Distortion of the Local Magnetic Field Appears to Neither Disrupt Nocturnal Navigation nor Cue Shelter Recognition in the Amblypygid \u3ci\u3eParaphrynus laevifrons\u3c/i\u3e

Many arthropods are known to be sensitive to the geomagnetic field and exploit the field to solve spatial problems. The polarity of the geomagnetic field is used, for instance, as an orientation cue by leafcutter ants as they travel on engineered trails in a rainforest and by Drosophila larvae as they move short distances in search of food. A ubiquitous orientation cue like the geomagnetic field may be especially useful in complex, cluttered environments like rainforests, where the reliability of celestial cues used to navigate in more open environments may be poor. The neotropical amblypygid Paraphrynus laevifrons is a nocturnal arachnid that wanders nightly in the vicinity of its shelter and occasionally travels 30 m or more in the rainforest understory before it returns to its shelter. Here, we conducted a field experiment to determine whether navigation by P. laevifrons is guided by the ambient magnetic field and a complementary laboratory experiment to assess whether a magnetic anomaly could be used to pinpoint the entrance of a shelter. In the field experiment, subjects were fitted with a radio transmitter and a small, powerful magnet or a similar-sized brass disk and displaced 10 m from their shelter. The return rate of magnet-fitted subjects was similar to that of brass-fitted subjects and to that of subjects in an earlier study fitted with only a radio transmitter. In the laboratory experiment, we trained P. laevifrons with a protocol under which the amblypygid Phrynus marginemaculatus rapidly learns—in 1–14 trials over two daily sessions—to associate an olfactory stimulus with access to a shelter. The conditioned stimulus here was a magnetic anomaly characterized by a high total field intensity and a 180° reversal of the polarity of the ambient magnetic field. The magnetic anomaly–shelter contingency was not learned in 50 trials conducted over 10 daily sessions. These results imply prima facie that P. laevifrons does not rely on a magnetic compass to locate or recognize a shelter and, perhaps, that the magnetic field cannot be detected, but alternative explanations are discussed

Characterizing problematic hypoglycaemia: iterative design and preliminary psychometric validation of the Hypoglycaemia Awareness Questionnaire (HypoA-Q)

AIMS: To design and conduct preliminary validation of a measure of hypoglycaemia awareness and problematic hypoglycaemia, the Hypoglycaemia Awareness Questionnaire. METHODS: Exploratory and cognitive debriefing interviews were conducted with 17 adults (nine of whom were women) with Type 1 diabetes (mean &plusmn; sd age 48&plusmn;10 years). Questionnaire items were modified in consultation with diabetologists/psychologists. Psychometric validation was undertaken using data from 120 adults (53 women) with Type 1 diabetes (mean &plusmn; sd age 44&plusmn;16 years; 50% with clinically diagnosed impaired awareness of hypoglycaemia), who completed the following questionnaires: the Hypoglycaemia Awareness Questionnaire, the Gold score, the Clarke questionnaire and the Problem Areas in Diabetes questionnaire. RESULTS: Iterative design resulted in 33 items eliciting answers on awareness of hypoglycaemia when awake/asleep and hypoglycaemia frequency, severity and impact (healthcare utilization). Psychometric analysis identified three subscales reflecting \u27impaired awareness\u27, \u27symptom level\u27 and \u27symptom frequency\u27. Convergent validity was indicated by strong correlations between the impaired awareness subscale and existing measures of awareness: (Gold: rs =0.75, P&lt;0.01; Clarke: rs =0.76, P&lt;0.01). Divergent validity was indicated by weaker correlations with diabetes-related distress (Problem Areas in Diabetes: rs =0.25, P&lt;0.01) and HbA1c (rs =-0.05, non-significant). The impaired awareness subscale and other items discriminated between those with impaired and intact awareness (Gold score). The impaired awareness subscale and other items contributed significantly to models explaining the occurrence of severe hypoglycaemia and hypoglycaemia when asleep. CONCLUSIONS: This preliminary validation shows the Hypoglycaemia Awareness Questionnaire has robust face and content validity; satisfactory structure; internal reliability; convergent, divergent and known groups validity. The impaired awareness subscale and other items contribute significantly to models explaining recall of severe and nocturnal hypoglycaemia. Prospective validation, including determination of a threshold to identify impaired awareness, is now warranted.<br /

Metabolic analysis of the interaction between plants and herbivores

Insect herbivores by necessity have to deal with a large arsenal of plant defence metabolites. The levels of defence compounds may be increased by insect damage. These induced plant responses may also affect the metabolism and performance of successive insect herbivores. As the chemical nature of induced responses is largely unknown, global metabolomic analyses are a valuable tool to gain more insight into the metabolites possibly involved in such interactions. This study analyzed the interaction between feral cabbage (Brassica oleracea) and small cabbage white caterpillars (Pieris rapae) and how previous attacks to the plant affect the caterpillar metabolism. Because plants may be induced by shoot and root herbivory, we compared shoot and root induction by treating the plants on either plant part with jasmonic acid. Extracts of the plants and the caterpillars were chemically analysed using Ultra Performance Liquid Chromatography/Time of Flight Mass Spectrometry (UPLCT/MS). The study revealed that the levels of three structurally related coumaroylquinic acids were elevated in plants treated on the shoot. The levels of these compounds in plants and caterpillars were highly correlated: these compounds were defined as the ‘metabolic interface’. The role of these metabolites could only be discovered using simultaneous analysis of the plant and caterpillar metabolomes. We conclude that a metabolomics approach is useful in discovering unexpected bioactive compounds involved in ecological interactions between plants and their herbivores and higher trophic levels.

Temporal changes in frequency of severe hypoglycemia treated by emergency medical services in types 1 and 2 diabetes:a population-based data-linkage cohort study

Background&nbsp; Almost 20 years ago, the frequencies of severe hypoglycemia requiring emergency medical treatment were reported in people with types 1 and 2 diabetes in the Tayside region of Scotland. With subsequent improvements in the treatment of diabetes, concurrent with changes in the provision of emergency medical care, a decline in the frequency of severe hypoglycemia could be anticipated. The present population-based data-linkage cohort study aimed to ascertain whether a temporal change has occurred in the incidence rates of hypoglycemia requiring emergency medical services in people with types 1 and 2 diabetes.&nbsp; Methods&nbsp; The study population comprised all people with diabetes in Tayside, Scotland over the period 1 January 2011 to 31 December 2012. Patients&rsquo; data from different healthcare sources were linked anonymously to measure the incidence rates of hypoglycemia requiring emergency medical services that include treatment by ambulance staff and in hospital emergency departments, and necessitated hospital admission. These were compared with data recorded in 1997&ndash;1998 in the same region.&nbsp; Results&nbsp; In January 2011 to December 2012, 2029 people in Tayside had type 1 diabetes and 21,734 had type 2 diabetes, compared to 977 and 7678, respectively, in June 1997 to May 1998. In people with type 2 diabetes, the proportion treated with sulfonylureas had declined from 36.8 to 22.4% (p&lt;0.001), while insulin-treatment had increased from 11.7 to 18.7% (p&lt;0.001). The incidence rate of hypoglycemia requiring emergency medical treatment had significantly fallen from 0.115 (95% CI: 0.094&ndash;0.136) to 0.082 (0.073&ndash;0.092) events per person per year in type 1 diabetes (p&lt;0.001), and from 0.118 (0.095&ndash;0.141) to 0.037 (0.003&ndash;0.041) in insulin-treated type 2 diabetes (p=0.008). However, the absolute annual number of hypoglycemia events requiring emergency treatment was 1.4-fold higher.&nbsp; Conclusions&nbsp; Although from 1998 to 2012 the incidences of hypoglycemia requiring emergency medical services appeared to have declined by a third in type 1 diabetes and by two thirds in insulin-treated type 2 diabetes, because the prevalence of diabetes was higher (2.7 fold), the number of severe hypoglycemia events requiring emergency medical treatment was greater

Hydrophilic and lipophilic radiopharmaceuticals as tracers in pharmaceutical development: In vitro – In vivo studies

BACKGROUND: Scintigraphic studies have been performed to assess the release, both in vitro and in vivo, of radiotracers from tablet formulations. Four different tracers with differing physicochemical characteristics have been evaluated to assess their suitability as models for drug delivery. METHODS: In-vitro disintegration and dissolution studies have been performed at pH 1, 4 and 7. In-vivo studies have been performed by scintigraphic imaging in healthy volunteers. Two hydrophilic tracers, ((99m)Tc-DTPA) and ((99m)Tc-MDP), and two lipophilic tracers, ((99m)Tc-ECD) and ((99m)Tc-MIBI), were used as drug models. RESULTS: Dissolution and disintegration profiles, differed depending on the drug model chosen. In vitro dissolution velocity constants indicated a probable retention of the radiotracer in the formulation. In vivo disintegration velocity constants showed important variability for each radiopharmaceutical. Pearson statistical test showed no correlation between in vitro drug release, and in vivo behaviour, for (99m)Tc-DTPA, (99m)Tc-ECD and (99m)Tc-MIBI. High correlation coefficients were found for (99m)Tc-MDP not only for in vitro dissolution and disintegration studies but also for in vivo scintigraphic studies. CONCLUSION: Scintigraphic studies have made a significant contribution to the development of drug delivery systems. It is essential, however, to choose the appropriate radiotracers as models of drug behaviour. This study has demonstrated significant differences in release patterns, depending on the model chosen. It is likely that each formulation would require the development of a specific model, rather than being able to use a generic drug model on the basis of its physicochemical characteristics

Cardiovascular risk factors and cognitive decline in older people with type 2 diabetes

AIMS/HYPOTHESIS: The aim of this work was to assess the role of well-established cardiovascular risk factors in the late-life cognitive decline of patients with type 2 diabetes. METHODS: Data from 831 participants (aged 60-75 years) attending the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used. Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were determined at baseline clinics (single time measurements) and/or from serial data recorded on a clinical management database from diagnosis until recruitment ('historical' data). Principal component analysis derived a factor, g, of general ability from seven cognitive tests. Linear regression models of follow-up g were adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late-life cognitive decline' was defined as scoring in the lowest tertile of '4 year cognitive change' regression scores. Analyses controlled for age and sex. RESULTS: A baseline history of moderate/heavy smoking (>/= 10 pack-years) and a 1% increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a 64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45; p = 0.046) increased risk of accelerated cognitive decline, respectively. When treated as continuous measures, higher pack-years, historical HbA1c and historical BP emerged as significant independent predictors of 4 year decline in g (standardised beta range -0.07 to -0.14; all p </= 0.05). CONCLUSIONS/INTERPRETATION: Increased smoking and poorer glycaemic control (with relatively weaker findings for BP) during the life-course were independently associated with accelerated late-life cognitive decline. Where possible, evaluation is warranted of these risk factors as targets for intervention to reduce the burden of cognitive impairment in diabetes

Perspectives of Patients with Insulin-Treated Type 1 and Type 2 Diabetes on Hypoglycemia: Results of the HAT Observational Study in Central and Eastern European Countries

INTRODUCTION: The aim of this study was to determine the level of awareness of hypoglycemia, the level of fear for hypoglycemia, and the response to hypoglycemic events among insulin-treated diabetes patients from Central and Eastern Europe (CEE). The impact of hypoglycemia on the use of healthcare resources and patient productivity was also assessed. METHODS: This was a multicenter, non-interventional, two-part, patient self-reported questionnaire study that comprised both a retrospective cross-sectional evaluation and a prospective observational evaluation. Study participants were insulin-treated adult patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) from CEE. RESULTS: Most patients (85.4% T1DM and 83.6% T2DM) reported normal hypoglycemia awareness. The median hypoglycemia fear score was 5 out of 10 for T1DM and 4 out of 10 for T2DM patients. Patients increased glucose monitoring, consulted a doctor/nurse, and/or reduced the insulin dose in response to hypoglycemia. As a consequence of hypoglycemia, patients took leave from work/studies or arrived late and/or left early. Hospitalization was required for 31 (1.2%) patients with T1DM and 66 (2.1%) patients with T2DM. CONCLUSION: Hypoglycemia impacts patients' personal and social functioning, reduces productivity, and results in additional costs, both direct (related to increased use of healthcare resources) and indirect (related to absenteeism. FUNDING: Novo Nordisk

The Equifinality of Archaeological Networks: an Agent-Based Exploratory Lab Approach

When we find an archaeological network, how can we explore the necessary versus contingent processes at play in the formation of that archaeological network? Given a set of circumstances or processes, what other possible network shapes could have emerged? This is the problem of equifinality, where many different means could potentially arrive at the same end result: the networks that we observe. This paper outlines how agent-based modelling can be used as a laboratory for exploring different processes of archaeological network formation. We begin by describing our best guess about how the (ancient) world worked, given our target materials (here, the networks of production and patronage surrounding the Roman brick industry in the hinterland of Rome). We then develop an agent-based model of the Roman extractive economy which generates different kinds of networks under various assumptions about how that economy works. The rules of the simulation are built upon the work of Bang (2006; 2008) who describes a model of the Roman economy which he calls the ‘imperial Bazaar’. The agents are allowed to interact, and the investigators compare the kinds of networks this description generates over an entire landscape of economic possibilities. By rigorously exploring this landscape, and comparing the resultant networks with those observed in the archaeological materials, the investigators will be able to employ the principle of equifinality to work out the representativeness of the archaeological network and thus the underlying processes