bluuebunny/crossref_metadata_2025 huggingface dataset:
Conformational Maturation and Post-ER Multisubunit Assembly of Gap Junction Proteins
Authors: VanSlyke Judy K. , Naus Christian C. , Musil Linda S.
Published: March 2009

For all previously well-characterized oligomeric integral membrane proteins, folding, multisubunit assembly, and recognition of conformationally immature molecules for degradation occurs at their organelle of synthesis. This cannot, however, be the case for the gap junction–forming protein connexin43 (Cx43), which when endogenously expressed undergoes multisubunit assembly into connexons only after its transport to the trans-Golgi network. We have developed two novel assays to assess Cx43 folding and assembly: acquisition of resistance of disulfide bonds to reduction by extracellularly added DTT and Triton X-114 detergent phase partitioning. We show that Cx43 synthesized at physiologically relevant levels undergoes a multistep conformational maturation process in which folding of connexin monomers within the ER is a prerequisite for multisubunit assembly in the TGN. Similar results were obtained with Cx32, disproving the widely reported contention that the site of endogenous β connexin assembly is the ER. Exogenous overexpression of Cx43, Cx32, or Cx26 allows these events to take place within the ER, the first example of the TGN and ER as alternative sites for oligomeric assembly. Our findings also constitute the first biochemical evidence that defective connexin folding is a cause of the human disorder X-linked Charcot-Marie-Tooth disease.
3 Agency and Intentionality
Authors: Rotman Andy
Published: March 2009

Part II focuses on the practice of prasāda, which like śraddhā originates with a visual interaction and culminates in giving, but which suggests a different epistemology, for it arises without one’s consent or even, necessarily, one’s awareness. It also suggests a different sociology of practice, both in terms of eligible participants and the visual objects engaged. Chapter 3 considers prasāda as a mental state—why it arises, in whom it arises, and what its arising leads to—as well as the various “agents of prasāda” (prāsādika) and the visual medium through which they operate. The chapter also discusses the meaning of prasāda, the domains in which it operates, and its connection with the visual. This discussion culminates in an analysis of prasāda-initiated offerings, the intentionality with which they are made, and the implications this has for Buddhist notions of charity.
Synergy Disequilibrium Plots: graphical visualization of pairwise synergies and redundancies of SNPs with respect to a phenotype
Authors: Watkinson John , Anastassiou Dimitris
Published: March 2009

Summary:We present a visualization tool applied on genome-wide association data, revealing disease-associated haplotypes, epistatically interacting loci, as well as providing visual signatures of multivariate correlations of genetic markers with respect to a phenotype.

Availability:Freely available on the web at: http://www.ee.columbia.edu/~anastas/sdplots

Contact:  anastas@ee.columbia.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Quantifying and reducing the surface blind zone and the seabed dead zone using new technology
Authors: Totland Atle , Johansen Geir O. , Godø Olav R. , Ona Egil , Torkelsen Terje
Published: March 2009

Totland, A., Johansen, G. O., Godø, O. R., Ona, E., and Torkelsen, T. 2009. Quantifying and reducing the surface blind zone and the seabed dead zone using new technology. – ICES Journal of Marine Science, 66: 1370–1376. The surface blind zone and the seabed dead zone are unobservable with hull-mounted acoustic systems. These constraints may seriously limit the effectiveness of acoustic observations in studies of ecosystem dynamics. In this paper, new technologies are used to make observations in these boundary zones, by augmenting conventional acoustic observations from transducers mounted in a retractable keel with simultaneous observations from two autonomous acoustic systems, one sampling the surface blind zone and the other the seabed dead zone. These observations to some extent overlap in depth, which allows comparisons between data collected with the vessel and the corresponding data from the two autonomous systems. The main targets of the investigation were young-of-the-year gadoids in the surface blind zone and older cod at least partly in the seabed dead zone. Species and their sizes were identified from trawl samples. The advantages and limitations of using new autonomous equipment for quantifying the acoustic backscattering within otherwise unobservable zones are discussed. The magnitudes of potential measurement biases in acoustic data collected with the vessel are also estimated for this survey.
Reduced abundance of insects and spiders linked to radiation at Chernobyl 20 years after the accident
Authors: Møller Anders Pape , Mousseau Timothy A.
Published: March 2009

Effects of low-level radiation on abundance of animals are poorly known. We conducted standardized point counts and line transects of bumble-bees, butterflies, grasshoppers, dragonflies and spider webs at forest sites around Chernobyl differing in background radiation by over four orders of magnitude. Abundance of invertebrates decreased with increasing radiation, even after controlling for factors such as soil type, habitat and height of vegetation. These effects were stronger when comparing plots differing in radiation within rather than among sites, implying that the ecological effects of radiation from Chernobyl on animals are greater than previously assumed.
Stable isotopes document the trophic structure of a deep-sea cephalopod assemblage including giant octopod and giant squid
Authors: Cherel Y. , Ridoux V. , Spitz J. , Richard P.
Published: March 2009

Although deep-sea cephalopods are key marine organims, their feeding ecology remains essentially unknown. Here, we report for the first time the trophic structure of an assemblage of these animals (19 species) by measuring the isotopic signature of wings of their lower beaks, which accumulated in stomachs of stranded sperm whales. Overall, the species encompassed a narrow range in δ
13
C values (1.7‰), indicating that they lived in closely related and overlapping habitats. δ
13
C values can be interpreted in terms of distribution with the more
13
C-depleted species (e.g.
Stigmatoteuthis arcturi
,
Vampyroteuthis infernalis
) having a more pelagic habitat than the more
13
C-enriched, bathyal species (e.g.
Todarodes sagittatus
and the giant squid
Architeuthis dux
). The cephalopods sampled had δ
15
N values ranging 4.6‰, which is consistent with the species spanning approximately 1.5 trophic levels. Neither the giant octopod (
Haliphron atlanticus
) nor the giant squid reached the highest trophic position. Species δ
15
N was independent of body size, with large squids having both the highest (
Taningia danae
) and lowest (
Lepidoteuthis grimaldii
) δ
15
N values. Their trophic position indicates that some species share the top of the food web, together with other megacarnivores such as the sperm whale.
A microfabricated wedge-shaped adhesive array displaying gecko-like dynamic adhesion, directionality and long lifetime
Authors: Parness Aaron , Soto Daniel , Esparza Noé , Gravish Nick , Wilkinson Matt , Autumn Kellar , Cutkosky Mark
Published: March 2009

Gecko adhesion has become a paradigmatic example of bio-inspired engineering, yet among the many gecko-like synthetic adhesives (GSAs), truly gecko-like performance remains elusive. Many GSAs have previously demonstrated one or two features of the gecko adhesive. We present a new wedge-shaped GSA that exhibits several gecko-like properties simultaneously: directional features; zero force at detachment; high ratio of detachment force to preload force; non-adhesive default state; and the ability to maintain performance while sliding, even after thousands of cycles. Individual wedges independently detach and reattach during sliding, resulting in high levels of shear and normal adhesion during drag. This behaviour provides a non-catastrophic failure mechanism that is desirable for applications such as climbing robots where sudden contact failure would result in serious falls. The effects of scaling patch sizes up to tens of square centimetres are also presented and discussed. Patches of 1 cm
2
had an adhesive pressure of 5.1 kPa while simultaneously supporting 17.0 kPa of shear. After 30 000 attachment/detachment cycles, a patch retained 67 per cent of its initial adhesion and 76 per cent of its initial shear without cleaning. Square-based wedges of 20 μm and 50 μm are manufactured in a moulding process where moulds are fabricated using a dual-side, dual-angle lithography process on quartz wafers with SU-8 photoresist as the mould material and polydimethylsiloxane as the cast material.
Dynamics of subglacial floods
Authors: Fowler A.C.
Published: March 2009

The Nye model of jökulhlaups is able to explain both their periodicity and even the detailed shape of the flood hydrograph. In this paper, we show how the model can be used to predict the shape of the hydrographs from the subglacial lake Grímsvötn beneath Vatnajökull in Iceland, and we comment on three particular issues that have proved contentious in the application of the Nye model: the role of water temperature; the shape of the flood channel; and the value of the bed roughness coefficient.
Reduced biological control and enhanced chemical pest management in the evolution of fungus farming in ants
Authors: Fernández-Marín Hermógenes , Zimmerman Jess K. , Nash David R. , Boomsma Jacobus J. , Wcislo William T.
Published: March 2009

To combat disease, most fungus-growing ants (Attini) use antibiotics from mutualistic bacteria (
Pseudonocardia
) that are cultured on the ants' exoskeletons and chemical cocktails from exocrine glands, especially the metapleural glands (MG). Previous work has hypothesized that (i)
Pseudonocardia
antibiotics are narrow-spectrum and control a fungus (
Escovopsis
) that parasitizes the ants' fungal symbiont, and (ii) MG secretions have broad-spectrum activity and protect ants and brood. We assessed the relative importance of these lines of defence, and their activity spectra, by scoring abundance of visible
Pseudonocardia
for nine species from five genera and measuring rates of MG grooming after challenging ants with disease agents of differing virulence.
Atta
and
Sericomyrmex
have lost or greatly reduced the abundance of visible bacteria. When challenged with diverse disease agents, including
Escovopsis
, they significantly increased MG grooming rates and expanded the range of targets. By contrast, species of
Acromyrmex
and
Trachymyrmex
maintain abundant
Pseudonocardia.
When challenged, these species had lower MG grooming rates, targeted primarily to brood. More elaborate MG defences and reduced reliance on mutualistic
Pseudonocardia
are correlated with larger colony size among attine genera, raising questions about the efficacy of managing disease in large societies with chemical cocktails versus bacterial antimicrobial metabolites.
Biodiversity and body size are linked across metazoans
Authors: McClain Craig R. , Boyer Alison G.
Published: March 2009

Body size variation across the Metazoa is immense, encompassing 17 orders of magnitude in biovolume. Factors driving this extreme diversification in size and the consequences of size variation for biological processes remain poorly resolved. Species diversity is invoked as both a predictor and a result of size variation, and theory predicts a strong correlation between the two. However, evidence has been presented both supporting and contradicting such a relationship. Here, we use a new comprehensive dataset for maximum and minimum body sizes across all metazoan phyla to show that species diversity is strongly correlated with minimum size, maximum size and consequently intra-phylum variation. Similar patterns are also observed within birds and mammals. The observations point to several fundamental linkages between species diversification and body size variation through the evolution of animal life.
Post-weaning maternal effects and the evolution of female dominance in the spotted hyena
Authors: Watts Heather E. , Tanner Jaime B. , Lundrigan Barbara L. , Holekamp Kay E.
Published: March 2009

Mammalian societies in which females dominate males are rare, and the factors favouring the evolution of female dominance have yet to be clearly identified. We propose a new hypothesis for the evolution of female dominance and test its predictions with empirical data from the spotted hyena (Crocuta crocuta), a well-studied species characterized by female dominance. We suggest that constraints imposed by the development of a feeding apparatus specialized for bone cracking, in combination with the intensive feeding competition characteristic of spotted hyenas, led to the evolution of female dominance. Specifically, we propose that protracted development of the feeding apparatus in young hyenas led to selection for increased aggressiveness in females as a compensatory mechanism for mothers to secure food access for their young after weaning. Our analyses yielded results consistent with this hypothesis. Morphological and behavioural measurements indicate that skull development is indeed protracted in this species; spotted hyenas do not achieve adult skull size or feeding performance capabilities until after sexual maturity. The period between weaning and completed skull development is particularly challenging, as indicated by high mortality. Finally, maternal presence between weaning and full skull maturity, as well as the relative ability of females to aggressively displace conspecifics from food, are important determinants of offspring survival.
Alternative Ac/Ds transposition induces major chromosomal rearrangements in maize
Authors: Zhang Jianbo , Yu Chuanhe , Pulletikurti Vinay , Lamb Jonathan , Danilova Tatiana , Weber David F. , Birchler James , Peterson Thomas
Published: March 2009

Barbara McClintock reported that the Ac/Ds transposable element system can generate major chromosomal rearrangements (MCRs), but the underlying mechanism has not been determined. Here, we identified a series of chromosome rearrangements derived from maize lines containing pairs of closely linked Ac transposable element termini. Molecular and cytogenetic analyses showed that the MCRs in these lines comprised 17 reciprocal translocations and two large inversions. The breakpoints of all 19 MCRs are delineated by Ac termini and characteristic 8-base-pair target site duplications, indicating that the MCRs were generated by precise transposition reactions involving the Ac termini of two closely linked elements. This alternative transposition mechanism may have contributed to chromosome evolution and may also occur during V(D)J recombination resulting in oncogenic translocations.
Shugoshin prevents cohesin cleavage by PP2ACdc55-dependent inhibition of separase
Authors: Clift Dean , Bizzari Farid , Marston Adele L.
Published: March 2009

Chromosome segregation is triggered by separase, an enzyme that cleaves cohesin, the protein complex that holds sister chromatids together. Separase activation requires the destruction of its inhibitor, securin, which occurs only upon the correct attachment of chromosomes to the spindle. However, other mechanisms restrict separase activity to the appropriate window in the cell cycle because cohesin is cleaved in a timely manner in securin-deficient cells. We investigated the mechanism by which the protector protein Shugoshin counteracts cohesin cleavage in budding yeast. We show that Shugoshin can prevent separase activation independently of securin. Instead, PP2ACdc55 is essential for Shugoshin-mediated inhibition of separase. Loss of both securin and Cdc55 leads to premature sister chromatid separation, resulting in aneuploidy. We propose that Cdc55 is a separase inhibitor that acts downstream from Shugoshin under conditions where sister chromatids are not under tension.
Clinical trial: cyclophosphamide pulse therapy – a promising therapeutic alternative in refractory Crohn’s disease
Authors: SCHMIDT K. J. , FELLERMANN K. , WELLHÖNER P. , WEITZ G. , HOMANN N. , HERRLINGER K. , LEHNERT H. , LUDWIG D. , BÜNING J.
Published: March 2009

Background  In severe steroid‐refractory Crohn’s disease (CD), established therapies fail in a relevant proportion of patients. Recent pilot studies indicated the efficacy of cyclophosphamide pulse therapy in these patients.

Aim  To provide further and substantial evidence for the rationale to apply cyclophosphamide pulse therapy as therapeutic option in severe courses of CD.

Methods  Fifteen patients with steroid‐refractory (n = 13) or steroid‐dependent (n = 2) CD received 2–6 (median 3) monthly pulses of 750 mg cyclophosphamide in an open‐label fashion. Eleven patients were on concomitant immunosuppression (azathioprine/mercaptopurine n = 9; methotrexate n = 2).

Results  Thirteen of 15 patients (87%) had a clinical response (CDAI decrease >100). Ten patients (67%) went into remission (CDAI <150) after 8 weeks. Steroid‐free remission was achieved in eight patients (54%). Two patients (13%) failed to respond. Median CDAI decreased from 420 (245–550) to 100 (26–538) at week 8. Remission lasted 16 months (median, range 4–40). In three patients, arthritis, erythema nodosum and episcleritis completely resolved. Cyclophosphamide pulse therapy administration was well tolerated in all subjects.

Conclusions  Cyclophosphamide pulse therapy is safe and highly effective for induction and maintenance of remission in steroid‐refractory/‐dependent CD. There is a strong need for additional experience to improve the setting of the encouraging cyclophosphamide treatment in CD.
Higher diagnostic accuracy with the ThinPrep method in a simulated intraoperative environment
Authors: Ho C. , Khalil M. , Duggan M. A.
Published: March 2009

Objective:  To compare the accuracy of intraoperative fine needle aspiration cytology samples prepared by the ThinPrep method to conventional cytological methods. Specimen adequacy and turn around time (TAT) were also assessed.

Methods:  Fifty consecutive fresh tumours submitted for histological analysis were aspirated and each prepared as follows: (i) direct smear with H&E stain, (ii) direct smear with Pap stain, (iii) ThinPrep slide with H&E stain, and (iv) ThinPrep slide with Pap stain. The slides were randomly distributed to three cytopathologists for interpretation. The quality of the preparation, the diagnosis and the time needed for interpretation were recorded.

Results:  Accuracy was measured as the percentage of absolute agreement between the cytological and the histopathological diagnoses of the lesions. Histologically, there were 43 malignant and six benign lesions and one atypical lipoma. The TAT began when the slides/cytolyte specimens arrived at the lab and ended with the pathologist’s diagnosis.

Conclusions:  In terms of accuracy and specimen adequacy, ThinPrep slides with Pap stain is the best procedure. This advantage however is offset by the longer testing time.
Effect of gold nanoparticle on the microscopic morphology of white blood cell
Authors: Wiwanitkit V. , Sereemaspun A. , Rojanathanes R.
Published: March 2009

Background:  In medicine, there is limited knowledge on the toxicity of nanoparticles. In medicine, there has been limited knowledge on the effect of nanoparticles on the white blood cell.

Objective:  To evaluate the effect of gold nanoparticle on the microscopic morphology of white blood cell.

Setting:  Chulalongkorn Univesity, Bangkok, Thailand.

Method:  This study was performed as an experimental study. Mixture of gold nanoparticle solution and blood sample was prepared and analysed.

Result:  This work revealed that after mixing the blood sample with gold nanoparticle solution, accumulation of gold nanoparticle in the white blood cell was observed.

Conclusion:  The effect of gold nanoparticle on the white blood cell can be detected and this knowledge can be used in cytotoxic drug treatment.
Anti‐inflammatory effects of 5‐HT3 receptor antagonist, tropisetron on experimental colitis in rats
Authors: Mousavizadeh K. , Rahimian R. , Fakhfouri G. , Aslani F. S. , Ghafourifar P.
Published: March 2009

Background  There is a pressing need for research that will lead to the development of new therapeutic approaches for treating inflammatory bowel disease (IBD). The aim of this study was to investigate the effects of tropisetron, a 5‐Hydroxytryptamine (5‐HT)‐3 receptor antagonist with anti‐inflammatory properties in a model of experimental colitis in rat.

Materials and methods  Acetic acid model of colitis in rats was used. Colitis was induced by intracolonal instillation of 4% (v/v) acetic acid. One hour after induction of colitis, intraperitoneal (IP) or intrarectal (IR) tropisetron (2 mg kg−1, either route) or dexamethasone (1 mg kg−1, either route) was administered. The severity of colitis was assessed 24 h later using macroscopic and microscopic changes of damaged colon, measurement of inflammatory cytokines interleukin‐1β, interleukin‐6 and tumour necrosis factor‐α levels and oxidative stress markers myeloperoxidase (MPO) and malondialdehyde (MDA) in colonic tissues.

Results  Tropisetron decreased colonic macroscopic and microscopic damage scores. This was associated with significant reduction in both neutrophil infiltration indicated by decreased colonic MPO activity and lipid peroxidation measured by MDA content, as well as a decreased colonic inflammatory cytokines. IR tropisetron decreased colonic damage that was associated with decreased neutrophil infiltration, lipid peroxidation and colonic inflammatory cytokines. Beneficial effects of tropisetron were lower than those of dexamethasone. No significant differences were observed between IP and IR administration with the exception of MDA level more diminished by IP tropisetron and dexamethasone.

Conclusions  Tropisetron exert beneficial effects in experimental rat colitis and therefore might be useful in the treatment of IBD.
Transport and environmental temperature variability of eggs and larvae of the Japanese anchovy (Engraulis japonicus) and Japanese sardine (Sardinops melanostictus) in the western North Pacific estimated via numerical particle‐tracking experiments
Authors: ITOH SACHIHIKO , YASUDA ICHIRO , NISHIKAWA HARUKA , SASAKI HIDEHARU , SASAI YOSHIKAZU
Published: March 2009

Numerical particle‐tracking experiments were performed to investigate the transport and variability in environmental temperature experienced by eggs and larvae of Pacific stocks of the Japanese anchovy (Engraulis japonicus) and Japanese sardine (Sardinops melanostictus) using high‐resolution outputs of the Ocean General Circulation Model for the Earth Simulator (OFES) and the observed distributions of eggs collected from 1978 to 2004. The modeled anchovy individuals tend to be trapped in coastal waters or transported to the Kuroshio–Oyashio transition region. In contrast, a large proportion of the sardines are transported to the Kuroshio Extension. The egg density‐weighted mean environmental temperature until day 30 of the experiment was 20–24°C for the anchovy and 17–20°C for the sardine, which can be explained by spawning areas and seasons, and interannual oceanic variability. Regression analyses revealed that the contribution of environmental temperature to the logarithm of recruitment per spawning (expected to have a negative relationship with the mean mortality coefficient) was significant for both the anchovy and sardine, especially until day 30, which can be regarded as the initial stages of their life cycles. The relationship was quadratic for the anchovy, with an optimal temperature of 21–22°C, and linear for the sardine, with a negative coefficient. Differences in habitat areas and temperature responses between the sardine and anchovy are suggested to be important factors in controlling the dramatic out‐of‐phase fluctuations of these species.
Emerin immunohistochemistry reveals diagnostic features of nuclear membrane arrangement in thyroid lesions
Authors: Asioli Sofia , Bussolati Gianni
Published: March 2009

Aims:  Objective appreciation of irregularities of the nuclear shape is a key parameter in the diagnosis of thyroid lesions, since foldings of the nuclear membrane (NM) featuring indentations, grooves and pseudoinclusions characterize papillary thyroid carcinomas (PTC). The aim was to focus on the immunohistochemistry of emerin, a protein of the NM whose decoration best demarcates the nuclear shape.

Methods and results:  Immunohistochemistry of the NM with emerin as well as three‐dimensional reconstruction of the images (through deconvolution processing) performed on a series of 54 cases (processed following the tissue array procedure) revealed a uniform arrangement of the NM in non‐neoplastic lesions (thyroiditis, microfollicular goitre, follicular adenoma) and normal thyroid as well as in follicular carcinoma. In contrast, irregular folding of the membrane and presence of curling and invaginations, eventually leading to the formation of nuclear pseudoinclusions, was observed in PTC cells.

Conclusions:  Decoration of the NM represents an original approach to identify PTC nuclear shape, highlights new structural features and might be helpful in the differential diagnosis between so‐called nuclear pseudoinclusions and artefactual ‘bubbles’.
Phylogeography of the magpie‐robin species complex (Aves: Turdidae: Copsychus) reveals a Philippine species, an interesting isolating barrier and unusual dispersal patterns in the Indian Ocean and Southeast Asia
Authors: Sheldon Frederick H. , Lohman David J. , Lim Haw C. , Zou Fasheng , Goodman Steven M. , Prawiradilaga Dewi M. , Winker Kevin , Braile Thomas M. , Moyle Robert G.
Published: March 2009

Aim  The oriental magpie‐robin (Copsychus saularis) of South and Southeast Asia is a phenotypically variable species that appears to be closely related to two endemic species of the western Indian Ocean: the Madagascar magpie‐robin (Copsychus albospecularis) and the Seychelles magpie‐robin (Copsychus sechellarum). This unusual distribution led us to examine evolutionary relationships in magpie‐robins, and also the taxonomic significance of their plumage variation, via a molecular phylogenetic and population genetic analysis of C. saularis and C. albospecularis.

Location  Southern Asia from Nepal across Indochina to southern China, and the Indian Ocean from Madagascar to the Greater Sunda and Philippine islands.

Methods  We sequenced 1695 nucleotides of mitochondrial DNA comprising the complete second subunit of the nicotinamide adenine dinucleotide dehydrogenase (ND2) gene and 654 bases of the cytochrome c oxidase subunit I (COI) region in 51 individuals of eight C. saularis subspecies, 10 individuals of C. albospecularis (one subspecies) and single individuals of two other Copsychus species as outgroups. The data were analysed phylogenetically, with maximum likelihood, Bayesian, relaxed clock and parsimony methods, and geographically for patterns of genetic diversity.

Results  Phylogenetic analysis indicated that C. albospecularis lies within the nominal C. saularis, making C. saularis polyphyletic. Malagasy and non‐Philippine Asian populations form a monophyletic group that is sister to a clade of Philippine populations. Within non‐Philippine Asian populations, two groups are evident: black‐bellied birds in the eastern Greater Sunda islands and white‐bellied birds in the western Sundas and on mainland Asia.

Main conclusions  The phylogeny of magpie‐robins suggests a novel pattern of dispersal and differentiation in the Old World. Ancestral magpie‐robins appear to have spread widely among islands of the Indian Ocean in the Pliocene, probably aided by their affinity for coastal habitats. Populations subsequently became isolated in island groups, notably the Philippines, Madagascar and the Greater Sundas, leading to speciation in all three areas. Isolation in the Philippines may have been aided by competitive exclusion of C. saularis from Palawan by a congener, the white‐vented shama (Copsychus niger). In the Greater Sundas, white‐bellied populations appear to have invaded Borneo and Java recently, where they hybridize with resident black‐bellied birds.
Understanding pharmacist decision making for adverse drug event (ADE) detection
Authors: Phansalkar Shobha , Hoffman Jennifer M. , Hurdle John F. , Patel Vimla L.
Published: March 2009

Rationale, aims and objective  Manual chart review is an effective but expensive method for adverse drug event (ADE) detection. Building an expert system capable of mimicking the human expert's decision pathway, to deduce the occurrence of an ADE, can improve efficiency and lower cost. As a first step to build such an expert system, this study explores pharmacist's decision‐making processes for ADE detection.

Methods  Think‐aloud procedures were used to elicit verbalizations as pharmacists read through ADE case scenarios. Two types of information were extracted, firstly pharmacists' decision‐making strategies regarding ADEs and secondly information regarding pharmacists' unmet information needs for ADE detection. Verbal protocols were recorded and analysed qualitatively to extract ADE information signals. Inter‐reviewer agreement for classification of ADE information signals was calculated using Cohen's kappa.

Results  We extracted a total of 110 information signals, of which 73% consisted of information that was interpreted by the pharmacists from the case scenario and only about half (53%, n = 32) of the information signals were considered relevant for the detection of the ADEs. Excellent reliability was demonstrated between the reviewers for classifying signals. Fifty information signals regarding unmet information needs were extracted and grouped into themes based on the type of missing information.

Conclusions  Pharmacists used a forward reasoning approach to make implicit deductions and validate hypotheses about possible ADEs. Verbal protocols also indicated that pharmacists' unmet information needs occurred frequently. Developing alerting systems that meet pharmacists' needs adequately will enhance their ability to reduce preventable ADEs, thus improving patient safety.
Post‐operative anxiety and depression levels in orthopaedic surgery: a study of 56 patients undergoing hip or knee arthroplasty
Authors: Nickinson Richard S. J. , Board Timothy N. , Kay Peter R.
Published: March 2009

Objective  To investigate the presence and rates of anxiety and depression in postsurgical patients.

Methods  The Hospital Anxiety and Depression Scale was used to measure anxiety and depression levels. Patients completed the questionnaire on the day prior to surgery, then on each post‐operative day up to and including their day of discharge. Statistical analysis using logistic regression was performed to determine whether any variables were risk factors for developing anxiety or depression. Fifty‐six patients undergoing lower limb arthroplasty agreed to take part.

Results  Post‐operatively 17 patients became anxious prior to discharge. No variables were significant predictors of anxiety. Post‐operatively 28 subjects (50%) became depressed at some point prior to discharge. Females were more likely to become depressed than males odds ratio (OR) = 3.48 [95% confidence interval (CI) 1.01–11.88]. Those who had had a previous lower limb arthroplasty were more likely to develop post‐operative depression, OR = 3.92 (95% CI 1.05–14.6). Site of operation was not found to be significant, OR = 0.67 (95% CI 0.20–2.22). Age and anaesthetic method were not predictive of depression. The mean time point for development of depression was 2.43 days (SD = 1.40 days) and the time of deepest depression was 2.93 days (SD = 1.72 days). The mean length of depression was 1.93 days (SD = 1.21 days). The mean length of stay for depressed patients was 5 days (SD = 1.72), compared with 4 days for the non‐depressed patients (SD = 1.62 days).

Conclusion  The results suggest that post‐operative depression does occur in orthopaedic surgery. The prevalence may be higher than that reported in other surgical specialities. These findings emphasize the need for evaluation of patients' psychiatric state post‐operatively.
Cancer informational support and health care service use among individuals newly diagnosed: a mixed methods approach
Authors: Dubois Sylvie , Loiselle Carmen G.
Published: March 2009

Aim  To report on the integration of quantitative and qualitative findings to increase understanding of the role of cancer informational support and use of health care services among individuals newly diagnosed with breast or prostate cancer.

Methods  A mixed methods sequential design was used. First, a quantitative secondary analysis considered self‐report data from a large number of individuals newly diagnosed with cancer (n = 250); next, a follow‐up, in‐depth qualitative inquiry with distinct individuals also newly diagnosed was conducted (n = 20); last, using a quantitative‐hierarchical strategy, quantitative and qualitative findings were merged and re‐analyzed.

Results  Quantitative analyses showed significant relationships between informational support and health care services. For instance, individuals who received more intense cancer informational support [face‐to‐face and information technology (IT)] spent more time with nurses. Women with breast cancer as opposed to men with prostate cancer also were found to rely primarily on nurses for cancer information and information on health services available, whereas men relied mostly on their oncologists. In‐depth interviews revealed that informational support could be construed as positive, unsupportive, or mixed depending on context. The mixed design analysis documented positive experiences for individuals who reported to be better prepared for consultations and treatments with information provided by more than one source. Negative experiences with physicians were reported by both women and men but the former was about quality of cancer information provided and the latter in terms of quantity.

Conclusions  A mixed methods approach allowed a deeper understanding of the role of informational support on subsequent use of health care services by individuals with cancer. Further studies may include other types of cancer and diverse background characteristics to clarify how informational support and subsequent use of health services may be jointly determined by these factors.
Validity of overall self‐rated health as an outcome measure in small samples: a pilot study involving a case series
Authors: Rohrer James E. , Herman David C. , Merry Stephen P. , Naessens James M. , Houston Margaret S.
Published: March 2009

Objective  A single‐item measure of overall self‐rated health (SRH) commonly is used in population surveys, but has not been used in small pilot projects. The purpose of this study was to assess the validity of SRH in small samples.

Design  We used data from a prospective, observational weight‐loss project to compare change in SRH with change in body weight and physical activity (PA) (minutes) over 30 days (n = 34). Body mass index at baseline ranged from 25.5 to 50.4 (mean = 36.1, median = 34.6). SRH was self‐assessed using the following question: How would you rate your health overall?

Results  An increase in weight was associated with a reduction in SRH (r = 0.37, P = 0.03). An increase in PA was associated with improved SRH (r = 0.39, P = 0.02).

Conclusions  A single‐item SRH measure may be an efficient method for measuring programme outcomes, and may also be useful for comparing the relative effectiveness of different programmes in pilot projects and quality improvement studies.
Factors influencing acute stroke guideline compliance: a peek inside the ‘black box’ for allied health staff
Authors: Luker Julie , Grimmer‐Somers Karen
Published: March 2009

Rationale, aim and objective  The use of stroke clinical guidelines is widely encouraged yet variably operationalized. The factors which support, or hinder guideline compliance are poorly understood, and there is little research which pertains to the unique roles of Allied Health (AH) staff when operationalizing stroke clinical guidelines. This study identifies factors influencing AH staff compliance with guideline recommendations in an acute stoke unit.

Method  A retrospective audit was conducted of hospital records of stroke patients admitted to an Australian tertiary metropolitan hospital in 2005. The recorded clinical care provided by an AH team was audited against the 38 recommendations in the Australian acute stroke guidelines relevant to allied health.

Results  Compliance with guideline recommendations was variable, with better care compliance found for younger patients, patients admitted on weekdays, and patients with poorer functional ability on admission, longer lengths of stay and better functional improvements during admission. Compliance also reflected the congruence of guideline recommendations with ‘usual practice’.

Conclusions  A number of factors influenced AH staff compliance with acute stroke guidelines. These findings are a platform upon which further implementation research can be launched for AH professionals.
Water intake and risk of hyponatraemia in Prader–Willi syndrome
Authors: Åkefeldt A.
Published: March 2009

Background and Methods  Unusual water intake and drinking behaviour has occasionally been observed in individuals with Prader–Willi syndrome (PWS). The aim of this study is to explore whether this observation is a part of the PWS phenotype and what the consequences may be. The parents of 51 individuals with PWS (age range 2–40 years) were asked by questionnaire to answer on past and present water intake, drinking behaviour, fluid preferences and medical treatment in their PWS‐affected and unaffected children. Questionnaires with information on 47 PWS individuals and 17 without PWS were returned for analysis. The questionnaire information was complemented with information from the individual's medical records. Siblings to PWS individuals made up the control group. The study was approved by the regional medical research ethics committee.

Results  During infancy, 36 (76%) individuals with PWS disliked water without any flavouring and had an extremely small daily intake of water. Seven individuals (15%) increased the daily water intake to unusually high amounts. In 45 the clinical PWS diagnosis was confirmed by molecular (genetic) testing: nine of them with a confirmed PWS diagnosis had a deletion of chromosome 15q11‐13, in nine individuals no deletion was identified. The majority of individuals who increased their water consumption to extreme values belonged to the non‐deletion group. Two in the non‐deletion group developed hyponatraemia while receiving psychiatric medication.

Conclusions  Infants with PWS seem to be predisposed to unusual drinking behaviour. They dislike and have an unusually small intake of pure water without flavouring, and most of them continue this even after infancy. Some individuals, especially those without deletion, increase their fluid intake and also accept pure water. They have an increased risk of developing water retention and severe hyponatraemia if exposed to medication known to cause side effects like the syndrome of inappropriate antidiuretic hormone secretion. Perhaps this behaviour is just secondary to overeating; perhaps it is a result of a dysfunction of the hypothalamic nuclei engaged in antidiuretic hormone production.
TIRF microscopy evanescent field calibration using tilted fluorescent microtubules
Authors: GELL C. , BERNDT M. , ENDERLEIN J. , DIEZ S.
Published: March 2009

Total internal reflection fluorescence microscopy has become a powerful tool to study the dynamics of sub‐cellular structures and single molecules near substrate surfaces. However, the penetration depth of the evanescent field, that is, the distance at which the excitation intensity has exponentially decayed to 1/e, is often left undetermined. This presents a limit on the spatial information about the imaged structures. Here, we present a novel method to quantitatively characterize the illumination in total internal reflection fluorescence microscopy using tilted, fluorescently labelled, microtubules. We find that the evanescent field is well described by a single exponential function, with a penetration depth close to theoretically predicted values. The use ofin vitroreconstituted microtubules as nanoscale probes results in a minimal perturbation of the evanescent field; excitation light scattering is eliminated and the refractive index of the sample environment is unchanged. The presented method has the potential to provide a generic tool forin situcalibration of the evanescent field.
Developing dual‐beam methodologies for the study of heterogeneous polymer‐based systems
Authors: BENAWRA J. , DONALD A.M. , SHANNON M.
Published: March 2009

The use of a combined focused ion beam/environmental scanning electron microscope (FIB/ESEM) offers new possibilities for imaging the internal structure of complex heterogeneous polymeric samples. The use of the focused ion beam, using positively charged gallium ions in conjunction with a measured ‘defocused’ low‐energy primary electron beam, has permitted milling through the heterostructure to be achieved in a controlled way, exposing the inner structure, without introducing significant ion beam damage/destruction into the sample. The subsequent use of the environmental scanning electron microscope for imaging the revealed internal structure has then enabled insulating polymer structures to be imaged, without charging problems. Cross‐sections of a 900‐nm‐thick spun cast film of phase‐separated polystyrene–polybutadiene blends have been successfully milled and imaged; the morphology agreeing with previous results produced using ultramicrotomy and transmission electron microscopy.
Not just vicariance: phylogeography of a Sonoran Desert euphorb indicates a major role of range expansion along the Baja peninsula
Authors: GARRICK R. C. , NASON J. D. , MEADOWS C. A. , DYER R. J.
Published: March 2009

To examine the generality of population‐level impacts of ancient vicariance identified for numerous arid‐adapted animal taxa along the Baja peninsula, we tested phylogeographical hypotheses in a similarly distributed desert plant, Euphorbia lomelii (Euphorbiaceae). In light of fossil data indicating marked changes in the distributions of Baja floristic assemblages throughout the Holocene and earlier, we also examined evidence for range expansion over more recent temporal scales. Two classes of complementary analytical approaches — hypothesis‐testing and hypothesis‐generating — were used to exploit phylogeographical signal from chloroplast DNA sequence data and genotypic data from six codominant nuclear intron markers. Sequence data are consistent with a scenario of mid‐peninsular vicariance originating c. 1 million years ago (Ma). Alternative vicariance scenarios representing earlier splitting events inferred for some animals (e.g. Isthmus of La Paz inundation, c. 3 Ma; Sea of Cortez formation, c. 5 Ma) were rejected. Nested clade phylo‐geographical analysis corroborated coalescent simulation‐based inferences. Nuclear markers broadened the temporal spectrum over which phylogeographical scenarios could be addressed, and provided strong evidence for recent range expansions along the north–south axis of the Baja peninsula. In contrast to previous plant studies in this region, however, the expansions do not appear to have been in a strictly northward direction. These findings contribute to a growing appreciation of the complexity of organismal responses to past climatic and geological changes — even when taxa have evolved in the same landscape context.
The Interaction of Monocyte Chemoattractant Protein‐1 and Tumour Necrosis Factor‐α in Mycobacterium tuberculosis‐induced HIV‐1 Replication at Sites of Active Tuberculosis
Authors: Mayanja‐Kizza H. , Wu M. , Aung H. , Liu S. , Luzze H. , Hirsch C. , Toossi Z.
Published: March 2009

Tuberculosis (TB) is a prominent opportunistic infection in HIV‐1‐infected subjects and enhances HIV‐1 replication. TB is associated with excess monocyte chemoattractant protein (MCP)‐1 and tumour necrosis factor (TNF)‐α activity in situ, both of which are implicated in transcriptional activation of HIV‐1. The role of MCP‐1 and TNF‐α in activation of HIV‐1 during TB and by Mycobacterium tuberculosis (MTB) in mononuclear cells from HIV‐1/TB subjects with pleural TB was examined here. Extremely high levels of MCP‐1 (as compared with TNF‐α) protein and mRNA were found in pleural fluid and pleural fluid mononuclear cells. Levels of MCP‐1 mRNA were sustained during in vitro culture of pleural fluid mononuclear cells. Neutralization of MCP‐1 (but not TNF‐α), resulted in inhibition of MTB induced HIV‐1 gag/pol mRNA. Neutralization of both MCP‐1 and TNF‐α, however, abrogated the effect of anti‐MCP‐1 antibody on HIV‐1 mRNA. LMP‐420, a small molecular transcriptional inhibitor of both TNF‐α and MCP‐1 expression, did not reduce MTB‐induced HIV‐1 expression. These data imply that MCP‐1 activity may be critical to activation of HIV‐1 at sites of TB. An interplay of MCP‐1 and TNF‐α is also suggested.
Inbreeding variability and population structure in the invasive haplodiploid palm‐seed borer (Coccotrypes dactyliperda)
Authors: Holzman J. P. , Bohonak A. J. , Kirkendall L. R. , Gottlieb D. , Harari A. R. , Kelley S. T.
Published: March 2009

We investigated the mating system and population genetic structure of the invasive haplodiploid palm‐seed borerCoccotrypes dactyliperdain California. We focused on whether these primarily inbreeding beetles have a ‘mixed‐breeding’ system that includes occasional outbreeding, and whether local inbreeding coefficients (FIS) varied with dominant environmental factors. We also analysed the genetic structure ofC. dactyliperdapopulations across local and regional scales. Based on the analysis of genetic variation at seven microsatellite loci in 1034 individual beetles from 59 populations, we found both high rates of inbreeding and plentiful evidence of mixed‐breeding.FISranged from −0.56 to 0.90, the highest variability reported within any animal species. There was a negative correlation betweenFISand latitude, suggesting that some latitude‐associated factor affecting mating decisions influenced inbreeding rates. Multiple regressions suggested that precipitation, but not temperature, may be an important correlate. Finally, we found highly significant genetic differentiation among sites, even over short geographic distances (< 1000 m).
Architecture of developing multicellular yeast colony: spatio‐temporal expression of Ato1p ammonium exporter
Authors: Váchová Libuše , Chernyavskiy Oleksandr , Strachotová Dita , Bianchini Paolo , Burdíková Zuzana , Ferčíková Ivana , Kubínová Lucie , Palková Zdena
Published: March 2009

Yeasts, when growing on solid surfaces, form organized multicellular structures, colonies, in which cells differentiate and thus possess different functions and undergo dissimilar fate. Understanding the principles involved in the formation of these structures requires new approaches that allow the study of individual cells directly in situ without needing to remove them from the microbial community. Here we introduced a new approach to the analysis of whole yeast microcolonies either containing specific proteins labelled by fluorescent proteins or stained with specific dyes, by two‐photon excitation confocal microscopy. It revealed that the colonies are covered with a thin protective skin‐like surface cell layer which blocks penetration of harmful compounds. The cells forming the layer are tightly connected via cell walls, the presence of which is essential for keeping of protective layer function. Viewing the colonies from different angles allowed us to reconstruct a three‐dimensional profile of the cells producing ammonium exporter Ato1p within developing microcolonies growing either as individuals or within a group of microcolonies. We show that neighbouring microcolonies coordinate production of Ato1p‐GFP. Ato1p itself appears synchronously in cells, which do not originate from the same ancestor, but occupy specific position within the colony.