bluuebunny/crossref_metadata_2025 huggingface dataset:
Adults with acute lymphoblastic leukemia and translocation (1;19) abnormality have a favorable outcome with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high‐dose cytarabine chemotherapy
Authors: Garg Ravin , Kantarjian Hagop , Thomas Deborah , Faderl Stefan , Ravandi Farhad , Lovshe Denise , Pierce Sherry , O'Brien Susan
Published: March 2009

BACKGROUND:

Among the well described cytogenetic abnormalities in adults with acute lymphoblastic leukemia (ALL), a translocation involving chromosomes 1 and 19 (t[1;19] [q23;p13]) occurs in a small subset but has been associated variously with an intermediate prognosis or a bad prognosis in different studies.

METHODS:

Adults with ALL and t(1;19) who were treated at The University of Texas M. D. Anderson Cancer Center were reviewed. Their clinical features and outcomes were compared with those of patients who had other cytogenetic abnormalities. The study endpoints included the complete remission (CR) rate, the complete response duration (CRD), and overall survival (OS).

RESULTS:

Of 411 adults with pre‐B‐cell ALL, 12 patients had t(1;19). Ten of 12 patients with t(1;19) received hyperfractionated cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dexamethasone alternating with methotrexate and high‐dose cytarabine (hyper‐CVAD) chemotherapy; and the other 2 patients received combined vincristine, doxorubicin, and dexamethasone (VAD). All 12 patients achieved CR, and the 3‐year survival rate was 73%. Patients with t(1;19) had significantly better CRD and OS compared with all other patients combined and compared individually with patients who had Philadelphia chromosome‐positive, t(4;11), and lymphoma‐like abnormalities (deletion 6q, addition q14q, t[11;14], and t[14;18]).

CONCLUSIONS:

Adults with ALL and t(1;19) had an excellent prognosis when the received the hyper‐CVAD regimen. Cancer 2009. © 2009 American Cancer Society.
Mapping cancer mortality‐to‐incidence ratios to illustrate racial and sex disparities in a high‐risk population
Authors: Hébert James R. , Daguise Virginie G. , Hurley Deborah M. , Wilkerson Rebecca C. , Mosley Catishia M. , Adams Swann A. , Puett Robin , Burch James B. , Steck Susan E. , Bolick‐Aldrich Susan W.
Published: March 2009

BACKGROUND:

Comparisons of incidence and mortality rates are the metrics used most commonly to define cancer‐related racial disparities. In the US, and particularly in South Carolina, these largely disfavor African Americans (AAs). Computed from readily available data sources, the mortality‐to‐incidence rate ratio (MIR) provides a population‐based indicator of survival.

METHODS:

South Carolina Central Cancer Registry incidence data and Vital Registry death data were used to construct MIRs. ArcGIS 9.2 mapping software was used to map cancer MIRs by sex and race for 8 Health Regions within South Carolina for all cancers combined and for breast, cervical, colorectal, lung, oral, and prostate cancers.

RESULTS:

Racial differences in cancer MIRs were observed for both sexes for all cancers combined and for most individual sites. The largest racial differences were observed for female breast, prostate, and oral cancers, and AAs had MIRs nearly twice those of European Americans (EAs).

CONCLUSIONS:

Comparing and mapping race‐ and sex‐specific cancer MIRs provides a powerful way to observe the scope of the cancer problem. By using these methods, in the current study, AAs had much higher cancer MIRs compared with EAs for most cancer sites in nearly all regions of South Carolina. Future work must be directed at explaining and addressing the underlying differences in cancer outcomes by region and race. MIR mapping allows for pinpointing areas where future research has the greatest likelihood of identifying the causes of large, persistent, cancer‐related disparities. Other regions with access to high‐quality data may find it useful to compare MIRs and conduct MIR mapping. Cancer 2009. © 2009 American Cancer Society.
Analysing probabilistically constrained optimism
Authors: Lees Michael , Logan Brian , Theodoropoulos Georgios
Published: March 2009

In previous work we presented the DTRD algorithm, an optimistic synchronization algorithm for parallel discrete event simulation of multi‐agent systems, and showed that it outperforms Time Warp and time windows on a range of test cases. DTRD uses a decision‐theoretic model of rollback to derive an optimal time to delay read event so as to maximize the rate of LVT progression. The algorithm assumes that the inter‐arrival times (both virtual and real) of events are normally distributed. In this paper we present a more detailed evaluation of the DTRD algorithm, and specifically how the performance of the algorithm is affected when the inter‐arrival times do not follow the assumed distributions. Our analysis suggests that the performance of the algorithm is relatively insensitive to events whose inter‐arrival times are not normally distributed. However, as the variance of event inter‐arrival times increases, its performance degrades to that of Time Warp. The evaluation approach we present is generally applicable, and we sketch how a similar analysis may be performed for two other decision‐theoretic optimistic synchronization algorithms. Copyright © 2009 John Wiley & Sons, Ltd.
Organotypic glioma spheroids for screening of experimental therapies: How many spheroids and sections are required?
Authors: De Witt Hamer Philip C. , Leenstra Sieger , Van Noorden Cornelis J.F. , Zwinderman Aeilko H.
Published: March 2009

Cancer spheroids are a valuable model for screening anticancer strategies. However, studies are published using various numbers of spheroids and sections per spheroid. Here, we establish the sample size requirements for valid screening strategies to treat glioma: how many spheroids per experimental group and how many sections per spheroid are required to detect one‐third reduction in an endpoint measurement after treatment? From two glioblastoma patients, 32 untreated organotypic spheroids were cultured and sectioned entirely (14–100 sections per spheroid). The viable fraction was determined as endpoint by automated image analysis in sections and used to establish the minimally‐detectable difference between a treatment and reference group. Variance was considerable with a coefficient of variance of 21%. The biological variation in viability in sections of spheroids produced 97% of variance when sample size was large. Variance increased when numbers of spheroids but not numbers of sections per spheroid were reduced. A minimum of 12 spheroids per group and one section per spheroid was required for a valid comparison of a treatment group and a control group. When 10 treatment groups and one control group were compared, 16 spheroids per group were required. Thus, the statistical power depended almost entirely on the number of organotypic glioma spheroids and hardly on the number of sections per spheroid. The organotypic glioma spheroid model does not appear to be suitable for high‐throughput screening of anticancer strategies, because of the relatively large number of spheroids required. It is the model of choice for low‐throughput screening, because this model is far more representative for the parental tumor than any other more efficient glioma model. © 2009 International Society for Advancement of Cytometry
Effects of (−)‐carveol and HPMC on the in vitro ocular transport and the in vivo intraocular pressure lowering effects of dorzolamide formulations in normotensive New Zealand rabbits
Authors: Afouna Mohsen I. , Khedr Ala'a , Al‐Marzoqi Adnan
Published: March 2009

The objective of the current study was to maximize the ocular bioavailability of the carbonic anhydrase inhibitor, dorzolamide hydrochloride (DZD) via (a) enhancement of DZD corneal transport using terpene enhancers, (b) reducing pre‐corneal loss of the installed dose via increased formulation viscosity, and (c) assessment of the in vivo intraocular pressure (IOP) lowering effects of test formulations using rabbit. DZD was formulated as a 2% ophthalmic solution containing different concentrations of HPMC as a viscosity improving agent (VIA), and (−)‐carveol as a corneal penetration enhancer. The transport of DZD from test formulations was quantitatively determined using in vitro diffusion experiments, the permeability parameters were mathematically calculated, and the in vivo IOP lowering effects were assessed using a Tono‐Pen XL®tonometer. The results revealed a good correlation between the in vitro permeability parameters and the in vivo ΔIOP. The magnitude of the DZD‐IOP lowering effects and durations of actions for DZD formulations were dependent on (a) the concentration of (−)‐carveol, and (b) the contact period with ocular tissue which was found to be a single‐valued function of the HPMC as VIA. Drug Dev Res 70, 2009. © 2009 Wiley‐Liss, Inc.
Double bromodomain‐containing gene Brd2 is essential for embryonic development in mouse
Authors: Shang Enyuan , Wang Xiangyuan , Wen Duancheng , Greenberg David A. , Wolgemuth Debra J.
Published: March 2009

The BET subfamily of bromodomain‐containing genes is characterized by the presence of two bromodomains and a unique ET domain at their carboxyl termini. Here, we show that the founding member of this subfamily, Brd2, is an essential gene by generating a mutant mouse line lacking Brd2 function. Homozygous Brd2 mutants are embryonic lethal, with most Brd2−/− embryos dying by embryonic day 11.5. Before death, the homozygous embryos were notably smaller and exhibited abnormalities in the neural tube where the gene is highly expressed. Brd2‐deficient embryonic fibroblast cells were observed to proliferate more slowly than controls. Experiments to explore whether placental insufficiency could be a cause of the embryonic lethality showed that injecting diploid mutant embryonic stem cells into tetraploid wild‐type blastocysts did not rescue the lethality; that is Brd2‐deficient embryos could not be rescued by wild‐type extraembryonic tissues. Furthermore, there were enhanced levels of cell death in Brd2‐deficient embryos. Developmental Dynamics 238:908–917, 2009. © 2009 Wiley‐Liss, Inc.
1,7‐Electrocyclization Reactions of 2‐Aza‐4,5‐benzoheptatrienyl‐ and 4‐Aza‐6,7‐benzononatetraenyllithium Compounds: Synthesis of Novel 2‐Benzazepines and (Benzocyclooctenyl)amines
Authors: Sajitz Melanie , Fröhlich Roland , Würthwein Ernst‐Ulrich
Published: March 2009

Deprotonation reactions of N‐benzyl‐ and N‐allylimines 1 and 4 led to benzo‐annulated 2‐azaheptatrienyl‐ and 4‐azanonatetraenyllithium compounds, which underwent 1,7‐electrocyclization reactions to yield the novel 2,3‐dihydro‐1H‐benzo[c]azepines 3, 5, 11 and 13 or the (5,6‐dihydrobenzocycloocten‐5‐yl)amines 6 after subsequent addition of acyl chlorides, carbamoyl chlorides, imidoyl chlorides or pivaldehyde, respectively. Acyl and carbamoyl chlorides reacted as electrophiles at the nitrogen atom, whereas imidoyl halides and pivaldehyde attacked position C‐5 in the seven‐membered ring. In the case of pivaldehyde, the final tricyclic product 13 is the result of a subsequent nucleophilic attack at the imine moiety after a proton shift. The temperature dependence of the reaction cascades was studied, allowing preferred formation either of the seven‐membered heterocyclic systems 3 and 5 or of the eight‐membered carbocycles 6. All compounds were fully characterized, including by X‐ray diffraction studies of 6c, 6f, 11a and 13a. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
N‐Heterocyclic Carbene Derived Nickel–Pincer Complexes: Efficient and Applicable Catalysts for Suzuki–Miyaura Coupling Reactions of Aryl/Alkenyl Tosylates and Mesylates
Authors: Kuroda Jun‐ichi , Inamoto Kiyofumi , Hiroya Kou , Doi Takayuki
Published: March 2009

Catalytic activities of NHC‐derived nickel–pincer complexes for the Suzuki–Miyaura coupling reactions of aryl/alkenyl tosylates and mesylates are described. In the presence of a catalytic amount of nickelacycle 1a, a wide array of tosylates and mesylates reacted with several aryl‐ and alkenylboronic acids to afford the coupling products, generally in high yields. Fine tuning of the reaction conditions for each class of electrophiles was achieved only by choosing the appropriate reaction medium (DME for tosylates, dioxane for mesylates).(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Accreditation in the United States
Authors: Eaton Judith S.
Published: March 2009

This chapter provides an overview of self‐regulation of higher education through accreditation, the primary means by which U.S. colleges and universities assure and improve academic quality.
Concentration and drug prices in the retail market for malaria treatment in rural Tanzania
Authors: Goodman Catherine , Kachur S. Patrick , Abdulla Salim , Bloland Peter , Mills Anne
Published: March 2009

The impact of market concentration has been little studied in markets for ambulatory care in the developing world, where the retail sector often accounts for a high proportion of treatments. This study begins to address this gap through an analysis of the consumer market for malaria treatment in rural areas of three districts in Tanzania. We developed methods for investigating market definition, sales volumes and concentration, and used these to explore the relationship between antimalarial retail prices and competition.

The market was strongly geographically segmented and highly concentrated in terms of antimalarial sales. Antimalarial prices were positively associated with market concentration. High antimalarial prices were likely to be an important factor in the low proportion of care‐seekers obtaining appropriate treatment.

Retail sector distribution of subsidised antimalarials has been proposed to increase the coverage of effective treatment, but this analysis indicates that local market power may prevent such subsidies from being passed on to rural customers. Policymakers should consider the potential to maintain lower retail prices by decreasing concentration among antimalarial providers and recommending retail price levels. Copyright © 2009 John Wiley & Sons, Ltd.
Inhibiting glycosphingolipid synthesis ameliorates hepatic steatosis in obese mice #
Authors: Zhao Hongmei , Przybylska Malgorzata , Wu I-Huan , Zhang Jinhua , Maniatis Panagiotis , Pacheco Joshua , Piepenhagen Peter , Copeland Diane , Arbeeny Cynthia , Shayman James A. , Aerts Johannes M. , Jiang Canwen , Cheng Seng H. , Yew Nelson S.
Published: March 2009

Steatosis in the liver is a common feature of obesity and type 2 diabetes and the precursor to the development of nonalcoholic steatohepatitis (NASH), cirrhosis, and liver failure. It has been shown previously that inhibiting glycosphingolipid (GSL) synthesis increases insulin sensitivity and lowers glucose levels in diabetic rodent models. Here we demonstrate that inhibiting GSL synthesis in ob/ob mice not only improved glucose homeostasis but also markedly reduced the development of hepatic steatosis. The ob/ob mice were treated for 7 weeks with a specific inhibitor of glucosylceramide synthase, the initial enzyme involved in the synthesis of GSLs. Besides lowering glucose and hemoglobin A1c (HbA1c) levels, drug treatment also significantly reduced the liver/body weight ratio, decreased the accumulation of triglycerides, and improved several markers of liver pathology. Drug treatment reduced liver glucosylceramide (GL1) levels in the ob/ob mouse. Treatment also reduced the expression of several genes associated with hepatic steatosis, including those involved in lipogenesis, gluconeogenesis, and inflammation. In addition, inhibiting GSL synthesis in diet-induced obese mice both prevented the development of steatosis and partially reversed preexisting steatosis. Conclusion: These data indicate that inhibiting GSL synthesis ameliorates the liver pathology associated with obesity and diabetes, and may represent a novel strategy for treating fatty liver disease and NASH. (Hepatology 2009.)
HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity # †
Authors: Gurrin Lyle C. , Bertalli Nadine A. , Dalton Gregory W. , Osborne Nicholas J. , Constantine Clare C. , McLaren Christine E. , English Dallas R. , Gertig Dorota M. , Delatycki Martin B. , Nicoll Amanda J. , Southey Melissa C. , Hopper John L. , Giles Graham G. , Anderson Gregory J. , Olynyk John K. , Powell Lawrie W. , Allen Katrina J.
Published: March 2009

The risk of hemochromatosis-related morbidity is unknown among HFE compound heterozygotes (C282Y/H63D). We used a prospective population-based cohort study to estimate the prevalence of elevated iron indices and hemochromatosis-related morbidity for compound heterozygotes. In all, 31,192 subjects of northern European descent were genotyped for HFE C282Y and H63D. An HFE-genotype stratified random sample of 1,438 subjects, followed for an average of 12 years to a mean age of 65 years, completed questionnaires and gave blood. Clinical examinations were blinded to HFE genotype. A total of 180 (84 males) clinically examined C282Y/H63D participants were compared with 330 (149 males) controls with neither HFE mutation; 132 (65 males) and 270 (122 males), respectively, had serum iron measures at both timepoints. Mean serum ferritin (SF) and transferrin saturation (TS) were significantly greater for male and female compound heterozygotes than for wild-types at baseline and follow-up (all P < 0.02) except for females who were premenopausal at baseline, where SF was similar in both genotype groups. For subjects with serum measures from both baseline and follow-up, mean SF and TS levels did not change significantly for men or for postmenopausal women, but for premenopausal women SF levels increased from 43 to 109 μg/L for compound heterozygotes and from 35 to 64 μg/L for wild-types (both P < 0.001). Male and female compound heterozygotes had a similar prevalence of hemochromatosis-related morbidity to wild-types. One of 82 males and zero of 95 females had documented iron overload-related disease. Conclusion: For male compound heterozygotes, mean iron indices do not change during middle age but for female compound heterozygotes menopause results in increased mean SF. Although compound heterozygotes might maintain elevated iron indices during middle age, documented iron overload-related disease is rare. (Hepatology 2009;50:94–101.)
Joint interpretation of hydrological and geophysical data: electrical resistivity tomography results from a process hydrological research site in the Black Forest Mountains, Germany
Authors: Koch Kristof , Wenninger Jochen , Uhlenbrook Stefan , Bonell Mike
Published: March 2009

The use of electrical resistivity tomography (ERT; non‐intrusive geophysical technique) was assessed to identify the hydrogeological conditions at a surface water/groundwater test site in the southern Black Forest, Germany. A total of 111 ERT transects were measured, which adopted electrode spacings from 0·5 to 5 m as well as using either Wenner or dipole‐dipole electrode arrays. The resulting two‐dimensional (2D) electrical resistivity distributions are related to the structure and water content of the subsurface. The images were interpreted with respect to previous classical hillslope hydrological investigations within the same research basin using both tracer methods and groundwater level observations. A raster‐grid survey provided a quasi 3D resistivity pattern of the floodplain. Strong structural heterogeneity of the subsurface could be demonstrated, and (non)connectivities between surface and subsurface bodies were mapped. Through the spatial identification of likely flow pathways and source areas of runoff, the deep groundwater within the steeper valley slope seems to be much more connected to runoff generation processes within the valley floodplain than commonly credited in such environmental circumstances. Further, there appears to be no direct link between subsurface water‐bodies adjacent to the stream channel. Deep groundwater sources are also able to contribute towards streamflow from exfiltration at the edge of the floodplain as well as through the saturated areas overlying the floodplain itself. Such exfiltrated water then moves towards the stream as channelized surface flow. These findings support previous tracer investigations which showed that groundwater largely dominates the storm hydrograph of the stream, but the source areas of this component were unclear without geophysical measurements. The work highlighted the importance of using information from previous, complementary hydrochemical and hydrometric research campaigns to better interpret the ERT measurements. On the other hand, the ERT can provide a better spatial understanding of existing hydrochemical and hydrometric data. Copyright © 2009 John Wiley & Sons, Ltd.
A frequent target of paraproteins in the sera of patients with multiple myeloma and MGUS
Authors: Preuss Klaus‐Dieter , Pfreundschuh Michael , Ahlgrimm Manfred , Fadle Natalie , Regitz Evi , Murawski Niels , Grass Sandra
Published: March 2009

Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) paraproteins might play a role in the pathogenesis of these neoplasms. We screened a human fetal brain‐derived macroarray with the IgA or IgG containing sera of 192 consecutive MGUS and MM patients. Twenty‐nine of 192 (15.1%) paraproteins reacted with paratarg‐7, a protein of unknown function which is expressed in all human tissues. Paratarg‐7 reactivity was similarly frequent among IgA and IgG paraproteins, but all paratarg‐7 reactive IgG paraproteins belonged to the IgG3 subtype with 24/57 IgG3 (42.1%) paraproteins displaying this specificity. Sequence analysis of paratarg‐7 derived from patients having a paraprotein with specificity for paratarg‐7 revealed no differences to paratarg‐7 derived from patients with paraproteins of other specificities or healthy controls, excluding mutations or polymorphisms as a reason for its autoimmunogenicity. Similarly, Western‐blot analysis showed identical bands for paratarg‐7 derived from patients and controls. The above‐random frequency of paratarg‐7 as a paraprotein target suggests that paratarg‐7 might be involved in the development of the respective clonal proliferations. The identification of paratarg‐7 as an antigenic target enables the more detailed analysis of tumor–host interactions in these patients and their role in the pathogenesis of MM and MGUS. © 2009 UICC
Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo
Authors: Yamai Hiromichi , Sawada Naruhiko , Yoshida Takahiro , Seike Jyunichi , Takizawa Hiromitsu , Kenzaki Koichiro , Miyoshi Takanori , Kondo Kazuya , Bando Yoshimi , Ohnishi Yoshinari , Tangoku Akira
Published: March 2009

The antineoplastic effects of combinations of anticancer drugs (5‐fluorouracil, irinotecan and cisplatin) and triterpenes (ursolic acid, betulinic acid, oleanolic acid and a Japanese apricot extract (JAE) containing triterpenes) on esophageal squamous carcinoma cells were examined by the WST‐8 (2‐(2‐methoxy‐ 4‐nitrophenyl)‐3‐(4‐nitrophenyl)‐5‐(2,4‐disulfophenyl)‐2H‐tetrazolium, monosodium salt) assay in vitro and by an animal model in vivo. Triterpenes and JAE showed additive and synergistic cytotoxic effects, respectively, on esophageal squamous carcinoma cells (YES‐2cells) by combinational use of 5‐fluorouracil. JAE and 5‐fluorouracil induced cell cycle arrest at G2/M phase and at S phase, respectively, and caused apoptosis in YES‐2 cells. A new animal model of esophageal cancer causing tumor colonization of the peritoneal cavity and producing bloody ascites was made by injecting YES‐2 cells into the peritoneal cavity of a severe combined immunodeficiency mouse. In this model, 5‐fluorouracil inhibited colonization of tumor cells in the peritoneum. The addition of JAE to 5‐fluorouracil augmented the suppression of experimental metastasis of the peritoneum. The numbers of peritoneal nodules of more than 2 mm in diameter in mice treated with 5‐fluorouracil and JAE were less than those in mice treated with 5‐fluorouracil alone or JAE alone. These results suggest that triterpenes, especially JAE, are effective supplements for enhancing the chemotherapeutic effect of 5‐fluorouracil on esophageal cancer. © 2009 UICC
HOX D13 expression across 79 tumor tissue types
Authors: Cantile Monica , Franco Renato , Tschan Adrienne , Baumhoer Daniel , Zlobec Inti , Schiavo Giulia , Forte Iris , Bihl Michel , Liguori Giuseppina , Botti Gerardo , Tornillo Luigi , Karamitopoulou‐Diamantis Eva , Terracciano Luigi , Cillo Clemente
Published: March 2009

HOX genes control normal development, primary cellular processes and are characterized by a unique genomic network organization. Locus D HOX genes play an important role in limb generation and mesenchymal condensation. Dysregulated HOXD13 expression has been detected in breast cancer, melanoma, cervical cancer and astrocytomas. We have investigated the epidemiology of HOXD13 expression in human tissues and its potential deregulation in the carcinogenesis of specific tumors. HOXD13 homeoprotein expression has been detected using microarray technology comprising more than 4,000 normal and neoplastic tissue samples including 79 different tumor categories. Validation of HOXD13 expression has been performed, at mRNA level, for selected tumor types. Significant differences are detectable between specific normal tissues and corresponding tumor types with the majority of cancers showing an increase in HOXD13 expression (16.1% normal vs. 57.7% cancers). In contrast, pancreas and stomach tumor subtypes display the opposite trend. Interestingly, detection of the HOXD13 homeoprotein in pancreas‐tissue microarrays shows that its negative expression has a significant and adverse effect on the prognosis of patients with pancreatic cancer independent of the T or N stage at the time of diagnosis. Our study provides, for the first time, an overview of a HOX protein expression in a large series of normal and neoplastic tissue types, identifies pancreatic cancer as one of the most affected by the HOXD13 hoemoprotein and underlines the way homeoproteins can be associated to human cancerogenesis. © 2009 UICC
Design of a multiphase osteochondral scaffold III: Fabrication of layered scaffolds with continuous interfaces
Authors: Harley Brendan A. , Lynn Andrew K. , Wissner‐Gross Zachary , Bonfield William , Yannas Ioannis V. , Gibson Lorna J.
Published: March 2009

There is a need to improve current treatments for articular cartilage injuries. This article is the third in a series describing the design and development of an osteochondral scaffold based on collagen‐glycosaminoglycan and calcium phosphate technologies for regenerative repair of articular cartilage defects. The previous articles in this series described methods for producing porous, three‐dimensional mineralized collagen‐GAG (CGCaP) scaffolds whose composition can be reproducibly varied to mimic the composition of subchondral bone, and pore microstructure and mineral phase can be modified. This article describes a method, “liquid‐phase cosynthesis,” that enables the production of porous, layered scaffolds that mimic the composition and structure of articular cartilage on one side, subchondral bone on the other side, and the continuous, gradual or “soft” interface between these tissues: the tidemark of articular joints. This design enables the layered scaffolds to be inserted into the subchondral bone at an osteochondral defect site without the need for sutures, glue, or screws, with a highly interconnected porous network throughout the entire osteochondral defect. Moreover, the differential moduli of the osseous and cartilaginous compartments enable these layered scaffolds to exhibit compressive deformation behavior that mimics the behavior observed in natural articular joints. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Experimental determination of Anammox decay coefficient
Authors: Scaglione D. , Caffaz S. , Bettazzi E. , Lubello C.
Published: March 2009

This paper describes an experimental method used to evaluate the anaerobic ammonium oxidation (Anammox) decay coefficient by means of a batch test. The test was carried out using an experimental procedure based on manometric measurements of the dinitrogen gas that is produced by the Anammox process. The accuracy of the procedure had previously been assessed, and the method was used to determine the specific Anammox activity (SAA mg N2‐N g VSS−1 d−1,) and the maximum nitrogen production rate (MNPR, NmL N2 L−1 d−1) under several different conditions. A specific batch test, which lasted for 148 days, was performed to assess the decay coefficient. The activity decrease was monitored and the estimated value of the decay coefficient was found to be 0.0048 d−1 at 35 °C, for which the corresponding half‐life time of the Anammox biomass was 145 days. This value is higher than other values reported in the literature, but in accordance with the slow growth rate of the Anammox bacteria. Copyright © 2009 Society of Chemical Industry
Mesoionic carbenes: Reactions of 1,3‐diphenyltetrazol‐5‐ylidene with electron‐deficient alkenes, and synthesis and catalytic activities of the (tetrazol‐5‐ylidene)rhodium(I) complexes
Authors: Araki Shuki , Yokoi Keisaku , Sato Ryosuke , Hirashita Tsunehisa , Setsune Jun‐Ichiro
Published: March 2009

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The reactions of 1,3‐diphenyltetrazol‐5‐ylidene, a rare example of mesoionic carbenes, with electron‐deficient unsaturated compounds were studied. The carbene reacted with dimethyl 1,2,4,5‐tetrazine‐3,6‐dicarboxylate to give a 5‐tetrazoliomethylide, together with hydrazine derivatives. The reaction with tetracyanoethylene gave another methylide in low yield. On the contrary, the reactions with weaker electrophiles, such as 3,6‐diphenyl‐1,2,4,5‐tetrazine, fumalonitrile, N‐phenylmaleimide, and dimethyl acetylenedicarboxylate, did not give any coupling products, but gave phenylated products and/or Michael addition products via the degradation of the 1,3‐diphenyltetrazole ring. Novel mesoionic mono‐ and bis(carbene)‐rhodium(I) complexes were synthesized and the structures were characterized by X‐ray crystallography. Their catalytic activities for the decarbonylative addition reaction of benzoyl chloride to ethynylbenzene were investigated. J. Heterocyclic Chem., (2009).
Predictors of smoking cessation and relapse after hospitalization for acute coronary syndrome
Authors: Holtrop Jodi Summers , Stommel Manfred , Corser William , Holmes‐Rovner Margaret
Published: March 2009

BACKGROUND:

A hospital admission for a serious cardiac event offers a unique opportunity for smoking cessation. Understanding the factors that predict and enhance cessation among smoking cardiac inpatients is important for hospital physicians and clinical staff.

STUDY OBJECTIVE:

To determine factors that predict smoking cessation, relapse, or continued smoking among posthospitalized cardiac patients who were smoking at the time of admission.

SAMPLE:

Patients hospitalized with acute coronary syndrome (ACS) were recruited from 5 hospitals in Michigan to participate in a study assessing hospital quality improvement plus at‐home health behavior change counseling.

MEASUREMENTS:

Patient interview data were collected shortly after discharge and 3 and 8 months later to describe patient demographics, clinical characteristics, tobacco use, and other behaviors. Multinomial logit regression was used to predict smoking cessation, relapse, and continued smoking.

RESULTS:

Of patients smoking at hospitalization who completed both follow‐up interviews, 56.8% (n = 111) were not smoking at 8 months. A significant predictor of successful cessation was higher household income (odds ratio [OR] = 4.72; P = 0.003), while having other smokers in the household decreased the odds of cessation (OR = 0.20; P = 0.001). History of depression increased the odds of relapse (OR = 6.38; P = 0.002) and being a lighter smoker decreased the odds (OR = 0.16; P = 0.026).

CONCLUSIONS:

Although approximately one‐half of the smokers in this study reported successful cessation, interventions are still needed to assist all smokers to successfully quit smoking after an ACS hospitalization. Our data suggest targeting follow‐up programs to include other family members and using specialized methods for heavy smokers. Journal of Hospital Medicine 2009;4:E3–E9. © 2009 Society of Hospital Medicine.
Biochemical analysis of oligomerization of expanded polyalanine repeat proteins
Authors: Nojima Jun , Oma Yoko , Futai Eugene , Sasagawa Noboru , Kuroda Reiko , Turk Boris , Ishiura Shoichi
Published: March 2009

Many human proteins contain amino acid repeats that can form homopolymeric amino acid (HPAA) tracts. HPAA tract proteins that contain polyalanine sequences promote diseases, including oculopharyngeal muscular dystrophy. The pathological properties of these proteins develop when the repeats match or exceed ∼20 residues. We analyzed the oligomerization of yellow fluorescent protein (YFP) and GST fusion proteins containing >20 alanine repeats by using sucrose density gradient centrifugation. YFP and GST fusion proteins having 23 polyalanine residues sedimented readily in sucrose density gradients, suggesting instability and oligomerization of proteins with an excess of 20 alanine repeats. Moreover, GST fusion proteins were resistant to trypsin digestion after oligomerization. Oligomerized artificial proteins with long polyalanine repeats may be suitable models for studying polyalanine‐related diseases. © 2009 Wiley‐Liss, Inc.
Supracricoid laryngectomy: Age influence on long‐term functional results
Authors: Schindler Antonio , Favero Elena , Capaccio Pasquale , Albera Roberto , Cavalot Andrea L. , Ottaviani Francesco
Published: March 2009

Objectives/Hypothesis:

Supracricoid laryngectomies (SCL) are conservative surgical techniques for the treatment of selected laryngeal carcinomas, currently adopted also in old patients. Long‐term functional results have not been reported in elderly patients. The aim of this study is to compare voice and swallowing in elderly and younger patients following SCL.

Study Design:

Cross‐sectional study.

Methods:

Twenty male patients who underwent SCL were recruited in the study; 10 were younger than 65 years at the time of surgery and 10 were older. Video‐endoscopic ratings were taken of neoglottic vibration patterns and bolus transit. Voices were perceptually rated using the GIRBAS scale. The maximum phonation time (MPT) and the syllables diadochokinesis were measured. Spectrograms were recorded. All of the patients completed a self‐assessment questionnaire for both voice and swallowing. The data obtained from the two groups were compared through the Mann‐Whitney test.

Results:

Video‐endoscopic ratings of neoglottal vibration and bolus transit showed no difference between the two groups. The perceptual assessment showed a harsh voice in both groups. No significant difference was found for mean syllable diadochokinesis and the mean MPT was 6.3 seconds and 8.8 seconds, respectively in the younger and older group. The mean value of the Yanagihara scale of voice spectrogram was 3.8 and 3.7. Voice and swallowing quality‐of‐life questionnaires revealed satisfied patients in both age groups.

Conclusions:

Age by itself does not have a significant impact on long‐term functional results following SCL. Meticulous selection of the candidate to SCL allows the application of this surgical technique with adequate long‐term functional results. Laryngoscope, 2009
Nutritionally optimized ice cream fats
Authors: Persson Marcus
Published: March 2009

Fats (triacylglycerols) can crystallize in different forms each with its own unique packing of the molecules. This influences the density, melting point, the way the crystals grow, and the way they respond to cooling and shearing etc. In this work we have studied several different ice cream fats in healthier ice creams containing less saturated fatty acids (SFA). Where the amount of SFA has been greatly reduced it is necessary to design ice cream fats that crystallize and grow crystals in a specific way. The fat systems form crystals within the emulsion drops during cooling and freezing of the mix. In this part of the process we also see a destabilization of droplets creating an opportunity for the fat crystals to continue to grow and form a network in the bulk phase and lock the ice crystals. This is important since ice melts as the temperature fluctuates even at temperatures well below zero degrees because of sugars and salts from milk solids. By having a system where the crystals grow more as plates the crystals span a much greater volume. This facilitates the formation of agglomerated fat that encompasses small ice crystals giving ice creams with greater form stability and storage stability. Furthermore designing fat mixtures that crystallize in the beta form gives a higher melting point. This, together with the fact that these crystals have lower solubility than beta prime crystals gives a higher solid fat content which is beneficial when working with low SFA systems. In AAK's new generation of low SFA fats we have used this knowledge and this is why our Akomix LS range performs so well in application.
Almost sure central limit theorem for partial sums and maxima
Authors: Zuoxiang Peng , Lili Wang , Nadarajah Saralees
Published: March 2009

Let X, X1, X2, … be i.i.d. random variables with nondegenerate common distribution function F, satisfying EX = 0, EX2 = 1. Let Xi and Mn = max{Xi, 1 ≤ i ≤ n }. Suppose there exists constants an > 0, bn ∈ R and a nondegenrate distribution G (y) such that
equation image
Then, we have
equation image
almost surely, where f (x, y) denotes the bounded Lipschitz 1 function and Φ(x) is the standard normal distribution function (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Sural perforator flap: Assessment of the posterior calf region as donor site for a free fasciocutaneous flap
Authors: Shimizu Fumiaki , Kato Aiko , Sato Haruaki , Taneda Hiroko
Published: March 2009

Three kinds of free fasciocutaneous flap from the posterior calf region have been described in the literature: the medial sural perforator flap, the lateral sural perforator flap, and the traditional posterior calf fasciocutaneous flap that is supplied by superficial cutaneous vessels. Moreover, it has been reported that superficial cutaneous vessels are of a suitable size for microanastomosis when deep musclocutaneous perforators are absent or relatively tiny. To establish a safe technique for free fasciocutaneous flap elevation from the posterior calf region, we examined the number and location of the musculocutaneous perforators and the size of superficial cutaneous vessels at their origin from the popliteal artery in six formalinized cadavers. We found that all legs had at least one perforator either from the medial sural artery or the lateral sural artery. By contrast, we failed to find superficial cutaneous vessels of suitable size for microanastomosis in three legs, and there was no significant inverse relationship between the diameter of the superficial cutaneous artery and the number of musculocutaneous perforators. Our results suggest that the medial sural perforator flap and the lateral sural perforator flap might be the surgeon's first and second choice, respectively. The traditional posterior calf fasciocutaneous flap should be the third choice because our study suggests that its availability is doubtful. Another site is recommended, when preoperative Doppler study suggests that the existence of musculocutaneous perforator is in doubt. Two clinical cases, with a medial sural perforator flap and a lateral sural perforator flap, respectively, are presented. © 2009 Wiley‐Liss, Inc. Microsurgery, 2009.
Sarcoplasmic–endoplasmic–reticulum Ca2+‐ATPase and calsequestrin are overexpressed in spared intrinsic laryngeal muscles of dystrophin‐deficient mdx mice
Authors: Ferretti Renato , Marques Maria Julia , Pertille Adriana , Santo Neto Humberto
Published: March 2009

In the mdx mouse model of Duchenne muscular dystrophy, the lack of dystrophin is associated with increased calcium levels and skeletal muscle myonecrosis. The intrinsic laryngeal muscles (ILM) are protected and do not undergo myonecrosis. We investigated whether this protection is related to an increased expression of calcium‐binding proteins, which may protect against the elevated calcium levels seen in dystrophic fibers. The expression of sarcoplasmic–endoplasmic–reticulum Ca2+‐ATPase and calsequestrin was examined in ILM and in nonspared limb muscles of control and mdx mice using immunofluorescence and immunoblotting. Dystrophic ILM presented a significant increase in the proteins studied when compared to controls. The increase of Ca2+‐handling proteins in dystrophic ILM may permit better maintenance of calcium homeostasis, with the consequent absence of myonecrosis. The results further support the concept that abnormal Ca2+‐handling is involved in dystrophinopathies. Muscle Nerve, 2009
Complexity science of multiscale materials via stochastic computations
Authors: Liu Wing Kam , Siad Larbi , Tian Rong , Lee Sanghoon , Lee Dockjin , Yin Xiaolei , Chen Wei , Chan Stephanie , Olson Gregory B. , Lindgen Lars‐Erik , Horstemeyer Mark F. , Chang Yoon‐Suk , Choi Jae‐Boong , Kim Young Jin
Published: March 2009

New technological advances today allow for a range of advanced composite materials, including multilayer materials and nanofiber‐matrix composites. In this context, the key to developing advanced materials is the understanding of the interplay between the various physical scales present, from the atomic level interactions to the microstructural composition and the macroscale behavior. Using the developing ‘multiresolution data sets mechanics’, the ‘predictive science‐based governing laws of the materials microstructure evolutions’ are derived and melted into a ‘stochastic multiresolution design framework.’ Under such a framework, the governing laws of the materials microstructure evolution will be essential to assess, across multiple scales, the impact of multiscale material design, geometry design of a structure, and the manufacturing process conditions, by following the cause–effect relationships from structure to property and then to performance.

The future integrated multiscale analysis system will be constructed based on a probabilistic complexity science‐based mathematical framework. Its verification, validation and uncertainty quantification are done through carefully designed experiments, and the life‐cycled materials design for products design and manufacturing is performed through the use of petascale computing. The various techniques of microstructure reconstruction result in the generation of model microstructures that, at some level, has the same statistical properties as the real heterogeneous media. Having reconstructed the heterogeneous medium, one can then evaluate its effective properties via direct numerical simulation and compare these values with experimentally measured properties of the actual medium. The proposed analysis will be dynamic in nature to capture the multi‐stage historical evolvement of material/structure performance over the life span of a product. In addition to providing more accurate assessment of structure performance with stochastic multiscale analysis, our development will provide the capability of predicting structure failures and system reliability to enable more reliable design and manufacturing decisions in product development. Copyright © 2009 John Wiley & Sons, Ltd.
Adapting surveys for nonprofit research
Authors: Ritchie William J. , Sherlock John J.
Published: March 2009

Many useful survey instruments have been developed in the for‐profit management arena, but they often require varying levels of adaptation for relevant application in the nonprofit context. This research note first explains key steps in the process for adapting and testing a survey instrument. It then illustrates how each step should be applied and reported using a case study adaptation of Hodgkinson's (1992) strategic locus of control instrument for nonprofit use.
Oxygen isotope analysis in a land of environmental extremes: the complexities of isotopic work in the Andes
Authors: Knudson K. J.
Published: March 2009

The Andes, which have a wide variety of diverse and distinct environmental zones ranging from the hyperarid coast to the high‐altitude altiplano, are an ideal region in which to explore the use of oxygen isotope analyses to elucidate archaeological residential mobility. However, some questions remain, including the mobility of water through the environment, the seasonal and annual variability of precipitation in the past, and the role of water storage and beverage preparation techniques. Here, the advantages and disadvantages of oxygen isotope analysis in the Andes, and beyond, will be explored using oxygen isotope data from archaeological human enamel and bone from Peru, Bolivia and Chile (c. AD 1–1500). Although strontium isotope values from this region vary according to regional geology, oxygen isotope data do not always follow expected patterns based on known environmental variables, and probably reflect the movement of water throughout the Andes, complicating its use as a tool to identify human migration in the past. Copyright © 2009 John Wiley & Sons, Ltd.
A contribution to the study of diet of formative societies in northwestern Argentina: isotopic and archaeological evidence
Authors: Calo C. Marilin , Cortés Leticia I.
Published: March 2009

The present paper is aimed at presenting and discussing currently available isotopic values (δ13C) of human samples dated to the Formative Period in the Santa María Valley, adjacent to the Yungas and Puna regions of northwestern Argentina. Results show that the expected tendency of increasingly positive C4 isotopic values consistent with the hypothesis of maize agriculture consolidation during Formative times was only partially corroborated. A fuller understanding of this trend is limited by the scant number of samples as well as by the lack of local reference values. Notwithstanding, the revision of this evidence in light of relevant archaeobotanical data allows us to start building a more accurate reconstruction of the lifestyles of early agricultural societies settled in northwestern Argentina. Copyright © 2009 John Wiley & Sons, Ltd.
Identification of target antigens of self‐reactive IgG in intravenous immunoglobulin preparations
Authors: Bussone Guillaume , Dib Hanadi , Dimitrov Jordan D. , Camoin Luc , Broussard Cédric , Tamas Nicolas , Guillevin Loïc , Kaveri Srini V. , Mouthon Luc
Published: March 2009

Intravenous immunoglobulin (IVIg) contains a wide range of self‐reactive immunoglobulins (Ig) G. Acidic pH is known to increase the reactivity of purified IgG with self‐antigens. We describe here the target antigens of IgG autoantibodies in IVIg and analyze the influence of acidic pH on IgG reactivities. We used 2‐DE and immunoblotting with protein extracts of human umbilical vein endothelial cells (HUVEC) and HEp‐2 cells. Two IVIg preparations obtained by ethanol fractionation [one with an acidic pH step (acidic‐IVIg) and one with β‐propiolactone (propiolactone‐IVIg)] and a pool of sera from 12 healthy individuals were tested. Serum IgG of 3 healthy individuals and IgG purified from the same sera with elution at pH 2.8 were also tested individually. Finally, propiolactone‐IVIg was acidified at pH 2.8. IgG obtained with a step at low pH recognized many more target spots than IgG obtained without acidic pH. Our findings demonstrate that an acidic pH step artificially enlarges the repertoire of self‐reactive IgG. Thus, protein spots recognized by IgG in propiolactone‐IVIg represent the core set of self‐antigens targeted by IVIg. Overall, 96 proteins were identified by MS. Fourteen were recognized in both extracts including glycolysis proteins such as α‐enolase, RNA processing and cytoskeletal proteins such as lamin‐A/C.