On the study of the C6+ ion beam and γ-ray induced effect on structural and luminescence properties of Eu doped LiNaSO4: explanation of TSL mechanism using PL, TL and EPR study.

The present paper reports on the γ-ray and C6+ ion beam induced effect on the structural and luminescence properties of Eu doped LiNaSO4 phosphors synthesized via wet the chemical method. The material was irradiated by 60Co and 137Cs γ-rays and 75 MeV C6+ ions in a fluence range varying from 2 × 1010 to 1 × 1012 ion per cm2. The ion induced modified properties were investigated using X-ray diffraction (XRD), micro-Raman spectroscopy, photoluminescence (PL), thermoluminescence (TL) and electron paramagnetic resonance (EPR) studies. The XRD and micro-Raman results confirm the loss of crystallinity and elongation of the lattice parameters after ion beam irradiation. The presence of both divalent as well as trivalent states of Eu ions at multiple sites of LiNaSO4 is observed by PL study. Irradiation of the LiNaSO4:Eu phosphor with a C6+ ion beam modifies the population of the valence state of the doped rare earth Eu ion and enhances the TL sensitivity of this phosphor. The nature of the prominent TL glow curve is identical for both γ-ray and C6+ ion beam irradiated materials while additional deep trap levels appear in the latter due to the formation of several types of cation and anion vacancy. The electron paramagnetic resonance (EPR) technique also supports the presence of the Eu ion at multiple sites and provides information regarding several types of radical produced after γ-ray and C6+ ion irradiation. Finally, a mechanism is presented for the thermally stimulated luminescence phenomenon on the basis of our observed results from the PL, TL and EPR studies. The reason behind ion beam irradiation induced modification of the TL properties and enhancement of luminescence intensity is also explained in this report.

Luminescence properties of nanocrystalline Mg2 P2 O7 :Eu phosphor.

Thermoluminescence (TL) measurements were carried out on europium (Eu) doped magnesium pyrophosphate (Mg2 P2 O7 ) nanopowders using gamma irradiation in the dose range of 0.1 to 3 kGy. The powder samples were successfully synthesized by chemical co-precipitation synthesis route. The formation and crystallinity of the compound was confirmed by powder X-ray diffraction (PXRD) pattern. The estimated particle size was found to be in nanometer scale by using Debye Scherer's formula. A scanning electron microscopy (SEM) study was carried out for the morphological characteristics of as synthesized Mg2 P2 O7 :Eu phosphor. Photoluminescence (PL) study was carried out to confirm the presence of the rare-earth ion and its valence state. The TL analysis of synthesized samples were performed after the irradiation of Mg2 P2 O7 :Eu with cobalt-60 (60 Co) gamma rays. The high and low intensity peaks of TL glow curve appeared at around 400 K, 450 K, 500 K and 596 K respectively. The appreciable shift in peak positions has been observed for different concentrations of Eu ion. The trapping parameters, namely activation energy (E), order of kinetics (b) and frequency factor (s) have been determined using thermal cleaning process, peak shape (Chen's) method and glow curve deconvolution (GCD) functions.

Use of Polymethyl Methacrylate-Based Cement for Cosmetic Correction of Donor-Site Defect following Transposition of Temporalis Myofascial Flap and Evaluation of Results after Adjuvant Radiotherapy.

BACKGROUND: Temporalis myofascial flap is a versatile flap for reconstruction of the oral cavity defects, but results in an esthetically compromised deformity at the donor site. We used polymethyl methacrylate (PMMA) cement to correct the volume loss defect caused by temporalis myofascial flap and evaluated its results before and after adjuvant radiotherapy. METHODS: We discuss our experience of using PMMA cement to augment donor-site deformity in 25 patients (17 males, 8 females) between years 2005 and 2009. The primary defect was a result of the ablative surgery for squamous cell carcinoma of the upper alveolar and the buccoalveolar sulcus. A modified curved hemicoronal incision was used as an access for better cosmetic outcome. The volume of cement required was decided during the surgery. RESULTS: All patients are in regular follow-up, alive and free of complications at implant site, except one patient who developed wound dehiscence. The condition of the implant was evaluated by postoperative computed tomographic scan, repeated after adjuvant radiotherapy in cases required. There were no radiation-induced changes in the contour and volume of the implants. Cosmetic result of the implant was reported satisfactory by the patients postoperatively. CONCLUSION: Restoration of the temporal area defect after the temporalis myofascial flap harvest with the use of PMMA cement is an easy and safe method, with excellent esthetic results. The implant is stable and resistant to any changes in contour and loss of volume even after adjuvant radiotherapy, with no added morbidity to the patients.

Endoscopic repair of CSF rhinorrhea: necessity of fibrin glue.

OBJECTIVE: The aim of this study is to compare the efficacy of cerebrospinal fluid (CSF) repair with and without fibrin glue in pediatric patients with CSF rhinorrhea treated endoscopically. MATERIALS AND METHODS: This was a retrospective study carried out in the Departments of Otolaryngology and Neurosurgery at a tertiary care center between December 2005 and July 2010. RESULTS: The 27 patients with CSF rhinorrhea included in the study were divided into Group A: 13 patients who underwent endoscopic endonasal CSF repair using fibrin glue (Tisseel, Baxter, Vienna, Austria) by an endoscopic rhinologist and Group B: 14 patients who underwent endonasal CSF repair without fibrin glue. There was no statistically significant difference in endoscopic CSF repairs with or without fibrin glue (P = 0.48) in all the variables studied. CSF repair without fibrin glue appeared more cost saving as compared to repair with glue. CONCLUSION: CSF repairs with and without fibrin glue are equally effective and CSF repair without fibrin is costs saving.

EVALUATION OF ACCURACY AND INTRINSIC UNCERTAINTY OF AUTOMATED IMAGE REGISTRATION FOR A 6D KV-CBCT IMAGE GUIDANCE SYSTEM: A CONCURRENT ANALYSIS WITH A MACHINE PERFORMANCE CHECK.

The accuracy and uncertainty of the automated image registration (AIR) algorithm in a six-dimensional (6D) kilovoltage cone-beam computed tomography (kV-CBCT) image-guided radiation therapy (IGRT) system were evaluated with a concurrent analysis of machine performance check (MPC). The MPC was performed before (MPCpre) and after (MPCpost) each accuracy and intrinsic uncertainty measurement. The accuracy was evaluated for 25 sets of the known shifts applied to the Catphan-504 phantom through a 6D robotic couch in the head, thorax, and pelvis CBCT acquisition modes. The uncertainty was evaluated for the intensity range, soft tissue, and bone matching filters in the head, thorax and pelvis CBCT acquisition modes. The mean ΔMPC (MPCpost-MPCpre) for all test parameters was within 0.02 ± 0.08 mm and 0.00 ± 0.02°. The overall average accuracy in AIR of 6D kV-CBCT IGRT in all translational and rotational axes was within 0.05 ± 0.76 mm and 0.02 ± 0.07°, respectively, for all CBCT modes. The overall mean population (Mpop), systematic (Σ) and random (σ) errors were within 0.47, 0.53 and 0.24 mm and within 0.03, 0.08 and 0.07° in translational and rotational axes, respectively, for all matching filters in all CBCT modes. The accuracy and intrinsic uncertainty in the AIR of the 6D kV-CBCT IGRT were within acceptable limits for clinical use.

BIDS: Blockchain and Intrusion Detection System Coalition for Securing Internet of Medical Things Networks.

The benefits of the Internet of Medical Things (IoMT) in providing seamless healthcare to the world are at the forefront of technological advancement. However, security concerns of any IoMT systems are high since they threaten to compromise personal information of patients and can even cause health hazards. Researchers are exploring the use of various techniques to ensure a high level of security of IoMT systems. One key concern is that the computing power of any Internet of Things (IoT) device is relatively low, hence mechanisms that require low computational power are appropriate for designing Intrusion Detection Systems (IDS). In this research work, a blockchain IDS coalition is proposed for securing IoMT networks and devices. The blockchain ledger is compact and uses less processing resources. Additionally, the ledger requires less communication overhead. The cryptographic hashes in the suggested architecture ensure complete data secrecy and integrity between parties who are trusted and those who are untrustworthy. Peer-to-peer networks in both central and cluster networks are also included in this work for complete decentralization. The proposed model can counter various attacks, including Denial of Service (DoS), anonymity attacks, impersonation attacks, Man-In-The-Middle (MITM), and Cross-Site Scripting (XSS). The proposed method achieved an F1- score as high as 100% and reported an AUC value of over 99%.

Neurological involvement, immune response, and biomarkers in Kawasaki disease along with its pathogenesis, therapeutic and diagnostic updates.

Kawasaki disease is an acute, febrile disease that is not typically fatal if treated and affects infants and children more commonly. More than 80% of the afflicted patients are under the age of four. This disease most commonly affects coronary arteries. In a minority of cases, Aneurysms can burst or produce thrombosis, and they can cause infarction. The distinctive redness in the palms and soles of the feet might result from a delayed-type hypersensitivity reaction to a cross-reactive or recently discovered antigen (s). Autoantibodies against epithelial cells and smooth muscle cells are produced as a result of subsequent macromolecule synthesis and polyclonal white blood cell activation, which intensifies the redness. Kawasaki disease's clinical manifestations range from oral skin disease to the blistering of the mucosa, symptoms involving the hands and the feet, skin disease of the palms and soles, a desquamative rash, and cervical lymphatic tissue enlargement (so it is also referred to as tissue layer lymphatic tissue syndrome). Most untreated patients develop some vessel sequelae, from well-organized coronary inflammation to severe arterial blood vessel dilatation to giant artery aneurysms with rupture or occlusion, infarction, and thrombosis. With human gamma globulin administration, reasonable standards of medical care, and the use of analgesics, the speed of symptomatic progression and inflammatory artery changes are reduced. In this review, we have covered the immunology of Kawasaki disease, its biomarkers, and the neurological manifestations of this multisystem illness. We have also included a discussion on its pathogenesis, diagnosis, and treatment.

Impaired functional but preserved structural connectivity in limbic white matter tracts in youth with conduct disorder or oppositional defiant disorder plus psychopathic traits.

Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult antisocial behavior and psychopathy. Neuroimaging studies demonstrate functional abnormalities in orbitofrontal cortex and the amygdala in both youths and adults with psychopathic traits. Diffusion tensor imaging in psychopathic adults demonstrates disrupted structural connectivity between these regions (uncinate fasiculus). The current study examined whether functional neural abnormalities present in youths with CD/ODD+PT are associated with similar white matter abnormalities. Youths with CD/ODD+PT and comparison participants completed 3.0 T diffusion tensor scans and functional magnetic resonance imaging scans. Diffusion tensor imaging did not reveal disruption in structural connections within the uncinate fasiculus or other white matter tracts in youths with CD/ODD+PT, despite the demonstration of disrupted amygdala-prefrontal functional connectivity in these youths. These results suggest that disrupted amygdala-frontal white matter connectivity as measured by fractional anisotropy is less sensitive than imaging measurements of functional perturbations in youths with psychopathic traits. If white matter tracts are intact in youths with this disorder, childhood may provide a critical window for intervention and treatment, before significant structural brain abnormalities solidify.

QUANTIFICATION OF 6D INTER-FRACTION TUMOUR LOCALISATION ERRORS IN TONGUE AND PROSTATE CANCER USING DAILY KV-CBCT FOR 1000 IMRT AND VMAT TREATMENT FRACTIONS.

This study aimed to evaluate the 6D inter-fraction tumour localisation errors in 20 tongue and 20 prostate cancer patients treated with intensity-modulated radiation therapy and volumetric-modulated arc therapy. The patient tumour localisation errors in lateral, longitudinal and vertical translation axes and pitch, roll and yaw rotational axes were analysed by automatic image registration of daily pretreatment kilovoltage cone-beam computed tomography (kV-CBCT) with planning CT in 1000 fractions. The overall mean error (M), systematic error (Σ), random error (σ) and planning target volume (PTV) margins were evaluated. The frequency distributions of setup errors were normally distributed about the mean except for pitch in the tongue and prostate. The overall 3D vector length ≥ 5 mm was 14.2 and 49.8% in the ca-tongue and ca-prostate, respectively. The frequency of rotational errors ≥1 degree was a maximum of 37 and 59.5%, respectively, in ca-tongue and ca-prostate. The M, Σ and σ for all translational and rotational axes decreased with increasing frequency of verification correction in ca-tongue and ca-prostate patients. Similarly, the PTV margin was reduced with no correction to alternate day correction from a maximum of 4.7 to 2.5 mm in ca-tongue and from a maximum of 8.6 to 4.7 mm in ca-prostate. The results emphasised the vital role of the higher frequency of kV-CBCT based setup correction in reducing M, Σ, σ and PTV margins in ca-tongue and ca-prostate patients.

Evaluation of kV-CBCT based 3D dose calculation accuracy and its validation using delivery fluence derived dose metrics in Head and Neck Cancer.

PURPOSE: The purpose of this study is to evaluate the dosimetric impact of Hounsfield unit (HU) variations in kilovoltage cone-beam computed tomography (kV-CBCT) based 3D dose calculation accuracy in the treatment planning system and its validation using measured treatment delivery dose (MTDD) derived dose metrics for Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiotherapy (IMRT) plans in Head and Neck (HN) Cancer. METHODS: CBCT dose calculation accuracy was evaluated for 8 VMAT plans on inhomogeneous phantom and 40 VMAT and IMRT plans of HN Cancer patients and validated using ArcCHECK diode array MTDD derived 3D dose metric on CT and CBCT. RESULTS: The mean percentage dose difference between CBCT and CT in TPS (ΔD(CBCT-CT)TPS) and 3DVH (ΔD(CBCT-CT)3DVH) were compared for the corresponding evaluation dose metrics (D98%, D95%, D50%, D2%, Dmax, D1cc, D0.03cc, Dmean) of all PTVs and OARs in phantom and patients. ΔD(CBCT-CT)TPS and ΔD(CBCT-CT)3DVH for all evaluation dose points of all PTVs and OARs were less than 2.55% in phantom and 2.4% in HN patients. The Pearson correlation coefficient (r) between ΔD(CBCT-CT)TPS and ΔD(CBCT-CT)3DVH for all dose points in all PTVs and OARs showed a strong to moderate correlation in phantom and patients with p < 0.001. CONCLUSIONS: This study evaluated and validated the potential feasibility of kV-CBCT for treatment plan 3D dose reconstruction in clinical decision making for Adaptive radiotherapy on CT in Head and Neck cancer.

Development of detailed finite element models for in silico analyses of brain impact dynamics.

BACKGROUND AND OBJECTIVE: In the last few decades, several studies have been performed to investigate traumatic brain injuries (TBIs) and to understand the biomechanical response of brain tissues, by using experimental and computational approaches. As part of computational approaches, human head finite element (FE) models show to be important tools in the analysis of TBIs, making it possible to estimate local mechanical effects on brain tissue for different accident scenarios. The present study aims to contribute to the computational approach by means of the development of three advanced FE head models for accurately describing the head tissue dynamics, the first step to predict TBIs. METHODS: We have developed three detailed FE models of human heads from magnetic resonance images of three volunteers: an adult female (32 yrs), an adult male (35 yrs), and a young male (16 yrs). These models have been validated against experimental data of post mortem human subjects (PMHS) tests available in the literature. Brain tissue displacements relative to the skull, hydrostatic intracranial pressure, and head acceleration have been used as the parameters to compare the model response with the experimental response for validation. The software CORAplus (CORrelation and Analysis) has been adopted to evaluate the bio-fidelity level of FE models. RESULTS: Numerical results from the three models agree with experimental data. FE models presented in this study show a good bio-fidelity for hydrostatic pressure (CORA score of 0.776) and a fair bio-fidelity brain tissue displacements relative to the skull (CORA score of 0.443 and 0.535). The comparison among numerical simulations carried out with the three models shows negligible differences in the mechanical state of brain tissue due to the different morphometry of the heads, when the same acceleration history is considered. CONCLUSIONS: The three FE models, thanks to their accurate description of anatomical morphology and to their bio-fidelity, can be useful tools to investigate brain mechanics due to different impact scenarios. Therefore, they can be used for different purposes, such as the investigation of the correlation between head acceleration and tissue damage, or the effectiveness of helmet designs. This work does not address the issue to define injury thresholds for the proposed models.

Facile synthesis and thermoluminescence properties of nano bio-ceramic ß-Ca2P2O7:Dy phosphor irradiated with 75 meV C6+ ion beam.

Dy3+ doped ß-Ca2P2O7 phosphor has been synthesized using wet chemical method. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis confirmed the formation of ß-Ca2P2O7:Dy nano-phosphors. However, photoluminescence (PL) study was carried out to confirm the presence of dopant ion in the host matrix of ß-Ca2P2O7:Dy material. Thermoluminescence (TL) glow curves of ß-Ca2P2O7 were recorded for different concentrations of Dy3+ after exposure to various fluences of C6+ ion beam (75 meV). TL sensitivity of ß-Ca2P2O7:Dy3+ (0.1 mol%) phosphor was 3.79 times more than commercially available CaSO4:Dy3+. TRIM code based on the Monte Carlo simulation was used to calculate the absorbed doses, ion range and main energy loss. Glow curve de-convolution (GCD) method was used to determine the number of TL peaks and their trapping parameters. The wide linear response of ß-Ca2P2O7 nanoparticles along with high stability of TL glow curve makes this nanomaterial a good candidate for C6+ ion beam dosimetry.

MAC Attack: Clinical Correlates of Mycobacterium avium Complex Infection Among Patients With and Without Cancer.

BACKGROUND: In 2007 the American Thoracic Society (ATS) released guidelines on management of Mycobacterium avium complex (MAC), an increasingly common respiratory organism worldwide. Determining when this represents a true respiratory pathogen remains controversial and becomes increasingly challenging in patients with cancer. This study aims to 1) describe the phenotype that exists among cancer patients with MAC colonization and MAC pulmonary infection when compared to non-cancer patients; 2) assess whether cancer, symptoms, and radiographs, were associated with the decision to treat MAC pulmonary infection with antibiotics. METHODS: We retrospectively analyzed 550 adult, non-human immunodeficiency virus (HIV) patients, among whom MAC was identified in respiratory cultures or tissue. Radiographs, clinical symptoms and cancer status were studied. Patients were categorized as having MAC pulmonary infection based on 2007 ATS guidelines, and antibiotic treatment was thereafter reviewed. Fisher's exact test and Wilcoxon Rank sum assessed differences. RESULTS: Median age of the 550 patients was 68 years; most were female (56%) and white (83%). Symptoms and radiographic abnormalities accompanying MAC isolation were common, occurring among 83% and 99.6% respectively of all patients. There were 444 patients with MAC who had current or inactive cancers, most commonly hematologic (30%) and lung (25%) malignancies, while 106 patients never had cancer. Cancer patients were younger (P = 0.028), less often female (P < 0.001), and had less-frequent pre-existing lung disease (P = 0.017) than those without cancer. There were 196 (35%) patients determined to have MAC pulmonary infection, among whom 49 (9%) received directed antibiotics. Those receiving antibiotics had lower body mass index (BMI) (P < 0.0001), more frequent pre-existing lung disease (P = 0.003) and lower cancer rates (P = 0.008) than those not receiving antibiotics. Patients receiving antibiotics were more likely to have cavitary disease (P = 0.001), cough/dyspnea (P = 0.012), hemoptysis (P < 0.001), and constitutional symptoms (P = 0.001). CONCLUSIONS: In concordance with ATS guidelines, hemoptysis, constitutional symptoms, cough/dyspnea and cavitary disease were associated with highest likelihood to treat with antibiotics. The phenotype in cancer patients was quite different than the classic Lady Windermere syndrome. MAC pulmonary infection was treated less often in cancer patients. This study extends beyond the ATS guidelines to examine the potential import of malignancy on the colonization and potential treatment of MAC.

Does Continuing Medical Education (CME) Activity Contribute to Learning Gain: An Objective Evaluation.

Continuing medical education (CME) and work-shops go a long way to update and refresh medical education of the medical practitioners and help them to stay updated about latest advances in the medical field which helps them to impart latest and better treatment to the patients. This article aims at reporting the evaluation of the effectiveness of the learning in terms of knowledge gained immediately after the workshop and to objectively quantify the knowledge gain from the CME program. Pre- and post-CME survey of knowledge by the way of multiple choice question questionnaire was used to assess the efficacy of the CME and the learning gain of the participants. 42 participants were included in the assessment of the gain in knowledge after the CME. An increase of 17.9% in the scores of the participants was seen at the end of the CME, with a learning gain of 38%. Educational activity like CME can improve the knowledge base of the intended participants. Further research is required to evaluate if education delivered in a short workshop of this nature is retained for any length of time and if it results in any change in practice that affects health outcomes.

Oncological outcome following TORS in HPV negative supraglottic carcinoma.

OBJECTIVE: The aim of this study was to determine the oncological and functional outcomes following transoral robotic surgery (TORS) in human papilloma virus negative supraglottic cancers. STUDY DESIGN: A prospective observational study at a tertiary cancer care center, New Delhi, India. MATERIALS AND METHODS: From February, 2013 to December, 2015, 45 patients with supraglottic lesions underwent TORS using the da Vinci® surgical system. RESULTS: Forty-five patients underwent TORS for supraglottic laryngectomy (SGL), with all patients undergoing bilateral neck dissection. The most common site was Ary-epiglottic fold. 47.9% were cT1 and 52.1% were cT2. Average robotic set-up time was 8.8 min and average robotic operative time was 42.9 min. A positive or close margin was seen in 12 patients (26.7%) on frozen, which were revised intraoperatively. On final histology, 3 (6.7%) patients had a margin of <5 mm. The average closest margin was 5.7 mm. Patients tolerated oral feeds within 2 weeks of procedure. All patients were HPV negative. Postoperatively, all patients had adequate swallowing and speech. Follow-up ranged from 24 to 58 months. Thirty-eight (84.4%) patients were alive and disease free. CONCLUSION: TORS is a safe, feasible, minimally invasive, and oncologically safe procedure in patients with early HPV supraglottic cancers. It has less morbidity and offers benefits in terms of early airway and feeding rehabilitation and avoids complications resulting from radiation therapy for these patients.

Oncological outcome following initiation of treatment for stage III and IV HPV negative oropharyngeal cancers with transoral robotic surgery (TORS).

OBJECTIVE: To report long-term oncological and functional outcome of Transoral Robotic Surgery escalated treatment including radiotherapy or chemoradiotherapy for Stage III-IV HPV negative oropharyngeal malignancies. METHOD: From March 2013 to September 2015, 153 patients with oropharyngeal carcinoma were included in the study. Patients were evaluated for disease free survival, overall survival and post-treatment functional outcomes. RESULTS: 153 patients (96 males and 57 females) underwent TORS for oropharyngeal carcinoma. 142 patients on final histopathology had stage III and IV disease and received adjuvant treatment based on final histopathology. One hundred and sixteen (81.7%) patients were disease free on average follow-up of 48 months with an overall survival of 91.5% at mean follow-up of 48 months. CONCLUSION: TORS can be used to intensify treatment of Stage III/IV oropharyngeal carcinoma and avoid early and late toxicities due to higher doses of upfront RT/CTRT and achieve better oncological outcome.

Feasibility, Safety, and Surgical Outcome of Robotic Hemithyroidectomy Via Transaxillary and Retroauricular Approach: an Institutional Experience.

The aim of this observational prospective study was to determine the technical feasibility, safety, and adequacy of robotic hemithyroidectomy. From April 2015 to May 2016, 16 patients with solitary thyroid lesion underwent robotic hemithyroidectomy using the Da Vinci® Si Surgical system. Patients were observed and data were recorded on surgical time, blood loss, complications, and functional outcome of the patients. A total of 16 patients (3 males and 13 females; mean age 39.9 years) underwent robotic hemithyroidectomy after evaluation for solitary thyroid nodule with a mean nodule size of 2.2 ± 0.3 cm. Fiber-optic laryngoscopy (FOL) was normal in all cases pre-operatively. Five patients were operated by transaxillary approach, the rest by retroauricular (facelift) approach. Mean pocket dissection time was 42 min for transaxillary and 40 min for retroauricular approach. Mean operative console time was 59.4 min for transaxillary and 52.6 min for retroauricular approach. Average blood loss was 45 ml. Mean hospital stay was 1.5 days. None of the patients had any post-operative complication on follow-up. One patient had restricted left vocal cord mobility which improved in 3 months. Mean pain score was 0.25 ± 0.4 and average speech score was 0.5 ± 0.2 at 3 months. Post-operatively, all patients had adequate swallowing with no episode of aspiration. Robotic hemithyroidectomy is a safe, feasible, and oncologically safe procedure. It has benefits in terms of better scar cosmesis than open surgery.

Stem cell biomanufacturing under uncertainty: A case study in optimizing red blood cell production.

As breakthrough cellular therapy discoveries are translated into reliable, commercializable applications, effective stem cell biomanufacturing requires systematically developing and optimizing bioprocess design and operation. This article proposes a rigorous computational framework for stem cell biomanufacturing under uncertainty. Our mathematical tool kit incorporates: high-fidelity modeling, single variate and multivariate sensitivity analysis, global topological superstructure optimization, and robust optimization. The advantages of the proposed bioprocess optimization framework using, as a case study, a dual hollow fiber bioreactor producing red blood cells from progenitor cells were quantitatively demonstrated. The optimization phase reduces the cost by a factor of 4, and the price of insuring process performance against uncertainty is approximately 15% over the nominal optimal solution. Mathematical modeling and optimization can guide decision making; the possible commercial impact of this cellular therapy using the disruptive technology paradigm was quantitatively evaluated.