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Vaccines can play a crucial role in reducing the negative outcomes of pandemics. In this paper we explore how vaccine perceptions and uptake willingness can be affected by vaccine‐related information, the vaccine's country of origin, and national identity. Study 1 (N = 800) showed that a vaccine manufactured by China was perceived more negatively compared to vaccines from the UK, Germany, and Chile. Providing vaccine effectiveness information (83%) increased preference for waiting for an alternative vaccine and reduced perceived effectiveness of a vaccine from China. Brexit supporters perceived vaccines as less safe in general, and particularly thought of a vaccine from China as less competent, effective, and trustworthy, and were less prepared to have it. Study 2 (N = 601) largely replicated findings of Study 1 regarding the effects of a vaccine's country of origin. Moreover, participants who reported a higher sense of British superiority reported more negative attitudes towards a vaccine from China. However, apart from the aforementioned main effects of Study 2, our attempt to manipulate British identity vis a vis a Global identity in order to examine particular national‐identity related outcomes was not successful. Overall, vaccine characteristics can interact with various social psychological factors, potentially affecting people's perceptions and willingness to uptake particular measures to support personal and public health. [ABSTRACT FROM AUTHOR]

Background: No short patient-reported outcome (PRO) instruments assess overall health status across different obstructive lung diseases. Thus, the wording of the introduction to the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) was modified to permit use in asthma and/or COPD. This tool is called the Chronic Airways Assessment Test (CAAT). Methods: The psychometric properties of the CAAT were evaluated using baseline data from the NOVELTY study (NCT02760329) in patients with physician-assigned asthma, asthma + COPD or COPD. Analyses included exploratory/confirmatory factor analyses, differential item functioning and analysis of construct validity. Responses to the CAAT and CAT were compared in patients with asthma + COPD and those with COPD. Results: CAAT items were internally consistent (Cronbach's alpha: > 0.7) within each diagnostic group (n = 510). Models for structural and measurement invariance were strong. Tests of differential item functioning showed small differences between asthma and COPD in individual items, but these were not consistent in direction and had minimal overall impact on the total score. The CAAT and CAT were highly consistent when assessed in all NOVELTY patients who completed both (N = 277, Pearson's correlation coefficient: 0.90). Like the CAT itself, CAAT scores correlated moderately (0.4–0.7) to strongly (> 0.7) with other PRO measures and weakly (< 0.4) with spirometry measures. Conclusions: CAAT scores appear to reflect the same health impairment across asthma and COPD, making the CAAT an appropriate PRO instrument for patients with asthma and/or COPD. Its brevity makes it suitable for use in clinical studies and routine clinical practice. Trial registration: NCT02760329. Plain language summary: Chronic Airways Assessment Test: a questionnaire adapted to assess overall health in asthma and/or COPD What is it about? Asthma and chronic obstructive pulmonary disease (COPD) can have a significant effect on a person's health and wellbeing. For people with these conditions, most of the health questionnaires available for use in patient care are designed for one specific diagnosis – either asthma (e.g. Asthma Control Test) or COPD (e.g. COPD Assessment Test [CAT]). A small number of questionnaires are available for use in both asthma and COPD, but these either take too long to complete, or do not focus on the overall health of patients. Since the symptoms in asthma and COPD overlap, a health questionnaire is needed for use in both asthma and COPD that can be completed during a routine visit to a doctor. This questionnaire could also help with research into the impact of lung diseases in people who have an unclear diagnosis. The CAT was changed so that people with asthma or COPD (or both) could use the same test. We named this new version the Chronic Airways Assessment Test (CAAT). Our goal was to determine whether CAAT scores meant the same level of health in people with asthma, COPD, or both conditions. The CAAT has eight questions, each scored 0 to 5, and takes only a few minutes to complete. The first three questions ask about the person's symptoms, including how often they cough and whether they have chest mucus or chest tightness. The remaining five questions ask how the person's asthma or COPD (or both) affects their daily life. These questions ask about shortness of breath, difficulties doing activities at home, confidence in leaving their home, whether they sleep soundly and how much energy they have. We found that the CAAT performed similarly in people with asthma or COPD (or both). This indicates that the CAAT score means a similar thing for someone with asthma, COPD or both conditions. Why is it important? The CAAT is a quick and simple way for patients to share with their doctor how bad their symptoms are and how much they affect their daily life. The development of the CAAT means that only one questionnaire is needed to measure the effect of a person's symptoms on their current level of health, whether they have asthma, COPD, or both. This will allow doctors to improve the level of care patients receive. [ABSTRACT FROM AUTHOR]

Objectives: To examine the use of two coding systems used in the THIN UK primary care research database for the coding of telephone encounters between patient and healthcare professional in primary care. This is relevant to other research databases built on GP clinical systems. Consideration of telephone consultations was particularly important during the COVID-19 pandemic as remote interactions between patient and GP are more numerous than before and are likely to remain at a higher frequency. Results: Telephone encounters could either be indicated by a consultation-type code or by a Read code. All three possible combinations (coded by one method, the other method and both) were in use. In 2014, 30% were coded by the consultation-type, 55% by Read codes and 15% by both. In contrast, in 2000, 77% were coded by the consultation-type, 21% by Read codes and 2% by both. This has important implications because national and regional consultation rates by GPs are often estimated from these research databases by looking only at the consultation-type codes and consequently many encounters will not be detected. [ABSTRACT FROM AUTHOR]

Background: No short patient-reported outcome (PRO) instruments assess overall health status across different obstructive lung diseases. Thus, the wording of the introduction to the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) was modified to permit use in asthma and/or COPD. This tool is called the Chronic Airways Assessment Test (CAAT). Methods: The psychometric properties of the CAAT were evaluated using baseline data from the NOVELTY study (NCT02760329) in patients with physician-assigned asthma, asthma + COPD or COPD. Analyses included exploratory/confirmatory factor analyses, differential item functioning and analysis of construct validity. Responses to the CAAT and CAT were compared in patients with asthma + COPD and those with COPD. Results: CAAT items were internally consistent (Cronbach's alpha: > 0.7) within each diagnostic group (n = 510). Models for structural and measurement invariance were strong. Tests of differential item functioning showed small differences between asthma and COPD in individual items, but these were not consistent in direction and had minimal overall impact on the total score. The CAAT and CAT were highly consistent when assessed in all NOVELTY patients who completed both (N = 277, Pearson's correlation coefficient: 0.90). Like the CAT itself, CAAT scores correlated moderately (0.4–0.7) to strongly (> 0.7) with other PRO measures and weakly (< 0.4) with spirometry measures. Conclusions: CAAT scores appear to reflect the same health impairment across asthma and COPD, making the CAAT an appropriate PRO instrument for patients with asthma and/or COPD. Its brevity makes it suitable for use in clinical studies and routine clinical practice. Trial registration: NCT02760329. Plain language summary: Chronic Airways Assessment Test: a questionnaire adapted to assess overall health in asthma and/or COPD What is it about? Asthma and chronic obstructive pulmonary disease (COPD) can have a significant effect on a person's health and wellbeing. For people with these conditions, most of the health questionnaires available for use in patient care are designed for one specific diagnosis – either asthma (e.g. Asthma Control Test) or COPD (e.g. COPD Assessment Test [CAT]). A small number of questionnaires are available for use in both asthma and COPD, but these either take too long to complete, or do not focus on the overall health of patients. Since the symptoms in asthma and COPD overlap, a health questionnaire is needed for use in both asthma and COPD that can be completed during a routine visit to a doctor. This questionnaire could also help with research into the impact of lung diseases in people who have an unclear diagnosis. The CAT was changed so that people with asthma or COPD (or both) could use the same test. We named this new version the Chronic Airways Assessment Test (CAAT). Our goal was to determine whether CAAT scores meant the same level of health in people with asthma, COPD, or both conditions. The CAAT has eight questions, each scored 0 to 5, and takes only a few minutes to complete. The first three questions ask about the person's symptoms, including how often they cough and whether they have chest mucus or chest tightness. The remaining five questions ask how the person's asthma or COPD (or both) affects their daily life. These questions ask about shortness of breath, difficulties doing activities at home, confidence in leaving their home, whether they sleep soundly and how much energy they have. We found that the CAAT performed similarly in people with asthma or COPD (or both). This indicates that the CAAT score means a similar thing for someone with asthma, COPD or both conditions. Why is it important? The CAAT is a quick and simple way for patients to share with their doctor how bad their symptoms are and how much they affect their daily life. The development of the CAAT means that only one questionnaire is needed to measure the effect of a person's symptoms on their current level of health, whether they have asthma, COPD, or both. This will allow doctors to improve the level of care patients receive. [ABSTRACT FROM AUTHOR]

Some theories propose that human cumulative culture is dependent on explicit, system-2, metacognitive processes. To test this, we investigated whether access to working memory is required for cumulative cultural evolution. We restricted access to adults' working-memory (WM) via a dual-task paradigm, to assess whether this reduced performance in a cultural evolution task, and a metacognitive monitoring task. In total, 247 participants completed either a grid search task or a metacognitive monitoring task in conjunction with a WM task and a matched control. Participants' behaviour in the grid search task was then used to simulate the outcome of iterating the task over multiple generations. Participants in the grid search task scored higher after observing higher-scoring examples, but could only beat the scores of low-scoring example trials. Scores did not differ significantly between the control and WM distractor blocks, although more errors were made when under WM load. The simulation showed similar levels of cumulative score improvement across conditions. However, scores plateaued without reaching the maximum. Metacognitive efficiency was low in both blocks, with no indication of dual-task interference. Overall, we found that taxing working-memory resources did not prevent cumulative score improvement on this task, but impeded it slightly relative to a control distractor task. However, we found no evidence that the dual-task manipulation impacted participants' ability to use explicit metacognition. Although we found minimal evidence in support of the explicit metacognition theory of cumulative culture, our results provide valuable insights into empirical approaches that could be used to further test predictions arising from this account. [ABSTRACT FROM AUTHOR]

Population size has been proposed to promote cumulative culture in humans. Experimental evidence from adult humans suggests that one explanatory mechanism might involve combining beneficial information from multiple models. However, it is possible that such combinatory social learning requires cognitive capacities restricted to adult humans. In our task, children aged 5-10 were exposed to two models who consecutively searched a 333 array for rewards. Models revealed different correct and incorrect reward locations. This information could be used by the child to maximise their own score on the same task. We were interested in children's ability to select rewarded locations, and avoid unrewarded ones, revealed by both models. We also manipulated the spatial and temporal displacement of the information available. Results showed that the youngest children were unable to fully benefit from the additional information provided by the two models under spatial and/or temporal displacement. Such displacement likely applies in most real-world cases of cumulative culture therefore our result may offer insight into the constraints on cumulative culture in nonhumans. [ABSTRACT FROM AUTHOR]

Culture has an extraordinary influence on human behavior, unparalleled in other species. Some theories propose that humans possess learning mechanisms biologically selected specifically for social learning, which function to promote rapid enculturation. If true, it follows that information acquired via observation of another's activity might be responded to differently, compared with equivalent information acquired through one's own exploration, and that this should be the case in even very young children. To investigate this, we compared children's responses to information acquired either socially or from personal experience. The task we used allowed direct comparison between these alternative information sources, as the information value was equivalent across conditions, which has not been true of previous methods used to tackle similar questions. Across two 18-month- to 5-year-old samples (recruited in the United Kingdom and China), we found that children performed similarly following information acquired from social demonstrations, compared with personal experience. Children's use of the information thus appeared independent of source. Furthermore, children's suboptimal performance showed evidence of a consistent bias driven by motivation for exploration as well as exploitation, which was apparent across both conditions and in both samples. Our results are consistent with the view that apparent peculiarities identified in human social information use could be developmental outcomes of general-purpose learning and motivational biases, as opposed to mechanisms that have been biologically selected specifically for the acquisition of cultural information. [ABSTRACT FROM AUTHOR]

The use of 'explicitly metacognitive' learning strategies has been proposed as an explanation for uniquely human capacities for cumulative culture. Such strategies are proposed to rely on explicit, system-2 cognitive processes, to enable advantageous selective copying. To investigate the plausibility of this theory, we investigated participants' ability to make flexible learning decisions, and their metacognitive monitoring efficiency, under executive function (EF) load. Adult participants completed a simple win-stay lose-shift (WSLS) paradigm task, intended to model a situation where presented information can be used to inform response choice, by copying rewarded responses and avoiding those that are unrewarded. This was completed alongside a concurrent switching task. Participants were split into three conditions: those that needed to use a selective copying, WSLS strategy, those that should always copy observed information, and those that should always do the opposite (Expt 1). Participants also completed a metacognitive monitoring task alongside the concurrent switching task (Expt 2). Conditions demanding selective strategies were more challenging than those requiring the use of one rule consistently. In addition, consistently copying was less challenging than consistently avoiding observed stimuli. Differences between selectively copying and always copying were hypothesised to stem from working memory requirements rather than the concurrent EF load. No impact of EF load was found on participants' metacognitive monitoring ability. These results suggest that copying decisions are underpinned by the use of executive functions even at a very basic level, and that selective copying strategies are more challenging than a combination of their component parts. We found minimal evidence that selective copying strategies relied on executive functions any more than consistent copying or deviation. However, task experience effects suggested that ceiling effects could have been masking differences between conditions which might be apparent in other contexts, such as when observed information must be retained in memory. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is characterized by insulin deficiency resulting from the selective destruction of pancreatic β-cells by self-reactive T cells. Recent evidence demonstrates that innate immune responses substantially contribute to the pathogenesis of T1D, as they represent a first line of response to danger/damage signals. Here we discuss evidence on how, in a relapsing-remitting pattern, pancreas remodeling, diet, microbiota, gut permeability, and viral/bacterial infections induce the accumulation of leukocytes of the innate arm of the immune system throughout the pancreas. The subsequent acquisition and presentation of endocrine and exocrine antigens to the adaptive arm of the immune system results in a chronic progression of pancreatic damage. This process provides for the generation of self-reactive T-cell responses; however, the relative weight that genetic and environmental factors have on the etiopathogenesis of T1D is endotype imprinted and patient specific. With this Perspectives in Diabetes, our goal is to encourage the scientific community to rethink mechanisms underlying T1D pathogenesis and to consider therapeutic approaches that focus on these processes in intervention trials within new-onset disease as well as in efforts seeking the disorder's prevention in individuals at high risk. [ABSTRACT FROM AUTHOR]

Many human cultural traits become increasingly beneficial as they are repeatedly transmitted, thanks to an accumulation of modifications made by successive generations. But how do later generations typically avoid modifications which revert traits to less beneficial forms already sampled and rejected by earlier generations? And how can later generations do so without direct exposure to their predecessors' behavior? One possibility is that learners are sensitive to cues of non‐random production in others' behavior, and that particular variants (e.g., those containing structural regularities unlikely to occur spontaneously) have been produced deliberately and with some effort. If this non‐random behavior is attributed to an informed strategy, then the learner may infer that apparent avoidance of certain possibilities indicates that these have already been sampled and rejected. This could potentially prevent performance plateaus resulting from learners modifying inherited behaviors randomly. We test this hypothesis in four experiments in which participants, either individually or in interacting dyads, attempt to locate rewards in a search grid, guided by partial information about another individual's experience of the task. We find that in some contexts, valid inferences about another's behavior can be made from partial information, and these inferences can be used in a way which facilitates trait adaptation. However, the benefit of these inferences appears to be limited, and in many contexts—including some which have the potential to make inferring the experience of another individual easier—there appears to be no benefit at all. We suggest that inferring previous behavior from partial social information plays a minimal role in the adaptation of cultural traits. [ABSTRACT FROM AUTHOR]

This account presents information on all aspects of the biology of Lathraea clandestina L. (Purple Toothwort) that are relevant to understanding its ecological characteristics and behaviour. The main topics are presented within the standard framework of the Biological Flora of the British Isles: distribution, habitat, communities, responses to biotic factors, responses to environment, structure and physiology, phenology, floral and seed characters, hervbivores and disease, history and conservation.Lathraea clandestina is a holoparasitic perennial herb essentially devoid of chlorophyll which can parasitize a wide range of host plants. These include ferns, herbs and trees although it is most frequent on Populus spp., Salix spp. and Alnus glutinosa. It usually flowers between April and June. It is pollinated principally by long‐tongued bumblebees (Bombus spp.). The flowers arise directly from a subterranean stem and have specialised features to reduce nectar theft particularly by ants and birds. Seeds are explosively ejected and can spread up to 8 m. For most of the year, plants are not visible.Lathraea clandestina is native to Belgium, throughout much of western France as far north as Brittany, Andorra, the Pyrenees in France and Spain, northern Spain and in Italy where it has a very disjunct distribution. It has been widely introduced in Britain and Ireland and is extensively naturalised. It has been introduced and naturalised also in The Netherlands, Switzerland and Germany. It is very commonly a riparian plant and can spread downstream.As a parasite dwelling underground for most of the year, L. clandestina draws solutes from the xylem of the host root using hydathode glands on the inner surface of the scales. Consequently a stream of liquid is exuded which affects surrounding vegetation. Lathraea clandestina still exhibits vestiges of some of the enzyme activity associated with photosynthesis and has a very limited ability to assimilate inorganic nitrogen and carbon. Its chloroplast genome is less reduced than in many other holoparasitic plants. [ABSTRACT FROM AUTHOR]

Over the last two decades, increased availability of human pancreatic tissues has allowed for major expansions in our understanding of islet biology in health and disease. Indeed, studies of fixed and frozen pancreatic tissues, as well as efforts using viable isolated islets obtained from organ donors, have provided significant insights toward our understanding of diabetes. However, the procedures associated with islet isolation result in distressed cells that have been removed from any surrounding influence. The pancreas tissue slice technology was developed as an in situ approach to overcome certain limitations associated with studies on isolated islets or fixed tissue. In this Perspective, we discuss the value of this novel platform and review how pancreas tissue slices, within a short time, have been integrated in numerous studies of rodent and human islet research. We show that pancreas tissue slices allow for investigations in a less perturbed organ tissue environment, ranging from cellular processes, over peri-islet modulations, to tissue interactions. Finally, we discuss the considerations and limitations of this technology in its future applications. We believe the pancreas tissue slices will help bridge the gap between studies on isolated islets and cells to the systemic conditions by providing new insight into physiological and pathophysiological processes at the organ level. Article Highlights: Human pancreas tissue slices represent a novel platform to study human islet biology in close to physiological conditions. Complementary to established technologies, such as isolated islets, single cells, and histological sections, pancreas tissue slices help bridge our understanding of islet physiology and pathophysiology from single cell to intact organ. Diverse sources of viable human pancreas tissue, each with distinct characteristics to be considered, are available to use in tissue slices for the study of diabetes pathogenesis. [ABSTRACT FROM AUTHOR]

Languages spoken in larger populations are relatively simple. A possible explanation for this is that languages with a greater number of speakers tend to also be those with higher proportions of non‐native speakers, who may simplify language during learning. We assess this explanation for the negative correlation between population size and linguistic complexity in three experiments, using artificial language learning techniques to investigate both the simplifications made by individual adult learners and the potential for such simplifications to influence group‐level language characteristics. In Experiment 1, we show that individual adult learners trained on a morphologically complex miniature language simplify its morphology. In Experiment 2, we explore how these simplifications may then propagate through subsequent learning. We use the languages produced by the participants of Experiment 1 as the input for a second set of learners, manipulating (a) the proportion of their input which is simplified and (b) the number of speakers they receive their input from. We find, contrary to expectations, that mixing the input from multiple speakers nullifies the simplifications introduced by individuals in Experiment 1; simplifications at the individual level do not result in simplification of the population's language. In Experiment 3, we focus on language use as a mechanism for simplification, exploring the consequences of the interaction between individuals differing in their linguistic competence (as native and non‐native speakers might). We find that speakers who acquire a more complex language than their partner simplify their language during interaction. We ultimately conclude that adult learning can result in languages spoken by more people having simpler morphology, but that idiosyncratic simplifications by non‐natives do not offer a complete explanation in themselves; accommodation—by comparatively competent non‐natives to less competent speakers, or by native speakers to non‐natives—may be a key linking mechanism. [ABSTRACT FROM AUTHOR]

A number of studies have shown that the motor actions of one individual can affect the attention of an observer. In one notable example, “social inhibition of return,” observers are relatively slow to initiate a response to a location where another individual has just responded. In the present article we examine the degree to which this phenomenon can be considered a social effect. We find that unlike the related social, or “joint,” Simon effect, social inhibition of return is not influenced by competitive versus cooperative interaction, nor by live versus recorded interaction. We do find however that co-actors need to turn-take in order for the effect to occur. Thus, so-called “social” inhibition of return only reaches a minimal threshold to be considered a social phenomenon. [ABSTRACT FROM AUTHOR]

Despite considerable interest in both action perception and social attention over the last 2 decades, there has been surprisingly little investigation concerning how the manual actions of other humans orient visual attention. The present review draws together studies that have measured the orienting of attention, following observation of another’s goal-directed action. Our review proposes that, in line with the literature on eye gaze, action is a particularly strong orienting cue for the visual system. However, we additionally suggest that action may orient visual attention using mechanisms, which gaze direction does not (i.e., neural direct mapping and corepresentation). Finally, we review the implications of these gaze-independent mechanisms for the study of attention to action. We suggest that our understanding of attention to action may benefit from being studied in the context of joint action paradigms, where the role of higher level action goals and social factors can be investigated. [ABSTRACT FROM AUTHOR]

A number of studies have shown that observation of another person's actions can modulate one's own actions, such as when 2 individuals cooperate in order to complete a joint task. However, little is known about whether or not direct matching of specific movements is modulated by the goals of the actions observed. In a series of 7 experiments, we employed an action observation paradigm in which 2 coactors sat opposite each other and took turns to reach out to targets presented on a shared workspace. Importantly, coactors performed either the same goal at the reached-to location or a different goal. Although results consistently showed that the reaching action of 1 individual slows the observer's reaching action to the same spatial location, the effect was not modulated according to the adopted goals of coactors. These findings challenge the notion that the processes involved in the imitation of specific movements code for the action goals of those movements. [ABSTRACT FROM AUTHOR]

Background: Patients' smoking status is routinely collected by General Practitioners (GP) in UK primary health care. There is an abundance of Read codes pertaining to smoking, including those relating to smoking cessation therapy, prescription, and administration codes, in addition to the more regularly employed smoking status codes. Large databases of primary care data are increasingly used for epidemiological analysis; smoking status is an important covariate in many such analyses. However, the variable definition is rarely documented in the literature.Methods: The Secure Anonymised Information Linkage (SAIL) databank is a repository for a national collection of person-based anonymised health and socio-economic administrative data in Wales, UK. An exploration of GP smoking status data from the SAIL databank was carried out to explore the range of codes available and how they could be used in the identification of different categories of smokers, ex-smokers and never smokers. An algorithm was developed which addresses inconsistencies and changes in smoking status recording across the life course and compared with recorded smoking status as recorded in the Welsh Health Survey (WHS), 2013 and 2014 at individual level. However, the WHS could not be regarded as a "gold standard" for validation.Results: There were 6836 individuals in the linked dataset. Missing data were more common in GP records (6%) than in WHS (1.1%). Our algorithm assigns ex-smoker status to 34% of never-smokers, and detects 30% more smokers than are declared in the WHS data. When distinguishing between current smokers and non-smokers, the similarity between the WHS and GP data using the nearest date of comparison was κ = 0.78. When temporal conflicts had been accounted for, the similarity was κ = 0.64, showing the importance of addressing conflicts.Conclusions: We present an algorithm for the identification of a patient's smoking status using GP self-reported data. We have included sufficient details to allow others to replicate this work, thus increasing the standards of documentation within this research area and assessment of smoking status in routine data. [ABSTRACT FROM AUTHOR]

When two individuals alternate reaching responses to targets located in a visual display, reaction times are longer when responses are directed to where the co-actor just responded. Although an abundance of work has examined the many characteristics of this phenomenon it is not yet known why the effect occurs. In particular, some authors have argued that action representation mechanisms are central to the effect. However, here we present evidence in support of an account in which the representation of action is not necessary. First, the basic effect occurs even when participants cannot see their co-actor's movement but, importantly, have their attention shifted to a target side via an attentional cue. Second, its time course is too short-lasting to function effectively as a component of action planning. Finally, unlike other joint action phenomena, the effect is not modulated by higher order mechanisms concerned with the personal attributes of a co-actor. Taken together, these results suggest that this particular joint action phenomenon is due to attentional rather than action mechanisms. [ABSTRACT FROM AUTHOR]

The present study aimed to quantify the demand of seven generic, closed agility drills. Twenty males with experience in invasion sports volunteered to participate in this study. They performed seven, closed agility drills over a standardised 30-m distance. Physical demand measures of peak velocity, total foot contacts, peak impacts, completion time, and maximum heart rate were obtained via the use of wearable sensor technologies. A subjective rating of perceived exertion (RPE) was also obtained. All measures, with the exception of maximum heart rates and RPE were able to delineate drills in terms of physical and physiological demand. The findings of this study exemplify the differences in demand of agility-type movements. Drill demand was dictated by the type of agility movement initiated with the increase in repetitiveness of a given movement type also contributing to increased demand. Findings from this study suggest agility drills can be manipulated to vary physical and physiological demand. This allows for the optimal application of training principles such as overload, progression, and periodisation. [ABSTRACT FROM AUTHOR]

In humans, cultural traditions often change in ways that increase efficiency and functionality. This process, widely referred to as cumulative cultural evolution, sees beneficial traits preferentially retained, and it is so pervasive that we may be inclined to take it for granted. However, directional change of this kind appears to distinguish human cultural traditions from behavioral traditions that have been documented in other animals. Cumulative culture is therefore attracting an increasing amount of attention within psychology, and researchers have begun to develop methods of studying this phenomenon under controlled conditions. These studies have now addressed a number of different questions, including which learning mechanisms may be implicated and how the resulting behaviors may be influenced by factors such as population structure. The current article provides a synopsis of some of these studies and highlights some of the unresolved issues in this field. [ABSTRACT FROM AUTHOR]

A growing number of authors have argued that humans automatically compute the visual perspective of other individuals. Evidence for this has come from the dot perspective task in which observers are faster to judge the number of dots in a display when a human avatar has the same perspective as the observer compared to when their perspectives are different. The present experiment examined the ‘spontaneous perspective taking’ claim using a variant of the dot perspective paradigm in which we manipulated what the avatar could see via physical barriers that either allowed the targets to be seen by the avatar or occluded this view. We found a robust ‘perspective taking’ effect despite the avatar being unable to see the same stimuli as the participant. These findings do not support the notion that humans spontaneously take the perspective of others. [ABSTRACT FROM AUTHOR]

Increasing evidence, both functional and morphological, supports the concept of increased intestinal permeability as an intrinsic characteristic of type 1 diabetes ( T1D) in both humans and animal models of the disease. Often referred to as a 'leaky gut', its mechanistic impact on the pathogenesis of T1D remains unclear. Hypotheses that this defect influences immune responses against antigens (both self and non-self) predominate, yet others argue hyperglycemia and insulitis may contribute to increased gut permeability in T1D. To address these complicated issues, we herein review the many conceptual role(s) for a leaky gut in the pathogenesis of T1D and suggest ways that if true, therapeutic interventions aimed at the gut-pancreas axis may prove promising for future therapeutic interventions. [ABSTRACT FROM AUTHOR]

A learner’s linguistic input is more variable if it comes from a greater number of speakers. Higher speaker input variability has been shown to facilitate the acquisition of phonemic boundaries, since data drawn from multiple speakers provides more information about the distribution of phonemes in a speech community. It has also been proposed that speaker input variability may have a systematic influence on individual-level learning of morphology, which can in turn influence the group-level characteristics of a language. Languages spoken by larger groups of people have less complex morphology than those spoken in smaller communities. While a mechanism by which the number of speakers could have such an effect is yet to be convincingly identified, differences in speaker input variability, which is thought to be larger in larger groups, may provide an explanation. By hindering the acquisition, and hence faithful cross-generational transfer, of complex morphology, higher speaker input variability may result in structural simplification. We assess this claim in two experiments which investigate the effect of such variability on language learning, considering its influence on a learner’s ability to segment a continuous speech stream and acquire a morphologically complex miniature language. We ultimately find no evidence to support the proposal that speaker input variability influences language learning and so cannot support the hypothesis that it explains how population size determines the structural properties of language. [ABSTRACT FROM AUTHOR]

The article explores evolving concepts underlying the pathogenesis of type 1 diabetes. Particular focus is given to autoimmunity as the formative cause of diabetes during the 1980s, as well as efforts to preserve C-peptide production in clinical trials. Topics discussed include human immune response, disease subtypes, and inflammatory process in the pancreas. The role of coxsackievirus in the pathogenesis of type 1 diabetes and human pancreatic islets are also mentioned.

In the nearly 100 years since the discovery of therapeutic insulin, significant research efforts have been directed at finding the underlying cause of type 1 diabetes (T1D) and developing a "cure" for the disease. While progress has clearly been made toward each of these goals, neither vision has been fulfilled. With increasing pressure from both public and private funders of diabetes research, growing impatience of those with T1D at the lack of practical discoveries, increased competition for research funds, uncertainties on the reproducibility of published scientific data, and questions regarding the value of animal models, the current research environment has become extraordinarily difficult to traverse from the perspective of investigators. As a result, there is an increasing pressure toward performance of what might be considered "safe" research, where the aim is to affirm existing dogmas rather than to pioneer efforts involving unconventional thought. Psychologists refer to this practice as "observational bias" while cartoonists label the process the "streetlight effect." In this Perspective, we consider notions in T1D research that should be subject to bold question and provide additional concepts, many somewhat orphan to research efforts, whose investigation could lead to a means for truly identifying the cause of and a cure for T1D. [ABSTRACT FROM AUTHOR]

Abstract: When two individuals alternate reaching responses to visual targets presented on a shared workspace, one individual is slower to respond to targets occupying the same position as their partner’s previous response. This phenomenon is thought to be due to processes that inhibit the initiation of a movement to a location recently acted upon. However, two distinct forms of the inhibition account have been posited, one based on inhibition of an action, the other based on inhibition of an action and location. Furthermore, an additional recent explanation suggests the phenomenon is due to mechanisms that give rise to action congruency effects. Thus the three different theories differ in the degree to which action co-representation plays a role in the effect. The aim of the present work was to examine these competing accounts. Three experiments demonstrated that when identical actions are made, the effect is modulated by the configuration of the visual stimuli acted upon and the perceptual demands of the task. In addition, when the co-actors perform different actions to the same target, the effect is still observed. These findings support the hypothesis that this particular joint action phenomenon is generated via social cues that induce location-based inhibition of return rather than being due to shared motor co-representations. [Copyright &y& Elsevier]

• Social information use improved with age but only for exploration of alternatives. • Children were able to account for others' conflicting motivations from 4 years. • Alignment of the demonstrator's and children's goals did not influence performance. • From 6 years children could infer the outcome of others' behaviour. • Rates of copying were low at all ages, even when it was the appropriate response. The ability to take mental states such as goals into account when interpreting others' behavior has been proposed to be what sets human use of social information apart from that of other animals. If so, children's social information use would be expected to change as their understanding of others' mental states develops. We explored age-related changes in 3- to 7-year-old children's ability to strategically use social information by taking into account another's goal when it was, or was not, aligned with their own. Children observed as a puppet demonstrator selected a capsule, peeked inside, and chose to accept or reject it, following which children made their own selection. Children were able to account for others' conflicting motivations from around 4 years of age and reliably inferred the outcome of others' behavior from 6 years. However, using social information based on such inferences appeared to be challenging regardless of whether the demonstrator's goal was, or was not. aligned to that of the participant. We found that social information use improved with age; however, this improvement was restricted to cases in which the appropriate response was to avoid copying the demonstrator's selection. In contrast to previous research, appropriate copying responses remained at chance. Possible explanations for this unexpected pattern of results are discussed. The cognitive challenge associated with the ability to account for others' goals could offer humans a significant advantage over that of other animals in their ability to use social information. [ABSTRACT FROM AUTHOR]

The limited evidence of complex culture in non-human primates contrasts strikingly with human behaviour. This may be because non-human primates fail to use information acquired socially as effectively as they use information acquired individually. Here, monkeys were trained on a stimulus discrimination task with a win-stay, lose-shift (WSLS) reward structure. In a social learning condition, the experimenter performed an information trial by choosing between the available stimuli; in an individual condition, monkeys made this choice themselves. The monkeys' subsequent test trials displayed the same stimulus array. They were rewarded for repetition of rewarded ('win-stay') and avoidance of unrewarded ('lose-shift') information trial selections. Nine monkeys reached our pre-determined performance criterion on the initial two-stimulus stage. Their ability to generalise the WSLS strategy was then evaluated by transfer to a three-stimulus stage. Minimal differences were found in information use between the social and individual conditions on two-stimuli. However, a bias was found towards repetition of the information trial, regardless of information source condition or whether the information trial selection was rewarded. Proficient subjects were found to generalise the strategy to three-stimuli following rewarded information trials, but performed at chance on unrewarded. Again, this was not found to vary by source condition. Overall, results suggest no fundamental barrier to non-human primates' use of information from a social source. However, the apparent struggle to learn from the absence of rewards hints at a difficulty with using information acquired from unsuccessful attempts; this could be linked to the limited evidence for cumulative culture in non-human primates. [ABSTRACT FROM AUTHOR]

The article presents a case study of 26-year-old woman diagnosed with type 1 diabetes. Topics discussed include the medical history of the patient, the diagnosis and treatment of her disease, an overview of the disease, the cause of her death, the pancreatic transplantation, and the medical comorbidities of the disease.

Over the past decade, knowledge of the pathogenesis and natural history of type 1 diabetes has grown substantially, particularly with regard to disease prediction and heterogeneity, pancreatic pathology, and epidemiology. Technological improvements in insulin pumps and continuous glucose monitors help patients with type 1 diabetes manage the challenge of lifelong insulin administration. Agents that show promise for averting debilitating disease-associated complications have also been identified. However, despite broad organisational, intellectual, and fiscal investments, no means for preventing or curing type 1 diabetes exists, and, globally, the quality of diabetes management remains uneven. This Seminar discusses current progress in epidemiology, pathology, diagnosis, and treatment of type 1 diabetes, and prospects for an improved future for individuals with this disease. [ABSTRACT FROM AUTHOR]

Background: The ability to perform many daily tasks relies on good visual acuity at various distances. A review of existing measures of visual function revealed gaps in task content, particularly tasks that rely on intermediate vision. Purpose: This research sought to extend the content base and visual range coverage of tasks used to assess visual function. Methods: Ophthalmology patients ( n = 72) with myopia, hyperopia, presbyopia, astigmatism, cataracts, and/or glaucoma were involved in various qualitative sub-studies, including life event journaling, telephone interviews, and both on-line and face-to-face focus groups. The resulting journal entries and transcripts were thematically analyzed to identify visual tasks that rely on visual acuity in the near, intermediate, and distant visual ranges. Results: A wide variety of distance-specific visual tasks were identified. Certain types of tasks relied on distance vision, such as; ambulation, driving, leisure and sports, and social functions. Other task groupings such as technology use and activities of daily living relied primarily on near and intermediate vision. Two new content areas were identified, technology use and safe task performance. Conclusions: This thematic analysis provides a rich body of information about tasks that affect daily life and are made more difficult by poor visual acuity at various distance ranges. [ABSTRACT FROM AUTHOR]

This paper investigates the role that property titling legislation has had on the form of high-density residential development. A conceptual framework is developed for theorising the role of property legislation in moderating the impact of urban land use policy. It is argued that the impact of legislation on urban form is much more significant and direct than is often implied or suggested in reviews of planning policy. It is argued that property legislation has a greater role than simply supporting the implementation of urban planning policy. Property legislation has a moderating influence on policy and provides a barrier to the implementation of urban policy. To support this argument, the paper considers the development and implications of Western Australia’s strata titling legislation for the form of high-density development in that state’s capital city. [ABSTRACT FROM PUBLISHER]

A commentary on the role of β-cells in the development of type 1 diabetes is presented. The authors discussed the 1986 article "Death of a Beta Cell: Homicide or Suicide?" by Gian Franco Bottazzo. They considered the mechanisms of antigenic processing that resulted to immune responsiveness. They showed a prototypic model for the β-cell's death under the pathogenesis of type 1 diabetes.

Background: To develop a population-based cohort of people with ankylosing spondylitis (AS) in Wales using (1) secondary care clinical datasets, (2) patient-derived questionnaire data and (3) routinely-collected information in order to examine disease history and the health economic cost of AS. Methods: This data model will include and link (1) secondary care clinician datasets (i.e. electronic patient notes from the rheumatologist) (2) patient completed questionnaires (giving information on disease activity, medication, function, quality of life, work limitations and health service utilisation) and (3) a broad range of routinely collected data (including; GP records, in-patient hospital admission data, emergency department data, laboratory/pathology data and social services databases). The protocol involves the use of a unique and powerful data linkage system which allows datasets to be interlinked and to complement each other. Discussion: This cohort can integrate patient supplied, primary and secondary care data into a unified data model. This can be used to study a range of issues such as; the true economic costs to the health care system and the patient, factors associated with the development of severe disease, long term adverse events of new and existing medication and to understand the disease history of this condition. It will benefit patients, clinicians and health care managers. This study forms a pilot project for the use of routine data/patient data linked cohorts for other chronic conditions. [ABSTRACT FROM AUTHOR]

Patients' adherence to antiretroviral medications is a primary determinant of both the effectiveness of treatment and the clinical course of HIV/AIDS. This empirical review is intended to compare the relative importance of patient and treatment characteristics on nonadherence behavior and the impact of nonadherence on treatment failure. Articles cited in PubMed and published between 2006 and June 2008 ( n = 200) were reviewed to select those that address patient or treatment characteristics associated with nonadherence. Twenty-two articles were selected that provided odds ratio or hazard ratio statistics that quantified predictors of patients' level of nonadherence (e.g., <80%, 80%–95% and >95%). Results were summarized using random effects meta-analytic models. Predictors of nonadherence were divided into four predictive clusters (clinical predictors, comorbid predictors, treatment competence predictors, and dosing predictors). The summary odds ratios (ORs) of nonadherence for each cluster (in order of strength) were treatment competence 2.0 (95% confidence interval [CI]: 1.6–2.6), clinical predictors 1.6 (95% CI: 1.4–1.8), comorbid predictors 1.6 (95% CI: 1.4–1.8), and dosing predictors 1.5 (95% CI: 1.3–1.7). The effect of nonadherence on treatment failure supported the findings of two prior empirical reviews (OR 2.0, 95% CI: 1.6–2.5). Within dosing predictors, a pill burden of more versus less than 10 pills per day was associated with a much higher odds of nonadherence than twice versus once daily dosing or small differences in the number of types of antiretroviral treatments in a regimen. These results provide insight into the relative importance of various determinants of patient nonadherence that may inform the design of patient educational initiatives and initiatives to simplify treatment regimens. [ABSTRACT FROM AUTHOR]

In the present study we have purified and characterized murine pancreatic elastase. The enzyme was extracted from acetone powders of mouse pancreas, fractionally precipitated with ammonium sulfate, and further purified by ion exchange chromatography to a single band on SDS-PAGE. The mouse enzyme exists in a proform, which was activated by removing a signal peptide by tryptic cleavage. The active form of mouse pancreatic elastase was shown by ultracentrifugation to have a molecular weight of 25.9 kDa and a frictional ratio of 1.26. The pH optimum for proteolytic activity was 8.0. Kinetic measurements were made with a variety of substrates and inhibitors and compared with elastases from other sources. The enzymatic properties and kinetic profiles for mouse pancreatic elastase were similar to other known serine elastases. [ABSTRACT FROM AUTHOR]

It is often stated that type 1 diabetes results from a complex interplay between varying degrees of genetic susceptibility and environmental factors. While agreeing with this principal, our desire is that this Perspectives article will highlight another complex interplay potentially associated with this disease involving facets related to the gut, one where individual factors that, upon their interaction with each another, form a "perfect storm" critical to the development of type I diabetes. This trio of factors includes an aberrant intestinal microbiota, a "leaky" intestinal mucosal barrier, and altered intestinal immune responsiveness. Studies examining the microecology of the gastrointestinal tract have identified specific microorganisms whose presence appears related (either quantitatively or qualitatively) to disease; in type 1 diabetes, a role for microflora in the pathogenesis of disease has recently been suggested. Increased intestinal permeability has also been observed in animal models of type 1 diabetes as well as in humans with or at increased-risk for the disease. Finally, an altered mucosal immune system has been associated with the disease and is likely a major contributor to the failure to form tolerance, resulting in the autoimmunity that underlies type 1 diabetes. Herein, we discuss the complex interplay between these factors and raise testable hypotheses that form a fertile area for future investigations as to the role of the gut in the pathogenesis and prevention of type 1 diabetes. Diabetes 57: 2555-2562, 2008 [ABSTRACT FROM AUTHOR]

Abstract: Anaplasma ovis (Rickettsiales: Anaplasmataceae) is a tick-borne pathogen of sheep, goats and wild ruminants. The genetic diversity of A. ovis strains has not been well characterized due to the lack of sequence information. In this study, we evaluated bighorn sheep (Ovis canadensis) and mule deer (Odocoileus hemionus) from Montana for infection with A. ovis by serology and sequence analysis of the msp4 gene. Antibodies to Anaplasma spp. were detected in 37% and 39% of bighorn sheep and mule deer analyzed, respectively. Four new msp4 genotypes were identified. The A. ovis msp4 sequences identified herein were analyzed together with sequences reported previously for the characterization of the genetic diversity of A. ovis strains in comparison with other Anaplasma spp. The results of these studies demonstrated that although A. ovis msp4 genotypes may vary among geographic regions and between sheep and deer hosts, the variation observed was less than the variation observed between A. marginale and A. phagocytophilum strains. The results reported herein further confirm that A. ovis infection occurs in natural wild ruminant populations in Western United States and that bighorn sheep and mule deer may serve as wildlife reservoirs of A. ovis. [Copyright &y& Elsevier]

Asbestos inhaled into the lung is recognized as a potential causal agent for the development of diseases in man. The diseases induced by asbestos include lung cancer, fibrosis of the lung (asbestosis), and extrapulmonary tumors including mesothelioma (a tumor of the serosal membrane), as well as fibrosis and other changes in the pleura linings. The cause of these diseases can often be more specifically linked to asbestos exposure once tissue burden of asbestos is established. The asbestos burden in tissue can be defined as the number of asbestos bodies and/or the numbers and types of asbestos fibers found in the tissue. In either of these cases the quality of information is directly dependent on the preparative techniques and instrumentation used in the analysis. The present article will discuss the significance of findings of tissue burden based on both these variables. [ABSTRACT FROM AUTHOR]

Abstract: Type 1 diabetes results from the autoimmune destruction of the insulin producing pancreatic β-cells. For years, the notion that T-lymphocytes played a crucial role in the disorder''s formation was considered such sound dogma, that interest in B-lymphocytes and autoantibodies as pathogenic variables was largely relegated to second-class status. However, much of our knowledge regarding the pathogenesis and natural history of this disease has been afforded by analysis of subjects having type 1 diabetes associated autoantibodies. While autoantibodies to more than two dozen autoantigens have been associated with this disease, a majority of interest has been directed at four autoantibodies; islet cell cytoplasmic (ICA), insulin (IAA), glutamic acid decarboxylase (GADA), and IA2/ICA512 autoantigen (IA2A). These autoantibodies, combined with other metabolic and genetic markers, are extremely effective for predicting eventual development of type 1 diabetes in otherwise healthy individuals. These autoantibodies have also aided in our understanding of disease heterogeneity and suggest that the autoimmune processes underlying type 1 diabetes initiate in the earliest stages of life (e.g., initial autoantibody formation at 9–18 months of age). Additional improvements are needed to more accurately define the time to disease onset, response to therapeutic intervention, the pathogenic features of the autoimmune response, and perhaps even the quantity of residual beta cell function. [Copyright &y& Elsevier]

A recently published article by the Scientific Advisory Committee of the Medical Outcomes Trust presents guidelines for selecting and evaluating health status and health-related quality of life measures used in health outcomes research. In their article, they propose a number of validation and performance criteria with which to evaluate such self-report measures. We provide an alternate, yet complementary, perspective by extending the types of measurement models which are available to the instrument designer. During psychometric development or selection of a Patient Reported Outcome measure it is necessary to determine which, of the five types of measurement models, the measure is based on; 1) a Multiple Effect Indicator model, 2) a Multiple Cause Indicator model, 3) a Single Item Effect Indicator model, 4) a Single Item Cause Indicator model, or 5) a Mixed Multiple Indicator model. Specification of the measurement model has a major influence on decisions about item and scale design, the appropriate application of statistical validation methods, and the suitability of the resulting measure for a particular use in clinical and population-based outcomes research activities. [ABSTRACT FROM AUTHOR]

Objectives: This proof of concept (POC) study was designed to evaluate the use of an Internet-based bulletin board technology to aid parallel cross-cultural development of thematic content for a new set of patient-reported outcome measures (PROs). Methods: The POC study, conducted in Germany and the United States, utilized Internet Focus Groups (IFGs) to assure the validity of new PRO items across the two cultures - all items were designed to assess the impact of excess facial oil on individuals' lives. The on-line IFG activities were modeled after traditional face-to-face focus groups and organized by a common 'Topic' Guide designed with input from thought leaders in dermatology and health outcomes research. The two sets of IFGs were professionally moderated in the native language of each country. IFG moderators coded the thematic content of transcripts, and a frequency analysis of code endorsement was used to identify areas of content similarity and difference between the two countries. Based on this information, draft PRO items were designed and a majority (80%) of the original participants returned to rate the relative importance of the newly designed questions. Findings: The use of parallel cross-cultural content analysis of IFG transcripts permitted identification of the major content themes in each country as well as exploration of the possible reasons for any observed differences between the countries. Results from coded frequency counts and transcript reviews informed the design and wording of the test questions for the future PRO instrument(s). Subsequent ratings of item importance also deepened our understanding of potential areas of cross-cultural difference, differences that would be explored over the course of future validation studies involving these PROs. Conclusion: The use of IFGs for cross-cultural content development received positive reviews from participants and was found to be both cost and time effective. The novel thematic coding methodology provided an empirical platform on which to develop culturally sensitive questionnaire content using the natural language of participants. Overall, the IFG responses and thematic analyses provided a thorough evaluation of similarities and differences in cross-cultural themes, which in turn acted as a sound base for the development of new PRO questionnaires. [ABSTRACT FROM AUTHOR]

The identification of asbestos bodies in tissue sections is an indicator of past exposure to longer asbestos fibers. These structures are formed in lung tissue as a consequence of interactions with pulmonary macrophages resulting in the deposition of a ferroprotein (ferruginous) coating on the fiber. While the process of ferruginous body formation is known to take months in animal tissue, there is no published information on the stability of ferruginous bodies in tissue following death. The material assessed in the present study was obtained from lung material collected from an exhumed body approximately 8½ mo after death, embalmment, and burial. Tissue sections were reviewed for the presence of asbestos bodies. Additional pieces of lung tissue were digested, with the digestate being evaluated by light microscopy for ferruginous bodies and by electron microscopy for uncoated asbestos fibers and core analysis of asbestos bodies. Classical ferruginous (asbestos) bodies were found in abundance in the tissue sections including in areas with fibrosis. The levels of uncoated asbestos fibers and classical appearing ferruginous bodies (asbestos bodies) were consistent with occupational levels of tissue burden. The data from this study indicate that ferruginous bodies remain morphologically stable within the tissue for months following death, embalmment, and burial. Thus the lung tissue from this exhumed individual was usable not only to pathologically confirm asbestosis but also to provide quantitative data of occupational exposure to asbestos. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were twofold: 1) to evaluate the construct validity of the Treatment Satisfaction Questionnaire for Medication (TSQM v. II) using structural equation modeling (SEM); and 2) to assess its concurrent validity using medication adherence criteria. Methods: Pharmacy patients filling a new medication prescription (n = 342) were recruited from 14 Michigan pharmacies to participate in a 4-week treatment satisfaction study. The TSQM v. II was tested for model fit against an established theoretical model (the Decisional Balance Model of Treatment Satisfaction) using hierarchical confirmatory factor analysis (HCFA). Regression and discriminant analytic models were used to examine the criterion-related validity of the measure. Results: An exploratory factor analysis, used for TSQM v. II item reduction, revealed a strongly dimensional instrument (Effectiveness, Side Effects, and Convenience) and explained 88% of total pooled variance. Results of an HCFA using the final TSQM v. II items suggested a good model fit with the data ( P > 0.54). In support of concurrent validity, the TSQM scales explained between 9% and 20% of the variance in dosing adherence and 60% of the variance in the likelihood of future use. Discriminant analysis demonstrated the superior classification power of the hierarchical model of treatment satisfaction over the discrete attribute model when predicting medication discontinuation. Conclusions: The TSQM v. II has equivalent measurement characteristics as the TSQM v. I, yet uses four fewer items and more consistent wording. The value of the Decisional Balance Model for estimation of dosing adherence and medication persistence over time is discussed. [ABSTRACT FROM AUTHOR]

Abstract: The Mycobacterium tuberculosis FtsZ (FtsZTB), unlike other eubacterial FtsZ proteins, shows slow GTP-dependent polymerization and weak GTP hydrolysis activities [E.L. White, L.J. Ross, R.C. Reynolds, L.E. Seitz, G.D. Moore, D.W. Borhani, Slow polymerization of Mycobacterium tuberculosis FtsZ, J. Bacteriol. 182 (2000) 4028–4034]. In an attempt to understand the biological significance of these findings, we created mutations in the GTP-binding (FtsZG103S) and GTP hydrolysis (FtsZD210G) domains of FtsZ and characterized the activities of the mutant proteins in vitro and in vivo. We show that FtsZG103S is defective for binding to GTP and polymerization activities, and exhibited reduced GTPase activity whereas FtsZD210G protein is proficient in binding to GTP, showing reduced polymerization activity but did not show any measurable GTPase activity. Visualization of FtsZ-GFP structures in ftsZ merodiploid strains by fluorescent microscopy revealed that FtsZD210G is proficient in associating with Z-ring structures whereas FtsZG103S is not. Finally, we show that Mycobacterium smegmatis ftsZ mutant strains producing corresponding mutant FtsZ proteins are non-viable indicating that mutant FtsZ proteins cannot function as the sole source for FtsZ, a result distinctly different from that reported for Escherichia coli. Together, our results indicate that optimal GTPase and polymerization activities of FtsZ are required to sustain cell division in mycobacteria and that the same conserved mutations in different bacterial species have distinct phenotypes. [Copyright &y& Elsevier]

Objective--To determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after PO, SC, and IV administration of enrofloxacin to alpacas. Animals--6 adult female alpacas. Procedure--A crossover design was used for administration of 3 single-dose treatments of enrofloxacin to alpacas, which was followed by an observational 14-day multiple-dose regimen. Single-dose treatments consisted of IV and SC administration of injectable enrofloxacin (5 mg/kg) and PO administration of enrofloxacin tablets (10 mg/kg) dissolved in grain to form a slurry. Plasma enrofloxacin concentrations were measured by use of high-performance liquid chromatography. The multiple-dose regimen consisted of feeding a mixture of crushed and moistened enrofloxacin tablets mixed with grain. Behavior, appetite, and fecal quality were monitored throughout the 14-day treatment regimen and for 71 additional days following treatment. Results--Mean half-life following IV, SC, and PO administration was 11.2, 8.7, and 16.1 hours, respectively. For SC and PO administration, mean total systemic availability was 90.18% and 29.31%, respectively; mean maximum plasma concentration was 3.79 and 1.81 µg/mL, respectively; and area under the curve (AUC) was 50.05 and 33.97 (µg X h)/mL, respectively. The SC or PO administration of a single dose of enrofloxacin yielded a ratio for AUC to minimum inhibitory concentration > 100 for many gram-positive and gram-negative bacterial pathogens common to camelids. Conclusions and Clinical Relevance--The administration of enrofloxacin (5 mg/kg, SC, or 10 mg/kg, PO) may be appropriate for antimicrobial treatment of alpacas. [ABSTRACT FROM AUTHOR]

Thirty years ago, a convergence of investigational observations lead to the now widely accepted notion that type 1 diabetes results from an autoimmune destruction of insulin-producing β-cells in subjects genetically predisposed to the disease. Improvements in understanding of the natural history of type 1 diabetes, the biochemical identification of autoantigens, the discovery of spontaneous animal models for the disease, the availability of immune-modulating agents, and other important facets, including disease prediction, drove an early sense of optimista that the prevention of type 1 diabetes was possible and, in some research circles, that ability was thought to be within a not-to-distant reach. Unfortunately, those early expectations proved overly optimistic, and despite the aforementioned knowledge gains, the generation of improved investigational tools, the identification of methods to prevent the disease in animal models, and the formation of very large disease prevention trials, a means to prevent type 1 diabetes in humans continues to remain elusive. Believing in the concept of "informative failures" (a.k.a., wise people learn from their mistakes), this lecture reviews the knowledge base collected over this time period and, when combined with an analysis of those research experiences, sets forth a proposal for future investigations that will, hopefully, turn discoveries into a means for the prevention or reversal of type 1 diabetes. Diabetes 54:1253-1263, 2005 [ABSTRACT FROM AUTHOR]