The sweet spot in sustainability: a framework for corporate assessment in sugar manufacturing

The assessment of corporate sustainability has become an increasingly important topic, both within academia and in industry. For manufacturing companies to conform to their commitments to sustainable development, a standard and reliable measurement framework is required. There is, however, a lack of sector-specific and empirical research in many areas, including the sugar industry. This paper presents an empirically developed framework for the assessment of corporate sustainability within the Thai sugar industry. Multiple case studies were conducted, and a survey using questionnaires was also employed to enhance the power of generalisation. The developed framework is an accurate and reliable measurement instrument of corporate sustainability, and guidelines to assess qualitative criteria are put forward. The proposed framework can be used for a company’s self-assessment and for guiding practitioners in performance improvement and policy decision-maki

Changes in Timing and kinematics of goal directed eye-hand movements in early-stage Parkinson's disease

Objective: Many daily activities involve intrinsic or extrinsic goal-directed eye and hand movements. An extensive visuomotor coordination network including nigro-striatal pathways is required for efficient timing and positioning of eyes and hands. The aim of this study was to investigate how Parkinson's disease (PD) affects eye-hand coordination in tasks with different cognitive complexity.Methods: We used a touch screen, an eye-tracking device and a motion capturing system to quantify changes in eye-hand coordination in early-stage PD patients (H&Y < 2.5) and age-matched controls. Timing and kinematics of eye and hand were quantified in four eye-hand coordination tasks (pro-tapping, dual planning, anti-tapping and spatial memory task).Results: In the pro-tapping task, saccade initiation towards extrinsic goals was not impaired. However, in the dual planning and anti-tapping task initiation of saccades towards intrinsic goals was faster in PD patients. Hand movements were differently affected: initiation of the hand movement was only delayed in the pro-tapping and dual planning task. Overall, hand movements in PD patients were slower executed compared to controls.Interpretation: Whereas initiation of saccades in an extrinsic goal-directed task (pro-tapping task) is not affected, early stage PD patients have difficulty in suppressing reflexive saccades towards extrinsic goals in tasks where the endpoint is an intrinsic goal (e.g. dual planning and anti-tapping task). This is specific for eye movements, as hand movements have delayed responses in the pro-tapping and dual planning task. This suggests that reported impairment of the dorsolateral prefrontal cortex in early-stage PD patients affects only inhibition of eye movements. We conclude that timing and kinematics of eye and hand movements in visuomotor tasks are affected in PD patients. This result may have clinical significance by providing a behavioral marker for the early diagnosis of PD

Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose

[EN] Background Despite treatment with pancreatic enzyme replacement therapy (PERT), patients with cystic fibrosis (CF) can still suffer from fat malabsorption. A cause could be low intestinal pH disabling PERT. The aim of this study was to assess the association between faecal pH (as intestinal pH surrogate) and coefficient of fat absorption (CFA). Additionally, faecal free fatty acids (FFAs) were quantified to determine the amount of digested, but unabsorbed fat. Methods In a 24-h pilot study, CF patients followed a standardised diet with fixed PERT doses, corresponding to theoretical optimal doses determined by an in vitro digestion model. Study variables were faecal pH, fat and FFA excretion, CFA and transit time. Linear mixed regression models were applied to explore associations. Results In 43 patients, median (1st, 3rd quartile) faecal pH and CFA were 6.1% (5.8, 6.4) and 90% (84, 94), and they were positively associated (p < 0.001). An inverse relationship was found between faecal pH and total fat excretion (p < 0.01), as well as total FFA (p = 0.048). Higher faecal pH was associated with longer intestinal transit time (p = 0.049) and the use of proton pump inhibitors (p = 0.009). Conclusions Although the clinical significance of faecal pH is not fully defined, its usefulness as a surrogate biomarker for intestinal pH should be further explored. Impact Faecal pH is a physiological parameter that may be related to intestinal pH and may provide important physiopathological information on CF-related pancreatic insufficiency. Faecal pH is correlated with fat absorption, and this may explain why pancreatic enzyme replacement therapy is not effective in all patients with malabsorption related to CF. Use of proton pump inhibitors is associated to higher values of faecal pH. Faecal pH could be used as a surrogate biomarker to routinely monitor the efficacy of pancreatic enzyme replacement therapy in clinical practice. Strategies to increase intestinal pH in children with cystic fibrosis should be targeted.We acknowledge the support of the MyCyFAPP Project consortium. We especially thank the participation and the effort of the patients involved in the study and their families. This work was fully funded by the European Union and the Horizon 2020 Research and Innovation Framework Programme (PHC-26-2014 call Self management of health and disease: citizen engagement and mHealth) under grant number 643806.Calvo-Lerma, J.; Roca-Llorens, M.; Boon, M.; Colombo, C.; De Koning, B.; Fornés-Ferrer, V.; Masip, E.... (2021). Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose. Pediatric Research. 89(1):205-210. https://doi.org/10.1038/s41390-020-0860-3S205210891Turck, D. et al. ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin. Nutr. 35, 557–577 (2016).Borowitz, D., Baker, R. D. & Stallings, V. Consensus report on nutrition for pediatric patients with cystic fibrosis. J. Pediatr. Gastroenterol. Nutr. 35, 246–259 (2002).Fieker., A., Philpott, J. & Armand, M. Enzyme replacement therapy for pancreatic insufficiency: present and future. Clin. Exp. Gastroenterol. 4, 55 (2011).Sitrin, M. D. Digestion and Absorption of Carbohydrates and Proteins in the Gastrointestinal System 137–158 (Springer, Dordrecht, 2014).Gelfond, D. et al. Intestinal pH and gastrointestinal transit profiles in cystic fibrosis patients measured by wireless motility capsule. Dig. Dis. Sci. 58, 2275–2281 (2013).Robinson, P. J. et al. Duodenal pH in cystic fibrosis and its relationship to fat malabsorption. Dig. Dis. Sci. 35, 1299–1304 (1990).Hunter, J. E. Studies on effects of dietary fatty acids as related to their position on triglycerides. Lipids 36, 655–668 (2001).Hernell, O., Staggers, J. E. & Carey, M. C. Physical–chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 2. Phase analysis and aggregation states of luminal lipids during duodenal fat digestionin healthy adult human beings. Biochemistry 29, 2041–2056 (1990).Calvo-Lerma, J. et al. A first approach for an evidence-based in vitro method to adjust pancreatic enzyme replacement therapy in cystic fibrosis. PLoS ONE 14, e0212459 (2019).Aburub, A. Comparison of pH and motility of the small intestine of healthy subjects and patients with symptomatic constipation using the wireless motility capsule. Int. J. Pharm. 544, 158–164 (2018).Calvo-Lerma, J. et al. Innovative approach for self-management and social welfare of children with cystic fibrosis in Europe: development, validation and implementation of an mHealth tool (MyCyFAPP). Br. Med. J. Open. 7, e014931 (2017).Calvo-Lerma, J. et al. Clinical validation of an evidence-based method to adjust pancreatic enzyme replacement therapy through a prospective interventional study in paediatric patients with cystitic fibrosis. PLoS ONE 14, e0213216 (2019).Koumantakls, G. & Radciltf, F. J. Estimating fat in feces by near-infrared reflectance spectroscopy. Clin. Chem. 33, 502–506 (1987).Rivero-Marcotegui, A. et al. Water, fat, nitrogen, and sugar content in feces: reference intervals in children. Clin. Chem. 44, 1540–1544 (1998).Korpi-Steiner, N. L. et al. Comparative analysis of fecal fat quantitation via nuclear magnetic resonance spectroscopy (1H NMR) and gravimetry. Clin. Chim. Acta 400, 33–36 (2009).Dorsey, J. et al. Fat malabsorption in cystic fibrosis: comparison of quantitative fat assay and a novel assay using fecal lauric/behenic acid. J. Pediatr. Gastroenterol. Nutr. 50, 441–446 (2010).Proesmans, M. & De Boeck, K. Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes. Eur. J. Pediatr. 162, 760–763 (2003).Paz-Yépez, C. et al. Influence of particle size and intestinal conditions on in vitro lipid and protein digestibility of walnuts and peanuts. Food Res. Int. 119, 951–959 (2019).Moore, C. G. et al. Recommendations for planning pilot studies in clinical and translational sciences. Clin. Transl. Sci. 4, 332–337 (2011).Fitzpatrick, J. J. & Kazer, M. W. Encyclopedia of Nursing Research 3rd edn, Vol. 440 (Springer, New York, 2011).Isaac, S. & Michael, W. B. Handbook in Research and Evaluation (Educational and Industrial Testing Services, San Diego, 1995).Asensio-Grau, A. et al. Effect of cooking methods and intestinal conditions on lipolysis, proteolysis and xanthophylls bioaccessibility of eggs. J. Funct. Foods 46, 579–586 (2018).Asensio-Grau, A. et al. Fat digestibility in meat products: influence of food structure and gastrointestinal conditions. Int. J. Food Sci. Nutr. 70, 530–539 (2019).Regan, P. T. et al. Reduced intraluminal bile acid concentrations and fat maldigestion in pancreatic insufficiency: correction by treatment. Gastroenterology 7, 285–289 (1979).Fallingborg, J. et al. pH‐profile and regional transit times of the normal gut measured by a radiotelemetry device. Aliment. Phamacol. Ther. 3, 605–614 (1989).Fallingborg, J. Intraluminal pH of the human gastrointestinal tract. Dan. Med Bull. 46, 183–196 (1999).Calvo-Lerma, J. et al. In vitro digestion models to assess lipolysis: the impact of the simulated conditions for gastrointestinal pH, bile salts and digestion fluids. Food Res. Int. 125, 108511 (2019).Kalantzi, L. Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies. Pharm. Res. 23, 165–176 (2006).Zelles, L. & Bai, Q. Y. Fractionation of fatty acids derived from soil lipids by solid phase extraction and their quantitative analysis by GC-MS. Soil Biol. Biochem. 25, 495–507 (1993).Fiorentini, G. et al. Effect of lipid sources with different fatty acid profiles on intake, nutrient digestion and ruminal fermentation of feedlot nellore steers. Asian-Australas. J. Anim. Sci. 28, 1583 (2015).Perman, J. A., Modler, S. & Olson, A. C. Role of pH in production of hydrogen from carbohydrates by colonic bacterial flora. Studies in vivo and in vitro. J. Clin. Invest. 67, 643–650 (1981).Sellin, J. H. & Hart, R. Glucose malabsorption associated with rapid intestinal transit. Am. J. Gastroenterol. 87, 5 (1992).Tran, T. M. D. et al. Effects of a proton-pump inhibitor in cystic fibrosis. Acta Pediatr. 87, 553–558 (1998).Ayoub, F., Lascano, J. & Morelli, G. Proton pump inhibitor use is associated with an increased frequency of hospitalization in patients with cystic fibrosis. Gastroenterol. Res. 10, 288 (2017)

Dynamics of an Intruder in Dense Granular Fluids

We investigate the dynamics of an intruder pulled by a constant force in a dense two-dimensional granular fluid by means of event-driven molecular dynamics simulations. In a first step, we show how a propagating momentum front develops and compactifies the system when reflected by the boundaries. To be closer to recent experiments \cite{candelier2010journey,candelier2009creep}, we then add a frictional force acting on each particle, proportional to the particle's velocity. We show how to implement frictional motion in an event-driven simulation. This allows us to carry out extensive numerical simulations aiming at the dependence of the intruder's velocity on packing fraction and pulling force. We identify a linear relation for small and a nonlinear regime for high pulling forces and investigate the dependence of these regimes on granular temperature

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81

Sexual dimorphism in cancer.

The incidence of many types of cancer arising in organs with non-reproductive functions is significantly higher in male populations than in female populations, with associated differences in survival. Occupational and/or behavioural factors are well-known underlying determinants. However, cellular and molecular differences between the two sexes are also likely to be important. In this Opinion article, we focus on the complex interplay that sex hormones and sex chromosomes can have in intrinsic control of cancer-initiating cell populations, the tumour microenvironment and systemic determinants of cancer development, such as the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment

Embracing monogenic Parkinson's disease: the MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Michael J. Fox Foundation for Parkinson's Research. Grant Number: ID 15015.02. NIHR Cambridge Biomedical Research Centre. Grant Number: BRC-1215-20014info:eu-repo/semantics/publishedVersio

European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce