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PurposeThis paper aims to present a simple and innovative fuzzy methodology-based lean performance measurement system (L-PMS) for an Indian automotive supply chain. The paper also enlightens the influence of coronavirus disease 2019 (COVID-19) on supply chains and the practical implications of the unprecedented disruptions on the performance measurement systems.Design/methodology/approachThe L-PMS is divided into three phases. In the first phase, the key performance indicator (KPI) list, as deemed fit by the organization, is prepared using literature and suggestions from the case organization. The list contains 61 KPIs measuring 24 performance dimensions in seven functional areas of the supply chain. In the second phase, the KPI performance data (actual, best and worst) are collected using the enterprise resource planning (ERP) system. In the last phase, the leanness score of the case organization is calculated at four levels – KPI, dimension, functional area and overall organization.FindingsThe overall leanness score of the case organization is 60%. The case organization uses KPIs from all seven functional areas, but it needs to improve the number of KPIs in administration and supplier management functional areas. The case organization uses only quantitative KPIs. However, the performance dimensions at the middle level are adequate. The leanness level of the case organization in different areas is highly variable (ranges from 45% to 91%).Research limitations/implicationsThe major limitation of the study is that the case study is done at a single organization.Practical implicationsThe managers at the different levels of the hierarchy can use the lean performance measurement score to leverage the better performing areas/dimensions/KPIs and improve poor performing areas/dimensions/KPIs. The lean performance measurement at functional area level can help leadership to give responsibility to different people for the improvement of leanness with respect to different dimensions/functional areas. The disruptive impact of COVID-19 should clearly be understood by the managers to make appropriate decisions based on the severity as measured at different levels.Originality/valueAccording to the authors' best knowledge, this is the first lean performance measurement application at the four hierarchical levels (KPI, performance dimension, functional area and overall organization).

Background: Nutraceuticals have always been considered natural and safe supplements that may prevent disease, may substitute prescription drugs, compensate for a poor diet or promote health. Several nutraceutical products in the market today play roles as antioxidants and probiotics. One such nutraceutical is Astaxanthin, a red-pigmented keto-carotenoid, which offers a plethora of uses and health benefits. Astaxanthin, like many carotenoids, is a lipid-soluble pigment which faces solubility and bioavailability issues owing to its lipophilicity, due to which its estimation is challenging. And the analysis of a simple solvent extract of Astaxanthin would produce many ester-astaxanthin “peaks” and utilize costly organic solvents. Additionally, the literature review indicates the use of very complex mobile phases and tedious solvent extraction procedures involved in the estimation of Astaxanthin. Objective: The manuscript describes the development and validation of a rapid, sensitive and specific Reverse Phase-High Performance Liquid Chromatographic (RP-HPLC) method involving Ultraviolet (UV) detection for the determination and quantification of nutraceutical Astaxanthin in bulk and capsule dosage forms. Methods: Chromatography was carried out on an Inertsil ODS C18 (250 x 4.6 mm), 5µ, using a filtered and degassed mixture of Water: Acetonitrile (30:70% v/v) as the mobile phase at a flow rate of 1 mL /min with isocratic elution method and effluent was monitored at 478 nm. Results: The method was linear in the range of 5 – 15 μg mL-1 of Astaxanthin. The method was validated with respect to precision, accuracy, specificity and robustness. The run time of the analyte was 8.45 min. Conclusion: The developed method is simple, specific, precise, accurate, and robust and shows no interference with diluents which proves the adaptability of the method for routine analysis of the nutraceutical Astaxanthin in bulk and marketed formulations.

Splenic abscess is an unusual but potentially life-threatening illness, with a 0.7% incidence. The mortality rate for splenic abscess ranges from 15-20% in previously healthy patients with single unilocular leisons to 80% for multiple abscess in immunocompromised patients. An early diagnosis can be made by combining abdominal CT and/or US and clinical features. In this retrospective study of three years, there were a total 47 patients out of which 32 were males and 15 were females and the mean age was 38 years old. The most common symptoms at presentation were left upper quadrant or abdominal pain in all patients (100%), fever in 42 patients (89.36%) and nausea and vomiting in 26 patients (55.31%), breathlessness and tachypnea in 20 patients (42.5%) and 4 patients (8.5%) presented with palpable splenomegaly. A total of eight patients had pancreatitis, there were three patients with liver cirrhosis, two patients with history of splenic trauma, two patients with hiv , one patient with hbsag, two patients with tuberculosis and one patient with gastric neoplasm i.e. GIST. The majority of 41 patients i.e. 87.23% in our study had leukocytosis while other 19 patients i.e. 40.42% had anemia and 5 patient had blood culture positive.

Introduction: Amoebic liver abscess (ALA) is the most commonly seen extra intestinal manifestation of Entamoeba infection.[1] Out of which, a rare complication of amoebic liver abscess is rupture of liver abscess. We report 43 cases of ruptured amoebic liver abscess coming with acute abdomen which were operated at Department of Surgery, Dhiraj general hospital, Vadodara from January 2020 to December 2021. Surgical treatment in these cases should be carried out in a timely fashion prior to the presentation of systemic repercussions or death. result: Out of all patients, 37 patients were male and 6 were female and 37 patients were chronic alcoholic. The mean age was 47 years. At presentation, most cases had clinical signs of generalized peritonitis. Ultrasonography for collection in peritoneal cavity showed moderate free fluid with internal echoes suggestive of pyoperitoneum. Out of which 09 patients had free air under the diaphragm. All 43 patients underwent resuscitation and then shifted for surgery. All underwent exploratory laparotomy for ruptured liver abscess. Intraoperatively, 05 patients had a single abscess in the right lobe, 06 had abscess in both lobes of liver and 33 had multiple abscesses in right lobe.

PDF - 95K, Figure legends for the Supplemental Data.

The bromodomain and extra-terminal (BET) protein family members, including BRD4, bind to acetylated lysines on histones and regulate the expression of important oncogenes, for example, c-MYC and BCL2. Here, we demonstrate the sensitizing effects of the histone hyperacetylation-inducing pan–histone deacetylase (HDAC) inhibitor panobinostat on human acute myelogenous leukemia (AML) blast progenitor cells (BPC) to the BET protein antagonist JQ1. Treatment with JQ1, but not its inactive enantiomer (R-JQ1), was highly lethal against AML BPCs expressing mutant NPM1c+ with or without coexpression of FLT3-ITD or AML expressing mixed lineage leukemia fusion oncoprotein. JQ1 treatment reduced binding of BRD4 and RNA polymerase II to the DNA of c-MYC and BCL2 and reduced their levels in the AML cells. Cotreatment with JQ1 and the HDAC inhibitor panobinostat synergistically induced apoptosis of the AML BPCs, but not of normal CD34+ hematopoietic progenitor cells. This was associated with greater attenuation of c-MYC and BCL2, while increasing p21, BIM, and cleaved PARP levels in the AML BPCs. Cotreatment with JQ1 and panobinostat significantly improved the survival of the NOD/SCID mice engrafted with OCI-AML3 or MOLM13 cells (P < 0.01). These findings highlight cotreatment with a BRD4 antagonist and an HDAC inhibitor as a potentially efficacious therapy of AML. Mol Cancer Ther; 13(5); 1142–54. ©2014 AACR.

PDF - 352K, Supplemental Figure 1: Chemical structures of the molecules used in the studies. Supplemental Figure 2: Effects of (R)-JQ1 in AML cells. Supplemental Figure 3: ChIP of BRD4 and POLII in JQ1 treated AML cells. Supplemental Figure 4: JQ1 effects on CDK6 mRNA expression in AML cells. Supplemental Figure 5: JQ1 effects on mRNA and protein expression in FLT3-ITD expressing AML cells. Supplemental Figure 6: Isobologram analyses of BET protein antagonist and PS in AML cells. Supplemental Table 1: Clinical presentation and mutation status of primary AML samples. Supplemental Table 2: Top gene expression changes in AML cells following JQ1 treatment. Supplemental Table 3: Ingenuity Pathway analysis of AML cells following JQ1 treatment.

Supplemental Figure 1: Chemical structures the agents utilized in the study. Supplemental Table 1: Clinical presentation and mutational status of the primary AML samples. Supplemental Figure 2: BET protein antagonist and FLT3-TKI induces apoptosis of AML cells. Supplemental Figure 3: BET protein antagonist is synergistic with FLT3-TK inhibitors. Supplemental Figure 4: I-BET151 and FLT3-TKI is synergistic in FLT3-ITD expressing AML. Supplemental Figure 5: JQ1 and ponatinib or AC220 is synergistic against primary AML cells. Supplemental Figure 6: JQ1 and FLT3-TKI does not deplete FLT3 phosphorylation. Supplemental Table 2: Comparison of MOLM13 and MOLM13-TKIR response to anti-leukemia agents. Supplemental Figure 7: Effects of JQ1 and FLT3-TKI treatment in MOLM13-TKIR cells. Supplemental Figure 8: Knockdown of BRD4 enhances sensitivity to JQ1 in MOLM13-TKIR cells. Supplemental Figure 9: JQ1 and panobinostat is synergistic against MV4-11 TKIR cells.

Introduction: An anal fissure is a lacerate tear in inner thin lining of anus. The tear exposes the muscle (anal sphincter) around the anus. The damage leads to muscle spasm, which pull the fissure edges even more. The spasms lead to pain and it also slow down the healing. An anal fissure is considered acute anal fissure if it occurs in less than 6 weeks or if it recently happened. Treatment done by breaking the cycle of spasm, relieving pain, and to avoid ischemia, which all are cause for anal fissure. First-line of treatment to minimize anal trauma includes stool softeners, bulk agents, and warm sitz baths(5) if not relived then sphincterotomy open or closed type surgery can be done. Material & Methods: We had conducted a comparative observational study from May 2019 to April 2021 at Dhiraj General Hospital, Vadodara in General Surgery department. In admitted patients posted for Sphincterotomy after consent & explaining risk factor, patients were operated. Detailed clinical history, clinical examination including per abdominal and per rectal examination, routine blood investigations & chest x-ray screening was done. In all the patients undergoing Sphincterotomy done either with open or closed method.

Process Analytical Technology (PAT) is a proactive initiative published by the Food and Drug Administration so as to overcome the conventional way of batch testing. As per the documented guideline it can be stated as a system for designing, analyzing, and controlling pharmaceutical manufacturing through the timely measurement of critical quality and performance parameters. PAT is a quality driven approach with innovative, strategic and rapid systems, so as to clearly understand, predict, manipulate, control and refine manufacturing processes. Owing to its multidimensional applications, process analysis can be carried out even in the most critical processes, like crystallization, by the on-line technique.PAT is one of the prime objectives stressed in the Initiative for Pharmaceutical CGMPs for the 21st Century published by the Food and Drug Administration. The chief motive of this dynamic approach is to carry out measurements on raw materials and in the in process materials or process parameters with tight controls, with a prime goal to enhance final product quality and reduce the chances of error or default/defect. The prime inventiveness of the PAT initiative is to focus on building quality inside the product and the entire manufacturing processes, in addition to continuous process improvement. The adoption of PAT approach can provide a plethora of benefits to the pharmaceutical industry by enhancing product quality while providing supercilious asset utilization and niche financial value. PAT bestows better insight of raw materials, by characterizing it physically and chemically, detailed understanding of manufacturing parameters, all of which collectively decide the fate of the quality and appeal of the final product. Unlikely to the traditional approach of testing the product at its terminal stage, PAT is a dynamic approach to keeping an eye on the manufacturing and other related processes on a continuous basis compared to a discrete one, and keeps a strict check at all stages of production. Hence this detailed review will stress on the importance of PAT and its overall conceptualization, which shall be indeed propitious for furnishing an integrated systems approach for quality design, process analyses, understanding and control, continuous improvement, knowledge and risk-based management within the FDA 21st century framework of Good manufacturing initiative and will be a useful guide to the industry and academia personnel for better understanding of this approach. Additionally it also highlights the unique synergy of Quality by Design with PAT for establishing an in depth understanding of the manufacturing process.

The Covid-19 has shifted the face of many markets including e-commerce and online business with many bottlenecks to be cleared. The last-mile delivery project has the greatest effect on all types of e-commerce companies because it has many consumer touchpoints as well as the Covid-19 pain points. Due to these interconnected issues, the delivery projects itself requires modern solutions. The purpose of this paper is to identify, analyse and categorize the major factors that affect the last mile delivery projects in e-commerce, food sector, retail sector and so on using total interpretive structural modelling approach during the Covid-19. Ten major factors are identified from literature review, and expert opinions are collected from multiple organizations that are involved in the last mile delivery projects. The results indicate that types of goods, achieving routing efficiency and meeting fulfilment timeline are the key factors for last mile delivery projects during the time of Covid-19. This study helps the managers to identify the key factors and to focus on these factors for the successful implementation of last mile delivery project.

PurposeThe assorted piece-wise retail orders in a cosmetics warehouse are fulfilled through a separate fast-picking area called Forward Buffer (FB). This study determines “just-right” size of FB to ensure desired Customer Service Level (CSL) at least storage wastages. It also investigates the impact of FB capacity and demand variations on FB leanness.Design/methodology/approachA Value Stream Mapping (VSM) tool is applied to analyse the warehouse activities and mathematical model is implemented in MATLAB to quantify the leanness at desired CSL. A comprehensive framework is developed to determine lean FB buffer size for a Retail Distribution Centre (RDC) of a cosmetics industry.FindingsThe CSL increases monotonically; however, the results concerning spent efforts towards CSL improvement gets diminished with raised demand variances. The desired CSL can be achieved at least FB capacity and fewer Storage Waste (SW) as it shifts towards more lean system regime. It is not possible to improve Value Added (VA) time beyond certain constraints and therefore, it is recommended to reduce Non-Value Added (NVA) order processing activities to improve leanness.Research limitations/implicationsThis study determines “just-right” capacity and investigates the impact of buffer and demand variations on leanness. It helps managers to analyse warehouse processes and design customized distribution policies in food, beverage and retail grocery warehouse.Practical implicationsProposed buffering model offers customized strategies beyond pre-set CSL by varying it dynamically to reduce wastages. The mathematical model deriving lean sizing and mitigation guidelines are constructive development for managers.Originality/valueThis research provides an inventive approach of VSM model and Mathematical algorithm endorsing lean thinking to design effective buffering policies in a forward warehouse.

Patients suffering from end stage renal disease (ESRD) often present to the emergency with breathlessness, mostly due to fluid overload. We report a rare case of recurrent unilateral massive pleural effusion in an ESRD patient on maintenance hemodialysis (MHD). The patient was on MHD thrice weekly for the last 2 years with right internal jugular vein (IJV) tunneled cuffed catheter (TCC). Chylothorax was identified as the cause of recurrent pleural effusion which was due to superior vena cava stenosis (SVCO). It was managed successfully by balloon venoplasty of SVC and anticoagulation. SVCO is a rare but a serious complication in patients on long term indwelling dialysis catheters. Physicians involved in the care of dialysis patients must be aware about complications of long term dialysis catheters like central vein stenosis. A strong suspicion of chylothorax should be reserved for a patient with recurrent unilateral pleural effusion and long term dialysis catheters.

With an array of innovative technologies, the 21st century has struck at our door. Many sectors are embracing the implementation of a revolutionary technology called Big Data Analytics. The education sector has lately jumped on the bandwagon. With the new evolving education technology capable of generating Big Data, stakeholders have firmly started adopting the use of Big Data Analytics in the education sector. This paper proposes a model for Big Data Analytics depicting various required components, for the education sector. Various sources of education data provide the necessary input to the model and model produces useful results in the form of the output using various tools and technologies of Big Data ecosystem. The outputs are going to be consumed by various stakeholders of the education sector. The paper also describes the concept of Big Data, new technologies influencing the education sector and explains why Big Data Analytics is going to be core technology in analyzing the data and taking the world of education to new heights. We have also listed beneficiaries and benefits.

How the vascular and neural compartment cooperate to achieve such a complex and highly specialized structure as the central nervous system is still unclear. Here, we reveal a crosstalk between motor neurons (MNs) and endothelial cells (ECs), necessary for the coordinated development of MNs. By analyzing cell-to-cell interaction profiles of the mouse developing spinal cord, we uncovered semaphorin 3C (Sema3C) and PlexinD1 as a communication axis between MNs and ECs. Using cell-specific knockout mice and in vitro assays, we demonstrate that removal of Sema3C in MNs, or its receptor PlexinD1 in ECs, results in premature and aberrant vascularization of MN columns. Those vascular defects impair MN axon exit from the spinal cord. Impaired PlexinD1 signaling in ECs also causes MN maturation defects at later stages. This study highlights the importance of a timely and spatially controlled communication between MNs and ECs for proper spinal cord development.

Rationale: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months.Objectives: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe.Methods: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the Delta EBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores.Measurements and Main Results: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a Delta FEV1 greater than or equal to 15% (P Conclusions: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe.

Hypothyroidism is an endocrine condition. The signs and symptoms of Hypothyroidism match with the descriptions of several conditions like Vataja Shotha, Rasa Pradoshaja Vikara or a disorder Agni. In the current study two different dosage forms i.e., Vardhamana (IncreasingDecreasing pattern) and fixed Dosage to evaluate its efficacy on Primary Hypothyroidism.40 patients randomized into two groups Escalating and Fixed were administered Vardhamana Pippali in two dosage forms for 19 days. Serum TThe mean levels of TSH were 9.52 ± 3.97 mIU/ml, 10 ± 6.02 mIU/ml, and 10.21 ± 8.49 mIU/ml at baseline, 20th day and 40th day respectively in group A. In group B it was 9.21 ± 3.72 mIU/ml, 8.23 ± 4.62 mIU/ml, and 9.15 ± 4.67 mIU/ml at baseline, 20th day and 40th day respectively. The mean Zulewski's clinical score was 3.67 ± 1.49, 2.28 ± 1.32, and 2.06 ± 1.25 at baseline, 20th day, and 40th day respectively in Escalating group. In Fixed group it was 3.83 ± 1.20, 2.50 ± 1.42, and 3.44 ± 1.33 at baseline, 20th day, and 40th day respectively.Zulewski's clinical scores were statically non-significant in both the groups on the 20th-day respectively, suggesting minimal efficacy of the interventions. But subjects administered with Vardhamana Pippali exhibited better long-lasting effects suggesting sustained effects of the drug.Pippali is efficacious in reducing the signs and symptoms of Primary Hypothyroidism and also has a positive impact on the Thyroid profile but is more effective when administered in Vardhamana dosage compared to fixed dose.