Solving finite production rate model with scrap and multiple shipments using algebraic approach

This paper solves a finite production rate (FPR) model with scrap and multiple shipments using an algebraic method. Classic FPR model assumes a continuous inventory issuing policy to satisfy demand and perfect quality production for all items produced. However, in real life vendor-buyer integrated production-inventory system, multiple shipment policy is practically used in lieu of a continuous issuing policy and generation of defective items during production run is inevitable. In this study, it is assumed that all defective items are scrap and the perfect quality items can only be delivered to customers if the whole lot is quality assured at the end of the production run. A conventional approach for solving the FPR model is the use of differential calculus on the long-run average cost function with the need to prove optimality first. This paper demonstrates that optimal lot size and its overall costs for the aforementioned FPR model can be derived without derivatives. As a result, it enables students or practitioners who have little knowledge of calculus to understand and to handle with ease the real-life FPR model

Solving finite production rate model with scrap and multiple shipments using algebraic approach

This paper solves a finite production rate (FPR) model with scrap and multiple shipments using an algebraic method. Classic FPR model assumes a continuous inventory issuing policy to satisfy demand and perfect quality production for all items produced. However, in real life vendor-buyer integrated production-inventory system, multiple shipment policy is practically used in lieu of a continuous issuing policy and generation of defective items during production run is inevitable. In this study, it is assumed that all defective items are scrap and the perfect quality items can only be delivered to customers if the whole lot is quality assured at the end of the production run. A conventional approach for solving the FPR model is the use of differential calculus on the long-run average cost function with the need to prove optimality first. This paper demonstrates that optimal lot size and its overall costs for the aforementioned FPR model can be derived without derivatives. As a result, it enables students or practitioners who have little knowledge of calculus to understand and to handle with ease the real-life FPR model

Strained alkynes derived from 2,2′-dihydroxy-1,1′-biaryls ; synthesis and copper-free cycloaddition with azides

A series of strained alkynes were prepared from 2,2′-dihydroxy-biaryls. Several were characterised by X-ray crystallography, revealing strained C(sp)–C(sp)–C(sp3) bond angles in the range of 163–167°. Their cycloadditions with azides proceed without a catalyst. Functionalised versions of these reagents have potential applications to materials synthesis and bioconjugations

Economic evaluation of the introduction of the Prostate Health Index as a rule-out test to avoid unnecessary biopsies in men with prostate specific antigen levels of 4-10 in Hong Kong

A recent study showed that the Prostate Health Index may avoid unnecessary biopsies in men with prostate specific antigen 4-10ng/ml and normal digital rectal examination in the diagnosis of prostate cancer in Hong Kong. This study aimed to conduct an economic evaluation of the impact of adopting this commercially-available test in the Hong Kong public health service to determine whether further research is justified. A cost-consequence analysis was undertaken comparing the current diagnostic pathway with a proposed diagnostic pathway using the Prostate Health Index. Data for the model was taken from a prospective cohort study recruited at a single-institution and micro-costing studies. Using a cut off PHI score of 35 to avoid biopsy would cost HK$3,000 and save HK$7,988 per patient in biopsy costs and HK$511 from a reduction in biopsy-related adverse events. The net cost impact of the change was estimated to be HK$5,500 under base case assumptions. At the base case sensitivity and specificity for all grades of cancer (61.3% and 77.5% respectively) all grade cancer could be missed in 4.22% of the population and high grade cancer in 0.53%. The introduction of the prostate health index into the diagnostic pathway for prostate cancer in Hong Kong has the potential to reduce biopsies, biopsy costs and biopsy-related adverse events. Policy makers should consider the clinical and economic impact of this proposal

Effect of Sun and Planet-Bound Dark Matter on Planet and Satellite Dynamics in the Solar System

We apply our recent results on orbital dynamics around a mass-varying central body to the phenomenon of accretion of Dark Matter-assumed not self-annihilating-on the Sun and the major bodies of the solar system due to its motion throughout the Milky Way halo. We inspect its consequences on the orbits of the planets and their satellites over timescales of the order of the age of the solar system. It turns out that a solar Dark Matter accretion rate of \approx 10^-12 yr^-1, inferred from the upper limit \Delta M/M= 0.02-0.05 on the Sun's Dark Matter content, assumed somehow accumulated during last 4.5 Gyr, would have displaced the planets faraway by about 10^-2-10^1 au 4.5 Gyr ago. Another consequence is that the semimajor axis of the Earth's orbit, approximately equal to the Astronomical Unit, would undergo a secular increase of 0.02-0.05 m yr^-1, in agreement with the latest observational determinations of the Astronomical Unit secular increase of 0.07 +/- 0.02 m yr^-1 and 0.05 m yr^-1. By assuming that the Sun will continue to accrete Dark Matter in the next billions year at the same rate as in the past, the orbits of its planets will shrink by about 10^-1-10^1 au (\approx 0.2-0.5 au for the Earth), with consequences for their fate, especially of the inner planets. On the other hand, lunar and planetary ephemerides set upper bounds on the secular variation of the Sun's gravitational parameter GM which are one one order of magnitude smaller than 10^-12 yr^-1. Dark Matter accretion on planets has, instead, less relevant consequences for their satellites. Indeed, 4.5 Gyr ago their orbits would have been just 10^-2-10^1 km wider than now. (Abridged)Comment: LaTex2e, 17 pages, no figures, 7 tables, 61 references. Small problem with a reference fixed. To appear in Journal of Cosmology and Astroparticle Physics (JCAP

Hedgehog Pathway as a Potential Intervention Target in Esophageal Cancer

Esophageal cancer (EC) is an aggressive disease with a poor prognosis. Treatment resistance is a major challenge in successful anti-cancer therapy. Pathological complete response after neoadjuvant chemoradiation (nCRT) is low, thus requiring therapy optimization. The Hedgehog (HH) pathway has been implicated in therapy resistance, as well as in cancer stemness. This article focusses on the HH pathway as a putative target in the treatment of EC. Immunohistochemistry on HH members was applied to EC patient material followed by modulation of 3D-EC cell cultures, fluorescence-activated cell sorting (FACS), and gene expression analysis after HH pathway modulation. Sonic Hedgehog (SHH) and its receptor Patched1 (PTCH1) were significantly enriched in EC resection material of patients with microresidual disease (mRD) after receiving nCRT, compared to the control group. Stimulation with SHH resulted in an up-regulation of cancer stemness in EC sphere cultures, as indicated by increased sphere formation after sorting for CD44+/CD24- EC cancer stem-like cell (CSC) population. On the contrary, inhibiting this pathway with vismodegib led to a decrease in cancer stemness and both radiation and carboplatin resistance. Our results strengthen the role of the HH pathway in chemoradiotherapy resistance. These findings suggest that targeting the HH pathway could be an attractive approach to control CSCs.</p

Welfare-adjusted life years (WALY) : a novel metric of animal welfare that combines the impacts of impaired welfare and abbreviated lifespan

Currently, separate measures are used to estimate the impact of animal diseases on mortality and animal welfare. This article introduces a novel metric, the Welfare-Adjusted Life Year (WALY), to estimate disease impact by combining welfare compromise and premature death components. Adapting the Disability-Adjusted Life Year approach used in human health audits, we propose WALY as the sum of a) the years lived with impaired welfare due to a particular cause and b) the years of life lost due to the premature death from the same cause. The years lived with impaired welfare are the product of the average duration of each welfare impediment, reflecting the actual condition that compromises animal welfare, the probability of an incident case developing and impaired welfare weights, representing the degree of impaired welfare. The years of life lost are calculated using the standard expected lifespan at the time of premature death. To demonstrate the concept, we estimated WALYs for 10 common canine diseases, namely mitral valve disease, dilated cardiomyopathy, chronic kidney disease, diabetes mellitus, atopic dermatitis, splenic haemangiosarcoma, appendicular osteosarcoma, cranial cruciate ligament disease, thoracolumbar intervertebral disc disease and cervical spondylomyelopathy. A survey of veterinarians (n = 61) was conducted to elicit impaired welfare weights for 35 welfare impediments. Paired comparison was the primary method to elicit weights, whereas visual analogue scale and time trade-off approaches rescaled these weights onto the desired scale, from 0 (the optimal welfare imaginable) to 1 (the worst welfare imaginable). WALYs for the 10 diseases were then estimated using the impaired welfare weights and published epidemiological data on disease impacts. Welfare impediment “amputation: one limb” and “respiratory distress” had the lowest and highest impaired welfare weights at 0.134 and 0.796, rescaled with a visual analogue scale, and 0.117 and 0.857, rescaled with time trade-off. Among the 10 diseases, thoracolumbar intervertebral disc disease and atopic dermatitis had the smallest and greatest adverse impact on dogs with WALYs at 2.83 (95% UI: 1.54–3.94) and 9.73 (95% uncertainty interval [UI]: 7.17–11.8), respectively. This study developed the WALY metric and demonstrated that it summarises welfare compromise as perceived by humans and total impact of diseases in individual animals. The WALY can potentially be used for prioritisation of disease eradication and control programs, quantification of population welfare and longitudinal surveillance of animal welfare in companion animals and may possibly be extended to production animals

A Multivariable Approach Using Magnetic Resonance Imaging to Avoid a Protocol-based Prostate Biopsy in Men on Active Surveillance for Prostate Cancer-Data from the International Multicenter Prospective PRIAS Study

Publisher Copyright: Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.BACKGROUND: There is ongoing discussion whether a multivariable approach including magnetic resonance imaging (MRI) can safely prevent unnecessary protocol-advised repeat biopsy during active surveillance (AS). OBJECTIVE: To determine predictors for grade group (GG) reclassification in patients undergoing an MRI-informed prostate biopsy (MRI-Bx) during AS and to evaluate whether a confirmatory biopsy can be omitted in patients diagnosed with upfront MRI. DESIGN, SETTING, AND PARTICIPANTS: The Prostate cancer Research International: Active Surveillance (PRIAS) study is a multicenter prospective study of patients on AS (www.prias-project.org). We selected all patients undergoing MRI-Bx (targeted ± systematic biopsy) during AS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A time-dependent Cox regression analysis was used to determine the predictors of GG progression/reclassification in patients undergoing MRI-Bx. A sensitivity analysis and a multivariable logistic regression analysis were also performed. RESULTS AND LIMITATIONS: A total of 1185 patients underwent 1488 MRI-Bx sessions. The time-dependent Cox regression analysis showed that age (per 10 yr, hazard ratio [HR] 0.84 [95% confidence interval {CI} 0.71-0.99]), MRI outcome (Prostate Imaging Reporting and Data System [PIRADS] 3 vs negative HR 2.46 [95% CI 1.56-3.88], PIRADS 4 vs negative HR 3.39 [95% CI 2.28-5.05], and PIRADS 5 vs negative HR 4.95 [95% CI 3.25-7.56]), prostate-specific antigen (PSA) density (per 0.1 ng/ml cm3, HR 1.20 [95% CI 1.12-1.30]), and percentage positive cores on the last systematic biopsy (per 10%, HR 1.16 [95% CI 1.10-1.23]) were significant predictors of GG reclassification. Of the patients with negative MRI and a PSA density of <0.15 ng/ml cm3 (n = 315), 3% were reclassified to GG ≥2 and 0.6% to GG ≥3. At the confirmatory biopsy, reclassification to GG ≥2 and ≥3 was observed in 23% and 7% of the patients diagnosed without upfront MRI and in 19% and 6% of the patients diagnosed with upfront MRI, respectively. The multivariable analysis showed no significant difference in upgrading at the confirmatory biopsy between patients diagnosed with or without upfront MRI. CONCLUSIONS: Age, MRI outcome, PSA density, and percentage positive cores are significant predictors of reclassification at an MRI-informed biopsy. Patients with negative MRI and a PSA density of <0.15 ng/ml cm3 can safely omit a protocol-based prostate biopsy, whereas in other patients, a multivariable approach is advised. Being diagnosed with upfront MRI appears not to significantly affect reclassification risk; hence, a confirmatory MRI-Bx cannot totally be omitted yet. PATIENT SUMMARY: A protocol-based prostate biopsy while on active surveillance can be omitted in patients with negative magnetic resonance imaging (MRI) and prostate-specific antigen density <0.15 ng/ml cm3. A confirmatory biopsy cannot simply be omitted in all patients diagnosed with upfront MRI.Peer reviewe