Designa utomhusmiljöer för hotell och restauranger

Hotell och restauranger behöver en inbjudande miljö som för att locka och få sina gäster att trivas, stanna och återkomma. (Bitner 1990; Ryu & Han 2010) Hotell och restaurangers utemiljö är en av de vistelseytorna som kan vara med och bidra till människors välbefinnande oavsett om den ligger i staden eller på landsbygden. Avkoppling, möten med andra människor och en god måltid är de främsta aktiviteterna som pågår i den utvalda miljön. Återhämtning kan ske på flera sätt men att vistas i en grönskande miljö är ett av dom (Kaplan& Kaplan, 1989) att sitta ner och äta är en annan. Jan Gehls (2010) 12 kvalitetskriterier (se fig 1) är ett verktyg som visar vilka kriterier som behöver uppfyllas för att människor ska välja att stanna och uppehålla sig på en plats. I uppsatsen studeras just de faktorerna och hur de kan vara till grund för utformning av vistelseytor för hotell och restaurangers utomhusmiljö, specifikt de med en egen trädgård. Studien visar hur man kan skapa en trivsam vistelseyta genom skydd, möjlighet till komfort och njutning. Kvaliteter som en bekväm sittplats i solen, ibland i skuggan, en värmande filt och vikten av utsikt mot något estetiskt vackert så som grönska är för att nämna några faktorer som får människor att stanna på en plats. Genom att studera 3 objekt och göra ett enkelt idéförslag till ett av studieobjekten visas exempel på hur man kan gestalta en trivsam utomhusmiljö i anslutning till Hotell och restaurang. Slutsatsen av studien är att detta är en av många metoder för hur vi kan analysera och sedan utforma trivsamma utomhusmiljöer i detta specifika fall i anslutning till hotell och restauranger. Genom att använda verktyget de 12 kvalitetskriterierna kan man systematiskt kontrollera att så många faktorer som möjligt uppfylls. Med hjälp av att förstå vilka faktorer som påverkan människors användande av de offentliga rummen kan trivsamm avistelseytor skapas. Människan behöver skydd, komfort och njutning för att uppleva trivsel i offentlig miljö. Njutning kan vara i form av estetiska värden så som grönskande träd och blommor, komfort kan vara en sittplats och skydd kan vara belysning som skydd för mörker.Hotels and restaurants need an inviting environment that, to attract and make their guests feel comfortable, stay and return. (Bitner 1990; Ryu & Han 2010) The outdoor environment of hotels and restaurants is one of the living spaces that can contribute to people’s well-being, whether in the city or in the countryside. Relaxation, meetings with other people and a good meal are the main activities going on in the selected environment. Recovery can occur in several ways, but staying in a green environment is one of them (Kaplan & Kaplan, 1989) to sit down and eat is another. Jan Gehl’s (2010) 12 quality criteria (see Figure 1) is a tool that shows which criteria need to be met in order for people to choose to stay and stay in one place. The thesis examines precisely those factors and how they can form the basis for designing living spaces for hotels and restaurants’ outdoor environment, specifically those with their own garden. The study shows how to create a pleasant living space through protection, opportunity for comfort and enjoyment. Qualities like a comfortable seat in the sun, sometimes in the shade, a warm blanket and the importance of overlooking something aesthetically beautiful such as greenery are to name a few factors that make people stay in one place. By studying 3 objects and making a simple idea suggestion for one examples of how to create a pleasant outdoor environment in connection with hotels and restaurants are shown. The study also assumes that the more quality criteria a site can achieve, the more pleasant and used the site becomes. The conclusion of the study is that this is one of many methods for how we can analyze and then design pleasant outdoor environments in this specific case in connection with hotels and restaurants. By using the tool the 12 quality criteria, one can systematically verify that as many factors as possible are met. By understanding the factors that influence people’s use of the public space, pleasant accommodation areas can be created. Man needs protection, comfort and enjoyment in order to experience well-being in the public environment. Enjoyment can be in the form of aesthetic values such as lush trees and flowers, comfort can be a seat and protection can be lighting as protection for darkness

What opportunities do the New EU international investment agreements offer for developing countries?

Purpose: Cancer chemotherapy, although based on body surface area, often causes unpredictable myelosuppression, especially severe neutropenia. The aim of this study was to evaluate qualitatively and quantitatively the influence of patient-specific characteristics on the neutrophil concentration-time course, to identify patient subgroups, and to compare covariates on system-related pharmacodynamic variable between drugs. Experimental Design: Drug and neutrophil concentration, demographic, and clinical chemistry data of several trials with docetaxel (637 patients), paclitaxel (45 patients), etoposide (71 patients), or topotecan (191 patients) were included in the covariate analysis of a physiology-based pharmacokinetic-pharmacodynamic neutropenia model. Comparisons of covariate relations across drugs were made. Results: A population model incorporating four to five relevant patient factors for each drug to explain variability in the degree and duration of neutropenia has been developed. Sex, previous anticancer therapy, performance status, height, binding partners, or liver enzymes influenced system-related variables and alpha(1)-acid glycoprotein, albumin, bilirubin, concomitant cytotoxic agents, or administration route changed drug-specific variables. Overall, female and pretreated patients had a lower baseline neutrophil concentration. Across-drug comparison revealed that several covariates (e.g., age) had minor (clinically irrelevant) influences but consistently shifted the pharmacodynamic variable in the same direction. Conclusions: These mechanistic models, including patient characteristics that influence drug-specific parameters, form the rationale basis for more tailored dosing of individual patients or subgroups to minimize the risk of infection and thus might contribute to a more successful therapy. In addition, nonsignificant or clinically irrelevant relations on system-related parameters suggest that these covariates could be negligible in clinical trails and daily use

Mechanism-Based Pharmacokinetic and Pharmacodynamic Modelling of Paclitaxel

Paclitaxel (Taxol®) is now widely used against breast, ovarian and non-small-cell lung cancer. Anticancer agents generally have narrow therapeutic indices, often with myelosuppression (mainly neutropenia) as dose-limiting side effect. A further complicating factor is that paclitaxel when given as Taxol® has a nonlinear pharmacokinetic (PK) behaviour in plasma. Identifying risk groups more sensitive to chemotherapy due to either a PK or pharmacodynamic (PD) interindividual variability is of importance. The aim of the thesis was to develop predictive mechanism-based PK and PD models applicable for paclitaxel. PK and PK/PD models were developed for patient data from studies with relatively frequent sampling or sparse sampling schedules. Population analyses were performed using the software NONMEM. A pharmacokinetic model describing unbound, total plasma and blood concentrations of paclitaxel from known binding mechanisms was developed and validated. The nonlinear PK in plasma could to a large extent be explained by the micelle forming vehicle Cremophor EL (CrEL) and the unbound drug showed linear PK. Besides a binding component directly proportional to concentrations of CrEL, the model included both linear and nonlinear binding components in plasma and blood. Further, relations between the PK parameters and different demographic factors, including polymorphisms in the cytochrome P450s involved in paclitaxel metabolism, were investigated. A semi-physiological PD model for chemotherapy-induced myelosuppression was developed and applied to different anticancer drugs. The model included a self-renewal for proliferating cells, transit compartments describing the delay in observed myelosuppression and a feedback parameter reflecting the effect on the bone marrow from growth factors that can result in an overshoot in white blood cells. The system-related parameters estimated showed consistency across drugs and the difference in the drug-related parameter reflected the relative bone marrow toxicity of the drugs. Relations between demographic factors and the PD parameters were identified. The developed mechanism-based models promote a better understanding of paclitaxel PK and PD and may be used as tools in dosing individualisation and in development of dosing strategies for new administration forms and new drugs in the same area

Population pharmacokinetic-pharmacodynamic model for neutropenia with patient subgroup identification : comparison across anticancer drugs

Purpose: Cancer chemotherapy, although based on body surface area, often causes unpredictable myelosuppression, especially severe neutropenia. The aim of this study was to evaluate qualitatively and quantitatively the influence of patient-specific characteristics on the neutrophil concentration-time course, to identify patient subgroups, and to compare covariates on system-related pharmacodynamic variable between drugs. Experimental Design: Drug and neutrophil concentration, demographic, and clinical chemistry data of several trials with docetaxel (637 patients), paclitaxel (45 patients), etoposide (71 patients), or topotecan (191 patients) were included in the covariate analysis of a physiology-based pharmacokinetic-pharmacodynamic neutropenia model. Comparisons of covariate relations across drugs were made. Results: A population model incorporating four to five relevant patient factors for each drug to explain variability in the degree and duration of neutropenia has been developed. Sex, previous anticancer therapy, performance status, height, binding partners, or liver enzymes influenced system-related variables and alpha(1)-acid glycoprotein, albumin, bilirubin, concomitant cytotoxic agents, or administration route changed drug-specific variables. Overall, female and pretreated patients had a lower baseline neutrophil concentration. Across-drug comparison revealed that several covariates (e.g., age) had minor (clinically irrelevant) influences but consistently shifted the pharmacodynamic variable in the same direction. Conclusions: These mechanistic models, including patient characteristics that influence drug-specific parameters, form the rationale basis for more tailored dosing of individual patients or subgroups to minimize the risk of infection and thus might contribute to a more successful therapy. In addition, nonsignificant or clinically irrelevant relations on system-related parameters suggest that these covariates could be negligible in clinical trails and daily use

American Association for Cancer Research

Abstract Purpose: Cancer chemotherapy, although based on body surface area, often causes unpredictable myelosuppression, especially severe neutropenia. The aim of this study was to evaluate qualitatively and quantitatively the influence of patient-specific characteristics on the neutrophil concentration-time course, to identify patient subgroups, and to compare covariates on systemrelated pharmacodynamic variable between drugs. Experimental Design: Drug and neutrophil concentration, demographic, and clinical chemistry data of several trials with docetaxel (637 patients), paclitaxel (45 patients), etoposide (71 patients), or topotecan (191 patients) were included in the covariate analysis of a physiologybased pharmacokinetic-pharmacodynamic neutropenia model. Comparisons of covariate relations across drugs were made. Results: A population model incorporating four to five relevant patient factors for each drug to explain variability in the degree and duration of neutropenia has been developed. Sex, previous anticancer therapy, performance status, height, binding partners, or liver enzymes influenced system-related variables and a 1 -acid glycoprotein, albumin, bilirubin, concomitant cytotoxic agents, or administration route changed drug-specific variables. Overall, female and pretreated patients had a lower baseline neutrophil concentration. Across-drug comparison revealed that several covariates (e.g., age) had minor (clinically irrelevant) influences but consistently shifted the pharmacodynamic variable in the same direction. Conclusions: These mechanistic models, including patient characteristics that influence drugspecific parameters, form the rationale basis for more tailored dosing of individual patients or subgroups to minimize the risk of infection and thus might contribute to a more successful therapy. In addition, nonsignificant or clinically irrelevant relations on system-related parameters suggest that these covariates could be negligible in clinical trails and daily use. In cancer chemotherapy, despite dose adaptation to body surface area, the degree of interpatient variability in effects is large (1, 2). Some patients fail to respond, whereas others experience unacceptable toxicity (3). Myelosuppression is the most common, often dose-limiting toxicity. Neutropenia makes patients highly susceptible to pathogens resulting in lifethreatening infections or even death. Empirical pharmacodynamic models accounting for the entire concentration-time profile of neutrophils have been developed (4, 5). Recently, also (semi-)mechanistic models (6, 7) and a physiology-based pharmacokinetic-pharmacodynamic model describing neutropenia for several drugs (8) have been introduced. Mechanistic models have the great advantage that estimated variables may be attributed and compared with physiologic values. The contribution of pharmacokinetic or pharmacodynamic variability to the variable clinical outcome has clearly been shown (9, 10). A more rational approach for optimal dosing is based on elucidating the sources of variability (i.e., identifying patient characteristics responsible for variations between patients; refs. 11 -15). Mechanistic models allow to incorporate patient characteristics, which may improve patient predictions and help to identify therapeutic subgroups. The aim of this study was to develop a pharmacokineticpharmacodynamic model, including the characteristics responsible for variability in neutropenia following four cytotoxic drugs, and to quantify their relations to the pharmacodynamic parameters. In addition, an across-drug comparison could reveal whether there were common factors for system-related pharmacodynamic variables, such as baseline neutrophil concentration

Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward

Mood disorders are twice as frequent in women than in men. Risk mechanisms for major depression include adverse responses to acute changes in sex-steroid hormone levels, eg, postpartum in women. Such adverse responses may involve an altered processing of rewards. Here, we examine how women's vulnerability for mood disorders is linked to sex-steroid dynamics by investigating the effects of a pharmacologically induced fluctuation in ovarian sex steroids on the brain response to monetary rewards. In a double-blinded placebo controlled study, healthy women were randomized to receive either placebo or the gonadotropin-releasing hormone agonist (GnRHa) goserelin, which causes a net decrease in sex-steroid levels. Fifty-eight women performed a gambling task while undergoing functional MRI at baseline, during the mid-follicular phase, and again following the intervention. The gambling task enabled us to map regional brain activity related to the magnitude of risk during choice and to monetary reward. The GnRHa intervention caused a net reduction in ovarian sex steroids (estradiol and testosterone) and increased depression symptoms. Compared with placebo, GnRHa reduced amygdala's reactivity to high monetary rewards. There was a positive association between the individual changes in testosterone and changes in bilateral insula response to monetary rewards. Our data provide evidence for the involvement of sex-steroid hormones in reward processing. A blunted amygdala response to rewarding stimuli following a rapid decline in sex-steroid hormones may reflect a reduced engagement in positive experiences. Abnormal reward processing may constitute a neurobiological mechanism by which sex-steroid fluctuations provoke mood disorders in susceptible women