bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetic Retinopathy
Authors: Antonetti David A. , Barber Alistair J. , Bronson Sarah K. , Freeman Willard M. , Gardner Thomas W. , Jefferson Leonard S. , Kester Mark , Kimball Scot R. , Krady J. Kyle , LaNoue Kathryn F. , Norbury Christopher C. , Quinn Patrick G. , Sandirasegarane Lakshman , Simpson Ian A. ,   for the JDRF Diabetic Retinopathy Center Group
Published: August 2006

Diabetic retinopathy remains a frightening prospect to patients and frustrates physicians. Destruction of damaged retina by photocoagulation remains the primary treatment nearly 50 years after its introduction. The diabetes pandemic requires new approaches to understand the pathophysiology and improve the detection, prevention, and treatment of retinopathy. This perspective considers how the unique anatomy and physiology of the retina may predispose it to the metabolic stresses of diabetes. The roles of neural retinal alterations and impaired retinal insulin action in the pathogenesis of early retinopathy and the mechanisms of vision loss are emphasized. Potential means to overcome limitations of current animal models and diagnostic testing are also presented with the goal of accelerating therapies to manage retinopathy in the face of ongoing diabetes.
Heterozygosity for a POMC-Null Mutation and Increased Obesity Risk in Humans
Authors: Farooqi I. Sadaf , Drop Stenvert , Clements Agnes , Keogh Julia M. , Biernacka Joanna , Lowenbein Sarah , Challis Benjamin G. , O’Rahilly Stephen
Published: August 2006

Congenital deficiency of proopiomelanocortin (POMC) results in a syndrome of hypoadrenalism, severe obesity, and altered skin and hair pigmentation. The concept that subtle variation in POMC expression and/or function might contribute to common obesity is suggested by studies reporting linkage of obesity-related traits to a locus on chromosome 2p22 encompassing the POMC gene. We identified a novel homozygous frameshift (C6906del) mutation in POMC in a child of Turkish origin with severe obesity and hypoadrenalism. This mutation would be predicted to lead to the loss of all POMC-derived peptides. The availability of a large extended pedigree provided the opportunity to address whether loss of one copy of the POMC gene was sufficient to alter obesity risk. Twelve relatives were heterozygous for the mutation and 7 were wild type. Of the heterozygotes, 11 of 12 heterozygotes were obese or overweight compared with only 1 of 7 of the wild-type relatives. The mean BMI SD score was 1.7 ± 0.5 in heterozygotes and 0.4 ± 0.4 in the wild-type relatives. Parametric linkage analysis of the trait “overweight” provided statistically significant evidence of linkage with this locus, with a maximum “location score” (comparable with multipoint logarithm of odds scores) of 3.191. We conclude that loss of one copy of the POMC gene predisposes to obesity in humans. Thus, genetic variants having relatively subtle effects on POMC expression and function could influence susceptibility to obesity.
In Vivo Imaging of Immune Rejection in Transplanted Pancreatic Islets
Authors: Evgenov Natalia V. , Medarova Zdravka , Pratt John , Pantazopoulos Pamela , Leyting Simone , Bonner-Weir Susan , Moore Anna
Published: August 2006

As islet transplantation becomes an acceptable clinical modality for restoring normoglycemia in type 1 diabetic patients, there is a crucial need for noninvasive assessment of the fate of the grafts. In spite of the success of the Edmonton Protocol, a significant graft loss occurs due to immunological and nonimmunological events immediately after transplantation. Allogeneic rejection in graft recipients is one of the major reasons for islet death and graft failure. Therefore, monitoring the islet rejection using reliable noninvasive methods would significantly aid in clinical assessment of graft success. We have previously developed a method to detect transplanted islets noninvasively using magnetic resonance imaging (MRI). For this procedure, human pancreatic islets are labeled with an MRI contrast agent that enables their visualization on magnetic resonance images. In our present study, we not only detected labeled human islets in a preclinical intrahepatic model of human islet transplantation in mice but also showed that islet rejection can be monitored noninvasively and repeatedly in real time by MRI. In addition, in this study, we have adapted, for islet cell labeling, a Food and Drug Administration–approved commercially available contrast agent, Feridex, that is used clinically for liver imaging. We believe that this agent, in combination with our preclinical model of islet transplantation, will facilitate the transition of imaging immune rejection to clinical trials.
Persistent Renal Hypertrophy and Faster Decline of Glomerular Filtration Rate Precede the Development of Microalbuminuria in Type 1 Diabetes
Authors: Zerbini Gianpaolo , Bonfanti Riccardo , Meschi Franco , Bognetti Emilio , Paesano Pier Luigi , Gianolli Luigi , Querques Marialuisa , Maestroni Anna , Calori Giliola , Del Maschio Alessandro , Fazio Ferruccio , Luzi Livio , Chiumello Giuseppe
Published: August 2006

Soon after the onset of type 1 diabetes, renal hypertrophy and hyperfiltration become manifest, particularly among patients who will subsequently develop diabetic nephropathy. Whether these early renal dysfunctions are involved in the pathogenesis of diabetic nephropathy is currently unclear. We evaluated, during the same day, kidney volume and glomerular filtration rate (GFR) in 146 patients with type 1 diabetes and normal renal function. All the individuals were then monitored for a mean of 9.5 ± 4.4 years for the development of microalbuminuria. Kidney volume and GFR were reevaluated in a subset of 68 patients 4 years after baseline. During follow-up, microalbuminuria developed in 27 of 146 diabetic patients. At baseline, kidney volume (312.8 ± 52.6 vs. 281.4 ± 46.1 vs. 236.8 ± 41.6 ml/1.73 m2, P < 0.05) but not GFR was increased in patients predisposed to microalbuminuria. Risk of progression was higher in patients with increased kidney volume (P = 0.0058). Patients predisposed to microalbuminuria showed a stable increase in kidney volume (P = 0.003), along with a faster decline of GFR (P = 0.01). Persistent renal hypertrophy and faster decline of GFR precede the development of microalbuminuria in type 1 diabetes. These findings support the hypothesis that renal hypertrophy precedes hyperfiltration during the development of diabetic nephropathy.
Gestational Diabetes Mellitus Increases the Risk of Cardiovascular Disease in Women With a Family History of Type 2 Diabetes
Authors: Carr Darcy B. , Utzschneider Kristina M. , Hull Rebecca L. , Tong Jenny , Wallace Tara M. , Kodama Keiichi , Shofer Jane B. , Heckbert Susan R. , Boyko Edward J. , Fujimoto Wilfred Y. , Kahn Steven E. ,   the American Diabetes Association GENNID Study Group
Published: August 2006

OBJECTIVE— We sought to determine whether a history of gestational diabetes mellitus (GDM) further increases the risk of cardiovascular disease (CVD) in parous women with first-degree relatives with type 2 diabetes.

RESEARCH DESIGN AND METHODS— Women with (n = 332) and without (n = 663) a history of GDM were compared regarding 1) the revised National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria, 2) the prevalence of type 2 diabetes, and 3) self-reported CVD.

RESULTS— Women with prior GDM were younger (48.6 ± 0.7 vs. 52.4 ± 0.6 years [means ± SE];P < 0.001) and less likely to be postmenopausal (48.3 vs. 57.9%; P < 0.005). Although both groups were obese (BMI 34.4 ± 1.2 vs. 33.7 ± 0.6 kg/m2), women with prior GDM were more likely to have metabolic syndrome (86.6 vs. 73.5%; P < 0.001) and type 2 diabetes (93.4 vs. 63.3%; P < 0.001). Moreover, they had a higher prevalence of CVD (15.5 vs. 12.4%; adjusted odds ratio 1.85 [95% CI 1.21–2.82];P = 0.005) that occurred at a younger age (45.5 ± 2.2 vs. 52.5 ± 1.9 years;P = 0.02) and was independent of metabolic syndrome (1.74 [1.10–2.76]; P = 0.02) and type 2 diabetes (1.56 [1.002–2.43];P < 0.05).

CONCLUSIONS— Among women with a family history of type 2 diabetes, those with prior GDM were even more likely to not only have CVD risk factors, including metabolic syndrome and type 2 diabetes, but also to have experienced CVD events, which occurred at a younger age. Thus, women with both a family history of type 2 diabetes and personal history of GDM may be especially suitable for early interventions aimed at preventing or reducing their risk of CVD and diabetes.
Treating Postprandial Hyperglycemia Does Not Appear to Delay Progression of Early Type 2 Diabetes
Authors: Kirkman M. Sue , Shankar R. Ravi , Shankar Sudha , Shen Changyu , Brizendine Edward , Baron Alain , McGill Janet
Published: August 2006

OBJECTIVE—Postprandial hyperglycemia characterizes early type 2 diabetes. We investigated whether ameliorating postprandial hyperglycemia with acarbose would prevent or delay progression of diabetes, defined as progression to frank fasting hyperglycemia, in subjects with early diabetes (fasting plasma glucose [FPG] <140 mg/dl and 2-h plasma glucose ≥200 mg/dl).

RESEARCH DESIGN AND METHODS—Two hundred nineteen subjects with early diabetes were randomly assigned to 100 mg acarbose t.i.d. or identical placebo and followed for 5 years or until they reached the primary outcome (two consecutive quarterly FPG measurements of ≥140 mg/dl). Secondary outcomes included measures of glycemia (meal tolerance tests, HbA1c, annual oral glucose tolerance tests [OGTTs]), measures of insulin resistance (homeostasis model assessment [HOMA] of insulin resistance and insulin sensitivity index from hyperglycemic clamps), and secondary measures of β-cell function (HOMA-β, early- and late-phase insulin secretion, and proinsulin-to-insulin ratio).

RESULTS—Acarbose significantly reduced postprandial hyperglycemia. However, there was no difference in the cumulative rate of frank fasting hyperglycemia (29% with acarbose and 34% with placebo; P = 0.65 for survival analysis). There were no significant differences between groups in OGTT values, measures of insulin resistance, or secondary measures of β-cell function. In a post hoc analysis of subjects with initial FPG <126 mg/dl, acarbose reduced the rate of development of FPG ≥126 mg/dl (27 vs. 50%; P = 0.04).

CONCLUSIONS—Ameliorating postprandial hyperglycemia did not appear to delay progression of early type 2 diabetes. Factors other than postprandial hyperglycemia may be greater determinants of progression of diabetes. Alternatively, once FPG exceeds 126 mg/dl, β-cell failure may no longer be remediable.
Diabetes Does Not Influence Treatment Decisions Regarding Revascularization in Patients With Stable Coronary Artery Disease
Authors: Breeman Arno , Bertrand Michel E. , Ottervanger Jan Paul , Hoeks Sanne , Lenzen Mattie , Sechtem Udo , Legrand Victor , de Boer Menko-Jan , Wijns William , Boersma Eric ,   on behalf of the investigators of the Euro Heart Survey on Coronary Revascularization
Published: August 2006

OBJECTIVE—To evaluate whether in stable angina preference for coronary revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) is influenced by diabetes status and whether this has prognostic implications.

RESEARCH DESIGN AND METHODS—A total of 2,928 consecutive patients with stable angina who were enrolled in the prospective Euro Heart Survey on Coronary Revascularization were studied. Multivariable analyses were applied to evaluate the relation between diabetes, treatment decision, and 1-year outcome.

RESULTS—Diabetes was documented in 587 patients (20%) who had more extensive coronary disease. Revascularization was intended in 74% of patients with diabetes and in 77% of those without diabetes. In patients selected for revascularization, CABG was intended in 35% of diabetic and in 33% of nondiabetic patients. Multivariable analyses did not change these findings, but in some subgroups diabetes influenced treatment decisions. For example, diabetic subjects with mild heart failure had more often intended revascularization (91%) than those without diabetes (67%, P < 0.001). Treatment decisions in patients with more extensive (left main, multivessel, or proximal left anterior descending artery) disease were not influenced by diabetes status. Diabetes was not associated with an increased incidence of all-cause death, nonfatal cerebrovascular accident, or nonfatal myocardial infarction at 1 year, regardless of preferred treatment. The incidence of the combined end points was 7.3% in diabetic and 6.8% in nondiabetic patients (adjusted hazard ratio 1.0 [95% CI 0.7–1.4]).

CONCLUSIONS—In stable angina, treatment decisions regarding revascularization or the choice for CABG or PCI were not influenced by the presence of diabetes. Diabetes was not associated with a poor prognosis.
Natural History and Risk Factors for Microalbuminuria in Adolescents With Type 1 Diabetes
Authors: Stone Monique L. , Craig Maria E. , Chan Albert K. , Lee Jenny W. , Verge Charles F. , Donaghue Kim C.
Published: August 2006

OBJECTIVE— To describe the natural history and risk factors for persistent microalbuminuria in children and adolescents with type 1 diabetes followed for up to 15 years.

RESEARCH DESIGN AND METHODS— This study contained a longitudinal cohort of 972 patients; analysis of baseline risk factors was performed using logistic regression and predictors over time using survival analysis. Albumin excretion rate was measured on three consecutive timed overnight urine collections on at least two occasions. Normoalbuminuria was defined as a median albumin excretion rate <7.5 μg/min, borderline microalbuminuria as 7.5–20 μg/min, and microalbuminuria as 20–200 μg/min. Microalbuminuria was further classified as persistent if its duration was >12 months. Median age was 12.7 years (interquartile range 11.5–14.4) and diabetes duration 6.5 years (4.1–9.3) at first assessment, and median follow-up was 6.2 years (range 1–15.3).

RESULTS— The incidence of persistent microalbuminuria was 4.6 (95% CI 3.3–6.1) per 1,000 patient-years. Predictors of persistent microalbuminuria from the first assessment using multiple logistic regression were high cholesterol (odds ratio 2.2 [95% CI 1.2–4.0]) and borderline microalbuminuria (2.5 [1.2–5.2]). Predictors using Cox regression were HbA1c (hazard ratio 1.4 [95% CI 1.1–1.7]), age at diagnosis (1.2 [1.1–1.3]), obesity (3.6 [0.8–15.5]), and insulin dose (2.7 [1.0–7.5]).

CONCLUSIONS— Children and adolescents with type 1 diabetes who have borderline microalbuminuria are more than twice as likely to develop persistent microalbuminuria. In addition to poor glycemic control, clinical markers of insulin resistance were associated with an increased risk of microalbuminuria.
Synthesis, structure and biological activity studies of 2‐[(1H‐1,2,4‐triazol‐1‐yl)methyl]‐1‐aryl)‐3‐ferrocenyl prop‐2‐en‐1‐one derivatives
Authors: Liu Jianbing , Liu Tao , Dai Hong , Jin Zhong , Fang Jianxin
Published: August 2006

Fifteen new ferrocene derivatives containing 1H‐1,2,4‐triazole moiety were synthesized in various yields by the condensation of ferrocenecarboxaldehyde with 1‐aryl‐3‐(1H‐1,2,4‐triazo‐1‐yl)‐propen‐1‐ones in toluene. Their structures have been confirmed by 1H NMR, IR, MS and elemental analysis. In addition, the crystal structure of 4l was determined. The antifungal and plant growth regulatory activities of the title compounds are discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Interpenetrating Coordination Polymers from CuI or AgI and Flexible Ligands: 2D Polyrotaxanes and Interpenetrating Grids
Authors: Kasai Kayoko , Sato Mariko
Published: August 2006

The reaction of [Cu(CH3CN)4]NO3 or AgNO3 with flexible ligands 1,4‐bis(4‐pyridylmethyl)‐2,3,5,6‐tetrafluorobenzene (bpf) or 4,4′‐bis(4‐pyridylmethyl)‐2,2′,3,3′,5,5′,6,6′‐octafluorobiphenyl (bpfb) afforded two types of interpenetrating coordination polymers. The structures of [Cu2(bpf)3(NO3)2]n and [Ag2(bpf)3‐(NO3)2]n are 2D polyrotaxane networks in which 1D polymeric chains are aligned in a grid. The structure of {[Cu(bpfb)2]NO3}n is a 2D grid polymer with two‐fold parallel interpenetration.
Linking Chiral Clusters with Molybdate Building Blocks: From Homochiral Helical Supramolecular Arrays to Coordination Helices
Authors: Long De‐Liang , Kögerler Paul , Farrugia Louis J. , Cronin Leroy
Published: August 2006

The synthesis of four new oxo‐centered Fe clusters (1 a–c, 2) of the form [FeIII3(μ3‐O)(CH2=CHCOO)6] with acrylate as the bridging ligand gives rise to potentially intrinsically chiral oxo‐centered {M3} trimers that show a tendency to spontaneously resolve upon crystallization. For instance, 1 a, [FeIII3(μ3‐O)(CH2=CHCOO)6‐(H2O)3]+, crystallizes in the chiral space group P31 as a chloride salt. Crystallization of 1 b, [Fe3(μ3‐O)(C2H3CO2)6(H2O)3]NO3⋅4.5H2O, from aqueous solution followed by recrystallization from acetonitrile also gives rise to spontaneous resolution to yield the homochiral salt [Fe3(μ3‐O)(C2H3CO2)6‐(H2O)3]NO3⋅CH3CN of 1 c (space group P212121). Furthermore, the reaction of 1 a with hexamolybdate in acetonitrile gives the helical coordination polymer {[(Fe3(μ3‐O)L6(H2O))(MoO4)‐(Fe3(μ3‐O)L6(H2O)2)]⋅2CH3CN⋅H2O}∞ 2 (L: H2CCHCOO), which crystallizes in the space group P21. The nature of the ligand geometry allows the formation of atropisomers in both the discrete (1 a–c) and linked {Fe3} clusters (2), which is described along with a magnetic analysis of 1 a and 2.
The multidimensionality of cell behaviors underlying morphogenesis: a case study in ascidians
Authors: Di Gregorio Anna , Hadjantonakis Anna‐Katerina
Published: August 2006

Databases where different types of information from different sources can be integrated, cross‐referenced and interactively accessed are necessary for building a quantitative understanding of the molecular and cell biology intrinsic to the morphogenesis of an embryo. Tassy and colleagues1 recently reported the development of software tailor‐made to perform such a task, along with the generation and integration of three‐dimensional anatomical models of embryos. They convincingly illustrated the utility of their approach by applying it to the early ascidian embryo. BioEssays 28: 874–879, 2006. © 2006 Wiley periodicals, Inc.
A role for genetic accommodation in evolution?
Authors: Braendle Christian , Flatt Thomas
Published: August 2006

Whether evolutionary change can occur by genetic assimilation, or more generally by genetic accommodation, remains controversial. Here we examine some of the experimental evidence for both phenomena. Several experiments in Drosophila suggest that assimilation is possible, and a new paper1 shows that a color polyphenism in the tobacco hornworm, Manduca sexta, can evolve by genetic accommodation. We argue that genetic accommodation, including assimilation, is a plausible mechanism in evolution; however, more work is required to test how this mechanism acts and how often it is involved in evolutionary change. BioEssays 28: 868–873, 2006. © 2006 Wiley periodicals, Inc.
The isoform‐specific functions of the c‐Jun N‐terminal Kinases (JNKs): differences revealed by gene targeting
Authors: Bogoyevitch Marie A.
Published: August 2006

The c‐Jun N‐terminal kinases (JNKs) are members of the mitogen‐activated protein kinase (MAPK) family. In mammalian genomes, three genes encode the JNK family. To evaluate JNK function, mice have been created with deletions in one or more of three Jnk genes. Initial studies on jnk1−/− or jnk2−/− mice have shown roles for these JNKs in the immune system whereas studies on jnk3−/− mice have highlighted roles for JNK3 in the nervous system. Further studies have highlighted the contributions of JNK1 and/or JNK2 to a range of biological and pathological processes. These include bone remodelling and joint disease, inflammatory and autoimmune diseases, obesity, diabetes, cardiovascular disease, liver disease and tumorigenesis in addition to effects in neurons. These results emphasise the differences in the roles played by JNK isoforms in vivo and suggest that the design of JNK inhibitors for subsequent therapeutic uses may benefit from selective inhibition of individual JNK isoforms. BioEssays 28: 923–934, 2006. © 2006 Wiley periodicals, Inc.
The nuclear barrier is structurally and functionally highly responsive to glucocorticoids
Authors: Shahin Victor
Published: August 2006

Nuclear pore complexes mediate and control transport between the cytosol and the nucleus. They form a highly selective and, thus, tight nuclear barrier between these compartments. The nuclear barrier provides the cell with the opportunity to control access to its DNA, a defining feature of eukaryotes. The tightness of the nuclear barrier is therefore physiologically pivotal and any remarkable change in its structure and permeability can prove pathophysiological, e.g. as a result of viral attack. However, there is accumulating evidence that nuclear barrier structure and permeability are highly responsive to hydrophobic cargos of crucial physiological and therapeutic relevance, glucocorticoids (steroid hormones). The present review highlights the glucocorticoid‐induced effects on the nuclear barrier structure and permeability concluding that they are physiologically essential to mediate glucocorticoid action. BioEssays 28: 935–942, 2006. © 2006 Wiley periodicals, Inc.
Membrane fouling by cell‐protein mixtures: In situ characterisation using multi‐photon microscopy
Authors: Hughes David J. , Cui Zhanfeng , Field Robert W. , Tirlapur Uday K.
Published: August 2006

Fouling of the membrane by cell and protein mixtures can result in severe flux declines, leading to the eventual need to clean or replace the membrane. In this study multi‐photon microscopy, a fluorescence‐based technique is used to 3‐D image in situ the fouling of microfiltration membranes by suspensions containing combinations of washed yeast, bovine serum albumin (BSA) and ovalbumin. Appropriate fluorescent labelling allows the three foulant species to be clearly identified. Images correlate well with filtration data and clearly show the cake of yeast cells capturing protein aggregates. The proteins exhibited very different filtration behaviour. When filtering washed yeast together with ovalbumin and/or a 50:50 mixture by mass of BSA and ovalbumin, the ovalbumin fouling dominates the system. Capture of aggregates by the cake did not reduce fouling of the membrane by the protein and increased the resistance of the cake. For mixtures of BSA and washed yeast, the presence of a cake of yeast cells did reduce fouling of the membrane by the protein, however, the extra resistance due to the cake resulted in a flux lower than that when filtering BSA alone. Biotechnol. Bioeng. 2007;96:1083–1091. © 2006 Wiley Periodicals, Inc.
α,β‐Unsaturated δ‐Lactones from Copper‐Catalyzed Asymmetric Vinylogous Mukaiyama Reactions of Aldehydes: Scope and Mechanistic Insights
Authors: Bazán‐Tejeda Belén , Bluet Guillaume , Broustal Garance , Campagne Jean‐Marc
Published: August 2006

A direct regio‐, diastereo‐, and enantiocontrolled access to α,β‐unsaturated δ‐lactones is described, based on the reaction of a silyl dienolate and an aldehyde in the presence of 10 % of Carreira's catalyst. The scope and limitations of this reaction, as well as mechanistic insights concerning the reactivity of an allyl copper species, are discussed.
Diastereomeric Discrimination in the Lifetimes of Norrish Type II Triplet 1,4‐Biradicals and Stereocontrolled Partitioning of Their Reactivity (Yang Cyclization versus Type II Fragmentation)
Authors: Moorthy Jarugu Narasimha , Koner Apurba L. , Samanta Subhas , Singhal Nidhi , Nau Werner M. , Weiss Richard G.
Published: August 2006

The stereochemistry at C2 and C3 carbons controls the partitioning of triplet 1,4‐biradicals of ketones 2 among various pathways. Differences in the major reaction pathways, for example, cyclization (syn) and fragmentation (anti), adopted by the diastereomeric 1,4‐radicals of ketones 2 have permitted unprecedented diastereomeric discrimination in their lifetimes to be observed by nanosecond laser flash photolysis. From quantum yield measurements and transient lifetime data, the absolute rate constants for cyclization and fragmentation of a pair of diastereomeric triplet 1,4‐biradicals have been determined for the first time.
Outcomes and diffusion of doxorubicin‐based chemotherapy among elderly patients with aggressive non‐Hodgkin lymphoma
Authors: Grann Victor R. , Hershman Dawn , Jacobson Judith S. , Tsai Wei‐Yann , Wang Jian , McBride Russell , Mitra Nandita , Grossbard Michael L. , Neugut Alfred I.
Published: August 2006

BACKGROUND.

In the past 25 years, clinical trials have demonstrated the benefits of chemotherapy for patients with aggressive non‐Hodgkin lymphoma. The authors analyzed the predictors and outcomes of chemotherapy among elderly patients with lymphoma.

METHODS.

Patients age ≥65 years who were diagnosed with Stage III and IV diffuse large B‐cell lymphoma [according to the SEER Summary Staging Manual, 2000] between 1991 and 1999 in the Surveillance, Epidemiology, and End Results‐Medicare data base were categorized by treatment: no chemotherapy, a doxorubicin‐containing regimen, a regimen without doxorubicin, or chemotherapy not otherwise specified. Among the patients who survived for >6 weeks after diagnosis and who had a chemotherapy regimen specified, logistic regression analysis was used to identify predictors of doxorubicin‐based treatment, and Cox proportional‐hazards regression was used to analyze outcomes.

RESULTS.

Less than 66% of patients received any chemotherapy in the 6 months after diagnosis, and 42% of untreated patients died within 6 weeks. Older age, congestive heart failure, and other comorbidities were strong predictors of treatment without doxorubicin. From 1991 to 1999, the proportion of patients who received doxorubicin increased from <20% to >50%. Patients who received doxorubicin survived more than twice as long (24.4 months) as patients who did not receive doxorubicin (11.2 months). Survival was no better among patients who received chemotherapy without doxorubicin than among patients who received no chemotherapy.

CONCLUSIONS.

By 1999, doxorubicin‐based chemotherapy had gained general acceptance for use among the elderly, although nearly 50% of elderly patients still were not receiving it. Given the clinical trial‐based evidence of its benefits, in the absence of specific contraindications, most patients, including the elderly, should be treated with regimens that include doxorubicin. Cancer 2006. © 2006 American Cancer Society.
Treatment algorithm for locally recurrent osteosarcoma based on local disease‐free interval and the presence of lung metastasis
Authors: Nathan Saminathan S. , Gorlick Richard , Bukata Susan , Chou Alex , Morris Carol D. , Boland Patrick J. , Huvos Andrew G. , Meyers Paul A. , Healey John H.
Published: August 2006

BACKGROUND.

Local recurrence in osteosarcoma is clinically distinct from metastasis, although associated with a similar reduction in survival. The prognostic factors in locally recurrent osteosarcoma were investigated and these factors were translated into a management strategy.

METHODS.

In all, 407 consecutive patients with skeletal osteosarcoma between 1977 and 2002 were analyzed. Twenty‐three patients with resectable local recurrence were analyzed. Clinical and tumor‐related factors were assessed for significance in relation to survival and a management strategy was formulated based on factors found to be independently significant for survival.

RESULTS.

Seventeen of the 23 patients underwent primary resections and initial treatment, yielding an overall local recurrence rate of 4.2% for resectable cancer. Median time to local recurrence was 13 months (95% confidence interval, 9–16 months). The 5‐year and 10‐year survival rates in the recurrent cases were 29% and 10%, respectively. All patients received chemotherapy both for their primary and recurrent disease. Increased risk of local recurrence (P < .0001) was strongly correlated with positive margins of resection. The rate of local recurrence was not related to chemotherapy‐associated necrosis in the primary tumor. Nevertheless, neoadjuvant therapy halved the risk of local recurrence (odds ratio, 1.92; P = .3, power 10%). The strongest correlate with poor survival was local recurrence within the first year after primary resection (P = .001), followed by metastasis at the time of first local recurrence (P = .04) and failure to achieve clinical remission after disease recurrence (P = .04). Chemotherapy‐associated necrosis and margins of resection of the primary tumor were not significant prognostic variables for survival. Survival differed significantly among patients defined by local disease‐free interval and lung metastasis (P = .0001). They required an individualized approach as captured in the management algorithm.

CONCLUSION.

There is a residual risk of local recurrence in patients despite favorable chemotherapy‐associated necrosis and negative margins of resection. A treatment strategy emphasizing clinical remission at all identifiable sites offers the highest likelihood of survival in this patient population. Cancer 2006. © 2006 American Cancer Society.
An optimization approach for decentralized QoS‐based scheduling based on utility and pricing in Grid computing
Authors: Chunlin Li , Layuan Li
Published: August 2006

This paper presents an optimization approach for decentralized Quality of Service (QoS)‐based scheduling based on utility and pricing in Grid computing. The paper assumes that the quality dimensions can be easily formulated as utility functions to express quality preferences for each task agent. The utility values are calculated by the user‐supplied utility function that can be formulated with the task parameters. The QoS constraint Grid resource scheduling problem is formulated into a utility optimization problem. The QoS‐based Grid resource scheduling optimization is decomposed into two subproblems by applying the Lagrangian method. In the Grid, a Grid task agent acts as a consumer paying for the Grid resource and the resource providers receive profits from task agents. A pricing‐based QoS scheduling algorithm is used to perform optimally decentralized QoS‐based resource scheduling. The experiments investigate the effect of the QoS metrics on the global utility and compare the performance of the proposed algorithm with other economical Grid resource scheduling algorithms. Copyright © 2006 John Wiley & Sons, Ltd.
Kit signaling is essential for development and maintenance of interstitial cells of Cajal and electrical rhythmicity in the embryonic gastrointestinal tract
Authors: Beckett Elizabeth A. H. , Ro Seungil , Bayguinov Yulia , Sanders Kenton M. , Ward Sean M.
Published: August 2006

Interstitial cells of Cajal (ICC) are specialized cells in smooth muscle organs that generate and propagate pacemaker activity, receive inputs from motor neurons, and serve as mechanosensors. In the gastrointestinal tract, development and maintenance of the ICC phenotype have been linked to intracellular signaling via Kit, but its role in development of ICC during embryogenesis is controversial. Here we have studied the development of functional ICC‐MY during the late gestational period in mice. Blocking Kit with a neutralizing antibody before and after development of spontaneous electrical activity (E17 to P0) caused loss of ICC‐MY networks and pacemaker activity. ICC‐MY and pacemaker activity developed normally in W/+ and WV/+ heterozygotes, but failed to develop between E17 to P0 in W/WV embryos with compromised Kit function. Muscles treated with Kit neutralizing antibody or the tyrosine kinase inhibitor, imatinib mesylate (STI571), from E17‐P0 for 3 days caused loss of functionally developed ICC‐MY networks, but ICC‐MY and pacemaker activity recovered within 9 days after discontinuing treatment with neutralizing antibody or imatinib mesylate. These data suggest that Kit signaling is an important factor in lineage decision and in the development of functional ICC in late gestation. ICC‐MY demonstrate significant plasticity in gastrointestinal tissues. Manipulation of the ICC phenotype might provide useful therapies in gastrointestinal disease where the Kit‐positive cell population is either lost or amplified. Developmental Dynamics, 2006. © 2006 Wiley‐Liss, Inc.
Math6 expression during kidney development and altered expression in a mouse model of glomerulosclerosis
Authors: Ross Michael D. , Martinka Scott , Mukherjee Amitava , Sedor John R. , Vinson Charles , Bruggeman Leslie A.
Published: August 2006

Math6 is a tissue‐restricted member of the Atonal family of basic helix–loop–helix (bHLH) transcription factors and has been implicated in specification and differentiation of cell lineages in the brain. We identify here Math6 as a podocyte‐expressed bHLH protein that was down‐regulated in human immunodeficiency virus–associated nephropathy (HIVAN); a collapsing glomerulopathy characterized by podocyte dedifferentiation. Early in metanephric development, Math6 was expressed in metanephric mesenchyme but not ureteric bud‐derived cells, with overall Math6 expression most abundant in the nephrogenic zone, including developing glomeruli. In adult kidney, Math6 expression was restricted to podocytes. In adult podocyte cell lines and kidneys from the transgenic mouse model of HIVAN, Math6 podocyte expression was reduced concurrent with previously reported reductions in Nephrin and Synaptopodin expression, suggesting a correlation between the loss of Math6 expression and typical podocyte terminal differentiation markers. These studies suggest that Math6 may participate in kidney development and may be a permissive factor for podocyte differentiation. Developmental Dynamics 235:3102–3109, 2006. © 2006 Wiley‐Liss, Inc.
Human CD4+ T cells stimulated by conserved adenovirus 5 hexon peptides recognize cells infected with different species of human adenovirus
Authors: Veltrop‐Duits Louise A. , Heemskerk Bianca , Sombroek Claudia C. , van Vreeswijk Tamara , Gubbels Sophie , Toes René E. M. , Melief Cornelis J. M. , Franken Kees L. M. C. , Havenga Menzo , van Tol Maarten J. D. , Schilham Marco W.
Published: August 2006

The immune response against human adenovirus (HAdV) has gained interest because of the application of HAdV‐based vectors in gene therapy and the high incidence of infections in pediatric recipients of allogeneic stem cell grafts. Because antiviral medication is frequently ineffective, the option of adoptive transfer of HAdV‐specific donor‐derived T cells in these immunocompromised patients is investigated. To generate good manufacturing practice‐compatible reagents, a panel of 63 long, overlapping, peptides of the hexon protein was screened for recognition by T cells. Five conserved peptides of 30 amino acids were identified that were recognized by the majority of adult donors. CD4+ T cells from long‐term cultures of PBMC, stimulated with this set of five peptides, recognized cells infected with HAdV serotypes belonging to different species. These data demonstrate that adult human T cells preferentially recognize conserved sequences of amino acid residues from a structural protein of HAdV. In the context of gene therapy, this observation may limit the beneficial effect of switching to HAdV‐based vectors derived from less common serotypes of HAdV in an attempt to circumvent pre‐existing immunity. However, this cross‐reactivity benefits the application of HAdV‐specific T cells for adoptive immunotherapy in immunocompromised transplant recipients.
Regulatory T cells control autoimmunity following syngeneic bone marrow transplantation
Authors: Bénard Angèle , Ceredig Rhodri , Rolink Antonius G.
Published: August 2006

Sublethally irradiated, immunodeficient, C57BL/6 RAG‐2 gene‐deleted recipient mice reconstituted with T cell‐depleted bone marrow (BM) grafts frequently developed diarrhea, lost weight and showed signs of autoimmunity, dying between 4 and 7 weeks after reconstitution. Mice died despite evidence of efficient donor‐derived hemato‐lymphoid reconstitution, and disease was associated with the presence of IgG anti‐nuclear antibodies. Autoimmunity was initiated by T cells, but could be prevented by transfer of naturally arising regulatory T cells. In contrast, lethally irradiated, BM‐reconstituted immunocompetent, C57BL/6 mice survived without signs of autoimmunity. Survival of immunocompetent mice was shown to be due to the presence of residual, extra‐thymically located, radio‐resistant, functional regulatory T cells. The importance of regulatory T cells was further shown by the reduced survival of immunocompetent BM recipients whose CD25+ T cells had been depleted prior to bone marrow transplantation. The implications of these results in the context of syngeneic graft‐versus‐host disease following BM transplantation are discussed.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200636571
Strategic decision‐making in healthcare organizations: it is time to get serious
Authors: Young David W. , Ballarin Eduard
Published: August 2006

New and continuing environmental demands and competitive forces require healthcare organizations to be increasingly careful in thinking about their strategies. They must do so in a highly unusual (multi‐actor) marketplace where a variety of system interdependencies complicate decision‐making. A good strategy requires an attempt to understand the real, as distinct from the perceived, environment, and is characterized by explicit tradeoffs along three dimensions: service or program variety, patient needs, and patient access. The quality of these tradeoffs can be assessed in terms of whether the strategy is (a) attuned to critical success factors in the organization's environment, (b) highly focused, (c) linked to the organization's capabilities, and (d) accompanied by an activity set that is difficult for competitors to imitate. An organization also must be capable of adapting appropriately to changes in its environment. Thus, even the best strategy must be reviewed constantly if it is to remain viable. A strategy's sustainability can be adversely affected by increased buyer or supplier power, lowered barriers to entry, growing rivalry, the threat of substitutes, and increased slack in resource usage. By thinking more creatively in the future than they have in the past, healthcare organizations can make tradeoffs and choose a focused strategic position. They then can design an activity set that is appropriate for that position, and that will assist them to achieve both financial viability and superior programmatic performance. A well‐designed activity set also will assist them to sustain their performance in the face of changing environmental demands and competitive forces. Copyright © 2006 John Wiley & Sons, Ltd.
Urban employee health insurance reform and the impact on out‐of‐pocket payment in China
Authors: Liu Gordon G. , Zhao Zhongyun
Published: August 2006

Since the middle of the 1990s, China has undertaken a significant reform in urban employee health insurance programs. Using data from the pilot experiment conducted in Zhenjiang, this study examines changes in the pre‐ and post‐reform distributions of out‐of‐pocket (OOP) expenditures across four representative groups by chronic disease, income, education, and job status. Major findings suggested increased OOP expenditures for all groups after the reform. However, the redistributions in OOP appear to be in favor of the disadvantaged groups, suggesting a more equitable change led by the reform. This study concludes that the post‐reform insurance model did not compromise equity in cost‐sharing while containing cost inflation and increasing insurance coverage for the urban population. Copyright © 2006 John Wiley & Sons, Ltd.
Assessment and treatment of persistent pain in persons with cognitive and communicative impairment
Authors: Snow A. Lynn , Jr. John L. Shuster
Published: August 2006

Pain management is a challenge when working with persons who have cognitive impairment that affects their ability to understand and communicate. This article focuses on pain assessment and treatment in persons who have dementia, but the challenges and principles are relevant to the spectrum of cognitive impairment. Fundamental principles guiding pain assessment and treatment in this population are (1) that behavioral disturbance is the result of an unmet need that causes discomfort, (2) that the behavioral disturbances that result from the unmet need of uncontrolled pain may be identical to those caused by other unmet needs (e.g., thirst, needing to toilet, understimulation, overstimulation, depression, psychosis, uncomfortable clothing), and therefore (3) that any pain treatment protocol for this population must target discomfort behaviors in general and then attempt to determine their causes. Pain assessment and treatment approaches based on these principles are outlined, and then two cases are presented to illustrate the application of these approaches. © 2006 Wiley Periodicals, Inc. J Clin Psychol: In Session 62: 1379–1387, 2006.
Cognitive‐Behavioral self‐help for chronic pain
Authors: Buenaver Luis F. , McGuire Lynanne , Haythornthwaite Jennifer A.
Published: August 2006

Cognitive behavioral self‐help is a potentially cost‐saving method of delivering evidence‐based treatment to a wide range of chronic pain patients. This article provides a rationale for self‐help and focuses on the effectiveness of self‐help in the management of chronic pain, which typically includes some degree of lay leader or professional facilitation. The evidence for these treatments is generally positive (e.g., reductions in pain and pain‐related disability) across such illnesses as arthritis, back pain, headache, and temporomandibular joint disorders. When implementing self‐help, professionals need to consider individual differences in suitability for using a self‐management treatment and evaluate the outcome in the context of a stepped care approach. This article uses three case examples to illustrate the use of cognitive behavioral self‐help delivered in the care of scleroderma patients. © 2006 Wiley Periodicals, Inc. J Clin Psychol: In Session 62: 1389–1396, 2006.
Integrative behavioral couple therapy for chronic pain: Promoting behavior change and emotional acceptance
Authors: Cano Annmarie , Leonard Michelle
Published: August 2006

Couple therapy has been used with success in treating marital distress, psychological distress, and other problems. Researchers in the pain field have also shown that the inclusion of the spouse in pain treatment may be beneficial to the patient. In this article, we present integrative behavioral couple therapy (IBCT) as one option for therapists treating patients who have pain and marital distress. IBCT improves on traditional behavior therapy because it promotes processes that have been shown to be lacking in pain patients' relationships: emotional acceptance and empathy. After reviewing the use of behavior change and emotional acceptance strategies in couples, we describe a couple for whom IBCT improved functioning. © 2006 Wiley Periodicals, Inc. J Clin Psychol: In Session 62: 1409–1418, 2006.
Complementary and alternative medicine approaches to pain management
Authors: Tan Gabriel , Alvarez Julie A. , Jensen Mark P.
Published: August 2006

This article argues for and illustrates incorporating complementary and alternative medicine (CAM) interventions into pain treatment plans. Two CAM treatments, cranial electrotherapy stimulation (CES) and self‐hypnosis training, are offered in a multidisciplinary pain treatment program. Because these interventions focus on pain relief, they may be of particular interest to patients who have chronic pain who begin treatment with a primary interest in pain reduction. Two cases that illustrate the clinical application of CES and self‐hypnosis are presented. When effective, these interventions can help patients have greater confidence in treatments offered by psychologists for pain management and may help make them more open to participating in other psychological interventions that have established efficacy for pain management (e.g., cognitive‐behavioral therapy). Because of their brevity, these treatments also can be offered alone to patients who may not have the resources or time to participate in more time‐intensive treatment. © 2006 Wiley Periodicals, Inc. J Clin Psychol: In Session 62: 1419–1431, 2006.
Relative sea‐level observations in western Scotland since the Last Glacial Maximum for testing models of glacial isostatic land movements and ice‐sheet reconstructions
Authors: Shennan Ian , Hamilton Sarah , Hillier Caroline , Hunter Amanda , Woodall Ruth , Bradley Sarah , Milne Glenn , Brooks Anthony , Bassett Sophie
Published: August 2006

Observations of relative sea‐level change and local deglaciation in western Scotland provide critical constraints for modelling glacio‐isostatic rebound in northern Britain over the last 18 000 years. The longest records come from Skye, Arisaig and Knapdale with a shorter, Holocene, record from Kintail. Biostratigraphic (diatom, pollen, dinoflagellate, foraminifera and thecamoebian), lithological and radiocarbon analyses provide age and elevation parameters for each sea‐level index point. All four sites reveal relative sea‐level change that is highly non‐monotonic in time as the local vertical component of glacio‐isostatic rebound and eustasy (or global meltwater influx) dominate at different periods. Copyright © 2006 John Wiley & Sons, Ltd.
Latent polyphenol oxidase from quince fruit pulp (Cydonia oblonga): purification, activation and some properties
Authors: Orenes‐Piñero Esteban , García‐Carmona Francisco , Sánchez‐Ferrer Alvaro
Published: August 2006

Quince fruit polyphenol oxidase (PPO) was partially purified using a combination of phase partitioning in Triton X‐114 and PEG 8000/phosphate with a final ammonium sulfate fractionation between 30% and 75%, to avoid the deep browning of the enzyme due to the high amount of oxidizing substances present in the quince pulp. The clean and stable enzyme was partially purified in a latent form and could be optimally activated by the presence of 0.5 g dm−3 sodium dodecyl sulfate (SDS) with an optimum pH of 5.0. In the absence of SDS, the enzyme showed maximum activity at acid pH. The apparent kinetic parameters of the latent enzyme were determined at pH 5.0, the Vm value being 15 times higher in the presence of SDS than in its absence, whereas the KM was the same in both cases, with a value of 1.2 mmol L−1. The effect of several inhibitors was studied, tropolone being the most active with a Ki value of 4.7 µmol L−1. In addition, the effect of cyclodextrins was studied, and the complexation constant (Kc) between 4‐tert‐butylcatechol and cyclodextrins was calculated using an enzymatic method. The value obtained for Kc was 15 310 mol L−1. Copyright © 2006 Society of Chemical Industry
3D Nanometer‐Scale Study of Coexisting Bicontinuous Morphologies in a Block Copolymer/Homopolymer Blend
Authors: Jinnai Hiroshi , Hasegawa Hirokazu , Nishikawa Yukihiro , Sevink G. J. Agur , Braunfeld Michael B. , Agard David A. , Spontak Richard J.
Published: August 2006

Summary:Coexisting bicontinuous morphologies, one ordered and one disordered, are investigated in a macrophase‐separated poly(styrene‐block‐isoprene) diblock copolymer/homopolystyrene (SI/hS) blend. Two‐phase behavior is attributed to the relatively high hS/S mass ratio (0.92). According to its crystallographic signature and channel coordination as discerned from three‐dimensional (3D) images generated by transmission electron microtomography (TEMT), the ordered morphology is classified as gyroid. The 3D local and global topological characteristics of both bicontinuous morphologies as measured directly from TEMT images are reported. The disordered morphology is further compared with molecular‐field simulations to ascertain the spatial distribution of the constituent species within the blend, thereby demonstrating the utility of high‐resolution 3D imaging coupled with molecular‐level simulations.

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