Humans and animals face decision tasks in an uncertain multi-agent environment where an agent's strategy may change in time due to the co-adaptation of others strategies. The neuronal substrate and the computational algorithms underlying such adaptive decision making, however, is largely unknown. We propose a population coding model of spiking neurons with a policy gradient procedure that successfully acquires optimal strategies for classical game-theoretical tasks. The suggested population reinforcement learning reproduces data from human behavioral experiments for the blackjack and the inspector game. It performs optimally according to a pure (deterministic) and mixed (stochastic) Nash equilibrium, respectively. In contrast, temporal-difference(TD)-learning, covariance-learning, and basic reinforcement learning fail to perform optimally for the stochastic strategy. Spike-based population reinforcement learning, shown to follow the stochastic reward gradient, is therefore a viable candidate to explain automated decision learning of a Nash equilibrium in two-player games. Socio-economic interactions are captured in a game theoretic framework by multiple agents acting on a pool of goods to maximize their own reward. Neuroeconomics tries to explain the agent's behavior in neuronal terms. Classical models in neuroeconomics use temporal-difference(TD)-learning. This algorithm incrementally updates values of state-action pairs, and actions are selected according to a value-based policy. In contrast, policy gradient methods do not introduce values as intermediate steps, but directly derive an action selection policy which maximizes the total expected reward. We consider a decision making network consisting of a population of neurons which, upon presentation of a spatio-temporal spike pattern, encodes binary actions by the population output spike trains and a subsequent majority vote. The action selection policy is parametrized by the strengths of synapses projecting to the population neurons. A gradient learning rule is derived which modifies these synaptic strengths and which depends on four factors, the pre- and postsynaptic activities, the action and the reward. We show that for classical game-theoretical tasks our decision making network endowed with the four-factor learning rule leads to Nash-optimal action selections. It also mimics human decision learning for these same tasks. Neuroeconomics is an interdisciplinary research field that tries to explain human decision making in neuronal terms. Behavioral outcomes are construed as results of brain activity and the neuronal correlates of the quantities relevant for the decision making process are identified. Humans, as economic agents, attempt to optimize some reward function by participating in the production, exchange and maintenance of goods. Reward for the individuals will depend in general not merely upon their own actions but also on those of the other players and, furthermore, these will adapt their own strategies.Classical models in neuroeconomics are based on temporal difference (TD) learning Here we show that for classical two-player games The current paper follows a long tradition of explaining human and animal behavior by simple models of reward-based learning, starting from Thorndike's law of effect The network representing a player consists of a population of rn , see . The decThe synapses feeding the stimulating spike pattern to the population neurons are updated according to a multi-factor plasticity rule involving the reward, the behavioral decision, the single neuron decision and the eligibility trace which depends on the post- and pre-synaptic activity:activity , and  islearning . TechnicWhile most of the terms in Our neuronal implementation is as simple as possible to provide the required computational properties. The lack of feedback connectivity avoids issues relating to population spike correlations The simplified version of blackjack considered here was played in 18th century France and is the precursor of the version played in casinos nowadays. The card decks used consist of The described rules of the game result in the payoff-matrix  comprisiectively . The gamWe first simulated two neural networks playing against each other. Each hand value between We next simulated the gambler by a neural net and the croupier by a computer algorithm which follows right from the beginning a fixed strategy. The resulting drawing probabilities after Hence, from playing against another network and against the croupier, we conclude that a neuronal population endowed with the plasticity rule (1) is able to learn the optimal strategies in blackjack, determined either by the pure Nash equilibrium, or by the croupier's fixed strategy. Replacement of the neural net by a TD-learner yields similar results for both scenarios  covariance rules. We considered the version where the mean In Whereas we do not consider the neural mechanisms supporting the readout of the decision, such a mechanism has been studied in the context of matching The Replicator equation is widely used in evolutionary game theory and provides a good phenomenological description of choice behavior in many repeated-choice experiments. A different phenomenological description has been suggested in than pRL . After  We considered a population of spiking neurons which represent an adaptive agent in a dynamic environment including other adaptive agents. The agent's adaptation was implemented as population reinforcement learning algorithm (pRL) which was previously shown to perform stochastic gradient ascent in the reward for partially observable Markov decision processes (POMDPs) For mathematical clarity we presented the spike-based pRL for an episodic learning scenario. But a biologically plausible implementation of a fully online scheme is also possible: to avoid an explicit separation of stimuli in time, the rectangular window function used to temporally integrate the eligibility trace  can be rThe mixed Nash equilibrium represents a special case of Herrnstein's matching law The performance of spike-based pRL is also superior to TD-learning Different generalizations have been considered to approach the shortcomings of algorithms in socio-economic games. TD-learning has been extended to not only assign values to its own decisions, but to pairs of own and opponent decisions. This enables the learning of minimax strategies where reward is maximized for the worst of the opponents actions Although under the specific experimental conditions of the inspector game humans did not show cooperation, they often do so in other game-theoretic paradigms, as e.g. in the prisoner's dilemma, and hence deviate from the Nash equilibrium .The evolution of the rates in time in Text S1We present further results for temporal-difference learning and elaborate on its failure to learn mixed Nash equilibria.(PDF)Click here for additional data file.Text S2We show how the plasticity rule presented in the main text is based on a gradient ascent procedure maximizing the average reward.(PDF)Click here for additional data file.Text S3We demonstrate that the heuristic rules of Erev and Roth (PDF)Click here for additional data file.


Near the end of the nineteenth century the hypothesis was presented for the homology of book lungs in arachnids and book gills in the horseshoe crab. Early studies with the light microscope showed that book gill lamellae are formed by outgrowth and possibly some invagination (infolding) of hypodermis (epithelium) from the posterior surface of opisthosomal limb buds. Scorpion book lungs are formed near the bilateral sites of earlier limb buds. Hypodermal invaginations in the ventral opisthosoma result in spiracles and sac-like cavities (atria). In early histological sections of embryo book lungs, widening of the atrial entrance of some lamellae  was interpreted as an indication of invagination as hypothesized for book gill lamellae. The hypodermal infolding was thought to produce the many rows of lamellar precursor cells anterior to the atrium. The ultrastructure of scorpion book lung development is compared herein with earlier investigations of book gill formation.In scorpion embryos, there is ingression (inward migration) of atrial hypodermal cells rather than invagination or infolding of the atrial hypodermal layer. The ingressing cells proliferate and align in rows anterior to the atrium. Their apical-basal polarity results in primordial air channels among double rows of cells. The cuticular walls of the air channels are produced by secretion from the apical surfaces of the aligned cells. Since the precursor cells are in rows, their secreted product is also in rows . For each double row of cells, their opposed basal surfaces are gradually separated by a hemolymph channel of increasing width.The results from this and earlier studies show there are differences and similarities in the formation of book lung and book gill lamellae. The homology hypothesis for these respiratory organs is thus supported or not supported depending on which developmental features are emphasized. For both organs, when the epithelial cells are in position, their apical-basal polarity results in alternate page-like channels of hemolymph and air or water with outward directed hemolymph saccules for book gills and inward directed air saccules for book lungs. At the end of the ninteenth century and in the early twentieth century numerous papers were published comparing the development of book gills in the horseshoe crab with the development of book lungs in arachnids, especially spiders. As reviewed by Farley , this woIn early studies with the light microscope and histological sections, the air sacs  of developing spider and scorpion book lungs were suggested to be infoldings of the hypodermis from the spiracular invagination  posterior to opisthosomal limb buds. This process was thought to be similar to the small amount of invagination that may occur along with outgrowth folds for book gill development at the posterior surface of branchial appendages in horseshoe crabs -10,18-22Cupiennius salei [engrailed-1 is reported to be expressed as five stripes at the site where lamellae originate posterior to the second opisthosomal limb buds. The primordial site is invaginated and covered ventrally by the posterior folding and flattening of the preceding limb bud, as reported in earlier histological studies [C. salei, the developmental gene pdm/nubbin is expressed in a striped pattern possibly related to lamellar formation [More recently for the spider us salei , the seg studies ,23. Alsoormation .In his diagram of histological sections of scorpion embryos, Brauer  showed sAs pointed out earlier , lamellaThe scanning electron microscope (SEM) was used in recent developmental investigations of the respiratory organs in the scorpion  and horsBook lung formation in scorpions is a slow and gradual process . It begiInformation about scorpion anatomy and morphology and the general organization of scorpion book lungs and horseshoe crab book gills is provided in earlier publications ,29-31.Centruroides gracilis [Gravid females of gracilis  were purgracilis , Sissom gracilis , Ades [3gracilis  and Fet gracilis . For taxgracilis  is avail4 in 0.1 M cacodylate buffer. Tissues were dehydrated in a graded series of ethanol and embedded in Spurr's [2O.Maintenance of animals and the dissection and preparation of tissues for SEM were done as described by Farley . For TEM Spurr's  plastic. Spurr's  and examShown herein are typical examples of lamellar formation in successive developmental stages, but early book lung development is a continuum rather than a series of discrete steps related to the age of the individual. Within each scorpion there is a longitudinal gradation in the rate at which the book lungs develop, with the posteriormost pair  the most advanced. In the early embryo, the limb buds of the third mesosomal segment gradually develop the features of pectines that temporarily overlap on the ventral surface of segment four ,40-42. TAs reported earlier ,40-43, tThe spiracles open into the atrium, a sac-like cavity formed by invagination of the external hypodermis at the spiracle site Figures  and 3. TFigures Figures Beginning at the atrium, the aligned precursor cells soon begin to show indications of the polarity that is common among epithelial cells, i.e., secretion at the apical surface while the basal surface is in contact with hemolymph where nutrient transport can occur . This diIn this scorpion investigation, some widening of the air sac entrance was seen for some more advanced air sacs Figures , 3, but In the initial stages of air sac formation, a thin line of osmiophilic material suggests merocrine secretion from the apical surface of the aligned cells Figures , 6, and Figures Within the primordial air channels, the cell fragments appear to fuse together to form more elongate strands of membrane-bound cytoplasm Figures , 10, 11.In these early stages of book lung development, cells with large (~1 μm dia.) electron-opaque granules are sometimes seen among the other precursor cells. Examples were seen where these cells release fragments with large granules that become part of the developing air sac. Once inside the primordial air sac, these granules make the air sac somewhat wider and more dense than the other air sacs without these granules Figures , 11. TheAs shown in Figures As shown in Figures Within the air channel lumen, trabeculae may be formed by fusion of the cuticularized walls of the former cell fragments Figures , 13. CelAs shown in Figure Some of the first instars examined in this investigation were thought to be close to their first molt, but in the sections there was no indication that lamellar epithelial cells were secreting new cuticle walls as preparation for the first molt. As shown in an example of first-molt exuvium , some reFigure Figure Cells with large (~1 μm dia.), electron-opaque granules did not appear to be abundant among the book lung tissue in the early stages of this investigation. Short lengths of air sacs contain these granules Figures , 11, butAs reviewed by Fristrom , epithelEpithelial cells commonly exist in sheets and provide protective coverings and barriers for the external surface and for tubes, vessels and channels inside the animal. They are commonly in a single layer with a basement membrane secreted from their basal surface. Fristrom  notes thEpithelial cells undergo many different morphological changes during development; invagination of a specific region of the epithelium Figures , 2A, B iAs explained in Background, the invagination or infolding of the atrial epithelium for each lamella of arachnid book lungs was proposed to be a continuation of the small amount of invagination that may occur along with outgrowth (evagination) in the formation of book gills of horseshoe crabs . Slight In the present investigation, widening of the air sac entrance was seen at the atrial origin of some advanced lamellae Figures , 3 but nCalodipoena incredula and Mysmenella samoensis  of the book gill lamellae from the posterior surface of opisthosomal branchial appendages differs substantially from the ingression process in extant scorpions Figures  and 3 11,6,7, buAs pointed out by Fristrom , epithelThe precursor cells for book gills are aligned in rows by hypodermal evagination ,7 while The results in this and earlier studies with SEM ,27 thus in vitro model using Madin-Darby canine kidney (MDCK) epithelial cells [Numerous model systems  are presently being used to study the cellular and molecular basis of epithelial morphogenesis -74. Cellal cells . StartinDrosophila is receiving much attention for the genetic determination of cell activity during tubulogenesis [Among the model systems, tracheal development in ogenesis ,88-90. Sogenesis ,76,91.The development of arachnid book lungs is another example of epithelial morphogenesis with some features well suited for comparative studies. The book lungs are relatively large and tractable, even in embryos. There are 2, 4, or 8 book lungs in each individual ,30,49,50The results herein show that some cellular activities are similar for book gill and book lung formation, but there are also important differences. The present investigation thus provides evidence for and against the hypothesis for book gill/book lung homology. The features of cell alignment and apical-basal polarity described herein are common among epithelial cells in animals, but the precursor cells for book gills and book lungs are distinctive in organizing themselves into a compact mass of many parallel, non-branching rows, i.e., the page-like pattern of alternating hemolymph and air or water channels.Drosophila. Book lung formation in scorpions is another example of epithelial cell morphogenesis, and many genetic and molecular features now being demonstrated in model systems in other animals may also be applicable for the development of book lungs.The genetic and molecular basis of epithelial morphogeneis is presently receiving much research attention using model systems such as the tracheae of The author declares that he has no competing interests.


Childhood chronic disease may affect patients' and their family's functioning. Particularly parents, who play an important role in cooperation between patient and health care professionals, report impaired health - related quality of life (HRQOL). The aim of this study was development, evaluation and validation of a new instrument: Quality of Life in a Child's Chronic Disease Questionnaire (QLCCDQ). The questionnaire is addressed to parents of children with a chronic disease.Study design included semi structured interview and qualitative study, which allowed to identify most troublesome problems. Following the results the questionnaire was developed, which consists of 15 questions and covers domains - emotions, patients -perceived symptoms, roles limitations. An observational study involving parents of asthma and diabetes children was conducted to assess the psychometric characteristics of the measure. Psychometric testing was based on the reliability of defined subscales, construct validity, reproducibility assessment, as well as comparison between stable/unstable disease stages and parents of healthy children.Most troublesome concerns for parents of child with chronic disease included emotional distress and feeling depressed due to child's disease, avoiding social interactions due to child's disease or symptoms. 98 parents of children with asthma or insulin - depended diabetes participated in the psychometric testing of QLCCDQ. Internal consistency reliability for the defined subscales ranged between 0.77 and 0.93. Reproducibility based on the weighted kappa coefficients showed expected level of agreement and was almost perfect in case of 8 questions, substantial for 5 questions and moderate for 2 questions. QLCCDQ demonstrated very good construct validity - all subscales showed statistically significant correlations ranging from 0.4 to 0.9. QLCCDQ scores differed significantly by clinical status - parents of children qualified as stable presented higher scores in most subscales in comparison to parents of children with unstable disease.The QLCCDQ shows good internal consistency, test-retest reliability, and construct validity. The questionnaire may be useful in helping to understand the impact of chronic child's disease on parental perception of health outcomes. An increasing interest of the impact of disease on everyday functioning is leading to the development and implementation of health - related quality of life (HRQOL) measures in many studies. Chronic disease may affect not only patients' functioning, but other family members as well. Childhood chronic disease involves all family members, particularly parents, who play an important role in the cooperation between patients and health care professionals. Higher level of psychological distress in parents of children with chronic disease has been reported in several studies -5. ParenHRQOL assessment in childhood chronic disease could either be measured as parent-proxy measures of the child's quality of life or as self-reported parental quality of life. Several studies show that parents are reliable at reporting symptoms and physical function, but less reliable at reporting cognitive and emotional well-being of the child .HRQOL of parents could be assessed by a wide range of general status questionnaires such as the Medical Outcomes Survey Short Form 36 (SF 36) , EuroQolMost of the existing validated measures are specific - questionnaires, dedicated to parents of children with a particular disease and are not recommended as a measure of HRQOL assessment for other clinical conditions. HRQOL of parents of children with diabetes could be assessed by Well-being and Satisfaction of Caregiver's of Children with Diabetes Questionnaire (WE-CARE) , ParentsThe proposed questionnaire, the Quality of Life in the Child's Chronic Disease Questionnaire (QLCCDQ) deals with daily problems and limitations that concern parents of children with chronic disease. Compared to existing HRQOL measures in parents - the newly developed parental HRQOL assessment and symptom proxy measure could be implemented in different clinical conditions and covers both impact of disease on family and psychosocial aspects of parental functioning. Parental HRQOL assessment would be helpful to optimize clinical judgment as well as to improve clinical decisions. Childhood diabetes and asthma are examples of chronic disease which require continuous monitoring and treatment and were chosen for questionnaire development and validation. The purpose of this paper is to describe the development of the QLCCDQ and report on the assessment of its validity and reliability.The QLCCDQ is a self - report measure of the parent's HRQOL. Only the symptoms subscale is a proxy measure of the parent's HRQOL. The QLCCDQ consists of 15 questions and covers: emotions (4 questions); patient-perceived symptoms (3 questions); and role limitations (8 questions) including social (3 questions), occupational (3 questions), and family roles (2 questions). The QLCCDQ is a self - administered questionnaire, based on a 7 point Likert scale from 1 (most bothered or limited) to 7 (not bothered or limited). The responses concern parental perceptions of the child and their condition over a previous two-week period. Examples of questions representing each domain of QLCCDQ have been demonstrated in Table The questionnaire was devised based on the multi-step procedure ,21 whichParticipants of the study were chosen based on convenience samples. Approval from an ethics committee at the authors' university was obtained by the study center.Questionnaire development was based on a multi-stage procedure which included the processes of item identification, questionnaire development, and psychometric testing:Process of item identification:- Semi structured interview with health professionals and parents of children with chronic disease - identification of most the troublesome problems- initial inventory development with a 5 point Likert scale rating the importance of each item- qualitative study among parents of children with chronic diseaseProcess of questionnaire development:- questionnaire development based on results of qualitative study- cognitive debriefing (to assess the comprehension of the questionnaire)- development of the final version of the questionnaire- cognitive debriefing of the final version of the questionnaireThe last phase of the study was psychometric testing.- The validation process included internal consistency, construct validity, reproducibility, and known- group analysis (children with asthma and diabetes)Semi structured interviews and a literature review were used to develop an initial inventory listing the most troublesome problems for parents of children with chronic disease. Health professionals  and parents of children with diabetes, asthma or eczema were invited for an interview to help develop this inventory. In the qualitative study which followed, parents were asked to choose from the inventory, which concerns were relevant to their situation and rate the importance of several troublesome issues (from 1 - not important/troublesome to 5 very important/troublesome). Not all parents rated all the items. Inclusion criteria for participation in this phase of the questionnaire development required the child to have a clinical diagnosis of asthma  or eczema or diabetes; symptoms presence or the diagnose was established at least 12 months before the study; no other social and psychological problems which may have an impact on family functioning or ability to respond , and; willingness to provide consent to participate.In the next phase, cognitive debriefing interviews were conducted involving parents recruited from the qualitative study. Cognitive debriefing was done twice - first on the primary version and second on the revised questionnaire to ensure that respondents could understand and complete the questionnaire.The psychometric testing phase to validate the questionnaire consisted of measuring internal consistency, construct validity, reproducibility, and known - group analysis. Psychometric testing was conducted in outpatient departments involving parents of children with asthma or diabetes. Asthma children represented a wide range of severity: episodic, mild and moderate. Children with diabetes were insulin - dependent with or without complications. Both asthma and diabetes study groups included patients with and without satisfactory disease control. Subjects were excluded if there were significant co-morbidities in the child that could impact their quality of life and other social and psychological problems which could have an impact on family functioning or ability to respond. Once completed, the questionnaires were returned to study physicians.Comparison of HRQOL results in parents whose child was assessed as stable and parents with uncontrolled asthma or diabetes were conducted for both groups. Asthma control is defined based on GINA guidelines as daytime symptoms present less than twice a week, rescue medication use less than twice a week, no nocturnal symptoms, no limitations in physical activity, normal or near normal lung function values in lung function test .Diabetes control was based on glucose and hemoglobin A1c (Hb A1c) levels. Patients were classified as stable if Hb A1c below 6.5% was achieved, as well as glucose if fasted and between meals ranged between 3.9 and 6.1 mmol/l, after meals less than 8.9 mmol/l .The control group for the psychometric testing consisted of a volunteer group of parents of healthy children. The final version of QLCCDQ was completed. As typical childhood diseases or even prophylaxis (vaccinations) could focus parental attention on health - related problems it was important to find out if all questions included in the questionnaire were clearly related to chronic disease conditions. For this reason, we included a control group.The statistical analysis was performed using standard procedures available in the Statistica 7.1 package  and SAS, version 9.2 . Normality of distributions of continuous variables was assessed by the Shapiro-Wilk test. Statistical significance of differences between continuous variables was analyzed by the Student's t-test and Analysis of Variance. If a non-normal distribution was found, the Mann-Whitney U test and Kruskal-Wallis tests were used, respectively. Differences between categorical variables were examined by the Chi-square test. Correlations between variables with non-normal distributions were measured by Spearman's rank correlation coefficient. The reliability of the defined subscales was measured by the Cronbach's alpha. The statistical inferences were based on the level of significance of p < 0.05.Semi structured interviews were conducted on the group of health professionals  and 22 parents of children with diabetes, asthma or eczema. Health care professionals raised the emotional context of disease, distress and anxiety, potential limitation of occupational roles as troublesome areas for parents. Parents identified emotional distress, time limited for other family members and professional career, and decreased social interactions as troublesome areas. All important issues raised by respondents were incorporated into the initial inventory, which was distributed during qualitative study.The qualitative study was conducted among 65 parents of children aged 6-14 years old, mean age 9.23 (SD 2.06), with chronic disease including asthma, eczema or diabetes  with asthma or diabetes [Table The reliability of the defined subscales was evaluated by Cronbach's α. All subscales that were supposed to represent a single - construct scale achieved Cronbach's alpha at least 0.7. The values for subscales ranged between 0.77 and 0.93 Table  thus sugStatistically important positive correlations were observed between all QLCCDQ dimensions defined by questionnaire's subscales Table . Better Reproducibility of answers was examined in a subgroup of 22 parents of asthma patients. The questionnaire was distributed twice - parents were asked to complete the questionnaire again 2 hours after first completion. According to the values of weighted kappa coefficients the level of agreement was almost perfect in case of 8 questions (0.81-1.00), substantial for 5 questions (0.61-0.80) and moderate for 2 questions (0.41-0.60) [Table The discriminative validity was determined by comparing mean scores between parents of children with conditions and parents of control children as well as between parents of children with stable conditions and those with unstable conditions. Higher HRQOL scores were found in parents of control children than parents of children with a chronic condition Table . EmotionAt this stage, the analysis revealed, that QLCCDQ results showed that mother's scores were lower in comparison with father's scores in most subscales Table .As chronic child's disease may have an impact on the entire family functioning - parents of children representing common chronic diseases in childhood were invited to participate in a qualitative study to identify their most troublesome concerns. Most parents identified emotional concerns and impact on roles functioning as primary concerns. Parents complained about their limitation in attention and time offered to other family members, limitation in work related activities, as well as daily house-hold activities. Based on the qualitative study, the questionnaire was developed and cognitive debriefing was subsequently used to generate the final version of the new tool.This study investigated the validity of newly developed questionnaire addressing the HRQOL of parents of children with a chronic condition. Psychometric analyses based on a sample of 65 parents of children with asthma or diabetes was used to evaluate the validity of the questionnaire. With the satisfactory results of the QLCCDQ found in this study, our results would suggest that this questionnaire could be used in clinical practice. Psychometric properties for the questionnaire including internal consistency, construct validity and reproducibility were satisfactory. Internal consistency of QLCCDQ scores achieved acceptable levels of Cronbach' alpha. The QLCCDQ demonstrated good reproducibility with kappa coefficients of at least substantial for most questions.Construct validity of the questionnaire demonstrated positive correlations between all defined subscales. Parents of children with chronic disease demonstrated lower HRQOL mean scores in all subscales in comparison to parents of control children. The comparison between QLCCDQ scores of parents of stable children and unstable children has shown that clinical status had an impact on parental functioning. Significantly lower QLCCDQ scores have been observed for most subscales for parents of children with unstable conditions. The only exception was the occupational roles subscale where no differences were found between parents of stable and unstable children.The initial inventory didn't show that parental concerns due to a child' disease differed between mothers and fathers. Thus HRQOL questionnaire should not include different items for mothers and fathers. As it was found in other studies our analysis of QLCCDQ results showed that the HRQOL due to child's disease was more impaired in mothers .Our study showed that the QLCCDQ could bring new insights into health related outcomes in childhood diseases. The questionnaire showed that HRQOL scores in parents were statistically lower in the case of chronic disease in comparison with parents of healthy children for all subscales. It is worthwhile noting that answers to only one question, feeling guilty due to the child's disease, didn't showed any differences between the control and the chronic condition group in the psychometric testing. Despite of qualitative study results showing that guilty feeling as the result of child's disease were found as an important concern, no differences were found between scores of controls and chronic conditions. This may be important when using the QLCCDQ in other childhood chronic diseases as the child's disease may have an impact on contexts such as emotional functioning.Parental HRQOL assessment using QLCCDQ could be beneficial in clinical practice. The implementation of the tool with parents of children with asthma or diabetes was successful and would be helpful in team-oriented approaches in patient care, where parents would become integral part of the team involved in therapy.QLCCDQ has a potential to contribute to many aspects of routine care including improved detection of emotional consequences of child's disease and assessment of treatment outcomes in the context of family functioning. The HRQOL feedback can provide important information for both child and family tailored approach in treatment. Studying the feasibility of this questionnaire to measure HRQOL of parents of children with other chronic conditions as the result of child' s disease would be of great interest and subject to further research.The QLCCDQ shows good internal consistency, test-retest reliability, and construct validity. The questionnaire may be useful in helping to understand the impact chronic child's disease on parental perception of health outcomes.CHQ PF 50: Child Health Outcomes Questionnaire Parent Form; HRQOL: health - related quality of life; PACQLQ: Pediatric Asthma Caregiver's Quality of Life Questionnaire; PAQLQ: Pediatric Asthma Quality of Life Questionnaire; PDQOL: Pediatric Diabetes Quality of Life Questionnaire; QLCCDQ: Quality of Life in a Child's Chronic Disease Questionnaire; SF 36: Medical Outcomes Survey Short Form; WE-CARE: Well being and Satisfaction of CAREgivers for Children with Diabetes Questionnaire.The authors declare that they have no competing interests.MF, JZ, WP and GB conceived of the study and participated in study design, data interpretation. ŁW MF conducted qualitative study, cognitive debriefing and developed the questionnaire, MF, GB, MS JZ WP conducted psychometric study, GB, ŁW, MS were responsible for statistical analysis. MF, GB, ŁW worked on manuscript. All authors read and approved the final manuscript.


The primary aim of this study was to provide an estimate of effect size for the functional outcome of operative versus non-operative treatment for patients with an acute rupture of the Achilles tendon using accelerated rehabilitation for both groups of patients. The secondary aim was to assess the use of a comprehensive cohort research design  in improving the accuracy of this estimate within an orthopaedic trauma setting.Pragmatic randomised controlled trial and comprehensive cohort study within a level 1 trauma centre. Twenty randomised participants (10 operative and 10 non-operative) and 29 preference participants (3 operative and 26 non-operative). The ge range was 22-72 years and 37 of the 52 patients were men. All participants had an acute rupture of their Achilles tendon and no other injuries. All of the patients in the operative group had a simple end-to-end repair of the tendon with no augmentation. Both groups then followed the same eight-week immediate weight-bearing rehabilitation programme using an off-the-shelf orthotic. The disability rating index , EQ-5D, Achilles Total Rupture Score and complications were assessed ed at two weeks, six weeks, three months, six months and nine months after initial injury.At nine months, there was no significant difference in DRI between patients randomised to operative or non-operative management. There was no difference in DRI between the randomised group and the parallel patient preference group. The use of a comprehensive cohort of patients did not provide useful additional information as to the treatment effect size because the majority of patients chose non-operative management.Recruitment to clinical trials that compare operative and non-operative interventions is notoriously difficult; especially within the trauma setting. Including a parallel patient preference group to create a comprehensive cohort of patients has been suggested as a way of increasing the power of such trials. In our study, the comprehensive cohort model doubled the number of patients involved in the study. However, a strong preference for non-operative treatment meant that the increased number of patients did not significantly increase the ability of the trial to detect a difference between the two interventions.ISRCTN29053307ISRCTN:  Randomised controlled trials are accepted as the 'gold standard' in trial design for evaluating the effectiveness of a single intervention, such as a drug. Within This study design has been successfully implemented within musculoskeletal elective settings . HoweverThe management of Achilles tendon rupture is one such complex intervention. It is a serious and disabling condition affecting approximately 18 per 100,000 people each year, based on data from Scandinavian countries,5. It isOur primary aim was to provide an estimate of possible effect size for the functional outcome of operative versus non-operative treatment of patients with an acute rupture of the Achilles tendon with accelerated rehabilitation for both groups of patients. This would inform the design of subsequent larger trials and enable a sample size analysis to be performed. The secondary aim was to assess the use of a comprehensive cohort research design  in improving the accuracy of this estimate within an orthopaedic trauma setting.This study was funded by the British Orthopaedic Foundation (Joint Action) with the kind support of the Rosetrees Trust. Funding was provided to support data collection in the randomised group of patients, but was not available for the inclusion of an additional patient-preference group. Ethical approval for the trial was obtained from Oxfordshire Research Ethics Committee A. The patient-preference data was collected as part of an ongoing service evaluation in this area.Patients were recruited from a fracture clinic within a University Hospital. All patients gave informed consent before taking part in the study. Patients were eligible if they presented with an acute rupture of the Achilles tendon (presentation within 10 days of injury) diagnosed through clinical assessment, had no previous history of Achilles tendon rupture and had no contraindications to surgery. All patients were screened for eligibility by the principal investigator. We invited any eligible patients who did not want to take part in the randomised trial because of a strong preference about treatment, to join one of two non-randomised preference arms.Recruitment took place betweenAugust 2007 and December 2008. Figure Both randomised and preference operative groups underwent surgical repair of the Achilles tendon on the next available 'trauma' operating list (within 10 days of injury). The details of the repair technique were recorded but left to the preference of the surgeon. Both operative and non-operative groups followed identical immediate weight bearing rehabilitation protocols. Three one-centimetre heel raises were used within a walking boot . Patients were encouraged to remove the boot and move the ankle joint within the limits of their comfort four times each day. Patients then attended fracture clinic every two weeks for eight weeks. At each visit to clinic, one heel wedge was removed and then the boot was removed at week eight. At eight weeks all patients were referred for physiotherapy. The detail of the physiotherapy treatment was left to the preference of the physiotherapist but followed guidelines that allowed gradual progression of strengthening activities. Participation in high-impact sports training was allowed at six months and return to competitive sports at nine months.The primary patient reported functional outcome was the Disability Rating Index at nine months. This isOne-hundred percent of outcomes were collected for the randomised groups at baseline, 6 weeks and three months. One patient in the randomised non-operative arm was lost to follow-up at 6 and 9 months. Within the preference arms 100% of outcomes were collected at baseline, 97% at 6 weeks (28/29), 86% at 3 months and 6 months (25/29) and 79% at 9 months (23/29).This was a pilot study and a sample size of ten patients in each of the randomised treatment arms was deemed to be sufficient after discussion with clinical experts and the trial statistician, No formal sample size calculation was performed for the pilot but the information from this study will informa power analysis for any larger trial. All of the patients who declined to take part in the randomised trial throughout the recruitment period were offered the option of taking part in the preference study - these patients chose their own treatment but were followed up in the same way as the randomised patientsA computer-generated 1:1 randomisation sequence was produced and administered by an independent researcher. The treatment allocation was provided by telephone after consent was obtained. The research physiotherapist was not blinded to treatment allocation and it was not possible to blind patients in either group.Observed data for the trial outcome measures were summarised using means and medians as appropriate, depending on the assumed normality or otherwise of each outcome. Variability was assessed using a standard deviation or inter-quartile range. Temporal changes in the relationship between operative and non-operative treatment groups, and associated variability, were demonstrated using box-and-whisker plots. Independent sample t-tests were used to assess the significance of observed differences between operative  and non-operative (conservative) groups and between randomised and preference groups, for the primary outcome measure (DRI) at nine months post-injury; significance was set at the 5% level. In addition to the main analysis, a multiple regression analysis was undertaken to adjust for the potential confounding effects of patient age and gender prior, to assessing the effects of the main trial treatment factors.Table Clinical trials involving surgery are difficult to conduct and especially so in the context of acute injury. The patients are frequently in pain and are admitted into an unfamiliar acute care setting which makes the process of obtaining informed consent problematic. Trials comparing operative and non-operative treatment are particularly difficult as the patient may see the non-operative optionas a 'lesser intervention'. These factors, coupled with the aforementioned difficulties associated with comparing any two complex interventions, have led some authors to question whether randomised controlled trials are possible in this setting.A comprehensive cohort study, where all patients fulfilling the eligibility criteria for a trial are followed up regardless of their consent to randomisation, may be an alternative trial design to overcome these obstacles. Comprehensive cohort designs within the elective setting have demonstrated an 'equal split' within the preference arms . HoweverThe results of this study have shown that a comprehensive cohort design is acceptable to patients, demonstrated by only 2/51 eligible participants refusing to take part. The high participation rate enables the results to be generalised within the wider context of the NHS. This pilot trial has also shown no clinically relevant or statistically significant differences between operative and non-operatively managed patients, although there is obviously a great potential for type II error . (The stAlthough practically feasible, the benefit of a parallel preference group was undermined in this trauma trial, due to a large majority of patients preferring non-operative management. Consequentially, the estimate of the magnitude of the effect size remains imprecise. Therefore, it has to be questioned whether the increase in staff time and resources required to follow-up the preference group is appropriate.Conclusive evidence for the management of acute ruptures of the Achilles tendon is lacking. This is a complex intervention and the Medical Research Council has suggested that the 'traditional' randomised controlled trial design may not be appropriate to evaluate complex interventions. The inclusion of a parallel preference group alongside a randomised controlled trial may increase the sample size, but has cost and resource implications.Funding bodies appear reluctant to provide the extra cost associated with a comprehensive cohort study design. Inclusion of the parallel preference group increased the number of patients in this trauma study. However, this did not increase the accuracy of the estimate of the treatment effect because of the strong patient preference for one treatment arm.The authors declare that they have no competing interests.RSK was involved in the acquisition, analysis and interpretation of data, drafting and revising the article and final approval. JA was involved in the conception and design, critically evaluating the article and final approval. NRP was involved in the analysis and interpretation, critically evaluating the article and final approval. MLC was involved in the conception and design, interpretation of data, drafting and evaluating the article and final approval.All authors have read and approved the submissionThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2288/11/39/prepub


Defects in head and neck after tumor resection often provide significant functional and cosmetic deformity. The challenge for reconstruction is not only the aesthetic result, but the functional repair. Cancer may involve composite elements and the in sano resection may lead to an extensive tissue defect. No prospective randomized controlled studies for comparison of different free flaps are available. There are many options to cover defects and restore function in the head and neck area, however we conclude from experience that nearly all defects in head and neck can be closed by 5 different free flaps: radial forearm flap, free fibula flap, anterior lateral thigh flap, lateral arm flap and parascapular flap. Resection of advanced-staged malignancies of the upper aerodigestive tract often require advanced reconstructive procedures. Many patients suffer from poor nutrition, pulmonary disease, arteriosclerosis, liver insufficiency and clotting disorders.The ideal reconstruction should be performed in a single stage operation, should be reliable and restore swallowing. Besides direct closure, healing by secondary intention, skin grafts and local flaps, free flaps should be performed depending on the patient's needs. Limited life expectancy in tumor patients argues for a reconstructive method that will return the patient to reasonable function in a time appropriate to the history of the tumor.deltopectoral flap came up in the 70ies, first described in 1971 by Bakamjian [The akamjian . The recThe pectoralis maior musculocutaneous flap is sourced by the pectoral branch of the acromiothoracic branch and became a workhorse for head and neck reconstruction. Aryian was first to describe this flap in 1979 . The limThe pedicled latissimus dorsi musculocutaneous flap was first described to cover defects in head and neck in 1978 by Quillen , the flaThe internal mammary artery perforator flap (IMAP) is a new flap, which can be harvested from the ventral thorax either horizontally or vertically orientated. Rotation arc allows defect closure at the neck and lower head. However, its application has to be defined yet .The radial forearm flap Table  is the wIn patients with arteriosclerosis a reversed Allen test or an angiogram is advised.- Skin incision preserving fascia at the ulnar border of skin paddle- Radial to flexor carpi radialis tendon: radial artery taken with fascia- Dissection of artery and veins proximally; including subcutaneous veins- Ligating distal artery and veins- Primary skin closure or split thickness skin graft (in combination with collagen matrix)The lateral arm flap Table  was firs- Skin incision at the posterior circumference of the flap, taken with the underlaid fascia- Dissection to the lateral intermuscular septum and including into the flap: posterior radial collateral artery- Flap raising at the anterior margin of the flap sacrificing the posterior cutaneous nerve of the forearm and the radial nerve (loop)- Dividing the intermuscular septum directly at the humerus- Primary skin closure or split thickness skin graftThe anterior lateral thigh flap (ALT) Table  was deli- Preoperative hand held doppler examination half way between the ASIS and the lateral patella border to evaluate the perforating vessels- Incision over the rectus femoris muscle 3 cm from the lateral intermuscular septum taken with fascia to include the intermuscular septum- Identification of the pedicle, if necessary: muscular perforators , circumcision of the skin island- Dissection of the vascular pedicle to the lateral circumflex femoral arteryThe scapular flap Table  was depi- Medial incision with fascia overlying the infraspinatus muscle, blunt dissection of the flap from teres minor and infraspinatus muscle to the posterior muscle triangle: circumflex scapular artery- Vessel loop around circumflex scapular artery and dissecting the pedicle preserving the bone perforators, if bone has to be harvested- If necessary osteotomy of the scapula bone segmentThe parascapular flap Table  was desc- Flap elevation from distal to proximal preserving fascia- Vascular pedicle appears immediately superior to the superior border of teres maior muscle, superior skin incision after exposure of the vessels, dissection proceeds from superior to inferior , elevation of the muscle creating a muscle strip between the cranial pole of the skin paddle and the vascular pedicle- Dividing side branches of the thoracodorsal vessels (use for the TAP flap without any muscle)The transverse rectus abdominis flap (TRAM) Table  was firsThe rectus abdominis muscle can also be taken on the same pedicle with or without a skin island to fill up dead space after soft tissue or bone removal, and if necessary covered with skin graft. If the skin is orientated vertically, the flap is named VRAM flap .- Skin incision in the lower abdominal wall, dissection of the subcutaneous fat preserving superficial inferior epigastric artery and vein (in case of performing a SIEA flap), cranial skin incision- Dissection from the lateral to the medial aspect taken care of the perforators in the lateral and medial line on both sides- Pick the best perforator, temporarily clip out the other perforators and watch the flap's circulation- Selection of the best perforator (sometimes 2-4 perforators are necessary), incision of the fascia longitudinally in direction of the pubis, intramuscular dissection of the perforator, save segmental intercostals nerves, rectus muscle can be taken with the perforators (TRAM)- Deep inferior epigastric artery is taken as long as necessary for the pedicle length- After flap transplantation repair of the anterior sheath of the rectus with a braided resorbable suture (mesh at big fascia defects which cannot be closed without tension), adherence zone undermining up to the xiphoid process, closure of abdomen in layers after exteriorizing the umbilicusIn 1989 Hildago performed the first fibula osteocutaneous flap - Circumcision of the skin paddle, elevation bone, skin paddle and posterior intermuscular septum- Distal osteotomy of fibula (6-8 cm distance to the ankle), proximal osteotomy of fibula (5 cm distance to fibula head)- Anterior septum incised between the osteotomies, periosteum remains untouched; harvesting of bone and distal ligation of fibular artery and vein after dislocation of fibula and incising interosseous membraneThe free jejunal graft Table  was the - Midline laparotomy, ligament of Treitz is identified in the left upper quadrant, small bowel is followed 40-60 cm below ligament of Treitz- Vascular arcades identified by transillumination, jejunal segment longer than the defect has to be selected, marking the segment's proximal portion- Complete division of mesentery, vasa recta are clamped- Bowel clamping with atraumatic clamps, isolation of the jejunal segment, harvesting of the bowel using intestinal stapling- Free dissection of the jejunal artery and veinSanders described the first iliac crest flap Table  using th- Incision 2 cm superior to the connection of pubic tubercle and anterior superior iliac spine, starting lateral from femoral artery- Ligature of the superficial epigastric vessels- Incision of the inguinal ligament parallel to its fibers, transsection of the internal oblique muscle, deep circumflex iliac artery is palpated in the groove formed by transverses and iliacus muscle, blunt dissection (vessel loop)- Transsection of the muscles from the iliac crest- Distal osteotomy of the iliac crest, ligation of the vascular pedicle at the distal osteotomy, proximal osteotomy, flap harvestingEvery particular area requires special qualities and tissues to restore function by flap transplantation. Choosing the most appropriate flap implies the proper diagnosis of defect size and its complexity, as well as necessary tissue components and the patient's condition.®) underneath the skin graft. In this way the aesthetic outcome and the range of motion are improved.The radial forearm flap requires the integrity and patency of the palmar arch. Disadvantages are possible cold intolerance and an unsightly scar at the donor site with limitation in motion. The large diameter of the vessels and the long pedicle are very helpful when planning and performing the anastomoses. The radial forearm flap can be harvested in parallel to tumor resection which helps to keep operation time low. To minimize problems with skin graft healing due to underlying tendons it is suggested to harvest the flap without fascia and to use a collagen matrix (such as MatridermThe lateral arm flap can be used the restore intraoral defects. Koapting the posterior cutaneous nerve with the lingual nerve was described to feature a high success rate of neurocutaneous reinnervation . In compThe ALT flap shows difficulties in obese patients because of the thickness of the subcutaneous fat tissue. In these cases it can be derogatory to cover defects in the oral cavity and the hypopharyngeal region due to its thickness. The course of the pedicle shows enormous variation: the pedicle can run through the vastus lateralis instead of going through the intermuscular septum . One advThe latissimus dorsi flap shows constant anatomy with a reliable pedicle and an enormous length and width. A simultaneous harvesting of the flap to head and neck cancer surgery is nearly impossible, which prolongs operation time and demands intraoperative position change of the patient. The donor site morbidity of the latissimus dorsi is quite high: seroma can occur, and shoulder function can be impaired . The latAs in the latissimus dorsi flap scapular/parascapular flaps cannot be raised at the same time as tumor ablation. The donor site of the scapular/parascapular flap has fewer complications compared to the latissimus donor site, as it creates no hole.TRAM/DIEP and isolated rectus abdominis muscle flaps can be harvested parallel to tumor resection, no intraoperative patient change is necessary. These flaps show a save and certain blood supply with a long pedicle. The thickness of these flaps depends on the patient's general size. If possible, DIEP flap should be chosen rather than TRAM flap to avoid abdominal wall weakness and herniation .Muscle flaps provide good tissue bulk, but in the long run they begin to shrink and sag, which makes long-term results inconstant to the postoperative situation.The free jejunal graft and its complications were described by Coleman . DespiteFor restoration of bony defects the fibula osteocutaneous flap is convenient because of the possibility to raise the flap parallel to tumor resection in a two team approach. The quality of the skin paddle is comparable to the radial forearm flap but the hairiness of the skin paddle can incommode the patient, especially in intraoral situations. The vascular pedicle can reach up to 15 cm with a large diameter which allows performing anastomoses easily . The higThe iliac crest flap has a reliable pedicle and offers a wide variation of combinations of bone, muscle and skin flap. This flap is highly suited to reconstruct mandible. The skin paddle is often bulky; especially in obese patients it is difficult to harvest this flap. If the flap is too bulky for the recipient site it can be harvested as crest bone with oblique abdominis muscle and a skin graft without a skin paddle. In many times herniation occurs, even long lasting pain, neuropathy, gait disturbance and impotence were described . The natDisa found that most defects can be reconstructed with jejunum, rectus, forearm and fibula flap . NeliganReconstruction of hypopharynx is a challenge for the plastic surgeon. A watertight conduit is needed, that can be punctated tracheoesophageal for speech. This is rarely successful in free jejunal transfers due to the mucus that leads to a wet-sounded voice and a loss of stability .Depending on defects size, required pedicle length and individual donor site situation we recommend reconstruction of soft tissue in oral cavity and hypopharynx with fasciocutaneous tissue from radial forearm, lateral arm, anterior lateral thigh or parascapular/scapular Table . Due to In our experience procedures should be performed in a single stage procedure to reduce hospitalisation and complications which in many cases can be attributed to secondary wound infections, radiation depending problems and strictures due to secondary healing. ENT surgeons and Plastic surgeons have to establish an attentive multi disciplinary approach to provide optimal oncologic and reconstructive procedures for their patients.Written informed consent was obtained from the patients for publication the accompanying images in this review. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.ICW and HF worked on the literature research and assembled the article together. All authors read and approved the final manuscript.


Nature-based tourism has the potential to enhance global biodiversity conservation by providing alternative livelihood strategies for local people, which may alleviate poverty in and around protected areas. Despite the popularity of the concept of nature-based tourism as an integrated conservation and development tool, empirical research on its actual socioeconomic benefits, on the distributional pattern of these benefits, and on its direct driving factors is lacking, because relevant long-term data are rarely available. In a multi-year study in Wolong Nature Reserve, China, we followed a representative sample of 220 local households from 1999 to 2007 to investigate the diverse benefits that these households received from recent development of nature-based tourism in the area. Within eight years, the number of households directly participating in tourism activities increased from nine to sixty. In addition, about two-thirds of the other households received indirect financial benefits from tourism. We constructed an empirical household economic model to identify the factors that led to household-level participation in tourism. The results reveal the effects of local households' livelihood assets  on the likelihood to participate directly in tourism. In general, households with greater financial , physical , human , and social  capitals and less natural capital  were more likely to participate in tourism activities. We found that residents in households participating in tourism tended to perceive more non-financial benefits in addition to more negative environmental impacts of tourism compared with households not participating in tourism. These findings suggest that socioeconomic impact analysis and change monitoring should be included in nature-based tourism management systems for long-term sustainability of protected areas. Establishing protected areas is among the major strategies for stemming the rapid loss of global biodiversity. Over the last half century the total coverage of protected areas worldwide has increased by ten-fold whereas the trend in global biodiversity loss continues Although the new approaches have gradually become mainstream concepts in conservation programs, there is still a lack of convincing empirical evidence that they are effective in achieving desired and balanced social, economic, and ecological goals Livelihood assets refer to the capital endowments owned by a household and include financial, human, natural, physical, and social capital Different assets are required to achieve different livelihood goals. Households with more assets tend to be more versatile in choosing livelihood strategies Nature-based tourism is an important ecosystem service and one key activity in which rural households in developing countries can engage with and which has been used pervasively in ICDPs Despite all the promises, in practice nature-based tourism sometimes results in significant negative environmental and socioeconomic impacts. The lack of local community involvement was found to be one of the top reasons behind such failures To better understand the role that tourism plays in biodiversity conservation, systematic research with empirical data and quantitative analysis on the various direct and indirect financial and non-financial benefits and impacts that tourism brings to local communities in and near protected areas is needed The aim of the study was to examine the nature, extent, and drivers of local households' participation in, and benefiting from, nature-based tourism in a biosphere reserve during a period of fast economic transition from agriculture and natural resources extraction to tourism. Applying the tourism area life theory, we identified various types of direct and indirect financial and non-financial benefits from tourism development over multiple life stages and modeled the determinants of household-level tourism participation. This study expands the understanding of the diverse socioeconomic impacts of tourism in protected areas.The specific objectives of the study were to (1) enrich the conservation literature with longitudinal analysis of residents' participating and benefiting from tourism in protected areas, (2) demonstrate that livelihood assets can be a valid predictor of households' likelihood of tourism participation, (3) illustrate the relationship between tourism participation and local residents' environmental awareness and conservation attitudes, and (4) provide protected area managers with useful policy options that may encourage and facilitate more tourism participation at local levels to assist rural residents and to enhance biodiversity conservation. From these objectives, three research questions emerged:What are the various ways that local residents participate in and benefit from tourism?How do the quantity and structure of livelihood assets owned by local households affect their likelihood to participate in tourism?Do people in tourism-participating households have particular perceptions of the socioeconomic and environmental impacts of tourism development?http://www.humanresearch.msu.edu/).Permission from the Wolong Administration Bureau was sought and obtained before the individual subjects were contacted. Because many adult subjects were not literate, a verbal consent process was used. A verbal consent script was read to the subjects. Interviews proceeded only after the subjects gave their verbal consent. In case of non-consent, no further information was recorded. Because signed consent forms constitute a possible source of concern for the protection of respondents' confidentiality, signatures were collected during the verbal consent process. The study, including the verbal consent process and script, was reviewed and approved by the Institutional Review Board (IRB) of the Michigan State University , a global conservation icon 2 in 1975 Wolong Nature Reserve  is home to the largest wild population of Giant Pandas  of local croplands were reclaimed into tree plantation under a series of local and national payment for ecosystem services programs. Other similar programs were also implemented to pay local households to stop logging, to monitor the forests, and to plant trees in previously logged land Tourism has been proposed and adopted as a new development tool to provide alternative income to local farmers and generate additional funds for conservation in the reserve since 1980s In the early 2000s, the reserve's first ecotourism development master plan was approved by the provincial and central government and the reserve entered a fast tourism development stage. A series of tourism infrastructure development projects, mainly spurred by outside investments, were implemented. For instance, six million dollars were invested to remodel the then largest hotel in the reserve into a new four-star hotel Tourists from around the globe came to the reserve. Seeing pandas in captivity was the top reason for tourists, especially international tourists, to visit the reserve. Many also came to enjoy the forests and the mountainous landscape and to observe wildlife, mainly birds . The Wolong township, where the Wolong Giant Panda Museum, China's first museum for single species, and most of the accommodation facilities were located, hosted the majority of the panda and nature tourists. These tourists usually stayed one to two days and spent almost all their time in key tourism sites and had little interaction with local people, except private hotel owners and managers and souvenir and grocery sellers. While in the other township, Gengda, a different type of tourism started to emerge in 2003. Because of the high elevation, the summer temperature in the reserve is much cooler than that in the nearby cities, every year hundreds of urban residents in Chengdu metropolitan areas came to Gengda township and stayed over a prolonged period in the summer While overall numbers of tourists and receipts from tourism increased sharply and peaked in 2006 , signs oOver the last three decades tourism in the reserve seemed to have followed the model of tourism area life cycle and had gone through the exploration stage in 1980s and involvement stage in 1990s and entered the development stage in 2000s. It was expected that tourism in the reserve would reach a new peak when the road upgrade was completed in early 2008 to welcome the Beijing Olympic Game visitors. However, on 12 May 2008, a devastating (7.9 Mw) earthquake struck the reserve and the surrounding area in Sichuan province. The earthquake and its associated landslides caused extensive damage to the reserve's forests and infrastructure, including the main road and many tourism facilities As households are the basic units in which people organize activities such as food and energy consumption, and household members usually make joint or coordinated decisions regarding resource allocation, employment opportunities, and economic production In 1999, we conducted an initial round of a questionnaire survey to collect baseline information on the socioeconomic status of local households. Because groups are the basic units of human organization in rural China, we conducted in-house personal interviews with a random sample of 220 households  stratified on all groups in the reserve We revisited the sampled households in 2005, 2006, and 2007, the peak tourism development period prior to the earthquake. Besides collecting similar demographic and socioeconomic data as in 1999, we paid special attention to the financial benefits local households received from tourism development. Data required for traditional economic impact analysis are often unavailable in under-developed rural areas because of the lack of reliable accounting/tax systems for small entrepreneurs In 2005, we conducted an additional questionnaire survey  and askeThe locations of households and of key tourism sites inside the reserve, including two township centers and the entrances of two major tourism attractions , were obIn this study, a tourism household was defined as having at least one of its members working on activities directly related to the tourism sector between 2005 and 2007. All other households were classified as non-tourism households. Only tourism households received direct financial benefits from tourism, while both tourism and non-tourism households may have received indirect financial benefits from tourism. The non-financial benefits of tourism were measured based on the interviewees' perceptions of the social benefits of tourism.We used existing information from the longitudinal survey data to construct household livelihood asset portfolios. Surrogates for all five types of capital were computed : a) finak represents the effect parameter of the explanatory variables, and Xk represents the explanatory variables in the model, which include livelihood asset variables and township as a contextual factor. Coefficients in a logistic model give the change in the log-odds of tourism participation for a unit change in the explanatory variables. To facilitate interpretation of the coefficients, we report the odds ratios, which are interpreted as the amount by which the odds of tourism participation are multiplied for each unit change in the explanatory variable. Odds ratios equal to 1 represent no effect; odds ratios greater than 1 represent positive effects; and odds ratios less than 1 represent negative effects.We used logistic regression procedures to estimate parameter values in multivariate models of household-level tourism participation. Logistic regression is an appropriate statistical technique for analyzing models of dichotomous dependent variables. We report parameters from the logistic regression equations in the form:To estimate the accuracy and reliability of the model we conducted a ten-fold cross validation We further examined how household-level tourism participation might affect local residents' perceptions and attitudes toward tourism development in the reserve. Because local households' choice of participating in tourism was not the result of a randomized or natural experiment, systematic differences between tourism and non-tourism households may constitute confounding effects, thus making it spurious to estimate the effects of household-level tourism participation on the interviewees' perceptions/attitudes. The self-selection nature of tourism participation creates a counterfactual question – “what would be the perception/attitude of a person in a tourism household if his/her household were not directly participating in tourism?” Ignoring this issue may lead to invalid inferences We approached this issue with a propensity score weighting methodology Therefore, a tourism household is weighted by 1/e(x) and a non-tourism household is weighted by 1/(1−e(x)). In this way, more weight is assigned to a tourism household with a lower propensity score and to a non-tourism household with a higher propensity score, such that the estimation of the average causal effect focuses mainly on the strongest overlap in propensity between the two groups. The weight is then used in a series of weighted linear regressions  and weighted logistic regressions (for Yes/No questions in category a). In addition to the household-level participation in tourism, we controlled for the household's locations (township and travel cost distance to key tourism sites) and social ties and the respondent's age, education, gender, and occupation as covariates in these regression models (see detailed descriptive statistics of these control variables in Supporting Information www.spss.com). Significance levels were set at 0.05, 0.01, and 0.001.All statistical modeling and analyses were conducted using PASW Statistics 18, Release Version 18.0.0  out of the 220 households sampled directly participated in tourism-related activities, with four owning private hotels and five selling souvenirs . The numDuring the peak tourism development period (2005–2007) many local households also received indirect financial benefits from tourism development . For insChanges in the basic socioeconomic status of the randomly sampled households from the tourism involvement stage (late 1990s) to the peak development stage (2005–2007) are listed in A final sample of 215 households was included in the logistic regression model after excluding two households whose income data in the tourism involvement stage were incomplete and three households that were not present in 2005 (due to death or emigration). The binomial logistic regression model on household tourism participation includes 11 independent variables, the descriptive statistics of which are listed in All five categories of capital seem to influence the likelihood of household-level participation in tourism. The annual household income in 1998  was a significant explanatory variable and higher income in tourism involvement stage increased the odds of tourism participation (p<0.05), but the non-agriculture income percentage in 1998, an indicator of the household's economic reliance on non-farm income opportunities before the tourism boom, was not significant. In terms of human capital, households with more laborers were significantly more likely (p<0.05) to be involved in tourism with each additional laborer increased the odds of household tourism participation by 2.06. Education had a positive effect on the likelihood of the household's participation in tourism (p<0.01), but household size did not. Households with more cropland  tended not to participate in tourism (p<0.001). The more it cost physically to travel between a household and the closest key tourism site , the less likely (p<0.01) the household would participate in tourism. A household's social capital has some influence on its likelihood to take part in tourism. Having a kinship relationship with government officials and village or group heads increased the odds of tourism participation by nine times (p<0.01) and three times (p<0.05), respectively. Township was also a significant predictor since households located in Wolong township, where the main tourism attractions were located, were significantly more likely (p<0.05) to participate in tourism than households in Gengda township.In 2005, households were revisited and the heads or their spouses were asked a series of questions on their knowledge and perceptions of tourism development in the reserve. A total of 192 households answered the questions, including 55 tourism households and 137 non-tourism households. When the non-tourism household heads (or their spouses) were asked about what prevented their household members from participating in tourism, a variety of barriers were reported. Financial and physical limitations were mentioned most often, including lack of start-up funds (60.1%), household location being far from key tourism sites (57.5%), and lack of land and housing to start a tourism business (27.5%). Fifteen interviewees (10.1%) stated that the lack of transparent and supportive local tourism policies made them feel uncertain about the economic potential of tourism development. Other respondents referred to human and social capitals, such as the lack of social connections (9.4%), the lack of labor (6.5%), being too old to have a business (5.1%), and the lack of experience (4.3%). These responses are consistent with the logistic model results on determinants of household-level tourism participation.We measured tourism's non-financial benefits on the basis of local people's perceptions in 2005. The interviewees were asked about how they interacted with tourists. Being in a tourism household increased the odds of communicating with tourists and receiving information about job opportunities from tourists by 7.17 (p<0.001) and 3.44 times (p<0.001), respectively . In contResidents perceived socioeconomic benefits occurring to their households from tourism . Almost Local people's perceptions of the environmental impacts of tourism development are listed in Despite the high level of overall economic leakage reported in a previous study Nevertheless, the overall magnitude of economic benefit that local community received from tourism was yet limited and there was still disparity in the tourism-derived benefit distribution within the local community. Slightly over one-quarter of our sampled households earned some income directly from tourism. This direct tourism income was not the most important source of income for most households, except those who owned or managed a year-around hotel or restaurant (∼5%). At a reserve level in 2006, income from the service sector represented only 7.4% of the total rural economic income in the two townships Our results showed households receiving more direct financial benefits tended to perceive more non-financial benefits. They tended to communicate more with tourists and exchange information with tourists; and they perceived more positive impacts of tourism on their standards of living. Despite some minor conflicts reported, the advantages of tourist-resident contact seem to outweigh the disadvantages, because such communications may help to break the feeling of isolation of rural minorities and visitors in the reserve, create mutual awareness of each group, and provide an opportunity to learn from each other. Such contact can be a starting point for more fundamental inter-cultural encounters, through which the educational potential of nature-based tourism can be realized. As these financial and non-financial benefits accrue faster to some tourism households than others, the existing disparity in the livelihood assets between tourism and non-tourism households may increase. This may further augment social and economic differentiation within the community.Besides the socioeconomic benefits to local residents, nature-based tourism also has the potential to enhance the environmental awareness and attitudes of local residents From a policy perspective, the experience learned from past tourism development in Wolong Nature Reserve is of great value for making relevant interventions in the future. The 2008 earthquake, which reset the tourism development in the area, offers an opportunity for the reserve to develop tourism that may better benefit the poor. The post-earthquake reconstruction plan includes a new round of local household relocations from remote mountainous areas to roadside areas, with their cropland being reclaimed for tree and bamboo plantation as one way to restore more habitats for the giant panda and other wildlife species. To construct new tourism facilities in the Gengda township, a significant amount of cropland was requisitioned with cash compensation to the affected households. While growing cash crop still constitutes an important and stable income source of many households, those who had to trade their cropland with cash compensation will inevitably be facing more limited livelihood options in the future. In the short run, many households may earn wage-labor income from the ongoing infrastructure reconstruction projects. But after the completion of reconstruction, as tourism has been identified as the major economic development tool in the reserve and the surrounding region, the importance of tourism-related income for the local households will be even greater in the future than before the earthquake. The Wolong Administration Bureau needs to design and implement policies to improve local households' capacities to pursue tourism as a major livelihood strategy. On the one hand, policies that specifically target the poor and help augment their livelihood assets  are needed. On the other hand, other regulations that encourage tourism operators to transfer significant amounts of benefits to the poor are also needed. For example, the government may require outside tourism operators or developers to preferentially provide job opportunities to people from the poorer households, rather than letting nepotism prevail as it has in the past Perhaps more importantly, involvement and integration of local communities into the entire tourism development process is critical for achieving ecological and socioeconomic sustainability in protected areas Last but not least, our results highlight the strength of longitudinal data and quantitative analysis in understanding the impacts and effectiveness of nature-based tourism and ICDPs in general. While the need to conduct environmental monitoring of nature-based tourism is well recognized Supporting Information S1The questionnaire on local residents' perceptions and attitude toward tourism development in Wolong Nature Reserve, China.(DOC)Click here for additional data file.Table S1Descriptive statistics of the household and individual level variables in estimating the effects of household-level tourism participation on local residents' perceptions.(DOC)Click here for additional data file.


Hospital-acquired infections create a significant burden to the healthcare system. To understand the economic impact, a model was developed to assess the cost of differences in catheter-related bloodstream infections (BSI) in ICUs based on either closed or open albumin systems.A model was developed with the aim of showing the economic consequences of differences between intravenous (i.v.) infusions of albumin via open or closed infusion containers. The model took a healthcare perspective in the UK. The impact of central venous catheter-related BSI was evaluated. The model took differences in BSI rates and the associated cost consequences for the hospital into account. The model bases on the evidence that closed system delivery helps to reduce the risk of external contamination, which decreases the BSI rate and reduces overall mortality -3. We asThe economic model shows the potential cost saving by switching from open to closed albumin administration systems. It is measured in occurrence of BSI in the ICU, estimated occurrence of BSI in the albumin population and incidence of overall mortality in the ICU and cost of BSI per albumin patient. Finally, the model describes the potential cost savings by switching to a closed system. Using closed albumin delivery systems may overall provide a cost saving for the hospital and healthcare sector. Assuming 800 patients treated in an ICU per year with all in all 4,800 ml albumin, the total annual cost saving would be £24,000 switching from open to closed albumin infusions.Switching from an open to a closed albumin infusion system may result in a reduction in the risk of external contamination, resulting in less infection and may provide a cost saving for the healthcare system.