Supply chain optimisation of pyrolysis plant deployment using goal programming

This paper presents a goal programming model to optimise the deployment of pyrolysis plants in Punjab, India. Punjab has an abundance of waste straw and pyrolysis can convert this waste into alternative bio-fuels, which will facilitate the provision of valuable energy services and reduce open field burning. A goal programming model is outlined and demonstrated in two case study applications: small scale operations in villages and large scale deployment across Punjab's districts. To design the supply chain, optimal decisions for location, size and number of plants, downstream energy applications and feedstocks processed are simultaneously made based on stakeholder requirements for capital cost, payback period and production cost of bio-oil and electricity. The model comprises quantitative data obtained from primary research and qualitative data gathered from farmers and potential investors. The Punjab district of Fatehgarh Sahib is found to be the ideal location to initially utilise pyrolysis technology. We conclude that goal programming is an improved method over more conventional methods used in the literature for project planning in the field of bio-energy. The model and findings developed from this study will be particularly valuable to investors, plant developers and municipalities interested in waste to energy in India and elsewhere

Environmental Management and Corporate Social Responsibility Practices of Small and Medium-sized Enterprises

The main aim of this paper is to facilitate small and medium sized enterprises (SMEs) to adopt environmental management (EM) and corporate social responsibility (CSR) practices. The study reveals SMEs‟ motivation, pressure, targets and methods for EM and CSR practices. Additionally, the paper investigates how these variables relate to employee number, turnover and geographical locations. The outcomes of the research will add value to SMEs decision-making processes in both strategic and policy levels (e.g. supplier selection) and policymakers‟ initiatives to make SMEs environment and socially friendly. Although there are studies on EM and CSR practices of SMEs, they mainly focus on impact of EM and CSR practices on business performance, and SMEs‟ motivation for adopting EM and CSR practices in specific country. Studies that reveal SMEs‟ motivation, pressure, targets and methods for EM and CSR practices and their relationship with their characteristics (e.g. size, turn over, and geographical location) are scant. This research bridges this gap. Our data originates from 223 carefully selected representative SMEs in the West Midlands, UK (105) and Kolkata, India (118) covering manufacturing and process industries. The relevant data was collected using questionnaires and analysed using Analysis of Variance (ANOVA) and Multivariate Analysis of Variance (MANOVA) methods. The results reveal that perceptions of SMEs‟ motivation, pressure, targets and methods of EM and CSR practices vary considerably with respect to size, turn over and geographical location. The findings are significant to policymakers, client organizations and individual SME for improving EM and CSR practices

Modelling neurological diseases in large animals: criteria for model selection and clinical assessment

Issue: The impact of neurological disorders is recognised globally, with one in six people affected in their lifetime and few treatments to slow or halt disease progression. This is due in part to the increasing ageing population, and is confounded by the high failure rate of translation from rodent-derived therapeutics to clinically effective human neurological interventions. Improved translation is demonstrated using higher order mammals with more complex/comparable neuroanatomy. These animals effectually span this translational disparity and increase confidence in factors including routes of administration/dosing and ability to scale, such that potential therapeutics will have successful outcomes when moving to patients. Coupled with advancements in genetic engineering to produce genetically tailored models, livestock are increasingly being used to bridge this translational gap. Approach: In order to aid in standardising characterisation of such models, we provide comprehensive neurological assessment protocols designed to inform on neuroanatomical dysfunction and/or lesion(s) for large animal species. We also describe the applicability of these exams in different large animals to help provide a better understanding of the practicalities of cross species neurological disease modelling. Recommendation: We would encourage the use of these assessments as a reference framework to help standardise neurological clinical scoring of large animal models

Exoplanet Diversity in the Era of Space-based Direct Imaging Missions

This whitepaper discusses the diversity of exoplanets that could be detected by future observations, so that comparative exoplanetology can be performed in the upcoming era of large space-based flagship missions. The primary focus will be on characterizing Earth-like worlds around Sun-like stars. However, we will also be able to characterize companion planets in the system simultaneously. This will not only provide a contextual picture with regards to our Solar system, but also presents a unique opportunity to observe size dependent planetary atmospheres at different orbital distances. We propose a preliminary scheme based on chemical behavior of gases and condensates in a planet's atmosphere that classifies them with respect to planetary radius and incident stellar flux.Comment: A white paper submitted to the National Academy of Sciences Exoplanet Science Strateg

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Preclinical and clinical evaluation of German-sourced ONC201 for the treatment of H3K27M-mutant diffuse intrinsic pontine glioma

Background Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood brainstem tumor for which radiation is the only treatment. Case studies report a clinical response to ONC201 for patients with H3K27M-mutant gliomas. Oncoceutics (ONC201) is only available in the United States and Japan; however, in Germany, DIPG patients can be prescribed and dispensed a locally produced compound-ONC201 German-sourced ONC201 (GsONC201). Pediatric oncologists face the dilemma of supporting the administration of GsONC201 as conjecture surrounds its authenticity. Therefore, we compared GsONC201 to original ONC201 manufactured by Oncoceutics Inc. Methods Authenticity of GsONC201 was determined by high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Biological activity was shown via assessment of on-target effects, in vitro growth, proliferation, and apoptosis analysis. Patient-derived xenograft mouse models were used to assess plasma and brain tissue pharmacokinetics, pharmacodynamics, and overall survival (OS). The clinical experience of 28 H3K27M+ mutant DIPG patients who received GsONC201 (2017-2020) was analyzed. Results GsONC201 harbored the authentic structure, however, was formulated as a free base rather than the dihydrochloride salt used in clinical trials. GsONC201 in vitro and in vivo efficacy and drug bioavailability studies showed no difference compared to Oncoceutics ONC201. Patients treated with GsONC201 (n = 28) showed a median OS of 18 months (P = .0007). GsONC201 patients who underwent reirradiation showed a median OS of 22 months compared to 12 months for GsONC201 patients who did not (P = .012). Conclusions This study confirms the biological activity of GsONC201 and documents the OS of patients who received the drug; however, GsONC201 was never used as a monotherapy

Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep

CLN1 disease, also called infantile neuronal ceroid lipofuscinosis (NCL) or infantile Batten disease, is a fatal neurodegenerative lysosomal storage disorder resulting from mutations in the CLN1 gene encoding the soluble lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). Therapies for CLN1 disease have proven challenging because of the aggressive disease course and the need to treat widespread areas of the brain and spinal cord. Indeed, gene therapy has proven less effective for CLN1 disease than for other similar lysosomal enzyme deficiencies. We therefore tested the efficacy of enzyme replacement therapy (ERT) by administering monthly infusions of recombinant human PPT1 (rhPPT1) to PPT1-deficient mice (Cln1(–/–)) and CLN1(R151X) sheep to assess how to potentially scale up for translation. In Cln1(–/–) mice, intracerebrovascular (i.c.v.) rhPPT1 delivery was the most effective route of administration, resulting in therapeutically relevant CNS levels of PPT1 activity. rhPPT1-treated mice had improved motor function, reduced disease-associated pathology, and diminished neuronal loss. In CLN1(R151X) sheep, i.c.v. infusions resulted in widespread rhPPT1 distribution and positive treatment effects measured by quantitative structural MRI and neuropathology. This study demonstrates the feasibility and therapeutic efficacy of i.c.v. rhPPT1 ERT. These findings represent a key step toward clinical testing of ERT in children with CLN1 disease and highlight the importance of a cross-species approach to developing a successful treatment strategy

What proportion of riverine nutrients reaches the open ocean?

Globally, rivers deliver significant quantities of nitrogen (N) and phosphorus (P) to the coastal ocean each year. Currently, there are no viable estimates of how much of this N and P escapes biogeochemical processing on the shelf to be exported to the open ocean; most models of N and P cycling assume that either all or none of the riverine nutrients reach the open ocean. We address this problem by using a simple mechanistic model of how a low-salinity plume behaves outside an estuary mouth. The model results in a global map of riverine water residence times on the shelf, typically a few weeks at low latitudes and up to a year at higher latitudes, which agrees well with observations. We combine the map of plume residence times on the shelf with empirical relationships that link residence time to the proportions of dissolved inorganic N (DIN) and P (DIP) exported and use a database of riverine nutrient loads to estimate the global distribution of riverine DIN and DIP supplied to the open ocean. We estimate that 75% of DIN and 80% of DIP reaches the open ocean. Ignoring processing within estuaries yields annual totals of 17 Tg DIN and 1.2 Tg DIP reaching the open ocean. For DIN this supply is about 50% of that supplied via atmospheric deposition, with significant east-west contrasts across the main ocean basins. The main sources of uncertainty are exchange rates across the shelf break and the empirical relationships between nutrient processing and plume residence time