28232 research outputs found
Sort by
Animal Models and Their Role in Imaging-Assisted Co-Clinical Trials
No full textThe availability of high-fidelity animal models for oncology research has grown enormously in recent years, enabling preclinical studies relevant to prevention, diagnosis, and treatment of cancer to be undertaken. This has led to increased opportunities to conduct co-clinical trials, which are studies on patients that are carried out parallel to or sequentially with animal models of cancer that mirror the biology of the patients’ tumors. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are considered to be the models that best represent human disease and have high translational value. Notably, one element of co-clinical trials that still needs significant optimization is quantitative imaging. The National Cancer Institute has organized a Co-Clinical Imaging Resource Program (CIRP) network to establish best practices for co-clinical imaging and to optimize translational quantitative imaging methodologies. This overview describes the ten co-clinical trials of investigators from eleven institutions who are currently supported by the CIRP initiative and are members of the Animal Models and Co-clinical Trials (AMCT) Working Group. Each team describes their corresponding clinical trial, type of cancer targeted, rationale for choice of animal models, therapy, and imaging modalities. The strengths and weaknesses of the co-clinical trial design and the challenges encountered are considered. The rich research resources generated by the members of the AMCT Working Group will benefit the broad research community and improve the quality and translational impact of imaging in co-clinical trials.</jats:p
Transport signatures of Majorana quantum criticality realized by dissipative resonant tunneling
No full textWe consider theoretically the transport properties of a spinless resonant electronic level coupled to strongly dissipative leads, in the regime of circuit impedance near the resistance quantum. Using the Luttinger liquid analogy, one obtains an effective Hamiltonian expressed in terms of interacting Majorana fermions, in which all environmental degrees of freedom (leads and electromagnetic modes) are encapsulated in a single fermionic bath. General transport equations for this system are then derived in terms of the Majorana T-matrix. A perturbative treatment of the Majorana interaction term yields the appearance of a marginal, linear dependence of the conductance on temperature when the system is tuned to its quantum critical point, in agreement with recent experimental observations. We investigate in detail the different crossovers involved in the problem, and analyze the role of the interaction terms in the transport scaling functions. In particular, we show that single barrier scaling applies when the system is slightly tuned away from its Majorana critical point, strengthening the general picture of dynamical Coulomb blockade. © 2014 American Physical Society
Protocol of a Multicenter Prospective Trial of Office-Based Carpal Tunnel Release With Ultrasound Guidance (ROBUST).
No full textBackground Carpal tunnel release (CTR) is a common surgical procedure for patients with severe or refractory carpal tunnel syndrome (CTS) symptoms. Historically, CTR procedures have been performed in a hospital or an ambulatory surgery center (ASC). However, due to advancements in techniques, greater patient demand, and concerns about growing healthcare costs, there is a distinct trend toward performing CTR procedures in an office-based setting. Several small studies with limited follow-up duration have demonstrated the feasibility of CTR with ultrasound guidance (CTR-US) when performed in an office-based setting. The objective of this study is to evaluate the safety and effectiveness of office-based CTR-US in a large cohort of patients (n=140) with symptomatic CTS followed for two years post-treatment. Design and methods ROBUST is a prospective multicenter observational study in which 140 subjects at up to 12 sites in the United States will be treated with CTR-US in an office-based setting. The primary endpoint of the study is the change in the Boston Carpal Tunnel Questionnaire Symptom Severity Scale score. Secondary endpoints include time to return to normal daily activities, time to return to work among employed subjects, change in the Boston Carpal Tunnel Questionnaire Functional Status Scale score, change in the Michigan Hand Questionnaire overall and domain scores, change in the Numeric Pain Scale score, change in the EuroQoL-5 Dimension 5-Level score, global satisfaction scores, and the incidence of device or procedure-related adverse events. The primary analysis of study endpoints will occur three months post-treatment. Patient follow-up in this study will continue for two years. Conclusions A central institutional review board approved the study protocol, and a data safety monitoring board will provide study oversight. The authors plan to report study results at medical conferences and in peer-reviewed medical journals. The outcomes of ROBUST will provide physicians, patients, and payors with important safety and effectiveness data regarding the clinical utility of CTR-US when performed in an office setting
Tracking the Benefits of Natural & Working Lands in the United States: Dataset Evaluation and Readiness Assessment
No full textNatural and working lands (NWL) in the United States provide many benefits, including food, climate mitigation, recreational opportunities, jobs, and many more. There is currently no coordinated approach in the United States to track how provision of these benefits is changing over time. This project begins to fill this gap by identifying datasets that can be used to track the status and trends of NWL benefits (i.e., ecosystem services), assessing their readiness for use in the near-term, and highlighting data gaps and limitations that need to be addressed for a national assessment
When Capacity Encounters Crisis: Subnational Governments' Heterogeneous Response to the "Zero-Covid" Policy in China
No full textNearly three years after the first pandemic outbreak, China relaxed its Zero-Covid policy. During the period of strict control, some local officials flexibly achieved both pandemic control and economic recovery with targeted measures, while others insisted on stringent policies with large-scale lockdowns even when the number of infected cases was low. Under the uniform Zero-Covid policy, why did subnational governments facing a similar level of infection adopt different lockdown decisions? This paper argues that state capacity is key to understanding heterogeneity in policy implementation. Specifically, using a two-way fixed effects model, this paper provides robust evidence that, first, fiscal capacity, the conventional dimension of state capacity, does not significantly influence lockdown decisions. Second, medical capacity, the capacity closely related to the policy goal, explains the variation: cities with weaker medical capacity, i.e., fewer medical workers for achieving pandemic control, are more likely to prefer strict measures with large-scale lockdowns, while high-capacity cities prefer targeted measures with small-scale lockdowns. Third, different dimensions of capacity are not necessarily correlated: cities with strong fiscal capacity do not necessarily have strong medical capacity. In sum, state capacity is multidimensional and varies across localities, and heterogeneity in policy implementation is shaped by capacity contingent on the policy goal, especially in times of crisis.</p
Transiciones inconclusas: los caminos de la interculturalidad en el Sistema Integral para la Paz en Colombia
No full textEste artículo aborda los avances de la justicia transicional colombiana creada por el Acuerdo Final de Paz de 2016. Un argumento central es que las organizaciones étnicas han sido actores centrales en el diseño y la puesta en marcha de la Jurisdicción Especial para la Paz (JEP), la Comisión para el Esclarecimiento de la Verdad, la Convivencia y no Repetición (CEV) y, en menor medida, la Unidad de Búsqueda de Personas dadas por Desaparecidas (UBPD). A la vez, discutimos fricciones, limitaciones y conflictos que han emergido al reconocer la diversidad étnica en estos mecanismos transicionales. De manera crítica y reflexiva, analizamos discursos y prácticas ligadas al multiculturalismo liberal y exploramos alternativas desde los movimientos étnicos. Aunque el camino hacia la interculturalidad es complejo, este permite alcanzar un enfoque transformador y garantizar la no-continuidad de las violencias estructurales, relacionadas con una institucionalidad reticente a pensarse desde una interculturalidad crítica</jats:p
Contour interpolation by deep learning approach.
No full textPurposeContour interpolation is an important tool for expediting manual segmentation of anatomical structures. The process allows users to manually contour on discontinuous slices and then automatically fill in the gaps, therefore saving time and efforts. The most used conventional shape-based interpolation (SBI) algorithm, which operates on shape information, often performs suboptimally near the superior and inferior borders of organs and for the gastrointestinal structures. In this study, we present a generic deep learning solution to improve the robustness and accuracy for contour interpolation, especially for these historically difficult cases.ApproachA generic deep contour interpolation model was developed and trained using 16,796 publicly available cases from 5 different data libraries, covering 15 organs. The network inputs were a 128×128×5 image patch and the two-dimensional contour masks for the top and bottom slices of the patch. The outputs were the organ masks for the three middle slices. The performance was evaluated on both dice scores and distance-to-agreement (DTA) values.ResultsThe deep contour interpolation model achieved a dice score of 0.95±0.05 and a mean DTA value of 1.09±2.30 mm , averaged on 3167 testing cases of all 15 organs. In a comparison, the results by the conventional SBI method were 0.94±0.08 and 1.50±3.63 mm , respectively. For the difficult cases, the dice score and DTA value were 0.91±0.09 and 1.68±2.28 mm by the deep interpolator, compared with 0.86±0.13 and 3.43±5.89 mm by SBI. The t-test results confirmed that the performance improvements were statistically significant ( pConclusionsA deep learning method was developed to enhance the process of contour interpolation. It could be useful for expediting the tasks of manual segmentation of organs and structures in the medical images
Factors associated with surgeon recommendation for additional cast immobilization of a CT-verified nondisplaced scaphoid waist fracture.
No full textIntroductionData from clinical trials suggest that CT-confirmed nondisplaced scaphoid waist fractures heal with less than the conventional 8-12 weeks of immobilization. Barriers to adopting shorter immobilization times in clinical practice may include a strong influence of fracture tenderness and radiographic appearance on decision-making. This study aimed to investigate (1) the degree to which surgeons use fracture tenderness and radiographic appearance of union, among other factors, to decide whether or not to recommend additional cast immobilization after 8 or 12 weeks of immobilization; (2) identify surgeon factors associated with the decision to continue cast immobilization after 8 or 12 weeks.Materials and methodsIn a survey-based study, 218 surgeons reviewed 16 patient scenarios of CT-confirmed nondisplaced waist fractures treated with cast immobilization for 8 or 12 weeks and recommended for or against additional cast immobilization. Clinical variables included patient sex, age, a description of radiographic fracture consolidation, fracture tenderness and duration of cast immobilization completed (8 versus 12 weeks). To assess the impact of clinical factors on recommendation to continue immobilization we calculated posterior probabilities and determined variable importance using a random forest algorithm. Multilevel logistic mixed regression analysis was used to identify surgeon characteristics associated with recommendation for additional cast immobilization.ResultsUnclear fracture healing on radiographs, fracture tenderness and 8 (versus 12) weeks of completed cast immobilization were the most important factors influencing surgeons' decision to recommend continued cast immobilization. Women surgeons (OR 2.96; 95% CI 1.28-6.81, p = 0.011), surgeons not specialized in orthopedic trauma, hand and wrist or shoulder and elbow surgery (categorized as 'other') (OR 2.64; 95% CI 1.31-5.33, p = 0.007) and surgeons practicing in the United States (OR 6.53, 95% CI 2.18-19.52, p = 0.01 versus Europe) were more likely to recommend continued immobilization.ConclusionAdoption of shorter immobilization times for CT-confirmed nondisplaced scaphoid waist fractures may be hindered by surgeon attention to fracture tenderness and radiographic appearance
Getting Up Close and Personal: What Makes an Endosome Special in GPCR Signaling
No full textG protein-coupled receptors (GPCRs), a class of critical regulators of mammalian physiology, can initiate unique functional responses depending on the subcellular compartment of their activation. Yet, how endosomal receptors transduce location-biased outcomes remains poorly understood. Efforts to uncover the mechanistic basis of compartmentalized GPCR signaling have largely focused on the biochemical aspect of this regulation through dissection of the relevant factors. Here, we assessed the biophysical positioning of receptor-containing endosomes as an alternative salient mechanism coordinating the transduction of spatially-biased responses. We focused on the beta2-adrenergic receptor (β2AR), a prototypical GPCR that signals from early endosomes via cyclic AMP (cAMP) production. We examined the role of endosome positioning in the context of gene transcription as a representative signaling readout, because endosomal β2ARs are well-known to selectively stimulate transcriptional reprogramming. First, we developed subcellular-localized cAMP and protein kinase A (PKA) sensors to enable selective quantification of endosomal GPCR-mediated activity. We also generated two complementary optical readouts that enable robust measurements of bulk- and gene-specific GPCR/cAMP-dependent transcription with single-cell resolution. We next overcame a technical challenge that has hindered the direct assessment of the functional role of endosome positioning by devising a strategy to selectively and rapidly redistribute receptor-containing endosomes ‘on command’ in intact cells without perturbing their biochemical composition. By combining these readouts with rapid endosome relocalization, we established that disruption of native endosome positioning inhibits the initiation of the endosome-dependent responses. Lastly, utilizing the cAMP and PKA sensors, we demonstrated a prominent mechanistic role of local PKA activity and phosphodiesterase (PDE)-mediated cAMP hydrolysis in this process. This dissertation work, therefore, illuminates a novel mechanism regulating GPCR function by identifying endosome positioning as the principal mediator of spatially-selective receptor signaling. </p
Radiographic outcomes of adult spinal deformity correction: A critical analysis of variability and failures across deformity patterns
No full textStudy Design Multicenter, prospective, consecutive, surgical case series from the International Spine Study Group. Objectives To evaluate the effectiveness of surgical treatment in restoring spinopelvic (SP) alignment. Summary of Background Data Pain and disability in the setting of adult spinal deformity have been correlated with global coronal alignment (GCA), sagittal vertical axis (SVA), pelvic incidence/lumbar lordosis mismatch (PI-LL), and pelvic tilt (PT). One of the main goals of surgery for adult spinal deformity is to correct these parameters to restore harmonious SP alignment. Methods Inclusion criteria were operative patients (age greater than 18 years) with baseline (BL) and 1-year full-length X-rays. Thoracic and thoracolumbar Cobb angle and previous mentioned parameters were calculated. Each parameter at BL and 1 year was categorized as either pathological or normal. Pathologic limits were: Cobb greater than 30°, GCA greater than 40 mm, SVA greater than 40 mm, PI-LL greater than 10°, and PT greater than 20°. According to thresholds, corrected or worsened alignment groups of patients were identified and overall radiographic effectiveness of procedure was evaluated by combining the results from the coronal and sagittal planes. Results A total of 161 patients (age, 55 ± 15 years) were included. At BL, 80% of patients had a Cobb angle greater than 30°, 25% had a GCA greater than 40 mm, and 42% to 58% had a pathological sagittal parameter of PI-LL, SVA, and/or PT. Sagittal deformity was corrected in about 50% of cases for patients with pathological SVA or PI-LL, whereas PT was most commonly worsened (24%) and least often corrected (24%). Only 23% of patients experienced complete radiographic correction of the deformity. Conclusions The frequency of inadequate SP correction was high. Pelvic tilt was the parameter least likely to be well corrected. The high rate of SP alignment failure emphasizes the need for better preoperative planning and intraoperative imaging. © 2014 Scoliosis Research Society