bluuebunny/crossref_metadata_2025 huggingface dataset:
Using 3D Virtual Models for Real-Time Operations: A Practical Case Study
Authors: Stafford B. , Hauser M.
Published: February 2010

As an industry we often say that we should learn from the lessons of others. This is an example of such a case. The United States Department of Defense is developing the next generation Battlefield of the Future concept, and as a part of that effort they are using gaming technology to create a situational awareness tool for the operating theater. Chevron Corporation and Science Applications International Corporation (SAIC) have teamed to develop a proof of concept using this approach to evaluate its usefulness for operations and simulation/modeling in the oilfield environment, in addition to the proven applicability for training personnel.

A virtual model of a Chevron Corporation onshore brownfield asset was developed using a commercially available game development engine. Geospatial information, real-time operational data and organizational knowledge were integrated into the 3-dimensional (3-D) models to provide a virtual operating environment. Such an environment would enable operators to virtually ‘tour’ the fields and prioritize activities before leaving their consoles, and provide engineers a richer understanding of the interaction between wells, facilities, and gathering systems. In addition, by integrating specialized tools (e.g., network optimizers); ‘what-if’ scenarios can be visually interpreted within the virtual world for easier assimilation and learning. The resulting virtual model also facilitates collaboration functionality due to its inherent support for multiple users (avatars and instant messaging) and the rich 3-D visual capability, making it easy to facilitate field planning activities like well placements, as well as road and facility construction before construction actually starts.

Future functionality could include real-time personnel and asset tracking using live global positioning system (GPS) data fed into the 3-D virtual model. This platform can also lead to the development of ‘intelligent’ workflows based on best practices, which can be refined and captured through the environment, and then guide users through routine troubleshooting and surveillance tasks based on those workflows (guided workflows). The next phase in the evolution of this paradigm is to be able to exercise supervisory control of field facilities through this environment by interfacing with the underlying supervisory control and data acquisition (SCADA) and distributed control system (DCS) systems.

A live demo of this proof of concept will be presented along with current findings.
Predictive Analytics and Collaboration Drive Reliability Performance
Authors: Snyder Tim
Published: February 2010

The business of reliability management is to keep equipment up and running or available to run while managing the costs to operate and maintain it. Companies have made significant investments in condition-monitoring instrumentation and information infrastructure, but each firm will have a unique point of diminishing returns. Some companies have established centralized collaboration centers and have re-engineered their work processes in order to break through this diminishing- returns barrier. Others that are not yet ready to make the full change can apply five critical success factors observed in established collaboration centers that have demonstrated reliability-performance improvements: Putting equipment operating condition into context. Dynamic equipment requires views of mechanical condition in the context of the overall process. This applies both to rotating equipment and to processing equipment.Managing data by exception. The blizzard of data now available requires machine learning and management by exception to reduce data into usable information.Using both predictive analytics and deep diagnostics as complementary technologies that operate in different timeframes. Deep diagnostics include vibration signature analysis and cylinder performance analysis, while predictive analytics employs pattern recognition algorithms to detect minor events and anomalies.Communicating observations, diagnoses, recommendations, and learnings through collaboration tools. Such tools add value on multiple fronts that include knowledge transfer and equipment-specific learning such as Root Cause Analysis.Managing the findings in an asset-management system or collaboration system. This provides feedback for further improvement.

A case-study example that uses predictive analytics will demonstrate these concepts, beginning at event detection and extending through diagnostics, collaboration, field action, and information consolidation.

The direct deliverable is time: time for engineers to focus where they add most value, time to plan equipment outages that might otherwise have been unplanned, and time to produce oil and gas that might be lost to unplanned downtime.
Mega I-Field Application in the World's Largest Oil Increment Development
Authors: Al-Mulhim Waleed A. , Faddagh Hussain A. , Shehab Mahdi A. , Shamrani Sultan S.
Published: February 2010

This paper describes the mega application of I-Field concept in Khurais Increment, the world's largest oil increment development in history. The field was developed to be fully intelligent from day one, thus, I-field infrastructure was part of the initial development plan and investment. Leveraging experience and lessons learned from previous I- Fields, and utilizing advances in technology, this application has better surveillance, higher reliability, and more utilities for end-users to manage and translate data into actionable information.

Khurais Increment benefited from I-Field prior to field commissioning allowing the optimization of requirements and enhancing development. I-Field enabled drilling wells using real-time remote geosteering. It also enabled reservoir characterization by facilitating the performance of several reservoir interference tests including field-wide test within the reservoir and full reservoir-to-reservoir test to understand communication.

Khurais I-Field also played a key role for a smooth, expedited, and optimized increment commissioning. Engineers were able to have precise and remote control over well rates to perform capacity tests and meet start up targets. It also enabled them to pinpoint wells and equipments that require attention immediately upon problem occurrence, thus allocating the required resources in a timely manner.

Finally, post-field commissioning, Khurais I-Field enabled engineers to manage production and injection strategies, integrate, and collaborate. With a full suite of applications integrated at the engineer's desktop, he or she is able to monitor over 50 different well parameters, intelligently by exception, and make faster more informed decisions to achieve real-time reservoir management. And although the field was only put on production recently, I-Field has made a significant impact which translated into achieving uniform pressure propagation across the field which is expected to prevent pre-mature water encroachment and enhance ultimate recovery.
Overview of Saudi Aramco's Intelligent Field Program
Authors: AbdulKarim Abdulaziz , AL-Dhubaib Tofig , Elrafie Emad , Alamoudi Mohammad O.
Published: February 2010

Recent advancement in well technologies, communications and field instrumentation has made it possible to achieve total asset awareness and optimize operations over the field's development lifecycle. This is achieved by leveraging fields’ real-time data for continuous monitoring and right-time response throughout the development processes. Right-time response has two components: Fast Interventions being done today as a product of an intra-process optimization, and Strategic Interventions based on more detailed modeling, discussed in the next steps section. The results of this integration have led to optimized drilling operations and well placements, increased production rates, and improved reservoir management and production operations. Real-time integration in the business processes, in turn, has introduced further opportunities for higher hydrocarbon recoveries and lower operating costs and capital expenditures. In the industry, integration of the various digital surface and subsurface technologies into E&P business processes has been given different names, such as Smart fields, Intelligent Field (I-Field), Digital Oil Field Of the Future (DOFOF), integrated field (i-field) and Integrated Operations (IO). Four major projects have been implemented in Saudi Aramco to take advantage of the digital field development opportunities in major E&P upstream business processes.

This paper provides an overview of Saudi Aramco's implementation approach and experience in integrating real-time data in the upstream business processes, such as Drilling and Completions through Real-time Drilling Operation and Geosteering, Production Operations and Reservoir Management through Intelligent Field, and Development Planning and Optimization through Event Solution.
Failing Our Children: Lead in U.S. School Drinking Water
Authors: Lambrinidou Yanna , Triantafyllidou Simoni , Edwards Marc
Published: February 2010

Lead is the most prevalent toxicant in U.S. school drinking water. Yet for the vast majority of schools, federal regulation for testing taps and remediating contamination is voluntary. Using school case studies, this article discusses the regulatory vacuum that leaves children unprotected from potential exposure to very high lead doses through consumption of school water. Controlling lead hazards from water fountains, coolers, and other drinking water outlets in schools requires improved sampling protocols that can capture the inherent variability of lead release from plumbing and measure both the particulate and dissolved lead present in water. There is a need to reevaluate the potential public health implications of lead-contaminated drinking water in schools. Accounting for this misunderstood and largely overlooked exposure source is necessary in order to better understand and address childhood lead poisoning in the U.S.
The CO Oxidation Mechanism Over Ag-Co And Co-Ce Mixed Oxide Catalysts
Authors: Balikçi Derekaya Filiz , Guldur Cigdem
Published: February 2010

Carbonmonoxide oxidation mechanism was studied over the 50/50 Ag-Co and 50/50 Co-Ce mixed oxide catalysts. The temperature programmed methods (TPR-H2 and TPD-CO) were used to characterize the catalysts. FTIR spectrums were collected under different feed conditions in order to determine the reaction mechanism. The carbonates adsorption bands and gas phase CO2 bands were obtained for both of the catalysts. CO linearly bounded to Ag+ sites at 2164 cm-1 and to Co3+ sites at 2105 cm-1 for 50/50 Ag-Co mixed oxide catalyst. CO linearly bounded to Co3+ sites at 2173 cm-1 and 2108 cm-1 for 50/50 Co-Ce mixed oxide catalyst. The CO adsorption studies showed that the CO reacted with surface oxygen species. The CO2 adsorbed on the catalyst surface as surface carbonate species. The oxidation of CO with surface oxygen species is probably via a non-competitive Langmuir-Hinshelwood mechanism on the catalysts.
Surfactant Aggregates in Ionic Liquids and Reactivity in Media
Authors: Gayet Florence , Patrascu Cosmin , Marty Jean-Daniel , Lauth-de Viguerie Nancy
Published: February 2010

In this paper the association of different families of amphiphilic compounds in room temperature ionic liquids in micelles, vesicles and reverse microemulsions was demonstrated. First the formation of nonionic polyoxyethylene-type surfactant micelles in the ionic liquid 1-butyl-3-methyl-imidazolium tetrafluoroborate is clearly evidenced using tensiometry and dynamic light scattering measurements. Critical micellar concentrations, object sizes and aggregation numbers are given and compared to aqueous and formamide systems. Then, vesicular aggregation of glycerophospholipid DPPC in two ionic liquids bmimBF4 and emimNTf2 was evidenced. Lastly, the phase diagram and microstructure of the ternary system ionic liquid (benzylpyridinium bis(trifluoromethanesulfonyl) imide)/nonionic surfactant (octylphenol ethoxylate)/toluene were studied. Phase stability and small-angle neutron scattering data show the formation of ionic liquid-in-oil microemulsion droplets. These reverse microemulsions were used as nanoreactors to perform a Matsuda-Heck reaction. The reaction yields obtained were greater in microemulsions (67%) than in bulk IL (33%) highlighting a strong effect of confinement. The reactivity in these confined media led to promising results.
Righting Writing: Strategies for Improving Nursing Student Papers
Authors: Bickes Joan T , Schim Stephanie M
Published: February 2010

The ability to clearly express complex ideas in writing is necessary for nurses in professional practice at all levels from novice to expert. The community health nursing course is specially designated as writing intensive to provide students with the experience of preparing a major scholarly paper. To address issues of poor paper quality and grade inflation we implemented a program including a writing workshop for faculty, a revision of the grading rubric, and a system of blind review for grading student papers. Changes resulted in a major shift in paper grades which more closely reflects the actual quality of the work.
Development of Pulmonary Arterial Hypertension in Women: Interplay of Sex Hormones and Pulmonary Vascular Disease
Authors: Pugh Meredith E , Hemnes Anna R
Published: February 2010

Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature, ultimately resulting in right heart failure and death. This disease is strongly predominant in females, although little is known regarding how sex influences disease development. Recent developments highlighting the importance of estrogen metabolites in both animal models and human disease have substantially increased our understanding of PAH in women. This review will focus on general knowledge of PAH, translational and basic science data regarding sex hormones in the pulmonary vasculature and on clinical issues that are particular to women with PAH. Future directions for study include the influence of sex hormones on right ventricular responses, improving the understanding of the influence of estrogen exposure in human disease and the study of dehydroepiandrosterone in basic science and human disease.
Risks and Benefits of Physical Activity among Breast Cancer Survivors who have Completed Treatment
Authors: Schmitz Kathryn H , Speck Rebecca M
Published: February 2010

Worldwide, over 1 million cases of breast cancer are diagnosed each year. In the USA, approximately 185,000 women are newly diagnosed annually. Nearly 90% of newly diagnosed cancer patients in the USA will live for 5 years beyond diagnosis and there are estimated to be 2.4 million breast cancer survivors currently living in the USA. There are unique challenges in meeting the medical needs of these survivors. Persistent impairment and increased medical risks can occur as a result of treatment, including changes to the cardiovascular, pulmonary, endocrine, immune, musculoskeletal, neurological and lymphatic systems. Physical activity can cause positive changes in each of these body systems. However, physiologic impairments and altered risks for cardiopulmonary, bone health, neurosensory and other outcomes among breast cancer survivors can cause confusion regarding the safety of returning to exercise after treatment. In this article, we review the adverse effects of cancer treatments on the body systems affected by and used to perform exercise, the risks of exercise among breast cancer survivors, the effects of exercise on persistent treatment toxicities, whether exercise may prevent recurrence or mortality, as well as providing guidance for exercise testing and prescription among breast cancer survivors.
Acute Leukemia in Women
Authors: Lo-Coco Francesco , Fouad Tamer M , Ramadan Safaa M
Published: February 2010

The treatment and survival outcome of acute leukemia in women is generally similar to that of men. However, acute leukemia in women poses additional challenges in clinical practice. In addition to important precautions during therapy, such as prevention of abnormal uterine bleeding in premenopausal women and therapy during pregnancy, women who are survivors of acute leukemia face unique and potentially long-term health-related problems. In this review, we address the aforementioned issues, as well as the various health and psychosocial challenges faced by women who survive childhood leukemia during their path to adulthood. Finally, we address the issue of therapy-related acute leukemia in the category of women who are survivors of breast and ovarian cancer.
MRI and PET Scans for Primary Staging and Detection of Cervical Cancer Recurrence
Authors: Liyanage Sidath H , Roberts Charlotte A , Rockall Andrea G
Published: February 2010

Worldwide, cervical cancer is the second most common malignancy in women, and is a major cause of morbidity and mortality. Accurate tumor staging is essential for optimal treatment planning and prognosis. Cervical cancer is staged by clinical examination according to the International Federation of Gynecology and Obstetrics staging system. However, clinical staging has inherent deficiencies in evaluating several parameters that are critical for treatment planning. It is now widely accepted that cross-sectional imaging, and in particular MRI, has an important role to play in the staging of these tumors. MRI is an excellent modality for depicting invasive cervical cancer: it can provide objective measurement of tumor size and provides a high negative predictive value for parametrial invasion and stage IVA disease. MRI and PET/computed tomography (CT) play key roles in identifying recurrent disease. PET/CT is also useful in detecting nodal and distant metastases and in radiotherapy planning. Diffusion-weighted MRI is an emerging imaging technique that is currently being evaluated for the detection of primary and recurrent disease and in the assessment of treatment response.
Maternal Obesity and Associated Reproductive Consequences
Authors: Brown Kelecia , Apuzzio Joseph , Weiss Gerson
Published: February 2010

The prevalence of obesity is continuing to increase among women. Women who are in their reproductive years are disproportionately affected by obesity. The link between obesity and increased morbidity from various conditions, including cardiovascular disease, Type 2 diabetes, osteoarthritis and malignancies, is well established. This article discusses the current state of obesity among reproductive age women in the USA and reviews the impact of maternal obesity on reproduction. The genetic contribution to human obesity is also discussed, as is reproduction following weight reduction surgery.
On functions of Arakawa and Kaneko and multiple zeta values
Authors: Kuba Markus
Published: February 2010

We study two functions ?k(s) and ?k1?kr(s) introduced by Arakawa and Kaneko [3] and relate them with (finite) multiple zeta values and multiple zeta star values using elementary methods. In particular, we give an alternative proof of a result of Ohno [14].
Numerical analysis meets number theory: Using rootfinding methods to calculate inverses mod pn
Authors: Knapp Michael , Xenophontos Christos
Published: February 2010

We show how classical rootfinding methods from numerical analysis can be used to calculate inverses of units modulo prime powers.
Characteristics of (γ,3)-critical graphs
Authors: Mojdeh D.A. , Firoozi P.Y.
Published: February 2010

In this note the (?,3)-critical graphs are fairly classified. We show that a (?,k)- critical graph is not necessarily a (?,k?)-critical for k?? k and k,k? E {1,2,3}. The (2,3)-critical graphs are definitely characterized. Also the properties of (?,3)-critical graphs are verified once their edge connectivity are 3.
Voting 'Against' in regular and nearly regular graphs
Authors: Wang Changping
Published: February 2010

Let G = (V,E) be a graph. A function f : V (G)-> {-1,1} is called negative if ?vEN[v] f(v)?1 for every v E V(G): A negative function f of a graph G is maximal if there exists no negative function g such that g ? f and g(v) ? f(v) for every v E V: The minimum of the values of ?vEV f(v); taken over all maximal negative functions f, is called the lower against number and is denoted by ?*N (G): In this paper, we present lower bounds on this number for regular graphs and nearly regular graphs, and we characterize the graphs attaining those bounds.
Convergence properties of the q-deformed binomial distribution
Authors: Zeiner Martin
Published: February 2010

We consider the q-deformed binomial distribution introduced by S.C. Jing 1994: The q-deformed binomial distribution and its asymptotic behaviour, J. Phys. A 27 (2) (1994), 493{499 and W.S. Chung et al.: q-deformed probability and binomial distribution, Internat. J. Theoret. Phys. 34 (11) (1995), 2165{2170 and establish several convergence results involving the Euler and the exponential distribution; some of them are q-analogues of classical results.
Some results on matching and total domination in graphs
Authors: Shiu Chee , Chen Xue-Gang , Chan Hong
Published: February 2010

Let G be a graph. A set S of vertices of G is called a total dominating set of G if every vertex of G is adjacent to at least one vertex in S. The total domination number ?t(G) and the matching number ??(G) of G are the cardinalities of the minimum total dominating set and the maximum matching of G, respectively. In this paper, we will introduce an upper bound of the di?erence between ?t(G) and ??(G). We will also characterize every tree T with ?t(T)? ??(T), and give a family of graphs with ?t(G)???(G).
Correlation of hearing function findings in patients suffering from diabetes mellitus type 1 in regard to age and gender
Authors: Pudar Goran , Vlaski Ljiljana , Filipovic Danka , Tanackov Ilija
Published: February 2010

Ageing of an individual affects hearing impairment and associated diseases can have a cumulative affect. In 50 examined subjects suffering from Diabetes Mellitus type 1, who were divided into groups according to age, gender and disease duration, auditory function was tested by analyzing results of pure-tone audiometry and brainstem auditory evoked potentials. The obtained results were correlated with the results of 30 healthy controls adequately represented by age and gender. Starting from the age group 30-39 we noticed a significant reduction in the percentage of regular findings in comparison with the control group, as well as an increase in the percentage of sensorineural hearing impairment and mean values of hearing impairment (-dB). In regard to gender, we found a continuing and significant increase in sensorineural hearing impairment in the examined male subjects from the group with the disease. The analysis and correlation of brainstem auditory evoked potentials regarding the age of the examinees did not show any significant impact on the increase in the mean values of the diseased and the controls, whereas regarding the gender, we noticed a significant impact on the increase in the mean values of absolute latencies II (Fd/l=5.1249/9.8144), III (Fd/l=14.0413/9.3169), IV (Fd/l=7.1413/6.3410) and V (Fd/l=12.8753/6.1208) waves as well as of interwave latencies I-III (Fd/l=5.2193/4.9628) mutually in the male examinees. In the diseased group there were significant differences of interwave latencies I-III in men and women both on the left and the right side, where the values in the female subjects were significantly shorter than in the males.
Hedgehog Signaling in Pancreas Epithelium Regulates Embryonic Organ Formation and Adult β-Cell Function
Authors: Lau Janet , Hebrok Matthias
Published: February 2010

OBJECTIVE

Current studies indicate that Hedgehog (Hh) signaling must be excluded during early stages of pancreas formation. However, conflicting evidence suggests that Hh signaling may be active later during pancreas formation and that it is required for insulin production and secretion in cultured β-cell lines. The objective of this study was to address these discrepancies by assessing the in vivo role of epithelial Hh signaling in the pancreas.

RESEARCH DESIGN AND METHODS

To identify Hh-active cells in the developing and adult pancreas epithelium, we characterized transgenic reporter Patched1-LacZ mice. To determine the requirement for epithelial Hh signaling in the pancreas, we eliminated an essential Hh signaling component, Smoothened (Smo), in the pancreatic epithelium, and assessed pancreatic development and adult β-cell physiology phenotypes.

RESULTS

Characterization of Patched1-LacZ reporter mice revealed low-level LacZ expression in pancreatic epithelial cells throughout development until birth, when LacZ activity increases in intensity specifically in endocrine and ductal cells. In the absence of Hh signaling, Smo-deficient mice have delayed pancreas formation leading to a temporary reduction in pancreatic epithelium and β-cell numbers. Although β-cell numbers recover by birth, adult Smo-deficient mice display glucose intolerance, increased insulin sensitivity, and reduced total insulin production.

CONCLUSIONS

These data show that Hh signaling functions early during pancreas morphogenesis to regulate epithelial and β-cell expansion and to modulate glucose metabolism by regulating insulin production in adult mice.
Lipoprotein Particle Size and Concentration by Nuclear Magnetic Resonance and Incident Type 2 Diabetes in Women
Authors: Mora Samia , Otvos James D. , Rosenson Robert S. , Pradhan Aruna , Buring Julie E. , Ridker Paul M.
Published: February 2010

OBJECTIVE

Diabetic dyslipoproteinemia is characterized by low HDL cholesterol and high triglycerides. We examined the association of lipoprotein particle size and concentration measured by nuclear magnetic resonance (NMR) spectroscopy with clinical type 2 diabetes.

RESEARCH DESIGN AND METHODS

This was a prospective study of 26,836 initially healthy women followed for 13 years for incident type 2 diabetes (n = 1,687). Baseline lipids were measured directly and lipoprotein size and concentration by NMR. Cox regression models included nonlipid risk factors (age, race, smoking, exercise, education, menopause, blood pressure, BMI, family history, A1C, and C-reactive protein). NMR lipoproteins were also examined after further adjusting for standard lipids.

RESULTS

Incident diabetes was significantly associated with baseline HDL cholesterol, triglycerides, and NMR-measured size and concentration of LDL, IDL, HDL, and VLDL particles. The associations of these particles differed substantially by size. Small LDLNMR and small HDLNMR were positively associated with diabetes (quintile 5 vs. 1 [adjusted hazard ratios and 95% CIs], 4.04 [3.21–5.09] and 1.84 [1.54–2.19], respectively). By contrast, large LDLNMR and large HDLNMR were inversely associated (quintile 1 vs. 5, 2.50 [2.12–2.95] and 4.51 [3.68–5.52], respectively). For VLDLNMR, large particles imparted higher risk than small particles (quintile 5 vs. 1, 3.11 [2.35–4.11] and 1.31 [1.10–1.55], respectively). Lipoprotein particle size remained significant after adjusting for standard lipids and nonlipid factors.

CONCLUSIONS

In this prospective study of women, NMR lipoprotein size and concentrations were associated with incident type 2 diabetes and remained significant after adjustment for established risk factors, including HDL cholesterol and triglycerides.
Associations of Hyperglycemia and Insulin Usage With the Risk of Cancer in Type 2 Diabetes: The Hong Kong Diabetes Registry
Authors: Yang Xilin , Ko Gary T.C. , So Wing Yee , Ma Ronald C.W. , Yu Linda W.L. , Kong Alice P.S. , Zhao Hailu , Chow Chun-Chung , Tong Peter C.Y. , Chan Juliana C.N.
Published: February 2010

OBJECTIVE

Insulin has mitogenic effects, although hyperglycemia may be a risk factor for cancer in type 2 diabetes. It remains uncertain whether use of insulin increases cancer risk because of its effect on cell growth and proliferation or decreases cancer risk because of its glucose-lowering effect.

RESEARCH DESIGN AND METHODS

A 1:2-matched new insulin user cohort on age (±3 years), smoking status, and likelihood of initiating insulin therapy (±0.05) was selected from a cohort of 4,623 Chinese patients with type 2 diabetes, free of cancer, and naive to insulin at enrollment. Stratified Cox regression analysis on the matched pairs was used to obtain hazard ratios (HRs) of insulin therapy and A1C for cancer risk. A structured adjustment scheme was used to adjust for covariates.

RESULTS

Of 973 new insulin users, 971 had matched nonusers (n = 1935). The cancer incidence in insulin nonusers was much higher than that in insulin users (49.2 vs. 10.2, per 1,000 person-years, P < 0.0001). After further adjustment for all other covariates with a P value less than 0.3 and nonlinear associations with cancer, A1C was associated with an increased cancer risk (HR per percentage 1.26, 95% CI 1.03–1.55), whereas use of insulin was associated with a decreased cancer risk (HR of insulin users vs. nonusers: 0.17, 0.09–0.32). Consistent results were found in analyses including all 973 insulin users and 3,650 nonusers.

CONCLUSIONS

In Chinese patients with type 2 diabetes, hyperglycemia predicts cancer, whereas insulin usage was associated with a reduced cancer risk.
Molecular Characterization of Insulin-Mediated Suppression of Hepatic Glucose Production In Vivo
Authors: Ramnanan Christopher J. , Edgerton Dale S. , Rivera Noelia , Irimia-Dominguez Jose , Farmer Ben , Neal Doss W. , Lautz Margaret , Donahue E. Patrick , Meyer Catalina M. , Roach Peter J. , Cherrington Alan D.
Published: February 2010

OBJECTIVE

Insulin-mediated suppression of hepatic glucose production (HGP) is associated with sensitive intracellular signaling and molecular inhibition of gluconeogenic (GNG) enzyme mRNA expression. We determined, for the first time, the time course and relevance (to metabolic flux) of these molecular events during physiological hyperinsulinemia in vivo in a large animal model.

RESEARCH DESIGN AND METHODS

24 h fasted dogs were infused with somatostatin, while insulin (basal or 8× basal) and glucagon (basal) were replaced intraportally. Euglycemia was maintained and glucose metabolism was assessed using tracer, 2H2O, and arterio-venous difference techniques. Studies were terminated at different time points to evaluate insulin signaling and enzyme regulation in the liver.

RESULTS

Hyperinsulinemia reduced HGP due to a rapid transition from net glycogen breakdown to synthesis, which was associated with an increase in glycogen synthase and a decrease in glycogen phosphorylase activity. Thirty minutes of hyperinsulinemia resulted in an increase in phospho-FOXO1, a decrease in GNG enzyme mRNA expression, an increase in F2,6P2, a decrease in fat oxidation, and a transient decrease in net GNG flux. Net GNG flux was restored to basal by 4 h, despite a substantial reduction in PEPCK protein, as gluconeogenically-derived carbon was redirected from lactate efflux to glycogen deposition.

CONCLUSIONS

In response to acute physiologic hyperinsulinemia, 1) HGP is suppressed primarily through modulation of glycogen metabolism; 2) a transient reduction in net GNG flux occurs and is explained by increased glycolysis resulting from increased F2,6P2 and decreased fat oxidation; and 3) net GNG flux is not ultimately inhibited by the rise in insulin, despite eventual reduction in PEPCK protein, supporting the concept that PEPCK has poor control strength over the gluconeogenic pathway in vivo.
Mortality Associated With Acute Charcot Foot and Neuropathic Foot Ulceration
Authors: van Baal Juliette , Hubbard Richard , Game Fran , Jeffcoate William
Published: February 2010

OBJECTIVE

To compare the mortality of patients with an acute Charcot foot with a matched population with uninfected neuropathic foot ulcers (NFUs).

RESEARCH DESIGN AND METHODS

Data were extracted from a specialist departmental database, supplemented by hospital records. The findings were compared with the results of earlier populations with Charcot foot and uninfected NFUs managed from 1980. Finally, the results of all patients with acute Charcot foot and all control subjects managed between 1980 and 2007 were compared with normative mortality data for the U.K. population.

RESULTS

A total of 70 patients presented with an acute Charcot foot (mean age 57.4 ± 12.0 years; 48 male [68.6%]) between 2001 and 2007; there were 66 matched control subjects. By 1 October 2008, 13 (eight male; 18.6%) patients with a Charcot foot had died, after a median of 2.1 years (interquartile range 1.1–3.3). Twenty-two (20 male; 33.3%) control subjects had also died after a median of 1.3 years (0.6–2.5). There was no difference in survival between the two groups (log-rank P > 0.05). Median survival of all 117 patients with acute Charcot foot managed between 1980 and 2007 was 7.88 years (4.0–15.4) and was not significantly different from the control NFU patients (8.43 years [3.4–15.8]). When compared with normative U.K. population data, life expectancy in the two groups was reduced by 14.4 and 13.9 years, respectively.

CONCLUSIONS

These data confirm that the mortality in patients presenting to our unit with either an acute Charcot foot and an uninfected neuropathic ulcer was unexpectedly high.
Racial Disparity in A1C Independent of Mean Blood Glucose in Children With Type 1 Diabetes
Authors: Kamps Jodi L. , Hempe James M. , Chalew Stuart A.
Published: February 2010

OBJECTIVE

Mean blood glucose (MBG) and MBG-independent factors both influence A1C levels. Race was related to A1C independent of MBG in adults. The goal of this study was to determine if racial disparity exists in A1C independent of MBG in children with diabetes.

RESEARCH DESIGN AND METHODS

Participants included 276 children with type 1 diabetes. A1C and MBG were obtained from multiple clinic visits, and a hemoglobin glycation index (HGI) (an assessment of A1C levels independent of MBG) was calculated. A1C and HGI were analyzed controlling for age, diabetes duration, and MBG.

RESULTS

African Americans had statistically significantly higher A1C (9.1 ± 0.1) and HGI (0.64 ± 0.11) than Caucasians (A1C 8.3 ± 0.1, HGI −0.15 ± 0.07) independent of covariates.

CONCLUSIONS

Because of racial disparity in A1C, which is independent of MBG, we recommend that A1C and MBG be used together to make therapeutic decisions for children with diabetes.
Is Pulse Pressure a Predictor of New-Onset Diabetes in High-Risk Hypertensive Patients?
Authors: Yasuno Shinji , Ueshima Kenji , Oba Koji , Fujimoto Akira , Hirata Masakazu , Ogihara Toshio , Saruta Takao , Nakao Kazuwa
Published: February 2010

OBJECTIVE

Hypertensive patients have an increased risk of developing diabetes. Accumulating evidence suggests a close relation between metabolic disturbance and increased arterial stiffness. Here, we examined the association between pulse pressure and the risk of new-onset diabetes in high-risk Japanese hypertensive patients.

RESEARCH DESIGN AND METHODS

The Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial examined the effects of candesartan and amlodipine on the incidence of cardiovascular events in 4,728 high-risk Japanese hypertensive patients. In the present study, we analyzed the relationship between pulse pressure at baseline and new-onset diabetes in 2,685 patients without diabetes at baseline (male 1,471; mean age 63.7 years; mean BMI 24.8 kg/m2) as a subanalysis of the CASE-J trial.

RESULTS

During 3.3 ± 0.8 years of follow-up, 97 patients (3.6%) developed diabetes. In multiple Cox regression analysis, pulse pressure was an independent predictor for new-onset diabetes (hazard ratio [HR] per 1 SD increase 1.44 [95% CI 1.15–1.79]) as were male sex, BMI, and additional use of diuretics, whereas age and heart rate were not. Plots of HRs for new-onset diabetes considering both systolic and diastolic blood pressure (DBP) revealed that a higher pulse pressure with a lower DBP, indicating that the increased pulse pressure was largely due to increased arterial stiffness, was strongly associated with the risk of new-onset diabetes.

CONCLUSIONS

Pulse pressure is an independent predictor of new-onset diabetes in high-risk Japanese hypertensive patients. Increased arterial stiffness may be involved in the development of diabetes.
Association of Diabetes, Comorbidities, and A1C With Functional Disability in Older Adults
Authors: Kalyani Rita Rastogi , Saudek Christopher D. , Brancati Frederick L. , Selvin Elizabeth
Published: February 2010

OBJECTIVE

To examine the relationship of diabetes and functional disability in older adults and the possible mediating roles of comorbidities and A1C.

RESEARCH DESIGN AND METHODS

We analyzed data from a nationally representative sample of 6,097 participants aged ≥60 years in the National Health and Nutrition Examination Survey, 1999–2006. Diabetes was defined by self-report. Disability was defined as difficulty performing a physical task. We evaluated disability by grouping 19 physical tasks into five functional groups: lower-extremity mobility (LEM), general physical activities (GPA), activities of daily living (ADL), instrumental activities of daily living (IADL), and leisure and social activities (LSA).

RESULTS

Older U.S. adults with diabetes had the greatest disability in GPA (prevalence 73.6% [95% CI 70.2–76.9]), followed by LEM (52.2% [48.5–55.9]), IADL (43.6% [40.1–47.2]), ADL (37.2% [33.1–41.3]), and LSA groups (33.8% [30.8–36.9]). Diabetes was associated with two to three times increased odds of disability across functional groups (all P < 0.05). Comorbidities, mostly cardiovascular disease and obesity, and poor glycemic control (A1C ≥8%) together explained up to 85% of the excess odds of disability associated with diabetes, whereas poor glycemic control alone explained only ∼10% of the excess odds. Adjustment for comorbidities, A1C, and diabetes duration fully attenuated the associations of diabetes with disability in all functional groups (all P > 0.05).

CONCLUSIONS

Older adults with diabetes have a high prevalence of disabilities with variable associations attributable to comorbidities and A1C. Aggressive management of cardiovascular risk factors and obesity may significantly reduce the burden of disability in this population.
Health-Related Quality of Life, Treatment Satisfaction, and Costs Associated With Intraperitoneal Versus Subcutaneous Insulin Administration in Type 1 Diabetes
Authors: Logtenberg Susan J. , Kleefstra Nanne , Houweling Sebastiaan T. , Groenier Klaas H. , Gans Reinold O. , Bilo Henk J.
Published: February 2010

OBJECTIVE

To investigate the effects of continuous intraperitoneal insulin infusion (CIPII) compared with subcutaneous insulin on health-related quality of life (HRQOL) and treatment satisfaction, and to perform a cost analysis in type 1 diabetes.

RESEARCH DESIGN AND METHODS

We used an open-label, prospective, crossover, randomized, 16-month study (N = 24). HRQOL and patient satisfaction were assessed with questionnaires (the 36-item short-form health survey [SF-36], the World Health Organization-Five Well-Being Index [WHO-5], and the Diabetes Treatment Satisfaction Questionnaire [DTSQ]). Direct costs of CIPII and continuous subcutaneous insulin infusion (CSII) were compared.

RESULTS

Questionnaire scores were higher with CIPII than with subcutaneous therapy. Yearly direct pump- and procedure-associated costs for CIPII were estimated at €10,910 compared with €4,810 for CSII.

CONCLUSIONS

Apart from improving glycemic control, CIPII improved HRQOL and treatment satisfaction compared with subcutaneous insulin. Direct pump- and procedure-associated costs are considerably higher for CIPII, however.
High Baseline Insulin Levels Associated With 6-Year Incident Observed Sleep Apnea
Authors: Balkau Beverley , Vol Sylviane , Loko Sandrine , Andriamboavonjy Tiana , Lantieri Olivier , Gusto Gaelle , Meslier Nicole , Racineux Jean-Louis , Tichet Jean ,   and the Data from an Epidemiologic Study on the Insulin Resistance Syndrome (D.E.S.I.R.) Study Group
Published: February 2010

OBJECTIVE

Obstructive sleep apnea is common in patients with type 2 diabetes, and its association with insulin and insulin resistance has been examined in cross-sectional studies. We evaluate risk factors for incident observed sleep apnea in a general population not selected for sleep disturbances.

RESEARCH DESIGN AND METHODS

A total of 1,780 men and 1,785 women, aged 33 to 68 years, from the cohort Data from an Epidemiologic Study on the Insulin Resistance Syndrome (D.E.S.I.R.) responded to the question, “Has someone said to you that you stop breathing during your sleep?” at baseline and 6 years. Anthropometric, clinical, and biological factors were recorded at both time points.

RESULTS

At baseline, 14% of men and 7% of women reported having observed sleep apnea (positive response to question); 6-year incidences were 14 and 6%, respectively. Age, anthropometric parameters, blood pressure, and sleep characteristics were all associated with prevalent, observed apnea episodes, in both sexes. Baseline waist circumference was the strongest predictor of incident apnea: standardized odds ratio (OR), adjusted for age and sex, 1.34 (95% CI 1.19–1.52). After adjustment for age, sex, and waist circumference, the standardized ORs for incident observed apnea were identical for fasting insulin and the homeostasis model assessment of insulin resistance: 1.31 (1.13–1.51) and 1.24 (1.09–1.41) for triglycerides and 1.52 (1.12–2.05) for smoking. Observed apnea at baseline was not associated with changes in anthropometric or biological parameters over the 6-year follow-up.

CONCLUSIONS

The most important baseline risk factor for incident apnea was adiposity. After accounting for adiposity, other risk factors were high insulin, insulin resistance, high triglycerides, and smoking, factors amenable to lifestyle intervention.
Long-Acting Insulin Analogs and the Risk of Diabetic Ketoacidosis in Children and Adolescents With Type 1 Diabetes
Authors: Karges Beate , Kapellen Thomas , Neu Andreas , Hofer Sabine E. , Rohrer Tilman , Rosenbauer Joachim , Wolf Johannes , Holl Reinhard W. ,   for the Diabetes Prospective Documentation (DPV) Initiative and the German Federal Ministry for Education and Research (BMBF) Competence Network of Diabetes Mellitus
Published: February 2010

OBJECTIVE

To investigate if long-acting insulin analogs decrease the risk of diabetic ketoacidosis (DKA) in young individuals with type 1 diabetes.

RESEARCH DESIGN AND METHODS

Of 48,110 type 1 diabetic patients prospectively studied between 2001 and 2008, the incidence of DKA requiring hospitalization was analyzed in 10,682 individuals aged ≤20 years with a diabetes duration of ≥2 years.

RESULTS

The overall rate of DKA was 5.1 (SE ± 0.2)/100 patient-years. Patients using insulin glargine or detemir (n = 5,317) had a higher DKA incidence than individuals using NPH insulin (n = 5,365, 6.6 ± 0.4 vs. 3.6 ± 0.3, P < 0.001). The risk for DKA remained significantly different after adjustment for age at diabetes onset, diabetes duration, A1C, insulin dose, sex, and migration background (P = 0.015, odds ratio 1.357 [1.062–1.734]).

CONCLUSIONS

Despite their long-acting pharmacokinetics, the use of insulin glargine or detemir is not associated with a lower incidence of DKA compared with NPH insulin.
Age at Onset and the Risk of Proliferative Retinopathy in Type 1 Diabetes
Authors: Hletala Kustaa , Harjutsalo Valma , Forsblom Carol , summanen Paula , Groop Per-Henrik ,   on behalf of the flnndlane study Group
Published: February 2010

OBJECTIVE

Age at onset of type 1 diabetes influences the risk of microvascular complications. However, the long-term risk of proliferative retinopathy within the wide spectrum of age at onset of type 1 diabetes is less well known.

RESEARCH DESIGN AND METHODS

A sample of 1,117 consecutively recruited patients was drawn from the FinnDiane Study population (4,800 patients). Type 1 diabetes was defi ned as age at onset ≤40 years, insulin treatment initiated within 1 year, and C-peptide ≤0.3 nmol/1. Retinopathy status was graded based on ophthalmic records and/or fundus photographs. The risk of proliferative retinopathy was studied in age-at-onset groups 0–4, 5–14, and 15–40 years.

RESULTS

The mean durations to proliferative retinopathy were 24.3 (22.7–25.9) years in the 0–4 years group, 20.1 (19.2–21.1) years in the 5–14 years group, and 21.6 (19.8–23.3) years in the 15–40 years group (P < 0.001). In a Cox regression model, with A1C, blood pressure, sex, and BMI as covariates, the highest risk of proliferative retinopathy was observed in the 5–14 years group (hazard ratio 1.90 [95% CI 1.45–2.48], P < 0.001). Diabetes onset 0–4 vs. 5–14 years made no difference in the long-term risk of proliferative retinopathy (P = 0.2). When split into two groups, age at onset < 15 years was associated with a higher long-term risk than age at onset >15 years (1.82 [1.40–2.36], P < 0.001).

CONCLUSIONS

Age at onset significantly modifies the long-term risk of proliferative retinopathy. The highest risk is in age-at-onset group 5–14 years, whereas the lowest risk is in age-at-onset group 15–40 years.
The Latitude Wise Prevalence of the CCR5-Δ32-HIV Resistance Allele in India
Authors: Bhatnagar I , Singh M , Mishra N , Saxena R , Thangaraj K , Singh L , Saxena S
Published: February 2010

The Latitude Wise Prevalence of the CCR5-Δ32-HIV Resistance Allele in India

The chemokine receptor CCR5 plays a crucial role during CD4-mediated entry of HIV-1 in macrophages and a 32 bp deletion in the CCR5 gene (CCR5-Δ32) confers protection against HIV infection and AIDS progression. To evaluate the contribution of this host genetic factor in aggravating India's HIV/AIDS problem, we exclusively examined the frequency of CCR5-Δ32 in 43 different ethnic endogamous Indian populations comprising 1,882 individuals and its latitude-wise distribution in India. This is the first report of prevalence and latitude-wise distribution of CCR5-Δ32 in such large scale in India, which indicates that most of the Indian populations lack the CCR5-Δ32 mutation. This mutation was exhibited in only 13 out of the 43 ethnic populations of India studied with allelic frequency 0.62 - 5%. Southward decreasing cline was observed for frequencies of CCR5-Δ32 (0.79% to 5.0% in North vs. 0.62% to 1.4% South). These results are in accordance with HIV/AIDS prevalence in India, and suggest that absence of CCR5-Δ32 mutation may be one of the important factors for HIV/AIDS incidence in India.
Molecular Diagnostics of Duchenne/Becker Muscular Dystrophy Patients by Multiplex Ligation-Dependent Probe Amplification Analysis and Direct Sequencing
Authors: Todorova A , Guergueltcheva V , Genova J , Mihaylova V , Todorov T , Tchamova T , Georgieva B , Kremensky I , Tournev I , Mitev V
Published: February 2010

Molecular Diagnostics of Duchenne/Becker Muscular Dystrophy Patients by Multiplex Ligation-Dependent Probe Amplification Analysis and Direct Sequencing

Duchenne/Becker muscular dystrophy (DMD/BMD), the most common X-linked muscular dystrophy is caused by mutations in the enormously large DMD gene. We screened this gene in 51 unrelated Bulgarian DMD/BMD patients and four families with no living index patient available, by multiplex ligation-dependent probe amplification (MLPA) analysis, which is a powerful tool for detecting deletion/duplication along the DMD gene. This, in combination with direct sequencing, characterized the mutation in all patients, which comprised 42 deletions (82%), six duplications (12%) and three point mutations (6%), and precisely determined all deletion/duplication borders. In all the families with no living index patient available, deletions were detected by direct analysis on the patients' mothers and sisters, proving the value of MLPA for carrier status determination.