Production Planing and Control PRODUCTIVITY EFFECTS OF STARTING AS EARLY AS POSSIBLE IN HOSPITAL CONSTRUCTION

ABSTRACT Critical Path Method (CPM) is the standard scheduling methodology for building construction in the US. The objective of this research is to determine the effect of management strategies focusing on early starts (ASAP strategy) on the production and productivity rates of "critical path" tasks in a construction schedule. In this study, two healthcare projects were followed over the course of construction to document the effects of field management decisions on production. On project one, a CPM schedule and ASAP strategy was used exclusively to manage subcontractor resources. On project two, both CPM/ASAP and Location Based Management System (LBMS) strategies were used in parallel, on similar location groups, enabling direct comparison. Actual activity start dates, finish dates, demobilizations and remobilizations, productivity and production rates, and manpower were recorded weekly for analysis. On project one, the actual dates and rates are compared against the CPM plan to determine how reliably the tasks could be completed using the ASAP "work in place" management strategy. Results show that certain deviations from the CPM plan, such as starting early, relocating resources before completing a location, and deploying resources to multiple locations at a time cause unpredictable dates of completion and frequent changes to the "critical path". On project two, actual productivity and production rates for selected tasks are compared between the CPM/ASAP and LBMS location groups. Results show that deploying resources to a location as soon as it is available can have a negative effect on the productivity and overall production rates of critical tasks

A search for radioactive 26Al in the nova-like variable V4332 Sagittarii

We have searched for the important radioactive isotope 26Al in the nova-like source V4332 Sgr. Recent results from gamma ray astronomy show that there is pervasive emission of the 1.809 MeV gamma ray photon, arising from the decay of 26Al to 26Mg, from all over the galactic plane. Though the sites from where this emission originates are not clearly established, novae are believed to be an important contributing source. In this context, V4332 Sgr presented a rare opportunity to observationally investigate whether novae or novae-like sources synthesize 26Al and to what extent. Strong AlO bands in the near-IR have been reported in this object recently. As molecular bands of different isotopic compositions are readily resolved spectroscopically (e.g. 12CO and 13CO), it was thought that the components of AlO associated with 26Al and stable 27Al could be detected as separate bands. Our spectra indicate that there is no strong presence of 26Al in V4332 Sgr. A reliable upper limit of 0.10 for the 26Al/27Al ratio is determined which constitutes the first observational constraint for this ratio in a potential 26Al producing source. While V4332 Sgr is not a typical nova, its outburst amplitude and light-curve behaviour bear close similarity to that of novae. Hence, although the results from V4332 Sgr cannot be directly extended to novae in general, the limit on the observed 26Al/27Al ratio could be a useful input in constraining rather uncertain nucleosynthesis models for the production of 26Al in novae/novae-like sources. By comparing the observed 26Al/27Al ratio in V4332 Sgr with that expected in classical novae it appears unlikely that the progenitor of V4332 Sgr is an Oxygen-Neon-Magnesium white dwarf.Comment: 9 pages, 2 figures, to appear in Ap.J(L) July 200

Validity of fatty liver disease indices in the presence of alcohol consumption

Background & aims Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease frequently coexist. While several blood-based indices exist for the detection of NAFLD, few studies have examined how alcohol use possibly impacts their diagnostic performance. We analysed the effects of alcohol use on the performance of indices for detecting fatty liver disease (FLD). Methods We included participants from the Cardiovascular Risk in Young Finns Study (Finnish sample) and KORA study (German sample) who underwent abdominal ultrasound or magnetic resonance imaging, respectively, for detection of FLD and had serum analyses available for calculation of Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), Lipid Accumulation Product (LAP), and Dallas Steatosis Index (DSI). Alcohol use was estimated by questionnaires as mean daily consumption and binge drinking (Finnish sample only). Predictive performance for FLD was assessed according to alcohol consumption. Results The study included 1426 (Finnish sample) and 385 (German sample) individuals, of which 234 (16%) and 168 (44%) had FLD by imaging. When alcohol consumption was 50 g/day). AUROCs decreased to 0.74-0.80 in the highest binge-drinking category (>2 times/week). Alcohol use correlated with FLI and LAP (r-range 0.09-0.16, p-rangePeer reviewe

Differentiation status of primary chronic myeloid leukemia cells affects sensitivity to BCR-ABL1 inhibitors

Tyrosine kinase inhibitors (TKI) are the mainstay treatment of BCR-ABL1-positive leukemia and virtually all patients with chronic myeloid leukemia in chronic phase (CP CML) respond to TKI therapy. However, there is limited information on the cellular mechanisms of response and particularly on the effect of cell differentiation state to TKI sensitivity in vivo and ex vivo/in vitro. We used multiple, independent high-throughput drug sensitivity and resistance testing platforms that collectively evaluated 295 oncology compounds to characterize ex vivo drug response profiles of primary cells freshly collected from newly-diagnosed patients with BCR-ABL1positive leukemia (n = 40) and healthy controls (n = 12). In contrast to the highly TKI-sensitive cells from blast phase CML and Philadelphia chromosome-positive acute lymphoblastic leukemia, primary CP CML cells were insensitive to TKI therapy ex vivo. Despite maintaining potent BCR-ABL1 inhibitory activity, ex vivo viability of cells was unaffected by TKIs. These findings were validated in two independent patient cohorts and analysis platforms. All CP CML patients under study responded to TKI therapy in vivo. When CP CML cells were sorted based on CD34 expression, the CD34-positive progenitor cells showed good sensitivity to TKIs, whereas the more mature CD34-negative cells were markedly less sensitive. Thus in CP CML, TKIs predominantly target the progenitor cell population while the differentiated leukemic cells (mostly cells from granulocytic series) are insensitive to BCR-ABL1 inhibition. These findings have implications for drug discovery in CP CML and indicate a fundamental biological difference between CP CML and advanced forms of BCR-ABL1-positive leukemia.Peer reviewe

Gut Microbiome Metagenomics Analysis Suggests a Functional Model for the Development of Autoimmunity for Type 1 Diabetes

Peer reviewe

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Marginal structural models using calibrated weights with SuperLearner: application to longitudinal diabetes cohort.

Although machine learning has permeated many disciplines, the convergence of causal methods and machine learning remains sparse in the existing literature. Our aim was to formulate a marginal structural model in which we envisioned hypothetical (i.e. counterfactual) dynamic treatment regimes using a combination of drug therapies to manage diabetes: metformin, sulfonylurea and SGLT-2. We were interested in estimating “diabetes care provision” in next calendar year using a composite measure of chronic disease prevention and screening elements. We demonstrated the application of dynamic treatment regimes using the National Diabetes Action Canada Repository in which we applied a collection of mainstream statistical learning algorithms. We generated an ensemble of statistical learning algorithms using the SuperLearner based on the following base learners: (i) least absolute shrinkage and selection operator, (ii) ridge regression, (iii) elastic net, (iv) random forest, (v) gradient boosting machines, (vi) neural network. Each statistical learning algorithm was fitted using the pseudo-population with respect to the marginalization of the time-dependent confounding process. The covariate balance was assessed using the longitudinal (i.e. cumulative-time product) stabilized weights with calibrated restrictions. Our results indicated that the treatment drop-in cohorts (with respect to metformin, sulfonylurea and SGLT-2) may improve diabetes care provision in relation to treatment naïve cohort. As a clinical utility, we hope that this article will facilitate discussions around the prevention of adverse chronic outcomes associated with diabetes through the improvement of diabetes care provisions in primary care

Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs