bluuebunny/crossref_metadata_2025 huggingface dataset:
The external anal sphincter and the role of surface electromyography
Authors: Enck P. , Hinninghofen H. , Merletti R. , Azpiroz F.
Published: April 2005

Abstract  Assessment of the neuronal control of the external anal sphincter (EAS) has long been restricted to investigating patients with defecation disorders by invasive tools such as needle electromyography (EMG), while less invasive techniques have been regarded as non‐suitable for diagnostic purposes. Multichannel surface EMG by means of electrode arrays applied to anal sphincter muscle records and identifies individual motor unit action potentials, their place of origin along the circumference, their repetitive firing frequency, and their progression along the muscle fibres at different levels within the anal canal. These data shed doubts on conventional knowledge about the anatomy of the EAS muscle, and confirms new concepts of anatomical differences between gender. This may eventually be transferred to a new understanding of the role of symmetry and asymmetry of pelvic floor innervation and its role in the pathogenesis of fecal incontinence.
The upper oesophageal sphincter
Authors: Singh S. , Hamdy S.
Published: April 2005

Abstract The upper oesophageal sphincter (UOS) is a high‐pressure zone comprising functional activity of three adjacent muscles together with cartilage and connective tissue. Its primary function is to allow food into the oesophagus and prevent air ingestion. However, it must also allow the reflux of material during belching or vomiting. Cricopharyngeus is the most important muscle with contributions from inferior pharyngeal constrictor and cervical oesophagus. Basal tone within the UOS is contributed to by all three muscles with asymmetry in the axial plane. Relaxation of the UOS occurs during swallowing as well as in sleep while UOS pressure rises with stress, slow oesophageal distension, intra‐oesophageal acid infusion and pharyngeal stimulation with air or water. Many physiological characteristics have been attributed to UOS function following videofluoroscopic swallow examinations, manometry and electromyography but a range of normal values remains controversial and their utility uncertain. The result has been that pathological change is inconsistently characterized and management is instigated without a satisfactory evidence base. In this article, we review the anatomy, physiology and pathophysiology of the UOS along with the current opinions on investigation and treatment of UOS dysfunction.
Experimental sexual selection in Chlamydomonas
Authors: BELL G.
Published: April 2005

Sexual and asexual lines of the unicellular chlorophyte Chlamydomonas reinhardtii were propagated for about 100 sexual cycles and 1000 vegetative cycles in contrasted environments, liquid and solid growth media, in order to generate divergent natural and sexual selection. Sexual lines were transferred by many zygotes or by a single zygote in each sexual generation. By the end of the experiment zygote production was in the order sexual mass‐transfer > sexual single‐zygote > asexual > ancestor. The direct response to sexual selection was large, with zygote production increasing by about two orders of magnitude, mainly because mating had become spontaneous instead of being invoked by nitrogen starvation. Asexual lines became sexually sterilized by the fixation of a single mating type. Sexual selection caused a radical shift in the gender system, with homothallism spreading to high frequency in all sexual lines of this normally heterothallic species. This may have been caused by the transposition of a mating‐type gene to an autosome. No substantial degree of environment‐specific mating evolved, however, and thus no sexual isolation indicative of incipient speciation. It is possible that selection experiments of this kind are unlikely to induce sexual isolation because mating‐type genes evolve in a saltatory fashion.
Hamilton's rule, imprinting and parent–offspring conflict over seed mass in partially selfing plants
Authors: DE JONG T. J. , VAN DIJK H. , KLINKHAMER P. G. L.
Published: April 2005

When genes in the offspring control the provisioning of the seed, the optimal seed size can be calculated exactly by applying Hamilton's rule. When seed size is a compromise between mother and offspring, we predict that outcrossing plant species produce larger seeds than selfers. This trend was found in the British flora and in a number of well‐studied plant families. The analysis was extended to imprinting, a conditional strategy in which a gene in the offspring takes more resources when derived from the father than from the mother. The conditions for imprinting to be selected were rather restrictive. The analysis is relevant for the current debate about the evolution of imprinting in Arabidopsis thaliana.
Within clutch co‐variation of egg mass and sex in the black‐headed gull
Authors: MÜLLER W. , GROOTHUIS T. G. G. , EISING C. M. , DAAN S. , DIJKSTRA C.
Published: April 2005

Female birds of several species have control over the production of daughters and sons. However, most studies failed to find a relationship between egg size and sex. This is intriguing as adjustment of egg size would constitute a powerful tool for the female to meet different resource demands of the sexes, particularly in size dimorphic species. Our results show that, within clutches of black‐headed gulls (Larus ridibundus) the proportion of males was positively associated with egg mass. This applied for all three laying positions, independently of the absolute egg mass. There was a significant relationship between the distribution of the sexes over the laying sequence and the egg mass change. When egg mass decreased over the sequence, first‐laid eggs were male biased and last‐laid eggs female biased, and vice versa. The potential adaptive value of this allocation strategy is evaluated with regard to male sensitivity to egg quality and competitive differences between the sexes.
Contemporary gene flow and the spatio‐temporal genetic structure of subdivided newt populations (Triturus cristatus,T. marmoratus)
Authors: JEHLE R. , WILSON G. A. , ARNTZEN J. W. , BURKE T.
Published: April 2005

Gene flow and drift shape the distribution of neutral genetic diversity in metapopulations, but their local rates are difficult to quantify. To identify gene flow between demes as distinct from individual migration, we present a modified Bayesian method to genetically test for descendants between an immigrant and a resident in a nonmigratory life stage. Applied to a metapopulation of pond‐breeding European newts (Triturus cristatus,T. marmoratus) in western France, the evidence for gene flow was usually asymmetric and, for demes of known census size (N), translated into maximally seven reproducing immigrants. Temporal sampling also enabled the joint estimation of the effective demic population size (Ne) and the immigration ratem(including nonreproductive individuals).Neranged between 4.1 and 19.3 individuals,Ne/Nranged between 0.05 and 0.65 and always decreased withN;mwas estimated as 0.19–0.63, and was possibly biased upwards. We discuss how genotypic data can reveal fine‐scale demographic processes with important microevolutionary implications.
A chemical level in the coevolutionary arms race between an ant social parasite and its hosts
Authors: BRANDT M. , HEINZE J. , SCHMITT T. , FOITZIK S.
Published: April 2005

Here we investigate the coevolutionary interactions between the slavemaking antProtomognathus americanusand itsTemnothoraxhosts on a chemical level. We show that, although this social parasite is principally well‐adapted to its hosts’ cuticular hydrocarbon profile, there are pronounced differences in the fine‐tuning of this adaptation. Between populations, chemical adaptation varies with host community composition, as the parasite faces a trade‐off when confronted with more than one host species. In addition to adaptation of its own chemical signature, the slavemaker causes a reciprocal adjustment in its slaves’ cuticular profile, the degree of which depends on the slave species. On the host side, successful parasite defence requires efficient enemy recognition, and in behavioural aggression trials, host colonies could indeed discriminate between invading slaves, which commonly accompany slavemakers on raids, and free‐living conspecifics. Furthermore, hosts shifted their acceptance threshold over the seasons, presumably to reduce the costs of defence.
Natural selection and genetic variation for female resistance to harm from males
Authors: LINDER J. E. , RICE W. R.
Published: April 2005

The sexual conflict hypothesis predicts that males evolve traits that exploit the higher parental investment of females, which generates selection for females to counter‐evolve resistance. In Drosophila melanogaster it is now established that males harm females and that there is genetic variation among males for the degree of this harm. Genetic variation among females for resistance to harm from males, and the corresponding strength of selection on this variation, however, have not been quantified previously. Here we carryout a genome‐wide screen for female resistance to harm from males. We estimate that the cost of interactions with males depresses lifetime fecundity of females by 15% (95% CI: 8.2–22.0), that genetic variation for female resistance constitutes 17% of total genetic variation for female adult fitness, and that propensity to remate in response to persistent male courtship is a major factor contributing to genetic variation for female resistance.
Competing dwarf males: sexual selection in an orb‐weaving spider
Authors: FOELLMER M. W. , FAIRBAIRN D. J.
Published: April 2005

Hypotheses for the adaptive significance of extreme female‐biased sexual size dimorphism (SSD) generally assume that in dimorphic species males rarely interfere with each other. Here we provide the first multivariate examination of sexual selection because of male–male competition over access to females in a species with ‘dwarf’ males, the orb‐weaving spider Argiope aurantia. Male A. aurantia typically try to mate opportunistically during the female's final moult when she is defenceless. We show that, contrary to previous hypotheses, the local operational sex ratio (males per female on the web) is male‐biased most of the season. Both interference and scramble competition occur during opportunistic mating, the former leading to significant selection for large male body size. Male condition and leg length had no effect on mating success independent of size. We discuss these findings in the context of the evolution of extreme female‐biased SSD in this clade.
The evolution of self‐fertilization and inbreeding depression under pollen discounting and pollen limitation
Authors: PORCHER E. , LANDE R.
Published: April 2005

We model the evolution of plant mating systems under the joint effects of pollen discounting and pollen limitation, using a dynamic model of inbreeding depression, allowing for partial purging of recessive lethal mutations by selfing. Stable mixed mating systems occur for a wide range of parameter values with pollen discounting alone. However, when typical levels of pollen limitation are combined with pollen discounting, stable selfing rates are always high but less than 1 (0.9 < s < 1 in most cases); in this situation, complete selfing does not evolve because pollen discounting becomes very large at high selfing rates, so that the automatic advantage of selfing changes to a disadvantage. These results suggest that mixed mating systems with high selfing rates can be maintained by selection, whereas mixed mating systems with low to moderate selfing rates are more likely attributable to unavoidable geitonogamous selfing.
Benign Giant Cell Tumour of Tendon Sheaths in a European Lynx (Lynx lynx)
Authors: Malatesta D. , Cuomo A. , Marà M. , Di Guardo G. , Gentile L. , Macolino A. , Della Salda L.
Published: April 2005

The histological, histochemical, immunohistochemical and ultrastructural features of a benign giant cell tumour (BGCT) of tendon sheaths in a 12‐year‐old male European lynx (Lynx lynx) are reported herein. The neoplastic mass involved the subcutaneous and inter‐muscular tissues of the first, second, third and fourth digit of the left forelimb, from the phalanxes up to the carpus. The tumour appeared as a grey‐whitish tissue mottled with darker areas, along with several scattered foci of orange colour. Histologically, the lesion consisted of a mixed population of numerous, multinucleated giant cells and epithelioid or spindle‐shaped mononuclear cells embedded in a loose, highly vascular stroma. Neoplastic cells lined cleft formations and synovial‐like projections into cystic spaces. No osteoid matrix could be detected. Haemorrhage and necrosis were also observed. The mononuclear and the giant cells were tartrate‐resistant acid phosphatase and periodic acid‐Schiff positive, being also immunohistochemically reactive for lysozyme and vimentin, with a few cells showing immunopositivity also for α‐1‐antitrypsin. Ultrastructurally, histiocyte‐like cells, fibroblast‐like cells and multinucleated giant cells were observed, but no virus‐like particles could be detected in any of the above cell types. The BGCT of tendon sheaths, a fairly uncommon neoplasm in animals, has not been previously reported in the lynx.
The species–area–energy relationship
Authors: Storch David , Evans Karl L. , Gaston Kevin J.
Published: April 2005

Area and available energy are major determinants of species richness. Although scale dependency of the relationship between energy availability and species richness (the species–energy relationship) has been documented, the exact relationship between the species–area and the species–energy relationship has not been studied explicitly. Here we show, using two extensive data sets on avian distributions in different biogeographic regions, that there is a negative interaction between energy availability and area in their effect on species richness. The slope of the species–area relationship is lower in areas with higher levels of available energy, and the slope of the species–energy relationship is lower for larger areas. This three‐dimensional species–area–energy relationship can be understood in terms of probabilistic processes affecting the proportions of sites occupied by individual species. According to this theory, high environmental energy elevates species’ occupancies, which depress the slope of the species–area curve.
Damage, digestion, and defence: the roles of alarm cues and kairomones for inducing prey defences
Authors: Schoeppner Nancy M. , Relyea Rick A.
Published: April 2005

Inducible defences are widely used for studying phenotypic plasticity, yet frequently we know little about the cues that induce these defences. For aquatic prey, defences are induced by chemical cues from predators (kairomones) and injured prey (alarm cues). Rarely has anyone determined the separate and combined effects of these cues, particularly across phylogenetically diverse prey types. We examined how tadpoles (Hyla versicolor) altered their defences when 10 different prey were either crushed by hand or consumed by predators. Across all prey types, crushing induced only a subset of the defences induced by consumption. Consuming vs. crushing produced additive responses for behaviour but synergistic responses for morphology and growth. Moreover, we discovered the first extensive evidence that prey responses to different alarm cues depends on prey phylogeny. These results suggest that the amount of information available to the prey affects both the quantitative and qualitative nature of the defended phenotype.
Incubation reduces microbial growth on eggshells and the opportunity for trans‐shell infection
Authors: Cook Mark I. , Beissinger Steven R. , Toranzos Gary A. , Arendt Wayne J.
Published: April 2005

Avian eggshells harbour microbes shortly after laying, and under appropriate ambient conditions they can multiply rapidly, penetrate through shell pores, infect egg contents and cause embryo mortality. We experimentally examined how incubation affects bacterial processes on the eggshells of pearl‐eyed thrashers Margarops fuscatus nesting in tropical montane and lowland forests in Puerto Rico. Bacteria and fungi grew rapidly on shells of newly laid, unincubated eggs exposed to ambient conditions, but declined to low levels on shells of eggs incubated by thrashers. Divergence in bacterial growth between incubated and exposed eggs was more marked at the montane forest than at the lowland site. Pathogenic microorganisms became increasingly dominant on shells of exposed eggs, but these groups were relatively rare on incubated eggs, where more benign, less invasive groups prevailed. Some incubation during laying may be necessary to decrease the probability of trans‐shell infection by reducing the growth of harmful bacteria and fungi on eggshells, although it may increase hatching asynchrony and the likelihood of brood reduction.
Extinction order and altered community structure rapidly disrupt ecosystem functioning
Authors: Larsen Trond H. , Williams Neal M. , Kremen Claire
Published: April 2005

By causing extinctions and altering community structure, anthropogenic disturbances can disrupt processes that maintain ecosystem integrity. However, the relationship between community structure and ecosystem functioning in natural systems is poorly understood. Here we show that habitat loss appeared to disrupt ecosystem functioning by affecting extinction order, species richness and abundance. We studied pollination by bees in a mosaic of agricultural and natural habitats in California and dung burial by dung beetles on recently created islands in Venezuela. We found that large‐bodied bee and beetle species tended to be both most extinction‐prone and most functionally efficient, contributing to rapid functional loss. Simulations confirmed that extinction order led to greater disruption of function than predicted by random species loss. Total abundance declined with richness and also appeared to contribute to loss of function. We demonstrate conceptually and empirically how the non‐random response of communities to disturbance can have unexpectedly large functional consequences.
Phylogenetic analysis of Macrobiotidae (Eutardigrada, Parachela): a combined morphological and molecular approach
Authors: Guidetti Roberto , Gandolfi Andrea , Rossi Valeria , Bertolani Roberto
Published: April 2005

Combined analyses of morphological and molecular data were used to resolve phylogenetic relationships within Macrobiotidae (Eutardigrada). Morphological data were analysed using a cladistic approach with a matrix comprising 15 taxa with 17 characters to obtain a phylogenetic reconstruction. Molecular data were obtained by sequencing the cytochromecoxidase subunit I gene in seven species of Macrobiotidae and one of Eohypsibiidae (used as outgroup). The morphological character defining the family, symmetrical claw on each leg, turns out to be plesiomorphic. Moreover, neither morphological nor molecular analyses supports a monophyletic clade for the subfamily Macrobiotinae, whereas both support a well defined evolutionary line (Murrayinae) within the family. We propose elevating the latter to family level (Murrayidae) while temporarily retaining as valid the family Macrobiotidae (amending its diagnosis, including within it only Macrobiotinae). Murrayidae opens an interesting evolutionary prospective, because the entire line has differentiated without sexual reproduction, constituting an example of evolution of asexual lineages.
A randomized study of orlistat in combination with a weight management programme in obese patients with Type 2 diabetes treated with metformin
Authors: Berne C. ,   the Orlistat Swedish Type 2 diabetes Study Group
Published: April 2005

Aims  To assess the effects of orlistat vs. placebo, in combination with a weight management programme, on weight loss and metabolic control in obese patients with Type 2 diabetes.

Methods  Patients treated with either metformin alone or metformin in combination with sulphonylurea were randomized to double‐blind treatment with orlistat or placebo (120 mg) three times daily, combined with a mildly reduced calorie diet and a weight management programme for 52 weeks. Changes in body weight, anthropometry, glycaemic control and lipid profile were assessed.

Results  After 52 weeks, orlistat‐treated patients achieved an almost threefold greater reduction in weight compared with placebo recipients (−5.0% vs. −1.8%; P < 0.0001). The decrease in waist circumference was significantly greater with orlistat than placebo (−4.8 cm vs. −2.8 cm; P = 0.0022). Orlistat treatment was also associated with significantly greater reductions in haemoglobin A1c (−1.1% vs. −0.2%; P < 0.0001), fasting plasma glucose (−1.9 mmol/l vs. −0.3 mmol/l; P < 0.0001), total cholesterol (−0.2 mmol/l vs. 0.1 mmol/l; P = 0.03) and apolipoprotein B (−0.08 g/l vs. 0.01 g/l; P = 0.0085) and greater improvements in beta‐cell function (P = 0.031) and insulin resistance (P = 0.001) assessed using the homeostasis model assessment (HOMA). Similar results were obtained for subgroups of patients treated with metformin alone or metformin in combination with sulphonylurea. Orlistat treatment reduced the requirement for anti‐diabetic medication more than placebo.

Conclusions  Orlistat, in combination with a reduced calorie diet and a weight management programme, promotes weight loss and clinically relevant improvements in glycaemic control and other cardiovascular risk factors in obese patients with Type 2 diabetes.
Abnormal ventilatory responses to hypoxia in Type 2 diabetes
Authors: Weisbrod C. J. , Eastwood P. R. , O'Driscoll G. , Green D. J.
Published: April 2005

Aims  The incidence of Type 2 diabetes is increasing, along with its associated micro‐ and macrovascular disease manifestations. Previous studies indicate that patients with Type 2 diabetes exhibit abnormal cardiopulmonary reflex responses to various stimuli, although the impact of hypoxia, a common physiological stimulus, on ventilatory responses has not previously been studied in humans with Type 2 diabetes.

Methods  Minute ventilation (V̇E) breathing pattern responses (total breath time, TTOT; expiratory time, TE; inspiratory time, TI; inspiratory duty cycle, TI/TTOT) were measured during 5 min each of normoxia and isocapnic hypoxia (arterial O2 saturation ∼85%) in eight subjects with Type 2 diabetes and seven age‐ and body mass index‐matched healthy subjects.

Results  During normoxia, V̇E was similar in control and diabetic subjects (6.4 ± 1.2, 6.4 ± 1.1 l/min, respectively). In response to hypoxia, V̇E significantly increased in both groups (to 17.0 ± 5.0 and 9.5 ± 2.0 l/min, respectively, P < 0.05), but the magnitude of increase in V̇E was significantly less in diabetic than in control subjects (P < 0.05). In addition, the breathing pattern response to hypoxia differed between groups in terms of TI/TTOT and TTOT (P < 0.05), with control subjects significantly decreasing TTOT and TE (P < 0.05) while diabetic subjects tended to increase both.

Conclusions  Relative to matched control subjects, Type 2 diabetic subjects exhibit blunted V̇E responses to acute isocapnic hypoxia, suggesting that this group of diabetic subjects possesses a chemoreflex ill‐equipped to respond homeostatically to hypoxic challenge.
Predictors of first stroke in Type 1 diabetes: The Fremantle Diabetes Study
Authors: Davis T. M. E. , Bruce D. G. , Davis W. A.
Published: April 2005

Aims  To examine prospectively the relationship between vascular risk factors and stroke in Type 1 diabetes.

Methods  A community‐based sample of 126 adult Type 1 patients was recruited between 1993 and 1996 and followed annually for a mean ±sd of 7.2 ± 1.6 years. Cerebrovascular events before and after recruitment were identified from history and examination findings, hospital morbidity data and death notifications.

Results  Six patients suffered a first stroke during follow‐up, of which five were ischaemic and one a subarachnoid haemorrhage on cranial computed tomography. Patients were subdivided into those with no history of stroke/transient ischaemic attack (TIA) at baseline and no subsequent ischaemic stroke (Group 1, n = 114), those with a history of stroke/TIA at baseline (Group 2, n = 7), and those with no history of stroke/TIA at baseline but who suffered a first ischaemic stroke during follow‐up (Group 3, n = 5). Group 1 patients were the youngest, had the shortest diabetes duration and were the least likely to be taking antihypertensive medication or aspirin. Amongst a range of potential baseline predictors of first stroke including glycated haemoglobin, only serum HDL‐cholesterol differentiated Group 3 patients (0.69 ± 0.17 mmol/l) from those in the other groups (1.26 ± 0.42 and 1.28 ± 0.45 mmol/l for Groups 1 and 2 respectively, P < 0.05).

Conclusions  The present association between low serum HDL‐cholesterol and ischaemic stroke patients suggests that aggressive management of dyslipidaemia may protect against cerebrovascular disease in Type 1 diabetes.
A multivariate logistic regression equation to screen for dysglycaemia: development and validation
Authors: Tabaei B. P. , Engelgau M. M. , Herman W. H.
Published: April 2005

Aims  To develop and validate an empirical equation to screen for dysglycaemia [impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and undiagnosed diabetes].

Methods  A predictive equation was developed using multiple logistic regression analysis and data collected from 1032 Egyptian subjects with no history of diabetes. The equation incorporated age, sex, body mass index (BMI), post‐prandial time (self‐reported number of hours since last food or drink other than water), systolic blood pressure, high‐density lipoprotein (HDL) cholesterol and random capillary plasma glucose as independent covariates for prediction of dysglycaemia based on fasting plasma glucose (FPG) ≥ 6.1 mmol/l and/or plasma glucose 2 h after a 75‐g oral glucose load (2‐h PG) ≥ 7.8 mmol/l. The equation was validated using a cross‐validation procedure. Its performance was also compared with static plasma glucose cut‐points for dysglycaemia screening.

Results  The predictive equation was calculated with the following logistic regression parameters: P = 1 + 1/(1 + e−X) = where X = −8.3390 + 0.0214 (age in years) + 0.6764 (if female) + 0.0335 (BMI in kg/m2) + 0.0934 (post‐prandial time in hours) + 0.0141 (systolic blood pressure in mmHg) − 0.0110 (HDL in mmol/l) + 0.0243 (random capillary plasma glucose in mmol/l). The cut‐point for the prediction of dysglycaemia was defined as a probability ≥ 0.38. The equation's sensitivity was 55%, specificity 90% and positive predictive value (PPV) 65%. When applied to a new sample, the equation's sensitivity was 53%, specificity 89% and PPV 63%.

Conclusions  This multivariate logistic equation improves on currently recommended methods of screening for dysglycaemia and can be easily implemented in a clinical setting using readily available clinical and non‐fasting laboratory data and an inexpensive hand‐held programmable calculator.
Insulin aspart improves meal time glycaemic control in patients with Type 2 diabetes: a randomized, stratified, double‐blind and cross‐over trial
Authors: Perriello G. , Pampanelli S. , Porcellati F. , Avogaro A. , Bosi E. , Petrella G. , Squatrito S. , Furneri S. , Marra G. , Vitali L. , Previti M. , Cucinotta D.
Published: April 2005

Aims  This randomized, multi‐centre, double‐blind, stratified, two period, cross‐over trial was undertaken to assess the pharmacokinetics and pharmacodynamics of insulin aspart injected immediately before compared with regular human insulin injected 30 min before a Mediterranean‐style meal in 37 (23 M, 14 F) patients with Type 2 diabetes.

Methods  Insulin aspart or regular human insulin was given subcutaneously (0.15 U/kg) in random sequence, using a double‐dummy technique (at one visit: human regular insulin at t = −30 min and placebo at t = 0; at the other visit: placebo at t = −30 min and aspart insulin at t = 0). Serum glucose and insulin concentrations (15 points) were measured after each meal for 240 min.

Results  Post‐prandial glycaemic excursions were 20% lower with insulin aspart (IAsp) compared with regular human insulin (HI) treatment [ratio (Iasp/HI) = 0.80, CI = (0.66–0.98), P = 0.034]. The maximum serum glucose (SG) concentration was similar for the two treatments (P = NS). The (median) time to maximum SG was 25 min shorter for IAsp compared with HI (P = 0.048). Maximum serum insulin concentration was higher after IAsp compared with HI (P = 0.023) as well as the area under the 4‐h serum insulin curve (P = 0.006). Furthermore, the time to maximum serum insulin concentration was 27 min shorter after IAsp (P = 0.039), even though IAsp was injected 30 min after HI. No adverse events occurred during the trial.

Conclusions  In patients with Type 2 diabetes a more favourable insulin profile and a better glycaemic control were found with IAsp injected immediately before compared with HI injected 30 min before a Mediterranean‐style meal.
Continuing metformin when starting insulin in patients with Type 2 diabetes: a double‐blind randomized placebo‐controlled trial
Authors: Douek I. F. , Allen S. E. , Ewings P. , Gale E. A. M. , Bingley P. J. ,   for the Metformin Trial Group
Published: April 2005

Aims  To test the effect of continuing metformin on weight gain and glycaemic control in patients with poorly controlled Type 2 diabetes who need to start insulin.

Methods  Patients with Type 2 diabetes on maximum tolerated oral agents referred for insulin conversion were recruited from hospital diabetes clinics into a double‐blind randomized placebo‐controlled trial. The 183 participants received metformin or placebo, titrated up to 2 g a day or maximum tolerated dose, with insulin started according to local practice. The main outcome measures were weight change over 12 months, HbA1c, insulin dose, frequency of hypoglycaemia, treatment satisfaction, and well‐being.

Results  Over 12 months, metformin was associated with less weight gain than placebo [mean 6.1 kg vs. 7.6 kg; adjusted difference 1.5 kg (95% confidence interval 0.2–2.9); P = 0.02], a greater reduction in HbA1c[1.5% vs. 1.3%; adjusted difference 0.5% (0.1–0.9); P = 0.02] and a lower insulin requirement [62 units vs. 86; adjusted difference 25 units (15–34); P < 0.001], but also more hypoglycaemia [relative risk of any episode 1.24 (1.02–1.1); P = 0.03]. Treatment satisfaction improved more in patients on metformin than on placebo (P < 0.001), as did the positive well‐being score (P = 0.02).

Conclusions  Metformin decreases weight gain, lowers insulin requirement, and improves glycaemic control, and should be continued in patients with Type 2 diabetes who transfer to insulin.
Resistin polymorphisms are associated with cerebrovascular disease in Finnish Type 2 diabetic patients
Authors: Kunnari A. , Ukkola O. , Kesäniemi Y. A.
Published: April 2005

Aims  Resistin is a hormone secreted by adipocytes and it is also expressed in monocytes. Resistin has been found to increase insulin resistance, a key feature in Type 2 diabetes. The aim of this study was to investigate whether resistin polymorphisms are associated with Type 2 diabetes and its clinical characteristics.

Methods  We studied the allele and genotype frequencies of the single‐nucleotide polymorphisms (SNPs) −420 (C > G), +157 (T > C) and +299 (G > A) in the resistin gene in 258 Finnish Type 2 diabetics and 494 controls.

Results  These three markers were in significant linkage disequilibrium with each other. No significant (P < 0.05) differences in the allele or genotype frequencies were observed between the study groups. Subjects with Type 2 diabetes showed a significant association between cerebrovascular disease and the SNPs −420 (P = 0.004) and +299 (P = 0.007), the G‐G and A‐A genotypes, respectively, had the highest frequencies. SNPs −420 (P = 0.000) and +299 (P = 0.002) in men and SNP +157 in men (P = 0.005) and in women (P = 0.019) showed significant association with higher mean blood glucose. The rare allele homozygotes also had the highest mean blood glucose values. We also observed associations between at least one of the SNPs and fasting blood glucose, glycosylated haemoglobin A1 (GHbA1), low‐density lipoprotein (LDL) cholesterol and systolic and diastolic blood pressure. After correction for multiple comparisons, the association between the promoter variant SNP −420 and cerebrovascular disease in both genders and the associations between mean blood glucose and SNP −420 and SNP +299 in men remained significant.

Conclusions  The results suggest that resistin may play a role in atherogenesis probably through increasing insulin resistance.
Prognostic value of the Framingham cardiovascular risk equation and the UKPDS risk engine for coronary heart disease in newly diagnosed Type 2 diabetes: results from a United Kingdom study
Authors: Guzder R. N. , Gatling W. , Mullee M. A. , Mehta R. L. , Byrne C. D.
Published: April 2005

Aims  To determine the prognostic value of the Framingham equation and the United Kingdom Prospective Diabetes Study (UKPDS) risk engine in patients with newly diagnosed Type 2 diabetes.

Methods  A community‐based cohort (n = 428; aged 30–74 years) free of clinically evident CVD and newly diagnosed with Type 2 diabetes were studied over a median 4.2 (sd ± 0.62) years. Predicted (using baseline variables at diagnosis) and observed proportions of primary CVD and CHD events were compared using the Framingham equations and the UKPDS risk engine (only CHD events). The discrimination (c‐statistic) and calibration (HLχ2) of the risk equations were calculated. The sensitivity and specificity of the Framingham equation at a 15%, 10‐year CHD risk threshold (NICE guidelines) was compared with that of the ADA lipid threshold (LDLc ≥ 2.6 mmol/l or triglycerides ≥ 4.5 mmol/l).

Results  The Framingham equations underestimated the overall number of cardiovascular events by 33% and coronary events by 32% and showed modest discrimination and poor calibration for CVD [c = 0.673; HLχ2 = 32.8 (P < 0.001)] and CHD risk [c = 0.657; HLχ2 = 19.8 (P = 0.011)]. Although the overall underestimate was lower and non‐significant with the UKPDS risk engine for CHD (13%), its performance in terms of discrimination and calibration were similar [c = 0.670; HLχ2 = 17.1 (P = 0.029)]. The 15%, 10‐year CHD risk threshold with both the Framingham and UKPDS risk engines had similar sensitivity for primary CVD as the lipid level threshold [85.7 and 89.8% vs. 93.9% (P = 0.21 and 0.34)] and both had greater specificity [33.0 and 30.3% vs. 12.1% (P < 0.001 and P < 0.001)].

Conclusions  In people with newly diagnosed Type 2 diabetes, both the Framingham equation and UKPDS risk engine are moderately effective at identifying those at high‐risk (discrimination) and are poor at quantifying risk (calibration). Nonetheless, at a population level, a 15% 10‐year CHD risk threshold using either risk calculator has similar sensitivity as an approach based on a single lipid risk factor level and may have benefits in terms of cost‐effectiveness given the improved specificity.
Childhood diabetes presenting with hyperosmolar dehydration but without ketoacidosis: a report of three cases
Authors: Kershaw M. J. R. , Newton T. , Barrett T. G. , Berry K. , Kirk J.
Published: April 2005

Background  Diabetic ketoacidosis (DKA) is a common mode of presentation of diabetes mellitus in children, accounting for 26% of new cases. Rarely, children with diabetes may develop other forms of metabolic decompensation associated with hyperglycaemia and hyperosmolality. Hyperglycaemia and hyperosmolality without ketoacidosis has high mortality in adults, although there is no data on mortality in children.

Case reports  We deseribe three children who presented to Birmingham Children's Hospital and were initially suspected to have DKA. Each child was severely hyperglycaemic and hyperosmolar but without significant ketosis or acidosis. In two of the three children, the hyperosmolar state was associated with the ingestion of large volumes of high calorie fluids preceding the presentation. These children were exquisitely sensitive to insulin and may be at a significantly higher risk of cerebral oedema in view of their hyperosmolar state.

Conclusions  Hyperosmolar hyperglycaemia is a serious and rare complication at presentation of diabetes in children, and should be distinguished from DKA. These children are at an increased risk of cerebral oedema compared with DKA, and one should have a low threshold for suspicion of this complication.
Winners and Losers
Authors: Clements Luke
Published: April 2005

This paper considers whether the Human Rights Act 1998 is, in itself, capable of materially improving the lives of those who experience social exclusion – or whether it is likely to exacerbate their difficulties. It draws on the relevant post‐2000 research concerning the Act's impact on socially excluded groups which suggests that the response of the statutory agencies has been disappointing – that ‘not being proactive’ has proved to be the most attractive option. It then addresses the incongruity between the government's strategies for combating social exclusion and civil justice.
Lost on the Way Home? The Right to Life in Northern Ireland
Authors: Bell Christine , Keenan Johanna
Published: April 2005

This article starts from the premise that, through the Belfast Agreement, the Human Rights Act 1998 (HRA) was invested with a ‘transitional justice’ function in Northern Ireland, unlike in the rest of the United Kingdom. The article evaluates how far the HRA has met this challenge by examining a case study of the right to life. The European Court's development of a procedural aspect to the right to life in the form of a right to an effective investigation, has implicated both institutional reform for the future, and also a need to revisit past state killings with their ‘transitional justice’ implications. There have been some positive developments, but, despite this, domestic institutions and courts have largely failed to deliver on Article 2's procedural aspect. The article concludes by questioning whether the very design of the HRA has limited the possibilities for a ‘transformational constitutionalism’ capable of incorporating Article 2's procedural right.
Rapid growth in infancy and childhood and obesity in later life – a systematic review
Authors: Monteiro P. O. A. , Victora C. G.
Published: April 2005

The association between obesity and morbidity resulting from chronic diseases is well known. This systematic review addresses studies of the role of rapid growth in infancy and childhood as possible determinants of overweight and obesity later in the life course. We reviewed MEDLINE for studies reporting on growth in infancy and childhood, as well as measures of weight or adiposity in later childhood, adolescence or adulthood. The methodological quality of the papers was assessed using the criteria suggested by Downs and Black. Sixteen articles that fulfilled review criteria were located. There was wide variability in the indicators used for defining rapid growth as well as overweight or obesity. The age range in which weight or adiposity was measured ranged from 3 to 70 years. In spite of differences in definitions used, 13 articles that reported on early rapid growth found significant associations with later overweight or adiposity. Efforts should be made to standardize the definition of rapid growth, as well as that of overweight and obesity in children and adolescents. The most frequent definition for rapid growth in this review was a Z‐score change greater than 0.67 in weight for age between two different ages in childhood. Regarding obesity, the definition proposed by the International Obesity Task Force also appears to be most appropriate. The present results indicate that early growth is indeed associated with the prevalence of obesity later in the life course.
Anion variations at semiconductor interfaces: ZnSe(100)/GaAs(100) superlattices
Authors: Farrell H. H. , LaViolette Randall A.
Published: April 2005

We extended our study of heterovalent interfaces between ZnSe(100) and GaAs(100) in superlattices using first-principles, density-functional theory calculations. Here, we concentrate on the changes in interfacial binding energy that occur when the stoichiometry is varied in the anion layer adjacent to the interface. This follows earlier work where the cation stoichiometry was varied. We studied three general categories of simple heterojunctions: those with only As–Zn bonding, those with only Se–Ga bonding, and those with mixed As–Zn and Se–Ga bonding. We also considered more complex interface configurations. Several different variations in interfacial stoichiometry that are conceptually based on the heteroepitaxial growth of ZnSe(100) on the GaAs(100)(2×4)β2 surface structure were studied. In addition, the effects induced by the presence of vacancies in the vicinity of the surface were investigated. These more complex interfaces are discussed in terms of published experimental results. Finally, the possibility that the energy of the interface can be described in terms of the energy of the bonds that span that interface was also examined. We find that, for all of the 14 interfaces studied, the interface energy can be expressed as a simple sum of the per-bond-pair energies with an average error of less than 3%. Therefore, in these systems, the energies of the interfacial bonds are “additive” to a good approximation.
Desorption/ionization mass spectrometry on array of silicon microtips
Authors: Gorecka-Drzazga Anna , Dziuban Jan , Drzazga Wlodzimierz , Kraj Agnieszka , Silberring Jerzy
Published: April 2005

The matrix-free laser desorption/ionization of the biosamples for time-of-flight mass spectrometry from an array of gated silicon tips has been presented. The gated silicon tips were fabricated similar to the well-known electron-field-emitters gated sources. In this method, called desorption/ionization on silicon tips array, an array of gated silicon sharp tips covered with a biosample and irradiated by a pulsed ultraviolet laser serves as the effective source of ions, replacing standard ionization platforms. Tests have confirmed that the effective laser desorption/ionization of the low-mass biosamples, such as dopamine and leucyl-glycyl-glycine tripeptide, may be obtained. It is possible that the method will play a very important role in post-genetic proteomic investigations.
Three-dimensional multilayered microstructure fabricated by imprint lithography
Authors: Ooe H. , Morimatsu M. , Yoshikawa T. , Kawata H. , Hirai Y.
Published: April 2005

The fabrication of a three-dimensional multilayered microstructure is demonstrated by the imprint and reversal imprint technique. We have studied polymer properties and pressing conditions as important parameters for selecting the reversal imprint modes. We investigated the conditions that are required to form the fluid channels and the through holes. Using these advanced processes, three-dimensional microfluid channels with through holes were successfully fabricated at low cost and high throughput. This technique is one of the most promising methods for making various advanced microstructures such as compact and multifunctional chemical devices.
Effects of B content on microstructure and mechanical properties of nanocomposite Ti–Bx–Ny thin films
Authors: Lu Y. H. , Sit P. , Hung T. F. , Chen Haydn , Zhou Z. F. , Li K. Y. , Shen Y. G.
Published: April 2005

Thin films of Ti–Bx–Ny were deposited on Si(100) at room temperature by reactive unbalanced dc magnetron sputtering in an Ar–N2 gas mixture. The effects of B content on microstructure and mechanical properties of these films have been analyzed using x-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, x-ray diffraction, transmission electron microscopy, atomic force microscopy, micro-indentation measurements, and an optical interference method. Microstructure studies revealed that depending upon the amount of B addition, the films showed two- or three-phase nanocomposite structure. At B contents below about 10at.%, the films consisted of mainly TiN bondings with a small amount of TiB and BN bondings. As the B content increased, TiB gradually transformed to TiB2 and the films consisted of nanocrystalline (nc-) TiN embedded in an amorphous (a-) TiB2 matrix. A maximum hardness of ∼44GPa was observed in a film with B content of 19at.%. The improved mechanical properties of Ti–Bx–Ny films with the addition of B into TiN were attributed to their densified microstructure with development of fine grain size and different phase combination. The reduction in grain size has also been supported by means of a Monte Carlo simulation. When B contents reached ∼42at.% or above, an amorphous-like nanocomposite of nc-TiN∕a-TiB2∕a-BN was formed. The effect of thin a-TiB2 layer in stabilizing nc-TiN structure is also elucidated and explained on the basis of structural and thermodynamic stability.
Synthesis of multiwalled carbon nanotubes using C14H10O7W catalyst
Authors: Huh Yoon , Lee Jeong Yong , Choi Sang Kyu , Lee Cheol Jin
Published: April 2005

High-purity carbon nanotubes were synthesized using a novel catalyst: tungsten-containing complex (C14H10O7W). The carbon nanotubes have a multiwalled structure that is hollow on the inside and a clean surface without carbonaceous particles. The carbon nanotubes have average diameters in the range of 20–60nm and lengths of 30μm. Transmission electron microscopy analysis reveals that the inner graphite sheets of these nanotubes are highly crystallized, but the outer graphite sheets are defective. The microstructures of the carbon nanotubes produced from C14H10O7W, tungsten hexacarbonyl [W(CO)6], and iron pentacarbonyl [Fe(CO)5] were analyzed using high-resolution transmission electron microscopy. We demonstrate that the tungsten-based catalyst can effectively be used to produce the carbon nanotubes.
Optical measurement and fabrication from a Morpho-butterfly-scale quasistructure by focused ion beam chemical vapor deposition
Authors: Watanabe Keiichiro , Hoshino Takayuki , Kanda Kazuhiro , Haruyama Yuichi , Kaito Takashi , Matsui Shinji
Published: April 2005

The Morpho-butterfly wing reflects interfered brilliant blue, which originates from nanostructures on its scales, for any incidence angle of white light. We have fabricated a Morpho-butterfly-scale quasistructure using focused ion beam chemical vapor deposition and observed brilliant blue reflection from this quasistructure with an optical microscope. We measured the reflection from real Morpho-butterfly scales and from the quasistructure with a photonic multichannel spectral analyzer system. The reflection spectra of the quasistructure were very similar to those of Morpho-butterfly scales.
Space-charge effects of electrons and ions on the steady states of field-emission-limited diodes
Authors: Lin Ming-Chieh
Published: April 2005

Space-charge effects of electrons and ions on the steady state of a field-emission-limited diode (FELD) are investigated via a self-consistent approach. The field-emission process is described quantum mechanically by the Fowler–Nordheim equation. The cathode plasma and surface properties are considered within the framework of the effective work function approximation. Ionization effects at the anode as well as electron space-charge effects are described by Poisson’s equation. The numerical calculations are carried out self-consistently to yield the steady states of the bipolar field-emission-limited flow of the FELD. We found that the stationary state of the diode exhibits a cut-off voltage. The electric field on the cathode surface is found to be saturated in the high voltage regime and is determined by the effective work function approximately. In addition, the ion current included in the Poisson’s equation has been treated as a tuning parameter. The analytical formula of the electron current density has been derived. The field-emission currents in the presence of saturated ion currents can be enhanced to be nearly 1.8 times of the case with no ion current.