RESOLUTION DEPENDENCE OF ACOUSTIC SCATTERING STATISTICS FOR COMPLEX SEAFLOORS

Unmanned underwater vehicles (UUVs) utilize sonar perception to conduct sea floor mapping and target detection operations. However, systems with different resolutions may generate different probability density functions (PDFs) of the magnitude of the complex pressure. An area of research that has not been adequately studied is the effects of resolution manipulation during the post-processing of high-resolution data from complex seafloor environments. This work analyzed synthetic aperture sonar (SAS) data collected from multiple seafloor geomorphologies surrounding Bergen, Norway, to study the resolution dependence of scattering statistics for complex seafloors. Multi-look methods were applied to reduce the resolution. The original data and reduced resolution data were compared in terms of PDF amplitude and evaluated by standard goodness of fit tests with heavy-tailed statistical models that are commonly used in the radar and sonar community, including mixture models. Top-performing physics-based distributions were analyzed by how well they model how background and clutter parameters change with resolution manipulation. Empirical equations and a table of environmental constants were developed to allow a user to understand better how sonar data behaves at a given resolution and bottom type.Office of Naval Research, Arlington, VA, 22217Lieutenant Commander, United States NavyApproved for public release. Distribution is unlimited

EQUIP: Implementing chronic care principles and applying formative evaluation methods to improve care for schizophrenia: QUERI Series

<p>Abstract</p> <p>Background</p> <p>This paper presents a case study that demonstrates the evolution of a project entitled "Enhancing QUality-of-care In Psychosis" (EQUIP) that began approximately when the U.S. Department of Veterans Affairs' Quality Enhancement Research Initiative (QUERI), and implementation science were emerging. EQUIP developed methods and tools to implement chronic illness care principles in the treatment of schizophrenia, and evaluated this implementation using a small-scale controlled trial. The next iteration of the project, EQUIP-2, was further informed by implementation science and the use of QUERI tools.</p> <p>Methods</p> <p>This paper reports the background, development, results and implications of EQUIP, and also describes ongoing work in the second phase of the project (EQUIP-2). The EQUIP intervention uses implementation strategies and tools to increase the adoption and implementation of chronic illness care principles. In EQUIP-2, these strategies and tools are conceptually grounded in a stages-of-change model, and include clinical and delivery system interventions and adoption/implementation tools. Formative evaluation occurs in conjunction with the intervention, and includes developmental, progress-focused, implementation-focused, and interpretive evaluation.</p> <p>Results</p> <p>Evaluation of EQUIP provided an understanding of quality gaps <it>and </it>how to address related problems in schizophrenia. EQUIP showed that solutions to quality problems in schizophrenia differ by treatment domain and are exacerbated by a lack of awareness of evidence-based practices. EQUIP also showed that improving care requires creating resources for physicians to help them easily implement practice changes, plus intensive education as well as product champions who help physicians use these resources. Organizational changes, such as the addition of care managers and informatics systems, were shown to help physicians with identifying problems, making referrals, and monitoring follow-up. In EQUIP-2, which is currently in progress, these initial findings were used to develop a more comprehensive approach to implementing and evaluating the chronic illness care model.</p> <p>Discussion</p> <p>In QUERI, small-scale projects contribute to the development and enhancement of hands-on, action-oriented service-directed projects that are grounded in current implementation science. This project supports the concept that QUERI tools can be useful in implementing complex care models oriented toward evidence-based improvement of clinical care.</p

Freehand Juxtapedicular Screws Placed in the Apical Concavity of Adult Idiopathic Scoliosis Patients: Technique, Computed Tomography Confirmation, and Radiographic Results

Objective The purpose of this study is to highlight our technique for freehand placement of juxtapedicular screws along with intraoperative computed tomography (CT) and radiographic results. Methods Consecutive patients with adult idiopathic scoliosis undergoing primary surgery by the senior author were identified. All type D (absent/slit like channel) pedicles were identified on preoperative CT. Three-dimensional visualization software was used to measure screw angulation and purchase. Radiographs were measured by a fellowship trained spine surgeon. The freehand technique was used to place all screws in a juxtapedicular fashion without any fluoroscopic, radiographic, navigational or robotic assistance. Results Seventy-three juxtapedicular screws were analyzed. The most common level was T7 (9 screws) on the left and T5 (12 screws) on the right. The average medial angulation was 20.7° (range, 7.1°–36.3°), lateral vertebral body purchase was 13.4 mm (range, 0–28.9 mm), and medial vertebral body purchase was 21.1 mm (range, 8.9–31.8 mm). More than half (53.4%) of the screws had bicortical purchase. Two screws were lateral on CT scan, defined by the screw axis lateral to the lateral vertebral body cortex. No screws were medial. There was a difference in medial angulation between screws with (n = 58) and without (n = 15) lateral body purchase (22.0±4.9 vs. 15.5±4.5, p < 0.001). Three of 73 screws were repositioned after intraoperative CT. There were no neurovascular complications. The mean coronal cobb corrections for main thoracic and lumbar curves were 83.0% and 80.5%, respectively, at an average of 17.5 months postoperative. Conclusion Freehand juxtapedicular screw placement is a safe technique for type D pedicles in adult idiopathic scoliosis patients

Organizational Readiness in Specialty Mental Health Care

Implementing quality improvement efforts in clinics is challenging. Assessment of organizational “readiness” for change can set the stage for implementation by providing information regarding existing strengths and deficiencies, thereby increasing the chance of a successful improvement effort. This paper discusses organizational assessment in specialty mental health, in preparation for improving care for individuals with schizophrenia. To assess organizational readiness for change in specialty mental health in order to facilitate locally tailored implementation strategies. EQUIP-2 is a site-level controlled trial at nine VA medical centers (four intervention, five control). Providers at all sites completed an organizational readiness for change (ORC) measure, and key stakeholders at the intervention sites completed a semi-structured interview at baseline. At the four intervention sites, 16 administrators and 43 clinical staff completed the ORC, and 38 key stakeholders were interviewed. The readiness domains of training needs, communication, and change were the domains with lower mean scores (i.e., potential deficiencies) ranging from a low of 23.8 to a high of 36.2 on a scale of 10–50, while staff attributes of growth and adaptability had higher mean scores (i.e., potential strengths) ranging from a low of 35.4 to a high of 41.1. Semi-structured interviews revealed that staff perceptions and experiences of change and decision-making are affected by larger structural factors such as change mandates from VA headquarters. Motivation for change, organizational climate, staff perceptions and beliefs, and prior experience with change efforts contribute to readiness for change in specialty mental health. Sites with less readiness for change may require more flexibility in the implementation of a quality improvement intervention. We suggest that uptake of evidence-based practices can be enhanced by tailoring implementation efforts to the strengths and deficiencies of the organizations that are implementing quality improvement changes

Implementation of a Family Intervention for Individuals with Schizophrenia

Families are rarely included in clinical care despite research showing that family involvement has a positive effect on individuals with schizophrenia by reducing relapse, improving work functioning, and social adjustment. The VA QUERI study, EQUIP (Enhancing QUality of care In Psychosis), implemented family services for this population. At two VA medical centers, veterans with schizophrenia and their clinicians were interviewed separately at baseline and 15 months. A family intervention was implemented, and a process evaluation of the implementation was conducted. Veterans with schizophrenia (n = 173) and their clinicians (n = 29). Consent to contact family was obtained, mailers to engage families were sent, families were prioritized as high need for family services, and staff volunteers were trained in a brief three-session family intervention. Of those enrolled, 100 provided consent for family involvement. Seventy-three of the 100 were sent a mailer to engage them in care; none became involved. Clinicians were provided assessment data on their patients and notified of 50 patients needing family services. Of those 50, 6 families were already involved, 34 were never contacted, and 10 were contacted; 7 new families became involved in care. No families were referred to the family psychoeducational program. Uptake of the family intervention failed due to barriers from all stakeholders. Families did not respond to the mailer, patients were concerned about privacy and burdening family, clinicians had misperceptions of family-patient contact, and organizations did not free up time or offer incentives to provide the service. If a full partnership with patients and families is to be achieved, these barriers will need to be addressed, and a family-friendly environment will need to be supported by clinicians and their organizations. Applicability to family involvement in other disorders is discussed

Simulation of Ground-Truth Validation Data Via Physically- and Statistically-Based Warps

Abstract. The problem of scarcity of ground-truth expert delineations of medi-cal image data is a serious one that impedes the training and validation of medi-cal image analysis techniques. We develop an algorithm for the automatic generation of large databases of annotated images from a single reference data-set. We provide a web-based interface through which the users can upload a reference data set (an image and its corresponding segmentation and landmark points), provide custom setting of parameters, and, following server-side com-putations, generate and download an arbitrary number of novel ground-truth data, including segmentations, displacement vector fields, intensity non-uniformity maps, and point correspondences. To produce realistic simulated data, we use variational (statistically-based) and vibrational (physically-based) spatial deformations, nonlinear radiometric warps mimicking imaging non-homogeneity, and additive random noise with different underlying distributions. We outline the algorithmic details, present sample results, and provide the web address to readers for immediate evaluation and usage

Immunization with Cocktail of HIV-Derived Peptides in Montanide ISA-51 Is Immunogenic, but Causes Sterile Abscesses and Unacceptable Reactogenicity

BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). METHODS: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51)Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. RESULTS: 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. CONCLUSIONS: The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000886

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Template-Directed Ligation of Tethered Mononucleotides by T4 DNA Ligase for Kinase Ribozyme Selection

Background: In vitro selection of kinase ribozymes for small molecule metabolites, such as free nucleosides, will require partition systems that discriminate active from inactive RNA species. While nucleic acid catalysis of phosphoryl transfer is well established for phosphorylation of 59 or 29 OH of oligonucleotide substrates, phosphorylation of diffusible small molecules has not been demonstrated. Methodology/Principal Findings: This study demonstrates the ability of T4 DNA ligase to capture RNA strands in which a tethered monodeoxynucleoside has acquired a 59 phosphate. The ligation reaction therefore mimics the partition step of a selection for nucleoside kinase (deoxy)ribozymes. Ligation with tethered substrates was considerably slower than with nicked, fully duplex DNA, even though the deoxynucleotides at the ligation junction were Watson-Crick base paired in the tethered substrate. Ligation increased markedly when the bridging template strand contained unpaired spacer nucleotides across from the flexible tether, according to the trends: A2.A1.A3.A4.A0.A6.A8.A10 and T2.T3.T4.T6&lt;T1.T8.T10. Bridging T’s generally gave higher yield of ligated product than bridging A’s. ATP concentrations above 33 mM accumulated adenylated intermediate and decreased yields of the gap-sealed product, likely due to re-adenylation of dissociated enzyme. Under optimized conditions, T4 DNA ligase efficiently (.90%) joined a correctly paired, or T:G wobble-paired, substrate on the 39 side of the ligation junction while discriminating approximately 100-fold against most mispaire