Explore the vast range of titles available.

Nestle's Moga factory was set up in 1961 and comprises of the primary milk collection area for Nestle s operations. Since its inception in Moga, Nestle has been working with its milk farmers and ancillary suppliers towards improving quality and productivity. The study presented in this book (carried out by the Third World Centre for Water Management, Mexico) highlights Nestle's way of doing business through its philosophy of Creating Shared Value (CSV) and how it contributed to the development of the region over the past 50 years through direct and indirect employment, steady income for milk and other suppliers, and technology transfer. The main objective of the study is to learn to what extent has Nestle contributed to fulfilling the societal aspirations and expectations of the people working in and around its factory in terms of employment generation, poverty alleviation, general improvements in the community s standards of living and environmental conservation. The study also tried to determine to what extent has the company created shared value for itself, milk farmers, ancillary firms, and the community at large. This effort aims at encouraging more research to be carried out to comprehensively and authoritatively look into the impacts private sector can have on and around the area where their factories are located and that way, contribute to our understanding of social-corporate-government interdependency.

An unplanned ICU admission of an inpatient is a serious adverse event (SAE). So far, no in depth-study has been performed to systematically analyse the root causes of unplanned ICU-admissions. The primary aim of this study was to identify the healthcare worker-, organisational-, technical,- disease- and patient- related causes that contribute to acute unplanned ICU admissions from general wards using a Root-Cause Analysis Tool called PRISMA-medical. Although a Track and Trigger System (MEWS) was introduced in our hospital a few years ago, it was implemented without a clear protocol. Therefore, the secondary aim was to assess the adherence to a Track and Trigger system to identify deterioration on general hospital wards in patients eventually transferred to the ICU. Retrospective observational study in 49 consecutive adult patients acutely admitted to the Intensive Care Unit from a general nursing ward. 1. PRISMA-analysis on root causes of unplanned ICU admissions 2. Assessment of protocol adherence to the early warning score system. Out of 49 cases, 156 root causes were identified. The most frequent root causes were healthcare worker related (46%), which were mainly failures in monitoring the patient. They were followed by disease-related (45%), patient-related causes (7, 5%), and organisational root causes (3%). In only 40% of the patients vital parameters were monitored as was instructed by the doctor. 477 vital parameter sets were found in the 48 hours before ICU admission, in only 1% a correct MEWS was explicitly documented in the record. This in-depth analysis demonstrates that almost half of the unplanned ICU admissions from the general ward had healthcare worker related root causes, mostly due to monitoring failures in clinically deteriorating patients. In order to reduce unplanned ICU admissions, improving the monitoring of patients is therefore warranted.

Key Points The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gut-derived hormones that potentiate insulin secretion and contribute to glucose metabolism through a wide range of physiological actions Inhibitors of the incretin-inactivating enzyme dipeptidyl peptidase 4 (DPP-4) and DPP-4-resistant injectable GLP-1 receptor agonists have been developed for the treatment of hyperglycaemia in type 2 diabetes mellitus (T2DM) GLP-1 and other gut-derived hormones might directly and/or indirectly regulate electrolyte and fluid homeostasis by influencing feeding and drinking behaviour as well as electrolyte transport in the kidneys and gastrointestinal tract GLP-1 receptor (GLP-1R) agonists and DPP-4 inhibitors increase natriuresis in T2DM, possibly through overlapping and distinct mechanisms, and might slightly improve renal haemodynamics in the setting of diabetes-related glomerular hyperfiltration Incretin-based therapies seem to directly influence renal physiology and have indirect metabolic and haemodynamic actions that might reduce renal risk in T2DM; considerable interest exists in identifying these glucose-independent renoprotective actions Data from clinical trials suggest that GLP-1R agonists and, to a lesser extent, DPP-4 inhibitors marginally improve surrogate renal end points, plausibly beyond the effects of improved glycaemic control The incretin hormone glucagon-like peptide 1 (GLP-1) has been implicated in the gut–renal axis and incretin-based therapies might reduce the burden of diabetic kidney disease. Here, the authors review the physiological roles of GLP-1, the potential renoprotective mechanisms of incretin-based therapies and the available renal outcome data from clinical trials. The gastrointestinal tract — the largest endocrine network in human physiology — orchestrates signals from the external environment to maintain neural and hormonal control of homeostasis. Advances in understanding entero-endocrine cell biology in health and disease have important translational relevance. The gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) is secreted upon meal ingestion and controls glucose metabolism by modulating pancreatic islet cell function, food intake and gastrointestinal motility, amongst other effects. The observation that the insulinotropic actions of GLP-1 are reduced in type 2 diabetes mellitus (T2DM) led to the development of incretin-based therapies — GLP-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors — for the treatment of hyperglycaemia in these patients. Considerable interest exists in identifying effects of these drugs beyond glucose-lowering, possibly resulting in improved macrovascular and microvascular outcomes, including in diabetic kidney disease. As GLP-1 has been implicated as a mediator in the putative gut–renal axis (a rapid-acting feed-forward loop that regulates postprandial fluid and electrolyte homeostasis), direct actions on the kidney have been proposed. Here, we review the role of GLP-1 and the actions of associated therapies on glucose metabolism, the gut–renal axis, classical renal risk factors, and renal end points in randomized controlled trials of GLP-1 receptor agonists and DPP-4 inhibitors in patients with T2DM.

Aims/hypothesis This study aimed to investigate the acute renal effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes patients. Methods We included overweight (BMI 25–40 kg/m 2 ) men and postmenopausal women, aged 35–75 years with type 2 diabetes (HbA 1c 48–75 mmol/mol; 6.5–9.0%) and estimated GFR ≥ 60 ml min −1 1.73 m −2 . Exenatide or placebo (NaCl solution, 154 mmol/l) was administrated intravenously in an acute, randomised, double-blind, placebo-controlled trial conducted at the Diabetes Center VU University Medical Center (VUMC). GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance, respectively, based on timed urine sampling. Filtration fraction (FF) and effective renal vascular resistance (ERVR) were calculated, and glomerular hydrostatic pressure (P GLO ) and vascular resistance of the afferent (R A ) and efferent (R E ) renal arteriole were estimated. Tubular function was assessed by absolute and fractional excretion of sodium (FE Na ), potassium (FE K ) and urea (FE U ), in addition to urine osmolality, pH and free water clearance. Renal damage markers, BP and plasma glucose were also determined. Results Of the 57 patients randomised by computer, 52 were included in the final analyses. Exenatide ( n  = 24) did not affect GFR (mean difference +2 ± 3 ml min −1 1.73 m −2 , p  = 0.489), ERPF, FF, ERVR or P GLO , compared with placebo ( n  = 28). Exenatide increased R A ( p  < 0.05), but did not change R E . Exenatide increased FE Na , FE K , urine osmolality and pH, while FE U , urinary flow and free water clearance were decreased (all p  < 0.05). Osmolar clearance and renal damage makers were not affected. Diastolic BP and mean arterial pressure increased by 3 ± 1 and 6 ± 2 mmHg, respectively, whereas plasma glucose decreased by 1.4 ± 0.1 mmol/l (all p  < 0.05). Conclusions/interpretation Exenatide infusion does not acutely affect renal haemodynamics in overweight type 2 diabetes patients at normal filtration levels. Furthermore, acute GLP-1RA administration increases proximal sodium excretion in these patients. Trial registration ClincialTrials.gov NCT01744236 Funding The research leading to these results has been funded from: (1) the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 282521 – the SAFEGUARD project; and (2) the Dutch Kidney Foundation, under grant agreement IP12.87.

The Modified Early Warning Score (MEWS) was developed to timely recognise clinically deteriorating hospitalised patients. However, the ability of the MEWS in predicting serious adverse events (SAEs) in a general hospital population has not been examined prospectively. The aims were to (1) analyse protocol adherence to a MEWS protocol in a real-life setting and (2) to determine the predictive value of protocolised daily MEWS measurement on SAEs: death, cardiac arrests, ICU-admissions and readmissions. All adult patients admitted to 6 hospital wards in October and November 2015 were included. MEWS were checked each morning by the research team. For each critical score (MEWS ≥ 3), the clinical staff was inquired about the actions performed. 30-day follow-up for SAEs was performed to compare between patients with and without a critical score. 1053 patients with 3673 vital parameter measurements were included, 200 (19.0%) had a critical score. The protocol adherence was 89.0%. 18.2% of MEWS were calculated wrongly. Patients with critical scores had significant higher rates of unplanned ICU admissions [7.0% vs 1.3%, p < 0.001], in-hospital mortality [6.0% vs 0.8%, p < 0.001], 30-day readmission rates [18.6% vs 10.8%, p < 0.05], and a longer length of stay [15.65 (SD: 15.7 days) vs 6.09 (SD: 6.9), p < 0.001]. Specificity of MEWS related to composite adverse events was 83% with a negative predicting value of 98.1%. Protocol adherence was high, even though one-third of the critical scores were calculated wrongly. Patients with a MEWS ≥ 3 experienced significantly more adverse events. The negative predictive value of early morning MEWS < 3 was 98.1%, indicating the reliability of this score as a screening tool.

Aims/hypothesis Glucagon-like peptide (GLP)-1-based therapies have been suggested to improve hepatic steatosis. We assessed the effects of the GLP-1 receptor agonist liraglutide and the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin on hepatic steatosis and fibrosis in patients with type 2 diabetes. Methods In this 12 week, parallel, randomised, placebo-controlled trial, performed at the VU University Medical Center between July 2013 and August 2015, 52 overweight patients with type 2 diabetes treated with metformin and/or sulphonylurea agent ([mean ± SD] age 62.7 ± 6.9 years, HbA 1c 7.3 ± 0.7% or 56 ± 1 mmol/mol) were allocated to once daily liraglutide 1.8 mg ( n  = 17), sitagliptin 100 mg ( n  = 18) or matching placebos ( n  = 17) by computer generated numbers. Both participants and researchers were blinded to group assignment. Hepatic fat content was measured using proton magnetic resonance spectroscopy ( 1 H-MRS). Hepatic fibrosis was estimated using three validated formulae. Results One patient dropped out in the sitagliptin group owing to dizziness, but no serious adverse events occurred. At week 12, no between-group differences in hepatic steatosis were found. Liraglutide reduced steatosis by 10% (20.9 ± 3.4% to 18.8 ± 3.3%), sitagliptin reduced steatosis by 12.1% (23.9 ± 3.0% to 21.0 ± 2.7%) and placebo lessened it by 9.5% (18.7 ± 2.7% to 16.9 ± 2.7%). Neither drug affected hepatic fibrosis scores compared with placebo. Conclusions/interpretation Twelve-week liraglutide or sitagliptin treatment does not reduce hepatic steatosis or fibrosis in type 2 diabetes. Trial registration ClinicalTrials.gov NCT01744236 Funding Funded by the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 282521 – the SAFEGUARD project.

Objectives: As laboratory medicine continues to undergo digitalization and automation, clinical laboratorians will likely be confronted with the challenges associated with artificial intelligence (AI). Understanding what AI is good for, how to evaluate it, what are its limitations, and how it can be implemented are not well understood. With a survey, we aimed to evaluate the thoughts of stakeholders in laboratory medicine on the value of AI in the diagnostics space and identify anticipated challenges and solutions to introducing AI. Methods: We conducted a web-based survey on the use of AI with participants from Roche's Strategic Advisory Network that included key stakeholders in laboratory medicine. Results: In total, 128 of 302 stakeholders responded to the survey. Most of the participants were medical practitioners (26%) or laboratory managers (22%). AI is currently used in the organizations of 15.6%, while 66.4% felt they might use it in the future. Most had an unsure attitude on what they would need to adopt AI in the diagnostics space. High investment costs, lack of proven clinical benefits, number of decision makers, and privacy concerns were identified as barriers to adoption. Education in the value of AI, streamlined implementation and integration into existing workflows, and research to prove clinical utility were identified as solutions needed to mainstream AI in laboratory medicine. Conclusions: This survey demonstrates that specific knowledge of AI in the medical community is poor and that AI education is much needed. One strategy could be to implement new AI tools alongside existing tools. Key Words: Artificial intelligence; Laboratory medicine; Diagnostics; Medical education

Tracking knee joint movement during activities of daily living can have the potential to transform the rehabilitation and functional assessment of patients. The present study evaluated the validity of a low-cost, instrumented knee brace to determine whether it was appropriate for the monitoring and quantification of human knee function during five activity-of-daily-living (ADL) tasks including walking, inclined walking, stepping, sitting, and object manipulation. A sensor platform was designed to acquire sagittal plane knee data from 13 healthy participants across five different tasks and compared to gold-standard motion analysis. The brace showed good-to-excellent validity (RMSE: 4.97–8.65°), with differences in knee joint angles and angular velocities noted during various ADLs, specifically during early and late portions of a given movement. The results for instantaneous knee joint angles and angular velocities were very similar to those of the gold-standard system (mean bias: 0.59–9.52°·s−1), which may be applicable to everyday movement tasks, but may preclude analyses at a clinical level. Although the low-cost sensor platform shows promise an effective monitoring tool, it is not ready yet for a clinical application.

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) lower blood pressure (BP). When SGLT2i and GLP-1RA are combined, synergistic effects on BP have been observed. The mechanisms underlying these BP reductions are incompletely understood. The aim of this study was to assess the mechanisms underlying the BP reduction with the SGLT2i dapagliflozin, GLP-1RA exenatide, and dapagliflozin-exenatide compared with placebo in people with obesity and type 2 diabetes. Methods Sixty-six people with type 2 diabetes were randomized to 16 weeks of dapagliflozin 10 mg/day, exenatide 10 µg twice daily, dapagliflozin-exenatide, or placebo treatment. The effect of treatments on estimates of: (1) plasma volume (calculated by Strauss formula, bioimpedance spectroscopy, hematocrit, (2) autonomic nervous system activity (heart rate variability), (3) arterial stiffness (pulse wave applanometry), (4) systemic hemodynamic parameters including peripheral vascular resistance, cardiac output and stroke volume (all derived from non-invasively systemic hemodynamic monitoring), and (5) natriuresis (24-hour urine collection) were assessed after 10 days and 16 weeks of treatment. Results After 10 days, dapagliflozin reduced systolic BP (SBP) by − 4.7 mmHg, and reduced plasma volume. After 16 weeks, dapagliflozin reduced SBP by − 4.4 mmHg, and reduced sympathetic nervous system (SNS) activity. Exenatide had no effect on SBP, but reduced parasympathetic nervous system activity after 10 days and 16 weeks. After 10 days, dapagliflozin-exenatide reduced SBP by − 4.2 mmHg, and reduced plasma volume. After 16 weeks, dapagliflozin-exenatide reduced SBP by − 6.8 mmHg, and the reduction in plasma volume was still observed, but SNS activity was unaffected. Conclusions The dapagliflozin-induced plasma volume contraction may contribute to the initial SBP reduction, while a reduction in SNS activity may contribute to the persistent SBP reduction. Dapagliflozin-exenatide resulted in the largest decrease in SBP. The effect on plasma volume was comparable to dapagliflozin monotherapy, and SNS activity was not reduced, therefore other mechanisms are likely to contribute to the blood pressure lowering effect of this combination, which need further investigation. Trial registration  Clinicaltrials.gov, NCT03361098.

Striatal parvalbumin (PV) and cholinergic interneurons (CHIs) are poised to play major roles in behavior by coordinating the networks of medium spiny cells that relay motor output. However, the small numbers and scattered distribution of these cells have hindered direct assessment of their contribution to activity in networks of medium spiny neurons (MSNs) during behavior. Here, we build on recent improvements in single-cell calcium imaging combined with optogenetics to test the capacity of PVs and CHIs to affect MSN activity and behavior in mice engaged in voluntary locomotion. We find that PVs and CHIs have unique effects on MSN activity and dissociable roles in supporting movement. PV cells facilitate movement by refining the activation of MSN networks responsible for movement execution. CHIs, in contrast, synchronize activity within MSN networks to signal the end of a movement bout. These results provide new insights into the striatal network activity that supports movement.Causal manipulations combined with simultaneous recordings of both interneurons and medium spiny neurons in the striatum reveal dissociable contributions of cholinergic and parvalbumin interneurons in movement initiation and termination.