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Healthcare expenditure on pharmaceuticals, especially innovative oncology drugs, is escalating. Current knowledge on this topic is largely limited to studies conducted upon reimbursement of new drugs. We investigated how endogenous factors (e.g., changed reimbursement criteria, such as an expanded indication) and exogenous factors (e.g., competing drugs) affect the level and trends of innovative oncology drug utilization in the Taiwan National Health Insurance (NHI) system, both upon reimbursement and afterward. This retrospective longitudinal study analyzed monthly data (January 2009 to December 2014) from the NHI Research Database on the consumption (prescribing volume) of 15 innovative oncology drugs reimbursed by the NHI between 2007 and 2013. Effects of endogenous and exogenous factors on drug utilization were evaluated using interrupted time series analyses. In segmented regression analyses, changed drug prescribing volume after the indication expanded (endogenous factor) was statistically significant; however, drug volume did not change significantly after prescription restrictions changed. First‐competitors and non‐first‐competitors (exogenous factors) were significantly associated with drug prescription levels or utilization rates. Taking sorafenib as an example, the post‐reimbursement drug prescribing volume did not change significantly after its therapy line changed (endogenous factor), whereas the reimbursement of first‐competitors (exogenous factor) was significantly associated with a lower level or usage rate of sorafenib. Utilization of innovative oncology drugs in Taiwan changed dramatically after NHI reimbursement, driven largely by expanded indications and new competitors. Drug utilization evaluations should investigate both endogenous and exogenous factors.

Nowadays, many consumers prefer foods with a high content of nutraceuticals that contribute to the prevention or healing of chronic diseases. Therefore, in recent years, more and more researchers have studied the bioefficiency, safety, and toxicity of nutraceutical-enriched foods. The key stage of nutraceutical bioefficiency is oral bioavailability, which involves the following processes: the release of nutraceuticals from food matrices or nanocarriers in gastrointestinal fluids, the solubilization of nutraceuticals and their interaction with other components of gastrointestinal fluids, the absorption of nutraceuticals by the epithelial layer, and the chemical and biochemical transformations into epithelial cells. These processes are endogenous factors that greatly influence the bioavailability of nutraceuticals. In addition to endogenous factors, the bioavailability of nutraceuticals is also affected by exogenous factors, such as: physicochemical properties of nutraceuticals, food matrix, food processing and storage, and so forth. Both the endogenous and exogenous factors are comprehensively analyzed in this review. Thus, the physicochemical and enzymatic processes involved in food digestion are described, highlighting the role of each stage of gastrointestinal tract (mouth, stomach, and intestine) in nutraceuticals bioaccessibility. The structure and functions of the mucus and epithelial layers, the mechanisms involved in the active and passive transport of nutraceuticals through the cell membrane, and phase I and phase II metabolism reactions are also discussed. Finally, this review focuses on several types of bioactive-loaded nanocarriers such as lipid-based, surfactant-based, and biopolymeric nanocarriers that improve the bioavailability of nutraceuticals.

As heterogeneous immune cells, macrophages mount effective responses to various internal and external changes during disease progression. Macrophage polarization, rather than macrophage heterogenization, is often used to describe the functional differences between macrophages. While macrophage polarization partially contributes to heterogeneity, it does not completely explain the concept of macrophage heterogeneity. At the same time, there are abundant and sophisticated endogenous and exogenous substances that can affect macrophage heterogeneity. While the research on endogenous factors has been systematically reviewed, the findings on exogenous factors have not been well summarized. Hence, we reviewed the characteristics and inducing factors of heterogeneous macrophages to reveal their functional plasticity as well as their targeting manoeuvreability. In the process of constructing and analysing a network organized by disease‐related cells and molecules, paying more attention to heterogeneous macrophages as mediators of this network may help to explore a novel entry point for early prevention of and intervention in disease.

Summary Woody plants store large quantities of carbon (C) and nutrients. As plants senesce and decay, these stores transfer to the soil or other organisms or are released to the atmosphere. Exogenous factors such as topographic position and microclimatic and edaphic conditions tied to locations affect decay rates; however, we know less about how exogenous relative to endogenous factors such as morphological, anatomical and chemical construction tied to plant species affect these rates, especially across different tissue types. We monitored stem, fine branch and leaf decay over 1 year in ‘rot plots’ distributed across four watersheds in ridge top and valley bottom habitats in a temperate deciduous oak-hickory forest at Tyson Research Center, MO, USA, in the Ozark Highlands for 21 species of woody plants that vary in their constructions. We found poor coordination across tissues in construction and decay, which likely reflects how functional constraints on living tissues influence recalcitrance to decay. Additionally, for all three tissues, species membership and construction were better predictors of decay than was location. Of the construction traits, chemical composition including total fibre, lignin, cellulose, hemicellulose and concentrations of multiple microelements were the best predictors of decay, although the strength of these relationships differed among tissues. Synthesis. We have long known that rates of biogeochemical cycling are influenced by exogenous factors, such as climatic and edaphic factors. Here, we show across plant tissues that endogenous factors, including species identity and tissue construction, can have stronger controls on rates of decay within our study system than do exogenous factors. However, it is likely that the relative strengths of these different controls change through time and among tissues. We predict that anatomical and morphological controls may be more important at early stages and exogenous factors may be more important at later stages of decay.

The role of endogenous (i.e. limited dispersal, intraspecific competition, aggregation) and exogenous (i.e. resource patchiness, heterogeneous landscapes, spatially structured habitat) factors on the spatial distribution of herbivores can be inferred from theoretical models in intensively managed or heterogeneous landscapes but not in extensively managed crops. In the present study, we examined aggregation patterns and the influence of environmental and spatial factors on the distribution of Altica sylvia Malloch larvae within extensively managed blueberry fields to determine how exogenous and endogenous factors affect this defoliator. Altica sylvia larvae and defoliation exhibited clumped within-field distributions. A lack of correspondence between larval density and defoliation indicated that oviposition habitat selection is occasionally suboptimal in this species. Clumped distribution patterns were not explained by endogenous factors or associations with spatially structured variables. Conversely, exogenous factors acting at the patch scale affected distribution patterns because larvae were less abundant in patches located close to forest edges, as well as in patches where weeds or a nonhost blueberry plant occurred. As a result of exogenously-produced variability in A. sylvia spatial distribution, we suggest that focused sampling methods be used to monitor this herbivore. We emphasize the need for similar assessments for herbivores that forage in extensively managed crops or somewhat heterogeneous monocultures.

BACKGROUND: Knowledge on the chemical composition of foods, and on the variation in such components as influenced by endogenous factors, is required for nutritional labelling, dietetic planning and food processing. This study examined the effects of endogenous factors (gender, size and life-cycle stage) on the chemical components (proximate, amino acid, fatty acid, mineral and mercury contents) of smoothhound shark (Mustelus mustelus) meat. RESULTS: Levels of moisture, protein, lipids, ash, amino acids and most minerals were not affected (P>0.05) by the gender, size or life-cycle stages of the sharks. The fatty acid content was higher in females than in males, as well as in non-pregnant females compared to pregnant females. Certain fatty acids decreased in quantity in medium-sized sharks (prior to maturity). Pregnant females had higher aluminium (Al) and copper (Cu) levels than non-pregnant females and mercury (Hg) levels were highest in large male sharks. CONCLUSION: This study has, for the first time, established that endogenous factors have minimal influence on the chemical composition of M. mustelus meat, demonstrating the feasibility of describing an average composition for this species. Additionally, new insights have been obtained on potential safety concerns (mercury) associated with consumption of the meat that require further investigation.

In applied population dynamics the choice of stochastic per capita growth function has implications for population viability analyses, management recommendations, and pest control. This model choice is often based on statistical criteria, mathematical tractability or personal preferences, and general ecological guidelines are either too vague or entirely missing. To identify such guidelines, it is important to understand how exogenous and endogenous factors interact at the individual level and re-emerge at the aggregated population level. We therefore study different types of resource competition (contest vs. scramble competition) and different types of exogenous fluctuations (food and weather fluctuations) at the individual level in a simple individual-based simulation model. We statistically fit the resulting time series to find out (1) which functional form of the growth function (‘hyperbolic’ or ‘exponential’) better describes contest and scramble competition and (2) whether the pattern of population fluctuations resulting from the simulations can be assigned to vertical, lateral or nonlinear perturbations in the stochastic growth function (a classification scheme suggested by Royama 1992, Analytical Population Dynamics, Chapman and Hall, London). We found that the same type of competition can result in ‘hyperbolic’ or ‘exponential’ functional forms, depending on the type of exogenous fluctuations. So it is the interplay between exogenous variability and endogenous resource competition that affects model performance. In contrast to the widespread assumption of vertical (additive) perturbations, our findings highlight the importance of (non-additive) lateral and nonlinear perturbations and their combinations with vertical perturbations. The choice of the stochastic growth function should therefore consider not only statistical criteria but also ecological guidelines. We derive such ecological guidelines from our analysis.

The goal of executive control is to adjust our behaviour to the environment. It involves not only the continuous planning and adaptation of actions but also the inhibition of inappropriate movements. Recently, a proactive form of inhibitory control has been shown, demonstrating that actions can be withheld, in an uncertain environment, thanks to the proactive locking of the mechanism by which motor commands are triggered (e.g. while waiting at traffic lights in a dense pedestrian zone, one will refrain in anticipation of a brisk acceleration when the green light comes on). However, little is known about this executive function and it remains unclear whether the overall amount of inhibitory control can be modulated as a function of the context. Here, we show that the level of this control varies parametrically as a function of the exogenous and endogenous factors setting the task context. We also show that the level of implemented proactive inhibitory control is dynamically readjusted to match the implicit temporal structure of the environment. These observations are discussed in relation to possible underlying functional substrates and related neurological and psychiatric pathologies.

Question: What is the role of exogenous and endogenous factors in determining fluctuations in plant populations? Methods: A total of 29 long-term time series from different plant species was analysed. Data were obtained from the literature as well as from our own surveys. For each series we calculated the autocorrelation function to identify the presence of cyclic dynamics. The existence and the order of density-dependent processes were examined by calculating the partial rate correlation function to obtain the global Lyapunov exponent to assess whether populations exhibited chaotic dynamics. To test the effect of exogenous factors on each population, we used regression analyses to relate mean annual temperature and total annual precipitation to population abundance. Finally, we employed a Mann-Whitney U-test to analyse whether populations that showed endogenous regulation occurred in less variable environments. © 2012 International Association for Vegetation Science., This work was partially funded by FEDER funds and the Spanish Ministry of Innovation and Science (Projects AGL2009-7883 and AGL2007-65698-C03-03) and Junta de Castilla-La Mancha (Project POII10-0123-5554).

We explored the role that exogenous and endogenous competitors for attention play in infants' abilities to encode and retain information over a 6-month period. Sixty-six children visited the laboratory at 15 months, and 32 returned for a second visit at 21 months. Children observed models of conventional- relation and enabling-relation action sequences. Half the children were distracted by a "Mister Monkey" mechanical toy during the conventional-relation sequence, while the other half was distracted during the enabling-relation sequence. The Early Childhood Behavior Questionnaire indexed endogenous factors at both ages. Immediate postmodel production of target actions indexed encoding efficiency, and 6-month production of target actions indexed long-term recall. The exogenous distracter impacted encoding efficiency (i.e., immediate recall), but not long-term recall. Endogenous factors (i.e., temperament) were primarily associated with long-term recall. Of special interest was our finding that endogenous factors, especially surgency, moderated the effect of the exogenous distracter. It appears that when learning conventional-relation sequences in the presence of exogenous distracters, surgency mobilizes attentional resources toward the learning objective; however, when learning enabling-relation sequences under the same conditions, surgency either boosts the saliency of the distracters or boosts children's susceptibility to them.

Aim To investigate spatial autocorrelation of taxonomic stream invertebrate groups (richness and composition) at a large geographical scale and to analyse the importance of exogenous and endogenous factors. Location The Mediterranean Basin. Methods For exogenous factors, we used large-scale factors related to climate, geology and river zonation; for endogenous factors, we used the dispersal mode of each taxonomic group. After describing and analysing spatial patterns of genus richness and genus composition of stream invertebrate groups in the Mediterranean Basin, we computed Moran’s I before and after accounting for the exogenous factors and related it to the endogenous factors. Results In relation to genus richness, most of the taxonomic groups did not show significant spatial autocorrelation, suggesting that no main large-scale exogenous or endogenous factors were important and that local-scale factors were probably controlling taxonomic richness. In contrast, for genus composition, all taxonomic groups except Odonata had significant spatial autocorrelation before accounting for the environment. After accounting for the environment, most taxonomic groups still had a significant spatial autocorrelation, but it decreased with their increasing dispersal ability (from Crustacea to Coleoptera). Thus, spatial taxonomic composition of groups with the strongest dispersal potential is mainly related to exogenous factors, whereas that of groups with weaker dispersal potential is related to a combination of exogenous and endogenous factors. Main conclusions Our results illustrate the importance of dispersal as an endogenous factor causing spatial autocorrelation and suggest that ignoring endogenous factors can lead to misunderstandings when explaining large-scale community patterns.

The reversible cessation of metabolism and growth is a unique biological state. There are two types of organisms which are normally capable of of entering this state (cryptobiosis): (1) propagules of certain organisms and (2) certain rotifers, tardigrades, and nematodes. The latter group of organisms offer a unique opportunity to study the discontinuity of life processes, uncomplicated by simultaneous developmental processes and complex endogenous factors such as those responsible for the maintenance of dormancy. Working hypotheses and lines of research are pointed out in the areas of (1) metabolism during anhydrobiosis, (2) biochemical adaptations to desiccation, (3) morphological adaptations to desiccation.

Since the first report of elevated serum levels of C-reactive protein (CRP) predicting all cause and cardiovascular mortality more than 10 years ago, many other studies have recognized that the uremic milieu is associated with a state of chronic inflammation. The causes for inflammation are multiple and have been well studied in the past 10 years. Nondialysis, uremia related and endogenous factors as well as the dialysis procedure itself may be responsible for the high prevalence of inflammation in dialysis patients. Today, CRP serves to improve overall vascular risk stratification and, in the individual, to detect sources of specific infections. Because multiple factors contribute to the milieu of inflammation, the predictive value of CRP is rather nonspecific in dissecting a cause, with respect to the subcomponents of cardiac, vascular, and even noncardiovascular causes of mortality. So far, no specific pharmacologic treatment, including atorvastatin, has been identified that can substantially reduce CRP and accompanying inflammation.

Cancer appears to be the result of a series of complex biological events of which only the first may involve the genome of a somatic cell. These events originate from endogenous as well as exogenous factors. Among the endogenous factors are the genetic, endocrine and immunologic constitution of the host. The exogenous factors include nutrition, exposure to environmental chemicals, and possible viral infection and are often identified as cocarcinogenic factors (Sivak, 1979; Clayson, 1981). Since these modifying factors are among the critical ones in determining whether a cancer .will arise and threaten its host, the identification o f tumor-promoting agents would be an important public health strategy for the prevention of cancer (Falk, 1976). Tumor promotion is one phenomenon under the rubric of cocarcinogenesis that has been demonstrated in several organ systems in experimental animals and for which strong circumstantial evidence is available that it occurs in humans (Boutwell, 1974; Slaga et al., 1978; Weinstein et al., 1975; Diamond et al., 1978, 1980). In

In this article, we consider the possible reasons and supporting evidence for the comorbidity of chronic pain conditions. To simplify the discussion, we primarily focus on the epidemiology of headache with other pain conditions, dividing studies into those based on children or adolescents and those based on adults. We consider exogenous and endogenous factors, and methodological challenges, in understanding whether and how 2 pain conditions may be related.

Offspring size is thought to strongly affect offspring fitness and many studies have shown strong offspring size/fitness relationships in marine and terrestrial organisms. This relationship is strongly mitigated by local environmental conditions and the optimal offspring size that mothers should produce will vary among different environments. It is assumed that offspring size will consistently affect the same traits among populations but this assumption has not been tested. Here I use a common garden experiment to examine the effects of offspring size on subsequent performance for the marine bryozoan Bugula neritina using larvae from two very different populations. The local conditions at one population (Williamstown) favour early reproduction whereas the other population (Pt. Wilson) favours early growth. Despite being placed in the same habitat, the effects of parental larval size were extremely variable and crossed generations. For larvae from Williamstown, parental larval size positively affected initial colony growth and larval size in the next generation. For larvae from the other population, parental larval size positively affected colony fecundity and negatively affected larval size in the next generation. Traditionally, exogenous factors have been viewed as the sole source of variation in offspring size/fitness relationship but these results show that endogenous factors (maternal source population) can also cause variation in this crucial relationship. It appears offspring size effects can be highly variable among populations and organisms can adapt to local conditions without changing the size of their offspring.

The concept of local development is defined as a particular form of regional development, one in which endogenous factors occupy a central position. A stages model of local development is proposed: 1) the emergence of local entrepreneurship; 2) the “take off” of local enterprises; 3) the expansion of these enterprises beyond the local region; and 4) the achievement of a regional economic structure that is based upon local initiatives and locally created comparative advantages. The theoretical and empirical foundations of this model are examined, with particular emphasis upon the roles of the entrepreneur and of human capital in the process of economic growth, and upon the spatial effects of the expansion of the firm.

Prostate cancer has the highest prevalence of any nonskin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating androgens will develop microscopic prostate cancer if they live long enough. This review is a contemporary and comprehensive, literature-based analysis of the putative risk factors for human prostate cancer, and the results were presented at a multidisciplinary consensus conference held in Crystal City, Virginia, in the fall of 2002. The objectives were to evaluate known environmental factors and mechanisms of prostatic carcinogenesis and to identify existing data gaps and future research needs. The review is divided into four sections, including 1) epidemiology (endogenous factors [family history, hormones, race, aging and oxidative stress] and exogenous factors [diet, environmental agents, occupation and other factors, including lifestyle factors]); 2) animal and cell culture models for prediction of human risk (rodent models, transgenic models, mouse reconstitution models, severe combined immunodeficiency syndrome mouse models, canine models, xenograft models, and cell culture models); 3) biomarkers in prostate cancer, most of which have been tested only as predictive factors for patient outcome after treatment rather than as risk factors; and 4) genotoxic and nongenotoxic mechanisms of carcinogenesis. The authors conclude that most of the data regarding risk relies, of necessity, on epidemiologic studies, but animal and cell culture models offer promise in confirming some important findings. The current understanding of biomarkers of disease and risk factors is limited. An understanding of the risk factors for prostate cancer has practical importance for public health research and policy, genetic and nutritional education and chemoprevention, and prevention strategies.

Recent successes in identifying the genes and associated proteins underlying several familial neurodegenerative conditions have not always resulted in accounts as to why the associated patterns of neuronal damage are so specific and limited. Here, with reference to Huntington's disease, we present a general scheme to show how the mutant protein could interact with associated proteins to form an aggregation product. This could lead to neuronal death by direct actions on caspases, or by raising the levels of intracellular calcium ions and reactive oxygen species above a threshold that cannot be resisted by the protection normally conferred by endogenous factors such as calcium binding proteins, free radical scavengers and trophic factors. The local distributions of vulnerability and protective factors could ultimately dictate the pattern of damage induced by the mutant gene. IUBMB Life, 55: 293-298, 2003

Irritant contact dermatitis (ICD) is a common dermatological diagnosis in which endogenous and exogenous factors have been implicated. This review explores ethnicity as a possible endogenous factor. While there is a clinical consensus that blacks are less reactive and Asians are more reactive than Caucasians, the data supporting this hypothesis rarely reaches statistical significance. The studies reviewed do not provide sufficient evidence to determine that race is a predisposing factor to the degree of irritation in ICD. We conclude that race could be a factor in ICD, which has practical consequences regarding topical product testing requirements, an ever-expanding global market, occupational risk assessment, and the clinical thinking about ICD. Pitfalls in defining differences are discussed.

Administration of autoantigens through DNA immunizations or via the oral route can prevent progression of islet destruction and lower the incidence of type 1 diabetes in animal models. This beneficial effect is mediated by autoreactive regulatory CD4 lymphocytes, and it is known that their induction depends on the precise dose and route of antigen administration. However, it is not clearwhich endogenous factors determine when such immunizations lead to activation of regulatory versus aggressive autoreactive lymphocytes and how a deleterious outcome can be avoided. Here we describenovel observations made in an animal model for virally induced type 1 diabetes, showing that the endogenous expression levels of the islet antigens and glutamic acid decarboxylase determine whetherimmunization with these antigens is beneficial or detrimental. Lower expression levels in β-cells support immune regulation resulting in induction of autoreactive, regulatory cells characterized by increased IL-4 production (Th2-like), whereas higher levels favor Th1-like autoaggressive responses characterized by augmented IFN-γ generation. Co-immunization with an IL-4-expessing plasmid reduces the risk of augmenting autoaggression and in this way increases the safety margin of this immune-based therapy. Our findings will be of importance for designing safe antigen-specific interventions for human type 1 diabetes.

Carcinogenesis may be effected not only through exposure to exogenous stimuli but also by genetic and epigenetic influences derived from endogenous factors. In the latter case, the mechanisms are still largely obscure because of the limited availability of appropriate in vivo experimental models. However, continuous feeding of a diet deficient in choline and methionine is well known to cause hepatocellular carcinomas (HCC) in rats in the absence of any known exogenous carcinogens and can serve as a good research model. A semi-synthetic, choline-deficient, L-amino acid-defined (CDAA) diet, containing practically no choline and low methionine, induces HCC with a background of fatty liver and hepatocyte death, subsequent regeneration and fibrosis resulting in cirrhosis. Using the CDAA diet, we have revealed the participation of oxidative injury to DNA and other subcellular components and of alteration in intrahepatic signal transduction pathways in the mechanisms underlying this rat liver carcinogenesis model. In the present paper, the current understanding of endogenous rat liver carcinogenesis, due to dietary choline deficiency, is reviewed.

Projects are a potential source of considerable rent-seeking which detracts from their contributions to rural development. It is the purpose of this paper to out-line the nature of the problems caused by rent-seeking in projects in developing countries, and to identify those situations in which rent-seeking is more likely to be prevalent. Factors influencing susceptibility to rent-seeking are categorized according to whether they are exogenous or endogenous to a particular project. Endogenous factors are decomposed into those embodied in planning and management processes, project attributes or attributes of beneficiaries. This identification provides a platform for suggesting ways of minimizing rent-seeking in rural development projects. © 1998 John Wiley & Sons, Ltd.

Background Gastro-esophageal reflux disease (GERD) is very prevalent and has a high burden on health security system costs. Nevertheless, pathophysiology is complex and not well-understood. Several mechanisms have been proposed: decreased salivation, impaired esophageal clearance, decreased lower esophageal sphincter pressure resting tone, presence of hiatal hernia, increased number of transient lower esophageal sphincter relaxations (TLESRs), increased acid, and pepsin secretion, pyloric incompetence provoking duodeno-gastro-esophageal reflux of bile acids and trypsin. Independent of the relevance of each mechanism, the ultimate phenomenon is that mucosal epithelium is exposed for a longer time to agents as acid and pepsin or is in contact to luminal agents not commonly present in gastric refluxate as trypsin or bile acids. This leads to a visible damage of the epithelium (erosive esophagitis -EE) or impairing mucosal integrity without any sign of macroscopic alteration as occurs in non-erosive reflux disease (NERD). Luminal factors are not the only responsible for such impairment; more recent data indicate that endogenous factors may also play a role. Purpose This review will update the most recent findings on the putative pathophysiological mechanisms and specially will focus on the role of esophageal mucosal integrity in GERD. Methodologies used for the evaluation of mucosal integrity, its relevance in EE and NERD, its involvement in symptoms perception and the effect of luminal and endogenous factors will be discussed.

The lack of organizational adaptability to the external environment has been blamed for the poor development achievements in the less developed countries. Two distinct Papua New Guinea agricultural organizations are used as case studies to illustrate the need for a cultural fit between the external socio-cultural factors and the internal organizational culture for survival. The case studies show that the management of ‘wantokism’ was an important external societal factor, whereas the integration of internal organizational cultural factors, such as those induced by structural changes and the shared norms and expectations of management, are important endogenous factors. The case studies also show that in a high uncertainty/avoidance environment the use of a role-oriented culture is more conducive to sustaining change than a laissez faire people-oriented culture. Some suggestions about how to achieve the best external/internal interaction are offered for consideration. There are, however, methodological and practical management issues that are yet to be resolved before the maximum benefit of organizational culture is realized.

In this paper a new encompassing flexible diffusion model of the epidemic type is proposed and its properties explored. Economic factors are incorporated directly into the model. The new model allows freer interaction between exogenous and endogenous factors in the diffusion process than existing models of this type. The model is applied to the diffusion of colour television ownership in the UK and outperforms the existing models in the literature. The exogenous factors are shown to play a more dominant role in the diffusion of colour television in the UK than existing models allow.

Plant species distributions are generally thought to be chiefly under environmental control, although they may be affected by disturbance events or dispersion properties of the species. The relative importance of these different factors is not easy to evaluate because they often share common spatial patterns, such that an inextricable network of relationships occurs between plant distributions, environmental conditions, disturbance events and endogenous factors such as propagule dispersion. In this paper we propose a method for untangling the common spatial component from the relationship between environmental conditions and the distribution of tree species. Using partial Mantel tests and path analysis, we test models of relationships between these data sets. Results show that in our study area, spatial patterns of species associated with hydric conditions remain largely correlated with environmental conditions. However, mesic sites show more complex forest covers, in which a significant spatial component persists when environmental variation is statistically controlled for. This remaining spatial variability suggests that other factors possessing spatial structure partly explain species distributions.

We propose a change in the use of “appetite suppressant” medication in the treatment of obesity: use it on a long-term basis or not at all. This proposal is based on the theory that “appetite suppressant” medication acts primarily by lowering the regulated level of body weight. We review the concept of the regulation of body weight and present evidence that body weight is regulated in animals of normal weight and in some obese animals. We show that the concept of the regulation of body weight also applies to variations of body weight produced by endogenous factors, such as those related to hibernation, as well as by experimental interventions, such as brain lesions and “appetite suppressant” medication. Evidence of body weight regulation in normal weight and obese humans is presented and clinical significance discussed. We conclude with a discussion of a new role for “appetite suppressant” medication in the treatment of obesity. © 1992 Wiley-Liss, Inc.

Occupational contact dermatitis (OCD) take the first rank of all occupational diseases in many countries. The incidence rate is believed to be around 0.5 to 1.9 cases per 1000 full-time workers per year. However, the true incidence of work-related hand eczema (mostly irritant hand eczema) is highly underreported. The development of OCD is determined by a combination of individual susceptibility (endogenous factors) and exposure characteristics (exogenous factors). Skin contact with irritants and/or allergens is a necessary condition of contact dermatitis and the probability and severity of a reaction depend on the type and intensity of exposure. Epidemiological studies play an important role in observing disease trends, analysing risk factors, and monitoring the effect of preventive measures. Occupational Contact Dermatitis (OCD) has become an issue of increasing importance world-wide, not only due to cost- intensification for employers but also due to impairment of employees’ quality of life. This lecture summarizes some important causes of occupational contact dermatitis in Europe, demonstrates possibilities of prevention based on recently conducted epidemiological studies, and ends by highlighting important future health service and population research issues. The following questions will be discussed: • How common are OCD in different industries and what is the extent of underestimation • What kind of regulations are needed to prevent OCD • How to deal with high risk individuals (atopics) Research into the causes and prevention of occupational contact dermatitis using an epidemiological approach is still in its infancy, yet already there are some pointers that OCD can be prevented effectively.

Mechanical stimulation of dorsal mouse skin by skin massage or removal of the horny layer results in a mutually comparable increase in DNA-labelling and mitotic activity. However, only after injury such as removal of the horny layer hyperplasia develops. This phenomenon, called "hyperplastic transformation" is characterized by a transient abolition of the epidermal G1 chalone responsiveness. There is some indication that the susceptibility to a heat labile factor, probably the epidermal G2 chalone, is not affected. Skin massage neither interferes with the responsiveness to epidermal G1 chalone nor induces "hyperplastic transformation". Mouse tail epidermis shows a "functional hyperplasia" and responds to the G1 chalone. To explain these observations, it is assumed that the epidermal stem cell population is heterogeneous consisting of G1 chalone-sensitive and G1 chalone-insensitive cells.

This paper surveys the possibility and importance of studying social behavior of rats in pharmacology. Social behavior of rats tested in dyadic encounters can be used for studying experimentally induced changes in this behavior. Different exogenous factors like administering psychopharmacological agents or changes in the test environment can easily and reproducibly affect social behavior of rats. The involvement of endogenous factors in social behavior is discussed. In this respect, especially the hormones β-endorphin and γ-MSH seem to act as intrinsic factors involved in the regulation of social behavior. The models described are useful tools for studying the interaction between psychopharmaca and social behavior and may be of importance for studying mechanisms underlying psychopathological disturbances in humans.

Summary A study has been made of the endogenous factors controlling lateral bud initiation and development in the variety Craigella, and two isogenic lines of this variety, Craigella Blind (blbl) and Craigella Lateral Suppressor (isls), in both of which side shoot growth is suppressed to varying degrees. Winter- and summer-sown plants are compared. Lateral Suppressor plants contained higher endogenous levels of auxin in their apices, mature leaves and stems than did normal plants, but lower level of cytokinins in all parts except the stem, where the levels were similar in both types. The levels of abscisic acid-like substances were consistently higher in the stems of Lateral Suppressor plants than in the corresponding tissue of normal plants, but other plant parts showed a more variable pattern. Lateral Suppressor plants contained higher levels of gibberellin than did normal plants. Blind plants contained higher levels of auxin in the apices and stem than did normal plants, but the levels in mature leaves showed no consistent pattern. Higher levels of abscisic acid-like substances were present in the stem and axillary buds of blind plants than in normal plants, with again a more variable pattern in other plant parts. The levels of cytokinins and gibberellins varied considerably between the two sowing dates. A possible hormonal mechanism of control of axillary bud development is discussed.

Tuberization and tuber growth in potato as affected by exogenous and endogenous factors Tuberisation et croissance du tubercule de pomme de terre influencees par les facteurs endogenes et exogenes

All living organisms respond to stimulation, reacting more or less sensitively and more or less typically to a wide variety of energy forms such as light, heat, gravity, pressure (sound), electricity—and chemicals. A living organism responds to an irritation by releasing irritants which—as potential defense substances—are directed against the attacker or assist the organism endogenously in an intrinsic defense reaction. Often very small energy changes perceived by the plant are enough to induce a series of physiological processes ultimately manifested as a glandular reaction or even movement. The irritants involved in these processes act on membranes as defense substances in the presence of an attacker, or as endogenous factors in their own cellular environment. These chemically very diverse low-molecular active principles have been found in many parts of plants and in many plant families. For this reason alone we could speak of a chemical herbarium, but the case is even stronger because, in this botanical documentation, not only the individual chemicals are considered in context but also whole sets of interacting substances, since it is only in these sets that optimal activity is found (just as one considers not only the parts of a plant but also the whole plant in botany).

The literature on the blood chemistry of rainbow trout, Salmo gairdneri Rich., is reviewed from the aspects of experimental methods, electrophoresis, normal values, environmental and endogenous factors including toxic substances and diseases.

Political organization is a contingent, not a fixed, factor for most social groups. For such groups to gain electoral success, they must at some stage take a formal decision to construct a political organization and fight elections. Traditionally, political science has concentrated on the exogenous factors conducive to electoral success: it has rarely examined the endogenous factors which have brought political groups to adopt an electoral strategy and a differentiated organization. This paper argues that exogenous theories are by their nature only partial explanations, in so far as they ignore the endogenous factors of change within political groups. The argument is illustrated by a comparison of three minority nationalist groups in the United Kingdom: the Scottish National Party, Plaid Cymru in Wales, and the Northern Ireland Social Democratic and Labour Party. The paper examines the endogenous organizational changes which have ultimately resulted in each winning a measure of electoral success in the past decade.

The skin, respiratory tract, and gastrointestinal tract are the organ systems through which environmental carcinogenic agents gain entry into the host. Of the several sources of carcinogenic agents, this report is concerned with the two most common in the respiratory environment—urban polluted air and cigarette smoke. Carcinogenic polycyclic aromatic hydrocarbons (PAH) are the most ubiquitous and are present in the highest concentrations. Certain exogenous and endogenous factors significantly modify the biologic action of carcinogenic hydrocarbons. Exogenous factors includes (1) the simultaneous presence and action of anticarcinogenic agents in the environment, (2) their occurrence in a physical state compatible with inhalation and deposition in the respiratory tract, and (3) the presence of factors modifying the host response, particularly in relation to the normal physiologic defenses. The endogenous factors include: (1) the vehicle serving the carcinogenic agents as it affects persistence at site of entry and rate of systemic distribution, (2) the rate of metabolism in the hepatobiliary system, and (3) the existence of anatomic or metabolic abnormalities modifying the tissue response. The metabolism of carcinogenic P AH is, in the truest sense, a pharmacologic detoxification process since the metabolites are either weakly or, as is more common, wholly noncarcinogenic. This suggests that carcinogenic PAH, as they occur in the environment, are the proximate carcinogens. The complexity of the carcinogenic process is emphasized by the multiplicity of factors, many of them noncarcinogenic in themselves, that are concerned with the pathogenesis of neoplastic disease.

The observ·ed rhythmic growth of trees under relatively uniform environmental conditions has been ascribed by some authors to endogenous factors, by others to slight fluctua­ tions of environmental factors. A model for the simulation of rhythmic growth was developed based on the assumption that endogenous rhythms can result from feedback inter­ action between two potentially continuous processes, like shoot and root growth, if the slower process is rate limiting for the faster one. Rhythmic growth in trees would be the consequence of feedback mechanisms needed for maintaining a constant shoot : root ratio. Period length of the rhythms depends upon the rates of the growth processes involved. Em·ironmental factors modify period length through affect­ ing growth rates. Growth patterns predicted by the model compare well with growth measurements of tropical trees. The transition from intermittent to continuous growth, as ob­ served under certain. conditions, can be simulated by varying a single parameter in the model.

Current understanding of the major aspects of breast cancer epidemiology is reviewed. These include exogenous factors such as viruses, and the use of oral contraceptives and of estrogens. Endogenous factors are also described, especially those relating to reproductive experience. Current endocrine hypotheses relating to breast cancer etiology are described, and the estrogen balance hypothesis is presented in detail. A new area of epidemiologic research is now developing rapidly. This relates to the value of the parenchymal pattern as a marker of risk in young women. The role of this factor per se and in relation to other risk factors is described. Current approaches to breast cancer control are inadequate but will be discussed.