bluuebunny/crossref_metadata_2025 huggingface dataset:
HbA1c and the Risks for All-Cause and Cardiovascular Mortality in the General Japanese Population
Authors: Sakurai Masaru , Saitoh Shigeyuki , Miura Katsuyuki , Nakagawa Hideaki , Ohnishi Hirofumi , Akasaka Hiroshi , Kadota Aya , Kita Yoshikuni , Hayakawa Takehito , Ohkubo Takayoshi , Okayama Akira , Okamura Tomonori , Ueshima Hirotsugu ,   for the NIPPON DATA90 Research Group
Published: July 2013

OBJECTIVE

Associations between HbA1c and cardiovascular diseases (CVD) have been reported mainly in Western countries. It is not clear whether HbA1c measurements are useful for assessing CVD mortality risk in East Asian populations.

RESEARCH DESIGN AND METHODS

The risk for cardiovascular death was evaluated in a large cohort of participants selected randomly from the overall Japanese population. A total of 7,120 participants (2,962 men and 4,158 women; mean age 52.3 years) free of previous CVD were followed for 15 years. Adjusted hazard ratios (HRs) and 95% CIs among categories of HbA1c (<5.0%, 5.0–5.4%, 5.5–5.9%, 6.0–6.4%, and ≥6.5%) for participants without treatment for diabetes and HRs for participants with diabetes were calculated using a Cox proportional hazards model.

RESULTS

During the study, there were 1,104 deaths, including 304 from CVD, 61 from coronary heart disease, and 127 from stroke (78 from cerebral infarction, 25 from cerebral hemorrhage, and 24 from unclassified stroke). Relations to HbA1c with all-cause mortality and CVD death were graded and continuous, and multivariate-adjusted HRs for CVD death in participants with HbA1c 6.0–6.4% and ≥6.5% were 2.18 (95% CI 1.22–3.87) and 2.75 (1.43–5.28), respectively, compared with participants with HbA1c <5.0%. Similar associations were observed between HbA1c and death from coronary heart disease and death from cerebral infarction.

CONCLUSIONS

High HbA1c levels were associated with increased risk for all-cause mortality and death from CVD, coronary heart disease, and cerebral infarction in general East Asian populations, as in Western populations.
New-Onset Diabetes in Elderly Subjects
Authors: Twito Orit , Ahron Ella , Jaffe Anat , Afek Shani , Cohen Efrat , Granek-Catarivas Martine , Klein Pinchas , Hermoni Doron
Published: July 2013

OBJECTIVE

New-onset diabetes mellitus (DM) in elderly patients is associated with increased risk of diabetes complications and mortality. It is unknown whether glycemic control in this population influences the mortality risk.

RESEARCH DESIGN AND METHODS

The current study was conducted using the computerized database of the Sharon-Shomron District of Clalit Health Services in Israel. Included in the study were subjects 65 years of age and above with new-onset DM. The primary outcome measures were all-cause mortality and coronary revascularization procedures with either percutaneous coronary intervention or coronary artery bypass grafting.

RESULTS

Participants (n = 2,994) were stratified into four groups according to their mean HbA1c levels during the follow-up period (<6.5% [48 mmol/mol], 6.5–6.99% [48–52 mmol/mol], 7–7.49% [53–57 mmol/mol], and ≥7.5% [58 mmol/mol]). During a mean follow-up of 5.54 ± 2.1 years, 1,173 (39.17%) participants died and 285 (9.51%) underwent coronary revascularization. An HbA1c level >7.5% (58 mmol/mol) was associated with a significantly increased all-cause mortality rate (hazard ratio [HR] 1.74 [95% CI 1.2–1.8], P < 0.0001). This difference remained statistically significant after a multivariate model adjusted for the conventional cardiovascular risk factors and for the use of hypoglycemic agents and statins. Kaplan-Meier survival plots revealed lower survival rates in this group of patients. Coronary revascularization rates were highest among subjects with HbA1c 6.5–6.99% (48–52 mmol/mol) (HR 1.6 [1.01–2.4], P < 0.05) and lowest in patients with HbA1c ≥7.5% (58 mmol/mol).

CONCLUSIONS

An HbA1c level >7.5% (58 mmol/mol) is associated with increased risk for all-cause mortality and with a lower revascularization rate in elderly patients with new-onset DM.
Impact of Specific Glucose-Control Strategies on Microvascular and Macrovascular Outcomes in 58,000 Adults With Type 2 Diabetes
Authors: Neugebauer Romain , Fireman Bruce , Roy Jason A. , O’Connor Patrick J.
Published: July 2013

OBJECTIVE

Comparative effectiveness research methods are used to compare the effect of four distinct glucose-control strategies on subsequent myocardial infarction and nephropathy in type 2 diabetes.

RESEARCH DESIGN AND METHODS

A total of 58,000 adults with type 2 diabetes and A1C <7% (53 mmol/mol) while taking two or more oral agents or basal insulin had subsequent A1C ≥7% (53 mmol/mol) to 8.5% (69 mmol/mol). Follow-up started on date of first A1C ≥7% and ended on date of a specific clinical event, death, disenrollment, or study end. Glucose-control strategies were defined as first intensification of glucose-lowering therapy at A1C ≥7, ≥7.5, ≥8, or ≥8.5% with subsequent control for treatment adherence. Logistic marginal structural models were fitted to assess the discrete-time hazards for each dynamic glucose-control strategy, adjusting for baseline and time-dependent confounding and selection bias through inverse probability weighting.

RESULTS

After adjustment for age, sex, race/ethnicity, comorbidities, blood pressure, lipids, BMI, and other covariates, progressively more aggressive glucose-control strategies were associated with reduced onset or progression of albuminuria but not associated with significant reduction in occurrence of myocardial infarction or preserved renal function based on estimated glomerular filtration rate over 4 years of follow-up.

CONCLUSIONS

In a large representative cohort of adults with type 2 diabetes, more aggressive glucose-control strategies have mixed short-term effects on microvascular complications and do not reduce the myocardial infarction rate over 4 years of follow-up. These findings are consistent with the results of recent clinical trials, but confirmation over longer periods of observation is needed.
Risk of a Recurrent Cardiovascular Event in Individuals With Type 2 Diabetes or Intermediate Hyperglycemia
Authors: van der Heijden Amber A.W.A. , van’t Riet Esther , Bot Sandra D.M. , Cannegieter Suzanne C. , Stehouwer Coen D.A. , Baan Caroline A. , Dekker Jacqueline M. , Nijpels Giel
Published: July 2013

OBJECTIVE

To investigate risk of a recurrent cardiovascular event and its predictors in a population-based cohort.

RESEARCH DESIGN AND METHODS

Participants of the Hoorn Study who had experienced a first cardiovascular event after baseline (n = 336) were followed with respect to a recurrent event. Absolute risk of a recurrent event was calculated for individuals with normal glucose metabolism, intermediate hyperglycemia, and type 2 diabetes. Cox regression models were used to investigate which variables, measured before the first vascular event, predicted a recurrent event using the stepwise backward procedure.

RESULTS

During a median follow-up of 4.1 years, 44% (n = 148) of the population developed a recurrent vascular event. The rate of recurrent events per 100 person-years was 7.2 (95% CI 5.8–8.7) in individuals with normal glucose metabolism, compared with 9.8 (6.6–14.0) in individuals with intermediate hyperglycemia and 12.5 (8.5–17.6) in individuals with type 2 diabetes. Higher age (hazard ratio 1.02 [95% CI 1.00–1.04]), male sex (1.56 [1.08–2.25]), waist circumference (1.02 [1.02–1.03]), higher systolic blood pressure (1.01 [1.01–1.02]), higher HbA1c (%, 1.13 [0.97–1.31]/ mmol/mol, 1.01 [1.00–1.03]), and family history of myocardial infarction (1.38 [0.96–2.00]) predicted a recurrent cardiovascular event.

CONCLUSIONS

Individuals with type 2 diabetes, but not individuals with intermediate hyperglycemia, are at increased risk for a recurrent vascular event compared with individuals with normal glucose metabolism. In people with a history of cardiovascular disease, people at increased risk of a recurrent event can be identified based on the patient’s risk profile before the first event.
Matrix Gla Protein Species and Risk of Cardiovascular Events in Type 2 Diabetic Patients
Authors: Dalmeijer Geertje W. , van der Schouw Yvonne T. , Magdeleyns Elke J. , Vermeer Cees , Verschuren W.M. Monique , Boer Jolanda M.A. , Beulens Joline W.J.
Published: July 2013

OBJECTIVE

To investigate the relationship of circulating matrix Gla protein (MGP) species with incident cardiovascular disease (CVD) or coronary heart disease (CHD) in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS

EPIC-NL is a prospective cohort study among 40,011 Dutch men and women. At baseline (1993–1997), 518 participants were known to have type 2 diabetes. MGP levels were measured by ELISA techniques in baseline plasma samples. The incidence of fatal and nonfatal CVD and CVD subtypes—CHD, peripheral arterial disease (PAD), heart failure, and stroke—were obtained by linkage to national registers. Cox proportional hazard models were used to calculate hazard ratios (HRs), adjusted for sex, waist-to-hip ratio, physical activity, and history of CVD.

RESULTS

During a median 11.2 years of follow-up, 160 cases of CVD were documented. Higher circulating desphospho-uncarboxylated MGP (dp-ucMGP) levels were significantly associated with higher risk of CVD, with an HR per SD (HRSD) of 1.21 (95% CI 1.06–1.38), PAD (HRSD 1.32 [95% CI 1.07–1.65]), and heart failure (HRSD 1.75 [95% CI 1.42–2.17]) after adjustment. Higher circulating dp-ucMGP levels were not related to risk of CHD (HRSD 1.12 [95% CI 0.94–1.34]) or stroke (HRSD 1.05 [95% CI 0.73–1.49]). Circulating desphospho-carboxylated MGP and circulating total-uncarboxylated MGP levels were not associated with CVD or CVD subtypes.

CONCLUSIONS

High dp-ucMGP levels were associated with increased CVD risk among type 2 diabetic patients, especially with the subtypes PAD and heart failure, while other MGP species were not related to CVD risk. These results suggest that a poor vitamin K status is associated with increased CVD risk.
Subarachnoid Hemorrhage in Type 1 Diabetes
Authors: Korja Miikka , Thorn Lena M. , Hägg Stefanie , Putaala Jukka , Liebkind Ron , Harjutsalo Valma , Forsblom Carol M. , Gordin Daniel , Tatlisumak Turgut , Groop Per-Henrik ,   on behalf of the FinnDiane Study Group
Published: July 2013

OBJECTIVE

To estimate for the first time the incidence of subarachnoid hemorrhage (SAH) in type 1 diabetes.

RESEARCH DESIGN AND METHODS

Using the nationwide Finnish Diabetic Nephropathy (FinnDiane) Study cohort of 4,083 patients with type 1 diabetes (mean age of 37.4 ± 11.8 years at enrollment), we analyzed the incidence of first-ever SAH events.

RESULTS

During the follow-up time of 36,680 person-years (median 9.4 years), 15 patients with type 1 diabetes experienced an aneurysmal or nonaneurysmal SAH, and thus the crude incidence of SAH was 40.9 (95% CI 22.9–67.4) per 100,000 person-years. One patient had a verified aneurysmal SAH, and four patients died suddenly of an SAH, which was most likely caused by an aneurysm. SAHs in 10 out of 15 patients were classified as nonaneurysmal SAH, and thus the crude incidence of nonaneurysmal SAH was 27.3 (13.1–50.1) per 100,000 person-years. None of the nonaneurysmal SAHs were fatal. In univariate analysis, current smokers had a hazard ratio of 4.82 (95% CI 1.31–17.81) for nonaneurysmal SAH.

CONCLUSIONS

The incidence of nonaneurysmal SAH is high among patients with type 1 diabetes. Our findings suggest that nonaneurysmal SAH is a distinct new microvascular complication in type 1 diabetes.
Cancer Incidence Among Those Initiating Insulin Therapy With Glargine Versus Human NPH Insulin
Authors: Stürmer Til , Marquis M. Alison , Zhou Haibo , Meigs James B. , Lim Soo , Blonde Lawrence , MacDonald Eileen , Wang Ray , LaVange Lisa M. , Pate Virginia , Buse John B.
Published: July 2013

OBJECTIVE

To add to the evidence on comparative long-term effects of insulin analog glargine versus human NPH insulin on the risk for cancer.

RESEARCH DESIGN AND METHODS

We identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) between January 2003 and December 2010. Patients were required to have a second prescription of the same insulin within 180 days and to be free of cancer. We balanced cohorts on risk factors for cancer outcomes based on comorbidities, comedication, and health care use during the prior 12 months using inverse probability of treatment weighting. Incident cancer was defined as having two claims for cancer (any cancer) or the same cancer (breast, prostate, colon) within 2 months. We estimated adjusted hazard ratios (HRs) and their 95% CI using weighted Cox models censoring for stopping, switching, or augmenting insulin treatment, end of enrollment, and mortality.

RESULTS

More patients initiated glargine (43,306) than NPH (9,147). Initiators of glargine (NPH) were followed for 1.2 (1.1) years and 50,548 (10,011) person-years; 993 (178) developed cancer. The overall HR was 1.12 (95% CI 0.95–1.32). Results were consistent for breast cancer, prostate cancer, and colon cancer; various durations of treatment; and sensitivity analyses.

CONCLUSIONS

Patients initiating insulin glargine rather than NPH do not seem to be at an increased risk for cancer. While our study contributes significantly to our evidence base for long-term effects, this evidence is very limited mainly based on actual dynamics in insulin prescribing.
Safety and Efficacy of Sitagliptin Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes
Authors: Umpierrez Guillermo E. , Gianchandani Roma , Smiley Dawn , Jacobs Sol , Wesorick David H. , Newton Christopher , Farrokhi Farnoosh , Peng Limin , Reyes David , Lathkar-Pradhan Sangeeta , Pasquel Francisco
Published: July 2013

OBJECTIVE

This study investigated the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients.

RESEARCH DESIGN AND METHODS

In this pilot, multicenter, open-label, randomized study, patients (n = 90) with a known history of T2D treated with diet, oral antidiabetic agents, or low total daily dose of insulin (≤0.4 units/kg/day) were randomized to receive sitagliptin alone or in combination with glargine insulin (glargine) or to a basal bolus insulin regimen (glargine and lispro) plus supplemental (correction) doses of lispro. Major study outcomes included differences in daily blood glucose (BG), frequency of treatment failures (defined as three or more consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL), and hypoglycemia between groups.

RESULTS

Glycemic control improved similarly in all treatment groups. There were no differences in the mean daily BG after the 1st day of treatment (P = 0.23), number of readings within a BG target of 70 and 140 mg/dL (P = 0.53), number of BG readings >200 mg/dL (P = 0.23), and number of treatment failures (P > 0.99). The total daily insulin dose and number of insulin injections were significantly less in the sitagliptin groups compared with the basal bolus group (both P < 0.001). There were no differences in length of hospital stay (P = 0.78) or in the number of hypoglycemic events between groups (P = 0.86).

CONCLUSIONS

Results of this pilot indicate that treatment with sitagliptin alone or in combination with basal insulin is safe and effective for the management of hyperglycemia in general medicine and surgery patients with T2D.
Clinical Inertia in People With Type 2 Diabetes
Authors: Khunti Kamlesh , Wolden Michael L. , Thorsted Brian Larsen , Andersen Marc , Davies Melanie J.
Published: July 2013

OBJECTIVE

To determine time to treatment intensification in people with type 2 diabetes treated with one, two, or three oral antidiabetes drugs (OADs) and associated levels of glycemic control.

RESEARCH DESIGN AND METHODS

This was a retrospective cohort study based on 81,573 people with type 2 diabetes in the U.K. Clinical Practice Research Datalink between January 2004 and December 2006, with follow-up until April 2011.

RESULTS

In people with HbA1c ≥7.0, ≥7.5, or ≥8.0% (≥53, ≥58, or ≥64 mmol/mol), median time from above HbA1c cutoff to intensification with an additional OAD was 2.9, 1.9, or 1.6 years, respectively, for those taking one OAD and >7.2, >7.2, and >6.9 years for those taking two OADs. Median time to intensification with insulin was >7.1, >6.1, or 6.0 years for those taking one, two, or three OADs. Mean HbA1c at intensification with an OAD or insulin for people taking one, two, or three OADs was 8.7, 9.1, and 9.7%. In patients taking one, two, or three OADs, median time from treatment initiation to intensification with an OAD or insulin exceeded the maximum follow-up time of 7.2 years. The probability of patients with poor glycemic control taking one, two, or three OADs, intensifying at end of follow-up with an OAD, was 21.1–43.6% and with insulin 5.1–12.0%.

CONCLUSIONS

There are delays in treatment intensification in people with type 2 diabetes despite suboptimal glycemic control. A substantial proportion of people remain in poor glycemic control for several years before intensification with OADs and insulin.
Sex-Specific Associations of Gestational Glucose Tolerance With Childhood Body Composition
Authors: Regnault Nolwenn , Gillman Matthew W. , Rifas-Shiman Sheryl L. , Eggleston Emma , Oken Emily
Published: July 2013

OBJECTIVE

To examine the associations of maternal gestational glucose tolerance with offspring body composition in late childhood.

RESEARCH DESIGN AND METHODS

Among 958 women in the prebirth cohort Project Viva, glucose tolerance was assessed in the second trimester by nonfasting 50-g 1-h glucose challenge test (GCT), followed if abnormal by fasting 100-g 3-h oral glucose tolerance test (OGTT). We categorized women as normoglycemic (83.3%) if GCT was ≤140 mg/dL, isolated hyperglycemia (9.1%) if GCT was abnormal but OGTT normal, intermediate glucose intolerance (IGI) (3.3%) if there was one abnormal value on OGTT, or gestational diabetes mellitus (GDM) (4.5%) if there were two or more abnormal OGTT values. Using multivariable linear regression, we examined adjusted associations of glucose tolerance with offspring overall (N = 958) and central (N = 760) adiposity and body composition using dual X-ray absorptiometry (DXA) measured at the school-age visit (95 ± 10 months).

RESULTS

Compared with that in the male offspring of normoglycemic mothers, DXA fat mass was higher in male offspring of GDM mothers (1.89 kg [95% CI 0.33–3.45]) but not in male offspring of mothers with IGI (0.06 kg [−1.45 to 1.57]). DXA trunk-to-peripheral fat mass, a measure of central adiposity, was also somewhat higher in male offspring of GDM mothers (0.04 [−0.01 to 0.09]). In girls, DXA fat mass was higher in offspring of mothers with IGI (2.23 kg [0.12–4.34]) but not GDM (−1.25 kg [−3.13 to 0.63]). We showed no association of gestational glucose tolerance with DXA lean mass.

CONCLUSIONS

In this study, only male offspring of GDM mothers manifested increased adiposity, whereas only female offspring of mothers with IGI did so. Sex differences in glycemic sensitivity may explain these findings.
Evaluation of a point-of-care glucose and β-hydroxybutyrate meter operated in various environmental conditions in prepartum and postpartum sheep
Authors: Hornig Katlin J. , Byers Stacey R. , Callan Robert J. , Holt Timothy , Field Megan , Han Hyungchul
Published: July 2013

Objective—To compare β-hydroxybutyrate (BHB) and glucose concentrations measured with a dual-purpose point-of-care (POC) meter designed for use in humans and a laboratory biochemical analyzer (LBA) to determine whether the POC meter would be reliable for on-farm measurement of blood glucose and BHB concentrations in sheep in various environmental conditions and nutritional states.

Animals—36 pregnant mixed-breed ewes involved in a maternal feed restriction study.

Procedures—Blood samples were collected from each sheep at multiple points throughout gestation and lactation to allow for tracking of gradually increasing metabolic hardship. Whole blood glucose and BHB concentrations were measured with the POC meter and compared with serum results obtained with an LBA.

Results—464 samples were collected. Whole blood BHB concentrations measured with the POC meter compared well with LBA results, and error grid analysis showed the POC values were acceptable. Whole blood glucose concentrations measured with the POC meter had more variation, compared with LBA values, over the glucose ranges evaluated. Results of error grid analysis of POC-measured glucose concentrations were not acceptable, indicating errors likely to result in needless treatment with glucose or other supplemental energy sources in normoglycemic sheep.

Conclusions and Clinical Relevance—The POC meter was user-friendly and performed well across a wide range of conditions. The meter was adequate for detection of pregnancy toxemia in sheep via whole blood BHB concentration. Results should be interpreted with caution when the POC meter is used to measure blood glucose concentrations.
Comparison of two analyzers for measurement of plasma total carbon dioxide concentration in horses
Authors: Constable Peter D. , Tinkler Stacy H. , Couëtil Laurent. L.
Published: July 2013

Objective—To determine the degree of agreement between 2 analyzers for measurement of total CO2 concentration (ctCO2) in equine plasma.

Animals—6 healthy untrained horses, 6 trained Standardbreds undergoing a simulated race protocol, and 135 trained Standardbreds at a racetrack.

Procedures—Jugular venous blood samples were obtained from all horses. Two analyzers (commonly used analyzer A and less expensive analyzer B) were used to measure plasma ctCO2 in each sample. Validation of both analyzers was conducted in accordance with guidelines established by the Clinical and Laboratory Standards Institute and involved characterization of linearity, total analytic error, and bias estimation.

Results—Total analytic error (instrument SD) was 0.58 mmol/L (coefficient of variation, 1.6%) and 0.49 mmol/L (coefficient of variation, 1.4%) for analyzers A and B, respectively, when measuring an aqueous standard containing 36.0 mmol of CO2/L. A 1 g/L decrease in plasma protein concentration corresponded to an increase in ctCO2 measured with analyzer B of 0.065 mmol/L. A difference plot indicated that analyzer B produced values 2.7% higher than analyzer A for 103 samples from the 6 trained and exercised Standardbreds (mean plasma protein concentration, 67 g/L).

Conclusions and Clinical Relevance—Analyzer B provided adequate precision and linearity for measurement of ctCO2 from 5 to 40 mmol/L and was therefore suitable for measuring ctCO2 in equine plasma, provided allowances are made for changes in plasma protein concentration.
In vivo and in vitro evaluation of the effects of domperidone on the gastrointestinal tract of healthy horses
Authors: Nieto Jorge E. , Maher Omar , Stanley Scott D. , Larson Richard , Snyder Jack R.
Published: July 2013

Objective—To determine the effects of domperidone on in vivo and in vitro measures of gastrointestinal tract motility and contractility in healthy horses.

Sample—18 adult horses and tissue samples from an additional 26 adult horses.

Procedures—Domperidone or placebo paste was administered to healthy horses in a 2-period crossover study. Gastric emptying was evaluated after oral administration of domperidone paste (1.1 or 5.0 mg/kg) or placebo paste by means of the acetaminophen absorption test in 12 horses. Frequency of defecation, weight of feces produced, fecal moisture, and stomach-to-anus transit time of microspheres were evaluated after administration of domperidone paste (1.1 mg/kg) or placebo paste in 6 horses. The effect of domperidone on smooth muscle contractile activity in samples of duodenum, jejunum, ileum, or colon obtained from 26 horses immediately after euthanasia (for nonsystemic medical problems) was investigated.

Results—Oral administration of 5.0 mg of domperidone/kg increased peak plasma acetaminophen concentration and area under the curve, indicating increased gastric emptying. Administration of 1.1 mg of domperidone/kg had no effect on gastric emptying, transit time, defecation frequency, or amount and moisture of excreted feces. Contractile activities of circular and longitudinal muscle strips from the duodenum, jejunum, ileum, or colon were not altered by domperidone. Dopamine increased contractile activity of longitudinal muscle strips but not that of circular muscle strips from the midjejunum. Domperidone decreased the dopamine-induced contractile activity of midjejunal longitudinal muscle strips.

Conclusions and Clinical Relevance—The potential beneficial effects of domperidone in horses with ileus need to be evaluated in horses with decreased gastric emptying or adynamic ileus.
Effect of treatment with simvastatin and cyclosporine on neurotransmitter concentrations in cerebrospinal fluid after subarachnoid hemorrhage in dogs
Authors: Platt Simon R. , Coates Joan R. , Eifler Danielle M. , Edwards Gaylen L. , Kent Marc , Bulsara Ketan R.
Published: July 2013

Objective—To measure concentrations of glutamate, aspartate, γ-aminobutyric acid (GABA), and glycine in CSF of dogs with experimentally induced subarachnoid hemorrhage (SAH) and to assess effects of cyclosporine and simvastatin on these concentrations.

Sample—CSF samples from 13 dogs.

Procedures—In a previous study, SAH was induced in dogs via 2 injections of autologous blood into the cerebellomedullary cistern 24 hours apart. Dogs were untreated (control; n = 5) or received simvastatin alone (4) or simvastatin in combination with cyclosporine (4). Samples of CSF were collected before the first blood injection (baseline; time 0), before the second blood injection, and on days 3, 7, and 10. For the study reported here, neurotransmitter concentrations in CSF were analyzed via high-performance liquid chromatography. Data were analyzed with a repeated-measures model with adjustments for multiple comparisons by use of the Tukey method.

Results—In control dogs, the glutamate concentration peaked on day 3 and there was a significant increase in GABA and glutamate concentrations. Glutamate concentrations were significantly lower and glycine concentrations significantly higher on day 3 after administration of simvastatin alone or simvastatin in combination with cyclosporine, compared with concentrations for the control group. No significant differences in GABA and aspartate concentrations were detected among treatment groups at any time point.

Conclusions and Clinical Relevance—Glutamate concentrations were increased in the CSF of dogs with SAH. Simvastatin administration attenuated high glutamate concentrations. A combination of immunosuppression and upregulation of nitric oxide synthase may be useful in lowering high glutamate concentrations in ischemic CNS conditions.
Evaluation of serosal patch supplementation of surgical anastomoses in intestinal segments from canine cadavers
Authors: Hansen Lane A. , Monnet Eric L.
Published: July 2013

Objective—To compare leakage and maximum intraluminal pressures of intestinal anastomoses with and without serosal patch supplementation in dogs.

Sample—Healthy small intestine segments from cadavers of 2 dogs euthanized for reasons unrelated to the study.

Procedures—12 enterectomy constructs were created by anastomosis of intestinal segments with a standard simple continuous suture pattern. Half of the constructs were randomly selected for additional serosal patch support. Leakage and maximum intraluminal pressures were measured in and compared between patch-supplemented and nonsupplemented constructs.

Results—Mean ± SD leakage pressure was significantly greater for the patch-supplemented anastomoses (81.8 ± 6.7 mm Hg) than for the nonsupplemented anastomoses (28.0 ± 6.7 mm Hg). Maximum intraluminal pressures were not significantly different between the groups.

Conclusions and Clinical Relevance—Serosal patch–supplemented anastomoses were able to sustain a significantly higher pressure before leakage than were nonsupplemented anastomoses in intestinal specimens from canine cadavers. The serosal patch supplementation may protect against leakage immediately after enterectomy in dogs.
Language development in infants
Authors: Langus Alan , Nespor Marina
Published: July 2013

In this article we discuss experimental work on language acquisition that we have carried out in recent years. We first describe the most common methods used in infant research, then we concentrate on linguistic rhythm and the aspects of language that might be learned in the first year of life on the basis of signals contained in the speech stream. These include the basic level of rhythm carried by the two most basic phonological categories of consonants and vowels, and rhythmic alternation at the phrase level and its signal to syntax. Because linguistic rhythm is one of the first aspects of language that infants perceive and represent, the research discussed may help to diagnose hearing problems and lead to new ways of training individuals with speech impairments.
Safety and School Travel
Authors: Larsen Kristian , Buliung Ron N. , Faulkner Guy E. J.
Published: July 2013

This study examines the relationship between safety, the built environment, and the mode of travel to and from school. The paper contributes to the literature by analyzing the actual route traveled through the use of objective traffic data within school neighborhoods. Parents and children completed a survey and mapping exercise to obtain travel routes to and from school, a methodological improvement over network shortest-path analysis. Manual traffic counts around the sampled schools (n = 17) were conducted. Logistic regression analysis confirmed a priori expectations about the effects of distance, gender, and the number of vehicles per licensed driver. New insights into safety were produced through inclusion of objective metrics designed to explore the safety of the pedestrian environment. A higher number of vehicles, a higher number of crossing streets, incomplete sidewalk networks, and the presence of parking facilities emerged as potentially important transport supply-, design-, and safety-related factors. If children perceived their neighborhood to be a safe area in which to walk alone, they were also more likely to walk. For parents, the perception that strangers were present and the presence of busy streets influenced the mode of travel. Different effects were produced across separately estimated home-to-school and school-to-home models.
The First Year of Driving
Authors: Farah Haneen , Musicant Oren , Shimshoni Yaara , Toledo Tomer , Grimberg Einat , Omer Haim , Lotan Tsippy
Published: July 2013

This study examines the impact of the provision of feedback and guidance about parental monitoring on the safety performance of young male drivers during their first year of driving. The research used an in-vehicle data recorder (IVDR), which documented events of extreme gravitational forces measured in the vehicles that participated in the experiment. Two hundred forty-two families of young male drivers participated in the research. Participants were randomly allocated into four groups: (a) family feedback, no guidance, in which all members of a family were exposed to feedback on their own driving and on that of other family members; (b) family feedback, parental guidance, in which, in addition to the family feedback, parents received personal guidance on ways to enhance their involvement with and monitor their sons' driving; (c) individual feedback, no guidance, in which family members received feedback only on their own driving behavior and not that of other family members; and (d) a control group, which received no feedback at all. IVDRs were installed in family cars for 12 months, starting from the time that the young driver received his driver's license. This period included the initial 3 months of the accompanied driving phase and 9 months of independent driving. The driving exposure of young drivers increased significantly during the solo period compared with that during the accompanied period. The results indicate substantial differences in behavior between young drivers in the control group and the group that received both feedback and guidance on parental involvement.
Effects of License Plate Attributes on Automatic License Plate Recognition
Authors: Findley Daniel J. , Cunningham Christopher M. , Chang Jeffrey C. , Hovey Kyle A. , Corwin Michael A.
Published: July 2013

This paper describes an experiment designed to develop a comprehensive and thorough understanding of the readability of North Carolina's license plates with an automatic license plate recognition system. This research focused on law enforcement applications and used two infrared camera systems for data collection in a controlled environment involving more than 900 license plates. The field test was conducted in a controlled environment under the following settings and conditions: a test vehicle traveling at 25 mph, nighttime evaluation, closed test track, 40 ft of spacing of license plates, 9 ft of lateral offset between the license plates and camera, standard issue and specialty plate types, standard syntax and personalized plates, and various license plate ages and conditions. The key finding of this research project is that the current, standard issue license plate with characters in blue ink has the highest capture and read rates among the plates tested in this study. Factors that decreased the capture and read rates were personalized syntax, specialty license plates, and the presence of stacked characters on a specialty license plate.
Estimating the Impacts of Police Enforcement Stops on Freeway Operations and Capacity
Authors: Carrick Grady , Washburn Scott
Published: July 2013

Over the years, some police agencies have sought to be good stewards of urban traffic flow by reducing their emergency lights while on roadside enforcement stops, particularly during peak hours. Over the past decade, however, move-over laws that require motorists to slow down or vacate the lane adjacent to the stopped emergency vehicle have been implemented in every state. As a consequence, the traffic impacts of police enforcement stops have shifted from a distraction that might slow traffic to a mandate for drivers to change lanes or slow down. From a highway capacity standpoint, the enforcement stop can be modeled as a theoretical lane-blocking event adjusted for motorists' compliance with move-over laws. This research examined 13,416 enforcement stops conducted near roadway traffic detectors on Florida freeways and shows that police enforcement stops reduced the available capacity by between 54% and 58% on two-lane freeways, 35% and 41% on three-lane facilities, 23% and 30% on four-lane facilities, and 14% and 22% when five lanes were present. Regression analysis examined factors to explain the speed of vehicles passing stops and showed that the number of lanes, posted speed limits, and ambient lighting conditions were statistically significant factors. Police agencies should therefore consider implementing policies in which they use their emergency lighting equipment throughout the duration of enforcement stops since they improve compliance with move-over laws and, ostensibly, safety. Breakdowns were not explicitly modeled and are likely not a deterministic measure, so police activity during periods of high traffic flow and congestion should be reserved for compelling traffic safety needs.
Effectiveness and Site Selection Criteria for Red Light Camera Systems
Authors: Ko Myunghoon , Geedipally Srinivas Reddy , Walden Troy Duane
Published: July 2013

The objective of this paper is to evaluate the safety effectiveness of automated traffic enforcement systems, that is, red light cameras, installed at 254 signalized intersections in 32 jurisdictions in Texas. In addition, criteria for site selection were evaluated to provide analytical resources for camera installation. A before–after study by the empirical Bayesian methodology was performed to remove the regression-to-mean bias during the evaluation of treatments. The results indicate significant decreases in the incidences of all types of red light running (RLR) crashes and right-angle RLR crashes by 20% and 24%, respectively. A significant increase of 37% for rear-end RLR crashes was discovered. The study results suggest that a significant safety benefit for red light cameras is achieved if intersections have four or more RLR crashes per year or have two or more RLR crashes per 10,000 vehicles. Red light cameras show counterproductive results if intersections experience fewer than two RLR crashes per year or have one crash per 10,000 vehicles per year.
Emerging Role of Sphingosine-1-phosphate in Inflammation, Cancer, and Lymphangiogenesis
Authors: Huang Wei-Ching , Nagahashi Masayuki , Terracina Krista , Takabe Kazuaki
Published: July 2013

The main function of the lymphatic system is to control and maintain fluid homeostasis, lipid transport, and immune cell trafficking. In recent years, the pathological roles of lymphangiogenesis, the generation of new lymphatic vessels from preexisting ones, in inflammatory diseases and cancer progression are beginning to be elucidated. Sphingosine-1-phosphate (S1P), a bioactive lipid, mediates multiple cellular events, such as cell proliferation, differentiation, and trafficking, and is now known as an important mediator of inflammation and cancer. In this review, we will discuss recent findings showing the emerging role of S1P in lymphangiogenesis, in inflammation, and in cancer.
Genetic Deletion of Prostacyclin IP Receptor Exacerbates Transient Global Cerebral Ischemia in Aging Mice
Authors: Shakil Hania , Saleem Sofiyan
Published: July 2013

Transient global cerebral ischemia causes delayed neuronal death in the hippocampal CA1 region. It also induces an up regulation of cyclooxygenase 2 (COX-2), which generates several metabolites of arachidonic acid, known as prostanoids, including Prostaglandin I2 (PGI2). The present study investigated whether the PGI2 IP receptor plays an important role in brain injury after global cerebral ischemia in aged mice. Adult young (2–3 months) and aged (12–15 months) male C57Bl/6 wild-type (WT) or IP receptor knockout (IP KO) mice underwent a 12 min bilateral common carotid artery occlusion (BCCAO) or a sham surgery. Behavior tests (neurologic deficit and T-maze) were performed 3 and 7 days after BCCAO. After seven days of reperfusion, the numbers of cells positive for markers of neurons, astrocytes, microglia, myeloperoxidase (MPO) and phosphorylated CREB (p-CREB) were evaluated immunohistochemically. Interestingly, in young and aged IP KO ischemic mice, there was a significant increase (p < 0.01) in cognitive deficit, hippocampal CA1 pyramidal neuron death, microglia and MPO activation, while p-CREB was reduced as compared to their corresponding WT controls. These data suggest that following ischemia, IP receptor deletion contributes to memory and cognitive deficits regulated by the CREB pathway and that treatment with IP receptor agonists could be a useful target to prevent harmful consequences.
Astrocyte Regulation of CNS Inflammation and Remyelination
Authors: Claycomb Kumiko , Johnson Kasey , Winokur Paige , Sacino Anthony , Crocker Stephen
Published: July 2013

Astrocytes regulate fundamentally important functions to maintain central nervous system (CNS) homeostasis. Altered astrocytic function is now recognized as a primary contributing factor to an increasing number of neurological diseases. In this review, we provide an overview of our rapidly developing understanding of the basal and inflammatory functions of astrocytes as mediators of CNS responsiveness to inflammation and injury. Specifically, we elaborate on ways that astrocytes actively participate in the pathogenesis of demyelinating diseases of the CNS through their immunomodulatory roles as CNS antigen presenting cells, modulators of blood brain barrier function and as a source of chemokines and cytokines. We also outline how changes in the extracellular matrix can modulate astrocytes phenotypically, resulting in dysregulation of astrocytic responses during inflammatory injury. We also relate recent studies describing newly identified roles for astrocytes in leukodystrophies. Finally, we describe recent advances in how adapting this increasing breadth of knowledge on astrocytes has fostered new ways of thinking about human diseases, which offer potential to modulate astrocytic heterogeneity and plasticity towards therapeutic gain. In summary, recent studies have provided improved insight in a wide variety of neuroinflammatory and demyelinating diseases, and future research on astrocyte pathophysiology is expected to provide new perspectives on these diseases, for which new treatment modalities are increasingly necessary.
Construction Delay Analysis Techniques—A Review of Application Issues and Improvement Needs
Authors: Braimah Nuhu
Published: July 2013

The time for performance of a project is usually of the essence to the employer and the contractor. This has made it quite imperative for contracting parties to analyse project delays for purposes of making right decisions on potential time and/or cost compensation claims. Over the years, existing delay analysis techniques (DATs) for aiding this decision-making have been helpful but have not succeeded in curbing the high incidence of disputes associated with delay claims resolutions. A major source of the disputes lies with the limitations and capabilities of the techniques in their practical use. Developing a good knowledge of these aspects of the techniques is of paramount importance in understanding the real problematic issues involved and their improvement needs. This paper seeks to develop such knowledge and understanding (as part of a wider research work) via: an evaluation of the most common DATs based on a case study, a review of the key relevant issues often not addressed by the techniques, and the necessary improvements needs. The evaluation confirmed that the various techniques yield different analysis results for the same delay claims scenario, mainly due to their unique application procedures. The issues that are often ignored in the analysis but would also affect delay analysis results are: functionality of the programming software employed for the analysis, resource loading and levelling requirements, resolving concurrent delays, and delay-pacing strategy. Improvement needs by way of incorporating these issues in the analysis and focusing on them in future research work are the key recommendations of the study.
Dye Modification Effects on TaON for Photocatalytic Hydrogen Production from Water
Authors: Hagiwara Hidehisa , Nagatomo Masakiyo , Seto Chihiro , Ida Shintaro , Ishiahara Tatsumi
Published: July 2013

Modification effects of porphyrin dyes on the photocatalytic activity of tantalum (oxy)nitride (TaON) were investigated. The nitrogen content in tantalum (oxy)nitride was increased by increasing the heat treatment period. The optimized nitridation conditions were found to be calcination at 800 °C for 14 h under a NH3 gas flow (25 mL min−1). Among the porphyrin dyes examined, pentamethylene bis[4-(10,15,20-triphenylporphine-5-yl) benzoate]-dizinc (II) (Zn-TPPD) showed the most positive effect on the photocatalytic activity of TaON for H2 production from Na2S aqueous solution. From the results of the photocatalytic reaction using various combinations of catalyst components, it was found that the modification dye and PtOx co-catalysts were necessary to achieving photocatalytic H2 formation. In the PtOx/Zn-TPPD/TaON photocatalyst, the expected charge transfer mechanism was a two-step excitation of both TaON and Zn-TPPD, and the oxidation and reduction sites were TaON and PtOx co-catalyst, respectively. These results indicate that dye modification has the potential to improve the photocatalytic activity of various (oxy)nitride photocatalysts.
Linking Informal and Formal Electronics Recycling via an Interface Organization
Authors: Williams Eric , Kahhat Ramzy , Bengtsson Magnus , Hayashi Shiko , Hotta Yasuhiko , Totoki Yoshiaki
Published: July 2013

Informal recycling of electronics in the developing world has emerged as a new global environmental concern. The primary approach to address this problem has been command-and-control policies that ban informal recycling and international trade in electronic scrap. These bans are difficult to enforce and also have negative effects by reducing reuse of electronics, and employment for people in poverty. An alternate approach is to link informal and formal sectors so as to maintain economic activity while mitigating environmental damages. This article explores the idea of an interface organization that purchases components and waste from informal dismantlers and passes them on to formal processors. Environmental, economic and social implications of interface organizations are discussed. The main environmental questions to resolve are what e-scrap components should be targeted by the interface organization, i.e., circuit boards, wires, and/or plastic parts. Economically, when formal recycling is more profitable (e.g., for circuit boards), the interface organization is revenue positive. However, price subsidies are needed for copper wires and residual waste to incentivize informal dismantlers to turn in for formal processing. Socially, the potential for corruption and gaming of the system is critical and needs to be addressed.
In Vivo Cytogenotoxicity and Oxidative Stress Induced by Electronic Waste Leachate and Contaminated Well Water
Authors: Bakare Adekunle , Alabi Okunola , Gbadebo Adeyinka , Ogunsuyi Olusegun , Alimba Chibuisi
Published: July 2013

Environmental, plant and animal exposure to hazardous substances from electronic wastes (e-wastes) in Nigeria is increasing. In this study, the potential cytogenotoxicity of e-wastes leachate and contaminated well water samples obtained from Alaba International Electronic Market in Lagos, Nigeria, using induction of chromosome and root growth anomalies in Allium cepa, and micronucleus (MN) in peripheral erythrocytes of Clarias gariepinus, was evaluated. The possible cause of DNA damage via the assessments of liver malondialdehyde (MDA), catalase (CAT), reduced glutathione (GSH) and superoxide dismutase (SOD) as indicators of oxidative stress in mice was also investigated. There was significant (p < 0.05) inhibition of root growth and mitosis in A. cepa. Cytological aberrations such as spindle disturbance, C-mitosis and binucleated cells, and morphological alterations like tumor and twisting roots were also induced. There was concentration-dependent, significant (p < 0.05) induction of micronucleated erythrocytes and nuclear abnormalities such as blebbed nuclei and binucleated erythrocytes in C. gariepinus. A significant increase (p < 0.001) in CAT, GSH and MDA with concomitant decrease in SOD concentrations were observed in the treated mice. Pb, As, Cu, Cr, and Cd analyzed in the tested samples contributed significantly to these observations. This shows that the well water samples and leachate contained substances capable of inducing somatic mutation and oxidative stress in living cells; and this is of health importance in countries with risk of e-wastes exposure.