bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilocus genotypes from Charles Darwin's finches: biodiversity lost since the voyage of theBeagle
Authors: Petren Kenneth , Grant Peter R. , Grant B. Rosemary , Clack Andrew A. , Lescano Ninnia V.
Published: March 2010

Genetic analysis of museum specimens offers a direct window into a past that can predate the loss of extinct forms. We genotyped 18 Galápagos finches collected by Charles Darwin and companions during the voyage of theBeaglein 1835, and 22 specimens collected in 1901. Our goals were to determine if significant genetic diversity has been lost since the Beagle voyage and to determine the genetic source of specimens for which the collection locale was not recorded. Using ‘ancient’ DNA techniques, we quantified variation at 14 autosomal microsatellite loci. Assignment tests showed several museum specimens genetically matched recently field-sampled birds from their island of origin. Some were misclassified or were difficult to classify. Darwin's exceptionally large ground finches (Geospiza magnirostris) from Floreana and San Cristóbal were genetically distinct from several other currently existing populations. Sharp-beaked ground finches (Geospiza difficilis) from Floreana and Isabela were also genetically distinct. These four populations are currently extinct, yet they were more genetically distinct from congeners than many other species of Darwin's finches are from each other. We conclude that a significant amount of the finch biodiversity observed and collected by Darwin has been lost since the voyage of theBeagle.
Differential activation and antagonistic function of HIF-α isoforms in macrophages are essential for NO homeostasis
Authors: Takeda Norihiko , O'Dea Ellen L. , Doedens Andrew , Kim Jung-whan , Weidemann Alexander , Stockmann Christian , Asagiri Masataka , Simon M. Celeste , Hoffmann Alexander , Johnson Randall S.
Published: March 2010

Hypoxic response and inflammation both involve the action of the hypoxia-inducible transcription factors HIF-1α and HIF-2α. Previous studies have revealed that both HIF-α proteins are in a number of aspects similarly regulated post-translationally. However, the functional interrelationship of these two isoforms remains largely unclear. The polarization of macrophages controls functionally divergent processes; one of these is nitric oxide (NO) production, which in turn is controlled in part by HIF factors. We show here that the HIF-α isoforms can be differentially activated: HIF-1α is induced by Th1 cytokines in M1 macrophage polarization, whereas HIF-2α is induced by Th2 cytokines during an M2 response. This differential response was most evident in polarized macrophages through HIF-α isoform-specific regulation of the inducible NO synthase gene by HIF-1α, and the arginase1 gene by HIF-2α. In silico modeling predicted that regulation of overall NO availability is due to differential regulation of HIF-1α versus HIF-2α, acting to, respectively, either increase or suppress NO synthesis. An in vivo model of endotoxin challenge confirmed this; thus, these studies reveal that the two homologous transcription factors, HIF-1α and HIF-2α, can have physiologically antagonistic functions, but that their antiphase regulation allows them to coordinately regulate NO production in a cytokine-induced and transcription-dependent fashion.
Imaging Embryonic Development in Caenorhabditis elegans
Authors: Mohler William A. , Isaacson Ariel B.
Published: March 2010

INTRODUCTION

Embryos are remarkable for their combination of pluripotency, three-dimensionality, and swiftness of subcellular and developmental rearrangements. Embryogenesis in the nematode Caenorhabditis elegans is uniquely suited among model systems to high-resolution dynamic imaging. Within a single high-magnification, high-numerical aperture (NA) microscope field, at submicrometer resolution, it is possible to observe several entire animals taking form. The full ~14-h course of embryonic cleavage and morphogenesis of this transparent, free-living worm is essentially invariant. Observing specific fluorescently labeled components during embryonic development promises to reveal the roles of organelles and molecules in an extremely diverse and reproducible set of contexts. The C. elegans community has created a growing collection of hundreds of transgenic strains expressing green fluorescent protein (GFP)-labeled versions of distinct endogenously expressed genes. The task of correlating the resulting expression and localization patterns in space and time is simultaneously alluring and technically demanding. This article describes the use of four-dimensional (4D) laser-scanning microscopy and subsequent data processing to record, portray, analyze, and compare the expression of fluorescently tagged gene products during development of the nematode embryo.
Introduction to Linkage Disequilibrium, the HapMap, and Imputation
Authors: Neale Benjamin M.
Published: March 2010

INTRODUCTION

Throughout the human genome, a correlation structure exists across genetic variation of different loci. Such a correlation structure means that knowing the genotype at one locus might provide information about the genotype at a second locus. This correlation between variation at different loci is termed linkage disequilibrium (LD). LD has implications in numerous avenues of genetic research. This article discusses the importance of LD in genetics, touching on both population genetics and association studies. It then introduces the seminal collaborative scientific endeavor to map LD in the human genome--the International HapMap Project--and its relevance for imputation.
SOMBRERO, BEARSKIN1, and BEARSKIN2 Regulate Root Cap Maturation inArabidopsis
Authors: Bennett Tom , van den Toorn Albert , Sanchez-Perez Gabino F. , Campilho Ana , Willemsen Viola , Snel Berend , Scheres Ben
Published: March 2010

The root cap has a central role in root growth, determining the growth trajectory and facilitating penetration into the soil. Root cap cells have specialized functions and morphologies, and border cells are released into the rhizosphere by specific cell wall modifications. Here, we demonstrate that the cellular maturation of root cap is redundantly regulated by three genes, SOMBRERO (SMB), BEARSKIN1 (BRN1), and BRN2, which are members of the Class IIB NAC transcription factor family, together with the VASCULAR NAC DOMAIN (VND) and NAC SECONDARY WALL THICKENING PROMOTING FACTOR (NST) genes that regulate secondary cell wall synthesis in specialized cell types. Lateral cap cells in smb-3 mutants continue to divide and fail to detach from the root, phenotypes that are independent of FEZ upregulation in smb-3. In brn1-1 brn2-1 double mutants, columella cells fail to detach, while in triple mutants, cells fail to mature in all parts of the cap. This complex genetic redundancy involves differences in expression, protein activity, and target specificity. All three genes have very similar overexpression phenotypes to the VND/NST genes, indicating that members of this family are largely functionally equivalent. Our results suggest that Class IIB NAC proteins regulate cell maturation in cells that undergo terminal differentiation with strong cell wall modifications.
Determination of the optimal stylet strategy for the C‐MAC® videolaryngoscope
Authors: McElwain J. , Malik M. A. , Harte B. H. , Flynn N. H. , Laffey J. G.
Published: March 2010

The C‐MAC® videolaryngoscope is a novel intubation device that incorporates a camera system at the end of its blade, thereby facilitating obtaining a view of the glottis without alignment of the oral, pharyngeal and tracheal axes. It retains the traditional Macintosh blade shape and can be used as a direct or indirect laryngoscope. We wished to determine the optimal stylet strategy for use with the C‐MAC. Ten anaesthetists were allowed up to three attempts to intubate the trachea in one easy and three progressively more difficult laryngoscopy scenarios in a SimMan® manikin with four tracheal tube stylet strategies: no stylet; stylet; directional stylet (Parker Flex‐It™); and hockey‐stick stylet. The use of a stylet conferred no advantage in the easy laryngoscopy scenario. In the difficult scenarios, the directional and hockey‐stick stylets performed best. In the most difficult scenario, the median (IQR [range]) duration of the successful intubation attempt was lowest with the hockey‐stick stylet; 18 s (15–22 [12–43]) s, highest with the unstyletted tracheal tube; 60 s (60–60 [60, 60]) s and styletted tracheal tube 60 s (29–60 [18–60]) s, and intermediate with the directional stylet 21 s (15–60 [8–60]) s. The use of a stylet alone does not confer benefit in the setting of easy laryngoscopy. However, in more difficult laryngoscopy scenarios, the C‐MAC videolaryngoscope performs best when used with a stylet that angulates the distal tracheal tube. The hockey‐stick stylet configuration performed best in the scenarios tested.
Effects of woohwangcheongsimwon suspension on the pharmacokinetics of bupropion and its active metabolite, 4‐hydroxybupropion, in healthy subjects
Authors: Kim Hyunmi , Bae Soo Kyung , Park Soo‐Jin , Shim Eon‐Jeong , Kim Ho‐Sook , Shon Ji‐Hong , Liu Kwang‐Hyeon , Shin Jae‐Gook
Published: March 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Woohwangcheongsimwon suspension has traditionally been used for the treatment and prevention of stroke, hypertension, palpitations, convulsions and unconsciousness in various Asian countries.

• Woohwangcheongsimwon suspensions showed an inhibitory effect on CYP2B6 activityin vitro. Two terpenoids, borneol and isoborneol, are major constituents of woohwangcheongsimwon suspension, and show a competitive inhibition of CYP2B6 withKivalues of 9.5 and 5.9 µm, respectively.

• Bupropion undergoes metabolic transformation to the active metabolite, 4‐hydroxybupropion, primarily via CYP2B6 bothin vivoandin vitro. It is often used as a CYP2B6 substrate for clinical drug–drug interaction studies.

• Drug interactions may occur between woohwangcheongsimwon suspension and bupropion.

WHAT THIS STUDY ADDS

• Co‐administration with woohwangcheongsimwon suspension did not alter the pharmacokinetics of bupropion or its metabolite, 4‐hydroxybupropion.

• Dosage adjustment of bupropion is unnecessary in patients concomitantly administered the highest recommended daily dose of woohwangcheongsimwon suspension.

AIMS

To examine the effects of woohwangcheongsimwon suspension on the pharmacokinetics of bupropion and its active metabolite, 4‐hydroxybupropion, formed via CYP2B6in vivo.

METHODS

A two‐way crossover clinical trial with a 2 week washout period was conducted in 14 healthy volunteers. In phases I and II, subjects received 150 mg bupropion with or without woohwangcheongsimwon suspension four times (at −0.17, 3.5, 23.5 and 47.5 h, with the time of bupropion administration taken as 0 h) in a randomized balanced crossover order. Bupropion and 4‐hydroxybupropion plasma concentrations were measured for up to 72 h by LC‐MS/MS. Urine was collected up to 24 h to calculate the renal clearance. In addition, theCYP2B6*6 genotype was also analyzed.

RESULTS

The geometric mean ratios and 90% confidence interval of bupropion with woohwangcheongsimwon suspension relative to bupropion alone were 0.976 (0.917, 1.04) for AUC(0,∞) and 0.948 (0.830,1.08) forCmax, respectively. The corresponding values for 4‐hydroxybupropion were 0.856 (0.802, 0.912) and 0.845 (0.782, 0.914), respectively. Thetmaxvalues of bupropion and 4‐hydroxybupropion were not significantly different between the two groups (P > 0.05). The pharmacokinetic parameters of bupropion and 4‐hydroxybupropion were unaffected by woohwangcheongsimwon suspension.

CONCLUSIONS

These results indicate that woohwangcheongsimwon suspension has a negligible effect on the disposition of a single dose of bupropionin vivo. As a result, temporary co‐administration with woohwangcheongsimwon suspension does not seem to require a dosage adjustment of bupropion.
Advances in the understanding of haemoglobin switching
Authors: Sankaran Vijay G. , Xu Jian , Orkin Stuart H.
Published: March 2010

The study of haemoglobin switching has represented a focus in haematology due in large part to the clinical relevance of the fetal to adult haemoglobin switch for developing targeted approaches to ameliorate the severity of the β‐haemoglobinopathies. Additionally, the process by which this switch occurs represents an important paradigm for developmental gene regulation. In this review, we provide an overview of both the embryonic primitive to definitive switch in haemoglobin expression, as well as the fetal to adult switch that is unique to humans and old world monkeys. We discuss the nature of these switches and models of their regulation. The factors that have been suggested to regulate this process are then discussed. With the increased understanding and discovery of molecular regulators of haemoglobin switching, such as BCL11A, new avenues of research may lead ultimately to novel therapeutic, mechanism‐based approaches to fetal haemoglobin reactivation in patients.
Disconnect between standardized field‐based testing and mannitol challenge in Scottish elite swimmers
Authors: Clearie K. L. , Williamson P. A. , Vaidyanathan S. , Short P. , Goudie A. , Burns P. , Hopkinson P. , Meldrum K. , Howaniec L. , Lipworth B. J.
Published: March 2010

Background
Elite swimmers have high rates of rhinoconjunctivitis and exercise‐induced bronchoconstriction. Moreover, exposure to chlorine and chlorine metabolites is known to induce bronchial hyper‐reactivity.

Objective
To assess the early and late effects of chlorine and exercise on the unified airway of elite swimmers, and to compare the response to mannitol and field‐based exercise challenge.

Methods
The Scottish national squad underwent exhaled tidal (FENO) and nasal (NNO) nitric oxide measurement, peak nasal inspiratory flow (PNIF), and forced expiratory volume in 1 s before, immediately after, and 4–6 h post‐swimming. A sport‐specific exercise test was carried out during an intensive lactate set (8 min at 80% maximum hear rate). All swimmers underwent mannitol challenge, and completed a health questionnaire.

Results
N=61 swimmers were assessed: 8/59 (14%) of swimmers had a positive mannitol challenge. Nine out of 57 (16%) of swimmers had a positive exercise test. Only one swimmer was positive to both. Swimmers with a positive mannitol had a significantly higher baseline FENO (37.3 vs. 18.0 p.p.b., P=0.03) than those with a positive exercise challenge. A significant decrease in FENO was observed pre vs. immediate and delayed post‐chlorine exposure: mean (95% CI) 18.7 (15.9–22.0) p.p.b. vs. 15.9 (13.3–19.1) p.p.b. (P<0.01), and 13.9 (11.5–16.7) p.p.b. (P<0.01), respectively. There were no significant differences in NNO. Mean PNIF increased from 142.4 L/min (5.8) at baseline to 162.6 L/min (6.3) immediately post‐exposure (P<0.01). Delayed post‐exposure PNIF was not significantly different from pre‐exposure.

Conclusions
No association was found between mannitol and standardized field‐based testing in elite swimmers. Mannitol was associated with a high baseline FENO; however, exercise/chlorine challenge was not. Thus, mannitol may identify swimmers with a ‘traditional’ inflammatory asthmatic phenotype, while field‐based exercise/chorine challenge may identify a swimmer‐specific bronchoconstrictor response. A sustained fall in FENO following chlorine exposure suggests that a non‐cellular, perhaps neurogenic, response may be involved in this group of athletes.

Cite this as: K. L. Clearie, P. A. Williamson, S. Vaidyanathan,
P. Short, A. Goudie, P. Burns, P. Hopkinson, K. Meldrum, L. Howaniec and B. J. Lipworth, Clinical & Experimental Allergy, 2010 (40) 731–737.
Mismatch between the timing of oviposition and the seasonal optimum. The stochastic phenology of Mediterranean acorn weevils
Authors: BONAL RAUL , MUÑOZ ALBERTO , MARÍA ESPELTA JOSEP
Published: March 2010

1. The timing of reproduction is predicted to match the period of maximum food availability. In this sense, the case of many phytophagous insects in temperate regions is very illustrative, as their larvae usually depend on a resource only available for a limited period of time each year.

2. For 3 years the interactions between the weevil Curculio elephas and the Mediterranean Holm oak Quercus ilex were studied. Weevil larvae grow within the acorns, feeding on the cotyledons. The timing of oviposition will determine food availability for the larvae, as acorns stop growing once they are attacked.

3. Acorn temporal growing patterns did not change between years and food availability for larvae was at its highest in October, when temperature was still suitable for larval development. However, oviposition phenology did change between years. In 2002 females oviposited later, larvae grew within larger acorns, and their body mass was significantly higher than in 2003 or 2004, when females oviposited into early acorns.

4. Thus, weevils do not always adjust oviposition to the best possible feeding conditions for their offspring. Rather, they seem to maximise their own lifetime fitness, ovipositing as soon as they emerge in late summer. Emergence, in turn, depends strongly on stochastic events such as summer storms in the Mediterranean region.

5. Under a climate change perspective, the trend towards higher August rainfall recorded in our study area may alter oviposition phenology, with the subsequent cascade effects on weevil body size and fitness
Ex vivo assessment of irrigant penetration and renewal during the cleaning and shaping of root canals: a digital subtraction radiographic study
Authors: Bronnec F. , Bouillaguet S. , Machtou P.
Published: March 2010

Bronnec F, Bouillaguet S, Machtou P.
Ex vivo assessment of irrigant penetration and renewal during the cleaning and shaping of root canals: a digital subtraction radiographic study. International Endodontic Journal, 43, 275–282, 2010.

Aim  To assess radiographically irrigant penetration in the root canal system of curved roots during root canal shaping procedures ex vivo.

Methodology  Thirty extracted mandibular molar teeth with moderate to severe curvature were used. A special aiming device was used to guarantee that each successive radiograph was taken with the same positioning. The mesiolingual canal of each tooth was instrumented using the ProTaper system. For each step of the shaping procedure, two irrigation modalities were repeated in the same order. Active irrigation consisted of a 0.5‐mL flush of sodium diatrizoate solution (Hypaque 50%) immediately followed by agitation with a size 08 K‐file. Passive irrigation consisted of a 0.5‐mL flush of sodium hypochlorite solution delivered with a syringe through a 27‐gauge notched tip needle. A digital radiograph was taken after each modality and stored on computer for subsequent digital subtraction and measures of the depths of irrigant penetration. Comparisons were performed within an analysis‐of‐variance framework in a repeated‐measures approach.

Results  The penetration of irrigants was significantly greater for each successive step of the shaping procedure when the two modalities were analysed separately (P < 0.001). The difference between the two modalities was statistically significant for each step of the shaping procedure (P < 0.0001).

Conclusions  Shaping root canals improved both penetration and exchange of irrigant inside the root canal system. Complete renewal of the solution was impossible to achieve with a conventional syringe delivery system and a limited volume of solution. Recapitulation with a K‐file after flushing improved irrigant penetration.
Technical quality of root fillings performed by undergraduate students in Saudi Arabia
Authors: Balto H. , Al Khalifah Sh. , Al Mugairin S. , Al Deeb M. , Al‐Madi E.
Published: March 2010

Balto H, Al Khalifah Sh, Al Mugairin S, Al Deeb M, Al‐Madi E. Technical quality of root fillings performed by undergraduate students in Saudi Arabia. International Endodontic Journal, 43, 292–300, 2010.

Aim  To evaluate the technical quality of root fillings performed in the undergraduate clinic of the Dental College, King Saud University, Saudi Arabia and to compare the technical quality of root canal treatment between the 4th‐ and 5th‐year students.

Methodology  A random sample of 710 records of patients who had received dental treatment by undergraduate students at the College of Dentistry (Malaz University Campus), between the years of 2005–2008, was investigated. The final sample consisted of 550 root filled teeth in 459 patients. For each root filled tooth, at least three periapical radiographs were examined: preoperative, working length determination and postoperative. The length, density and taper of root fillings, as well as the presence of procedural errors, were recorded. ‘Acceptable’ filling quality was defined as having adequate length, density and taper with the absence of any procedural error. Results were evaluated statistically using chi‐square test.

Results  One hundred and twenty‐five of 550 root filled teeth (23%) had a root filling that was classified as ‘acceptable’. There was no statistical significant association between the 4th‐ and 5th‐year students in terms of length (P = 0.134), density (P = 0.081) and taper (P = 0.590). Seventy‐five (14%) treated teeth had ledges, 40 (7%) had apical transportation and 37 (7%) had apical root perforation. Ledges had significant association with the level of student (P < 0.0001) and were greater in the cases of 4th‐year students (18%) compared to the 5th‐year students (8%), whilst root perforations had also significant association with level of students (P = 0.016) and were more in the 5th‐year cases (3%) compared to the 4th‐year cases (0.3%).

Conclusions  The technical quality of root fillings placed by undergraduate dental students was classified as ‘acceptable’ in 23% of cases. There was little difference between 4th‐ and 5th‐year students in the overall quality of root fillings.
The extreme Beringian/Atlantic disjunction in Saxifraga rivularis (Saxifragaceae) has formed at least twice
Authors: Westergaard Kristine Bakke , Jørgensen Marte Holten , Gabrielsen Tove M. , Alsos Inger Greve , Brochmann Christian
Published: March 2010

Aim  The oceanic Saxifraga rivularis L. presents one of the most extreme disjunctions known in the arctic flora: it has a small amphi‐Beringian range and a larger amphi‐Atlantic one. It was recently suggested to have had a single allopolyploid origin in Beringia at least one glacial cycle ago, followed by gradual expansion in a more humid period and differentiation into two allopatric subspecies (the Atlantic ssp. rivularis and the Beringian ssp. arctolitoralis). Here we explore the history of its extreme disjunction.

Location  The amphi‐Beringian and northern amphi‐Atlantic regions.

Methods  We obtained amplified fragment length polymorphisms (AFLPs) and chloroplast DNA sequences from 36 populations (287 individuals) and 13 populations (15 individuals), respectively. The data were analysed using principal coordinates analyses, Bayesian clustering methods, and analyses of molecular variance.

Results  Two distinctly divergent AFLP groups were observed, corresponding to the two described subspecies, but, surprisingly, four of the West Atlantic populations belonged to the supposedly Beringian endemic ssp. arctolitoralis. This was confirmed by re‐examination of their morphological characteristics. The overall AFLP diversity in the species was low (26.4% polymorphic markers), and there was no variation in the five investigated chloroplast DNA (cpDNA) regions. There was little geographic structuring of the AFLP diversity within each subspecies, even across the extreme disjunction in ssp. arctolitoralis, across the Bering Sea, and across the Atlantic Ocean, except that most plants from the arctic Svalbard archipelago formed a separate genetic group with relatively high diversity.

Main conclusions  The extreme disjunction in S. rivularis has evidently formed at least twice. The first expansion from Beringia was followed by allopatric differentiation into one Beringian and one Atlantic subspecies, which are distinctly divergent at AFLP loci but still harbour identical cpDNA haplotypes, suggesting that the expansion was quite recent but before the last glaciation. The next expansion from Beringia probably occurred by means of several long‐distance dispersals in the current interglacial, resulting in the colonization of the western Atlantic region by ssp. arctolitoralis. The poor geographic structuring within each subspecies suggests frequent long‐distance dispersals from two main Weichselian refugia, one Beringian and one western‐central European, but it is possible that the genetic group in Svalbard originates from an additional refugium.
Mycoplasma pneumoniae Community Acquired Respiratory Distress Syndrome toxin expression reveals growth phase and infection‐dependent regulation
Authors: Kannan T. R. , Musatovova Oxana , Balasubramanian Sowmya , Cagle Marianna , Jordan Jarrat L. , Krunkosky Thomas M. , Davis Alan , Hardy Robert D. , Baseman Joel B.
Published: March 2010

Mycoplasma pneumoniae causes acute and chronic respiratory infections, including tracheobronchitis and community acquired pneumonia, and is linked to asthma and an array of extra‐pulmonary disorders. Recently, we identified an ADP‐ribosylating and vacuolating toxin of M. pneumoniae, designated Community Acquired Respiratory Distress Syndrome (CARDS) toxin. In this study we analysed CARDS toxin gene (annotated mpn372) transcription and identified its promoter. We also compared CARDS toxin mRNA and protein profiles in M. pneumoniae during distinct in vitro growth phases. CARDS toxin mRNA expression was maximal, but at low levels, during early exponential growth and declined sharply during mid‐to‐late log growth phases, which was in direct contrast to other mycoplasma genes examined. Between 7% and 10% of CARDS toxin was localized to the mycoplasma membrane at mid‐exponential growth, which was reinforced by immunogold electron microscopy. No CARDS toxin was released into the medium. Upon M. pneumoniae infection of mammalian cells, increased expression of CARDS toxin mRNA was observed when compared with SP‐4 broth‐grown cultures. Further, confocal immunofluorescence microscopy revealed that M. pneumoniae readily expressed CARDS toxin during infection of differentiated normal human bronchial epithelial cells. Analysis of M. pneumoniae‐infected mouse lung tissue revealed high expression of CARDS toxin per mycoplasma cell when compared with M. pneumoniae cells grown in SP‐4 medium alone. Taken together, these studies indicate that CARDS toxin expression is carefully controlled by environmental cues that influence its transcription and translation. Further, the acceleration of CARDS toxin synthesis and accumulation in vivo is consistent with its role as a bona fide virulence determinant.
Representativeness of child controls recruited by random digit dialling
Authors: Bailey Helen D. , Milne Elizabeth , de Klerk Nicholas , Fritschi Lin , Bower Carol , Attia John , Armstrong Bruce K.
Published: March 2010

Bailey HD, Milne E, de Klerk N, Fritschi L, Bower C, Attia J, Armstrong BK. Representativeness of child controls recruited by random digit dialling. Paediatric and Perinatal Epidemiology 2010.

Recruiting control subjects who are representative of the population from which the cases are drawn is a challenge in case–control studies. This paper examines the performance of random digit dialling (RDD) in obtaining a control sample, and the sample's representativeness of the population with respect to socio‐economic status.

The study subjects were recruited from 2003 to 2006 for a national, population‐based case–control study investigating causes of acute lymphoblastic leukaemia (ALL) in children <15 years of age in Australia. Control families' addresses were linked to Australian Bureau of Statistics Census 2006 Collection Districts and thus to Socio‐Economic Indexes for Area scores, which are area‐based measures of socio‐economic status. These scores were compared with those of all collection districts where families lived.

We estimate that 55% of eligible families in the RDD sample agreed to participate in the study. Participation was directly related to socio‐economic status with those of highest economic status most likely to participate. Completeness of participation in the components of data collection was similarly related to socio‐economic status. This evidence of selection according to socio‐economic status indicates that there may also be selection with respect to other factors potentially important in the aetiology of ALL.
Does children's energy intake at one meal influence their intake at subsequent meals? Or do we just think it does?
Authors: Hanley James A. , Hutcheon Jennifer A.
Published: March 2010

Hanley JA, Hutcheon JA. Does children's energy intake at one meal influence their intake at subsequent meals? Or do we just think it does? Paediatric and Perinatal Epidemiology 2010.

It is widely believed that young children are able to adjust their energy intake across successive meals to compensate for higher or lower intakes at a given meal. This conclusion is based on past observations that although children's intake at individual meals is highly variable, total daily intakes are relatively constant. We investigated how much of this reduction in variability could be explained by the statistical phenomenon of the variability of individual components (each meal) always being relatively larger than the variability of their sum (total daily intake), independent of any physiological compensatory mechanism. We calculated, theoretically and by simulation, how variable a child's daily intake would be if there was no correlation between intakes at individual meals. We simulated groups of children with meal/snack intakes and variability in meal/snack intakes based on previously published values. Most importantly, we assumed that there was no correlation between intakes on successive meals.

In both approaches, the coefficient of variation of the daily intakes was roughly 15%, considerably less than the 34% for individual meals. Thus, most of the reduction in variability found in past studies was explained without positing strong ‘compensation’. Although children's daily energy intakes are indeed considerably less variable than their individual components, this phenomenon was observed even when intakes at each meal were simulated to be totally independent. We conclude that the commonly held belief that young children have a strong physiological compensatory mechanism to adjust intake at one meal based on intake at prior meals is likely to be based on flawed statistical reasoning.
Importance of pre‐anthesis anther sink strength for maintenance of grain number during reproductive stage water stress in wheat
Authors: JI XUEMEI , SHIRAN BEHROUZ , WAN JIANLIN , LEWIS DAVID C. , JENKINS COLIN L. D. , CONDON ANTHONY G. , RICHARDS RICHARD A. , DOLFERUS RUDY
Published: March 2010

Reproductive stage water stress leads to spikelet sterility in wheat. Whereas drought stress at anthesis affects mainly grain size, stress at the young microspore stage of pollen development is characterized by abortion of pollen development and reduction in grain number. We identified genetic variability for drought tolerance at the reproductive stage. Drought‐tolerant wheat germplasm is able to maintain carbohydrate accumulation in the reproductive organs throughout the stress treatment. Starch depletion in the ovary of drought‐sensitive wheat is reversible upon re‐watering and cross‐pollination experiments indicate that the ovary is more resilient than the anther. The effect on anthers and pollen fertility is irreversible, suggesting that pollen sterility is the main cause of grain loss during drought conditions in wheat. The difference in storage carbohydrate accumulation in drought‐sensitive and drought‐tolerant wheat is correlated with differences in sugar profiles, cell wall invertase gene expression and expression of fructan biosynthesis genes in anther and ovary (sucrose : sucrose 1‐fructosyl‐transferase, 1‐SST; sucrose : fructan 6‐fructosyl‐transferase, 6‐SFT). Our results indicate that the ability to control and maintain sink strength and carbohydrate supply to anthers may be the key to maintaining pollen fertility and grain number in wheat and this mechanism may also provide protection against other abiotic stresses.
Relations of sugar composition and δ13C in phloem sap to growth and physiological performance of Eucalyptus globulus (Labill)
Authors: MERCHANT ANDREW , TAUSZ MICHAEL , KEITEL CLAUDIA , ADAMS MARK A.
Published: March 2010

We characterized differences in carbon isotopic content (δ13C) and sugar concentrations in phloem exudates from Eucalyptus globulus (Labill) plantations across a rainfall gradient in south‐western Australia. Phloem sap δ13C and sugar concentrations varied with season and annual rainfall. Annual bole growth was negatively related to phloem sap δ13C during summer, suggesting a water limitation, yet was positively related in winter. We conclude that when water is abundant, variations in carboxylation rates become significant to overall growth. Concentrations of sucrose in phloem sap varied across sites by up to 600 mm, and raffinose by 300 mm. These compounds play significant roles in maintaining osmotic balance and facilitating carbon movement into the phloem, and their relative abundances contribute strongly to overall δ13C of phloem sap. Taken together, the δ13C and concentrations of specific sugars in phloem sap provide significant insights to functions supporting growth at the tree, site and landscape scale.
Investigation on the effects of ciclosporin (Atopica) on intradermal test reactivity and allergen‐specific immunoglobulin (IgE) serology in atopic dogs
Authors: Goldman Candice , Rosser Jr Edmund , Petersen Annette , Hauptman Joe
Published: March 2010

The ability to use ciclosporin (Atopica®: Novartis Animal Health, Greensboro, NC, USA) prior to intradermal testing (IDT) would help avoid exacerbation of clinical disease that can be associated with drug withdrawal. This study evaluated the effects of 30 days of administration of ciclosporin at a dose of 5 mg/kg once daily on IDT reactivity (immediate phase reactions) in a group of dogs with atopic dermatitis (AD) with initial positive IDT reactions. 16 dogs diagnosed with AD were included in the study. Eight dogs (group A) were treated with ciclosporin orally at 5 mg/kg once daily for 30 days. Eight dogs (group P) were treated with a placebo orally once daily for 30 days. IDT was performed at day 0 and day 30 on all dogs enrolled using a standardized panel of 45 aqueous allergens (Greer Laboratories, Lenoir, NC, USA) appropriate to our geographical region. IDT reactivity was assessed by both subjective and objective methods at 15 min post‐intradermal injection. Serum for allergen‐specific immunoglobulin (IgE) serology was obtained at day 0 and day 30. The study was designed as a double‐blinded, placebo‐controlled, cross‐over study. Data were analysed using a split‐plot analysis of variance with the grouping factor of treatment and the repeat factor of time (SAS System for Windows). At week 4, ciclosporin did not have a statistically significant effect on IDT reactivity or serology results. It therefore appears that, no withdrawal is recommended to evaluate immediate phase reactions.
Cysteamine Supplementation ofIn vitroMaturation Media: A Review
Authors: Deleuze S , Goudet G
Published: March 2010

Contents

Underin vitroculture conditions, oxidative modifications of cell components via increased reactive oxygen species (ROS) represent a major culture induced stress. Anti‐oxidant systems such as glutathione (GSH) can attenuate the deleterious effects of oxidative stress by scavenging ROS. It has been suggested that GSH content in oocytes may serve as a reservoir protecting the zygote and the early embryos from oxidative damage before genomic activation andde novoGSH synthesis occur. Addition of low molecular weight compounds to culture media, such as cysteamine, can increase GSH levels by increasing cysteine uptake. Quite naturally, effects of supplementation ofin vitromaturation (IVM) media with low molecular weight thiols have been studied in various species. This article reviews the use of cysteamine supplementation for IVM, its effects on maturation rates and further embryo development.
Adrenal androgen levels as predictors of outcome in castration‐resistant prostate cancer patients treated with combined androgen blockade using flutamide as a second‐line anti‐androgen
Authors: Narimoto Kazutaka , Mizokami Atsushi , Izumi Kouji , Mihara Shinya , Sawada Kiyoshi , Sugata Toshiaki , Shimamura Masayoshi , Miyazaki Kimiomi , Nishino Akio , Namiki Mikio
Published: March 2010

Objectives:  To analyze the clinical effects of flutamide as a second‐line anti‐androgen for combined androgen blockade in patients with castration‐resistant prostate cancer (CRPC) initially treated with bicalutamide as a first‐line anti‐androgen.

Methods:  Our study population consisted of 16 patients with CRPC who were treated with flutamide (375 mg daily) as second‐line hormonal therapy. Dehydroepiandrosterone (DHEA), androstenedione, androstenediol, testosterone and dihydrotestosterone were measured to investigate the relationship between plasma androgens and outcome following treatment. Furthermore, adrenal androgen levels in a medium of adrenal cancer cell line were also measured.

Results:  Second‐line hormonal therapy using flutamide resulted in a reduction of the prostate‐specific antigen (PSA) level in 14 (87.5%) of 16 patients. A PSA decline greater than 50% was observed in 8 (50%) of the 16 patients. The duration of median responsiveness was 6.25 months. PSA elevation of baseline androstenediol level was a predictive factor of PSA responsiveness. The lower DHEA group improved the duration of responsiveness to flutamide. In vitro, 3 µmol/L flutamide suppressed DHEA, androstenedione and androstenediol synthesis compared with bicalutamide in a medium of adrenal cancer cell line.

Conclusions:  Our data show that flutamide suppresses the adrenal androgens in comparison with bicalutamide. The responsiveness and response duration of flutamide can be predicted in patients with a higher baseline androstenediol level and a lower DHEA level. Metabolites from adrenal androgens contribute to the progression of prostate cancer.
A bioregional analysis of the distribution of rainforest cover, deforestation and degradation in Papua New Guinea
Authors: SHEARMAN PHIL , BRYAN JANE
Published: March 2010

Papua New Guinea (PNG) is an extensively forested country. Recent research suggests that despite commencing a trajectory of deforestation and degradation later than many counties in the Asia–Pacific region, PNG is now undergoing comparable rates of forest change. Here we explore the bioregional distribution of changes in the forest estate over the period 1972–2002 and examine their implications for forest protection. This is undertaken through the development of a novel bioregional classification of the country based on biogeographic regions and climatic zones, and its application to existing forest cover and forest‐cover change data. We found that degradation and deforestation varied considerably across the 11 defined biogeographic regions. We report that the majority of deforestation and degradation has occurred within all the lowland forests, and that it is these forests that have the greatest potential for further losses in the near term. The largest percentage of total change occurred in the east of PNG, in the islands and lowlands of the Bismarck, D'Entrecasteaux, East Papuan Islands and in the South‐East Papua–Oro region. The only region with a significant highlands component to undergo deforestation at a comparable magnitude to the islands and lowland regions was the Huon Peninsula and Adelbert region. Significant changes have also occurred at higher elevations, especially at the interface of subalpine grasslands and upper montane forests. Lower montane forests have experienced proportionally less change, yet it is these forests that constitute the majority of forests enclosed within the protected area system. We find that protected areas are not convincingly protecting either representative areas of PNG's ecosystems, nor the forests within their borders. We conclude by suggesting a more expansive and integrated approach to managing the national forest estate.
Ecological processes shaping Central Patagonian salt marsh landscapes
Authors: IDASZKIN YANINA L. , BORTOLUS ALEJANDRO , BOUZA PABLO J.
Published: March 2010

Plant zonation is one of the most conspicuous ecological features of salt marshes worldwide. In this work we used a combination of field transplant and greenhouse experiments to evaluate the importance of interspecific interactions and physical stress in the determination of the major plant zonation patterns in Central Patagonian salt marshes. There, Spartina alterniflora dominates the low marsh, and Sarcocornia perennis the high marsh. We addressed two questions: (i) What prevents Spartina alterniflora from colonizing the Sarcocornia perennis‐dominated high marsh zone? and (ii) What prevents Sarcocornia perennis from colonizing the Spartina alterniflora‐dominated low marsh zone? Our experimental transplants combined with neighbour exclusion treatments showed that the presence of Sarcocornia perennis negatively affects Spartina alterniflora, preventing it from surviving and/or spreading. Complementary field transplant and greenhouse experiments showed that Sarcocornia perennis did not survive the frequent tidal submersion by approximately 1.5 m of turbid seawater in the Spartina alterniflora zone, but its survival was independent of the presence of Spartina neighbours, and of the strong soil anoxia as well. Our results suggest that Spartina alterniflora is excluded by Sarcocornia perennis towards the low marsh, where frequent and prolonged submersion limit the survival of the latter. We provide and discuss key baseline information to facilitate the future design of ecophysiological experiments designed to accurately identify the exact mechanisms acting in every situation.
Transurethral endoscopic treatment of patients with upper tract urothelial carcinomas using neodymium‐YAG and/or holmium‐YAG laser ablation
Authors: Tada Yasuhiro , Yokomizo Akira , Koga Hirohumi , Seki Naruhito , Kuroiwa Kentaro , Tatsugami Katsunori , Yamaguchi Akito , Naito Seiji
Published: March 2010

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To report our experience of treating patients with original and recurrent upper tract urothelial carcinomas (UC) using endoscopic lasers, with holmium‐YAG and/or neodymium‐YAG laser ablation, and for whom tumour stage and grade were obtained by endoscopic biopsy.

PATIENTS AND METHODS

From March 2003 to March 2007, 15 patients with upper tract UC were treated with endoscopic laser ablation as the primary management. Patients were followed up by intravenous urography, computed tomography, urine cytology and/or ureteroscopic surveillance at 3‐ to 12‐month intervals. The median (range) follow‐up was 25.5 (13–51) months.

RESULTS

Of the 15 patients, five had an upper tract recurrence during the follow‐up. Three of these were treated with total nephroureterectomy and two had a progression in tumour stage or grade. Three patients had residual tumours; they were treated with repeated endoscopic laser treatments and had no recurrence over a median (range) of 24 (13–26) months. The renal preservation rate was 12/15 and the local recurrence rate was six/15 after the initial endoscopy. The median operative duration and tumour size were 60 min and 10 mm, respectively.

CONCLUSION

Patients with low‐grade and ‐stage disease and normal contralateral kidneys also benefit from this approach, if there is an adequate endoscopic biopsy. As the operative duration tended to be associated with the maximum tumour size, this treatment is potentially available for a maximum tumour size of <4 cm; if the tumour is <4 cm surgery will require <120 min.
Cytotoxicity and apoptosis by survivin small interfering RNA in bladder cancer cells
Authors: Ku Ja H. , Seo Soo Y. , Kwak Cheol , Kim Hyeon H.
Published: March 2010

OBJECTIVE

To investigate the effects of survivin gene RNA interference on cell growth and the cell cycle in the human bladder cancer cell line T24.

MATERIALS AND METHODS

A small interfering RNA (siRNA) targeting survivin was transfected into T24 cells using a liposome approach. Reverse transcription‐polymerase chain reaction and Western blot analysis were used to examine survivin gene expression in T24 cells. Cells densities were determined by haematocytometer counts and flow cytometry was used for cell cycle analysis. Caspase‐3 activity was quantified.

RESULTS

After treatment with survivin siRNA, the survivin gene expression in T24 cells was almost completely absent. The survivin siRNA treatment caused a profound decrease in survivin protein, which was correlated with a decrease in cell growth, G2/M arrest, and an increase in the fraction of cells undergoing apoptosis. The inhibition of survivin expression increased caspase‐3 activity in T24 cells, which led to apoptosis.

CONCLUSIONS

RNA interference can efficiently suppress survivin expression in T24 cells. Targeting survivin by siRNA may be a promising approach to block proliferation of bladder cancer cells and may provide a suitable adjuvant therapy for treatment of bladder cancer.
A comparison of efficacy and safety of vildagliptin and gliclazide in combination with metformin in patients with Type 2 diabetes inadequately controlled with metformin alone: a 52‐week, randomized study
Authors: Filozof C. , Gautier J.‐F.
Published: March 2010

Diabet. Med. 27, 318–326 (2010)

Aim  To demonstrate non‐inferiority of vildagliptin compared with gliclazide, as an add‐on therapy, in patients with Type 2 diabetes inadequately controlled with metformin in a 52‐week, randomized, double‐blind, active‐controlled study.

Methods  Patients receiving a stable dose of metformin (≥ 1500 mg) were randomized (1 : 1) to receive vildagliptin (50 mg twice daily; n = 513) or gliclazide (up to 320 mg/day; n = 494).

Results  Non‐inferiority of vildagliptin was demonstrated (95% confidence interval −0.11%, 0.20%) with a mean change (se) from baseline glycated haemoglobin (HbA1c) (∼ 8.5% in both groups) to a 52‐week endpoint of −0.81% (0.06) with vildagliptin and −0.85% (0.06) with gliclazide. Although a similar proportion of patients reached HbA1c < 7.0%, the total number of hypoglycaemic events was lower in the vildagliptin group (6 vs. 11 events). Vildagliptin was non‐inferior (margin 0.6 mmol/l) to gliclazide in reducing fasting plasma glucose (1.31 vs. 1.52 mmol/l, P = 0.257). The overall incidence of any adverse events was similar in both groups (∼ 61%), but the number of serious adverse events was higher in the gliclazide group (8.7 vs. 6.7%). The number of patients who discontinued as a result of an unsatisfactory effect was higher in the vildagliptin group (n = 22 vs. 13, respectively) compared with gliclazide, but vildagliptin did not induce weight gain.

Conclusion  In patients with Type 2 diabetes inadequately controlled with metformin, addition of vildagliptin provided similar HbA1c‐lowering efficacy compared with gliclazide after 52 weeks of treatment. Although both treatments were well tolerated, vildagliptin‐treated patients had fewer hypoglycaemic events and did not gain weight.