attended three live training sessions over 2-3 weeks, viewed multiple training videos, and read a detailed coaching manual developed by our team. Thereafter, they attended weekly supervision. Following their term, coaches completed an exit survey to assess their supervision and training experiences. A total of 37 of 70 (53%) graduate-level student coaches completed the survey. The experience was reported as very positive (95%). In particular, the majority reported feeling well prepared, more confident, and felt they had developed useful skills for their own practice

The decline and rise of neighbourhoods: the importance of neighbourhood governance

There is a substantial literature on the explanation of neighbourhood change. Most of this literature concentrates on identifying factors and developments behind processes of decline. This paper reviews the literature, focusing on the identification of patterns of neighbourhood change, and argues that the concept of neighbourhood governance is a missing link in attempts to explain these patterns. Including neighbourhood governance in the explanations of neighbourhood change and decline will produce better explanatory models and, finally, a better view about what is actually steering neighbourhood change

Effectiveness of a digital cognitive behavior therapy-guided self-help intervention for eating disorders in college women: A cluster randomized clinical trial

Importance: Eating disorders (EDs) are common, serious psychiatric disorders on college campuses, yet most affected individuals do not receive treatment. Digital interventions have the potential to bridge this gap. Objective: To determine whether a coached, digital, cognitive behavior therapy (CBT) intervention improves outcomes for college women with EDs compared with referral to usual care. Design, Setting, and Participants: This cluster randomized trial was conducted from 2014 to 2018 at 27 US universities. Women with binge-purge EDs (with both threshold and subthreshold presentations) were recruited from enrolled universities. The 690 participants were followed up for up to 2 years after the intervention. Data analysis was performed from February to September 2019. Interventions: Universities were randomized to the intervention, Student Bodies-Eating Disorders, a digital CBT-guided self-help program, or to referral to usual care. Main Outcomes and Measures: The main outcome was change in overall ED psychopathology. Secondary outcomes were abstinence from binge eating and compensatory behaviors, as well as ED behavior frequencies, depression, anxiety, clinical impairment, academic impairment, and realized treatment access. Results: A total of 690 women with EDs (mean [SD] age, 22.12 [4.85] years; 414 [60.0%] White; 120 [17.4%] Hispanic; 512 [74.2%] undergraduates) were included in the analyses. For ED psychopathology, there was a significantly greater reduction in the intervention group compared with the control group at the postintervention assessment (β [SE], -0.44 [0.10]; d = -0.40; t1387 = -4.23; P \u3c .001), as well as over the follow-up period (β [SE], -0.39 [0.12]; d = -0.35; t1387 = -3.30; P \u3c .001). There was not a significant difference in abstinence from any ED behaviors at the postintervention assessment (odds ratio, 1.48; 95% CI, 0.48-4.62; P = .50) or at follow-up (odds ratio, 1.51; 95% CI, 0.63-3.58; P = .36). Compared with the control group, the intervention group had significantly greater reductions in binge eating (rate ratio, 0.82; 95% CI, 0.70-0.96; P = .02), compensatory behaviors (rate ratio, 0.68; 95% CI, 0.54-0.86; P \u3c .001), depression (β [SE], -1.34 [0.53]; d = -0.22; t1387 = -2.52; P = .01), and clinical impairment (β [SE], -2.33 [0.94]; d = -0.21; t1387 = -2.49; P = .01) at the postintervention assessment, with these gains sustained through follow-up for all outcomes except binge eating. Groups did not differ in terms of academic impairment. The majority of intervention participants (318 of 385 participants [83%]) began the intervention, whereas only 28% of control participants (76 of 271 participants with follow-up data available) sought treatment for their ED (odds ratio, 12.36; 95% CI, 8.73-17.51; P \u3c .001). Conclusions and Relevance: In this cluster randomized clinical trial comparing a coached, digital CBT intervention with referral to usual care, the intervention was effective in reducing ED psychopathology, compensatory behaviors, depression, and clinical impairment through long-term follow-up, as well as realizing treatment access. No difference was found between the intervention and control groups for abstinence for all ED behaviors or academic impairment. Given its scalability, a coached, digital, CBT intervention for college women with EDs has the potential to address the wide treatment gap for these disorders. Trial Registration: ClinicalTrials.gov Identifier: NCT02076464

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript