Burgerville: Sustainability and Sourcing in a QSR Supply Chain

Jack Graves is considering buying chicken. More precisely, Jack is considering where to buy chicken. He needs to make a recommendation to the purchasing team soon, and the decision is complicated. Jack is a long-time employee of the Burgerville restaurant chain, a quick-serve restaurant chain in the Northwest USA. Burgerville prides itself in being true to its long-held values while maintaining profitability and growth. Graves’ primary job at Burgerville is to assure that the company’s values are embedded in all its actions, including its relationships to its supply chain. His current concern is the dilemma of which values to promote. Burgerville sells chicken, lots of chicken. So the purchase of chicken has significant impacts on the social and environmental impacts of Burgerville’s supply chain. Should Burgerville buy local, with the inherent social and environmental benefits, while paying attention to concerns about labor issues, animal treatment, and non-organic stewardship? Or should it find a supplier with some assurance that these potential problems are eliminated, regardless of location? Jack knows that Burgerville needs to address this issue soon, as the supply of chicken that is produced to Burgerville’s high standards is small and there are sure to be competitors seeking the same products. He will have to weigh the company’s values and make a recommendation soon. As the Chief Cultural Officer of The Holland Inc., Burgerville’s parent company, Jack Graves is constantly aware of the need to align the Burgerville culture and identity throughout all units of the business, including vendor partners. The chain’s slogan: Fresh. Local. Sustainable. proclaims its commitment to offering foods differently than other quick serve chains, with specific attention to where food is being sourced. Burgerville aims to deliver on this promise as often as possible, and has had success in the past. Over the past decade, Burgerville has made a concerted effort to ensure its purchasing supports it values. As of 2009, over 70% of Burgerville’s total spending on food products was from local suppliers, up from less than 60% in 2008. With chicken, though, Graves was faced with some difficult questions and hard choices: can Burgerville find a local supplier who can provide a sufficient quantity and quality of breaded and plain chicken breasts and chicken strips at a cost comparable to the existing national brand supplier? Is buying local the most important decision to make for Burgerville and its image? Is the issue more than simply reducing the distance the food travels from origin to the customer? Are Burgerville customers willing to pay a premium for locally sourced chicken? It makes sense to purchase from local farmers who may then become loyal customers, but what if distant farms operate more sustainably than the local farms? Is there a sustainable chicken farm that could handle Burgerville’s demand? These questions weigh on Graves’s mind as he struggles to balance the chain’s profitability with the company’s values

Another Shipment of Six Short-Period Giant Planets from TESS

We present the discovery and characterization of six short-period, transiting giant planets from NASA's Transiting Exoplanet Survey Satellite (TESS) -- TOI-1811 (TIC 376524552), TOI-2025 (TIC 394050135), TOI-2145 (TIC 88992642), TOI-2152 (TIC 395393265), TOI-2154 (TIC 428787891), & TOI-2497 (TIC 97568467). All six planets orbit bright host stars (8.9 <G< 11.8, 7.7 <K< 10.1). Using a combination of time-series photometric and spectroscopic follow-up observations from the TESS Follow-up Observing Program (TFOP) Working Group, we have determined that the planets are Jovian-sized (R$_{P}$ = 1.00-1.45 R$_{J}$), have masses ranging from 0.92 to 5.35 M$_{J}$, and orbit F, G, and K stars (4753 $<$ T$_{eff}$ $<$ 7360 K). We detect a significant orbital eccentricity for the three longest-period systems in our sample: TOI-2025 b (P = 8.872 days, $e$ = $0.220\pm0.053$), TOI-2145 b (P = 10.261 days, $e$ = $0.182^{+0.039}_{-0.049}$), and TOI-2497 b (P = 10.656 days, $e$ = $0.196^{+0.059}_{-0.053}$). TOI-2145 b and TOI-2497 b both orbit subgiant host stars (3.8 $<$ $\log$ g $<$4.0), but these planets show no sign of inflation despite very high levels of irradiation. The lack of inflation may be explained by the high mass of the planets; $5.35^{+0.32}_{-0.35}$ M$_{\rm J}$ (TOI-2145 b) and $5.21\pm0.52$ M$_{\rm J}$ (TOI-2497 b). These six new discoveries contribute to the larger community effort to use {\it TESS} to create a magnitude-complete, self-consistent sample of giant planets with well-determined parameters for future detailed studies.Comment: 20 Pages, 6 Figures, 8 Tables, Accepted by MNRA

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Pathophysiology, Management, and Therapeutics in Subarachnoid Hemorrhage and Delayed Cerebral Ischemia: An Overview

Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke resulting from the rupture of an arterial vessel within the brain. Unlike other stroke types, SAH affects both young adults (mid-40s) and the geriatric population. Patients with SAH often experience significant neurological deficits, leading to a substantial societal burden in terms of lost potential years of life. This review provides a comprehensive overview of SAH, examining its development across different stages (early, intermediate, and late) and highlighting the pathophysiological and pathohistological processes specific to each phase. The clinical management of SAH is also explored, focusing on tailored treatments and interventions to address the unique pathological changes that occur during each stage. Additionally, the paper reviews current treatment modalities and pharmacological interventions based on the evolving guidelines provided by the American Heart Association (AHA). Recent advances in our understanding of SAH will facilitate clinicians’ improved management of SAH to reduce the incidence of delayed cerebral ischemia in patients

Genetically Engineered Cancer Models, But Not Xenografts, Faithfully Predict Anticancer Drug Exposure in Melanoma Tumors

BACKGROUND. Rodent studies are a vital step in the development of novel anticancer therapeutics and are used in pharmacokinetic (PK), toxicology, and efficacy studies. Traditionally, anticancer drug development has relied on xenograft implantation of human cancer cell lines in immunocompromised mice for efficacy screening of a candidate compound. The usefulness of xenograft models for efficacy testing, however, has been questioned, whereas genetically engineered mouse models (GEMMs) and orthotopic syngeneic transplants (OSTs) may offer some advantages for efficacy assessment. A critical factor influencing the predictability of rodent tumor models is drug PKs, but a comprehensive comparison of plasma and tumor PK parameters among xenograft models, OSTs, GEMMs, and human patients has not been performed. METHODS. In this work, we evaluated the plasma and tumor dispositions of an antimelanoma agent, carboplatin, in patients with cutaneous melanoma compared with four different murine melanoma models (one GEMM, one human cell line xenograft, and two OSTs). RESULTS. Using microdialysis to sample carboplatin tumor disposition, we found that OSTs and xenografts were poor predictors of drug exposure in human tumors, whereas the GEMM model exhibited PK parameters similar to those seen in human tumors. CONCLUSIONS. The tumor PKs of carboplatin in a GEMM of melanoma more closely resembles the tumor disposition in patients with melanoma than transplanted tumor models. GEMMs show promise in becoming an improved prediction model for intratumoral PKs and response in patients with solid tumors

High Intra-abdominal Pressure Enhances the Penetration and Antitumor Effect of Intraperitoneal Cisplatin on Experimental Peritoneal Carcinomatosis

OBJECTIVE: To investigate the role of increased intra-abdominal pressure (IAP) on the intratumoral accumulation and the antitumor effect of intraperitoneal cisplatin in rats with advanced peritoneal carcinomatosis. To evaluate the tolerance of IAP in pigs, as it is a large animal with a body size equivalent to humans. SUMMARY BACKGROUND DATA: To investigate if an active convection, driven by a positive IAP, increases cisplatin penetration and antitumor effectiveness in a model of advanced peritoneal carcinomatosis in rats. EXPERIMENTAL DESIGN: BDIX rats with macroscopic peritoneal tumors received cisplatin administered as intravenous injection (IV), conventional intraperitoneal injection (IP), or sustained intraperitoneal injection of cisplatin given in a large volume of solvent for maintaining IAP for 1 hour. Platinum tissue concentration was measured by atomic absorption spectroscopy (AAS), and platinum distribution into the tumor nodules was assessed by the particular-induced x-ray emission (PIXE) method. The antitumor effect was assessed in a survival experiment. The hemodynamic, local, and systemic tolerance of IAP, with or without cisplatin, was evaluated in Large White pigs. RESULTS: The maximum tolerated IAP was 22 mm Hg for 1 hour in nonventilated rats. IAP, in comparison with IV or conventional IP injections, resulted in the increased concentration and depth of diffusion of platinum into diaphragm and peritoneal tumor nodules. Consequently, IAP treatment induced an extended survival of rats treated at an advanced stage of carcinomatosis. In 7 50- to 70-kg ventilated pigs, a 40-mm Hg IAP was well tolerated when maintained stable for 2 hours. Renal failure occurred in pigs receiving a total dose of 200 and 400 mg of cisplatin with IAP, but a dose of 100 mg was well tolerated. CONCLUSIONS: Intraperitoneal chemotherapy with increased IAP, in comparison with conventional IP or IV chemotherapy, improved the tumor accumulation and the antitumor effect of cisplatin in rats bearing advanced peritoneal carcinomatosis. In preclinical conditions, the tolerance of sustained IAP was manageable in ventilated pigs