Evaluation of a 3M (mistakes, mentoring, and mastery) training program for transfer of control situations in a level 2 automated driving system.

Drivers must actively supervise automation as it can only function in limited conditions. A failure to supervise the system has negative consequences in terms of missed requests to take over control and may cause crashes or jeopardize safety. The objective of this study is to determine the effect of a novel, 3M (Mistakes, Mentoring, and Mastery) training program on drivers' behavior while using level 2 driving automation systems. To achieve this, 36 participants were assigned randomly to three different training programs (3M training, User manual, and Placebo) and drove through scenarios on a fixed-based driving simulator. The results showed that drivers in the 3M training group took back control more effectively when the driving automation system reached its limits compared to drivers who received User manual or Placebo training. Drivers in the 3M training Group also had higher situation awareness and improved trust in automation. The results indicate that an interactive approach to training with regards to vehicle automation can help drivers more safely interact with automation systems.

Quantitative Detection of Thyroid-Stimulating Hormone in Patient Samples with a Nanomechanical Single-Antibody Spectro-Immunoassay.

Functional disorders of the thyroid remain a global challenge and have profound impacts on human health. Serving as the barometer for thyroid function, thyroid-stimulating hormone (TSH) is considered the single most useful test of thyroid function. However, the prevailing TSH immunoassays rely on two types of antibodies in a sandwich format. The requirement of repeated incubation and washing further complicates the issue, making it unable to meet the requirements of the shifting public health landscape that demands rapid, sensitive, and low-cost TSH tests. Herein, a systematic study is performed to investigate the clinical translational potential of a single antibody-based biosensing platform for the TSH test. The biosensing platform leverages Raman spectral variations induced by the interaction between a TSH antigen and a Raman molecule-conjugated TSH antibody. In conjunction with machine learning, it allows TSH concentrations in various patient samples to be predicted with high accuracy and precision, which is robust against substrate-to-substrate, intra-substrate, and day-to-day variations. It is envisioned that the simplicity and generalizability of this single-antibody immunoassay coupled with the demonstrated performance in patient samples pave the way for it to be widely applied in clinical settings for low-cost detection of hormones, other molecular biomarkers, DNA, RNA, and pathogens.

Leveraging Nanomechanical Perturbations in Raman Spectro-Immunoassays to Design a Versatile Serum Biomarker Detection Platform.

While immunoassays are pivotal to medical diagnosis and bioanalytical chemistry, the current landscape of public health has catalyzed an important shift in the requirements of immunoassays that demand innovative solutions. For example, rapid, label-free, and low-cost screening of a given analyte is required to inform the best countermeasures to combat infectious diseases in a timely manner. Yet, the current design of immunoassays cannot accommodate such requirements as constraint by accumulative challenges, such as repeated incubation and washing, and the need of two types of antibodies in the sandwich format. To provide a potential solution, herein, a plasmonic Raman immunoassay with single-antibody, multivariate regression, and shift-of-peak strategies, coined as the PRISM assay, for serum biomarkers detection, is reported. The PRISM assay relies on Raman reporter-antibody conjugates to capture analytes on a plasmonic substrate. The ensuing nanomechanical perturbations to vibration of Raman reporters induce subtle but characteristic spectral changes that encode rich information related to the captured analytes. By fusing Raman spectroscopy and chemometric analysis, both Raman frequency shift- and multivariate regression models for sensitive detection of biomarkers are developed. The PRISM assay is expected to find a wide range of applications in clinical diagnosis, food safety surveillance, and environmental monitoring.

A Dual-Modal Single-Antibody Plasmonic Spectro-Immunoassay for Detection of Small Molecules.

Small molecules play a pivotal role in regulating physiological processes and serve as biomarkers to uncover pathological conditions and the effects of therapeutic treatments. However, it remains a significant challenge to detect small molecules given the size as compared to macromolecules. Recently, the newly emerging plasmonic immunoassays based on surface-enhanced Raman scattering (SERS) offer great promise to deliver extraordinary sensitivity. Nevertheless, they are limited by the intrinsic SERS intensity fluctuations associated with the SERS uncertainty principle. The single transducer that relies on the intensity change is also prone to false signals. Additionally, the prevailing sandwich immunoassay format proves less effective towards detecting small molecules. To circumvent these critical issues, a dual-modal single-antibody approach that synergizes both the intensity and shift of the peak-based immunoassay with Raman enhancement, coined as the INSPIRE assay, is developed for small molecules detection. With two independent transduction mechanisms, it allows better prediction of analyte concentration and attenuation of signal artifacts, providing a new and robust strategy for molecular analysis. With a proof-of-concept demonstration for detection of free T4 and testosterone in serum matrix, the authors envision that the INSPIRE assay could be expanded for a wide spectrum of applications in biomedical diagnosis, discovery of new biopharmaceuticals, food safety, and environmental monitoring.

Plexcitonic Quasi-Bound States in the Continuum.

Enhancing light-matter interactions is fundamental to the advancement of nanophotonics and optoelectronics. Yet, light diffraction on dielectric platforms and energy loss on plasmonic metallic systems present an undesirable trade-off between coherent energy exchange and incoherent energy damping. Through judicious structural design, both light confinement and energy loss issues could be potentially and simultaneously addressed by creating bound states in the continuum (BICs) where light is ideally decoupled from the radiative continuum. Herein, the authors present a general framework based on the two-coupled resonances to first conceptualize and then numerically demonstrate a type of quasi-BICs that can be achieved through the interference between two bare resonance modes and is characterized by the considerably narrowed spectral line shape even on lossy metallic nanostructures. The ubiquity of the proposed framework further allows the paradigm to be extended for the realization of plexcitonic quasi-BICs on the same metallic systems. Owing to the topological nature, both plasmonic and plexcitonic quasi-BICs display strong mode robustness against parameters variation, thereby providing an attractive platform to unlock the potential of the coupled plasmon-exciton systems for manipulation of the photophysical properties of condensed phases.

Application of machine learning approaches to administrative claims data to predict clinical outcomes in medical and surgical patient populations.

OBJECTIVE: This study aimed to develop and validate a claims-based, machine learning algorithm to predict clinical outcomes across both medical and surgical patient populations. METHODS: This retrospective, observational cohort study, used a random 5% sample of 770,777 fee-for-service Medicare beneficiaries with an inpatient hospitalization between 2009-2011. The machine learning algorithms tested included: support vector machine, random forest, multilayer perceptron, extreme gradient boosted tree, and logistic regression. The extreme gradient boosted tree algorithm outperformed the alternatives and was the machine learning method used for the final risk model. Primary outcome was 30-day mortality. Secondary outcomes were: rehospitalization, and any of 23 adverse clinical events occurring within 30 days of the index admission date. RESULTS: The machine learning algorithm performance was evaluated by both the area under the receiver operating curve (AUROC) and Brier Score. The risk model demonstrated high performance for prediction of: 30-day mortality (AUROC = 0.88; Brier Score = 0.06), and 17 of the 23 adverse events (AUROC range: 0.80-0.86; Brier Score range: 0.01-0.05). The risk model demonstrated moderate performance for prediction of: rehospitalization within 30 days (AUROC = 0.73; Brier Score: = 0.07) and six of the 23 adverse events (AUROC range: 0.74-0.79; Brier Score range: 0.01-0.02). The machine learning risk model performed comparably on a second, independent validation dataset, confirming that the risk model was not overfit. CONCLUSIONS AND RELEVANCE: We have developed and validated a robust, claims-based, machine learning risk model that is applicable to both medical and surgical patient populations and demonstrates comparable predictive accuracy to existing risk models.

A Potent and Effective Suicidal Listeria Vaccine Platform.

Live-attenuated Listeria monocytogenes has shown encouraging potential as an immunotherapy platform in preclinical and clinical settings. However, additional safety measures will enable application across malignant and infectious diseases. Here, we describe a new vaccine platform, termed Lm-RIID (L. monocytogenes recombinase-induced intracellular death), that induces the deletion of genes required for bacterial viability yet maintains potent T cell responses to encoded antigens. Lm-RIID grows normally in broth but commits suicide inside host cells by inducing Cre recombinase and deleting essential genes flanked by loxP sites, resulting in a self-limiting infection even in immunocompromised mice. Lm-RIID vaccination of mice induces potent CD8+ T cells and protects against virulent challenges, similar to live L. monocytogenes vaccines. When combined with α-PD-1, Lm-RIID is as effective as live-attenuated L. monocytogenes in a therapeutic tumor model. This impressive efficacy, together with the increased clearance rate, makes Lm-RIID ideal for prophylactic immunization against diseases that require T cells for protection.

Recombinant Listeria promotes tumor rejection by CD8+ T cell-dependent remodeling of the tumor microenvironment.

Agents that remodel the tumor microenvironment (TME), prime functional tumor-specific T cells, and block inhibitory signaling pathways are essential components of effective immunotherapy. We are evaluating live-attenuated, double-deleted Listeria monocytogenes expressing tumor antigens (LADD-Ag) in the clinic. Here we show in numerous mouse models that while treatment with nonrecombinant LADD induced some changes in the TME, no antitumor efficacy was observed, even when combined with immune checkpoint blockade. In contrast, LADD-Ag promoted tumor rejection by priming tumor-specific KLRG1+PD1loCD62L- CD8+ T cells. These IFNγ-producing effector CD8+ T cells infiltrated the tumor and converted the tumor from an immunosuppressive to an inflamed microenvironment that was characterized by a decrease in regulatory T cells (Treg) levels, a proinflammatory cytokine milieu, and the shift of M2 macrophages to an inducible nitric oxide synthase (iNOS)+CD206- M1 phenotype. Remarkably, these LADD-Ag-induced tumor-specific T cells persisted for more than 2 months after primary tumor challenge and rapidly controlled secondary tumor challenge. Our results indicate that the striking antitumor efficacy observed in mice with LADD-based immunotherapy stems from TME remodeling which is a direct consequence of eliciting potent, systemic tumor-specific CD8+ T cells.

Prosthetic Jamming Terminal Device: A Case Study of Untethered Soft Robotics.

This article illuminates the major and often overlooked challenge of untethering soft robotic systems through the context of recent work, in which soft robotic gripper technology enabled by jamming of granular media was applied to a prosthetic jamming terminal device (PJTD). The PJTD's technical and market feasibility was evaluated in a pilot study with two upper-limb amputees. A PJTD prototype was tested against a commercial device (Motion Control electric terminal service with a one degree-of-freedom pinching mechanism) using two existing hand function tests: the first quantified the device's speed in picking and placing small blocks and the second evaluated a person's ability to perform activities of daily living (ADLs). The PJTD prototype performed slightly slower than its commercial counterpart in the first test. While both participants successfully completed all the ADLs with both devices in the second test, the commercial device scored marginally higher. Results suggested that PJTD can have potential benefits over existing terminal devices, such as providing the capability to firmly grasp tools due to the ability of PJTD to conform to arbitrary surfaces and reducing compensatory shoulder movements due to its axisymmetric design. Some downsides were that users reported fatigue while operating the PJTD, as most operations require pushing the PJTD against target objects to adequately conform to them. The greatest drawback for the PJTD is also a major roadblock preventing a number of soft robotic research projects from making an impact in real-world applications: pneumatic technology required for operating the PJTD is currently too large and heavy to enable compact untethered operation.

Evaluation of a new circuit configuration for the VDR-4 high-frequency percussive ventilator.

High-frequency percussive ventilation (HFPV) by the VDR-4(R) has been a successful mode of ventilation in the management of inhalation injuries for nearly 20 years. A limitation of the standard VDR-4 ventilator circuit is that the sliding venturi manifold is heavy in weight and is normally connected directly to the patient's endotracheal tube (ETT), resulting in potentially hazardous torque on the ETT. In this study, we evaluate the mechanics of a new circuit for the VDR-4 that relocates the sliding venturi manifold portion of the circuit away from the ETT into the ventilator proper. This new VDR-4 circuit configuration may have an important impact on patient safety.

Meta-analysis of psychological assessment as a therapeutic intervention.

This study entails the use of meta-analytic techniques to calculate and analyze 18 independent and 52 nonindependent effect sizes across 17 published studies of psychological assessment as a therapeutic intervention. In this sample of studies, which involves 1,496 participants, a significant overall Cohen's d effect size of 0.423 (95% CI [0.321, 0.525]) was found, whereby 66% of treatment group means fell above the control and comparison group means. When categorical variables were taken into account, significant treatment group effects were found for therapy process variables (d = 1.117, [0.679, 1.555]), therapy outcomes (d = 0.367, [0.256, 0.478]), and combined process/outcome variables (d = 0.547, [0.193, 0.901]). These findings appear to be robust on the basis of fail-safe N calculations. Taken together, they suggest that psychological assessment procedures-when combined with personalized, collaborative, and highly involving test feedback-have positive, clinically meaningful effects on treatment, especially regarding treatment processes. They also have important implications for assessment practice, training, and policy making, as well as future research, which are discussed in the conclusion of the article.

National survey of psychologists' test feedback training, supervision, and practice: a mixed methods study.

In this empirical, mixed methods study, we explored test feedback training, supervision, and practice among psychologists, focusing specifically on how feedback is provided to clients and whether feedback skills are taught in graduate programs. Based on a 48.5% return rate, this national survey of clinical, counseling, and school psychologists' suggests psychologists provide test feedback to clients but inconsistently. Most respondents, 91.7%, indicated they give verbal feedback at least some of the time, whereas 35% do so every time. However, 2.8% indicated they never give feedback. A negative correlation exists for clinical psychologists between years since graduation and providing verbal feedback. Of particular interest, approximately one third of respondents indicated predoctoral coursework, practica, and internship were of little-to-no help in preparing them to provide feedback. Also, feedback training in predoctoral coursework, practica, and internship was not correlated to actually providing feedback. There was, however, a significant correlation between postdoctoral training and providing feedback. Consistent with existing ethical exceptions, the most frequent reason for not providing feedback was using assessments in forensic settings. Individuals who indicated their training was not helpful cited "trial and error" and self-instruction as ways in which they learned feedback skills. We discuss implications and suggestions for feedback training, research, and practice.

National survey of psychologists' training and practice in breaking bad news: a mixed methods study of the MUM effect.

Research on breaking bad news has involved undergraduates, medical students, and physicians. However, to date, no studies have examined how, or whether, psychologists are trained to break bad news, as well as their current practice of breaking bad news. This mixed methods study explored the training and practice of 329 licensed psychologists/APA members in breaking bad news, using the MUM effect as a theoretical backdrop. Results suggest (1) psychologists are, as hypothesized, significantly more reluctant to break bad news than good news, (2) anxiety accounts for 30.6% of the variance in their reluctance, and (3) three-out-of-four psychologists break bad news "to some extent" or more, most typically related to a patient's psychological health, major Axis I diagnosis, or learning disability. Results also suggest most psychologists are not trained to break bad news, with only 2.7% being familiar with existing recommendations and guidelines; and anxiety, concerns for self/other, context, and norms play an important role in the bad news breaking process. Implications for theory, research, and practice are discussed and a training model is proposed.

A Phase II trial of brachytherapy alone after lumpectomy for select breast cancer: tumor control and survival outcomes of RTOG 95-17.

PURPOSE: Radiation Therapy Oncology Group 95-17 is a prospective Phase II cooperative group trial of accelerated partial breast irradiation (APBI) alone using multicatheter brachytherapy after lumpectomy in select early-stage breast cancers. Tumor control and survival outcomes are reported. METHODS AND MATERIALS: Eligibility criteria included Stage I/II breast carcinoma confirmed to be <3 cm, unifocal, invasive nonlobular histology with zero to three positive axillary nodes without extracapsular extension. APBI treatment was delivered with either low-dose-rate (LDR) (45 Gy in 3.5-5 days) or high-dose-rate (HDR) brachytherapy (34 Gy in 10 twice-daily fractions over 5 days). End points evaluated included in-breast control, regional control, mastectomy-free rate, mastectomy-free survival, disease-free survival, and overall survival. The study was designed to analyze the HDR and LDR groups separately and without comparison. RESULTS: Between 1997 and 2000, 100 patients were accrued and 99 were eligible; 66 treated with HDR brachytherapy and 33 treated with LDR brachytherapy. Eighty-seven patients had T1 lesions and 12 had T2 lesions. Seventy-nine were pathologically N0 and 20 were N1. Median follow-up in the HDR group is 6.14 years with the 5-year estimates of in-breast, regional, and contralateral failure rates of 3%, 5%, and 2%, respectively. The LDR group experienced similar results with a median follow-up of 6.22 years. The 5-year estimates of in-breast, regional, and contralateral failure rates of 6%, 0%, and 6%, respectively. CONCLUSION: Patients treated with multicatheter partial breast brachytherapy in this trial experienced excellent in-breast control rates and overall outcome that compare with reports from APBI studies with similar extended follow-up.

Adverse effects from environmental mercury loads on breeding common loons.

Anthropogenic inputs of mercury (Hg) into the environment have significantly increased in the past century. Concurrently, the availability of methylmercury (MeHg) in aquatic systems has increased to levels posing risks to ecological and human health. We use the common loon (Gavia immer) as an upper trophic level bioindicator of aquatic Hg toxicity in freshwater lakes. Multiple endpoints were selected to measure potential negative impacts from MeHg body burdens on behavior, physiology, survival and reproductive success. A robust spatio-temporal dataset was used that included nearly 5,500 loon Hg measurements over an 18-year period. We measured significant changes related to elevated MeHg body burdens, including aberrant incubation behavior, lethargy, and wing area asymmetry. Mercury body burdens in adult loons increased an average of 8.4% per year. Increasing Hg body burdens reduced the number of fledged chicks per territorial pair, with highest risk loons producing 41% fewer fledged young than our reference group. Our multiple endpoints establish adverse effect thresholds for adult loons at 3.0 ug/g (wet weight) in blood and 40.0 ug/g (fresh weight) in feathers. Mercury contamination in parts of Maine and New Hampshire is a driving stressor for creating breeding population sinks. Standardized monitoring programs are needed to determine if population sinks occur elsewhere and to track aquatic ecosystem responses to changes in Hg emissions and deposition.

Design, development, and implementation of the radiological physics center's pelvis and thorax anthropomorphic quality assurance phantoms.

The Radiological Physics Center (RPC) developed two heterogeneous anthropomorphic quality assurance phantoms for use in verifying the accuracy of radiation delivery: one for intensity-modulated radiation therapy (IMRT) to the pelvis and the other for stereotactic body radiation therapy (SBRT) to the thorax. The purpose of this study was to describe the design and development of these two phantoms and to demonstrate the reproducibility of measurements generated with them. The phantoms were built to simulate actual patient anatomy. They are lightweight and water-fillable, and they contain imageable targets and organs at risk of radiation exposure that are of similar densities to their human counterparts. Dosimetry inserts accommodate radiochromic film for relative dosimetry and thermoluminesent dosimetry capsules for absolute dosimetry. As a part of the commissioning process, each phantom was imaged, treatment plans were developed, and radiation was delivered at least three times. Under these controlled irradiation conditions, the reproducibility of dose delivery to the target TLD in the pelvis and thorax phantoms was 3% and 0.5%, respectively. The reproducibility of radiation-field localization was less than 2.5 mm for both phantoms. Using these anthropomorphic phantoms, pelvic IMRT and thoracic SBRT radiation treatments can be verified with a high level of precision. These phantoms can be used to effectively credential institutions for participation in specific NCI-sponsored clinical trials.

Consistency of absorbed dose to water measurements using 21 ion-chamber models following the AAPM TG51 and TG21 calibration protocols.

In 1999, the AAPM introduced a reference dosimetry protocol, known as TG51, based on an absorbed dose standard. This replaced the previous protocol, known as TG21, which was based on an air kerma standard. A significant body of literature has emerged discussing the improved accuracy and robustness of the absorbed dose standard, and quantifying the changes in baseline dosimetry with the introduction of the absorbed dose protocol. A significant component playing a role in the overall accuracy of beam output determination is the variability due to the use of different dosimeters. This issue, not adequately addressed in the past, is the focus of the present study. This work provides a comparison of absorbed dose determinations using 21 different makes and models of ion chambers for low- and high-energy photon and electron beams. The study included 13 models of cylindrical ion chambers and eight models of plane-parallel chambers. A high degree of precision (<0.25%) resulted from measurements with all chambers in a single setting, a sufficient number of repeat readings, and the use of high quality ion chambers as external monitors. Cylindrical chambers in photon beams show an improvement in chamber-to-chamber consistency with TG51. For electron dosimetry with plane-parallel chambers, the parameters Ngas and the product ND,w x k(ecal) were each determined in two ways, based on (i) an ADCL calibration, and (ii) a cross comparison with an ADCL-calibrated cylindrical chamber in a high-energy electron beam. Plane-parallel chamber results, therefore, are presented for both methods of chamber calibration. Our electron results with technique (i) show that plane-parallel chambers, as a group, overestimate the beam output relative to cylindrical chambers by 1%-2% with either protocol. Technique (ii), by definition, normalizes the plane-parallel results to the cylindrical results. In all cases, the maximum spread in output from the various cylindrical chambers is <2% implying a standard deviation of less than 0.5%. For plane-parallel chambers, the maximum spread is somewhat larger, up to 3%. A few chambers have been identified as outliers.

Phase II trial of brachytherapy alone after lumpectomy for select breast cancer: toxicity analysis of RTOG 95-17.

PURPOSE: Accelerated partial breast irradiation (APBI) can be delivered with brachytherapy within 4-5 days compared with 5-6 weeks for conventional whole breast external beam radiotherapy. Radiation Therapy Oncology Group 95-17 is the first prospective phase I-II cooperative group trial of APBI alone after lumpectomy in select patients with breast cancer. The toxicity rates are reported for low-dose-rate (LDR) and high-dose-rate (HDR) APBI on this trial. METHODS AND MATERIALS: The inclusion criteria for this study included invasive nonlobular tumors < or =3 cm after lumpectomy with negative surgical margins and axillary dissection with zero to three positive axillary nodes without extracapsular extension. The patients were treated with either LDR APBI (45 Gy in 3.5-5 days) or HDR APBI (34 Gy in 10 twice-daily fractions within 5 days). Chemotherapy (> or =2 weeks after APBI) and/or tamoxifen could be given at the discretion of the treating physicians. RESULTS: Between August 1997 and March 2000, 100 women were enrolled in this study, and 99 were evaluated. Of the 99 women, 33 were treated with LDR and 66 with HDR APBI. The median follow-up for all patients was 2.7 years (range, 0.6-4.4 years) and was 2.9 years for LDR and 2.7 years for HDR patients. Toxicities attributed to APBI included erythema, edema, tenderness, pain, and infection. Of the 66 patients treated with HDR APBI, 2 (3%) had Grade 3 or 4 toxicity. Of the 33 patients treated with LDR, 3 (9%) had Grade 3 or 4 toxicity during brachytherapy. Late toxicities included skin thickening, fibrosis, breast tenderness, and telangiectasias. No patient experienced late Grade 4 toxicity; the rate of Grade 3 toxicity was 18% for the LDR and 4% for the HDR groups. CONCLUSION: Acute and late toxicity for this invasive breast radiation technique was modest and acceptable. Patients receiving chemotherapy, a nonprotocol therapy, had a greater rate of Grade 3 toxicity. The study design did not allow for this to be tested statistically.

The impact of continuous pulse oximetry monitoring on intensive care unit admissions from a postsurgical care floor.

Continuous pulse oximetry (CPOX) has the potential to increase vigilance and decrease pulmonary complications and thus decrease intensive care unit (ICU) admissions. In a randomized nonblinded study of 1219 subjects we compared the effects of CPOX and standard monitoring on the rate of transfer to an ICU from a 33-bed postcardiothoracic surgery care floor. There was no difference in the rate of ICU readmission between the CPOX and standard monitor groups. Despite older age and comorbidity, estimated cost to time of censoring (enrollment to completion of the study) was less in the monitored patients who required ICU transfer than in the unmonitored patients who required ICU transfer (mean estimated cost difference of 28,195 dollars; P = 0.04). Use of CPOX altered the reasons that patients were transferred to an ICU but did not affect the rate of transfer. The duration, and thus estimated cost, of ICU stay was significantly less in the CPOX-monitored group. The potential for CPOX to allow for early intervention, or perhaps prevention of pulmonary complications, needs to be explored. Routine CPOX monitoring did not reduce transfer to ICU, mortality, or overall estimated cost of hospitalization, and it is unclear if there is any real benefit from the application of this technology in patients on a general care floor who are recovering from cardiothoracic surgery.