bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of bioassessment-based benchmarks for iron
Authors: Linton Tyler K. , Pacheco Manoel A. W. , McIntyre Dennis O. , Clement William H. , Goodrich-Mahoney John
Published: May 2007

Current water-quality criteria for metals typically are derived from toxicity tests with the metal dissolved in clean laboratory water. Estimating the toxicity of iron from such tests, however, is extremely difficult because of the complex solubility and toxicity characteristics of the ferrous and ferric forms of the metal in freshwater. Consequently, a criterion for dissolved iron in freshwater derived from standard laboratory bioassays may not accurately describe the actual bioavailability and toxicity of this metal. A new approach is necessary to adequately protect aquatic life from the direct (toxic) and indirect (physical) negative effects of iron. We present a novel methodology to derive bioassessment-based benchmarks for total iron. This approach involves the use of quantile regression to model the decline in maximum abundance of taxa along a gradient of increasing iron concentrations. The limiting function (e.g., 90th quantile) is used to project the iron concentration associated with a selected reduction in maximum number of organisms (e.g., 20%). The projected declines in abundance of aquatic organisms are interpreted within the larger context of biological responses to increasing levels of stress (i.e., a biological condition gradient). Projections of iron concentration associated with multiple levels of reduction are selected to establish acceptable levels of change in the various tiers of a biological community. The bioassessment-based benchmarks that we establish for total iron (0.21 and 1.74 mg/L) are based on the assumption that if ecological effects–based criteria for total iron are derived and applied, the structure and function of the aquatic community will be protected.
An exploration of the role of mysids in benthic-pelagic coupling and biomagnification using a dynamic bioaccumulation model
Authors: Patwa Zaheerabbas , Christensen Rebecca , Lasenby David C. , Webster Eva , Mackay Donald
Published: May 2007

A mass-balance model for the uptake of organic contaminants in the opposum shrimp (Mysis relicta) is developed. The model describes the concentration in the mysid as a function of time as it grows and its lipid content changes over a two-year life span. The model can describe uptake in varying proportions from pelagic and benthic sources. Four mysid scenarios are considered: entirely pelagic, entirely benthic, half-pelagic and half-benthic, and following the observed seasonal behavior patterns. The seasonal-scenario mysid yields results consistent with levels of total polychlorinated biphenyls reported for Lake Ontario (Canada/USA). The relative sediment and water fugacities are shown to play a critical role in determining the contamination level in mysids. Inclusion of mysids in a simple food-web model demonstrates higher concentrations in upper-trophic-level organisms by two effects: introduction of another trophic level in the food web, and increased benthic-pelagic coupling.
Comparison of the uptake of polycyclic aromatic hydrocarbons and organochlorine pesticides by semipermeable membrane devices and caged fish (Carassius carassius) in Taihu Lake, China
Authors: Ke Runhui , Xu Yiping , Huang Shengbiao , Wang Zijian , Huckins James N.
Published: May 2007

Uptake of polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) by triolein-containing semipermeable membrane devices (SPMDs) and by crucian carp (Carassius carassius) was studied in Taihu Lake, a shallow, freshwater lake in China. Crucian carp and SPMDs were deployed side by side for 32 d. The first-order uptake rate constants of individual PAHs and OCPs for the two matrices were calculated and compared to relate the amounts of chemicals accumulated by the matrices to dissolved water concentrations. On a wet-weight basis, total concentrations of PAHs and OCPs in crucian carp fillets averaged 49.5 and 13.6 ng/g, respectively, after the 32-d exposure, whereas concentrations in whole SPMDs averaged 716.9 and 62.3 ng/g, respectively. The uptake rate constants of PAHs and OCPs by SPMDs averaged seven- and fivefold higher, respectively, than those for crucian carp; however, the patterns of uptake rate constants derived from test chemical concentrations in the crucian carp and SPMDs were similar. Although equilibrium was not reached for some PAHs and OCPs during the 32-d exposure period, a reasonably good correlation between the concentration factors (CFs) and octanol/water partition coefficient (Kow) values of PAHs and OCPs in SPMDs (r = 0.86, p < 0.001) was observed when potential sorption to dissolved organic carbon was taken into account. Similar efforts to correlate the CFs and KOW values of PAHs and OCPs in crucian carp (r = 0.75, p < 0.001) were less successful, likely because of PAH metabolism by finfish. Overall, the present results suggest that SPMDs may serve as a surrogate for contaminant monitoring with fish in freshwater lake environments.
Importance of calcium in modifying the acute toxicity of sodium sulphate toHyalella aztecaandDaphnia magna
Authors: Davies Trevor D. , Hall Ken J.
Published: May 2007

Modification of the acute toxicity of sodium sulphate to Hyalella azteca and Daphnia magna was investigated using exposure water with different levels of water hardness (expressed as CaCO3 equivalents) and calcium–magnesium molar (Ca:Mg) ratios. The influence of Ca:Mg ratios on the toxicity of sodium and potassium chloride to D. magna also was investigated. For both species, the mean lethal concentrations that resulted in mortality of 50% of the sample population (LC50s), expressed as mg SO42–/L, were increased significantly in harder water and in water with higher Ca:Mg ratios. The LC50s for H. azteca increased from 569 to 5,259 mg/L with a change in water hardness from 25 to 250 mg/L. Furthermore, modifying the Ca:Mg ratio from 0.7 to 7.0 at a constant hardness of 100 mg/L significantly increased LC50s from 2,101 to 2,725 mg/L. The LC50s for D. magna were also significantly higher in harder water with LC50s increasing from 1,194 to 3,203 mg/L with a change in water hardness from 25 to 100 mg/L. In addition, modifying the Ca:Mg ratio from 0.7 to 7.0 significantly increased LC50s from 1,194 to 1,985 at a constant hardness of 25 mg/L, and from 3,203 to 4,395 mg/L at a constant hardness of 100 mg/L. No significant change in the toxicity of potassium or sodium chloride to D. magna was observed in waters with higher Ca:Mg ratios.
Influence of organism age on metal toxicity toDaphnia magna
Authors: Hoang Tham C. , Klaine Stephen J.
Published: May 2007

Aquatic organisms living in surface water experience contaminant exposure at different life stages. While some investigators have examined the influence of organism age on the toxicity of pollutants, the general assumption in toxicology has been that young organisms were more sensitive than older organisms. In fact, some standardized toxicity tests call for the use of organisms less than 24 h old. This research characterized the age sensitivity of the water flea Daphnia magna to copper, zinc, selenium, and arsenic. During 21-d toxicity tests, organisms were exposed to a single 12-h pulse of either 70 μg/L Cu, 750 μg/L Zn, 1,000 μg/L Se, or 5,000 μg/L As at different ages ranging from 3 h to 10 d old. Mortality and reproduction were compiled over 21 d. During the juvenile stage, mortality increased and cumulative reproduction decreased with age, respectively. However, mortality decreased and cumulative reproduction increased with age when organisms became adult. Peak sensitivity occurred in 4-d-old organisms exposed to Cu and Zn, while 2- to 3-d-old organisms were most sensitive to As and Se. Growth of D. magna over 21 d was not affected by the 12-h pulse of Cu, Zn, Se, or As given at any organism age. This indicates the recovery of the organisms after exposure termination.
Response spectrum of pentachlorobenzene and fluoranthene forChironomus tentansandHyalella azteca
Authors: Schuler Lance J. , Landrum Peter F. , Lydy Michael J.
Published: May 2007

The whole-body residues of pentachlorobenzene (PCBz) and fluoranthene (FLU) in Hyalella azteca and Chironomus tentans were determined for a variety of chronic sublethal effects. The endpoints evaluated for H. azteca included 28-d growth and survival and 42-d growth, survival, and reproduction. Adverse effects to C. tentans also were determined at multiple endpoints including 10-d growth, cumulative pupation and emergence, and reproduction. The lowest-observed-effect residue (LOER) based on whole-body residues associated with growth was consistent between compounds and species tested with concentrations ranging from 0.17 to 0.33 μmol/g. For H. azteca, the most sensitive endpoints were growth at 0.23 μmol/g and reproduction at 0.11 μmol/g for PCBz and FLU, respectively. For C. tentans, the most sensitive endpoints were emergence, development and reproduction at 0.02 μmol/g, and development and reproduction at 0.15 μmol/g for PCBz and FLU, respectively. Compared to residues associated with acute lethality, the most sensitive sublethal endpoints were approximately 4 and 60 times lower for PCBz and FLU, respectively. The relative consistency of the sublethal endpoints suggests that body residues can be a valuable tool to evaluate bioaccumulation data as part of a risk assessment to predict adverse effects to biota.
RAGE and its ligands: a lasting memory in diabetic complications?
Authors: Yan Shi-Fang , Ramasamy Ravichandran , Bucciarelli Loredana G , Wendt Thoralf , Lee Larisse K , Hudson Barry I , Stenr David M , Lalla Evanthia , Du Yan Shi , Rong Ling Ling , Naka Yoshifumi , Schmidt Ann Marie
Published: May 2007

The complications of diabetes are myriad and represent a rising cause of morbidity and mortality, particularly in the Western world. The update of the Diabetes Control and Clinical Trials Group/Epidemiology of Diabetes Interventions and Complications Research Group (DCCT/EDIC) suggested that previous strict control of hyperglycaemia was associated with reduced carotid atherosclerosis compared to conventional treatment, even after levels of glycosylated haemoglobin between the two treatment groups became indistinguishable. These intriguing findings prompt the key question, why does the blood vessel ‘remember’?

This review focuses on the hypothesis that the ligand/RAGE axis contributes importantly to glycaemic ‘memory’. Studies in rodent models of diabetes suggest that blockade or genetic modification of RAGE suppress diabetes-associated progression of atherosclerosis, exaggerated neointimal expansion consequent to acute arterial injury, and cardiac dysfunction.

We propose that therapeutic RAGE blockade will intercept maladaptive diabetes-associated memory in the vessel wall and provide cardiovascular protection in diabetes.
Pioglitazone plus a sulphonylurea or metformin is associated with increased lipoprotein particle size in patients with type 2 diabetes
Authors: Perez Alfonso , Khan Mehmood , Johnson Todd , Karunaratne Mahinda
Published: May 2007

Objective To determine the effect of pioglitazone plus metformin or a sulphonylurea on lipoprotein particle size and subclass distribution in patients with type 2 diabetes.

Methods Lipid profiles were determined for blood samples from patients participating in two randomised, double-blind, 24-week studies of pioglitazone 30 mg or 45 mg daily plus either metformin or a sulphonylurea.

Results Samples from 177 patients were evaluated; 96 of these patients received a sulphonylurea, and 81 received metformin. Pioglitazone combination treatment produced significant increases from baseline for average and peak low-density lipoprotein (LDL) particle size at weeks 12 and 24 (p<0.0001 for each; range 0.29–0.39 nm for average and 0.36–0.55 nm for peak particle size, respectively). Significant shifts in high-density lipoprotein (HDL) and LDL distribution showed an increase in large particles and a decrease in small particles. For pioglitazone plus metformin, significant increases in levels of apolipoprotein (Apo) AI, Apo AI/AII-containing HDL, and lipoprotein(a) also were noted, whereas Apo B levels decreased.

Conclusions These observed changes are thought to affect the atherogenic profile positively. Therefore, pioglitazone combination treatment may lead to decreased cardiovascular risk in patients with type 2 diabetes.
Effects of low-dose continuous combined HRT on vascular function in women with type 2 diabetes
Authors: Kernohan Andrew FB , Spiers Angela , Sattar Naveed , Hillier Chris , Cleland Steve J , Small Michael , Lumsden Mary-Ann , Connell John MC , Petrie John R
Published: May 2007

Background Improvement in vascular endothelial function is widely cited as a beneficial effect of hormone replacement therapy (HRT). Women with type 2 diabetes (T2DM) are at increased cardiovascular risk and have impaired endothelial function. Any benefits of HRT on endothelial function in this group are of particular interest.

Objectives We assessed effects on vascular function of oral 17β oestradiol (1 mg) and norethisterone (0.5 mg) in postmenopausal women with T2DM.

Design Double-blind, randomised, placebo-controlled trial.

Assessments Twenty-eight women had pulse wave velocity (PWV) and adhesion molecules VCAM-1 and ICAM-1 assessed before and after three months' treatment. Twenty-four women also had gluteal fat biopsy for assessment of resistance vessel function (using wire myography).

Results HRT did not affect PWV, VCAM-1, ICAM-1 or carbachol response. Effects of L-NAME and indomethacin on carbachol sensitivity were similar in both groups.

Conclusions This HRT preparation had no detectable effect on these measures of endothelial function in women with T2DM.
Enhanced left ventricular systolic function early in type 2 diabetic mice: clinical implications
Authors: Alvarez Jorge A , Reyes Maricela , Escobedo Daniel , Freeman Gregory L , Steinhelper Mark E , Feldman Marc D
Published: May 2007

It is unclear whether the increase in availability of substrates for energy production in diabetes can lead to enhanced systolic function early in the disease, before the onset of structural changes to the myocardium. To examine this issue, BKS. Cg- m +/+ Lepr db (db/db) mice with type 2 diabetes and wild type controls had left ventricular pressure-volume relationships determined in situ. We demonstrated that the db/db mice, when compared to their wild type controls, generated greater left ventricular pressure and an enhancement of left ventricular systolic function based on enhanced power/EDV, positive dP/dt, preload recruitable stroke work, dP/dt — EDV relationship, and curvilinear end-systolic elastance. This enhancement in systolic function occurred despite the db/db mice having greater body weight, but similar preload (end-diastolic volume) and afterload (effective arterial elastance).

We postulate that the previously described enhancement in renal glomerular filtration rate seen early in type 2 diabetes may be in part due to enhanced left ventricular systolic function early in this disease.
Metabolic syndrome-mediated inflammation following elective percutaneous coronary intervention
Authors: Marso Steven P , Murphy Joseph W , House John A , Safley David M , Harris William S
Published: May 2007

There are few data concerning the relationship between diabetes mellitus, the metabolic syndrome and inflammation following elective percutaneous coronary intervention (PCI). The purpose of this study was to assess basal and peak levels of candidate cytokines in 40 patients undergoing elective PCI. Patients were categorised as having diabetes mellitus, the metabolic syndrome, or neither.

Patients with the metabolic syndrome exhibited significantly greater levels of tumour necrosis factor-a over the study period, although this was unrelated to PCI. There was a trend for increased levels of interleukin-6 following PCI, primarily among patients with metabolic syndrome. Basal levels of monocyte chemoattractant protein-1 (MCP-1) were not different among study groups; however, the metabolic syndrome cohort had a trend towards increased circulating levels of MCP-1 after PCI. In this patient population, the metabolic syndrome correlates with a heightened inflammatory response following elective PCI.
Impaired glucose tolerance and impaired fasting glucose — a review of diagnosis, clinical implications and management
Authors: Petersen John L , McGuire Darren K
Published: May 2007

The diagnostic categories of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were established in an effort to identify populations at risk for developing type 2 diabetes mellitus (T2DM). Both IGT and IFG are associated with increased risk of developing T2DM, but recent analyses found that the thresholds of risk vary among different populations and an even lower diagnostic threshold of IFG may be appropriate. IGT has been linked with an increased risk of cardiovascular events and some analyses have demonstrated an increased mortality risk compared with patients with normal glucose tolerance. In contrast, a continuum of increased risk of microvascular manifestations of T2DM has been demonstrated with IFG but an association of IFG with cardiovascular events has not been well established.

Although both IGT and IFG are associated with resistance to insulin and increased insulin secretion, they do not identify the identical patient populations and are not equivalent in predicting development of T2DM or cardiovascular events. IFG and IGT have been associated with other features of insulin resistance, including dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of inflammation and hypercoagulability, traits collectively referred to as the metabolic syndrome. Analyses of combinations of these components have also been associated with progression to T2DM, cardiovascular disease and increased mortality.

The foundation of treatment for IGT, IFG, and the metabolic syndrome is lifestyle modification, including both dietary change and routine exercise. To date, several clinical trials have found that lifestyle modification is the most efficacious strategy to prevent progression to T2DM. Alternative treatments include pharmacotherapy with metformin or acarbose, both of which have been demonstrated to decrease the development of T2DM. Ongoing clinical trials are evaluating newer pharmacotherapies, including angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, metglitinides and thiazolidinediones, to prevent both T2DM and cardiovascular events. In combination with lifestyle modification, these therapies offer hope for effective prevention of T2DM and its consequences in high-risk patients.
The application of proteomics to diabetes
Authors: Scott Eleanor M , Carter Angela M , Findlay John BC
Published: May 2007

Proteomics is the investigation of all the proteins and their various modifications making up a system, be that a cell, tissue or organism. The techniques involved in proteomics allow the global screening of complex samples of proteins and provide qualitative and quantitative evidence of altered protein expression. This lends itself to the investigation of the molecular mechanisms underpinning disease processes and the effects of treatment. This review describes the main techniques of proteomics and how they have begun to be applied to diabetes research.
Cells expressing the stem cell factor receptor, c-kit, contribute to neoangiogenesis in diabetes
Authors: Kelly Darren J , Zhang Yuan , Gow Renae M , Itescu Silviu , Gilbert Richard E
Published: May 2007

While neoangiogenesis in diabetes is of greatest clinical significance in the retina, the pathological formation of new blood vessels also develops in other vascular beds in diabetes, including the mesentery of the streptozotocin-induced diabetic rat. However, the contribution of bone marrow-derived cells to this process of vasculogenesis is unknown.

In this study, male Sprague-Dawley rats were randomised to receive either streptozotocin or vehicle, and their mesenteric vasculature was examined after three weeks. Origins from bone marrow and endothelial cell differentiation were identified by immunolabelling for the stem cell factor receptor, c-kit and von Willebrand factor (vWF), respectively. Expression for the angiogenic chemokine, stromal derived factor-1 (SDF-1) was assessed by quantitative real-time polymerase chain reaction (PCR).

At three weeks, rats with diabetes had a dramatic (190-fold) increase in lectin-labelled blood vessel profiles in the mesenteric bed (p<0.0001) in association with a five-fold increase in SDF-1 mRNA (p<0.01). Immunohistochemical studies identified abundant large, ovoid, lumen-forming, c-kit+ cells in the mesentery of diabetic, but not control, rats. Many of these c-kit+ cells also showed positive immunolabelling for vWF, consistent with endothelial differentiation.

In conclusion, cells of bone marrow origin contribute to new vessel formation in the diabetic mesentery. This phenomenon may also apply to the neovascularisation that develops at clinically important sites such as in the retina.
Divergent effects of angiotensin-converting enzyme inhibition on blood pressure and endothelial function in obese humans
Authors: Williams Ian L , Chowienczyk Philip J , Wheatcroft Stephen B , Patel Ameet G , Sherwood Roy A , Shah Ajay M , Kearney Mark T
Published: May 2007

Endothelial dysfunction is a pivotal early event in the development of atherosclerosis and a characteristic feature of obesity. This study was designed to investigate the effect of angiotensin-converting enzyme (ACE) inhibition on endothelial function in people who were obese but otherwise healthy. We performed a double-blind, randomised, placebo-controlled study examining the effect of the ACE inhibitor perindopril (4 mg per day) on flow-mediated vasodilatation (FMD) of the brachial artery, arterial blood pressure, glucose homeostasis and inflammatory cytokines. Eighteen obese subjects (all body mass index > 30 kg/m2) were randomised to receive perindopril or placebo for four weeks. Perindopril led to a fall in systolic blood pressure from 131 (standard error of mean [SEM] 3) to 117(5) mmHg and diastolic blood pressure from 74(4) mmHg to 68(4) mmHg, both p<0.001. Despite this fall in blood pressure, ACE inhibition had no effect on FMD, 8.2 (1.2)% versus 8.3 (1.5)%, p=0.9. ACE inhibition had no effect on insulin, lipids or circulating cytokines. In healthy obese humans, despite a significant reduction in blood pressure, ACE inhibition had no effect on FMD.
Effects of improved metabolic control on platelet reactivity in patients with type 2 diabetes mellitus following coronary angioplasty
Authors: Yngen Marianne , Norhammar Anna , Hjemdahl Paul , Wallén N Håkan
Published: May 2007

The aim of this study was to investigate the impact of improved metabolic control on platelet reactivity in patients with type 2 diabetes undergoing percutaneous coronary intervention (PCI). Twenty-two patients were randomised to intensive insulin or conventional treatment for diabetes. Platelet P-selectin expression was analysed before and three months after PCI.

Metabolic control, as measured by level of glycosylated haemoglobin (HbA1C) and platelet P-selectin expression, was similar in the two treatment groups after three months. However, six of the 12 patients in the intensive group had increased levels of HbA1C after three months and three patients of the 10 in the conventionally treated group showed improved metabolic control.

A re-analysis was performed, based on metabolic control. It showed that patients with improved control at three months (HbA1C 6.1% ± 0.7 at baseline; 5.7% ± 0.5 at three months; p<0.01; n=9) had lower ADP-induced P-selectin expression (p<0.05) than patients with worsened glycaemic control (HbA1C 5.9% ± 1.0 at baseline; 6.5% ± 1.4 at three months; p<0.01; n=13). Levels of HbA1C and fasting glucose were correlated to P-selectin expression (R=0.34 and R=0.31; p<0.05).

We conclude from this study that improved glycaemic control reduces platelet reactivity in type 2 diabetes patients following PCI.
Thrifty genes for obesity and the metabolic syndrome — time to call off the search?
Authors: Speakman John R
Published: May 2007

Over the last 50 years there has been a major epidemic of obesity and associated co-morbidities, the so-called ‘metabolic syndrome’, mostly in the western world but with an increasingly global dimension. The development of such chronic diseases has a strong genetic component, yet the timescale of their increase cannot reflect a population genetic change. Consequently, the most accepted model is that obesity and its sequelae are a result of a gene-environment interaction, an ancient genetic selection to deposit fat efficiently that is maladaptive in modern society. Why we have this genetic predisposition has been a matter of much speculation.

Following the seminal contribution of Neel, 1 there has been a broad consensus that over evolutionary time we have been exposed to regular periods of famine, during which fatter individuals would have enjoyed a selective advantage by their greater survival. Consequently, individuals with genes promoting the efficient deposition of fat during periods between famines (‘thrifty genes’) would be favoured. In the modern environment this genetic predisposition prepares us for a famine that never comes, and an epidemic of obesity with all the attendant chronic illnesses follows.

In this review I present details of the evidence supporting the famine hypothesis and then show that this idea has five fundamental flaws. In essence, famines are a relatively modern phenomenon and occur only about once every 100–150 years. Consequently, most human populations have only experienced at most 100 famine events in their evolutionary history. Famines involve increases in total mortality that only rarely exceed 10% of the population. Moreover, most people in famines die of disease rather than starvation and the age distribution of mortality during famine would not result in differential mortality between lean and obese individuals. A simple genetic model shows that famines provide insufficient selective advantage over an insufficient time period for a thrifty gene to have any penetration in the modern human population.

Over the 40 or so years since Neel proposed the thrifty gene hypothesis, no convincing candidates for these genes have been discovered. My analysis suggests that perhaps it is time to call off the search.
A multinational assessment of complications in type 1 diabetes: the DiaMond substudy of complications (DiaComp) Level 1
Authors: Walsh Michael G , Zgibor Janice , Borch-Johnsen Knut , Orchard Trevor J
Published: May 2007

The objectives of this study were to describe the global geographic variation of microvascular and macrovascular complications in childhood onset type 1 diabetes (T1D) and to relate any such variation to diabetes care activities such as self blood glucose monitoring and intensive insulin therapy.

The DiaComp study is a multinational (17 countries) cross-sectional study of complications in T1D (n=2, 657). All participants were diagnosed at < 15 years of age and had a diabetes duration of 5-24 years when surveyed. Complications were assessed by self-report of physician diagnosis.

Twenty-two centres in 17 countries achieved at least a 67% response rate and are included in the analyses. Central European centres exhibited high rates of retinopathy (Lithuania=31. 6%, Romania=24. 2%), laser treatment (Lithuania=25. 4%) and neuropathy (Lithuania=29. 9%, Romania=12. 4%) in those with short duration of diabetes (5–15 years), as did Cuba for neuropathy (15. 4%). For retinopathy the geographic variation in the short-duration group was also pronounced, ranging from 1. 6% in Italy to 41. 6% in Lithuania, and from 0% in Brazil, Italy and Australia, to 29. 9% in Lithuania for laser treatment. Variation was less dramatic for the prevalence of complications in the long-duration group (15–25 years). Hypertension and duration were strong consistent predictors of all complications, while women had higher prevalence for half the complications (retinopathy, laser treatment and renal disease). Intensive insulin therapy and self-monitoring of blood glucose showed little association with prevalence of complications.

In conclusion, this first population-based account of the geographic variation of T1D complications has demonstrated substantial variation. However, the healthcare practice variables that were measured contributed little toward explaining this variation.
Inhaled insulin (Exubera®): combining efficacy and convenience
Authors: Bellary Srikanth , Barnett Anthony H
Published: May 2007

The pulmonary route, due to its rich vascularity, large surface area and immunotolerant characteristics, may be an ideal target for drug delivery. Although the inhaled route has been used to deliver drugs used in the management of respiratory disorders, success with peptide delivery has been limited by poor bioavailability. Recent advances in technology have overcome these barriers and have enabled new delivery devices to be developed. Insulin is the first peptide to be delivered successfully by this route and the first of the inhaled insulin delivery devices (Exubera®) has now been approved for clinical use. In clinical trials it has been shown to be effective, apparently safe and a preferred alternative to subcutaneously injected meal-time insulin. This new technology offers great convenience to patients needing insulin treatment. While it will considerably reduce the number of injections needed by people with type 1 and type 2 diabetes, it should also encourage more patients to start insulin treatment earlier. The potential benefits from improved adherence and better glycaemic control with this insulin are also significant.
Baseline characteristics of the randomised cohort from the Look AHEAD (Action for Health in Diabetes) study
Authors: Bray George A.
Published: May 2007

Objective. The Look AHEAD (Action for Health in Diabetes) study is a 16-centre randomised clinical trial in overweight and obese individuals with type 2 diabetes, designed to evaluate the long-term effects (up to 11.5 years) of intensive weight loss intervention on the time to incidence of major cardiovascular events.

Research design and methods. Eligibility requirements are diagnosis of type 2 diabetes (determined by self-report and verification) in individuals aged 45-74 years and body mass index (BMI) > 25 kg/m2 (> 27 kg/m2 if currently taking insulin). The intensive lifestyle intervention is designed to achieve and maintain weight loss through decreased caloric intake and increased physical activity. The study is designed to provide 90% probability of detecting an 18% difference in major cardiovascular disease event rates in patients randomised to the intensive lifestyle intervention compared to the control group receiving standard diabetes support and education.

Results. The 5, 145 participants who were randomised between 2001 and 2004 were 63.3% white, 15.6% African-American, 13.2% Hispanic, 5.0% American Indian and 1.0% Asian-American, which closely paralleled the ethnic distribution of diabetes in the National Health and Nutrition Examination Survey (NHANES) 1999-2000 survey. Their average age at entry was 59± 6.8 years (mean ± SD), and 60% were women. There were 31.5% between 45-55 years of age, 51.5% were 56-65, and 17.0% were 66-76 years of age. Some 15.4% of participants were taking insulin at the time of randomisation and 14.0% had a history of cardiovascular disease. More men (21.3%) than women (9.2%) had a history of cardiovascular disease. Few participants (4.4%) were current cigarette smokers, compared to 16.2% in the NHANES 1999-2000 survey. Furthermore, 65.0% of participants had a first-degree relative with diabetes. Overall, BMI averaged 36±5.9 kg/m2 at baseline, with 83.6% of the men and 86.1% of women having a BMI > 30 kg/m2 and 17.9% of men and 25.4% of women having a BMI > 40 kg/m2

Conclusions. The Look AHEAD study has successfully randomised a large cohort of participants who have type 2 diabetes with a wide distribution of age, obesity, ethnicity and racial background and will examine the effects of lifestyle intervention on the incidence of major cardiovascular events.
Inter-subject differences in constitutive expression levels of the clock gene in man
Authors: Balmforth Anthony J , Grant Peter J , Scott Eleanor M , Wheatcroft Stephen B , Kearney Mark T , Staels Bart , Marx Nikolaus
Published: May 2007

Circadian rhythms are generated, both at the level of the whole organism and at the cellular level, by biological clocks involving a set of clock genes. We previously performed a randomised, placebo-controlled, double-blind trial examining the effect of six months of pioglitazone (30 mg per day) therapy on neointima volume after coronary stenting in patients with coronary artery disease but without diabetes. In a subgroup of 15 patients from each group, a whole blood sample was taken at the beginning of the trial and at an eight-week clinical follow-up for isolation of total RNA using a PAXgene system. Using real time RT-PCR with relative quantitation, we investigated whether pioglitazone treatment altered clock gene expression in RNA extracted from peripheral white blood cells (PBCs). No significant changes in clock gene expression were noted in either placebo (99±45%) or pioglitazonetreated subjects (101±35%) after eight weeks. These data potentially extend previous findings that the clock gene is constitutively expressed over 24 hours to eight weeks.

We observed a large range of inter-subject differences in expression levels of the clock gene. The difference between the mean value for the lowest expression individual (ΔCT 8.8) and the highest expression individual (ΔCT 3.7) revealed an approximately 34-fold difference in relative clock gene expression levels. These differences may arise through differences in light exposure, polymorphic variants of the clock gene affecting gene expression and/or post-transcriptional regulation. They could influence susceptibility to disruption of normal circadian rhythms, which occur in pathophysiological conditions pertaining to diabetes and cardiovascular disease.
Human islet isolation: semi-automated and manual methods
Authors: Paget Michelle , Murray Hilary , Bailey Clifford J , Downing Richard
Published: May 2007

Large yields of high-viability human islets are necessary to service the expanding programmes of islet transplantation worldwide; similarly, there is an increasing demand from diabetes researchers for a reliable and cost-effective supply of human islets. The two main isolation methods are ‘semi-automated’ and ‘manual’. Both methods rely on prompt and careful removal and transfer of the donor pancreas to allow isolation to commence, preferably within eight hours. Each method involves exocrine digestion with high-activity collagenase (Liberase).

The semi-automated method is standardised, generally provides higher islet yields and is used for clinical transplant purposes, although it is not suitable for all donor pancreata. The manual method is less expensive and more adaptable and enables islets to be isolated for research from most donor pancreata.
Application of a Portable XRF Spectrometer for the Non‐Invasive analysis of Museum Metal Artefacts
Authors: Karydas A. G.
Published: May 2007

The present paper reviews examples of the application of a portable ‐ in house developed‐ XRF spectrometer for the analysis of museum metal artefacts in Greece. Specific topics are addressed, in particular, to which extent the qualitative or quantitative XRF analyses reveal important information about the raw materials and manufacture techniques used for gold, silver and bronze alloys in antiquity. The analytical information that it is gained by means of the XRF measurements is further assessed in comparison with the existing archaeometallurgical knowledge.
The Russian Avant‐Garde Painting Palette Documentary and Physicochemical Study of Inorganic Colorants
Authors: Kampasakali Elli , Papliaka Zoe Eirini , Christofilos Dimitirios , Varella Evangelia A.
Published: May 2007

In the present article an attempt is being made to elucidate the inorganic colorants encountered in the Russian avant‐garde painting palette by a combined art historical, documentary and physicochemical investigation; and to examine the influence of environmental factors on the chromatic profile originally sought by the artist. The overall approach based on written sources is confirmed by measurements on representative paintings from the Costakis Collection in the State Museum for Contemporary Art, Thessaloniki. The documentary research deals with the influences of Orthodox iconography, folkloric art, and occidental modernist tendencies on the Russian avant‐garde palette; and is studying the effects of contradictory historical processes in the chromatic profile of individual paintings. In the experimental section a series of colorants are investigated concerning the effects of accelerated ageing on experimental painting tables, prepared as watercolour and gouache layers on paper ground. The resulting samples are subject to colorimetric, and spectroscopic measurements; and analogous analytical procedures are applied on samples taken from selected paintings belonging to the Costakis Collection. A systematic comparative study of all data permits evaluating the materials used as to their stability towards exstrincic factors, and proposing degradation routes, in order to assist museum curators and conservators in every concrete case related to the broad spectrum of pigments examined.
Provenance Determination of Vinica Terra Cotta Icons Using Self‐Organising Maps
Authors: Tanevska Vinka , Kuzmanovski Igor , Grupče Orhideja
Published: May 2007

In the Vinica Fortress, Republic of Macedonia, 50 undamaged terra cotta icons and 100 fragments, all dated 6th–7th century, were found. In order to determine the provenance of these unique terra cotta icons, the mass fractions of 19 different chemical elements were previously determined in ten fragments of the terra cotta icons and thirty three samples of clays from eight different sites from the region. Due to the dimensionality and complexity of the experimental data, the archaeometric results were treated with self‐organising maps (SOM). The results obtained using SOM were compared with the ones obtained using principal component analysis. Both chemometric methods revealed that Vinica terra cotta icons were made from clay from Grnčarka, 2.5 km South‐East from the Vinica Fortress.
Modeling water flux in forward osmosis: Implications for improved membrane design
Authors: Mccutcheon Jeffrey R. , Elimelech Menachem
Published: May 2007

Osmotically‐driven membrane processes, such as forward osmosis and pressure retarded osmosis, operate on the principle of osmotic transport of water across a semipermeable membrane from a dilute feed solution into a concentrated draw solution. The major hindrance to permeate water flux performance is the prevalence of concentration polarization on both sides of the membrane. This article evaluates the external and internal boundary layers, which decrease the effective osmotic driving force. By modeling permeate flux performance, the role that feed and draw concentrations, membrane orientation, and membrane structural properties play in overall permeate flux performance are elucidated and linked to prevalence of external and internal concentration polarization. External concentration polarization is found to play a significant role in the reduction of driving force, though internal concentration polarization has a far more pronounced effect for the chosen system conditions. Reduction of internal concentration polarization by way of membrane modification was found to improve the predicted flux performance significantly, suggesting that alteration of membrane design will lead to improved performance of osmotically driven membrane processes. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Experimental investigation on diesel PM removal using uneven DBD reactors
Authors: Yao Shuiliang , Madokoro Kazuhiko , Fushimi Chihiro , Fujioka Yuichi
Published: May 2007

The removal of diesel particulate matter (PM) is experimentally carried out using two types of uneven dielectric barrier discharge (DBD) reactors driven by positive–negative pulse voltage power supplies. One uneven DBD reactor is fed with exhaust gases from a diesel engine at the exhaust gas temperature and another uneven DBD reactor is fed with PM dispersed in a gas mixture of oxygen and nitrogen at room temperature, where PM was collected from the exhaust gases of the diesel engine. PM emission rates, PM sizes, and PM oxidation products are measured using a PM emission rate monitor, a particle size spectrometer, and a gas chromatograph at various discharge energy densities. It has been found that most of PM is oxidized completely into gaseous products of CO and CO2 under plasma discharge conditions. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Microfibrous entrapped Ni/Al2O3 using SS‐316 fibers for H2 production from NH3
Authors: Liu Ye , Wang Hong , Li Jianfeng , Lu Yong , Xue Qingsong , Chen Jinchun
Published: May 2007

Using a high‐speed and low‐cost papermaking technology combined with subsequent sintering process, sinter‐locked three‐dimensional microfibrous networks consisting of ∼2 vol % of 6‐μm‐diameter SS‐316 microfibers were utilized to entrap ∼25 vol % of 100–200‐μm‐diameter porous Al2O3 support particulates. Nickel, a most active component for ammonia decomposition, was then dispersed onto the pore surface of the entrapped Al2O3 support particulates by incipient wetness impregnation method. The resulting microfibrous catalysts took advantage of large void volume, entirely open structure, high heat/mass transfer, good thermal stability, and unique form factors, thereby leading to good activity for ammonia decomposition and significant reduction of overall bed weight and volume. This composite bed reactor was capable of producing 215 sccm hydrogen over per cm3 bed volume with ammonia conversion of 99.5% at 650°C. © 2007 American Institute of Chemical Engineers AIChE J, 2007
A subgroup of Tourette's patients overexpress specific natural killer cell genes in blood: A preliminary report
Authors: Lit Lisa , Gilbert Donald L. , Walker Wynn , Sharp Frank R.
Published: May 2007

Gilles de la Tourette Syndrome (TS) is a heritable, neurodevelopmental disorder characterized by motor and vocal tics. As no single gene or region has emerged from standard linkage approaches, TS may result from several as‐yet‐unidentified genetic factors, and may also occur due to infection‐triggered, autoimmune processes. Etiological or pathogenic differences might result in clinically indistinguishable TS subgroups. We have previously used whole genome human oligonucleotide microarrays in an attempt to identify patterns of gene expression in blood linked with TS. In this proof‐of‐principle study, we applied Principal Components Analysis to a previously collected set of 16 familial TS and 16 control blood samples to identify subgroups. Fourteen genes, primarily Natural Killer Cell (NK) genes, discriminated between TS and all controls. Granzyme B and NKG7 were confirmed using RT‐PCR. Five probesets (four genes) reside in chromosomal regions previously linked to familial TS or obsessive‐compulsive disorder. Using the 14 genes, a Principal Components Analysis as well as a cluster analysis identified a TS subgroup (n = 10/16) that overexpressed the NK genes. 7/10 subjects within this subgroup were diagnosed with attention‐deficit hyperactivity disorder (ADHD), suggesting that this expression profile might be associated with TS and co‐morbid ADHD. Principal Components Analysis of gene expression in blood may be useful for identifying subgroups of other complex neurodevelopmental diseases, and the gene expression profile identified in this study may provide a biomarker for at least one subgroup of heritable TS. © 2007 Wiley‐Liss, Inc.
Thoracic skeletal morphology and high‐altitude hypoxia in Andean prehistory
Authors: Weinstein Karen J.
Published: May 2007

Living humans from the highland Andes exhibit antero‐posteriorly and medio‐laterally enlarged chests in response to high‐altitude hypoxia. This study hypothesizes that morphological responses to high‐altitude hypoxia should also be evident in pre‐Contact Andean groups. Thoracic skeletal morphology in four groups of human skeletons (N = 347) are compared: two groups from coastal regions (Ancón, Peru, n = 79 and Arica, Chile, n = 123) and two groups from high altitudes (San Pedro de Atacama, Chile, n = 102 and Machu Picchu and Cuzco, Peru, n = 43). Osteometric variables that represent proportions of chest width and depth include sternal and clavicular lengths and breadths and rib length, curvature, and area. Each variable was measured relative to body size, transformed into logarithmic indices, and compared across sex‐specific groups using ANOVA and Tukey multiple comparison tests. Atacama highlanders have the largest sternal and clavicular proportions and ribs with the greatest area and least amount of curvature, features that suggest an antero‐posteriorly deep and mediolaterally wide thoracic skeleton. Ancón lowlanders exhibit proportions indicating narrower and shallower chests. Machu Picchu and Cuzco males cluster with the other highland group in rib curvature and area at the superior levels of the thorax, whereas chest proportions in Machu Picchu and Cuzco females resemble those of lowlanders. The variation in Machu Picchu and Cuzco males and females is interpreted as the result of population migrations. The presence of morphological traits indicative of enlarged chests in some highland individuals suggests that high‐altitude hypoxia was an environmental stressor shaping the biology of highland Andean groups during the pre‐Contact period. Am J Phys Anthropol, 2007. © 2007 Wiley‐Liss, Inc.
Subcortical infarcts, Alzheimer's disease pathology, and memory function in older persons
Authors: Schneider Julie A. , Boyle Patricia A. , Arvanitakis Zoe , Bienias Julia L. , Bennett David A.
Published: May 2007

Objective

Examine the effects of subcortical infarcts with Alzheimer's disease (AD) pathology on dementia, episodic memory, and other cognitive abilities in older persons.

Methods

Participants included 148 autopsied subjects of the Rush Memory and Aging Project (mean age, 88.0 years), a longitudinal clinicopathological study. Cognition was assessed yearly with 21 neuropsychological tests. Infarcts were visualized on coronal slabs, and plaques and neurofibrillary tangles were counted and standardized to form a composite measure of AD pathology. Multiple regression analyses were used controlling for age, sex, and education.

Results

Fifty‐three (35.8%) subjects had cerebral infarcts. After accounting for AD pathology, infarcts increased the odds of dementia by 5.1‐fold (95% confidence interval, 1.98–12.92) and lowered cognitive function by 0.50 standard unit (p = 0.001). After controlling for cortical infarcts and AD pathology, subcortical infarcts, present in 39 of 53 (73.6%) subjects with infarcts, increased the odds of dementia by almost 4‐fold and reduced cognitive function by more than a third of a unit (parameter estimate = −0.37; p = 0.03). In analyses with cognitive abilities, subcortical infarcts were associated with lower episodic, semantic, and working memory (p ≤ 0.05), and had an interaction with AD pathology to further worsen working memory (p = 0.02).

Interpretation

Subcortical infarcts add to deleterious effects of AD pathology by increasing the odds of dementia and lowering memory function. Ann Neurol 2007