Secukinumab versus adalimumab for psoriatic arthritis: comparative effectiveness up to 48 weeks using a matching-adjusted indirect comparison

Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations. Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index score, presence of dactylitis and enthesitis, and previous anti-TNF therapy. Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 (placebo-adjusted), 16, 24, and 48 (nonplacebo-adjusted). After matching, the effective sample size for FUTURE 2 was 101. Week 12 American College of Rheumatology (ACR) response rates were not significantly different between secukinumab and adalimumab. Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab (P = 0.017, P = 0.033), as was ACR 50 for secukinumab 300 mg (P = 0.030). Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab (P = 0.001, P = 0.019), as was ACR 20 for secukinumab 300 mg (P = 0.048). Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab (P = 0.002, P = 0.027), as was ACR 50 for secukinumab 300 mg (P = 0.032). In our analysis, patients with PsA receiving secukinumab were more likely to achieve higher ACR responses through 1 year (weeks 16-48) than those treated with adalimumab. Although informative, these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can validate these findings. Novartis Pharma AG

ACR Accreditation for Utah Valley Hospital’s Radiation Oncology Center

Becoming an accredited clinic through the American College of Radiology (ACR) and their Radiation Oncology Practice Accreditation (ROPA) program will provide third-party evaluation of patient care to ensure the best treatment possible for patients. Talk of getting ACR accreditation has occurred in the past for Utah Valley Hospital/American Fork Hospital, but at the time it was seen as something that did not provide sufficient value vs. the cost. The recent One Intermountain restructuring is intended to unify all of the Intermountain Healthcare radiation oncology centers in Utah so the Radiation Oncology Director has set the goal that all Intermountain radiation oncology programs will be accredited. Intermountain Medical Center (IMC) and Dixie Regional Medical Center (DRMC) are currently ACR accredited and can be used as model programs. I started with an in-depth examination of our department’s workflow, documentation, and policies in order to determine where improvements to meet ACR accreditation standards could be made. I followed this up by working on implementing some of these improvements throughout the clinic and made sure they become routine and a standard in the department. An analysis of Dixie Regional Medical Center and Intermountain Medical Center’s ACR documents was performed to provide a baseline of an accredited-ACR program. Finally, a comprehensive checklist of everything that will need to be changed or implemented was presented in order to provide guidance for the future

Implications of multiply-charged anomalous cosmic rays

During the acceleration of anomalous cosmic rays (ACRs) some singly-charged ions are stripped of additional electrons. The resulting multiply-charged ions are accelerated more efficiently, and most ACRs with >=30 MeV/nuc are multiply-charged. This paper considers some implications of multiply-charged ACRs, including limits that they place on the time scales for ACR acceleration and transport, and their use in defining the cutoff in the accelerated ACR spectrum. Possible causes of the spectral cutoff in three ACR acceleration models are discussed

Further steps of hepatic stimulatory substance purification

The hepatic stimulatory substance (HSS) extracted from weanling rat livers was purified 381,000-fold using chromatographic techniques including nondissociating polyacrylamide gel electrophoresis (nondenaturing PAGE). The activity of this highly purified HSS, named Acr-F4, was assessed in two in vivo models. In 40% hepatectomized rats, it produced a fivefold increase in the proliferative rate normally seen following this partial hepatectomy. In Eck fistula dogs, the level of base increase in hepatocyte renewal was amplified threefold by an infusion of Acr-F4 (50 ng/kg/day). Acr-F4 had no influence on the regenerative response of the kidney following a unilateral nephrectomy or of the bowel following a 40% resection of the small bowel. On the basis of these findings, it can be concluded that HSS (Acr-F4) has a high biological activity and is organ specific. © 1991 Plenum Publishing Corporation

Finite time distributions of stochastically modeled chemical systems with absolute concentration robustness

Recent research in both the experimental and mathematical communities has focused on biochemical interaction systems that satisfy an "absolute concentration robustness" (ACR) property. The ACR property was first discovered experimentally when, in a number of different systems, the concentrations of key system components at equilibrium were observed to be robust to the total concentration levels of the system. Followup mathematical work focused on deterministic models of biochemical systems and demonstrated how chemical reaction network theory can be utilized to explain this robustness. Later mathematical work focused on the behavior of this same class of reaction networks, though under the assumption that the dynamics were stochastic. Under the stochastic assumption, it was proven that the system will undergo an extinction event with a probability of one so long as the system is conservative, showing starkly different long-time behavior than in the deterministic setting. Here we consider a general class of stochastic models that intersects with the class of ACR systems studied previously. We consider a specific system scaling over compact time intervals and prove that in a limit of this scaling the distribution of the abundances of the ACR species converges to a certain product-form Poisson distribution whose mean is the ACR value of the deterministic model. This result is in agreement with recent conjectures pertaining to the behavior of ACR networks endowed with stochastic kinetics, and helps to resolve the conflicting theoretical results pertaining to deterministic and stochastic models in this setting

The Transition from Singly to Multiply-Charged Anomalous Cosmic Rays: Simulation and Interpretation of SAMPEX Observations

Multiply-charged anomalous cosmic rays (ACRs) can arise when singly-charged ACR ions are stripped of one or more of their electrons during their acceleration via, e.g., the process of diffusive shock-drift acceleration at the solar-wind termination shock. Recent measurements of the charge states of ACR neon, oxygen, and nitrogen by SAMPEX at 1 AU have shown that above ≈ 25 MeV/nucleon these ions are multiply charged. In addition, SAMPEX observations have also established that the transition from mostly singly-charged to mostly multiply-charged ACRs (defined as the 50% point) occurs at a total kinetic energy of ≈ 350 MeV. Preliminary simulations for ACR oxygen based on a theory of multiply-charged ACRs were able to show a transition energy at ≈ 300 MeV. However, the simulated intensity distribution among the various charge states was inconsistent with observations. This paper reexamines the predictions of the theory in light of new SAMPEX ACR observations and recently developed and refined estimates of hydrogen-impact ionization cross sections. Based on simulations for multi-species ACR ions, we find that the transition energy is only weakly dependent on characteristic transport parameters, and that the new ionization rates distribute the intensity among the charge states in a manner consistent with observations. The calculated transition energy is in excellent agreement with the measured value

Usefulness of gene expression profiling of bronchoalveolar lavage cells in acute lung allograft rejection.

BackgroundChronic lung allograft dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Because effective therapies are lacking, early identification and mitigation of risk factors is a pragmatic approach to improve outcomes. Acute cellular rejection (ACR) is the most pervasive risk factor for CLAD, but diagnosis requires transbronchial biopsy, which carries risks. We hypothesized that gene expression in the bronchoalveolar lavage (BAL) cell pellet (CP) could replace biopsy and inform on mechanisms of CLAD.MethodsWe performed RNA sequencing on BAL CPs from 219 lung transplant recipients with A-grade ACR (n = 61), lymphocytic bronchiolitis (n = 58), infection (n = 41), or no rejection/infection (n = 59). Differential gene expression was based on absolute fold difference >2.0 and Benjamini-adjusted p-value ≤0.05. We used the Database for Annotation, Visualization and Integrated Discovery Bioinformatics Resource for pathway analyses. For classifier modeling, samples were randomly split into training (n = 154) and testing sets (n = 65). A logistic regression model using recursive feature elimination and 5-fold cross-validation was trained to optimize area under the curve (AUC).ResultsDifferential gene expression identified 72 genes. Enriched pathways included T-cell receptor signaling, natural killer cell-mediated cytotoxicity, and cytokine-cytokine receptor interaction. A 4-gene model (AUC = 0.72) and classification threshold defined in the training set exhibited fair performance in the testing set; accuracy was 76%, specificity 82%, and sensitivity 60%. In addition, classification as ACR was associated with worse CLAD-free survival (hazard ratio = 2.42; 95% confidence interval = 1.29-4.53).ConclusionsBAL CP gene expression during ACR is enriched for immune response pathways and shows promise as a diagnostic tool for ACR, especially ACR that is a precursor of CLAD

A prospective randomized trial of fk506 versus cyclosporine after human pulmonary transplantation

We have conducted a unique prospective randomized study to compare the effect of PK506 and cyclosporine (CsA) as the principal immunosuppressive agents after pulmonary transplantation. Between October 1991 and March 1993, 74 lung transplants (35 single lung transplants [SLT], 39 bilateral lung transplant [BLT]) were performed on 74 recipients who were randomly assigned to receive either FK or CsA. Thirty-eight recipients (19 SLT, 19 BLT) received FK and 36 recipients (16 SLT, 20 BLT) received CsA. Recipients receiving FK or CsA were similar in age, gender, preoperative New York Heart Association functional class, and underlying disease. Acute rejection (ACR) was assessed by clinical, radiographic, and histologic criteria. ACR was treated with methylprednisolone, 1 g i.v./day, for three days or rabbit antithymocyte globulin if steroid-resistant.During the first 30 days after transplant, one patient in the FK group died of cerebral edema, while two recipients treated with CsA died of bacterial pneumonia (1) and cardiac arrest (1) (P=NS). Although one-year survival was similar between the groups, the number of recipients free from ACR in the FK group was significantly higher as compared with the CsA group (P<0.05). Bacterial and viral pneumonias were the major causes of late graft failure in both groups. The mean number of episodes of ACR/ 100 patient days was significantly fewer in the FK group (1.2) as compared with the CsA group (2.0) (P<0.05). While only one recipient (1/36=3%) in the group treated with CsA remained free from ACR within 120 days of transplantation, 13% (5/38) of the group treated with FK remained free from ACR during this interval (P<0.05). The prevalence of bacterial infection in the CsA group was 1.5 episodes/100 patient days and 0.6 episodes/100 patient days in the FK group. The prevalence of cytomegaloviral and fungal infection was similar in both groups.Although the presence of bacterial, fungal, and viral infections was similar in the two groups, ACR occurred less frequently in the FK-treated group as compared with the CsA-treated group in the early postoperative period (<90 days). Early graft survival at 30 days was similar in the two groups, but intermediate graft survival at 6 months was better in the FK group as compared with the CsA group. © 1994 by Williams and Wilkins

Image blur estimation based on the average cone of ratio in the wavelet domain

In this paper, we propose a new algorithm for objective blur estimation using wavelet decomposition. The central idea of our method is to estimate blur as a function of the center of gravity of the average cone ratio (ACR) histogram. The key properties of ACR are twofold: it is powerful in estimating local edge regularity, and it is nearly insensitive to noise. We use these properties to estimate the blurriness of the image, irrespective of the level of noise. In particular, the center of gravity of the ACR histogram is a blur metric. The method is applicable both in case where the reference image is available and when there is no reference. The results demonstrate a consistent performance of the proposed metric for a wide class of natural images and in a wide range of out of focus blurriness. Moreover, the proposed method shows a remarkable insensitivity to noise compared to other wavelet domain methods