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Chemokine receptor CXCR4 antagonist plerixafor (Px) as well as high volume (HV) leukapheresis have been shown to reduce hematopoietic stem progenitor cell (HSPC) mobilization failure rates. However, no direct comparisons of such methods currently exists.We compared the HSPC collection yield based on basal peripheral blood CD34+ cell numbers in patients diagnosed with multiple myeloma or non-Hodgkin's lymphoma undergoing autologous stem cell transplantation in a retrospective chart review. The leukapheresis methods used included HV versus regular volume (RV) with or without Px. There were 116 patients in the study group while the historical control group had 34 patients.Control group underwent RV leukapheresis without Px. Addition of Px or HV in the study group failed to display significant improvement in CD34+ cell collection yield; however, when basal CD34+ cell numbers were taken into account, both Px + RV and HV without Px increased CD34+ cell collection yield. The collection failure rates of HV without Px group were comparable to Px + RV when the basal CD34+ cell numbers were over 20/μl. Of interest, multivariate linear regression analysis did not detect any significant difference between HV versus Px + RV or other leukapheresis methods in CD34 yields or collection failure rates from a single collection after controlling for other factors (sex, age, or underlying disease). In multivariate analysis, pre apheresis CD34+ cell number was significantly and positively associated with the CD34+ cell yields from a single apheresis. In our studies, the majority of patients can be rescued without Px by HV alone as a potential cost saving approach. In summary, trend in our studies reflects that both Px and HV are capable of reducing the mobilization failure rates except the poorest mobilizers, which will need to be validated in larger studies.

Blood and marrow transplantation (BMT) is rarely available in many low- to middle-income countries (LMICs). In 2012, Civil Service Hospital, a government hospital in Kathmandu, partnered with the University of Illinois at Chicago to consult on the establishment of BMT in their hospital, train staff, and promote educational activities. The implementation of BMT occurred in 3 phases over 4 years and included regular onsite visits, training of personnel in Chicago, continuous remote communication, and co-organization of educational events in Kathmandu. The Nepalese government funded the construction of a state-of-the art BMT unit and stem cell laboratory inside Civil Hospital. Autologous (auto) hematopoietic stem cell transplantation (HSCT) was started in 2016, and allogeneic (allo) HSCT from matched related donors (MRDs) or haploidentical (haplo) donors was initiated in 2017. The cost of transplantation was $5200 for auto-HSCT, $10,000 for MRD HSCT, and $13,300 for haplo HSCT. The major socioeconomic determinants reported by Nepalese BMT providers were the cost of transplantation, loss of revenue of the patient and/or caregiver, and cost of transportation. All patients (n = 66) received peripheral blood stem cell grafts, and all allo-HSCT recipients were given post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis. Among recipients of auto-HSCT (n = 30), with a median follow-up of 1029 days (range, 130 to 1653 days), 87% were alive, and transplantation-related mortality (TRM) was 10%. Among allo-HSCT recipients (n = 36), all patients engrafted, and at a median follow-up of 204 days (range, 12 to 1131 days), 75% of them were alive (MRD, 71%; haplo, 83%), with a TRM of 19%. Only 3 of 36 patients developed acute GVHD grade II-IV. The median overall survival in auto-HSCT recipients was 1610 days and was not reached in allo-HSCT recipients. The long-lasting partnership with University of Illinois at Chicago helped build capacity and allowed the Civil Service Hospital team to establish a BMT program in Nepal that has high quality standards at an affordable cost for the majority of patients.

The clinical benefits of treatments with a combination of two or more therapeutic monoclonal antibodies (mAbs) have emerged in recent years. Imaged capillary isoelectric focusing is a frequently used technology in the biopharmaceutical industry for charge variant analysis of protein therapeutics. However, with the wide concentration ranges of combination products, one component may fall within the linear detection range, whereas the other does not. Here, we report a novel methodology to explore charge variants of mAb mixtures using multiple detection techniques simultaneously. We use ultraviolet absorbance to monitor the charge variants of the high-concentration component and native fluorescence (FL) to monitor the variants of the low-concentration one. Charge variants of mixtures that span 40-fold in ratio differences can be accurately quantified with this approach. In contrast to the conventional methods, it is not necessary to prepare and analyze two samples at different concentrations and combine the results for combination product testing. Additionally, the use of FL detection enables the charge variant analysis of highly potent/low abundant mAbs in a mixture. This methodology is more quality-control friendly and efficient for the charge variant analysis of combination products with wide ratios.

Background Bevacizumab is increasingly used in children with pediatric low-grade glioma (PLGG) despite limited evidence. A nationwide UK service evaluation was conducted to provide larger cohort “real life” safety and efficacy data including functional visual outcomes. Methods Children receiving bevacizumab-based treatments (BBT) for PLGG (2009–2020) from 11 centers were included. Standardized neuro-radiological (RANO-LGG) and visual (logMAR visual acuity) criteria were used to assess clinical–radiological correlation, survival outcomes and multivariate prognostic analysis. Results Eighty-eight children with PLGG received BBT either as 3rd line with irinotecan (85%) or alongside 1st/2nd line chemotherapies (15%). Toxicity was limited and minimal. Partial response (PR, 40%), stable disease (SD, 49%), and progressive disease (PD, 11%) were seen during BBT. However, 65% progressed at 8 months (median) from BBT cessation, leading to a radiology-based 3 yr-progression-free survival (PFS) of 29%. Diencephalic syndrome (P = .03) was associated with adverse PFS. Pre-existing visual morbidity included unilateral (25%) or bilateral (11%) blindness. Improvement (29%) or stabilization (49%) of visual acuity was achieved, more often in patients’ best eyes. Vision deteriorated during BBT in 14 (22%), with 3-year visual-PFS of 53%; more often in patients’ worst eyes. A superior visual outcome (P = .023) was seen in neurofibromatosis type 1-associated optic pathway glioma (OPG). Concordance between visual and radiological responses was 36%; optimized to 48% using only best eye responses. Conclusions BBTs provide effective short-term PLGG control and delay further progression, with a better sustained visual (best > worst eye) than radiological response. Further research could optimize the role of BBT toward a potentially sight-saving strategy in OPG.

In this paper, a near-optimal tuning method for PID controller which is based on minimizing the Integral Square Error (ISE) is presented. Parseval’s theorem is used to find the ISE as a function of controller parameters. Guaranteed optimization of the ISE is achieved using the Moore Skelboe Algorithm and interval analysis for the given range of the controller parameter. For stability assurance, Routh Hurwitz criterion is used. This method is effective for finding PID values for given initial range and applicable for all first and second order linear time-invariant (LTI) system and some of the higher-order LTI systems. Simulation results are presented using the MATLAB and INTLAB software. Experimental results are presented for pitch and yaw angle control of Twin Rotor Multiple Input Multiple Output (MIMO) system.

The purpose of this study was to develop and evaluate a patient thickness-based protocol specifically for the confirmation of enteric tube placements in bedside abdominal radiographs. Protocol techniques were set to maintain image quality while minimizing patient dose.A total of 226 pre-intervention radiographs were obtained to serve as a baseline cohort for comparison. After the implementation of a thickness-based protocol, a total of 229 radiographs were obtained as part of an intervention cohort. Radiographs were randomized and graded for diagnostic quality by seven expert radiologists based on a standardized conspicuity scale (grades: 0 non-diagnostic to 3+). Basic patient demographics, body mass index, ventilatory status, and enteric tube type were recorded and subgroup analyses were performed. Effective dose was estimated for both cohorts.The dedicated thickness-based protocol resulted in a significant reduction in effective dose of 80% (p-value0.01). There was no significant difference in diagnostic quality between the two cohorts with 209 (92.5%) diagnostic radiographs in the baseline and 221 (96.5%) diagnostic radiographs in the thickness-based protocol (p-value 0.06).A protocol optimized for the confirmation of enteric tube placements was developed. This protocol results in lower patient effective dose, without sacrificing diagnostic accuracy. The technique chart is provided for reference. The protocol development process outlined in this work could be readily generalized to other imaging clinical tasks.

INTRODUCTION: Bevacizumab/Irinotecan is currently 3rd-line treatment in the UK for progressive Paediatric Low-Grade Glioma (PLGG) based on limited evidence. A nationwide service evaluation was conducted to review its safety and efficacy amongst a larger cohort. METHODS: Data from children with PLGG receiving Bevacizumab-based Treatments (BBT) from 11 UK Centres (2009-2020) were reviewed. Radiological and visual outcomes were based on standardized measurements. Clinical-radiological correlation was investigated. Time to progression from BBT stop, progression free-survival (PFS) curves and multivariate analysis of prognostic factors (p 0.05) were performed. RESULTS: 88 children with PLGG (88% OPG, 24% NF1) had BBT for radiological (43%), visual (20%) or combined (27%) progression, after 40 months (median) from diagnosis. Amongst OPG cases, visual acuity (VA) per eye (better/worse) before BBT was logMAR 0.0-0.3 (23/7) 0.3 - 1.0 (27/20), > 1.0 (14/18) and LP/NLP (8/27), with 19/8 children respectively blind (LP/NLP) in one or both eyes. Bevacizumab 10 mg/kg every 14 days (median 24 doses) was given as 3rd line+ with Irinotecan (85%) or alongside 1st/2nd line chemo (15%) leading to remarkable radiological (88%) and visual (74%) responses (stable or improved) within 3-6 months, with limited toxicity. 12% progressed on treatment, and 8% died unrelated to BBT. After initial response 65% progressed at a median of 8 months (4 - 23) after BBT, resulting in 3-year-all-causes-PFS of 16% and 3-yr-visual-PFS of 45% from start of BBT. Visual concordance with MRI was poor (36%) but increases (47%) when better-eye determines visual outcome. Lack of NF1 and diencephalic syndrome (DS) at presentation were independent negative prognostic factors for PFS. CONCLUSIONS: A remarkable but transient effect of BBT has been confirmed. Visual > radiological responses can be sustained after BBT. Variations in current BBT strategies justifies further research, including the potential upfront use alongside conventional first-line chemotherapy as sight-saving strategy.

In today's radiology workflow, free-text reporting is established as the most common medium to capture, store, and communicate clinical information. Radiologists routinely refer to prior radiology reports of a patient to recall critical information for new diagnosis, which is quite tedious, time consuming, and prone to human error. Automatic structuring of report content is desired to facilitate such inquiry of information. In this work, we propose an unsupervised machine learning approach to automatically structure radiology reports by detecting and normalizing anatomical phrases based on the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) ontology. The proposed approach combines word embedding-based semantic learning with ontology-based concept mapping to derive the desired concept normalization. The word embedding model was trained using a large corpus of unlabeled radiology reports. Fifty-six anatomical labels were extracted from SNOMED CT as class labels of the whole human anatomy. The proposed framework was compared against a number of state-of-the-art supervised and unsupervised approaches. Radiology reports from three different clinical sites were manually labeled for testing. The proposed approach outperformed other techniques yielding an average precision of 82.6%. The proposed framework boosts the coverage and performance of conventional approaches for concept normalization, by applying word embedding techniques in semantic learning, while avoiding the challenge of having access to a large amount of annotated data, which is typically required for training classifiers.

Big data analytics offers promise in many business sectors, and health care is looking at big data to provide answers to many age-related issues, particularly dementia and chronic disease management. The purpose of this review was to summarize the challenges faced by big data analytics and the opportunities that big data opens in health care. The top challenges were issues of data structure, security, data standardization, storage and transfers, and managerial skills such as data governance. The top opportunities revealed were quality improvement, population management and health, early detection of disease, data quality, structure, and accessibility, improved decision making, and cost reduction.

The use of multiparametric magnetic resonance (MR) imaging in prostate cancer therapy is increasing, as newer treatment methods and management approaches emerge. The mainstays of therapy-radiation and surgery-are being supplemented (and even replaced) by novel focal therapy methods. Laser and ultrasonographic ablation, photodynamic therapy, electroporation, and cryoablation are the most common focal therapies, each with its own imaging findings. Typical ablation zones have a central focus of enhancement with peripheral rim enhancement; thus, dynamic contrast material-enhanced (DCE) MR imaging is the most important sequence for evaluation of treatment in the immediate posttherapeutic setting. Detection of recurrence can initiate salvage therapy, but recurrence can be difficult to detect on T2-weighted images, again necessitating DCE MR imaging and also diffusion-weighted imaging. Furthermore, the location of recurrence can vary depending on the therapy. With radiation therapy, the most common site of recurrence is the prior tumor site, whereas after prostatectomy, the recurrence usually occurs around the vesicoureteral anastomosis. Regarding management, there is an increased emphasis on watchful waiting and active surveillance, for which MR imaging has a critical role in both selection and follow-up of patients who undergo active surveillance. As MR imaging is being increasingly used for imaging suspected recurrence, it is important for radiologists to be familiar with the normal posttreatment findings and patterns and MR imaging findings of recurrence. ©RSNA, 2018.

The importance of automatic analysis of Optical Character Recognition (OCR) documents has been increasingly recognized to assist with efficient data managements and accessibility. However, most OCR documents are unstructured, making the analysis extremely challenging. A document's Table Of Contents (TOC) provides an overall structure of a document, such as chapters and appendixes. Hence, TOC recognition enables more effect analyze OCR documents effectively. Most existing related works are based on textual features, such as keywords and font sizes. However, textual-based TOC recognition in OCR often fail when OCR documents are complex. In this study, we develop a novel image-based machine learning approach for recognition of TOC, where one-dimensional horizontal projections of TOC are proposed for classifying TOC and non-TOC. To the best of our knowledge, this is the first work to recognize TOC by image-based analysis. We evaluated the proposed methods with PDF documents of thesis and dissertations. The experimental results show that our proposed methods outperformed others.

Soil is one of the most important engineering materials. So to work with soils, there is a need to have proper knowledge about their properties and factors which affect their behavior. The geotechnical properties of a soil such as its plasticity, grain size distribution, compressibility, and shear strength can be evaluated by proper laboratory testing. Soils containing large quantity of clay and silt are the most burdensome to the engineer. These material exhibit marked changes in physical properties with a change in water contents. A hard, dry clay, for example, may be suitable as a foundation for heavy load so long as it remains dry but may become unstable when gets wet, whereas many of the fine soils shrink on drying and expand on wetting which may adversely affect structures founded/constructed upon them. The present review study encourages the utilization of fines as a good engineering material. In this regard, it is necessary to replace the soil with fine admixtures in a fixed proportion, to get an optimum percentage of fine admixture which gives the Maximum Dry Density (MDD) and maximum California Bearing Ratio (CBR) value. This review study shows the results obtained from experimental results by various researchers on the effects of different types of fine admixtures on MDD and CBR values of soil. This review study concentrates on the performance of soil by replacing it with some percentage of fines. From the review, it has been observed that the optimum percentage replacement of fines in soil is around 30%.

This article systematically reviews the rationale for magnetic resonance imaging in prostate cancer, in detection and following various treatment methods. A basic discussion of the identification of prostate cancer is imperative to understand postintervention imaging. Each available therapy, including surgery, radiation, hormone therapy, and focal therapies will be discussed along with associated imaging findings, providing the reader with a better understanding of current interventions in prostate cancer and imaging.

Novel methods of risk stratification are needed for men with prostate cancer. The Prostate Imaging Reporting and Data System (PI-RADS) uses multiparametric MRI (mpMRI) to assign a score indicating the likelihood of clinically significant prostate cancer. We evaluated pretreatment mpMRI findings, including PI-RADS score, as a marker for outcome in patients treated with primary radiation therapy (RT).One hundred and twenty-three men, 64% and 36% of whom had National Comprehensive Cancer Network (NCCN) intermediate-risk and high-risk disease, respectively, underwent mpMRI prior to RT. PI-RADS score and size of the largest nodule were analyzed with respect to freedom from biochemical failure (FFBF) and freedom from distant metastasis.A PI-RADS score of ≤3, 4, or 5 was defined in 7%, 49%, and 44%; with a median nodule size of 0, 8, and 18 mm, respectively (P0.001). Median follow-up was 67 months. Men with PI-RADS ≤ 3, 4, or 5 disease had 7-year FFBF of 100%, 92%, and 65% (P = 0.002), and a 7-year freedom from distant metastasis of 100%, 100%, and 82%, respectively (P = 0.014). PI-RADS (Hazard Ratio 5.4 for PI-RADS 5 vs. 4, P = 0.006) remained associated with FFBF when controlling for NCCN risk category (P = 0.063) and receipt of androgen deprivation therapy (P = 0.535). Nodule size was also associated with FFBF (Hazard Ratio 1.08 per mm, P0.001) after controlling for NCCN risk category (P = 0.156) and receipt of androgen deprivation therapy (P = 0.776).mpMRI findings, including PI-RADS score and nodule size, may improve risk stratification in men treated with primary RT.

OBJECTIVES/GOALS: Currently physicians are able to order CT Chest/Abd/Pelvis images as STAT or Routine. STAT images denote an emergency and are done immediately. We aim to determine the percentage of CT images that are inappropriately ordered as STAT, determine physician image ordering habits, and develop targeted interventions to encourage appropriate STAT image ordering. METHODS/STUDY POPULATION: A fishbone diagram helped reveal possible causes of inappropriate STAT image ordering. Based on the fishbone diagram, a survey was created to assess CT image ordering habits amongst radiology and internal medicine residents and attending physicians. All CT Chest/Abd/Pelvis images ordered over a 3 month period of time (July-Oct 2017) was obtained. The dataset included whether the image was ordered Stat vs Routine, time of image order, physician name and location, and reason for the imaging study.The STAT images were evaluated based on the explanation provided in the CT image order. Currently 2 radiology residents, 2 internal medicine residents, and 2 internal medicine hospitalists are evaluating all STAT CT images to determine appropriateness and how long they are willing to wait for the image to result in a read. RESULTS/ANTICIPATED RESULTS: Analysis of all CT Chest/Abd/Pelvis imaging orders revealed that 51% (1710/3345) of them were ordered as STAT. The preliminary analysis of 227 STAT images showed that 6% were inappropriate. We anticipate results of our survey to show differences in how long a STAT vs Routine image orders should take amongst Radiology and Internal Medicine clinicians. We also anticipate our survey to show differences in factors that warrant STAT imaging amongst the different medical fields. We anticipate that the clinician manual evaluation of all STAT CT image will reveal a large percentage of imaging orders to be inappropriate. All STAT imaging that were flagged as inappropriate will be characterized by the department who ordered the image and the reason provided for the imaging to assess for common themes. DISCUSSION/SIGNIFICANCE OF IMPACT: STAT images are the new routine with more images ordered STAT than Routine. Inappropriate STAT imaging results in truly urgent patients not getting the medical care they need. Many images ordered stat could potentially be switched to routine. By evaluating why clinicians are ordering STAT CT image inappropriately, we will be able to develop targeted interventions to decrease inappropriate STAT CT imaging.

The purpose of this study was to investigate the utility of pre-treatment multiparametric magnetic resonance imaging (mpMRI) in a modern cohort of intermediate and high-risk prostate cancer patients treated with primary radiotherapy.One hundred twenty three men with National Comprehensive Cancer Network (NCCN) intermediate or high-risk prostate cancer were treated with primary EBRT and/or brachytherapy and had evaluable pre-treatment mpMRI with endorectal coil. Images were assessed for the presence of radiographic extraprostatic extension (rEPE), seminal vesicle invasion (rSVI), lymph node involvement (LNI), sextant involvement, and largest axial tumor diameter. Imaging characteristics were analyzed along with clinical risk factors against freedom from biochemical failure (FFBF). Median follow-up time was 50 months.Fourteen (11%) men developed biochemical failure. The 5-year FFBF was 94% in intermediate-risk patients and 82% in high-risk patients (p0.01). mpMRI findings including rEPE (29% vs. 66%, p0.01), rSVI (6% vs. 25%, p0.01), LNI (1% vs. 30%, p0.01), and largest axial tumor size15 mm (27% vs. 48%, p = 0.02) were identified in men with intermediate vs. high risk prostate cancer, respectively. mpMRI features associated with 5-y FFBF biochemical failure on univariate analysis included rEPE (80% vs 98%), rSVI (55% vs. 96%), LNI (65% vs. 93%), and largest axial tumor size15mm (81% vs. 94%, all p0.01). Men without any high risk MRI finding had a 5-y FFBF of 100% vs. 81% (p0.01). Adverse imaging features (HR 8.9, p0.01) were independently associated with biochemical failure in a bivariate model analyzed alongside clinical risk category (HR 3.2, p = 0.04).Pre-treatment mpMRI findings are strongly associated with biochemical outcomes in a modern cohort of intermediate and high-risk patients treated with primary radiotherapy. mpMRI may aid risk stratification beyond clinical risk factors in men treated with radiation therapy; further study is warranted to better understand how mpMRI can be used to individualize therapy.

The Parenteral Drug Association conducted an anonymous global survey of quality culture in the pharmaceutical industry to determine whether there is a relationship between certain quality behaviors and certain quality attributes, and whether these quality attributes could be used as surrogates (or proxy variables) to assess quality culture. Other studies have shown that an unhealthy quality culture is a root cause of many quality or compliance issues seen by sites and organizations. Statistical analysis of survey data suggests that certain attributes are driving good behaviors, and the demographic data suggests that this relationship holds irrespective of the geographic location of the site. Executive survey respondents had a more optimistic view of the current state of quality culture than survey respondents at large, with cross-functional vision showing the biggest gap (P-value = 0.07, F-Test). The top five quality attributes that can serve as surrogates for quality culture were (1) Management communication that quality is everyone's responsibility, (2) Site has formal quality improvement objectives and targets, (3) Clear performance criteria for feedback and coaching, (4) Quality topics included in at least half of all-hands meetings, and (5) Collecting error prevention metrics. These identified mature quality attributes are related to management responsibility, and continual improvement of the pharmaceutical quality system sections of ICH Q10, and therefore may be amenable to be incorporated in audit programs or in regulatory inspections. Additional research and discussion is required to build a coherent approach, which the pharmaceutical industry and regulators can adopt.

Ferritin is required for iron storage in vertebrates and for iron transport and storage in invertebrates, specifically insects. Classical ferritins consist of 24 subunits configured as a polyhedron wherein iron is held. The 24 subunits include light and heavy chains, each with specific functions. Several homologues of the light and heavy chains have been sequenced and studied in insects. In addition to iron transport and storage, ferritin has a role in dietary iron absorption, and functions as a protective agent preventing iron overload, decreasing oxidative stress, and reducing infection in these animals. The expression profile and regulation of a second ferritin light chain homologue (LCH2) in Aedes aegypti [Linnaeus (Diptera: Culicidae), yellow fever mosquito] was characterized in cells, animal developmental stages, and tissues post bloodmeal (PBM) by real-time PCR and immunoblot. Two previously studied ferritin subunits from Ae. aegypti, HCH and LCH1, along with LCH2 were immunoprecipitated and analyzed by mass spectrometry. The three Ae. aegypti ferritin subunits, HCH, LCH1, and LCH2, have different expression profiles and regulation with iron exposure, developmental stage, and tissue response PBM. Ae. aegypti expresses multiple and unique ferritin light chain subunits. Ae. aegypti, the vector for Zika, Dengue, and yellow fever, requires iron for oogenesis that is transported and stored in ferritin; this vector expresses a second light chain ferritin subunit homologue unlike any other species in which ferritin has been studied to date.

In this phase 1 study, we tested increasing doses of total marrow irradiation (TMI) in addition to standard intravenous melphalan at 200 mg/m

Gastrointestinal stromal tumor (GIST) frequently metastasizes to the liver, and conventional staging computed tomography (CT) protocols use multiphasic contrast enhancement for detection of hepatic lesions. We evaluated the sensitivity of arterial phase CT imaging for hepatic GIST metastases compared with that of standard (portal venous [PV]) phase imaging. We conducted a retrospective review of patients who presented with hepatic GIST metastases identified on staging CT examinations between 2005 and 2015. Arterial and PV phase CT images were randomized and reviewed by 2 radiologists blinded to clinical history, correlative imaging, and number of controls. In total, 32 patients had hepatic metastases identified on multiphasic (arterial and PV) staging CT examinations. There was no significant difference in identification of metastases between arterial and PV phase imaging (31 vs 32, P = .32). Lesion size measurements did not significantly differ (P = .58). Arterial phase CT imaging did not significantly increase the sensitivity for hepatic GIST metastases compared with PV phase imaging alone.