SIVIC: Open-Source, Standards-Based Software for DICOM MR Spectroscopy Workflows

Quantitative analysis of magnetic resonance spectroscopic imaging (MRSI) data provides maps of metabolic parameters that show promise for improving medical diagnosis and therapeutic monitoring. While anatomical images are routinely reconstructed on the scanner, formatted using the DICOM standard, and interpreted using PACS workstations, this is not the case for MRSI data. The evaluation of MRSI data is made more complex because files are typically encoded with vendor-specific file formats and there is a lack of standardized tools for reconstruction, processing, and visualization. SIVIC is a flexible open-source software framework and application suite that enables a complete scanner-to-PACS workflow for evaluation and interpretation of MRSI data. It supports conversion of vendor-specific formats into the DICOM MR spectroscopy (MRS) standard, provides modular and extensible reconstruction and analysis pipelines, and provides tools to support the unique visualization requirements associated with such data. Workflows are presented which demonstrate the routine use of SIVIC to support the acquisition, analysis, and delivery to PACS of clinical 1H MRSI datasets at UCSF

Mindfulness-based cognitive therapy (MBCT) reduces the association between depressive symptoms and suicidal cognitions in patients with a history of suicidal depression.

Objective: In patients with a history of suicidal depression, recurrence of depressive symptoms can easily reactivate suicidal thinking. In this study, we investigated whether training in mindfulness, which is aimed at helping patients “decenter” from negative thinking, could help weaken the link between depressive symptoms and suicidal cognitions. Method: Analyses were based on data from a recent randomized controlled trial, in which previously suicidal patients were allocated to mindfulness-based cognitive therapy (MBCT), an active control treatment, cognitive psychoeducation (CPE), which did not include any meditation practice, or treatment as usual (TAU). After the end of the treatment phase, we compared the associations between depressive symptoms, as assessed through self-reports on the Beck Depression Inventory–II (Beck, Steer, & Brown, 1996), and suicidal thinking, as assessed through the Suicidal Cognitions Scale (Rudd et al., 2001). Results: In patients with minimal to moderate symptoms at the time of assessment, comparisons of the correlations between depressive symptoms and suicidal cognitions showed significant differences between the groups. Although suicidal cognitions were significantly related to levels of symptoms in the 2 control groups, there was no such relation in the MBCT group. Conclusion: The findings suggest that, in patients with a history of suicidal depression, training in mindfulness can help to weaken the association between depressive symptoms and suicidal thinking, and thus reduce an important vulnerability for relapse to suicidal depression

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy

Hemisphere-scale differences in conifer evolutionary dynamics

Fundamental differences in the distribution of oceans and landmasses in the Northern and Southern Hemispheres potentially impact patterns of biological diversity in the two areas. The evolutionary history of conifers provides an opportunity to explore these dynamics, because the majority of extant conifer species belong to lineages that have been broadly confined to the Northern or Southern Hemisphere during the Cenozoic. Incorporating genetic information with a critical review of fossil evidence, we developed an age-calibrated phylogeny sampling ∼80% of living conifer species. Most extant conifer species diverged recently during the Neogene within clades that generally were established during the later Mesozoic, but lineages that diversified mainly in the Southern Hemisphere show a significantly older distribution of divergence ages than their counterparts in the Northern Hemisphere. Our tree topology and divergence times also are best fit by diversification models in which Northern Hemisphere conifer lineages have higher rates of species turnover than Southern Hemisphere lineages. The abundance of recent divergences in northern clades may reflect complex patterns of migration and range shifts during climatic cycles over the later Neogene leading to elevated rates of speciation and extinction, whereas the scattered persistence of mild, wetter habitats in the Southern Hemisphere may have favored the survival of older lineages

The Development and Internal Evaluation of a Predictive Model to Identify for Whom Mindfulness-Based Cognitive Therapy Offers Superior Relapse Prevention for Recurrent Depression Versus Maintenance Antidepressant Medication

Depression is highly recurrent, even following successful pharmacological and/or psychological intervention. We aimed to develop clinical prediction models to inform adults with recurrent depression choosing between antidepressant medication (ADM) maintenance or switching to mindfulness-based cognitive therapy (MBCT). Using previously published data ( N = 424), we constructed prognostic models using elastic-net regression that combined demographic, clinical, and psychological factors to predict relapse at 24 months under ADM or MBCT. Only the ADM model (discrimination performance: area under the curve [AUC] = .68) predicted relapse better than baseline depression severity (AUC = .54; one-tailed DeLong’s test: z = 2.8, p = .003). Individuals with the poorest ADM prognoses who switched to MBCT had better outcomes compared with individuals who maintained ADM (48% vs. 70% relapse, respectively; superior survival times, z = −2.7, p = .008). For individuals with moderate to good ADM prognoses, both treatments resulted in similar likelihood of relapse. If replicated, the results suggest that predictive modeling can inform clinical decision-making around relapse prevention in recurrent depression

Atomic-Scale Patterning of Arsenic in Silicon by Scanning Tunneling Microscopy

Over the past two decades, prototype devices for future classical and quantum computing technologies have been fabricated by using scanning tunneling microscopy and hydrogen resist lithography to position phosphorus atoms in silicon with atomic-scale precision. Despite these successes, phosphine remains the only donor precursor molecule to have been demonstrated as compatible with the hydrogen resist lithography technique. The potential benefits of atomic-scale placement of alternative dopant species have, until now, remained unexplored. In this work, we demonstrate the successful fabrication of atomic-scale structures of arsenic-in-silicon. Using a scanning tunneling microscope tip, we pattern a monolayer hydrogen mask to selectively place arsenic atoms on the Si(001) surface using arsine as the precursor molecule. We fully elucidate the surface chemistry and reaction pathways of arsine on Si(001), revealing significant differences to phosphine. We explain how these differences result in enhanced surface immobilization and in-plane confinement of arsenic compared to phosphorus, and a dose-rate independent arsenic saturation density of 0.24 ± 0.04 monolayers. We demonstrate the successful encapsulation of arsenic delta-layers using silicon molecular beam epitaxy, and find electrical characteristics that are competitive with equivalent structures fabricated with phosphorus. Arsenic delta-layers are also found to offer confinement as good as similarly prepared phosphorus layers, while still retaining >80% carrier activation and sheet resistances of <2 kω/square. These excellent characteristics of arsenic represent opportunities to enhance existing capabilities of atomic-scale fabrication of dopant structures in silicon, and may be important for three-dimensional devices, where vertical control of the position of device components is critical. Copyright © 2020 American Chemical Society

Teachers "Finding Peace in a Frantic World": An Experimental Study of Self-Taught and Instructor-Led Mindfulness Program Formats on Acceptability, Effectiveness, and Mechanisms.

Mindfulness training (MT) is considered appropriate for school teachers and enhances well-being. Most research has investigated the efficacy of instructor-led MT. However, little is known about the benefits of using self-taught formats, nor what the key mechanisms of change are that contribute to enhanced teacher well-being. This study compared instructor-led and self-taught MT based on a book (Williams & Penman, 2011) in a sample of secondary school teachers. We assessed expectancy, the degree to which participants believed the intervention was effective, their program engagement, well-being and psychological distress, and evaluated whether mindfulness and self-compassion skills acted as mediators of outcomes. In total, 206 teachers from 43 schools were randomized by school to an instructor-led or self-taught course-77% female, mean age 39 years (SD = 9.0). Both MT formats showed similar rates of participant expectancy and engagement, but the instructor-led arm was perceived as more credible. Using linear mixed-effects models, we found the self-taught arm showed significant pre-post improvements in self-compassion and well-being, while the instructor-led arm showed such improvements in mindfulness, self-compassion, well-being, perceived stress, anxiety, depression, and burnout. Changes over time significantly differed between the groups in all these outcomes, favoring the instructor-led arm. The instructor-led arm, compared with the self-taught, indirectly improved teacher outcomes by enhancing mindfulness and self-compassion as mediating factors. Mindfulness practice frequency had indirect effects on teacher outcomes through mindfulness in both self-taught and instructor-led arms. Our results suggest both formats are considered reasonable, but the instructor-led is more effective than the self-taught. Trial registration: ISRCTN18013311

Update to the effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial.

BACKGROUND: MYRIAD (My Resilience in Adolescence) is a superiority, parallel group, cluster randomised controlled trial designed to examine the effectiveness and cost-effectiveness of a mindfulness training (MT) programme, compared with normal social and emotional learning (SEL) school provision to enhance mental health, social-emotional-behavioural functioning and well-being in adolescence. The original trial protocol was published in Trials (accessible at https://doi.org/10.1186/s13063-017-1917-4 ). This included recruitment in two cohorts, enabling the learning from the smaller first cohort to be incorporated in the second cohort. Here we describe final amendments to the study protocol and discuss their underlying rationale. METHODS: Four major changes were introduced into the study protocol: (1) there were changes in eligibility criteria, including a clearer operational definition to assess the degree of SEL implementation in schools, and also new criteria to avoid experimental contamination; (2) the number of schools and pupils that had to be recruited was increased based on what we learned in the first cohort; (3) some changes were made to the secondary outcome measures to improve their validity and ability to measure constructs of interest and to reduce the burden on school staff; and (4) the current Coronavirus Disease 2019 (SARS-CoV-2 or COVID-19) pandemic both influences and makes it difficult to interpret the 2-year follow-up primary endpoint results, so we changed our primary endpoint to 1-year follow-up. DISCUSSION: These changes to the study protocol were approved by the Trial Management Group, Trial Steering Committee and Data and Ethics Monitoring Committees and improved the enrolment of participants and quality of measures. Furthermore, the change in the primary endpoint will give a more reliable answer to our primary question because it was collected prior to the COVID-19 pandemic in both cohort 1 and cohort 2. Nevertheless, the longer 2-year follow-up data will still be acquired, although this time-point will be now framed as a second major investigation to answer some new important questions presented by the combination of the pandemic and our study design. TRIAL REGISTRATION: International Standard Randomised Controlled Trials ISRCTN86619085 . Registered on 3 June 2016

Use of an electronic administrative database to identify older community dwelling adults at high-risk for hospitalization or emergency department visits: The elders risk assessment index

<p>Abstract</p> <p>Background</p> <p>The prevention of recurrent hospitalizations in the frail elderly requires the implementation of high-intensity interventions such as case management. In order to be practically and financially sustainable, these programs require a method of identifying those patients most at risk for hospitalization, and therefore most likely to benefit from an intervention. The goal of this study is to demonstrate the use of an electronic medical record to create an administrative index which is able to risk-stratify this heterogeneous population.</p> <p>Methods</p> <p>We conducted a retrospective cohort study at a single tertiary care facility in Rochester, Minnesota. Patients included all 12,650 community-dwelling adults age 60 and older assigned to a primary care internal medicine provider on January 1, 2005. Patient risk factors over the previous two years, including demographic characteristics, comorbid diseases, and hospitalizations, were evaluated for significance in a logistic regression model. The primary outcome was the total number of emergency room visits and hospitalizations in the subsequent two years. Risk factors were assigned a score based on their regression coefficient estimate and a total risk score created. This score was evaluated for sensitivity and specificity.</p> <p>Results</p> <p>The final model had an AUC of 0.678 for the primary outcome. Patients in the highest 10% of the risk group had a relative risk of 9.5 for either hospitalization or emergency room visits, and a relative risk of 13.3 for hospitalization in the subsequent two year period.</p> <p>Conclusions</p> <p>It is possible to create a screening tool which identifies an elderly population at high risk for hospital and emergency room admission using clinical and administrative data readily available within an electronic medical record.</p