Average Lead Time Research Articles

МОДЕЛЮВАННЯ І РЕІНЖИНІРИНГ БІЗНЕС-ПРОЦЕСІВ МАГАЗИНУ КАНЦЕЛЯРСЬКИХ ТОВАРІВ НА ОСНОВІ МЕТОДУ ЕКСПЕРТНИХ ОЦІНОК ТА АЛГОРИТМУ ВИЗНАЧЕННЯ НАДІЙНОСТІ ПОСТАЧАЛЬНИКІВ

The segmentation of the stationery market, analyzes the demand, the main trends, the prospects for development and the existing problems are considered in the work. It has been established that the main two segments over the past years are office supplies and educationproducts. Modeling of business processes of the office supply store network was carried out, IDEF0, DFD, IDEF3 diagrams were constructed using the IDEF methodology for the AS-IS variant. The conclusion is that re-engineering requires wholesale business processes related to theevaluation of suppliers, which is currently determined by subjective judgments about their activities of the store director. The main criteria for evaluation of office supply store suppliers are analyzedand their classification is given. The main criteria for selecting suppliers, such as security of supply, price of goods, average lead time and financial position, are determined. It is revealed thatthe most promising method of supplier evaluation is the method of expert evaluation. The methodology of complex supplier evaluation, based on the matrix implementation of the method ofexpert assessments, as well as the algorithm for calculating the reliability of one supplier's supply, is presented. Measures to reengineer the modeling of business processes of the office supply stores'shopping network based on the mathematical model are proposed. IDEF3 diagrams were constructed using the IDEF methodology for the TO-BE variant, and a comparative analysis of the original and post-reengineering diagrams was performed. The conclusion is made about the prospects of re-engineering other wholesale business processes as such, which provides the main revenue for the stationery store.

Circulating Tumor DNA Using Tagged Targeted Deep Sequencing to Assess Minimal Residual Disease in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

In breast cancer patients undergoing neoadjuvant chemotherapy before surgery, there is an unmet need for noninvasive predictive biomarkers of response. The analysis of circulating tumor DNA (ctDNA) in particular has been the object of several reports, but few of them have studied the applicability of tagged targeted deep sequencing (tTDS) to clinical practice and its performance compared with droplet digital PCR (ddPCR). Here, we present the first results from an ongoing study involving a prospectively accrued, monocentric cohort of patients affected by invasive breast cancer, undergoing neoadjuvant chemotherapy followed by surgery with curative intent as per clinical practice. A pretreatment tumor biopsy and plasma samples were collected before and during treatment, after surgery, and every six months henceforth or until relapse, whichever came first. Pretreatment biopsies were sequenced with a 409-gene massive parallel sequencing (MPS) panel, allowing the identification of target mutations and their research in plasma by tTDS and ddPCR as a complementary approach. Using tTDS, we demonstrated the presence of at least one deleterious mutation in all the relapsed cases we studied (n = 4), with an average lead time of six months before clinical relapse. The association with ddPCR was suboptimal, and only one relapsed patient could be identified with such method. tTDS shows potential as an early noninvasive method for the detection of MRD in BC patients.

Time-varying lead–lag structure between investor sentiment and stock market

This paper uses the thermal path method to study the lead–lag structure of sentiment and the stock market. First, based on principal component analysis, four indicators are selected to construct the sentiment index. Furthermore, the effectiveness of the thermal path method is verified by numerical simulation. Finally, the lead-lag characteristics of the Shanghai Stock Index and the sentiment index are studied via the symmetric thermal optimal path method. The analysis results show that in the short term, investor sentiment has a leading position in the stock market, which may be related to the herd effect and buying the winners behavior. However, over a longer period of time, investor sentiment is affected mainly by fluctuation in the market, which may be related to the existence of cyclical fluctuations in the market and futures arbitrage. In addition, the stock market's leading effect appears mainly from January 2006 to January 2012, with an average lead time of one month.

Recent Trends in Real Estate Research: A Comparison of Recent Working Papers and Publications Using Machine Learning Algorithms

This paper is organized as follows. In Section 1, we describe the economic relevance of the real estate sector and its recent dynamics. Then, we identify the most mentioned keywords of working papers presented at the real estate conferences between 2015 and 2019 and showing network figures for them in Section 2. In order to identify the newest trends, we rely on working papers since they have an average lead time of at least 1 to 2 years before they are published. In addition, we give a short overview of the articles published in this special issue. To get a better overview of the relevance of real estate related topics in finance, we analyzed the most relevant finance conferences and journals between 2015 and May 2020 in Section 3. To find the topics, we apply the text mining approach Latent Dirichlet Allocation (LDA), an unsupervised machine learning method. The real estate trends (retail, e-commerce) and the potential impact of COVID-19 is described in Section 4.

Supply Chain Management Performance of HIV/AIDS Commodities and Factors Affecting It at Health Facilities of SNNPRS of Ethiopia; from the Perspective of Achieving 90-90-90 Strategies.

BackgroundHealth facilities (HFs) need an extensive range of antiretroviral (ARV) drugs and related HIV/AIDS commodities for diagnosis, prevention, and treatment of HIV/AIDS. This study was aimed to assess supply chain management performance from the perspective of achieving 90-90-90 treatment strategy at HFs of Southern Nations, Nationalities and People’s Regional State (SNNPRS), Ethiopia.MethodsFacilities based cross sectional study design in 30 HFs (9 hospitals and 21 health centers) and five pharmaceuticals fund and supply agencies (PFSAs) was conducted. The HFs were selected randomly. Semi-structured questionnaires and observation checklists with logistic indicators assessment tools (LIATs) were used to collect data for HIV/AIDS related services from November 2016 to May 2017. In addition, we used in-depth face to face interview and thematic approach. Quantitative data were entered into Epi-Data version 3.1 and transported to SPSS version 20 to analyze the result. Qualitative data were analyzed using thematic approach.ResultsOnly 9 (30%) HFs had received their orders from PFSA on time from date of report. Average lead time for ARV drugs was 46.4 days in hospitals and 59.2 days in health centers (HCs). Sixteen (60.7%) HFs reported their completed report and requisition format (RRF). From this, 53.3% HFs order was refilled correctly in quantity from that they need. Inventory accuracy rate was 77%. Major HFs, 20 (66.7%) faced at least one-time emergency order for ARV drugs, HIV test kits and viral load (VL) supplies. Whereas, 9 (30%) hospitals and 5 (16.67%) HCs were out of stock two and three times respectively. Sixteen (53.3%) commodities stocked out at least once in six months. Nevirapine (NVP) 10 mg/5 mL in 240 mL was the most stocked out (13 times) for an average 22 days. Uni gold was stocked out (16 times) with average of 34.5 days. Wastage rate was 2.5%. Twenty-five (83.3%) facilities had good storage conditions (>80% to the standard).ConclusionUnsatisfactory data records, stock-outs, interrupted reports, inaccurate inventory and wastage rates were indicators for defective supply chain management of HIV/AIDS commodities. Respective organizations should improve their responsible activities to secure commodities availability.

Parallel serial assessment of somatic mutation and methylation profile from circulating tumor DNA predicts treatment response and impending disease progression in osimertinib-treated lung adenocarcinoma patients.

Circulating tumor DNA (ctDNA) harboring tumor-specific genetic and epigenetic aberrations allows for early detection and real-time monitoring of tumor dynamics. In this study, we aimed to evaluate the potential of parallel serial assessment of somatic mutation and methylation profile in monitoring the response to osimertinib of epidermal growth factor receptor (EGFR) T790M-positive advanced lung adenocarcinoma patients. Parallel somatic mutation and DNA methylation profiling was performed on a total of 85 longitudinal plasma samples obtained from 8 stage IV osimertinib-treated EGFR T790M-positive lung adenocarcinoma patients. Our results revealed a significant correlation between the by-patient methylation level with the maximum allele fraction (maxAF, P=0.0002). The methylation levels were significantly higher in the plasma samples of patients with detectable somatic mutations than patients without somatic mutations (P=0.0003) and healthy controls (P=0.0018). Moreover, analysis of both the DNA methylation level and maxAF revealed four trends of treatment response. Collectively, the decrease in methylation level and maxAF reflected treatment efficacy, while the gradual increase reflected impending disease progression (PD). Elevated methylation levels and maxAF were observed in 6 and 5 patients in an average lead-time of 3.0 and 1.9 months, respectively, prior to evaluation of PD using radiological imaging. DNA methylation profiling has the potential to predict disease relapse prior to evaluation through radiological modalities, suggesting that serial assessment of methylation level in combination with somatic mutation profiling are reliable methods for treatment monitoring. These methods should thus be incorporated with imaging modalities for a more comprehensive work-up of treatment response, particularly for patients treated with targeted therapies.

How to compare energy efficiency inspection tests on TVs?

It is a case study conducted in company X of the electronic branch located in the Industrial Pole of Manaus (PIM), the capital of Amazonas–Brazil. The problem was the need to develop a benchmarking involving energy efficiency inspection tests on televisions. The objective is to compare the performance of the standard method and the new method of performing the energy efficiency inspection test. To this end, quality tools were applied with data collected from the use of the time study of each test step. After data collection and analysis, it was concluded that the new test: a) has 67% of its steps performed automatically and 43% manually, its average lead time is 4h14min34, a gain of 33.5% in total time required to perform the test; b) can be developed with the application of Brainstorming, Ishikawa Diagram, GUT Matrix, PDCA, Vertical Flowchart in conjunction with Chrono-analysis. It is worth highlighting the importance of the local top management support so that each of these tools is used with autonomy and creativity by the collaborators involved in the project.

Early Fever Detection By a Novel Wearable Continuous Temperature Monitor in Patients Undergoing Autologous Stem Cell Transplantation

Introduction Neutropenic fever following high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a common (incidence 63-100%) and potentially life-threatening complication. Recommended time to antibiotic (TTA) administration is within 1 hr of fever onset with delays associated with significant morbidity, prolonged hospitalization, and mortality. Standard of care guidelines emphasize patient self-monitoring for fever, with instructions to seek immediate medical attention if body temperature (temp) reaches 100.4°F or higher. In this study, we evaluated if a novel wearable, continuous temp monitor, tPatch, could reliably estimate core body temp and detect fever in an outpatient setting following ASCT. Additionally, we gathered preliminary data to explore early detection and prediction of clinically relevant temp rise in this clinical setting. Methods Patients (N = 86) with hematologic malignancies (62% multiple myeloma) who underwent high-dose chemotherapy followed by ASCT at Mayo Clinic, MN were prospectively enrolled between June 2018 and March 2019. Patients (82% male) wore an axilla-placed tPatch continuously for 7 days in an outpatient setting during the post ASCT period and were asked to record self-measured oral temp in 3-4 hr intervals daily using a standardized thermometer after appropriate training . Patients followed standard of care procedures with daily clinic assessment of temp, blood counts, and vital signs. An optional patient questionnaire was given at end-of-study. A model was trained using both patient- and clinic-assessed oral temp measures to estimate core temp from 2 sensors on the tPatch device. Core temp estimates and trends were then compared to patient- and clinic-assessed measurements. Fever was defined as a temperature ≥100.4°F for at least 1 hr. Results When compared to all oral temp reads, the tPatch estimated core temp within 0.03 ± 0.7℉. Among the 86 patients, clinic-assessed fever incidence was 29.4% while tPatch-assessed incidence was 58.8%. Using all clinic-recorded temp readings as "ground truth," the sensitivity and specificity of the tPatch algorithm in detecting fevers were 88% and 86%, respectively, while patient self fever detection sensitivity was 62% and specificity 93%. With "fever episode" defined as a temp ≥100.4°F for at least 1 hr, tPatch detected 9.6 times the number of fever episodes vs. clinic reads. The average lead time of tPatch detection of clinic-recorded fevers was 3.7 hours. In 25% of all intervals between clinic temp readings, either tPatch or patients detected at least 1 fever episode. The tPatch was well-tolerated, the only adverse events reported were grade 1 skin irritation and discomfort in 4 (5%) patients. Of 65 patients who completed the survey, 95% reported the tPatch as "quite" or "somewhat" comfortable and 94% stated no difficulty in using the tPatch. Exploration of tPatch temp trends over various time intervals for use in fever prediction is ongoing. Conclusions Patient self-monitoring of temp has low sensitivity and is not feasible for long intervals of time (e.g., overnight). Continuous temperature monitoring by a wearable device overcomes these challenges and has the potential to improve early detection and consequently shorten time to antibiotic initiation. A follow-up randomized study is planned to assess the clinical benefits of continuous temp monitoring through patient and clinician alerts triggering early clinical intervention for febrile neutropenia. Figure Disclosures Vera-Aguilera: Verily Life Sciences: Research Funding. Haji-Abolhassani:Verily Life Sciences: Employment. Kulig:Verily Life Sciences: Employment. Heitz:Verily Life Sciences: Employment. Paludo:Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding; Celgene: Research Funding; Celgene: Research Funding. Ghoreyshi:Verily Life Sciences: Employment. Scheevel:Verily Life Sciences: Research Funding. Schimke:Verily Life Sciences: Research Funding. Markovic:Verily Life Sciences: Research Funding.

No-Shows in Adult Urology Outpatient Clinics: Economic and Operational Implications.

We analyzed trends and explored implications of no-show rates in adult urology from provider related characteristics at an academic program. No-show rates were determined from electronic health records of appointments in adult urology at Duke University Medical Center and affiliated clinics between January 2014 and December 2016. t-Test, Wilcoxon rank sum and ANOVA were employed. Of 72,571 total appointments 13,219 (18.2%) were no-shows. The no-show rates per provider related characteristic were provider type (physician 22.1% vs advanced primary provider 34.0%), visit category (new 26.9% vs return 25.6% vs procedure 17.5%), faculty status (assistant 22.9% vs associate 21.9% vs professor 21.4%) and specialty (oncology 26.7% vs reconstructive 22.9% vs stones 25.4%). Average lead times of advanced primary practitioners and physicians were 47 and 62 days, respectively. There was a statistically significant difference in mean no-show rates by provider type (p <0.01) and new patient by provider type (p <0.01). However, there was no statistical difference in mean rates by specialty, faculty status, provider bump history, provider based visit types and average lead time. The potential loss in revenue from outpatient no-shows is at least $429,810 annually. Provider type and new patient visits by provider type have statistically different no-show rates. Missed appointments are costly and affect clinical efficiency, access to care and potentially patient outcomes. Given the shift toward value based care and future workforce changes, further investigations are needed to determine interventions to help reduce no-show rates. Models to predict and adjust clinics should be developed and deployed.

166P - Analysis of circulating tumour DNA for early relapse detection in stage III colorectal cancer after adjuvant chemotherapy

BackgroundCirculating tumor DNA (ctDNA) has emerged as a promising biomarker for early prediction of relapse across different tumor types. In patients with colorectal cancer (CRC), multiple studies have analyzed ctDNA to monitor tumor burden using fixed gene panels and droplet digital PCR. Here, we use a highly sensitive and specific, bespoke, whole exome-based NGS approach (Signatera™) for ctDNA monitoring. MethodsA cohort of 33 patients with stage III CRC who underwent surgery and were treated with at least 4 months of adjuvant chemotherapy was analyzed. Mutational profiles derived from primary tumor tissue and germline DNA whole exome were used to design assays targeting tumor-specific somatic variants. The bespoke assays were used for ctDNA detection in plasma samples. Relapse-free survival (RFS) was calculated for patients stratified by ctDNA status. ResultsPlasma samples (n=44; average volume=1.8mL) from patients (N=33) were analysed for the presence of ctDNA. Of the five ctDNA-positive patients, clinical follow-up was available for three patients, all of whom relapsed (100%; 3/3); three of 27 ctDNA-negative patients (11%) also clinically relapsed. Molecular relapse through ctDNA analysis was detected up to 668 days ahead of radiological imaging with an average lead time of 305 days. The majority of relapses in ctDNA-positive patients (67%; 2/3) occurred within a year of follow-up, while no relapses were observed in ctDNA-negative patients during the one-year time frame. All plasma samples (n=34) from 24 non-relapsing patients were ctDNA negative, corresponding to a specificity of 100%. The presence of ctDNA was associated with a markedly reduced RFS compared to ctDNA-negative patients (HR: 5.6; 95% CI: 0.6-52.1; p<0.01). ConclusionsThe study results indicate that ctDNA status is associated with high relapse risk in patients with CRC and can serve as a predictor of patient outcome. Despite low plasma volumes (<5mL) and lack of longitudinal samples for analysis, ctDNA was detected in 50% of relapse cases. Legal entity responsible for the studyNatera, Inc. and NSABP Foundation. FundingNatera, Inc., Bayer, NSABP Foundation. DisclosureH. Sethi: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. T.J. George: Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Pharmacyclics. S. Shchegrova: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A.S. Tin: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A. Olson: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. D. Renner: Full / Part-time employment: Natera, Inc. E. Kalashnikova: Full / Part-time employment: Natera, Inc. M. Louie: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. R. Salari: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. B. Zimmermann: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A. Aleshin: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. All other authors have declared no conflicts of interest.

Dynamic monitoring of HER2 amplification in circulating DNA of patients with metastatic colorectal cancer treated with cetuximab.

Cetuximab (CTX) has been used to treat metastatic colorectal cancer (mCRC) with wild-type (wt) RAS and BRAF genes. Meanwhile HER2 amplification reportedly denoted CTX-resistant mCRC tumors. We investigated whether monitoring of HER2 amplification in circulating DNA allowed early detection of mCRC progression and CTX resistance. We analyzed HER2 amplification in circulating DNA at 8-week intervals using ddPCR from 36 patients with RASwt/BRAFwt mCRC, who progressed after CTX treatments between July 2015 and January 2018. Of the 36 patients, 5 (13.9%) exhibited dynamic fluctuations of HER2 amplification in plasma in the course of CTX treatment, of whom 2 were positive for HER2 amplification in matched tumor specimens at baseline (per FISH). All 5 primary sites were left side: 3 rectums and 2 descending colon. HER2 ratio fluctuations in circulating DNA not only reflected changes in tumor volume, but their obvious increases presaged CT-documented progress by an average lead time of 2months. Interestingly, progression-free survival did not significantly differ between these 5 patients and those without HER2 amplification (HR 1.06, 95% CI 0.40-2.77, P = 0.909). Plasma HER2 amplification detected by ddPCR changed over time and predicted resistance to CTX, by an average lead time of 2months. Further study is needed to validate our findings.

Forecasting Tourism Demand with Composite Indicator Approach for Fiji

This study attempts to scrutinize the fluctuations of the Fijian tourism market and forecast the early warning signals of tourism market vulnerability using the tourism composite indicator (TCI). The data employed on a monthly basis from 2000M01 to 2017M12 and the indicator construction steps were adopted from the ideology of the National Bureau of Economic Research (NBER). A parsimonious macroeconomic and non-economic fundamental determinant are included for the construction of TCI. Subsequently, the procedure then employed the seasonal adjustment using Census X-12, Christiano-Fitzgerald filtering approach, and Bry-Boschan dating algorithm. Empirical evidence highlighted the signalling attributes against Fijian tourism demand with an average lead time of 2.75 months and around 54 percent of directional accuracy rate, which is significant at 5 percent significance level. Thus, the non-parametric technique can forecast the tourism market outlook and the constructed TCI can provide information content from a macroeconomic perspective for policymakers, tourism market players and investors.

Parallel Serial Assessment of Somatic Mutation and Methylation Profile from Circulating Tumor DNA Predicts Treatment Response and Impending Disease Progression in Osimertinib-Treated Lung Adenocarcinoma Patients

Background: Circulating tumor DNA (ctDNA) harboring tumor-specific genetic and epigenetic aberrations allows for early detection and real-time monitoring of tumor dynamics. In this study, we aimed to evaluate the potential of parallel serial assessment of somatic mutation and methylation profile in monitoring the response to osimertinib of EGFR T790M-positive advanced lung adenocarcinoma patients. Methods: Parallel somatic mutation and DNA methylation profiling was performed on a total of 85 longitudinal plasma samples obtained from eight stage IV osimertinib-treated EGFR T790M-positive lung adenocarcinoma patients. Findings: Our results revealed significant correlation between the by-patient methylation level with the maximum allele fraction (maxAF, P=0.0002). The methylation levels were significantly higher in the plasma samples of patients with detectable somatic mutations than patients without somatic mutations (P=0.0003) and healthy controls (P=0.0018). Moreover, analysis of both DNA methylation level and maxAF revealed four trends of treatment response. Collectively, the decrease in methylation level and maxAF reflected treatment efficacy, while the gradual increase reflected impending disease progression. Elevated methylation levels and maxAF were observed in six and five patients in an average lead-time of 3.0 and 1.9 months, respectively, prior to evaluation of disease progression using radiological imaging. Interpretation: DNA methylation profiling has the potential to predict disease relapse prior to being evaluated thru radiological modalities, suggesting that serial assessment of methylation level in combination with somatic mutation profiling are reliable methods for treatment monitoring and should be incorporated with imaging modalities for a more comprehensive work-up of treatment response, particularly for patients treated with targeted therapies. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (grant number 81772471 to S.Xia), Double First-Class University Plan funding of 2016 from Tongji Medical College, Huazhong University of Science and Technology (grant number 5001540022 to S.Xia) and Qinghai Science and Technology Department Funding (grant number 2017-ZJ-709 to S. Xia). Declaration of Interests: J.Ye, A.Lizaso, J.Su, H.Han-Zhang and S. Chuai are employees of Burning Rock Biotech. The other authors declare no potential conflicts of interest. Ethics Approval Statement: This study was performed according to the Helsinki Declaration of 1964 and its current amendments. The study protocol has been approved by the Ethics Committee of Huazhong University of Science and Technology (approval number: 2015L01374/2015L01373). Written informed consent was provided by all the patients included in the study.

Total lightning signatures of thunderstorms and lightning jumps in hailfall nowcasting in the Beijing area

Based on total lightning location data from the Beijing Lightning Network (BLNET) and hailfall reports from 2015 to 2017 in Beijing, as well as S-band radar data from the Beijing Meteorological Observation Center, the total lightning activities for 148 hailfall events are analyzed with the identification method of strong convective cells (CCs) (similar to Thunderstorm Identification Tracking Analysis and Nowcasting, TITAN). Most of the hailstorms have a very high flash rate (FR), and a significant increase in FR is observed before hailfall events. The 2σ lightning jump (LJ) algorithm (with 4 and 10 flashes/min activation thresholds for different districts of Beijing) is tested as a hailfall nowcasting predictor. The average LJ lead time is 27.1 min. LJs precede 81.8% of all hailfall events, and 38.6% of LJs are not followed by hailfall reports within one hour. The merging of two adjacent strong CCs usually forms hail-bearing severe thunderstorms producing a sudden increase in total lightning. In addition, most hailfall events occurred at the boundary of strong CCs instead of at the cell centers. This study shows that the total LJ is a potentially useful predictor for hail nowcasts in the Beijing area.

Importance of Lean Concepts and Its Need in Construction Projects

As we look through the lens of productivity, construction is extremely interesting industry. As researchers are coming up with various new techniques to transform the construction industry not all the efforts are completely used. Several technical and non-technical factors like poor work execution, congestion in the place of work, cleanliness issues, unavailability of resources, delay in the process, qualitymismatch and lack of proper management affects the whole process. Hence thereisarequirementforautomationinseveralareasintheentire process to keep the non-value-added activities in check. The main cause for reduction in performance in this field is lack of waste management something that is least considered. Therefore, proper management of waste materials to produce a leaner and fitter organization plays a very important role in raising the profits. Lean construction requires involvement of lean manufacturing principles along with operations research and construction process. A case study is made based on the observations in the ongoing construction process of a 5-storeyed building “Shrisham Housing Association” in Udupi for a duration of 7 months. This involved activities like Masonry work such as Blockwork and Plastering, Flooring and Tiling. Lean process aims at raising the value of the product for the customers along with least wastage and increased productivity. There are several tools used by the industry to adopt to lean process such as the 5 Whys, The 5S System, Value Stream Mapping, Regression Analysis, Pareto Chart, Failure Modes and Effects Analysis, Continuous Improvement and Mistake Proofing. In this study “MUDA Walks” and “Value Stream Mapping” tools are used for detection, “Fishbone Diagram” and “5 Whys” for processing and “Last Planner System”, “Daily Huddle Meeting”, “5 S Principle” and “First Run Studies” for mitigation. It is observed that the percentage excess of materials over a period of six months of M. SandandP.Sandhasbeenreducedby17%and9.1%respectively whereas the percentage shortage of solid blocks has been reduced by 1%. The frequency of occurrence of types of wastage due to work delay is ranked 1 and wastage due to human resources is ranked the least among the five categories of wastes consideredin this study. It is also observed that the average lead time of non-value added activities is 25.4% in tiling, plastering and block work.

Predictive and prognostic values of circulating tumor DNA (ctDNA) clearance in osimertinib treated advanced non-small cell lung cancer cohort.

3036 Background: Although growth advantage of certain clones would ultimately translate into a clinically visible disease progression, radiological imaging does not reflect clonal evolution at the molecular level. CtDNA, validated as a tool for mutation detection in lung cancer, reflects dynamic molecular changes. Here, we evaluated the potential of ctDNA in monitoring molecular changes and predicting clinical outcomes of EGFR T790M-positive osimertinib treated NSCLC pts. Methods: This prospective multicenter study, enrolled 72 T790M positive osimertinib-treated advanced NSCLC pts who progressed on prior EGFR-TKI to evaluate the potential of ctDNA in monitoring, is part of the ongoing ASTRIS study (NCT02474355). Longitudinal plasma samples, collected from 52 pts, were subjected to sequencing using a panel consisting of 168 lung cancer-related genes. Results: Genomic profile prior to the initiation of osimertinib revealed that mutations participating in cell cycle (14 pts, p = 0.004) and P53 pathways (43 pts, p = 0.032) were associated with shorter OS ( p53 was excluded from analysis due to high mutation frequency). Interestingly, pts with undetectable ctDNA at first follow-up (within 50 d, n = 41) were correlated with longer PFS (p = 0.009) and OS (p = 0.022). With a median follow-up of 168 d (ranged from 40 - 550 d), 32 pts experienced radiological disease progression. Among them, 11 (34%) experienced molecular progression reflected by emergency of new mutation or increased allelic frequency of existing mutation prior to radiological progression, with an average leading time of 74 days. Pts with molecular PD prior to radiological PD were more likely to harbor any gene copy number amplification (CNA, p = 0.035) and p53 (p = 0.023) mutations at radiological PD. In addition, pts with CNA at radiological PD had shorter PFS (p = 0.002) and OS (p = 0.052). Conclusions: This clinical trial study demonstrates that ctDNA clearance at first follow-up can serve as a predictive and a prognostic marker for pts undergoing osimertinib treatment. Furthermore, it revealed the potential of ctDNA in early detection of disease progression, preceding imaging modalities with an average lead time of 74 days.

Bowel symptoms predate the diagnosis among many patients with multiple sclerosis: A 14-year cohort study.

Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease frequently complicated by bowel symptoms. Multiple sclerosis typically first manifests with a demyelination event, also known as a clinically isolated syndrome (CIS). We sought to examine the prevalence of prodromal bowel symptoms predating a CIS in patients with MS as part of a recently characterized prodromal phase of disease. We constructed a retrospective cohort of MS patients with bowel symptoms and an identifiable CIS at two tertiary care centers over 14years using administrative and billing data. We determined the date of onset of reported bowel symptoms in comparison with the date of first CIS and determined the overall prevalence of prediagnosis bowel symptoms within 1, 2, 3, and >3years from a CIS. We used multivariable modeling to determine demographic and clinical risk factors for prediagnosis bowel symptoms. Among 385 MS patients with reported bowel symptoms, 122 (31.6%) reported bowel symptoms prior to CIS. The most common first bowel symptom was constipation (50.0%), followed by diarrhea (29.5%). The average lead time between a first bowel symptom and a CIS event was 3.7±3.4years. Pre-CIS fatigue (OR 4.48, 95% CI: 2.68-7.51, P<0.001) and pre-CIS sensory disturbances (OR 1.88, 95% CI: 1.15-3.08, P<0.05) were all associated with bowel symptoms prior to a CIS event. Nearly a third of MS patients with bowel symptoms reported bowel symptoms prior to a demyelinating event/CIS. Characterization of a prodromal phase of disease may provide important insights into understanding disease progression.

Wearable-sensor-based pre-impact fall detection system with a hierarchical classifier

Fall is a major threat to elder health, and fall detection has attracted considerable research attention recently. In our study, a novel method is proposed to detect falls prior to impact during walking. Angle and angular-velocity data from the waist and thigh are collected using two wearable sensors. By extracting and selecting distinctive features, we aim to identify falls at an early stage. To improve detection accuracy and reduce false alarms, a hierarchical classifier based on Fisher discriminant analysis is developed. With the hierarchical classifier, human activities are classified into three categories: non-fall, backward fall and forward fall. It can achieve average lead times of 376 ms for backward fall and 404 ms for forward fall. Meanwhile, it can achieve a sensitivity of 95.5% and specificity of 97.3%. The method can achieve a high accuracy for classifier, and a long lead time for pre-impact fall detection. Compared with single-sensor-based methods, the multi-sensor-based method achieves a better performance. The preliminary results indicate that our study has potential application in a fall-injury prevention system.

Serological Assessment of 18 Pathogens and Risk of AIDS-Associated Non-Hodgkin Lymphoma.

HIV infection is associated with increased susceptibility to common pathogens, which may trigger chronic antigenic stimulation and hyperactivation of B cells, events known to precede the development of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL). To explore whether cumulative exposure to infectious agents contributes to AIDS-NHL risk, we tested sera from 199 AIDS-NHL patients (pre-NHL, average lead time 3.9 years) and 199 matched HIV-infected controls from the Multicenter AIDS Cohort Study, for anti-IgG responses to 18 pathogens using multiplex serology. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression models. We found no association between cumulative exposure to infectious agents and AIDS-NHL risk (OR 1.01, 95% CI: 0.91 to 1.12). However, seropositivity for trichodysplasia spinulosa polyomavirus (TSPyV), defined as presence of antibodies to TSPyV capsid protein VP1, was significantly associated with a 1.6-fold increase in AIDS-NHL risk (OR 1.62, 95% CI: 1.02 to 2.57). High Epstein-Barr virus (EBV) anti-VCA p18 antibody levels closer to the time of AIDS-NHL diagnosis (<4 years) were associated with a 2.6-fold increase in AIDS-NHL risk (OR 2.59, 95% CI: 1.17 to 5.74). In addition, high EBV anti-EBNA-1 and anti-ZEBRA antibody levels were associated with 2.1-fold (OR 0.47, 95% CI: 0.26 to 0.85) and 1.6-fold (OR 0.57, 95% CI: 0.35 to 0.93) decreased risk of AIDS-NHL, respectively. Our results do not support the hypothesis that cumulative exposure to infectious agents contributes to AIDS-NHL development. However, the observed associations with respect to TSPyV seropositivity and EBV antigen antibody levels offer additional insights into the pathogenesis of AIDS-NHL.

Abstract P4-01-19: Liquid biopsy and re-biopsy: Tracking mutational trajectories in HER2+ breast cancer patients undergoing T-DM1 treatment

Abstract Background: The antibody-drug conjugate Trastuzumab emtansine (T-DM1, Kadcyla®) is standard of care in HER2+ breast cancer patients on clinical progression after Trastuzumab/Pertuzumab and taxanes. Despite considerable clinical benefits, most patients rapidly develop progressive disease due to adaptive resistance, the molecular bases of which remain largely unknown and/or controversial. Next generation sequencing (NGS) and digital PCR (dPCR) applied to serial biological samples obtained through liquid biopsy (LB) and re-biopsy (RB) offer a unique opportunity to intercept mutational trajectories and uncover molecular patterns linked to primary as well as adaptive resistance. Materials and methods: Tumor tissues (n=14), either from primary or metastatic lesions, and plasma samples (n=99) were collected, upon informed consent, from 9 breast cancer patients undergoing T-DM1 administration. Tissue (tDNA) and circulating tumor DNA (ctDNA) were extracted by the QIAmp DNA FFPE and CNA kits (Qiagen), respectively, and analyzed by ultra-deep sequencing and dPCR (IonTorrent S5 and QuantStudio 3D, LifeTechnologies) with commercial 400-gene panel and custom-designed dPCR assays. Genomic data were correlated with clinical imaging (CT/PET). Results: Six out 9 (66.7%) patients experienced progression within 1 year of treatment (mean 192±97 days), whereas the remaining 3 were stable at the last follow up (&amp;gt; 400 days). No correlation was found between outcome and HER2, ER or PR status in the latest available (prior to T-DM1) archival tissue, in which NGS revealed several pre-existing mutations, including some associated with resistance to ERBB2 blockade. LB analysis detected increases in both baseline and de novo occurring aberrations in 5/6 (83.4%) relapsing patients. As compared to clinical imaging, progression disease was anticipated by an average lead time of 1.9 months (range 0.7-2.8). Surprisingly, the sixth relapsing patient underwent rapid progression (3 months) in spite of decreased PIK3CA p.E545K in blood, further confirmed in the re-biopsy, thus suggesting heterogeneous response to T-DM1 across multiple cancer cell populations. Of note, we observed progressive accumulation of ERBB2 p.L755S (associated with Lapatinib resistance) in multiple biopsies of serial metastatic foci from a patient over 18 years of multimodal ERBB2 blockade. However, a single administration of T-DM1 resulted in ultra-fast (within few weeks) clearance of ERBB2 p.L755S ctDNA, and stabilization of two distinct 'bystander' TP53 ctDNAs (p.R273H and p.S241T). Conclusions: Non-invasive LB monitoring of a small cohort of T-DM1-treated patients provides proof of principle of intersecting mutational trajectories, anticipation and classification of resistance, as well as de novo appearance/clearance of resistance mutations. Thus, LB and RB may hint at disease evolution and successive lines of medical treatment. This work was supported by AIRC (Nuvenia Fellowship to MA, IG 19052 to PG), EU commission (grant #633937 – ULTRAPLACAD), and Regina Elena National Cancer Institute intramural funding. Citation Format: Allegretti M, Giordani E, Casini B, Romania P, Gasparro S, Russillo M, Gallo E, Buglioni S, Pescarmona E, Cognetti F, Ciliberto G, Giacomini P, Fabi A. Liquid biopsy and re-biopsy: Tracking mutational trajectories in HER2+ breast cancer patients undergoing T-DM1 treatment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-19.