Pragmatic fidelity measurement in youth service settings.

Background: Fidelity measurement is critical for developing, evaluating, and implementing evidence-based treatments (EBTs). However, traditional fidelity measurement tools are often not feasible for community-based settings. We developed a short fidelity rating form for the Collaborative Problem Solving (CPS) approach from an existing manualized coding system that requires extensive training. We examined the reliability and accuracy of this short form when completed by trained observers, untrained observers, and self-reporting providers to evaluate multiple options for reducing barriers to fidelity measurement in community-based settings. Methods: Community-based treatment providers submitted recordings of youth service sessions in which they did, or did not, use CPS. For 60 recordings, we compared short-form fidelity ratings assigned by trained observers and untrained observers to those provided by trained observers on the manualized coding system. For 141 recordings, we compared providers' self-reported fidelity on the short form to ratings provided by trained observers on the manualized coding system and examined providers' accuracy as a function of their global fidelity. Results & Conclusions: The short form was reliable and accurate for trained observers. An assigned global integrity score and a calculated average of component scores on the short form, but not component scores themselves, were reliable and accurate for observers who had CPS expertise but no specific training on rating CPS fidelity. When providers self-reported fidelity on the short form, their global integrity score was a reliable estimate of their CPS integrity; however, providers with better CPS fidelity were most accurate in their self-reports. We discuss the costs and benefits of these more pragmatic fidelity measurement options in community-based settings.

Developing brief, easy-to-use, and reliable tools to measure how well providers deliver evidence-based treatments (EBTs) in community clinical settings is critical to ensure the benefits of EBTs. However, reliable tools are often too time-consuming and not feasible to use in community settings because they require independent observers to receive intensive training on a coding system and to observe live or recorded treatment sessions for reliable and accurate evaluation. This paper describes steps we took to develop a more practical measure of how well providers deliver one EBT, Collaborative Problem Solving (CPS), based on a previously validated measure, to explore whether the quality of the measure can be maintained while reducing the need for training independent observers and the need for recording treatment sessions. This work contributes to the growing efforts of developing more pragmatic fidelity measures and introduces a new tool, the CPS Practice Integrity Form (CPS-PIF), as a promising measure for community-based clinical settings using CPS.

Facilitating cell segmentation with the projection-enhancement network.

Contemporary approaches to instance segmentation in cell science use 2D or 3D convolutional networks depending on the experiment and data structures. However, limitations in microscopy systems or efforts to prevent phototoxicity commonly require recording sub-optimally sampled data that greatly reduces the utility of such 3D data, especially in crowded sample space with significant axial overlap between objects. In such regimes, 2D segmentations are both more reliable for cell morphology and easier to annotate. In this work, we propose the projection enhancement network (PEN), a novel convolutional module which processes the sub-sampled 3D data and produces a 2D RGB semantic compression, and is trained in conjunction with an instance segmentation network of choice to produce 2D segmentations. Our approach combines augmentation to increase cell density using a low-density cell image dataset to train PEN, and curated datasets to evaluate PEN. We show that with PEN, the learned semantic representation in CellPose encodes depth and greatly improves segmentation performance in comparison to maximum intensity projection images as input, but does not similarly aid segmentation in region-based networks like Mask-RCNN. Finally, we dissect the segmentation strength against cell density of PEN with CellPose on disseminated cells from side-by-side spheroids. We present PEN as a data-driven solution to form compressed representations of 3D data that improve 2D segmentations from instance segmentation networks.

ADAD1 is required for normal translation of nuclear pore and transport protein transcripts in spermatids of Mus musculus†.

ADAD1 is a testis-specific RNA-binding protein expressed in post-meiotic spermatids whose loss leads to defective sperm and male infertility. However, the drivers of the Adad1 phenotype remain unclear. Morphological and functional analysis of Adad1 mutant sperm showed defective DNA compaction, abnormal head shaping, and reduced motility. Mutant testes demonstrated minimal transcriptome changes; however, ribosome association of many transcripts was reduced, suggesting ADAD1 may be required for their translational activation. Further, immunofluorescence of proteins encoded by select transcripts showed delayed protein accumulation. Additional analyses demonstrated impaired subcellular localization of multiple proteins, suggesting protein transport is also abnormal in Adad1 mutants. To clarify the mechanism giving rise to this, the manchette, a protein transport microtubule network, and the LINC (linker of nucleoskeleton and cytoskeleton) complex, which connects the manchette to the nuclear lamin, were assessed across spermatid development. Proteins of both displayed delayed translation and/or localization in mutant spermatids implicating ADAD1 in their regulation, even in the absence of altered ribosome association. Finally, ADAD1's impact on the NPC (nuclear pore complex), a regulator of both the manchette and the LINC complex, was examined. Reduced ribosome association of NPC encoding transcripts and reduced NPC protein abundance along with abnormal localization in Adad1 mutants confirmed ADAD1's impact on translation is required for a NPC in post-meiotic germ cells. Together, these studies lead to a model whereby ADAD1's influence on nuclear transport leads to deregulation of the LINC complex and the manchette, ultimately generating the range of physiological defects observed in the Adad1 phenotype.

An open trial of Collaborative Problem Solving in a naturalistic outpatient setting.

Collaborative Problem Solving (CPS) is an intervention for reducing children's challenging behaviors. The aim of the present study was to evaluate the effects of family therapy using CPS in an outpatient clinic that specializes in treating children with challenging behaviors. One hundred and twenty families presented for treatment. Diagnoses at intake were varied, and 100 children (83%) had symptoms that were in the clinical range at intake. Parents reported significant change in their understanding of challenging behavior and prediction of children's behavioral symptoms 3 months into treatment. Furthermore, children's improvement was predicted by their parents' increased understanding that cognitive skill deficits are responsible for challenging behavior. These results suggest that using CPS in community-based, outpatient family treatment is effective for helping children who exhibit a range of clinical symptoms. Results provide insights for clinical practice and research on CPS.

Morphodynamics facilitate cancer cells to navigate 3D extracellular matrix.

Cell shape is linked to cell function. The significance of cell morphodynamics, namely the temporal fluctuation of cell shape, is much less understood. Here we study the morphodynamics of MDA-MB-231 cells in type I collagen extracellular matrix (ECM). We systematically vary ECM physical properties by tuning collagen concentrations, alignment, and gelation temperatures. We find that morphodynamics of 3D migrating cells are externally controlled by ECM mechanics and internally modulated by Rho/ROCK-signaling. We employ machine learning to classify cell shape into four different morphological phenotypes, each corresponding to a distinct migration mode. As a result, we map cell morphodynamics at mesoscale into the temporal evolution of morphological phenotypes. We characterize the mesoscale dynamics including occurrence probability, dwell time and transition matrix at varying ECM conditions, which demonstrate the complex phenotype landscape and optimal pathways for phenotype transitions. In light of the mesoscale dynamics, we show that 3D cancer cell motility is a hidden Markov process whereby the step size distributions of cell migration are coupled with simultaneous cell morphodynamics. Morphological phenotype transitions also facilitate cancer cells to navigate non-uniform ECM such as traversing the interface between matrices of two distinct microstructures. In conclusion, we demonstrate that 3D migrating cancer cells exhibit rich morphodynamics that is controlled by ECM mechanics, Rho/ROCK-signaling, and regulate cell motility. Our results pave the way to the functional understanding and mechanical programming of cell morphodynamics as a route to predict and control 3D cell motility.

The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance.

Contact guidance is a major physical cue that modulates cancer cell morphology and motility, and is directly linked to the prognosis of cancer patients. Under physiological conditions, particularly in the three-dimensional (3D) extracellular matrix (ECM), the disordered assembly of fibers presents a complex directional bias to the cells. It is unclear how cancer cells respond to these noncoherent contact guidance cues. Here we combine quantitative experiments, theoretical analysis, and computational modeling to study the morphological and migrational responses of breast cancer cells to 3D collagen ECM with varying degrees of fiber alignment. We quantify the strength of contact guidance using directional coherence of ECM fibers, and find that stronger contact guidance causes cells to polarize more strongly along the principal direction of the fibers. Interestingly, sensitivity to contact guidance is positively correlated with cell aspect ratio, with elongated cells responding more strongly to ECM alignment than rounded cells. Both experiments and simulations show that cell-ECM adhesions and actomyosin contractility modulate cell responses to contact guidance by inducing a population shift between rounded and elongated cells. We also find that cells rapidly change their morphology when navigating the ECM, and that ECM fiber coherence modulates cell transition rates between different morphological phenotypes. Taken together, we find that subcellular processes that integrate conflicting mechanical cues determine cell morphology, which predicts the polarization and migration dynamics of cancer cells in 3D ECM.

Lessons from Fukushima: Potassium Iodide After a Nuclear Disaster.

ABSTRACT: The release of radioactive iodine after a nuclear disaster, such as those that occurred at the Fukushima Daiichi Nuclear Power Plant in Japan 10 years ago and Three Mile Island in Pennsylvania in 1979, increases thyroid cancer risk among people who are exposed. Certain populations are especially vulnerable, including pregnant and breastfeeding women, children, and neonates. Potassium iodide (KI) can effectively block radioactive iodine from being absorbed by the thyroid gland if taken immediately after a radiation release. This article examines lessons learned from Fukushima to enhance disaster readiness and nursing actions. Nurses should be directly involved in vulnerability assessments, emergency planning, and in ensuring the availability, accessibility, and distribution of KI within U.S. nuclear power plant emergency planning zones before a crisis occurs.

Modeling multicellular dynamics regulated by extracellular-matrix-mediated mechanical communication via active particles with polarized effective attraction.

Collective cell migration is crucial to many physiological and pathological processes such as embryo development, wound healing, and cancer invasion. Recent experimental studies have indicated that the active traction forces generated by migrating cells in a fibrous extracellular matrix (ECM) can mechanically remodel the ECM, giving rise to bundlelike mesostructures bridging individual cells. Such fiber bundles also enable long-range propagation of cellular forces, leading to correlated migration dynamics regulated by the mechanical communication among the cells. Motivated by these experimental discoveries, we develop an active-particle model with polarized effective attractions (APPA) to investigate emergent multicellular migration dynamics resulting from ECM-mediated mechanical communications. In particular, the APPA model generalizes the classic active-Brownian-particle (ABP) model by imposing a pairwise polarized attractive force between the particles, which depends on the instantaneous dynamic states of the particles and mimics the effective mutual pulling between the cells via the fiber bundle bridge. The APPA system exhibits enhanced aggregation behaviors compared to the classic ABP system, and the contrast is more apparent at lower particle densities and higher rotational diffusivities. Importantly, in contrast to the classic ABP system where the particle velocities are not correlated for all particle densities, the high-density phase of the APPA system exhibits strong dynamic correlations, which are characterized by the slowly decaying velocity correlation functions with a correlation length comparable to the linear size of the high-density phase domain (i.e., the cluster of particles). The strongly correlated multicellular dynamics predicted by the APPA model is subsequently verified in in vitro experiments using MCF-10A cells. Our studies indicate the importance of incorporating ECM-mediated mechanical coupling among the migrating cells for appropriately modeling emergent multicellular dynamics in complex microenvironments.

Intraoperative Sepsis: A Simulation Case for Anesthesiology Residents.

Introduction: Sepsis is a major cause of morbidity and mortality in medicine and is managed in ICUs daily. Critical care training is a vital part of anesthesiology residency, and understanding the presentation, management, and treatment of septic shock is fundamental to intraoperative patient care. Methods: This simulation involved a 58-year-old man undergoing surgical debridement of a peripancreatic cyst with hemodynamic instability and septic shock. We conducted the simulation yearly for clinical anesthesia year 2 residents (n = 26) in 1-hour sessions with three to five learners at a time. The simulation covered the six Anesthesiology Milestones related to sepsis and septic shock as outlined in the Anesthesiology Milestones Project. Results: To date, 155 anesthesiology residents have completed the simulation. Commonly missed critical actions included failure to recognize the need for invasive lines, provide appropriate volumes of fluid resuscitation, inquire about blood cultures and antibiotics, and recognize the need for the patient to remain intubated. Most participants could appropriately diagnose and treat intraoperative septic shock, but all had moments of action or inaction to discuss and improve upon, and all learned from this scenario. Discussion: Simulation is an optimal way to practice the more rare and life-threatening clinical events in medicine. Even though septic shock is commonly managed in the ICU, it is relatively uncommon for it to develop acutely in the OR. This simulation is an effective and educational way to discuss the most recent sepsis/septic shock definition and review evidence-based guidelines for treatment.

Collaborative Problem Solving reduces children's emotional and behavioral difficulties and parenting stress: Two key mechanisms.

OBJECTIVES: This study aimed to evaluate the effectiveness of the Collaborative Problem Solving (CPS) approach in home-based family therapy and to explore two hypothesized mechanisms of change. METHOD: Sixty-seven families with children aged 3-12 years old completed a 12-week home-based CPS treatment program. Parent-report measures were completed pre- and post-intervention, including measures on parents' fidelity of using CPS, parents' empathy, children's executive functioning, children's behavioral difficulties, and parenting stress. RESULTS: There were significant reductions in children's behavioral difficulties and parenting stress, and significant improvements in children's executive functioning and parents' empathy. These improvements were greatest for parents who had the greatest fidelity to CPS. Improvements in children's executive functioning and parents' empathy mediated the relationship between parents' CPS fidelity and outcomes. CONCLUSIONS: These results provide evidence that home-based family treatment with CPS may achieve positive child and family outcomes by building children's executive function skills and improving parents' empathy.

Absorbing-active transition in a multi-cellular system regulated by a dynamic force network.

Collective cell migration in 3D extracellular matrix (ECM) is crucial to many physiological and pathological processes. Migrating cells can generate active pulling forces via actin filament contraction, which are transmitted to the ECM fibers and lead to a dynamically evolving force network in the system. Here, we elucidate the role of this force network in regulating collective cell behaviors using a minimal active-particle-on-network (APN) model, in which active particles can pull the fibers and hop between neighboring nodes of the network following local durotaxis. Our model reveals a dynamic transition as the particle number density approaches a critical value, from an "absorbing" state containing isolated stationary small particle clusters, to an "active" state containing a single large cluster undergoing constant dynamic reorganization. This reorganization is dominated by a subset of highly dynamic "radical" particles in the cluster, whose number also exhibits a transition at the same critical density. The transition is underlaid by the percolation of "influence spheres" due to the particle pulling forces. Our results suggest a robust mechanism based on ECM-mediated mechanical coupling for collective cell behaviors in 3D ECM.

Traumatic brain injury, dry eye and comorbid pain diagnoses in US veterans.

AIMS: The purpose of the study is to evaluate the relationship between dry eye (DE) and pain diagnoses in US veterans with and without traumatic brain injury (TBI). METHODS: Retrospective cohort study of veterans who were seen in the Veterans Administration Hospital (VA) between 1 January 2010 and 31 December 2014. Veterans were separated into two groups by the presence or absence of an International Classification of Diseases, Ninth Revision diagnosis of TBI and assessed for DE and other comorbidities. A dendrogram was used to investigate the linkage between TBI, DE, chronic pain and other comorbid conditions. RESULTS: Of the 3 265 894 veterans seen during the 5-year period, 3.97% carried a diagnosis of TBI. Veterans with TBI were more likely to have a diagnosis of DE compared with their counterparts without TBI (37.2% vs 29.1%, p<0.0005). The association was stronger between TBI and ocular pain (OR 3.08; 95% CI 3.03 to 3.13) compared with tear film dysfunction (OR 1.09; 95% CI 1.07 to 1.10). Those with TBI were also about twice as likely to have a diagnosis of chronic pain, headache, depression or post-traumatic stress disorder compared with their counterparts without TBI. Cluster analysis of TBI, DE and pain diagnoses of interest revealed that central pain syndrome, cluster headache, sicca syndrome, keratoconjunctivitis sicca and late effect of injury to the nervous system (as can be seen after TBI) were all closely clustered together. CONCLUSIONS: DE and pain disorders occur at higher frequencies in patients with a diagnosis of TBI, suggesting a common underlying pathophysiology.

Comparing Physical Examination With Sonographic Versions of the Same Examination Techniques for Splenomegaly.

OBJECTIVES: To determine whether sonographic versions of physical examination techniques can accurately identify splenomegaly, Castell's method (Ann Intern Med 1967; 67:1265-1267), the sonographic Castell's method, spleen tip palpation, and the sonographic spleen tip technique were compared with reference measurements. METHODS: Two clinicians trained in bedside sonography patients recruited from an urban hematology clinic. Each patient was examined for splenomegaly using conventional percussion and palpation techniques (Castell's method and spleen tip palpation, respectively), as well as the sonographic versions of these maneuvers (sonographic Castell's method and sonographic spleen tip technique). Results were compared with a reference standard based on professional sonographer measurements. RESULTS: The sonographic Castell's method had greater sensitivity (91.7% [95% confidence interval, 61.5% to 99.8%]) than the traditional Castell's method (83.3% [95% confidence interval, 51.6% to 97.9%]) but took longer to perform [mean ± SD, 28.8 ± 18.6 versus 18.8 ± 8.1 seconds; P = .01). Palpable and positive sonographic spleen tip results were both 100% specific, but the sonographic spleen tip method was more sensitive (58.3% [95% confidence interval, 27.7% to 84.8%] versus 33.3% [95% confidence interval, 9.9% to 65.1%]). CONCLUSIONS: Sonographic versions of traditional physical examination maneuvers have greater diagnostic accuracy than the physical examination maneuvers from which they are derived but may take longer to perform. We recommend a combination of traditional physical examination and sonographic techniques when evaluating for splenomegaly at the bedside.

Feasibility of upright patient positioning and intubation success rates At two academic EDs.

OBJECTIVES: Endotracheal intubation is most commonly taught and performed in the supine position. Recent literature suggests that elevating the patient's head to a more upright position may decrease peri-intubation complications. However, there is little data on the feasibility of upright intubation in the emergency department. The goal of this study was to measure the success rate of emergency medicine residents performing intubation in supine and non-supine, including upright positions. METHODS: This was a prospective observational study. Residents performing intubation recorded the angle of the head of the bed. The number of attempts required for successful intubation was recorded by faculty and espiratory therapists. The primary outcome of first past success was calculated with respect to three groups: 0-10° (supine), 11-44° (inclined), and ≥45° (upright); first past success was also analyzed in 5 degree angle increments. RESULTS: A total of 231 intubations performed by 58 residents were analyzed. First pass success was 65.8% for the supine group, 77.9% for the inclined group, and 85.6% for the upright group (p=0.024). For every 5 degree increase in angle, there was increased likelihood of first pass success (AOR=1.11; 95% CI=1.01-1.22, p=0.043). CONCLUSIONS: In our study emergency medicine residents had a high rate of success intubating in the upright position. While this does not demonstrate causation, it correlates with recent literature challenging the traditional supine approach to intubation and indicates that further investigation into optimal positioning during emergency department intubations is warranted.

Cross-over study of novice intubators performing endotracheal intubation in an upright versus supine position.

There are a number of potential physical advantages to performing orotracheal intubation in an upright position. The objective of this study was to measure the success of intubation of a simulated patient in an upright versus supine position by novice intubators after brief training. This was a cross-over design study in which learners (medical students, physician assistant students, and paramedic students) intubated mannequins in both a supine (head of the bed at 0°) and upright (head of bed elevated at 45°) position. The primary outcome of interest was successful intubation of the trachea. Secondary outcomes included log time to intubation, Cormack-Lehane view obtained, Percent of Glottic Opening score, provider assessment of difficulty, and overall provider satisfaction with the position. There were a total of 126 participants: 34 medical students, 84 physician assistant students, and 8 paramedic students. Successful tracheal intubation was achieved in 114 supine attempts (90.5 %) and 123 upright attempts (97.6 %; P = 0.283). Upright positioning was associated with significantly faster log time to intubation, higher likelihood of achieving Grade I Cormack-Lehane view, higher Percent of Glottic Opening score, lower perceived difficulty, and higher provider satisfaction. A subset of 74 participants had no previous intubation training or experience. For these providers, there was a non-significant trend toward improved intubation success with upright positioning vs supine positioning (98.6 % vs. 87.8 %, P = 0.283). For all secondary outcomes in this group, upright positioning significantly outperformed supine positioning.

Accuracy of Spleen Measurement by Medical Residents Using Hand-Carried Ultrasound.

OBJECTIVES: Easily palpable splenomegaly can be identified on physical examination, but it is difficult to detect lesser degrees of splenomegaly. Rapid bedside assessment can be conducted with hand-carried ultrasound. We performed this study to determine whether medical residents could reliably assess spleen size using hand-carried ultrasound after a brief educational intervention. METHODS: Postgraduate year 1 internal medicine residents were shown a brief (45-minute) presentation on ultrasound basics, the use of hand-carried ultrasound, and principles of splenic ultrasound imaging. They practiced on each other, using hand-carried ultrasound to assess spleen size, for 1 hour in the presence of an instructor. Patients with varying degrees of splenomegaly and hospital staff were recruited at Vancouver General Hospital. A sonographer measured spleen size in each participant using conventional ultrasound. Subsequently, the trained residents scanned the participants using hand-carried ultrasound, blinded to the sonographer's measurements and the participants' diagnoses. The instructor was not present during scanning. RESULTS: Twelve first-year residents (8 male and 4 female; mean age ± SEM, 28 ± 1 years; all with limited prior ultrasound training) and 19 patients and staff members (10 male and 9 female; mean age, 60 ± 4 years; body mass index, 24 ± 2 kg/m(2)) were recruited. The greatest longitudinal measurements were 14.0 ± 0.7 cm with conventional ultrasound administered by the sonographer and 13.2 ± 0.9 cm with hand-carried ultrasound administered by the residents (P > .05, not significant). The correlation between conventional and hand-carried ultrasound was r = 0.81 (P < .001). CONCLUSIONS: Internal medicine residents can reliably assess spleen size at the point of care using hand-carried ultrasound with minimal training. Our findings, if replicated in other centers and in different clinical scenarios, may change the way that clinicians examine the spleen.

Prevalence, Knowledge, and Concern About Bed Bugs.

Recent research suggests that the resurgence of bed bugs in the U.S. has occurred at an alarming rate. Assumptions have been made that socioeconomic status is not associated with the prevalence of bed bug infestations. Little information is available at the local level, however, about the prevalence of bed bugs in private homes. The authors' pilot study aimed to identify prevalence, knowledge, and concern about bed bugs in one higher income village in Ohio utilizing survey methodology. Responses from 96 individuals who completed the Prevalence, Knowledge, and Concern About Bed Bugs survey were utilized for analysis. The majority of the sample respondents were white and 95% reported that they owned their residence. Only 6% knew someone with bed bugs. Additionally, 52% reported they were somewhat concerned about bed bugs. About 46% reported that they had changed their behavior. For a higher income area, the prevalence was dissimilar to the rate reported in the general public (about 20%). This suggests that bed bugs may be an environmental issue effecting low-income populations disproportionately. Further research is needed in areas of differing socioeconomic levels.