bluuebunny/crossref_metadata_2025 huggingface dataset:
Website navigation and surgical education
Authors: Mutter D , Becmeur F , Maisonneuve H , Kirch M , Chekan E , Marescaux J
Published: April 2006

We evaluated the way in which medical students interacted with a surgical education Website. Ten medical students on their paediatric surgery rotation were asked to study online a chapter on intussusception in young children, for a period of 1 h. The computer was connected by video link to a video-recorder that recorded their navigation movements, i.e. navigation time, time spent in front of each page, stepwise, progressive exploration of the surgical contents, and use of interactive links. The students were asked to complete a questionnaire to identify their overall competency in computers and Internet navigation capabilities. The mean time spent viewing the entire Website was 48 min (range 31–63) and the mean time spent on the assigned chapter was 38 min (range 8–53). Each page out of 14 within the chapter was visited a mean of 1.8 times (range 0–10). Access to video selections occurred after a mean of 10 min after beginning the session. A connection was made to the video a mean of 2.3 times per session. The mean time spent viewing video footage was 9 min (24% of the time spent viewing the chapter). The questionnaire results showed that few students regularly accessed the Internet for educational purposes.
Overview of Anaerobic Treatment: Thermophilic and Propionate Implications ‐ Keynote Address—Association of Environmental Engineering and Science Professors—78th Annual Water Environment Federation Technical Exposition and Conference, Washington, D.C., Oct. 29–Nov. 2, 2005
Authors: Speece R. E. , Boonyakitsombut Saroch , Kim Moonil , Azbar Nuri , Ursillo Pepi
Published: April 2006

Difficulties in achieving low propionate concentrations in anaerobically treated effluents are frequently reported in the literature (Ahring, 1994; Kugelman and Guida, 1989; Rimkus et al., 1982), especially at thermophilic temperatures, with concentrations as high as 1000 to 9600 mg/L sometimes produced. This paper will detail the effect of several variables on the performance of both mesophilic and thermophilic regimes. Studies concerning the effect of the following four important factors on performance are included: reactor configuration, inorganic nutrient supplementation, substrate characteristics, and the unique role of microbial consortia proximity in enhancing performance. Reactor configuration modifications, essential nutrient additions, and the importance of close microbial proximity were all found to contribute to improvement in thermophilic anaerobic digestion in all the studies. It was found that, in substrates that shunt significant amounts of the electron donor through propionate, performance was critically related to reactor optimization, with propionate removal efficiency considerably improved using intact upflow anaerobic sludge blanket granules, less so in a homogenized granule slurry blanket, and noticeably reduced even more when the completely stirred reactor configuration of homogenized granules was used. The critical importance of extremely close microbial consortia proximity in maintaining hydrogen intermediates at very low levels to efficiently convert propionate to hydrogen and acetate was demonstrated. Compared to mesophilic digestion, thermophilic digestion manifested elevated levels of propionate, except in the nonmixed reactors, which had close microbial consortia proximity. The reactor configuration with the best results was the anaerobic digestion elutriated phased treatment (ADEPT) scheme, in which the raw sludge was elutriated of its fermenting volatile fatty acids, as they are generated in a short 5‐ to 8‐day solids retention time (SRT) in one reactor and the elutriate then metabolized by passing up through a methanogenic granule or slurry blanket (with its close microbial consortia proximity) in a separate reactor with a 20‐ to 50‐day SRT. Loading rates and performance of the ADEPT reactor configuration were superior to the standard continuously stirred tank reactor, and ADEPT thermophilic temperatures allowed higher organic loading rates without high propionate concentrations in the effluent.
Human Rights Treaties, Invalid Reservations, and State Consent
Authors: Goodman Ryan
Published: April 2006

A continuing debate in international human rights law concerns the result of invalid reservations to multilateral treaties. The cardinal rule holds that a reservation cannot be incompatible with the object and purpose of a treaty. Yet a normative puzzle remains: what legal remedy should follow the determination of the invalidity of a reservation? Leading commentators have discussed a limited set of options. Three choices can be identified:
Legal Aspects of the IMF/WTO Relationship: The Fund’s Articles of Agreement and the Wto Agreements
Authors: Siegel Deborah E.
Published: April 2006

The relationship between the International Monetary Fund (Fund) and the World Trade Organization (WTO) is a continuation of the long-standing relationship between the Fund and the Contracting Parties to the General Agreement on Tariffs and Trade (GATT), as modified by new developments associated with the establishment of the WTO. The two organizations generally act in a complementary and cooperative fashion. Discussions about the legal aspects of the relationship, however, including recent WTO dispute settlement cases concerning the Fund, reflect misunderstandings about the legal nature of Fund activities and how they relate to the WTO provisions on this relationship. In addition, certain issues about the Fund/WTO relationship are not clearly resolved in the text of the WTO Agreements. This article discusses key legal provisions of the WTO Agreements that concern the Fund and explains the legal nature of the Fund’s activities relevant to these provisions.
Introduction and Overview
Authors: Bodansky Daniel , Crook John R.
Published: April 2006

In August 2001, the International Law Commission (ILC) adopted its “Draft Articles on the Responsibility of States for Internationally Wrongful Acts,” bringing to completion one of the Commission’s longest running and most controversial studies. On December 12, 2001, the United Nations General Assembly adopted Resolution 56/83, which “commend [ed the articles] to the attention of Governments without prejudice to the question of their future adoption or other appropriate action.”
Efforts to Address Iraqi Compliance with UN Weapons Inspections
Authors: Murphy Sean D.
Published: April 2006

At the conclusion of the 1991 UN enforcement action against Iraq, the Security Council adopted a resolution setting the terms for a cease-fire. The resolution required, among other things, that Iraq “unconditionally accept the destruction, removal, or rendering harmless, under international supervision,” of all chemical and biological weapons, all ballistic missiles with a range greater than 150 kilometers, and associated materials and facilities. Further, the resolution provided for the creation of a UN special commission to carry out “on-site inspection of Iraq's biological, chemical and missile capabilities,” and ordered Iraq to yield such weapons to the commission for “destruction, removal or rendering harmless.” Similar requirements were imposed with respect to the acquisition and development of nuclear weapons. While maintaining the economic sanctions imposed on Iraq after its invasion of Kuwait in August 1990, the Security Council allowed exports to Iraq of foodstuffs and medical supplies (on the condition that a UN sanctions committee had been notified) and also other commodities (if approved by the same committee). The Security Council decided that the sanctions regime would be lifted, however, once Iraq complied with its obligations on the destruction and monitoring of weapons of mass destruction.
Preemption, Iraq, and International Law
Authors: Taft William H. , Buchwald Todd F.
Published: April 2006

Preemption comes in many forms and what we think of it depends on the circumstances. One state may not strike another merely because the second might someday develop an ability and desire to attack it. Yet few would criticize a strike in the midst of an ongoing war against a second state’s program to develop new types of weapons. Between these two examples lie countless fact patterns.

In the end, each use offeree must find legitimacy in the facts and circumstances that the state believes have made it necessary. Each should be judged not on abstract concepts, but on the particular events that gave rise to it. While nations must not use preemption as a pretext for aggression, to be for or against preemption in the abstract is a mistake. The use of force preemptively is sometimes lawful and sometimes not.
What Happens Now? The United Nations After Iraq
Authors: Franck Thomas M.
Published: April 2006

Thirty-three years ago I published an article in this Journal entitled Who Killed Article 2 (4)? or: Changing Norms Governing the Use of Force by States, which examined the phenomenon of increasingly frequent resort to unlawful force by Britain, France, India, North Korea, the Soviet Union, and the United States. The essay concluded with this sad observation:

The failure of the U.N. Charter's normative system is tantamount to the inability of any rule, such as that set out in Article 2(4), in itself to have much control over the behavior of states. National self-interest, particularly the national self-interest of the super- Powers, has usually won out over treaty obligations. This is particularly characteristic of this age of pragmatic power politics. It is as if international law, always something of a cultural myth, has been demythologized. It seems this is not an age when men act by principles simply because that is what gentlemen ought to do. But living by power alone ... is a nerve-wracking and costly business.
International Law, Sovereignty, and American Constitutionalism: Reflections on the Customary International Law Debate
Authors: Akinikoff T. Alexander
Published: April 2006

The preceding contributions to this Agora investigate the discernible trend in Supreme Court decisions of citing international legal materials in support of a conclusion about domestic constitutional law. Discussion of this rather limited use of international law—far short of the notion that “[i] nternational law is part of our law”—implicates a deeper set of questions about democracy, sovereignty, and sources of law: Is recourse to international sources a fundamental affront to notions of democratic self-rule, or is it the natural development of a maturing legal system—one moving toward new understandings of sovereignty and popular sovereignty appropriate to an increasingly interconnected web of transnational legal relations? I will argue here for the latter position, and from this perspective the occasional illustrative citation to international norms in the course of a conventional constitutional law opinion is an invitation to broader thought more than a fire bell in the night.
Judicial Lawmaking at the WTO: Discursive, Constitutional, and Political Constraints
Authors: Steinberg Richard H.
Published: April 2006

Since the establishment of the World Trade Organization (WTO), commentators have debated the wisdom of replacing the model of political-diplomatic dispute settlement under the General Agreement on Tariffs and Trade (GATT) with a model of legalized dispute settlement. Under the GATT model, a dispute settlement panel report could be given full legal force only if adopted by a consensus of GATT Contracting Parties, including the party that lost the case. Under the WTO model, a report of the panel or the Appellate Body is adopted automatically unless WTO members, including the prevailing member, decide by consensus to block it, which is sometimes referred to as “negative consensus.” Many analysts whose work has focused on the politics of dispute settlement have emphasized the success, political flexibility, and apparent sustainability of the older model and cautioned that the legalized approach might be too cumbersome in various political contexts. Those favoring the legalized approach have emphasized its legitimizing capacity and potential to constrain more powerful WTO members from engaging in unilateral or rule-breaking behavior.
Justiciability of Economic, Social, and Cultural Rights: Should There Be an International Complaints Mechanism to Adjudicate the Rights to Food, Water, Housing, and Health?
Authors: Dennis Michael J. , Stewart David P.
Published: April 2006

Should all internationally recognized human rights—economic, social, and cultural rights, as well as civil and political rights—be subject to the same individual-complaints procedures? This issue is now before a newly convened working group of the UN Commission on Human Rights. At its first meeting, from February 23 to March 5,2004, the Working Group debated the feasibility of elaborating an optional protocol to the International Covenant on Economic, Social and Cultural Rights (ICESCR) that would provide for the adjudication of individual and group complaints against states under that Covenant. Participating states were in sharp disagreement over the viability of the proposal, however, and the session ended in disarray. Since the Commission has recommended renewal of the Working Group’s mandate for two years, the issue remains open.
Hyperownership in a Time of Biotechnological Promise: The International Conflict to Control the Building Blocks of Life
Authors: Safirin Sabrina
Published: April 2006

“Hyperownership” describes in a word the present international legal landscape with respect to genetic material. At issue is who should own or control access to the subcellular genetic sequences that direct the structure and characteristics of all living things, or, in popular usage, nature’s or God’s blueprints for life. Traditionally, genetic material belonged to a global commons or open system. No one exclusively owned this material and countries freely shared it. In sharp contrast, today exclusive ownership and restrictions on the sharing of genetic material are the international norm.
Transforming Growth Factor-β and Natural Killer T-Cells Are Involved in the Protective Effect of a Bacterial Extract on Type 1 Diabetes
Authors: Alyanakian Marie-Alexandra , Grela Françoise , Aumeunier Aude , Chiavaroli Carlo , Gouarin Christine , Bardel Emilie , Normier Gérard , Chatenoud Lucienne , Thieblemont Nathalie , Bach Jean-François
Published: April 2006

The onset of type 1 diabetes in NOD mice is delayed by oral administration of a bacterial extract (OM-85) and can be completely prevented by its intraperitoneal administration. Optimal prevention is observed when starting treatment at 3 or 6 weeks of age, and some effect is still observed with treatment at 10 weeks of age. Using genetically deficient mice and cytokine-neutralizing monoclonal antibodies, we demonstrate here that the therapeutic effect does not involve T-helper type 2 cytokines (interleukin [IL]-4 and -10) but is tightly dependent on transforming growth factor (TGF)-β. Natural killer T-cells also participate in the therapeutic effect because CD1d−/− NOD mice are partially resistant to the protective effect of OM-85. The question remains of the specificity of the protective effect of OM-85, which may include proinflammatory components. It will thus be important to further characterize the molecular components that afford protection from type 1 diabetes. Lipopolysaccharide is excluded, but other Toll-like receptor (TLR) agonists could be involved because OM-85 stimulated dendritic cells and induced TGF-β production by splenocytes in a TLR-2–, TLR-4–, and MyD88-dependent fashion.
Glibenclamide Treatment Recruits β-Cell Subpopulation Into Elevated and Sustained Basal Insulin Synthetic Activity
Authors: Ling Zhidong , Wang Qidi , Stangé Geert , In’t Veld Peter , Pipeleers Daniel
Published: April 2006

Use of sulfonylureas in diabetes treatment is based on their insulin-releasing effect on pancreatic β-cells. Prolonged action is known to degranulate β-cells, but functional consequences have not been examined at the cellular level. This study investigates influences of in vivo (48-h) and in vitro (24-h) glibenclamide treatment on the functional state of the β-cell population. Both conditions decreased cellular insulin content by >50% and caused an elevated basal insulin biosynthetic activity that was maintained for at least 24 h after drug removal. Glibenclamide stimulation of basal insulin synthesis was not achieved after a 2-h exposure; it required a calcium-dependent translational activity and involved an increase in the percent activated β-cells (50% after glibenclamide pretreatment vs. 8% in control cells). The glibenclamide-activated β-cell subpopulation corresponded to the degranulated β-cell subpopulation that was isolated by fluorescence-activated cell sorter on the basis of lower cellular sideward scatter. Glibenclamide pretreatment did not alter cellular rates of glucose oxidation but sensitized β-cells to glucose-induced changes in metabolic redox and insulin synthesis and release. In conclusion, chronic exposure to glibenclamide results in degranulation of a subpopulation of β-cells, which maintain an elevated protein and insulin synthetic activity irrespective of the presence of the drug and of glucose. Our study demonstrates that the in situ β-cell population also exhibits a functional heterogeneity that can vary with drug treatment. Glibenclamide induces degranulated β-cells with a sustained elevated basal activity that might increase the risk for hypoglycemic episodes.
Glucose-Induced Reactive Oxygen Species Cause Apoptosis of Podocytes and Podocyte Depletion at the Onset of Diabetic Nephropathy
Authors: Susztak Katalin , Raff Amanda C. , Schiffer Mario , Böttinger Erwin P.
Published: April 2006

Diabetic nephropathy is the most common cause of end-stage renal disease in the U.S. Recent studies demonstrate that loss of podocytes is an early feature of diabetic nephropathy that predicts its progressive course. Cause and consequences of podocyte loss during early diabetic nephropathy remain poorly understood. Here, we demonstrate that podocyte apoptosis increased sharply with onset of hyperglycemia in Ins2Akita (Akita) mice with type 1 diabetes and Leprdb/db (db/db) mice with obesity and type 2 diabetes. Podocyte apoptosis coincided with the onset of urinary albumin excretion (UAE) and preceded significant losses of podocytes in Akita (37% reduction) and db/db (27% reduction) mice. Increased extracellular glucose (30 mmol/l) rapidly stimulated generation of intracellular reactive oxygen species (ROS) through NADPH oxidase and mitochondrial pathways and led to activation of proapoptotic p38 mitogen-activated protein kinase and caspase 3 and to apoptosis of conditionally immortalized podocytes in vitro. Chronic inhibition of NADPH oxidase prevented podocyte apoptosis and ameliorated podocyte depletion, UAE, and mesangial matrix expansion in db/db mice. In conclusion, our results demonstrate for the first time that glucose-induced ROS production initiates podocyte apoptosis and podocyte depletion in vitro and in vivo and suggest that podocyte apoptosis/depletion represents a novel early pathomechanism(s) leading to diabetic nephropathy in murine type 1 and type 2 diabetic models.
Activation of AMP-Activated Protein Kinase Reduces Hyperglycemia-Induced Mitochondrial Reactive Oxygen Species Production and Promotes Mitochondrial Biogenesis in Human Umbilical Vein Endothelial Cells
Authors: Kukidome Daisuke , Nishikawa Takeshi , Sonoda Kazuhiro , Imoto Koujiro , Fujisawa Kazuo , Yano Miyuki , Motoshima Hiroyuki , Taguchi Tetsuya , Matsumura Takeshi , Araki Eiichi
Published: April 2006

We previously proposed that the production of hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) is a key event in the development of diabetes complications. The association between the pathogenesis of diabetes and its complications and mitochondrial biogenesis has been recently reported. Because metformin has been reported to exert a possible additional benefit in preventing diabetes complications, we investigated the effect of metformin and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on mtROS production and mitochondrial biogenesis in cultured human umbilical vein endothelial cells. Treatment with metformin and AICAR inhibited hyperglycemia-induced intracellular and mtROS production, stimulated AMP-activated protein kinase (AMPK) activity, and increased the expression of peroxisome proliferator–activated response-γ coactivator-1α (PGC-1α) and manganese superoxide dismutase (MnSOD) mRNAs. The dominant negative form of AMPKα1 diminished the effects of metformin and AICAR on these events, and an overexpression of PGC-1α completely blocked the hyperglycemia-induced mtROS production. In addition, metformin and AICAR increased the mRNA expression of nuclear respiratory factor-1 and mitochondrial DNA transcription factor A (mtTFA) and stimulated the mitochondrial proliferation. Dominant negative–AMPK also reduced the effects of metformin and AICAR on these observations. These results suggest that metformin normalizes hyperglycemia-induced mtROS production by induction of MnSOD and promotion of mitochondrial biogenesis through the activation of AMPK-PGC-1α pathway.
Racial Differences in Adiponectin in Youth
Authors: Lee SoJung , Bacha Fida , Gungor Neslihan , Arslanian Silva A.
Published: April 2006

OBJECTIVE—The purpose of this study was to investigate 1) whether adiponectin is associated with insulin sensitivity independent of visceral adipose tissue in African-American and Caucasian youth and 2) whether adiponectin is associated with racial differences in insulin sensitivity.

RESEARCH DESIGN AND METHODS—Total body fat was measured by dual-energy X-ray absorptiometry and abdominal adipose tissue with computed tomography. Insulin sensitivity was measured by a 3-h hyperinsulinemic-euglycemic clamp.

RESULTS—Adiponectin was inversely associated (P < 0.01) with visceral adipose tissue, fasting insulin, and proinsulin and was positively related (P < 0.01) to insulin sensitivity after controlling for Tanner stage and sex independent of race. Stepwise multiple regression revealed that adiponectin was a strong independent predictor of insulin sensitivity, explaining 27% of the variance in insulin sensitivity. When subjects were categorized into tertiles of visceral adipose tissue and further low (≤50th) and high (>50th) adiponectin groups, insulin sensitivity was significantly different across the visceral adipose tissue groups (main effect, P < 0.01) in both races. However, within each visceral adipose tissue group, subjects with high adiponectin had higher insulin sensitivity (main effect, P < 0.05) than subjects with low adiponectin, independent of race. Racial differences in insulin sensitivity remained significant (P < 0.01) after controlling for leptin and visceral adipose tissue but not (P > 0.05) after additional adjustment for adiponectin.

CONCLUSIONS—Adiponectin is associated with insulin sensitivity independent of visceral adipose tissue in both African-American and Caucasian youth. Low adiponectin in African-American youth may be a biological marker that predisposes them to a greater risk of insulin resistance.
Effects of Different Insulin Regimes on Postprandial Myocardial Perfusion Defects in Type 2 Diabetic Patients
Authors: Scognamiglio Roldano , Negut Christian , de Kreutzenberg Saula Vigili , Tiengo Antonio , Avogaro Angelo
Published: April 2006

OBJECTIVE—Postprandial glycemia is an independent risk factor for cardiovascular disease that is more powerful than fasting glycemia and determines myocardial perfusion defects in type 2 diabetes. We examined the efficacy of two different insulin regimes (regular insulin and insulin analog) in controlling postprandial hyperglycemia and in preventing myocardial perfusion abnormalities.

RESEARCH DESIGN AND METHODS—A total of 20 consecutive type 2 diabetic patients and 20 control subjects were enrolled in this randomized, three-way, cross-over, placebo-controlled study. Myocardial perfusion was assessed by myocardial contrast echocardiography (MCE) in fasting and postprandial (120 min) state.

RESULTS—Insulin analog was associated with lower, but not statistically significant, postprandial glycemia than regular insulin (glucose increase: 116 ± 8 vs. 136 ± 5%, P = NS). However, the area under the curve following insulin analog was significantly lower than regular insulin (18,354 ± 702 vs. 20,757 ± 738 mg per 120 min, P = 0.032). Fasting myocardial flow velocity (β), myocardial blood volume (MBV), and myocardial blood flow (MBF) did not differ between control and type 2 diabetic subjects. Postprandial β (0.67 ± 0.24 vs. 0.92 ± 0.25, P < 0.01), MBV (8.4 ± 2 vs. 10.9 ± 1.2, P < 0.01), and MBF (5.6 ± 2 vs. 9.9 ± 2.8, P < 0.01) increased significantly in control subjects. In type 2 diabetes, during placebo in the postprandial state, β increased (0.65 ± 0.27 vs. 0.89 ± 0.24, P < 0.01), while MBV (8.34 ± 1.2 vs. 4.3 ± 1.3, P < 0.01) and MBF (5.4 ± 1.5 vs. 3.4 ± 0.9, P < 0.01) decreased. Similar changes in MCE variables were observed after regular insulin: β increased (0.65 ± 0.22 vs. 0.92 ± 0.12, P < 0.01) and MBV (8.2 ± 2 vs. 5.2 ± 1.16, P < 0.01) and MBF (5.4 ± 1.9 vs. 4.2 ± 0.86, P < 0.01) were reduced. After insulin analog, postprandial β (0.66 ± 0.18 vs. 0.9 ± 0.18, P < 0.01), MBV (8.2 ± 1.6 vs. 9.6 ± 1.2, P < 0.01), and MBF (5.4 ± 2 vs. 7.2 ± 1.9, P < 0.01) increased. Values of postprandial MBV and MBF were higher after insulin analog than regular insulin treatment.

CONCLUSIONS—Insulin analog partially reversed myocardial perfusion abnormalities observed in postprandial state by improving glucose control.
The Fidgety Fetus Hypothesis
Authors: Zisser Howard , Jovanovic Lois , Thorsell Ashley , Kupperman Asher , Taylor Larisa J , Ospina Paulina , Hod Mosha
Published: April 2006

OBJECTIVE—To determine whether some offspring of women with diabetes are intrinsically more active than others in utero and whether those who are active are able to normalize their birth weight despite maternal hyperglycemia.

RESEARCH DESIGN AND METHODS—We conducted a three-phase study to view the relationship between fetal movements and subsequent birth weight in women with diabetes. Phase I was designed to assess maternal perception of fetal movements in a population of 10 women with diabetes. To improve our fetal monitoring techniques, in phase II we analyzed fetal movements using the Card Guard home fetal monitoring device (CG 900P) in a population of 13 women with gestational diabetes mellitus (GDM). To apply our observations of fetal movements to a larger population, during phase III we conducted a retrospective analysis of fetal monitoring strips (HP 8041A) from 46 women with GDM to examine the relationship between fetal heart rate (FHR) accelerations and percentile birth weight, corrected for gestational age.

RESULTS—Phase I confirmed that there is little variability in fetal movements (i.e., fetal kicks did not significantly deviate from one another on a day-to-day basis). In phase II, the fetal monitoring strips illustrated that the active fetuses (defined as ≥4 FHR accelerations in a 20-min period) were always active, and the inactive fetuses were always inactive. The mean birth weight percentile, corrected for gestational age, in the active group was 37 vs. 63% in the inactive group (P = 0.05). In phase III, the fetal monitoring strips showed an inverse correlation between the mean number of FHR accelerations and the birth weight of the fetus, corrected for gestational age. The mean birth weight percentile in the active group was 37 vs. 62% in the inactive group (P = 0.0017).

CONCLUSIONS—The fetus appears to play a role in determining its own destiny. Increased fetal activity may minimize the impact of hyperglycemia on subsequent birth weight. The inactive fetus appears to be at a higher risk for glucose-mediated macrosomia.
Impaired Glucose Tolerance of Pregnancy Is a Heterogeneous Metabolic Disorder as Defined by the Glycemic Response to the Oral Glucose Tolerance Test
Authors: Retnakaran Ravi , Zinman Bernard , Connelly Philip W. , Sermer Mathew , Hanley Anthony J.G.
Published: April 2006

OBJECTIVE—Gestational diabetes mellitus (GDM), defined by two abnormal glucose values on a 3-h oral glucose tolerance test (OGTT), is associated with insulin resistance and a low serum concentration of adiponectin. The metabolic implications of impaired glucose tolerance (IGT) of pregnancy (i.e., a single abnormal value on an OGTT), however, are not well established. We sought to evaluate the metabolic phenotype of pregnant women with IGT in relation to the timing of their isolated hyperglycemia.

RESEARCH DESIGN AND METHODS—A cross-sectional study was performed in pregnant women undergoing a 3-h, 100-g OGTT. The OGTT stratified participants into four groups: 1) GDM (n = 48), 2) 1-h IGT (single elevated value at 1 h) (n = 15), 3) 2-h/3-h IGT (single elevated value at either 2 or 3 h) (n = 23), and 4) normal glucose tolerance (NGT) (n = 93). Insulin sensitivity was measured by the validated insulin sensitivity index (ISOGTT) of Matsuda and DeFronzo.

RESULTS—Measures of severity of glycemia (fasting glucose, area under the glucose curve from the OGTT, and glucose challenge test result) were highest in the GDM group, followed by the 1-h IGT, 2-h/3-h IGT, and NGT groups, respectively (each trend P < 0.0001). Consistent with this finding, ISOGTT was highest in the NGT group (5.1), followed by the 2-h/3-h IGT (4.6), 1-h IGT (3.8), and GDM (3.2) groups (trend P < 0.0001). Furthermore, on multiple linear regression analysis of ISOGTT, both GDM and 1-h IGT were independently associated with reduced insulin sensitivity (whereas 2-h/3-h IGT was not). Mean adjusted adiponectin was highest in the NGT group (15.7 μg/ml), followed by the 2-h/3-h IGT (15.6 μg/ml), 1-h IGT (13.7 μg/ml), and GDM (12.0 μg/ml) groups (trend P = 0.0024).

CONCLUSIONS—The metabolic implications of IGT in pregnancy vary in relation to the timing of the abnormal glucose value from the diagnostic OGTT. The metabolic phenotype associated with 1-h IGT resembles that of GDM, whereas the phenotype associated with 2-h/3-h IGT exhibits similarity to that of NGT.
Relation Between Blood Glucose and Coronary Mortality Over 33 Years in the Whitehall Study
Authors: Brunner Eric J. , Shipley Martin J. , Witte Daniel R. , Fuller John H. , Marmot Michael G.
Published: April 2006

OBJECTIVE—Glucose intolerance is a risk factor for coronary disease, but there is uncertainty about the shape of the dose-response relationship between glucose level and risk of coronary mortality. We examined the prospective relation of 2-h postload blood glucose (2hBG) with coronary and other major causes of mortality over 33 years.

RESEARCH DESIGN AND METHODS—A 50-g oral glucose tolerance test (OGTT) was performed at baseline (1967–1969) in 17,869 male civil servants aged 40–64 years.

RESULTS—There were 3,561 coronary deaths during 451,787 person-years of observation. All-cause, cardiovascular, and respiratory mortality were elevated among participants with glucose intolerance. The hazard of coronary mortality rose from 2hBG = 4.6 mmol/l (83 mg/dl [95% CI 4.2–5.3]). The dose-response relation was best fitted by a single slope above this level, with no evidence of nonlinearity, compared with Cox models using other threshold levels, and those containing log 2hBG terms. There was no evidence for a dose-response relationship below 2hBG = 4.6 mmol/l. Between this level and 11.1 mmol/l (200 mg/dl), the age-adjusted hazard ratio was 3.62 (95% CI 2.3–5.6). The graded relationship was attenuated by 45% after adjustment for baseline coronary heart disease (CHD), BMI, systolic blood pressure, blood cholesterol, smoking, physical activity, lung function, and employment grade.

CONCLUSIONS—A threshold model with linear slope best described the dose-response relationship between postload blood glucose and CHD mortality risk.
Higher Levels of HDL Cholesterol Are Associated With a Decreased Likelihood of Albuminuria in Patients With Long-Standing Type 1 Diabetes
Authors: Molitch Mark E. , Rupp Demetra , Carnethon Mercedes
Published: April 2006

OBJECTIVE—The objective of this study was to determine whether high levels of HDL cholesterol are associated with a lower prevalence of albuminuria

RESEARCH DESIGN AND METHODS—We analyzed the lipid profiles of patients with type 1 diabetes of ≥20 years duration in 42 patients with albuminuria (28 microalbuminuria and 14 macroalbuminuria) and 65 patients without increased albumin excretion before any interventions with either statins or ACE inhibitors.

RESULTS—Several characteristics were similar in the two groups: sex, age, duration of diabetes, total cholesterol, LDL cholesterol, and triglycerides. By univariate analysis, significant differences (P < 0.01) were found in HDL cholesterol (albuminuria 1.42 mg/dl, no albuminuria 1.71 mg/dl, P < 0.01), HbA1c (A1C) (albuminuria 8.5%, no albuminuria 7.5%), and proportions with no, background, and proliferative retinopathy (albuminuria 2.4, 16.7, and 81%; no albuminuria 24.6, 52.3, and 23.1%, respectively). When adjusted for age and sex, a 0.26-mmol/l (10-mg/dl) increase in HDL cholesterol is associated with an odds ratio (OR) of 0.70 (95% CI 0.54–0.90) for having albuminuria. In a multivariate model that adjusted for age, sex, diabetes duration, and A1C, for every 0.54-mmol/l (21-mg/dl) increase in HDL cholesterol, patients are approximately half (OR 0.51 [95% CI 0.30–0.86]) as likely to have albuminuria, even after controlling for A1C.

CONCLUSIONS—Higher HDL cholesterol levels may be protective against the development of albuminuria in patients with type 1 diabetes. Whether this is due to the HDL cholesterol levels or whether they serve as a marker for some other mechanism remains to be determined.
Urinary Connective Tissue Growth Factor Excretion Correlates With Clinical Markers of Renal Disease in a Large Population of Type 1 Diabetic Patients With Diabetic Nephropathy
Authors: Nguyen Tri Q. , Tarnow Lise , Andersen Steen , Hovind Peter , Parving Hans-Henrik , Goldschmeding Roel , van Nieuwenhoven Frans A.
Published: April 2006

OBJECTIVE—Levels of connective tissue growth factor (CTGF; CCN-2) in plasma are increased in various fibrotic disorders, including diabetic nephropathy. Recently, several articles have reported a strong increase of urinary CTGF excretion (U-CTGF) in patients with diabetic nephropathy. However, these studies addressed too small a number of patients to allow general conclusions to be drawn. Therefore, we evaluated U-CTGF in a large cross-sectional study of patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Subjects were 318 type 1 diabetic patients and 29 normoglycemic control subjects. U-CTGF was measured by sandwich enzyme-linked immunosorbent assay. Groups were compared by Kruskal-Wallis and Mann-Whitney analysis. The relation between U-CTGF and markers of diabetic nephropathy was determined by regression analysis.

RESULTS—U-CTGF in patients with diabetic nephropathy (n = 89, median 155 pmol/24 h [interquartile range 96–258]) was significantly higher than in microalbuminuric (n = 79, 100 [65–78]) and normoalbuminuric (n = 150, 85 [48–127]) patients and control subjects (n = 29, 100 [78–114]). U-CTGF correlated with urinary albumin excretion (UAE) (R = 0.31) and glomerular filtration rate (R = −0.38) in patients with diabetic nephropathy. A standardized increase in U-CTGF was associated with diabetic nephropathy (odds ratio 2.3 [95% CI 1.7–3.1]), which was comparable with the odds ratios for diabetic nephropathy of increased HbA1c (2.0 [1.5–2.7]), and blood pressure (2.0 [1.5–2.6]).

CONCLUSIONS—This is the first large cross-sectional study addressing U-CTGF in human type 1 diabetes. The observed association of U-CTGF with UAE and glomerular filtration rate might reflect a role of CTGF as progression promoter in diabetic nephropathy.
Evaluation of phage assay for rapid phenotypic detection of rifampicin resistance in Mycobacterium tuberculosis
Authors: Yzquierdo Sergio Luis , Lemus Dihadenys , Echemendia Miguel , Montoro Ernesto , McNerney Ruth , Martin Anandi , Palomino Juan Carlos
Published: April 2006

Background

Conventional methods for susceptibility testing require several months before results can be reported. However, rapid methods to determine drug susceptibility have been developed recently. Phage assay have been reported as a rapid useful tools for antimicrobial susceptibility testing. The aim of this study was to apply the Phage assay for rapid detection of resistance on Mycobacterium tuberculosis strains in Cuba.

Methods

Phage D29 assay was performed on 102 M. tuberculosis strains to detect rifampicin resistance. The results were compared with the proportion method (gold standard) to evaluate the sensitivity and specificity of Phage assay.

Results

Phage assay results were available in 2 days whereas Proportion Methods results were obtain in 42 days. A total of 44 strains were detected as rifampicin resistant by both methods. However, one strains deemed resistant by Proportion Methods was susceptible by Phage assay. The sensitivity and specificity of Phage assay were 97.8 % and 100% respectively.

Conclusion

Phage assay provides rapid and reliable results for susceptibility testing; it's easy to perform, requires no specialized equipment and is applicable to drug susceptibility testing in low income countries where tuberculosis is a major public health problem.
The UN Convention on Jurisdictional Immunities of States and Their Property
Authors: Stewart David P.
Published: April 2006

On December 2, 2004, the UN General Assembly adopted the UN Convention on Jurisdictional Immunities of States and Their Property. Capping more than a quarter of a century of intense international negotiation, the new treaty is the first modern multilateral instrument to articulate a comprehensive approach to issues of state or sovereign immunity from suits in foreign courts. Notably, it embraces the so-called restrictive theory of sovereign immunity, under which governments are subject to essentially the same jurisdictional rules as private entities in respect of their commercial transactions. The treaty was opened for signature on January 17, 2005 (when Austria and Morocco became the first states to sign), and will enter into force when thirty states have deposited their instruments of ratification, acceptance, approval, or accession with the UN secretary-general.
Blind Spots, Shortcuts, and Automation Bias—Researchers Are Aiming to Improve AI Clinical Models
Authors: Abbasi Jennifer , Hswen Yulin
Published: February 2024

This Medical News article is an interview with University of Michigan computer scientist Jenna Wiens, whose research interests lie at the intersection of AI and health care, and JAMA Editor in Chief Kirsten Bibbins-Domingo.
Knowledge, Preference, and Adverse Effects of Xylazine Among Adults in Substance Use Treatment
Authors: Hochheimer Martin , Strickland Justin C. , Rabinowitz Jill A. , Ellis Jennifer D. , Dunn Kelly E. , Huhn Andrew S.
Published: February 2024

This cross-sectional study evaluates aspects of xylazine adulteration of opioids among individuals entering substance use disorder treatment.
Universal Vapor‐Phase Synthesis of Large‐Scale Ultrathin Perovskites with Superior Stability for Photodetectors and Image Sensors
Authors: He Xiaoyu , Hao Shiqiang , Ouyang Decai , Liu Shenghong , Zhang Na , Zeng Zihao , Zhang Yi , Spanopoulos Ioannis , Wolverton Chris , Li Yuan , Zhai Tianyou
Published: February 2024

Ultrathin halide perovskites have drawn tremendous attention in nano‐/micro‐optoelectronic devices due to their fascinating performance and capability for chip integration. Unfortunately, it is highly challenging to obtain large‐scale and chronically stable ultrathin halide perovskites for practical application. Herein, the universal low‐temperature vapor‐phase synthesis of ultrathin perovskite family materials with thickness down to 2D level and lateral size up to 1.5 cm × 1.5 cm is reported by developing a self‐limiting chemical vapor deposition strategy. The perovskite products are found to exhibit superior stability over 180 days under an air environment. The resultant photodetectors demonstrate charming optoelectronic properties such as superior responsivity (3.7 × 103 A W−1), ultrafast response time (<10 µs), and outstanding low‐level light image sensing capability. This universal perovskite synthesis strategy offers great potential for practical applications of halide perovskites in future nano‐/micro‐optoelectronic devices.
Single‐Atomic‐Site Platinum Steers Middle Hydroxyl Selective Oxidation on Amorphous/Crystalline Homojunction for Photoelectrochemical Glycerol Oxidation Coupled with Hydrogen Generation
Authors: Feng Xinyan , Sun Tingting , Feng Xuefan , Yu Hao , Yang Yu , Chen Limiao , Zhang Fuqin
Published: February 2024

Photoelectrochemical (PEC) organic conversion is a promising approach to convert low‐cost organics to value‐added chemicals, which urgently needs the development of efficient and highly selective photoanodes. Here, a Pt single‐atom dispersed WO3 amorphous/crystalline homojunction for anodic glycerol oxidation reaction (GOR) coupled with cathodic hydrogen generation is reported. In the coupled photoelectrocatalytic system, the novel Pt‐SA/WOx photoanode reaches a photocurrent density of 2.85 mA cm−2 at 1.2 V versus RHE, with up to 297.3 mmol m−2 h−1 of glycerol conversion rate and 60.2% of dihydroxyacetone (DHA) selectivity, realizing green synthesis of high‐value chemicals. The experimental data and theoretical calculations reveal the regulated band structure, build‐in electric field, and surface charge density of Pt‐SA/WOx, which can improve the carrier lifetime, accelerate charge transfer, and reduce the energy barrier for the GOR process, thus boosting PEC activity and DHA selectivity. This work provides a feasible plan for designing atomic‐level engineering and constructing amorphous/crystalline homojunction on photoanodes for efficient PEC high‐value products from biomass.
Herbal Products‐Powered Thermosensitive Hydrogel with Phototherapy and Microenvironment Reconstruction for Accelerating Multidrug‐Resistant Bacteria‐Infected Wound Healing
Authors: Zhao Gang , Lu Guanghua , Fan Huizhen , Wei Li , Yu Qiang , Li Ming , Li Hanqing , Yu Nuo , Wang Shen , Lu Min
Published: February 2024

Wound healing and infection remain significant challenges due to the ineffectiveness against multidrug‐resistant (MDR) bacteria and the complex oxidative wound microenvironments. To address these issues, thymoquinone‐reinforced injectable and thermosensitive TQ@PEG‐PAF‐Cur hydrogels with dual functions of microenvironment reshaping and photodynamic therapy are developed. The hydrogel comprises natural compound thymoquinone (TQ) and poly (ethylene glycol)‐block‐poly (alanine‐co‐phenyl alanine) copolymers (PEG‐PAF) conjugated with natural photosensitizer curcumin (Cur). The incorporation of TQ and Cur reduces the sol‐to‐gel transition temperature of TQ@PEG‐PAF‐Cur to 30°C, compared to PEG‐PAF hydrogel (37°C), due to the formation of strong hydrogen bonding, matching the wound microenvironment temperature. Under blue light excitation, TQ@PEG‐PAF‐Cur generates significant amounts of reactive oxygen species such as H2O2, 1O2, and ·OH, exhibiting rapid and efficient bactericidal capacities against methicillin‐resistant Staphylococcus aureus and broad spectrum β‐lactamases Escherichia coli via photodynamic therapy (PDT). Additionally, Cur effectively inhibits the expressions of proinflammatory cytokines in skin tissue‐forming cells. As a result, the composite hydrogel can rapidly transform into a gel to cover the wound, reshape the wound microenvironment, and accelerate wound healing in vivo. This collaborative antibacterial strategy provides valuable insights to guide the development of multifunctional materials for efficient wound healing.
Overcoming the Unfavorable Effects of “Boltzmann Tyranny:” Ultra‐Low Subthreshold Swing in Organic Phototransistors via One‐Transistor‐One‐Memristor Architecture
Authors: Yang Shuyuan , Yuan Jiangyan , Wang Zhaofeng , Wu Xianshuo , Shen Xianfeng , Zhang Yu , Ma Chunli , Wang Jiamin , Lei Shengbin , Li Rongjin , Hu Wenping
Published: February 2024

Organic phototransistors (OPTs), as photosensitive organic field‐effect transistors (OFETs), have gained significant attention due to their pivotal roles in imaging, optical communication, and night vision. However, their performance is fundamentally limited by the Boltzmann distribution of charge carriers, which constrains the average subthreshold swing (SSave) to a minimum of 60 mV/decade at room temperature. In this study, an innovative one‐transistor‐one‐memristor (1T1R) architecture is proposed to overcome the Boltzmann limit in conventional OFETs. By replacing the source electrode in an OFET with a memristor, the 1T1R device exploits the memristor's sharp resistance state transitions to achieve an ultra‐low SSave of 18 mV/decade. Consequently, the 1T1R devices demonstrate remarkable sensitivity to photo illumination, with a high specific detectivity of 3.9 × 109 cm W−1Hz1/2, outperforming conventional OPTs (4.9 × 104 cm W−1Hz1/2) by more than four orders of magnitude. The 1T1R architecture presents a potentially universal solution for overcoming the detrimental effects of “Boltzmann tyranny,” setting the stage for the development of ultra‐low SSave devices in various optoelectronic applications.
Controllable Fabrication of Organic Semiconductors for Aligned Microlasers and Integrated Photodetectors
Authors: Qian Mengdan , Zhang Qiaoyan , Zhang Hui , Tang Baolei , Yu Kun , Liu Yufang
Published: February 2024

Engineering of organic single crystal toward controllable and aligned patterns at microscale is crucial to the realization of highly integrated organic photonic devices and optoelectronics. However, precise positioning and controllable morphology of crystal structures is still challenging due to the strict conditions for crystal growth. In this paper, a solution based crystal regulation strategy with the assistance of template‐constrained growth method and femtosecond laser processing technology is developed to prepare aligned crystalline microribbon arrays. Simple solvent evaporation results in the random distribution and orientation of self‐assembled crystalline microribbons while it tends to form highly crystalline and orderly microribbon arrays assisted by the confined template microchannels. The large‐scale microribbon array can be fabricated as organic photodetectors with sensitive and fast response under 405 nm illumination. By virtue of the femtosecond laser processing technique, the microribbon arrays are precisely processed into a series of crystal subunits and each microribbon subunit can function as an individual microcavity resonator to produce stable, high‐quality organic laser. The facile solution based template‐constrained self‐assembly and femtosecond laser processing method provide novel strategies to generate highly oriented and controllable crystal structures for the potential applications in integrated organic lasers and optoelectronics.