Enabling quantitative robot-assisted compressional elastography via the extended Kalman filter.

Compressional or quasi-static elastography has demonstrated the capability to detect occult cancers in a variety of tissue types, however it has a serious limitation in that the resulting elastograms are generally qualitative whereas other forms of elastography, such as shear-wave, can produce absolute measures of elasticity for histopathological classification. We address this limitation by introducing a stochastic method using an extended Kalman filter and robot-assistance to obtain quantitative elastograms which are resilient to measurement noise and system uncertainty. In this paper, the probabilistic framework is described, which utilizes many ultrasound acquisitions obtained from multiple palpations, to fuse data and uncertainty from a robotic manipulator's joint encoders and force/torque sensor directly into the inverse reconstruction of the elastogram. Quantitative results are demonstrated over homogeneous and inclusion gelatin phantoms using a seven degree of freedom manipulator for a range of initial elasticity assumptions. Results imply resilience to poorly assumed initial conditions as all trials were within 5 kPa of the elasticity measured by a mechanical testing system. Moreover, the presence or absence of an inclusion is clear in all reconstructed elastograms even when artifacts are present in displacement fields, indicating further robustness to measurement noise. The proposed stochastic method allows fusion of data from a robot's sensors directly into compressional elastography image reconstruction which may stabilize optimization and improve accuracy. This approach provides a mathematical framework to readily incorporate measurements from additional sensors in future applications which may extend the capabilities of compressional elastography beyond that of producing quantitative elasticity measurements.

Engaging patients and parents to improve mental health intervention for youth with rheumatological disease.

BACKGROUND: Mental health disorders are common in youth with rheumatological disease yet optimal intervention strategies are understudied in this population. We examined patient and parent perspectives on mental health intervention for youth with rheumatological disease. METHODS: We conducted a mixed methods cross-sectional study, via anonymous online survey, developed by researchers together with patient/parent partners, to quantitatively and qualitatively examine youth experiences with mental health services and resources in North America. Patients ages 14-24 years with juvenile idiopathic arthritis, juvenile dermatomyositis, or systemic lupus erythematous, and parents of patients ages 8-24 with these diseases were eligible (not required to participate in pairs). Participants self-reported mental health problems (categorized into clinician-diagnosed disorders vs self-diagnosed symptoms) and treatments (e.g. therapy, medications) received for the youth. Multivariate linear regression models compared patient and parent mean Likert ratings for level of: i) comfort with mental health providers, and ii) barriers to seeking mental health services, adjusting for potential confounders (patient age, gender, disease duration, and patient/parent visual analog score for disease-related health). Participants indicated usefulness of mental health resources; text responses describing these experiences were analyzed by qualitative description. RESULTS: Participants included 123 patients and 324 parents. Patients reported clinician-diagnosed anxiety (39%) and depression (35%); another 27 and 18% endorsed self-diagnosed symptoms of these disorders, respectively. 80% of patients with clinician-diagnosed disorders reported receiving treatment, while 11% of those with self-diagnosed symptoms reported any treatment. Patients were less comfortable than parents with all mental health providers. The top two barriers to treatment for patients and parents were concerns about mental health providers not understanding the rheumatological disease, and inadequate insurance coverage. Over 60% had used patient mental health resources, and over 60% of these participants found them to be helpful, although text responses identified a desire for resources tailored to patients with rheumatological disease. CONCLUSION: Self-reported mental health problems are prevalent for youth in this sample with rheumatological disease, and obstacles to mental health treatment include disease-related and logistic factors. Strategies are needed to improve acceptance and accessibility of mental health intervention, including routine mental health screening and availability of disease-specific mental health resources.

Diminished PKC activity and decreased binding of transcription factors are involved in the impaired production of nitric oxide by macrophages from tumor-bearing mice.

In previous studies we have shown that peritoneal macrophages (PEM) from mammary tumor-bearing BALB/c mice (T-PEM) display a diminished ability to lyse tumor cells upon stimulation with LPS, a phenomenon that is associated to a lower production of nitric oxide, and that is reverted upon costimulation with IFN-gamma. The reduced lytic activity and NO production displayed by T-PEM upon LPS activation were earlier shown by us to be due to a diminished transcription of the inducible nitric oxide synthase (iNOS) gene. In the present study, we have investigated the participation of possible signaling molecules and transcription factors - PKC, NF-kappaB, C/EBP and IRF-1 - in the downregulation of NO production in LPS-activated T-PEM. It was found that PKC activity was greatly reduced in T-PEM as compared to normal macrophages, and did not respond to activation. Interestingly, the different PKC isozyme levels were not significantly altered in T-PEM, with the exception of PKC delta. Alterations in the binding activity of the transcription factors NF-kappaB and C/EBP appeared to be involved in the reduced transcription of iNOS previously observed in T-PEM after LPS activation. These results provide evidence that reductions in iNOS transcription secondary to alterations in cell signaling may be responsible for the diminished capacity of macrophages of LPS-activated tumor-bearers to produce NO and lyse tumor targets.