bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug‐specific in vitro release of IL‐2, IL‐5, IL‐13 and IFN‐γ in patients with delayed‐type drug hypersensitivity
Authors: Lochmatter P. , Beeler A. , Kawabata T. T. , Gerber B. O. , Pichler W. J.
Published: February 2009

Background:  The most prevalent drug hypersensitivity reactions are T‐cell mediated. The only established in vitro test for detecting T‐cell sensitization to drugs is the lymphocyte transformation test, which is of limited practicability. To find an alternative in vitro method to detect drug‐sensitized T cells, we screened the in vitro secretion of 17 cytokines/chemokines by peripheral blood mononuclear cells (PBMC) of patients with well‐documented drug allergies, in order to identify the most promising cytokines/chemokines for detection of T‐cell sensitization to drugs.

Methods:  Peripheral blood mononuclear cell of 10 patients, five allergic to β‐lactams and five to sulfanilamides, and of five healthy controls were incubated for 3 days with the drug antigen. Cytokine concentrations were measured in the supernatants using commercially available 17‐plex bead‐based immunoassay kits.

Results:  Among the 17 cytokines/chemokines analysed, interleukin‐2 (IL‐2), IL‐5, IL‐13 and interferon‐γ (IFN‐γ) secretion in response to the drugs were significantly increased in patients when compared with healthy controls. No difference in cytokine secretion patterns between sulfonamide‐ and β‐lactam‐reactive PBMC could be observed. The secretion of other cytokines/chemokines showed a high variability among patients.

Conclusion:  The measurement of IL‐2, IL‐5, IL‐13 or IFN‐γ or a combination thereof might be a useful in vitro tool for detection of T‐cell sensitization to drugs. Secretion of these cytokines seems independent of the type of drug antigen and the phenotype of the drug reaction. A study including a higher number of patients and controls will be needed to determine the exact sensitivity and specificity of this test.
Neuroticism, extraversion, stressful life events and asthma: a cohort study of middle‐aged adults
Authors: Loerbroks A. , Apfelbacher C. J. , Thayer J. F. , Debling D. , Stürmer T.
Published: February 2009

Background:  Stressful life events can trigger asthma exacerbations, but could also contribute to the development of incident asthma. However, only few studies have investigated the association between stressful life events and adult asthma prospectively. Likewise, stress‐related personality traits (e.g. neuroticism and extraversion) may increase asthma risk, but this has been examined in only one prospective study. We therefore aimed to investigate the association between neuroticism, extraversion, stressful life events and incident asthma.

Methods:  A population‐based sample of 5114 middle‐aged adults completed questionnaires between 1992 and 1995. Among those alive in 2002/2003, 4010 (83%) were followed‐up by questionnaires. Exposures of interest included neuroticism, extraversion and three stressful life events (unemployment, having broken off a life partnership and death of a close person). Associations with incident asthma were estimated by multivariable risk ratios (RR) and 95% confidence intervals (95% CI) using Poisson regression.

Results:  High vs low neuroticism predisposed to developing asthma (RR = 3.07, 95% CI = 1.71–5.48), but high extraversion did not (RR = 1.30, 95% CI = 0.79–2.15). Having broken off a life partnership significantly increased asthma risk (RR = 2.24, 95% CI = 1.20–4.21) in contrast to death of a close person (RR = 1.06, 95% CI = 0.64–1.75) or unemployment (RR = 1.65, 95% CI = 0.72–3.78).

Conclusions:  High levels of neuroticism may increase the risk of asthma in middle‐aged adults. Having broken off a life partnership was the only stressful event, which was associated with incident asthma. Synthesized with evidence from earlier studies, this could reflect that interpersonal conflicts may increase asthma risk, possibly along an immunological pathway.
Associations of β2‐adrenergic receptor genotypes and haplotypes with wheezing illness in Taiwanese schoolchildren
Authors: Lee Y.‐L. , Wang S.‐T. , Tsai C.‐H. , Guo Y. L.
Published: February 2009

Background: Increasing attention was focused on the β2‐adrenergic receptor gene (ADRB2), whose genetic variability has been implicated as a risk factor for asthma‐related phenotypes. However, only a few studies reported the associations by utilizing haplotypic approaches. We therefore examined the relationship of childhood wheezing illness with polymorphisms at codons 16 and 27, and evaluated the influence of polymorphisms individually and in combination as haplotypes.

Methods: We conducted a genetic case–control study comprising 215 wheezing children and 183 nonwheezing controls, all of whom were selected from 2524 fourth‐ to ninth‐grade schoolchildren in southern Taiwan.

Results: All participants were homozygous at the ADRB2 Thr164 locus. After controlling for possible confounders, ADRB2 Glu27 allele was significantly associated with wheezing illness in all genetic models, but the risks on Arg16Gly genotypes were inconclusive. Estimated frequencies for the three main hyplotypes were Arg16/Gln27 57.2%, Gly16/Gln27 35.3%, Gly16/Glu27 7.4% in wheezing children, and Arg16/Gln27 56.3%, Gly16/Gln27 32.2%, Gly16/Glu27 10.4% in controls. The protective effect of Gly16/Glu27 haplotype remained relative to all other ADRB2 haplotypes [adjusted relative risk (aRR) = 0.58; 95% confidence interval (CI) 0.35–0.97]. As compared with children without Gly16/Glu27 haplotype, those with Gly16/Glu27 haplotype had a significantly lower risk for wheezing illness (aRR = 0.56; 95% CI 0.33–0.99). The copy numbers of Gly16/Glu27 haplotype also showed a clear dose‐response relationship on the decreased risks. No significant association was found with the prevalence of wheezing illness for other haplotypes.

Conclusion: We concluded that ADRB2 Glu27 allele and Gly16/Glu27 haplotype were significantly protective factors for wheezing illness in Taiwanese schoolchildren.
Inbreeding, energy use and condition
Authors: KETOLA T. , KOTIAHO J. S.
Published: February 2009

In energetic terms, fitness may be seen to be dependent on successful allocation of energy between life‐history traits. In addition, fitness will be constrained by the energy allocation ability, which has also been defined as condition. We suggest here that the allocation ability, estimated as the difference between total energy budget and maintenance metabolism, may be used as a measure of condition. We studied this possibility by measuring the resting metabolic rate and metabolism during forced exercise in Gryllodes sigillatus crickets. To verify that these metabolic traits are closely related to fitness, we experimentally manipulated the degree of inbreeding of individuals belonging to the same pedigree, hence enabling analysis of both inbreeding depression and heritability of traits. We found that inbreeding increased maintenance metabolism, whereas total energy budget was rather insensitive to inbreeding. Despite this, inbreeding led to decreased allocation ability. Overall, metabolic traits exhibited strong inbreeding depression and rather low heritabilities, a pattern that is typical of traits under strong selection. However, traditionally used condition indices were not affected by inbreeding and did not covary with metabolic traits. Moreover, in contrast to the common, but largely untested, tenet, it seems that high resting metabolic rate is indicative of low rather than high quality.
Division of labour within flowers: heteranthery, a floral strategy to reconcile contrasting pollen fates
Authors: VALLEJO‐MARÍN M. , MANSON J. S. , THOMSON J. D. , BARRETT S. C. H.
Published: February 2009

In many nectarless flowering plants, pollen serves as both the carrier of male gametes and as food for pollinators. This can generate an evolutionary conflict if the use of pollen as food by pollinators reduces the number of gametes available for cross‐fertilization. Heteranthery, the production of two or more stamen types by individual flowers reduces this conflict by allowing different stamens to specialize in ‘pollinating’ and ‘feeding’ functions. We used experimental studies ofSolanum rostratum(Solanaceae) and theoretical models to investigate this ‘division of labour’ hypothesis. Flight cage experiments with pollinating bumble bees (Bombus impatiens) demonstrated that although feeding anthers are preferentially manipulated by bees, pollinating anthers export more pollen to other flowers. Evolutionary stability analysis of a model of pollination by pollen consumers indicated that heteranthery evolves when bees consume more pollen than should optimally be exchanged for visitation services, particularly when pollinators adjust their visitation according to the amount of pollen collected.
Body shape evolution among ploidy levels of the Squalius alburnoides hybrid complex (Teleostei, Cyprinidae)
Authors: CUNHA C. , BASTIR M. , COELHO M. M. , DOADRIO I.
Published: February 2009

Hybridization, ploidy level and genomic constitution may be important to respond to different environments, by producing different phenotypes and thus reducing competitive interaction. Through geometric morphometrics, we examined variation in body size and shape among biotypes of the Squalius alburnoides hybrid complex and their sperm donor (Squalius carolitertii). Results showed that S. carolitertii is significantly larger in size than the biotypes of the complex. No significant relationship was observed between ploidy and body size among S. alburnoides biotypes. Significant variation in body shape was found between S. carolitertii and S. alburnoides, and between tetraploids and the other biotypes. These differences in biotypes may reduce resource competition, highlighting the potential importance of resource availability favouring one biotype over another. In S. alburnoides, the adaptation to different trophic niches through modification of trophic morphology, body shapes, and feeding behaviour, may result from an increase in ploidy and genomic constitution. This adaptation may account also for the formation and maintenance of this nonsexual complex.
Detecting defects in conifers with ground penetrating radar: applications and challenges
Authors: Butnor J. R , Pruyn M. L. , Shaw D. C. , Harmon M. E. , Mucciardi A. N. , Ryan M. G.
Published: February 2009

Our objective was to test ground penetrating radar (GPR) to non‐destructively estimate decay volumes in living coniferous trees. GPR is geophysical tool which uses an antenna to propagate short bursts of electromagnetic energy in solid materials and measure the two‐way travel time and amplitude of reflected signals. We compared estimates of bole decay from data collected with a SIR 3000 GPR system equipped with a 900 MHz antenna to measurements of decay from stem cross sections and increment cores for three conifer species (Pseudotsuga menziesii, Thuja plicata and Tsuga heterophylla). We found that near‐surface decay, air‐filled voids and desiccated boles had unique electromagnetic signatures, which could be separated from other defects. GPR successfully estimated the percent area of air‐filled cavities and was not significantly different than results from destructive sampling. However, separation of incipient to severe decay from benign reflectors (e.g. moisture gradient between sapwood and heartwood) in conifers was much less diagnostic than with angiosperms. A limited assessment of Acer saccharum showed that GPR has potential to detect defects in angiosperms; however, more research is needed to outline the full range of detectable defects. Based on the trees in this study, the potential for GPR to detect decay‐related defects in conifers seems limited. Despite problems detecting decay, reflections originating from the sapwood : heartwood boundary may prove useful to determine thickness of functional sapwood in conifers, but accurate quantification will require further technical development.
Assessing the impacts and potential control of terrestrial plant colonization of a reservoir bed during an extreme drawdown event
Authors: Boulding A. , Baldwin D. S.
Published: February 2009

Extended periods of drawdown of reservoirs can result in the ‘terrestrialization’ of the lake bottom sediments, which describes the process whereby the exposed dry sediment takes on soil‐like qualities. Opportunistic colonization of lake bed by terrestrial plants can occur under such conditions. A survey of plant communities of a large reservoir (Lake Hume) following its extreme drawdown, resulted in significant quantities of carbon, nitrogen and phosphorus being bound up in the terrestrial vegetation that colonized the lake bed. The phosphorus uptake from the sediment into plant material particularly could represent a significant pathway for phosphorus re‐mobilization back into the lake. The potential of using stock grazing as a control measure for mitigating the effects of terrestrial plant colonization is also discussed.
A preliminary hydrosedimentary view of a highly turbid, tropical, manmade lake: Cointzio Reservoir (Michoacán, Mexico)
Authors: Anne‐Sophie Susperregui , Nicolas Gratiot , Michel Esteves , Christian Prat
Published: February 2009

This study represents the first limnological assessment of Cointzio Reservoir (Michoacán, Mexico). A full three‐dimensional scan of temperature, conductivity and turbidity was done for the reservoir during two field surveys at the end of the 2005 rainy season (December 2005), and before the beginning of the next season (May 2006). These parameters also were measured continuously during the 2006 rainy season. Analysis of data within the context of local climate trends at a multidecadal scale indicates the reservoir can amplify seasonal features because of its morphometric properties. Between June to December, the reservoir behaved as a fluvial system, exhibiting a rapid, efficient mixing of the water column. Between January to May, the reservoir developed substantial stratification, and exhibited typical lacustrine characteristics. These alternate phases of fluvial and lacustrine regimes, associated with a high water turbidity throughout the year (Secchi depth of ≈0.2 m) contributes to stress on this aquatic ecosystem.
Microbial processes at the land–water interface, and cross‐domain causal relationships, as influenced by atmospheric deposition of pollutants in three freshwater lakes in India
Authors: Pandey Jitendra , Pandey Usha
Published: February 2009

The effects of long‐term atmospheric deposition of pollutant elements on the trans‐surface causative relationships at three lake sites having different catchment characteristics were investigated in this study. The selected determinants included lake productivity, bottom sediment quality, and a suite of microbial variables (microbial biomass (Cmic); basal respiration; substrate‐induced respiration; bacterial:fungal ratio; metabolic quotient; and alkaline phosphatase and FDAase activities) measured at the land–water interface, in relation to atmospheric deposition of phosphate; nitrate; ammonium; sulphate; calcium; and magnesium. The results indicated significant between‐site differences (P < 0.001) in the atmospheric deposition of phosphate (0.21–1.96 kg.h−1.year−1); nitrate (2.77–28.05 kg.h−1.year−1); ammonium (0.58–11.60 kg.h−1.year−1); sulphate (5.64–32.15 kg.h−1.year−1); calcium (4.50–30.00 kg.h−1.year−1); and magnesium (1.50–12.15 kg.h−1.year−1), as well as a consistently increasing input of these ions across time. The catchment vegetation had important effects on microbial variables that, in turn, affected lake productivity. Interfaces of woodland lake were found to be rich in phenolics, supporting low Cmic and activities. Except for alkaline phosphatase, which declined over time, atmospheric deposition of pollutant elements increased the Cmic and activities at the land–water interface. The time lag correlation analysis indicated the Cmic and lake productivity relationships were significantly altered by atmospherically driven nitrogen and phosphorus inputs, with a time lag of 2–3 years. Despite being supportive, aerial nutrient inputs appeared to have a destabilizing effect on both, microbial biomass and lake productivity variables. These observations indicate that if present atmospheric deposition trends of pollutant elements continue, it will modify the cross‐domain causative relationships of inland lentic systems over the long term. These study results are relevant for the formulation of strategies for managing freshwater tropical lakes.
Spatial and seasonal variations in phytoplankton community structure in alkaline–saline Lake Nakuru, Kenya
Authors: Okoth Oyoo Elijah , Mucai Muchiri , Shivoga Wiliam A. , Miller Scott N. , Rasowo Joseph , Ngugi Charles Chege
Published: February 2009

Spatial and seasonal variations of phytoplankton, expressed in terms of species composition, cell density, biovolumes and biomass, collected at 10 sampling sites in alkaline–saline Lake Nakuru, Kenya, were investigated monthly from March 2004 to February 2005, in relation to selected physical and chemical water quality parameters. A total of eight species, belonging to five genera and three classes, were recorded. The Cyanophyceae comprised the bulk of the phytoplankton, followed by Euglenophyceae, while Bacillariophyceae were the least abundant. Arthrospira fusiformis was the most dominant species, in terms of density, among the Cyanophyceae, while Euglena spp. and Navicula elkabs dominated the Euglenophyceae and Bacillariophyceae density, respectively. Seasonal variations in phytoplankton species composition, density and biomass were significant (P < 0.05) with minimum cell density and biomass occurring during the dry season, and being maximum following the end of the two rainy seasons from May to November 2004, suggesting the possible influence of various environmental factors on the lake. Sampling sites located close to the inlets of inflowing rivers exhibited significantly (P < 0.05) higher phytoplankton cell density and biomass than those by the inshore sites. Soluble reactive phosphorus, ammonia‐nitrogen, conductivity and total alkalinity accounted for most of the variations in the cell densities of phytoplankton species.
Review of 120 anal cancer patients
Authors: Young S. C. , Solomon M. J. , Hruby G. , Frizelle F. A.
Published: February 2009

Objective  Chemoradiotherapy is the mainstay of treatment for the majority of patients with anal cancer, with abdominoperineal resection reserved for salvage. The purpose of this study was to evaluate our results after radiotherapy with or without chemotherapy, and/or surgery in terms of overall survival and colostomy free survival in patients with anal cancer.

Method  A review of patients diagnosed with anal cancer between 1991 and 2004 was performed. The principle end‐points of the study were overall and colostomy‐free survival.

Results  One hundred and twenty patients were identified. The T stage distribution was T1 32, T2 44, T3 19, T4 17 and TX 8. Eighteen patients had clinically involved regional nodes. Eighty patients received radiotherapy as a component of their treatment. Twenty‐four of the 80 patients had a colostomy. The most common late toxicity was faecal incontinence. The overall survival and colostomy‐free survival rates for all 120 patients were 58% and 79% at 5 years, respectively. For the 80 patients who received radiotherapy, the corresponding figures were 66% and 82% at 5 years, respectively.

Conclusion  Chemoradiation is effective organ preserving treatment for anal cancer. Grade 1 and 2 faecal incontinence is a relatively common late toxicity experienced by patients.
Restorative proctocolectomy. Does ethnicity affect outcome?
Authors: Norwood M. G. A. , Mann C. D. , West K. , Miller A. S. , Hemingway D.
Published: February 2009

Objective  Restorative proctocolectomy (RPC) with ileal pouch‐anal anastomosis (IPAA) is well‐established in the management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). We review outcome of pouch surgery from a single centre, comparing non‐South Asian and South Asian Caucasian populations.

Method  Patients undergoing RPC for UC and FAP during a 10‐year period between January 1997 and January 2007 were identified from hospital records. Data were collected retrospectively from case notes on early and long‐term results.

Results  A total of 107 patients underwent pouch formation for UC (94%) or FAP (6%) and 22 (21%) were from the Asian subcontinent. Eighty‐seven (81%) underwent a three‐stage procedure and 20 (19%) a two‐stage procedure. Postoperative complications occurred in 40 (37%) patients, being major in 11 (10%) patients with relaparotomy required in 9 (8%) with no difference between South Asian and non‐South Asian Caucasian patients. Long‐term pouch function, with a median of five times over 24 h (range 2–15), was similar between the two groups. The incidence of pouchitis was 57 (53%) and this was significantly greater in the South Asian population [17/21 (77%); 39/86 (46%); P = 0.006].

Conclusion  Surgical results were similar in South Asian and non‐South Asian Caucasian patients, but the incidence of pouchitis was greater in the former group.
Extent of prevalence and size of flat neoplasms in a heterogeneous population undergoing routine colorectal cancer screening
Authors: Kim J. , Rami P. , O’Toole J. , Llor X. , Carroll R. E. , Benya R. V.
Published: February 2009

Background  The importance of identifying flat colorectal neoplasms is increasingly appreciated, although the extent of prevalence of these lesions in a general population is not known.

Objective  To determine the extent of prevalence of flat neoplasms in a diverse population undergoing routine endoscopic screening for colorectal cancer.

Design  Patients referred to the Colorectal Cancer Screening Clinic over a 12‐month period (n = 642).

Results  The patient population was 56% African American and 21% Caucasian; with a mean age of 59 ± 9 years. Flat neoplasms were detected in 5.5% of all patients, similar to that reported elsewhere, with extent of prevalence being similar regardless of gender or race. Average size of flat neoplasms was of 2.8 ± 2.3 mm (range 1–20 mm). However, there was no evidence of advanced pathology in any of the flat neoplasms identified.

Conclusions  Flat neoplasms are common but may not be associated with advanced pathology in a population undergoing routine screening.
Urethrocutaneous fistula: preserve the tract and turn it inside out: the PATIO repair
Authors: Malone Peter R.
Published: February 2009

OBJECTIVE

To describe a novel technique for repairing penile urethrocutaneous (UC) fistula, by dissecting out the fistula tract, but instead of excising it, to preserve it and turn it inside out (PATIO); this creates a flap valve inside the urethral lumen that prevents the ingress of urine allowing the fistula to heal.

PATIENTS AND METHODS

Five UC fistulae in four patients (two adults and two children) were repaired using the PATIO technique over a 4‐year period. The two adults had developed the UC fistula after complex salvage hypospadias repair for failed surgery as children. In addition, three UC fistulae were recurrent after failed attempts to close them using conventional techniques, including the interposition of locally sourced ‘waterproofing’ subcutaneous tissue and, in one child, a rotational skin flap. One child had a difficult coronal UC fistula with little more than a skin bridge distally.

RESULTS

Four operations were performed as day‐cases with no catheter; one child was catheterized and kept in hospital overnight to prevent retention after a caudal anaesthetic. The catheter was removed, before discharge, the following morning. All five repairs were successful with no complications or recurrence, with a mean (range) follow‐up of 18 (2–50) months.

CONCLUSION

The PATIO technique is easy to perform and can be done as a day‐case with no need for urethral catheterization. It does not preclude the use of other techniques to minimize the risk of recurrence, but so far these have not been necessary. As with all new operations, reported after only a few cases, caution must be used when interpreting the results and more studies are needed. Nevertheless, the concept makes sense and the early results are encouraging, particularly as it has been used on UC fistulae most liable to recur.
Neuroendocrine tumours of the urinary system and male genital organs: clinical significance
Authors: Mazzucchelli Roberta , Morichetti Doriana , Lopez‐Beltran Antonio , Cheng Liang , Scarpelli Marina , Kirkali Ziya , Montironi Rodolfo
Published: February 2009

Two basic types of neuroendocrine (NE) tumours with diverse clinicopathological features and outcome are identified in the urinary system and male genital organs: carcinoid tumour and neuroendocrine carcinoma. Carcinoid, a rare tumour, occurs in the kidney, bladder, prostate and testis. It is morphologically, histochemically, immunohistochemically and ultrastructurally similar to its counterpart in other organs, such as lung or gastrointestinal tract. Metastases can be detected at the initial evaluation, although they have been reported up to several years after removal, emphasizing the need for a long‐term follow‐up. NE carcinoma occurs in the kidney, bladder and prostate, and includes small cell carcinoma (SCC) and large cell NE carcinoma (LCNEC), the latter being exceedingly rare. Both show the morphology and immunophenotype of NE carcinoma originating in other organs. Although the occurrence is rare, it is highly aggressive.
Cross‐cultural validation of a prognostic tool: example of the Kattan preoperative nomogram as a predictor of prostate cancer recurrence after radical prostatectomy
Authors: Rouprêt Morgan , Hupertan Vincent , Comperat Eva , Drouin Sarah J. , Phé Véronique , Xylinas Evanguelos , Demanse David , Sibony Mathilde , Richard Francois , Cussenot Olivier
Published: February 2009

OBJECTIVE

To establish the predictive accuracy of the Kattan preoperative nomogram by comparing predictions at 5 years with actual progression in patients who had a radical prostatectomy (RP).

MATERIALS AND METHODS

We reviewed the data for 928 patients treated by RP as a first‐line treatment for localized prostate cancer, between 1994 and 2005. Recurrence was defined as one prostate‐specific antigen (PSA) level of >0.4 ng/mL. The 5‐year progression‐free probability (PFP) rate was evaluated on censured data using the Kaplan‐Meier method. Relationships between all predictor variables included in the Kattan nomogram (PSA level, biopsy Gleason scores and clinical stage) and survival were evaluated by Cox proportional‐hazards regression analysis. The discriminating ability of the nomogram was assessed by the concordance index (c‐index). Bootstrapping was used to assess confidence intervals (CIs), and then the calibration was assessed.

RESULTS

The median follow‐up was 60 months. Overall, 177 (19%) patients had a recurrence; the 5‐year PFP rate (95% CI) was 80.9 (78–83)%. Of the three variables included in the nomogram, all were associated with recurrence in a multivariate analysis (P < 0.001). The c‐index (95% CI) was only 0.664 (0.584–0.744). In general, the nomogram was not well calibrated.

CONCLUSIONS

There was a discrepancy between the predicted PFP as estimated by the Kattan nomogram and actual relapse in this group of patients. Clinicians should be aware that the nomogram is less accurate when used outside the population used to formulate the nomogram. Although more accurate tools are needed, the Kattan nomogram is still the best choice for urologists so far.
Nateglinide combination therapy with basal insulin and metformin in patients with Type 2 diabetes
Authors: Juurinen L. , Tiikkainen M. , Saltevo J. , Nikkilä K. , Lanki H. , Leppävuori E. , Kock T. , Teikari‐Myyrä T. , Kauppinen‐Mäkelin R. , Kotronen A. , Yki‐Järvinen H.
Published: February 2009

Aims  To compare the effect of adding nateglinide or placebo on postprandial glucose excursions (PPGEs), glycated haemoglobin (HbA1c), diurnal glucose profiles and hypoglycaemia in patients with Type 2 diabetes treated with the combination of basal insulin and metformin.

Research design and methods  This was an investigator‐initiated, double‐blind, randomized, parallel‐group, study in five centres. Patients with Type 2 diabetes (n = 88, age 56.0 ± 0.9 years, duration of diabetes 9.4 ± 0.5 years, HbA1c 7.8 ± 0.1%, body mass index 32.4 ± 0.5 kg/m2) treated with basal insulin and metformin entered a 24‐week period, during which basal insulin was titrated to optimize glucose control. Thereafter, the patients were randomized to receive either nateglinide (120 mg three times daily) or placebo before their main meals for 24 weeks.

Results  During the optimization period, HbA1c decreased by −0.3 ± 0.1 and −0.4 ± 0.2% (NS) and insulin doses increased by 10.0 IU (2.0–32.0) [0.09 IU/kg (0.02–0.34)] and 10.0 IU (0.0–19.0) [0.11 IU/kg (0.0–0.25)] (NS) in the nateglinide and placebo groups. Mean postprandial glucose during weeks 20–24 averaged 9.0 ± 0.3 and 10.0 ± 0.3 mmol/l in the nateglinide and placebo groups (P = 0.025) and mean PPGE averaged 2.4 ± 0.2 and 3.1 ± 0.2 mmol/l, respectively (P = 0.019). At 24 weeks as compared with 0 weeks, mean HbA1c had decreased by 0.41 ± 0.12% in the nateglinide group and by 0.04 ± 0.12% in the placebo group (P = 0.023). The frequency of confirmed, symptomatic hypoglycaemia was 7.7 episodes/patient‐year vs. 4.7 episodes/patient‐year in the nateglinide and placebo groups (P = 0.031).

Conclusions  Addition of a short‐acting insulin secretagogue at main meals improves postprandial hyperglycaemia during combination therapy with basal insulin and metformin, but increases the frequency of hypolycaemia.
Road traffic accident risk in patients with diabetes mellitus receiving blood glucose‐lowering drugs. Prospective follow‐up study
Authors: Skurtveit S. , Strøm H. , Skrivarhaug T. , Mørland J. , Bramness J. G. , Engeland A.
Published: February 2009

Aim  To investigate, at a national level, whether patients using insulin or oral glucose‐lowering agents had an increased risk of road traffic accidents compared with non‐users.

Methods  All Norwegians aged 18–69 years (3.1 million) were followed from April 2004 until September 2006. Information on drug prescriptions, road traffic accidents and emigration/death was obtained from the following population‐based registries: the Prescription Database, the Road Accident Registry and the Central Population Registry. The exposure period was the time from the first prescription of insulin or oral glucose‐lowering agent during the study period. The incidence of accidents in the exposed person‐time was compared with the incidence of accidents in the unexposed person‐time by standardized incidence ratio (SIR).

Results  During the study period, 20 494 road traffic accidents with personal injuries were registered in Norway. One hundred and eighty‐three accidents were registered for insulin users not taking oral glucose‐lowering agents and 219 for users of oral blood glucose‐lowering drugs without insulin. The SIR (95% confidence interval) for all ages and both genders combined were: insulin 1.4 (1.2–1.6), oral glucose‐lowering agents 1.2 (1.0–1.3) and users of drugs for peptic ulcer and gastro‐oesophageal reflux disease (negative comparators) 1.3 (1.2–1.4). The highest SIRs were found among the youngest insulin users (18–34 years old).

Conclusions  A slightly increased risk of being involved in a road traffic accident was observed for drivers prescribed insulin, while no increased risk was observed for drivers prescribed oral glucose‐lowering agents. The increased risk observed for insulin users was similar to that observed for users of drugs for peptic ulcer and gastro‐oesophageal reflux disease.
A national consensus on outcomes and indicators for diabetes patient education
Authors: Colagiuri R. , Eigenmann C. A.
Published: February 2009

Aim  To develop a national evidence and consensus position on the desired goals, outcomes and indicators of diabetes patient education (DPE).

Methods  A mixture of qualitative and quantitative methods were used including: (i) literature reviews to identify existing definitions, issues and work in the area; (ii) interviews with key opinion leaders; (iii) focus groups with people with diabetes; (iv) a national survey of diabetes education service providers; (v) a systematic consultation process culminating in a national stakeholder forum.

Results  Three overarching goals were identified as the main purpose of diabetes patient education: (i) optimal adjustment to living with diabetes, (ii) optimal health outcomes and (iii) optimal cost‐effectiveness (for the individual and for society). Given the difficulty in attributing cause and effect between education and clinical or cost outcomes and that mechanisms already exist for collecting data on clinical endpoints and surrogate indicators, the development of education indicators concentrated on the goal of optimal adjustment to living with diabetes. Four key outcomes for this goal were listed in order as either directly attributable to DPE or in which DPE plays a discernable role: knowledge and understanding, self‐determination, self‐management and psychological adjustment.

Conclusions  The consensus position represents a sound evidence‐informed platform on which diabetes education policy, programmes, data collection and research can be based. However, further work was required to test and make recommendations about applying potentially relevant psychometric tools to measure changes in the identified indicators.
National guidelines for psychological care in diabetes: how mindful have we been?
Authors: Nicholson T. R. J. , Taylor J.‐P. , Gosden C. , Trigwell P. , Ismail K.
Published: February 2009

Aims  To assess the availability and types of psychological services for people with diabetes in the UK, compliance with national guidelines and skills of the diabetes team in, and attitudes towards, psychological aspects of diabetes management.

Methods  Postal questionnaires to team leads (doctor and nurse) of all UK diabetes centres (n = 464) followed by semi‐structured telephone interviews of expert providers of psychological services identified by team leads.

Results  Two hundred and sixty‐seven centres (58%) returned postal questionnaires; 66 (25%) identified a named expert provider of psychological services, of whom 53 (80%) were interviewed by telephone. Less than one‐third (n = 84) of responding centres had access to specialist psychological services and availability varied across the four UK nations (P = 0.02). Over two‐thirds (n = 182) of centres had not implemented the majority of national guidelines and only 2.6% met all guidelines. Psychological input into teams was associated with improved training in psychological issues for team members (P < 0.001), perception of better skills in managing more complex psychological issues (P ≤ 0.01) and increased likelihood of having psychological care pathways (P ≤ 0.05). Most (81%) expert providers interviewed by telephone were under‐resourced to meet the psychological needs of their population.

Conclusions  Expert psychological support is not available to the majority of diabetes centres and significant geographical variation indicates inequity of service provision. Only a minority of centres meet national guidelines. Skills and services within diabetes teams vary widely and are positively influenced by the presence of expert providers of psychological care. Lack of resources are a barrier to service provision.
DEVELOPMENT PRESSURES AND HERITAGE IN THE PERTH CENTRAL BUSINESS DISTRICT, 1950–90
Authors: Gregory Jenny
Published: February 2009

This article examines the remaking of Perth's Central Business District (CBD) during the 1950–90 period. It traces the establishment of a modernist development ethos in Perth's planning, outlines the inadequacy of the City's planning regulations, and analyses the impact on St George's Terrace, the city's main commercial thoroughfare. The City Council was largely incapable of restraining excessive development and the extension of its system of plot ratios encouraged manipulation to increase the height of developments. Several important historic buildings were demolished because there were no legal means of safeguarding the city's heritage until 1990.
Neighborhood: the “outside” space for girls in urban India
Authors: Singh Shweta
Published: February 2009

Singh S. Neighborhood: the “outside” space for girls in urban India Int J Soc Welfare 2010: 19: 206–214 © 2009 The Author(s), Journal compilation © 2009 Blackwell Publishing Ltd and the International Journal of Social Welfare.

This study explores the perspective of adolescent girls on the neighborhood as a social space that plays a role in the formation of their identity and agency. The study applies the ‘identities’ conceptual framework, which is a global, interdisciplinary, theoretical approach to understanding female identity. The study participants were girls enrolled in grades 7–10, from five schools in a district in the Northern State of India, who participated in structured focus group discussions. The study reports on the reduced relevance of neighborhood for girls and illustrates, through quotes, the reasons for their limited interaction.
Effects of Gender and Age on Paediatric Headache
Authors: Slater S , Crawford MJ , Kabbouche MA , LeCates SL , Cherney S , Vaughan P , Segers A , Manning P , Burdine D , Powers SW , Hershey AD
Published: February 2009

The aim of this study was to evaluate the impact of gender and age on headache characteristics and disability. Headache characteristics were assessed at an initial visit to a paediatric specialty care centre and five follow-up visits. A total number of 4121 patients were evaluated. Fifty-eight per cent of the sample was female. Boys were younger at their first headache and initial visit. They more frequently described headache pain as squeezing and location as top of the head. Girls reported more frequent and longer headaches. Girls more often described headache pain as sharp and location as back of the head. Age accounted for more variance than gender in headache severity, duration, frequency and disability. Gender differences exist in headache characteristics. Age is also an important factor in the variability in characteristics and disability. Longitudinal studies are needed to describe further the natural history of headaches in childhood and compare outcome between genders.
Visual orienting in the early broader autism phenotype: disengagement and facilitation
Authors: Elsabbagh Mayada , Volein Agnes , Holmboe Karla , Tucker Leslie , Csibra Gergely , Baron‐Cohen Simon , Bolton Patrick , Charman Tony , Baird Gillian , Johnson Mark H
Published: February 2009

Background:  Recent studies of infant siblings of children diagnosed with autism have allowed for a prospective approach to examine the emergence of symptoms and revealed behavioral differences in the broader autism phenotype within the early years. In the current study we focused on a set of functions associated with visual attention, previously reported to be atypical in autism.

Method:  We compared performance of a group of 9–10‐month‐old infant siblings of children with autism to a control group with no family history of autism on the ‘gap‐overlap task’, which measures the cost of disengaging from a central stimulus in order to fixate a peripheral one. Two measures were derived on the basis of infants’ saccadic reaction times. The first is the Disengagement effect, which measures the efficiency of disengaging from a central stimulus to orient to a peripheral one. The second was a Facilitation effect, which arises when the infant is cued by a temporal gap preceding the onset of the peripheral stimulus, and would orient faster after its onset.

Results and conclusion:  Infant siblings of children with autism showed longer Disengagement latencies as well as less Facilitation relative to the control group. The findings are discussed in relation to how differences in visual attention may relate to characteristics observed in autism and the broader phenotype.
Self‐referenced memory, social cognition, and symptom presentation in autism
Authors: Henderson Heather A. , Zahka Nicole E. , Kojkowski Nicole M. , Inge Anne P. , Schwartz Caley B. , Hileman Camilla M. , Coman Drew C. , Mundy Peter C.
Published: February 2009

Background:  We examined performance on a self‐referenced memory (SRM) task for higher‐functioning children with autism (HFA) and a matched comparison group. SRM performance was examined in relation to symptom severity and social cognitive tests of mentalizing.

Method:  Sixty‐two children (31 HFA, 31 comparison; 8–16 years) completed a SRM task in which they read a list of words and decided whether the word described something about them, something about Harry Potter, or contained a certain number of letters. They then identified words that were familiar from a longer list. Dependent measures were memory performance (d′) in each of the three encoding conditions as well as a self‐memory bias score (d′ self–d′ other). Children completed The Strange Stories Task and The Children’s Eyes Test as measures of social cognition. Parents completed the SCQ and ASSQ as measures of symptom severity.

Results:  Children in the comparison sample showed the standard SRM effect in which they recognized significantly more self‐referenced words relative to words in the other‐referenced and letter conditions. In contrast, HFA children showed comparable rates of recognition for self‐ and other‐referenced words. For all children, SRM performance improved with age and enhanced SRM performance was related to lower levels of social problems. These associations were not accounted for by performance on the mentalizing tasks.

Conclusions:  Children with HFA did not show the standard enhanced processing of self‐ vs. other‐relevant information. Individual differences in the tendency to preferentially process self‐relevant information may be associated with social cognitive processes that serve to modify the expression of social symptoms in children with autism.
Familial associations of intense preoccupations, an empirical factor of the restricted, repetitive behaviors and interests domain of autism
Authors: Smith Christopher J. , Lang Colleen M. , Kryzak Lauren , Reichenberg Abraham , Hollander Eric , Silverman Jeremy M.
Published: February 2009

Background:  Clinical heterogeneity of autism likely hinders efforts to find genes associated with this complex psychiatric disorder. Some studies have produced promising results by restricting the sample according to the expression of specific familial factors or components of autism. Previous factor analyses of the restricted, repetitive behaviors and interest (RRBI) domain of autism have consistently identified a two‐factor model that explains a moderate amount of variance. The identification of additional factors may explain more variance in the RRBI domain and provide an additional component of autism that may help in the identification of underlying genetic association.

Methods:  We conducted factor analyses of RRBI symptoms with a sample that included verbal subjects meeting full criteria for autism aged 5 to 22 years (n = 245). Among affected sibling pairs (n = 126) we examined the familial aggregation of the identified factors. We also examined the associations of the factors with autism‐related personality traits in fathers and mothers (n = 50).

Results:  The previously identified two‐factor model – insistence on sameness (IS) and repetitive stereotypic motor behaviors (RSMB) – was replicated in our sample. Next, a second factor analysis that included the item for verbal rituals resulted in a four‐factor model – IS, ‘simple’ RSMB, ‘complex’ RSMB, and a fourth factor including symptoms associated with intense preoccupations (IP). Of these four, both IS and IP were significantly familial among affected siblings, but only IP was significantly correlated with the broader autism phenotype traits of rigidity and aloofness in fathers.

Conclusions:  The results support previous evidence for the IS factor, its familiality, and the identification of IP as an additional strong candidate trait for genetic studies of autism.
Conscientiousness as a mediator of the association between masculinized finger‐length ratios and attention‐deficit/hyperactivity disorder (ADHD)
Authors: Martel Michelle M.
Published: February 2009

Background:  One often‐overlooked biological risk factor that may help explain sex‐biased prevalence rates in psychopathology is sex hormones. Personality traits, which also show sex differences, may mediate relations between biological risk factors like hormones and childhood psychopathology such as ADHD (or, alternatively, be independent risk factors).

Methods:  Three hundred and twelve children/adolescents (178 boys, 134 girls) between the ages of 8 and 17 completed a comprehensive, multistage, clinical diagnostic procedure; 168 children were diagnosed with ADHD and 144 were classified as non‐ADHD comparison controls. Primary caregivers completed the California Q‐sort in order to provide a measure of conscientiousness. Finger‐length ratios (specifically right 2D:4D) served as a proxy of prenatal testosterone exposure (relative to estrogen).

Results:  Lower levels of conscientiousness statistically mediated the relationship between more masculine right 2D:4D (i.e., increased prenatal testosterone exposure) and increased ADHD inattentive symptoms.

Conclusion:  More masculinized finger‐length ratios show associations with ADHD symptoms, possibly acting through the trait mechanism of conscientiousness.
Is prenatal alcohol exposure related to inattention and hyperactivity symptoms in children? Disentangling the effects of social adversity
Authors: Rodriguez A. , Olsen J. , Kotimaa A.J. , Kaakinen M. , Moilanen I. , Henriksen T.B. , Linnet K.M. , Miettunen J. , Obel C. , Taanila A. , Ebeling H. , Järvelin M.R.
Published: February 2009

Background:  Studies concerning whether exposure to low levels of maternal alcohol consumption during fetal development is related to child inattention and hyperactivity symptoms have shown conflicting results. We examine the contribution of covariates related to social adversity to resolve some inconsistencies in the extant research by conducting parallel analyses of three cohorts with varying alcohol consumption and attitudes towards alcohol use.

Methods:  We compare three population‐based pregnancy–offspring cohorts within the Nordic Network on ADHD from Denmark and Finland. Prenatal data were gathered via self‐report during pregnancy and birth outcomes were abstracted from medical charts. A total of 21,678 reports concerning inattention and hyperactivity symptoms in children were available from the Strengths and Difficulties Questionnaire or the Rutter Scale completed by parents and/or teachers.

Results:  Drinking patterns differed cross‐nationally. Women who had at least some social adversity (young, low education, or being single) were more likely to drink than those better off in the Finnish cohort, but the opposite was true for the Danish cohorts. Prenatal alcohol exposure was not related to risk for a high inattention‐hyperactivity symptom score in children across cohorts after adjustment for covariates. In contrast, maternal smoking and social adversity during pregnancy were independently and consistently associated with an increase in risk of child symptoms.

Conclusions:  Low doses of alcohol consumption during pregnancy were not related to child inattention/hyperactivity symptoms once social adversity and smoking were taken into account.