bluuebunny/crossref_metadata_2025 huggingface dataset:
A report of two novel NR5A1 mutation families: possible clinical phenotype of psychiatric symptoms of anxiety and/or depression
Authors: Suwanai Ayuko S. , Ishii Tomohiro , Haruna Hidenori , Yamataka Atsuyuki , Narumi Satoshi , Fukuzawa Ryuji , Ogata Tsutomu , Hasegawa Tomonobu
Published: October 2012

Objective

NR5A1 or steroidogenic factor 1 is a nuclear receptor that plays important roles in the hypothalamus–pituitary–steroidogenic axis. The clinical phenotype of most 46,XY mutation carriers includes disorders of sex development (DSD) without adrenal insufficiency, whereas 46,XX mutation carriers have phenotypes ranging from no symptoms to ovarian insufficiency. Although genetically engineered ventromedial hypothalamus‐specific Nr5a1 knockout mice show anxiety behaviour, no psychiatric symptoms have been reported in human NR5A1 mutation carriers. We report clinical and molecular findings for individuals (from two families) with NR5A1 mutations, showing psychiatric symptoms.

Design and methods

We screened for NR5A1 mutations in a cohort of 34 patients with 46,XY DSD using PCR‐based sequencing. Psychiatric symptoms were assessed using mental health assessment tools and structured clinical interviews. Functional properties of detected mutant NR5A1s were studied in silico and in vitro, including three‐dimensional (3D) mutation models, subcellular NR5A1 protein localization and transactivation assays.

Results

We found 2 (46,XY) patients with NR5A1 heterozygous novel mutations (p.D257fs and p.V424del), which were transmitted from their respective mothers. The patients' clinical findings indicated DSD without adrenal insufficiency. Both mothers showed psychiatric symptoms, including excessive anxiety and/or depression. The mother and grandmother of one patient had premature ovarian insufficiency. Functional studies showed altered 3D models of p.V424del and normal subcellular NR5A1 localization and impaired transcriptional activation without dominant‐negative effects in both mutations.

Conclusions

We found 2 (46,XX) NR5A1 mutation carriers with excessive anxiety and/or depression. These results suggest that excessive anxiety and/or depression are possible clinical phenotypes of 46,XX NR5A1 mutations.
Inheritance of the chronic myeloproliferative neoplasms. A systematic review
Authors: Ranjan A , Penninga E , Jelsig AM , Hasselbalch HC , Bjerrum OW
Published: October 2012

Ranjan A, Penninga E, Jelsig AM, Hasselbalch HC, Bjerrum OW. Inheritance of the chronic myeloproliferative neoplasms. A systematic review.

This systematic review investigated the inheritance of the classical chronic myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and chronic myelogenous leukemia (CML). Sixty‐one articles were included and provided 135 families with a total of 341 participants distributed to various subtypes of MPN: 50% PV, 23% ET, 14% PMF, 10% CML and 3% non‐MPN hematological disorder. Women developed the disease earlier than men (43.1 years vs 47.3 years; p = 0.074), while the general average age of onset was 46 years, notably younger than sporadic cases. The clinical phenotype of the families showed a homogenous (67%) and a heterogeneous (33%) pattern, with the majority being PV–PV pairs (36%) and PV–PMF pairs (17%), respectively. This observation suggests that the susceptibility gene (or genes) is not restricted to one subtype supporting the hypothesis of a mutation in an early multipotent stem cell. Furthermore, a major subgroup of families provided evidence of an autosomal dominant (AD) inheritance with reduced penetrance. This study suggests that the origin of MPNs may occur in at least three different settings: (i) a sporadic, (ii) genetic heterogeneity with polygenetic and environmental impact and (iii) a familial phenotype following an AD inheritance.
Does Grammatical Aspect Affect Motion Event Cognition? A Cross‐Linguistic Comparison of English and Swedish Speakers
Authors: Athanasopoulos Panos , Bylund Emanuel
Published: October 2012

In this article, we explore whether cross‐linguistic differences in grammatical aspect encoding may give rise to differences in memory and cognition. We compared native speakers of two languages that encode aspect differently (English and Swedish) in four tasks that examined verbal descriptions of stimuli, online triads matching, and memory‐based triads matching with and without verbal interference. Results showed between‐group differences in verbal descriptions and in memory‐based triads matching. However, no differences were found in online triads matching and in memory‐based triads matching with verbal interference. These findings need to be interpreted in the context of the overall pattern of performance, which indicated that both groups based their similarity judgments on common perceptual characteristics of motion events. These results show for the first time a cross‐linguistic difference in memory as a function of differences in grammatical aspect encoding, but they also contribute to the emerging view that language fine tunes rather than shapes perceptual processes that are likely to be universal and unchanging.
Lack of drug–drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and warfarin in healthy volunteers
Authors: Macha S. , Rose P. , Mattheus M. , Pinnetti S. , Woerle H. J.
Published: October 2012

Aim

To investigate potential drug–drug interactions between empagliflozin and warfarin.

Methods

Healthy subjects (n = 18) received empagliflozin 25 mg qd for 5 days (treatment A), followed by empagliflozin 25 mg qd for 7 days (days 6–12) with a single 25 mg dose of warfarin on day 6 (treatment B), and a single 25 mg dose of warfarin alone (treatment C), in an open‐label, crossover study. Subjects received treatments in sequence AB_C or C_AB with a washout period of ≥14 days between AB and C or C and AB.

Results

Warfarin had no effect on empagliflozin area under concentration‐time curve or maximum plasma concentration at steady‐state (AUCτ,ss or Cmax,ss): geometric mean ratios (GMRs) (90% confidence intervals [CI]) were 100.89% (96.86, 105.10) and 100.64% (89.79, 112.80), respectively. Empagliflozin had no effect on AUC from 0 h to infinity (AUC0–∞) or Cmax for R‐ or S‐warfarin (GMRs [90% CI] for AUC0–∞: 98.49% [95.29, 101.80] and 95.88% [93.40, 98.43], respectively; Cmax: 97.89% [91.12, 105.15] and 98.88% [91.84, 106.47], respectively). Empagliflozin had no clinically relevant effects on warfarin's anticoagulant activity (international normalised ratio [INR]) (GMR [95% CI] for peak INR: 0.87 [0.73, 1.04]; area under the effect‐time curve from 0 to 168 h: 0.88 [0.79, 0.98]. No drug‐related adverse events were reported for empagliflozin after monotherapy or combined administration. The combination of empagliflozin and warfarin was well tolerated.

Conclusions

No drug–drug interactions were observed between empagliflozin and warfarin, indicating that empagliflozin and warfarin can be co‐administered without dosage adjustments of either drug.
Matrix Metalloproteinase‐2 and ‐9 Levels in Patients with Dilated Ascending Aorta and Bicuspid Aortic Valve
Authors: Abaci Okay , Kocas Cuneyt , Kilickesmez Kadriye Orta , Uner Sinan , Kucukoglu Serdar
Published: October 2012

Background: Predictors of aortic dilatation are not well‐described in patients with bicuspid aortic valve (BAV). Changes in extracellular matrix composition in the aortic wall may play an important role. Our study aimed to examine the relationship between ascending aortic dilatation and biochemical markers for collagen metabolism, such as matrix metalloproteinase‐2 (MMP‐2) and matrix metalloproteinase‐9 (MMP‐9) levels in patients with BAV. Methods: All patients underwent cardiac echocardiography using a standard protocol, and aortic measurements were made in end‐diastole. One hundred twelve BAV patients with no or mild valvular impairment were recruited and grouped according to the aortic dimensions corrected for body surface area (BSA) and age. There were 54 patients with dilated ascending aorta (Group 1) and 58 patients with nondilated ascending aorta (group 2). The plasma levels of MMP‐2 and MMP‐9 were determined by ELISA. Results: The mean ascending aorta diameter was 4.49 ± 0.49 mm in group 1 and 3.51 ± 0.46 mm in group 2 (P < 0.001). There were no significant difference in gender, BSA, presence of hypertension, diabetes mellitus, hyperlipidemia, and smoking between the 2 groups. Nevertheless, no significant difference was observed in the levels of MMP‐2 and MMP‐9 between the 2 groups. The ascending aorta diameter correlated significantly with age (r = 0.438 P < 0.001). No significant correlation was observed between plasma MMP‐2 and MMP‐9 concentration and ascending aorta diameter, respectively (r = −0.005 P = 0.58, r = −0.106 P = 0.07). Multivariate analysis showed that age was independent predictor of aortic dilatation (P ≤ 0.001). Conclusion: Age was an independent predictor of aortic dilatation in patients with BAV, whereas MMP‐2 and 9 levels were not relevant by aortic dilatation.
Velocity Vector Imaging of Longitudinal Mechanical Properties of Upstream and Downstream Shoulders and Fibrous Cap Tops of Human Carotid Atherosclerotic Plaque
Authors: Huang Xiao‐Zhen , Wang Zhi‐Yun , Dai Xiao‐Hua , Yun‐Zhang  , Zhang Mei
Published: October 2012

Aims: Atherosclerotic plaque rupture is closely related to high regional mechanical stress in the plaque itself. We aimed to explore the longitudinal mechanical properties of upstream and downstream shoulders and fibrous cap tops of human atherosclerotic plaques in vivo by velocity vector imaging (VVI) combined with acoustic densitometry (AD) imaging. Methods and Results: We included 135 patients with carotid atherosclerotic plaque. VVI and AD were used to examine 3 regions of carotid plaque along the longitudinal‐axis view. A total of 405 regions were classified with low or high AD values by corrected averages image intensity (AIIc%) < or ≥50, respectively. Peak systolic strain, strain rate (SR), and velocity were significantly greater for upstream than downstream shoulders and fibrous cap tops of carotid plaque (P < 0.05 for both). AIIc% was significantly lower for upstream than downstream plaque shoulders (P < 0.05). Peak systolic SR of the plaque regions was negatively correlated with corresponding AIIc% (R2 = 0.499, P < 0.05). Conclusions: The longitudinal strain of human carotid atherosclerotic plaques as derived by VVI is associated with its corresponding AD but also in part with the internal position of the strain, with values greater for upstream than downstream shoulders and fibrous cap tops.
Delayed flow‐mediated vasodilation and carotid atherosclerosis
Authors: Irace Concetta , Carallo Claudio , Loprete Antonio , Tripolino Cesare , Scavelli Faustina , Gnasso Agostino
Published: October 2012

Eur J Clin Invest 2012

Background  In a previous study, we identified temporally distinct postischaemic flow‐mediated dilation (FMD) patterns comparing the standard clinical measurement time of 50s postcuff release with measurement at 2 min. The comparison revealed a cohort with the highest FMD at 50s (Early FMD), another cohort with the highest FMD at 2 min (Late FMD) and a third cohort with no FMD (Absent FMD). The aim of this study was to examine whether these temporally distinct FMD patterns associated with different degrees of carotid atherosclerosis.

Materials and methods  One hundred and twenty‐four free‐living white subjects, participating in a cardio‐vascular disease prevention campaign, were enrolled. FMD was measured at 50s, 2 min and 3 min after forearm ischaemia. The intima‐media thickness (IMT) of the common carotid artery was measured, and the artery was evaluated for the presence and number of carotid plaques.

Results  Fifty‐seven subjects had Early FMD, 34 had Late FMD and 33 had Absent FMD. The three groups were comparable for age, sex and cardiovascular risk factors. The number of plaques in the carotid arteries, and IMT, increased progressively from Early, to Late, and to Absent FMD (P < 0·03), indicating that the FMD pattern is an independent predictive variable for IMT and carotid atherosclerosis.

Conclusions  The present study demonstrates that temporal patterns associated with the degree of atherosclerosis of the carotid arteries. Patients with delayed vasodilation (Late FMD) had a higher degree of atherosclerosis than those with early vasodilation (Early FMD), and subjects with no postischaemic vasodilation (Absent FMD) had the most atherosclerosis.
Patrons of Rome: the cult of Sts Peter and Paul at court and in the city in the fourth and fifth centuries
Authors: Thacker Alan
Published: October 2012

This paper will focus primarily on that most potent of all symbols of the new Christian city of Rome, the cult of Peter embodied in the apostolic memoria on the Vatican Hill. It will consider the roles of emperor, pope and senatorial aristocracy in its promotion in the fourth and fifth centuries, together with the interconnected development of the cult of Rome's other apostle, Paul, entombed to the south of the city on the Via Ostiense. In particular, apostolic cult, the key element in the representation of Rome as the Christian caput urbium, will be examined in relation to the renewed imperial engagement with Rome evident from the late fourth century through to the last years of the western empire.
The scripts of the Prague Sacramentary, Prague Archivo O 83
Authors: McKitterick Rosamond
Published: October 2012

This article considers the light the scripts of the Prague Sacramentary throw on its place of production and early cultural and historical context. While various suggestions have been made about both its production and its early history, Bavaria and north Italy have been the generally agreed principal visible influences in its production, and the book's early history is associated with Carolingian Bavaria. The limitations of palaeographical evidence, in terms of using it to try and resolve issues of origin or place of production, are addressed first. The palaeography of the manuscript can tell us only the probable place where the scribes were trained and this cannot necessarily be equated with the origin of the book. These scribes were clearly open to Insular, Frankish and Italian influences, whether directly through the training and teaching process or indirectly through exemplars. The article concludes that the scribes of this codex had been trained to write in south‐east Bavaria.
The Merovingians from the French Revolution to the Third Republic
Authors: James Edward
Published: October 2012

In the early twentieth century, French schoolchildren were taught almost nothing about the Merovingians: a great change from a century earlier. This article explores some of the reasons why the public image of the Merovingians and their Frankish subjects altered in the course of the great political changes which unrolled in France in the century after the Revolution. A crucial figure was Augustin Thierry, whose eloquent rewriting of what Gregory of Tours had to say about the Merovingians in the 560s and 570s was widely read, and contributed towards the widespread neglect of early Frankish history. The article ends by examining a few of the artists who were inspired (partly by Thierry himself) to take the Merovingians for their subject matter, above all Laurens and Luminais.
Simvastatin induces osteogenic differentiation in human amniotic fluid mesenchymal stem cells (AFMSC)
Authors: de Lara Janz Felipe , Favero Giovani Marino , Bohatch Milton Sérgio , Aguiar Debes Adrianade , Bydlowski Sergio Paulo
Published: October 2012

Amniotic fluid is a complex mixture composed of water, salts and different cells types derived from embryo exfoliation. Some of these cells present similar characteristics to mesenchymal stem cells as adherent properties, typical surface antigens and differentiation capacity. These cells are called amniotic fluid‐derived mesenchymal stem cells (AFMSCs) and are easily obtained by amniocentesis, propagated in culture and differentiated in several cell types with specific inductions. In this study, we observe the ability of simvastatin, a 3‐HMG‐CoA reductase inhibitor, to induce AFSMCs osteogenic differentiation. When AFSMCs were incubated with medium containing simvastatin, it was observed morphological changes, calcium deposits formation confirmed by Alizarin Red stain. Differentiated cells also expressed typical osteogenic genes, as osteopontin and osteocalcin. In conclusion, simvastatin could be used as an optional osteogenic induction agent for amniotic fluid‐derived mesenchymal stem cells.
Round‐robin prediction of the fatigue limit of a ring of spheroidal graphite cast iron
Authors: HÄRKEGÅRD G. , SVENSSON T. , ZAMBRANO H. R.
Published: October 2012

A round‐robin investigation has been performed, where stress analysts from eight different organisations carried out a total of 11 predictions of the expected fatigue limit of a diametrically loaded cast ring subjected to fluctuating tensile or compressive loading. Whereas geometry, load parameters, and type and quality of material (spheroidal graphite cast iron EN‐GJS‐600‐3) had been prescribed, the participants were free to use computational tools and models, and fatigue assessment models and data of their own choice. The objectives of the investigation were to compare the 11 predictions (i) among themselves, and (ii) with a posteriori experimental fatigue limits determined by means of stair‐case testing. The fatigue limit predictions showed coefficients of variation of as large as 25%. Even for a group of analysts from a single organisation, the coefficients variation were around 15%. Fatigue tests gave mean fatigue limits 60% (tensile loading) and 30% (compressive loading) above the a priori predictions. Possible reasons for the large deviations between single predictions and for their conservatism have been proposed. It seems that design engineers (i) make use of the available room for interpretation of models and data, and (ii) have an unconscious tendency to make conservative assumptions. Only if models and data for fatigue assessment are prescribed in great detail, can the ‘scatter’ among fatigue limit predictions be expected to decrease below 15–25%. Improved ‘absolute’ predictions would require more accurate fatigue data.
Comparative study between the PNL method and a MN in modelling fatigue of composite materials
Authors: BELÍSIO A. SILVA , FREIRE JÚNIOR R. C. SILVERIO
Published: October 2012

The aim of this study was to compare the results obtained using the piecewise nonlinear model with those of a modular network (MN) architecture in modelling fatigue behaviour. We used a database consisting of ten materials derived from the literature and represented by the following acronyms: C10, C12, DD16, HTA‐913, IM7–977, MAT(0)2, T800–5245, T800H‐3631, QQ1 and QQ1T. The results obtained by MN were compared with those of the PNL. The results for both the PNL and MN model were satisfactory for the fatigue behaviour of glass fiber‐based composite materials, but for carbon fiber‐based composites only MN showed satisfactory results.
Static and fatigue characterization of the Ti5553 titanium alloy
Authors: BETTAIEB M. B. , LENAIN A. , HABRAKEN A. M.
Published: October 2012

This paper presents and discusses static (elastoviscoplastic and damage) and high‐cycle fatigue characterization of two microstructures of the Ti5553 alloy. The difference between these two microstructures is related to their heat treatment and precisely to the temperature of the final aging. For each microstructure, several tests were carried out to identify their static and fatigue properties and the test results were correlated to the microstructure. A fractographic analysis of the rupture sections was performed in order to investigate the fracture mechanisms of the two microstructures. Finally, the fatigue properties of the two microstructures were compared with those found in results reported in the literature for two other classical titanium alloys used for aeronautical applications.
Is proximity to the North Atlantic Drift and the Continental Shelf Current sustaining freshwater European eel populations in western Scotland?
Authors: ADAMS COLIN E. , GODFREY JASON D. , DODD JENNIFER A. , MAITLAND PETER S.
Published: October 2012

1. We report on freshwater resident eel numbers in western Scotland based on two time series of data, independent of each other, spanning 28 years and that do not rely upon fisheries information.

2. Data from eel captures on trash screens of a pumping station (1982–2003) on Loch Lomond and electrofishing data from a stream in Lochaber, the Allt Coire nan Con (1989–2010), are compared with similar time series eel population data from elsewhere in the British Isles and more widely in Europe.

3. Over the period of the study, indices of eel numbers from across Europe declined by between 72 and 95%; in stark contrast, neither time series from western Scotland showed evidence for decline between 1982 and 2010.

4. We provisionally conclude that freshwater populations in western Scotland are being maintained by regional processes directly related to the proximity of the leading edge of the North Atlantic Drift and the Continental Shelf Current and the direction of prevailing winds.
Effects of changes in the driving forces on water quality and plankton dynamics in three Swiss lakes – long‐term simulations with BELAMO
Authors: DIETZEL ANNE , MIELEITNER JOHANNA , KARDAETZ SASCHA , REICHERT PETER
Published: October 2012

1. With a modified version of the lake model BELAMO, we were able to describe the essential features of the dynamics of nutrients, dissolved oxygen, phyto‐ and zooplankton in three lakes of different trophic status over periods of 19–30 years, with essentially the same model parameters for all three lakes. This is remarkable, as the measured nutrient inputs decreased considerably during the simulated time period.

2. Despite having done this before for a period of 4 years with an earlier version of the model, a considerable effort was required that led to a series of model modifications without which the data could not be matched. This demonstrates that long‐term calibration of a model that combines processes in the water column with mineralisation in the sediment can be difficult.

3. Due to the necessarily simplified processes within the model, there is a bias in its output. We applied a recently developed technique for model calibration and uncertainty analysis to address bias and multiple calibration criteria. To account for the demanding long‐term simulations, a simplified numerical implementation of this technique was used.

4. Our results demonstrate good understanding of the chemical state of the lake during the calibration period but less of the biological variables. The credibility intervals used to visualise this knowledge widen substantially during the prediction period (consisting of the last 10 years of the simulation).

5. The joint calibration of the model with long‐term data from lakes of different trophic status is possible but only with considerable prediction uncertainty. Due to the explicit consideration of bias in our calibration technique, we are able to estimate quantitatively the uncertainty of our knowledge about chemical and biological variables in the lake.
Sociological Perspectives on the Economic Geography of Projects: The Case of Project‐Based Working in the Creative Industries
Authors: Watson Allan
Published: October 2012

In recent years, there has been a growing concern in economic geography with the organisational practices of project‐based working, involving a multiplicity of organisational and personal social networks. Paralleling this debate has been a growing academic interest in the cultural economy and the conditions of creative work, itself characterized by project‐based working. Cultural and creative workers are argued to symbolise contemporary transformations of work more than any other group of workers. However, despite this being a wide trans‐disciplinary area of enquiry, little economic geography literature has engaged explicitly with perspectives being developed in other disciplines, in particular sociology and cultural and media studies, on the experience and conditions of work in project‐based industries. In this paper I argue for the incorporation of sociological perspectives into our analyses of projects, in order to address the lack of attention to the sociological, political and cultural issues of work. Such an approach, I suggest, can contribute to the economic geography of projects in three ways; first it moves beyond structural analyses to allow for an understanding of the importance of agency in project work; second it allows us to move on from firm‐level analyses to develop an understanding of the complex social networks involved in project‐based working; and finally it moves on from research at the meso‐level on inter‐ and intra‐firm networks to provide micro‐level analyses of project work.
More lightweight and isodiametric seeds for C4than for C3grasses are associated with preference for open habitats of C4grasses in a temperate flora
Authors: Csontos P. , Kalapos T.
Published: October 2012

Seed mass and shape of grasses were analysed in a temperate flora containing 178 and 26 species belonging to C3and C4photosynthetic types respectively. The weedy character and the annual or perennial status were also considered. On the basis of the seed traits studied, three groups were distinguished: C4grasses, annual C3grasses of weedy character and perennial non‐weedy C3grasses. The C4group had more isodiametric (same diameter in all directions) seed shape and lower average seed mass than the C3group. To our knowledge, this has not yet been described for temperate C4grasses and is certainly associated with their preference for open habitats where competition for light is small. Weedy annual C3grasses had heavier and less isodiametric seeds than C4grasses did. These species are mostly specialized to establish in the dense cover of perennial vegetation, and this ability distinguishes them from the C4group. Non‐weedy perennial C3species possessed less isodiametric seeds than did C4grasses, but did not differ from weedy annual C3grasses. As most alien C4grasses naturalized in Hungary are annuals with small, isodiametric seeds, these traits are good candidates to be included in screening for potential future invasives in open habitats.
Growth promotion of Bifidobacterium and Lactobacillus species by proteinaceous hydrolysates derived from poultry processing leftovers
Authors: Lazzi Camilla , Meli Federica , Lambertini Francesca , Bottesini Chiara , Nikolaev Ilya , Gatti Monica , Sforza Stefano , Koroleva Olga , Popov Vladimir , Neviani Erasmo , Dossena Arnaldo
Published: October 2012

Bacterial growth media represent a high cost in industrial applications, and for this reason, it is economically important to find less expensive supplements to replace the traditional ones. In the present work, peptide hydrolysates obtained from poultry meat and bone residues (functional animal protein [FAP]) and from feathers (functional feather protein [FFP]) were studied to determine their ability for the production of microbial biomass with improved viability. The results obtained were compared with those obtained with other supplement nutritive compounds used in fermentation growth media. The molecular composition of the hydrolysates in terms of total and soluble nitrogen, molecular weight distribution, total and free amino acids, was determined. The growth and cellular state of Bifidobacterium and Lactobacillus strains were studied by turbidimetric measurements and direct count by fluorescence microscopy. Overall, this study suggested that by‐products from poultry industry provide a good alternative to substitute expensive supplements for growth of Lactobacillus and Bifidobacterium with a high level of viability.
Sensitivity of antennal gustatory receptor neurones to aphid honeydew sugars in the carabid Anchomenus dorsalis
Authors: MERIVEE ENNO , MUST ANNE , TOOMING ENE , WILLIAMS INGRID , SIBUL IVAR
Published: October 2012

Using electrophysiology, the stimulating effect of 13 sugars and three sugar alcohols (each at a concentration of 100 mm) to antennal gustatory receptor neurones (GRNs) is tested in the carabid beetle Anchomenus dorsalis (Pontoppidan, 1763) (Coleoptera, Carabidae). Maltose, sucrose, glucose and raffinose are the most stimulating sugars for the sugar‐sensitive neurone (SuN), evoking 6.7–18.6 spikes s−1 in fed insects, whereas the others had little or no effect. The firing rate of the antennal GRNs is not affected by any of the tested sugar alcohols, dulcitol, inositol and sorbitol. Additionally, concentration/response curves for sucrose and maltose are obtained in the range 0.01–100 mm. The responses of beetles starved for 96 h to this range of sucrose are two‐ to three‐fold higher compared with those of fed beetles. The presence of a terminal α‐glucose unit is an important feature of the molecular structure determining the stimulating properties of the two disaccharides, maltose and sucrose, as well as glucose. The other monosaccharide unit of the molecule is also of great importance in determining the stimulating properties of various disaccharides. The sensitivity of the SuN to the four most prevalent aphid honeydew sugars suggests that A. dorsalis uses these chemicals as sensory cues when searching for aphids as prey.
Intensive care and traumatic brain injury after the introduction of a treatment protocol: a prospective study
Authors: SCHIRMER‐MIKALSEN K. , MOEN K. G. , SKANDSEN T. , VIK A. , KLEPSTAD P.
Published: October 2012

Background

Traumatic brain injury (TBI) treatment protocols have been introduced in the intensive care unit (ICU) to avoid secondary brain injury. In this study, we aimed to evaluate the deviations from such a treatment protocol and the frequency of extracranial complications, and relate these findings to outcome.

Methods

During a 5‐year period (2004–2009), 133 patients with severe TBI [Glasgow Coma Scale (GCS) score ≤ 8] were prospectively included. The following deviations from treatment goals were studied: intracranial pressure (ICP), blood pressure, haemoglobin, blood glucose, serum sodium, serum albumin, body temperature and extracranial complications during the ICU stay. Outcome was assessed using Glasgow Outcome Scale Extended score at 12 months.

Results

The frequencies of deviations from the treatment goals were: episodes of intracranial hypertension 69.5% (of monitored patients), hypotension 20.3%, anaemia 77.4%, hyperglycaemia 42.9%, hyponatremia 34.6%, hypoalbuminemia 30.8% and hyperthermia 54.9%. Pulmonary complications were common (pneumonia 72.2%, acute respiratory distress syndrome/acute lung injury 31.6%). Thrombocytopenia (4.5%), severe sepsis (3.0%), renal failure (0.8%) and liver failure (0.8%) were infrequent. Twenty‐six (19.5%) patients died within the first 12 months due to the head injury. Age, GCS score, pupil dilation, Injury Severity Score (ISS), ICP > 25 mmHg, hyperglycaemia and pneumonia predicted a worse outcome.

Conclusions

Deviations from the TBI treatment protocol were frequent. Pneumonia was the most frequent extracranial complication. Age, GCS score, pupil dilation, ISS, high ICP, hyperglycaemia and pneumonia predicted a worse outcome.
Investigation of adaptation after liver transplantation using Roy's Adaptation Model
Authors: Ordin Yaprak S. , Karayurt Özgül , Wellard Sally
Published: October 2012

In this study we explored the adaptation of transplant recipients in Turkey using the Roy Adaptation Model. A descriptive qualitative design was used with data collected from liver transplant recipients in either individual or group interviews between May 2009 and February 2010. Using deductive content analysis, four themes were identified in the data: physiological mode, self‐concept mode, role function mode, and interdependence mode. Each theme included both adaptive and ineffective behaviors of liver transplant recipients. The findings of this study indicate that liver transplant recipients need information and support about their ineffective behaviors in all modes of the Roy Adaptation Model. The findings also support the use of a nursing model in the delivery of nursing care for liver transplantation recipients.
Association of asthma symptoms with cigarette smoking and alcohol consumption in Korean adolescents
Authors: Kim Oksoo , Kim Bo Hye
Published: October 2012

The association of asthma symptoms with cigarette smoking and alcohol consumption in Korean adolescents was investigated in this study using the data of Korean Youth Risk Behavior Survey. Associated risk factors for experiencing asthma symptoms were explored in 3432 adolescents. In the symptomatic group, 21.7% were current smokers, compared to 10.9% in the asymptomatic group. Current smokers in the symptomatic group also smoked more cigarettes than those in the asymptomatic group. In the symptomatic group, 27.4% were current drinkers, compared to 17.9% in the asymptomatic group. Current drinkers in the symptomatic group were more likely to drink alcohol and to have experienced severe intoxication than those in the asymptomatic group. Participants who had been diagnosed within one year (odds ratio = 5.19, 95% confidence interval = 4.17–6.44) and those who had smoked over 20 days during the past 30 days (odds ratio = 1.77, 95% confidence interval = 1.26–2.49) were more likely to experience asthma symptoms. Healthcare providers should identify the risk behaviors of adolescents with asthma and counsel them and their parents simultaneously.
Regulating drug information in Europe: a pyrrhic victory for pharmaceutical industry critics?
Authors: Mulinari Shai
Published: October 2012

Informed by recent sociological debates on pharmaceuticalisation, this article examines the evolution of the current EU legal proposal on prescription drug information to patients, as well as the surrounding controversies. In 2008 the European Commission proposed the relaxation of the existing rules governing drug information provision to patients by the pharmaceutical industry. Critics of the industry’s influence over health policy and markets, including consumer organisations, industry‐independent patient organisations and health professionals, rejected the Commission’s proposal, claiming that the industry cannot be considered a reliable source of patient information due to inherent financial conflicts of interest. Since these critics were at least partially successful in rallying opinion against the Commission proposal, they functioned as countervailing forces to promotion‐driven pharmaceuticalisation. Even so, as a watered‐down version of the proposal moved through the European Parliament it was further modified to ultimately resemble the Swedish system that was held up as a high‐quality example of industry‐based information provision. Yet this article contends that the Swedish system displays evidence of corporate bias. Significantly, basing EU policy on a drug information system not resistant to corporate bias risks creating practices that violate the legally mandated mission of EU drug regulation, which is to ‘promote and protect public health’.
How did international agencies perceive the avian influenza problem? The adoption and manufacture of the ‘One World, One Health’ framework
Authors: Chien Yu‐Ju
Published: October 2012

Over the past few years, a ‘One World, One Health’ (OWOH) policy framework has become the guiding principle for international responses to avian influenza and other zoonotic infectious diseases. Several specialised inter‐governmental agencies, including the World Health Organization, the Food and Agricultural Organization and World Organization for Animal Health, jointly endorsed and promoted this framework. This article attempts to explain why international agencies advocated OWOH despite its vagueness. By examining how these international agencies gradually reframed avian flu problems, this article illustrates the crucial roles of international agencies in constructing disease knowledge and relevant policy responses. It shows that the three agencies adopted an all‐inclusive approach to reduce conflicts, defend their legitimacy, and facilitate commitment for collaboration. Not only has this new framework reduced tensions between agencies, it has also reshaped the interests and interactions of other global actors. The case thus illustrates how these organisational actors actively manufacture new cognitive frames and policy regimes that advance their own legitimacy and influence.
West Nile virus: the production of a public health pandemic
Authors: Gislason Maya K.
Published: October 2012

The West Nile virus (WNV), as it was presented in the texts and discourses on the Public Health Agency of Canada’s (PHAC) website during its initial emergence, was an effect of the kinds of knowledge, techniques of power and disciplinary apparatuses that operate on that website and in society. With reference to Michel Foucault’s relations of power, this article offers an approach for translating theories of power into techniques and technologies of power that can be used to conduct a social construction discourse analysis, and gives examples from the use of surveillance, normalisation, exclusion and regulation in PHAC’s responses to the WNV epidemic in Canada. This study concludes with the assertion that shifting the ways in which social and political relations of power contour public health theories and practice is crucial. The present moment requires the development of global health responses to pandemics that are rooted less in the proliferation of apparatuses of control and more in epidemiological innovations and integrated, multi‐perspectival research approaches to infectious diseases research, and in the governance of pandemic control and prevention initiatives.
The market in freehold land, 1300–1509: the evidence of feet of fines
Authors: Yates Margaret
Published: October 2012

This article provides time series data on the medieval market in freehold land, including the changing social composition of freeholders, level of market activity, size and complexity of landholdings, and shifts in the market value of land. These are subjects hitherto largely ignored due, in part, to the disparate nature of the evidence. It argues that feet of fines, despite archival limitations, if employed with care and an understanding of the underlying changes in the common law of real property, are capable of providing quantifiable evidence spanning hundreds of years and comparable across large areas ofEngland.
Efficacy of botulinum toxin A in children with cerebral palsy in Gross Motor Function Classification System levels IV and V: a systematic review
Authors: PIN TAMIS W , ELMASRY JESSICA , LEWIS JENNY
Published: October 2012

Aim  Previous studies have shown the efficacy of botulinum toxin type A (BoNT‐A) in the management of ambulant individuals with cerebral palsy (CP). There is little evidence on its use in non‐ambulant children with CP. This review aimed to investigate indications and efficacy for BoNT‐A use in managing pain, care, and comfort, and improving function in children with CP in Gross Motor Function Classification System (GMFCS) levels IV and V.

Method  Electronic databases were searched from the earliest available date to June 2012 using a combination of subject headings and free text. Inclusion criteria consisted of studies with (1) participants aged 18 or under, (2) participants with CP in GMFCS levels IV and V, (3) participants receiving BoNT‐A treatment, and (4) studies published in English‐language peer‐reviewed journals.

Results  The search resulted in a total of 814 studies, of which 19 met the inclusion criteria. Eighteen studies provided level IV or V evidence and one level I evidence according to the American Academy for Cerebral Palsy and Developmental Medicine guidelines for the development of systematic reviews. Most of the studies were of weak to moderate methodological quality.

Interpretation  The evidence that BoNT‐A is effective in reducing postoperative pain in children with CP in GMCFS levels IV and V is limited, with only one level I study identified. Remaining indications were general pain reduction, maintaining hip integrity, achieving functional changes, and goal attainment. A high percentage of participants in the studies showed positive changes in these areas. With the poor level of evidence of the included studies, no definite conclusion could be drawn on the indications for BoNT‐A use in children with CP in GMCFS levels IV and V. Further investigation by rigorous studies is required.
Assessment of upper‐limb capacity, performance, and developmental disregard in children with cerebral palsy: validity and reliability of the revised Video‐Observation Aarts and Aarts module: Determine Developmental Disregard (VOAA‐DDD‐R)
Authors: HOUWINK ANNEMIEKE , GEERDINK YVONNE A , STEENBERGEN BERT , GEURTS ALEXANDER C H , AARTS PAULINE B M
Published: October 2012

Aim  To investigate the validity and reliability of the revised Video‐Observation Aarts and Aarts module: Determine Developmental Disregard (VOAA‐DDD‐R).

Method  Upper‐limb capacity and performance were assessed in children with unilateral spastic cerebral palsy (CP) by measuring overall duration of affected upper‐limb use and the frequency of specific behaviours during a task in which bimanual activity was demanded (‘stringing beads’) and stimulated (‘decorating a muffin’). Developmental disregard was defined as the difference in duration of affected upper‐limb use between both tasks. Raters were two occupational and one physical therapist who received 3 hours of training. Construct validity was determined by comparing children with CP with typically developing children. Intrarater, interrater, and test–retest reliability were determined using the intraclass correlation coefficient. Standard errors of measurement and smallest detectable differences were also calculated.

Results  Twenty‐five children with CP (15 females, 10 males; mean age 4y 9mo [SD 1y 7mo], range 2y 9mo–8y; Manual Ability Classification System levels I–III) scored lower on capacity (p=0.052) and performance (p<0.001), and higher on developmental disregard (p<0.001) than 46 age‐ and sex‐matched typically developing children (23 males; mean age 5y 3mo [SD 1y 5mo], range 2y 6mo–8y). The intraclass correlation coefficients (0.79–1.00) indicated good reliability. Absolute agreement was high, standard errors of measurement ranged from 4.5 to 6.8%, and smallest detectable differences ranged from 12.5 to 19.0%.

Interpretation  The VOAA‐DDD‐R can be reliably and validly used by occupational and physical therapists to assess upper‐limb capacity, performance, and developmental disregard in children (2y 6mo–8y) with CP.
Clinical association of intrathecal and mirrored oligoclonal bands in paediatric neurology
Authors: SINCLAIR ADRIANE J , WIENHOLT LOUISE , TANTSIS ESTHER , BRILOT FABIENNE , DALE RUSSELL C
Published: October 2012

Aim  Biomarkers such as autoantibodies, neopterin, and oligoclonal bands (OCBs) are increasingly used for the diagnosis of treatable inflammatory central nervous system (CNS) disorders. We investigated the correlation between the results of OCB testing and clinical diagnoses in a large contemporary cohort of children with a broad range of neurological conditions.

Method  Cerebrospinal fluid (CSF) and serum from 200 children (94 females, 106 males; age range 2mo–15y 10mo, mean age 6y 9mo, SD ±4.9) who underwent CSF investigation for their neurological condition were tested for OCBs using isoelectric focusing.

Results  The patients were divided into those with inflammatory (n=58) and non‐inflammatory (n=142) CNS disorders. Intrathecal OCBs (OCBs restricted to the CSF) were found in 11 out of 58 (19%) of those with inflammatory CNS disorders compared with none of the 142 patients with non‐inflammatory CNS disorders (p<0.001). Diseases associated with intrathecal OCB were multiple sclerosis, Rasmussen encephalitis, N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis, voltage‐gated potassium channel (VGKC) encephalopathy, herpes (HSV) encephalitis, ‘other’ encephalitides, acute cerebellar ataxia, and aseptic meningitis. Mirrored OCBs (identical OCBs in the serum and CSF) were less specific but were still found in 14 out of 58 (24%) children with inflammatory CNS disorders compared with only 6 out of 142 (4%) children with non‐inflammatory CNS disorders (p<0.001). Diseases associated with mirrored OCBs included acute disseminated encephalomyelitis (ADEM), VGKC encephalopathy, West syndrome, NMDAR encephalitis, ‘other’ encephalitides, polio‐like illness, Rasmussen encephalitis, cerebral vasculitis, metachromatic leukodystrophy, and bacterial meningitis. Intrathecal OCBs and mirrored OCBs had a positive predictive value for inflammatory CNS disease of 1 (95% confidence interval [CI] 0.68–1) and 0.7 (95% CI 0.46–0.87) respectively.

Conclusion  Intrathecal OCBs were restricted to patients with inflammatory CNS disorders. They are a useful, but non‐specific, biomarker of CNS inflammation of multiple causes. Mirrored OCBs are less specific, but still support a possible inflammatory CNS disorder. The presence of either intrathecal or mirrored OCBs should raise suspicion of an inflammatory CNS disorder.
Stability assessment of lyophilized intravenous immunoglobulin after reconstitution in glass containersand poly(vinyl chloride) bags
Authors: Parti Rajesh , Mankarious Samia
Published: October 2012

Human intravenous immunoglobulin (IGIV) has been in use for the past 20 years. This biological product is commonly provided in liquid or lyophilized dosage form. When the lyophilized product is rehydrated, it is usually administered within 2Ő3 h from time of complete dissolution. While this practice is advisable whenever possible, occasionally the patient or care‐giver may need to delay the infusion. Hence, a study of the stability of lyophilized IGIV after reconstitution with water for injection was conducted. The reconstituted product was stored either in its original glass container or pooled into poly(vinyl chloride) (PVC) bags. The effect of extended storage on the active ingredient (IgG), excipients (glucose, albumin) and extractables [sodium from glass vials, and di‐(2‐ethylhexyl) phthalate and cyclohexanone from PVC bags] was evaluated. The stability of the active ingredient was evaluated by physico‐chemical tests (molecular‐size distribution, pH, appearance, total protein), monitoring titres of a specific antibody (hepatitis B surface antigen) and an antibody functional test (bacterial opsonization). To evaluate the risk of microbial contamination during reconstitution and pooling procedures, sterility, pyrogen and animal‐safety tests were included in the protocol. The potential of IgG polymerizing in solution during storage and subsequent complement activation was evaluated by assaying for non‐specific binding of complement (anti‐complement activity). Results show that aseptically reconstituted IGIV is stable and remains sterile up to 48 h at 5 ° C. The reconstituted product was also found to be stable at room temperature (25 ° C) up to 12 h.