bluuebunny/crossref_metadata_2025 huggingface dataset:
Serial Glycosylated Hemoglobin Levels and Risk of Colorectal Neoplasia among Patients with Type 2 Diabetes Mellitus
Authors: Yang Yu-Xiao , Habel Laurel A. , Capra Angela M. , Achacoso Ninah S. , Quesenberry Charles P. , Ferrara Assiamira , Levin Theodore R. , Lewis James D.
Published: December 2010

Background: Hyperglycemia may increase the risk of colorectal neoplasia by serving as an energy source for neoplastic growth. We sought to determine whether glycemic control measured by serial hemoglobin A1c (HbA1c) was associated with the risk of colorectal adenoma.

Methods: Among a cohort of patients with type 2 diabetes mellitus who received health care within the Kaiser Permanente Northern California from 1994 to 2005, we conducted 2 case–control analyses. Cases had at least 1 colorectal adenoma identified at either colonoscopy (analysis 1) or sigmoidoscopy (analysis 2). Controls had no colorectal neoplasia identified at the corresponding endoscopic examination. Serial HbA1c levels between the cases and the controls were compared using a longitudinal model.

Results: Case–control analysis 1 included 4,248 patients, of whom 1,296 (31%) had at least 1 adenoma. The adjusted mean HbA1c levels among those without any adenomas was 8.20% versus 8.26% among those with at least 1 adenoma, a difference of 0.06% (95% CI = −0.02 to 0.14, P = 0.16). Case–control analysis 2 included 9,813 patients, of whom 951 (10%) had at least 1 distal adenoma. The adjusted mean HbA1c levels among those without any distal adenomas was 8.32% versus 8.37% among those with at least 1 distal adenoma, a difference of 0.05% (95% CI = −00.04 to 0.14, P = 0.25). The results were similar for advanced adenomas.

Conclusions: Glycemic control was not associated with the risk of colorectal adenoma among diabetic persons.

Impact: These results would suggest that glycemic control is unlikely to confound the reported association between diabetes medications and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 19(12); 3027–36. ©2010 AACR.
Polymorphisms inside MicroRNAs and MicroRNA Target Sites Predict Clinical Outcomes in Prostate Cancer Patients Receiving Androgen-Deprivation Therapy
Authors: Bao Bo-Ying , Pao Jiunn-Bey , Huang Chun-Nung , Pu Yeong-Shiau , Chang Ta-Yuan , Lan Yu-Hsuan , Lu Te-Ling , Lee Hong-Zin , Juang Shin-Hun , Chen Lu-Min , Hsieh Chi-Jeng , Huang Shu-Pin
Published: December 2010

Purpose: Recent evidence indicates that small noncoding RNA molecules, known as microRNAs (miRNAs), are involved in cancer initiation and progression. We hypothesized that genetic variations in miRNAs and miRNA target sites could be associated with the efficacy of androgen-deprivation therapy (ADT) in men with prostate cancer.

Experimental Design: We systematically evaluated 61 common single nucleotide polymorphisms (SNPs) inside miRNAs and miRNA target sites in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT were assessed by Kaplan–Meier analysis and Cox regression model.

Results: Four, seven, and four SNPs were significantly associated with disease progression, PCSM, and ACM, respectively, after ADT in univariate analysis. KIF3C rs6728684, CDON rs3737336, and IFI30 rs1045747 genotypes remained as significant predictors for disease progression; KIF3C rs6728684, PALLD rs1071738, GABRA1 rs998754, and SYT9 rs4351800 remained as significant predictors for PCSM; and SYT9 rs4351800 remained as a significant predictor for ACM in multivariate models that included clinicopathologic predictors. Moreover, strong combined genotype effects on disease progression and PCSM were also observed. Patients with a greater number of unfavorable genotypes had a shorter time to progression and worse prostate cancer-specific survival during ADT (P for trend < 0.001).

Conclusion: SNPs inside miRNAs and miRNA target sites have a potential value to improve outcome prediction in prostate cancer patients receiving ADT. Clin Cancer Res; 17(4); 1–9. ©2010 AACR.
Clinical Application of Proteomics in Breast Cancer: State of the Art and Perspectives
Authors: Goncalves Anthony , Bertucci François
Published: December 2010

Breast cancer is one of the most frequent and deadly cancers in industrialized countries. The identification of accurate biomarkers that improve the screening, diagnosis, prognostication and prediction of therapeutic response or toxicity, and the identification of novel molecular therapeutic targets are crucial. Today, high-throughput molecular techniques permit investigators to systematically interrogate the genome, transcriptome, and proteome of cancer cells. During the past decade, mRNA expression profiling has been successfully applied to the molecular characterization of breast cancers. Application of proteomics-based techniques is also considered crucial for detecting new biomarkers. In this review, we present the proteomics-based methods that have been applied to date to breast cancer samples for diagnostic and prognostic purposes. Despite their current limits, these pioneering techniques are promising. The most important results as well as the current limitations and perspectives are summarized and discussed.
Assessment of the Stability of Novel Antibacterial Triazolyl Oxazolidinones Using a Stability-Indicating High-Performance Liquid Chromatography Method
Authors: Phillips Oludotun A. , Sharaf Leyla H. , Abdel-Hamid Mohammed E. , Varghese Reny
Published: December 2010

Objectives: To evaluate the stability of 12 triazolyl oxazolidinone (TOZ) derivatives in simulated gastric and intestinal fluids as well as in human plasma at 37 ± 1°C. Materials and Methods: A stability-indicating high-performance liquid chromatography (HPLC) procedure with a C8 column (250 × 40 mm, 5 µm particle size) and a mobile phase of acetonitrile/H2O (50/50 v/v) at 1.0 ml/min was used. Accelerated stability studies were conducted at 37 ± 1°C in 0.1 M HCl solution as simulated gastric fluid and in phosphate buffer solution (pH about 7.4) as simulated intestinal fluid. The stability of TOZs in human plasma at a simulated biological temperature of 37 ± 1°C was evaluated as well. Results: The stability studies indicated that the examined TOZs were stable in the above media, with the exception of compounds 1a [tert- butyl 4-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-fluorophenyl)piperazine-1-carboxylate] and 1b [tert-butyl 4-(2-fluoro-4-((R)-5-((4-methyl-1H-1,2,3-triazol- 1-yl)methyl)-2-oxooxazolidin-3-yl)phenyl) piperazine-1-carboxylate], which underwent degradation in simulated gastric fluid. The degradation kinetics revealed degradation parameters (kdeg, t1/2, t90) of 0.180 h–1, 3.85 h, and 0.58 h for 1a and of 0.184 h–1, 3.76 h and 0.57 h for 1b, respectively. Furthermore, the degradation products were identified by mass-spectrometric analysis at mass-to-charge ratios 347.5 and 361.5, respectively, and proton nuclear magnetic resonance analysis. Conclusion: With the exception of compounds 1a and 1b, the TOZs are stable in simulated gastric and intestinal fluids as well as in human plasma. Being carbamate derivatives, compounds 1a and 1b underwent fast and complete degradation in simulated gastric fluid. The obtained results should be considered for future studies of formulation of structurally related TOZs in oral dosage forms.
Mortality of Neonatal Respiratory Failure Related to Socioeconomic Factors in Hebei Province of China
Authors: Ma Li , Liu Cuiqing , Wang Yuqi , Li Shufang , Zhai Shufen , Gu Xiaofeng , Liu Fang , Yan Aixia , Guo Wei , Li Yingyu , Xiao Min , Yin Jianying , Li Yanzhi , Liu Xia , Wang Rong , Kirpalani Haresh , Sun Bo ,   Hebei Neonatal Network Study Group
Published: December 2010

Dramatic progress has occurred in neonatal intensive care in tertiary centers in mid-eastern China. We investigated the characteristics of neonatal respiratory failure (NRF) including the incidence, management, outcomes and costs in 14 neonatal intensive care units (NICUs) of Hebei, a province at an intermediate economic level in China. Over a period of 12 consecutive months in 2007–2008, perinatal data were collected prospectively from all NICU admissions (n = 11,100). NRF was defined as severe hypoxemia requiring respiratory support for more than 24 h, and was diagnosed in 1,875 newborns (16.9%). The average birth weight of newborns with NRF was 2,200 g (range 600–5,500 g), with 60.9% <2,500 g, and 2% <1,000 g. The male:female ratio was 2.6:1. The leading diagnosis was respiratory distress syndrome; 58.3% of newborns with respiratory distress syndrome received surfactant. Continuous positive airway pressure was used more than ventilation (73.3 vs. 49.1%,p < 0.001). Overall, the mortality rate until discharge was 31.4% (583/1,859). Most deaths (432, 74.1%) followed a parental decision to withdraw care. NRF mortality varied in association with different gross domestic product levels, family annual income and nurse-to-bed ratios. The median cost of a hospital stay was 10,169 CNY (interquartile range: 6,745–16,386) for NRF survivors. We conclude that, despite the available respiratory support in these emerging NICUs, the mortality of NRF remains. This was associated with prematurity, standard of care but also with socioeconomic factors affecting treatment decisions. Assessment of efficacy of respiratory support for NRF in such emerging neonatal services should account for both standard of care and socioeconomic conditions.
Effects of Nadroparin, Enoxaparin, and Unfractionated Heparin on Endogenous Formation of Factor Xa and IIa and on Thrombelastometry Profiles in Cord versus Adult Blood
Authors: Cvirn Gerhard , Hoerl Gerd , Tafeit Erwin , Heinl Nikolaus , Wodrig Kathrin , Wagner Thomas , Koestenberger Martin , Juergens Guenther
Published: December 2010

Background: To date, only few pharmacokinetic studies on low-molecular-weight heparins (LMWHs) in neonates exist not allowing to formally assess pharmacodynamics of LMWHs in neonates. Objective: To evaluate the anticoagulant effects of the two LMWHs nadroparin and enoxaparin on endogenous formation of FXa or FIIa in cord versus adult platelet-poor plasma (PPP) and on thrombelastometry profiles in cord versus adult whole blood (WB). Unfractionated heparin (UH) was the reference antithrombotic drug. Methods: The effects of nadroparin, enoxaparin, or UH on endogenous formation of FXa or FIIa was investigated in tissue factor-activated PPP using a subsampling technique and chromogenic substrates. The anticoagulant efficacy of these drugs was also investigated in WB triggered by the physiological relevant activator collagen/endogenous thrombin using thrombelastometry. Results: The major findings are (i) nadroparin is as efficient as enoxaparin concerning inhibition of the endogenous formation of FXa and FIIa, (ii) cord PPP and WB are significantly more susceptible to the addition of LMWHs or UH than adult PPP or WB, and (iii) compared by equivalent anti-FXa activity, the anticoagulant action of UH is markedly higher than that of the LMWHs in PPP and WB of neonatal or adult origin. Conclusions: Administration of LMWHs in neonates has to be performed carefully to avoid bleeding side effects due to their high anticoagulant efficacy in cord PPP and WB.
Diagnostic Accuracy of Serum Parathyroid Hormone Levels in Kidney Transplant Recipients with Moderate-to-Advanced CKD
Authors: Kovesdy Csaba P. , Molnar Miklos Z. , Czira Maria E. , Rudas Anna , Ujszaszi Akos , Sarvary Eniko , Ambrus Csaba , Szathmari Miklos , Remport Adam , Mucsi Istvan
Published: December 2010

Background/Aims: Elevated parathyroid hormone (PTH) is used to diagnose high turnover bone disease in chronic kidney disease (CKD). The diagnostic accuracy of PTH in kidney transplant recipients with CKD is unknown. Methods: We examined kidney transplant recipients with CKD stages 3 (n = 498) and 4 (n = 141) to determine the sensitivity and specificity of the Kidney/Dialysis Outcome Quality Initiative (K/DOQI)-recommended PTH levels in detecting elevated serum β-CrossLaps (CTX) or osteocalcin (OC) levels. We performed receiver-operator curve analyses to determine CKD stage-specific PTH levels that provide optimal diagnostic accuracy. Results: PTH below the lower limits of the K/DOQI ranges (35 and 70 pg/ml in CKD stages 3 and 4, respectively) showed sensitivity of >90% in diagnosing increases in biochemical markers. The upper limits (70 and 110 pg/ml), however, showed poor specificity. A specificity of >90% for detecting increased biochemical markers was seen with PTH of >140 and >240 pg/ml in CKD stages 3 and 4, respectively. Conclusion: Currently applied cutoffs for PTH in kidney transplant recipients with CKD stages 3 and 4 do not appear to adequately detect increased biochemical markers of bone turnover. Diagnostic uncertainty exists in patients with CKD stage 3 and PTH between 35 and 140 pg/ml, and CKD stage 4 and PTH between 70 and 240 pg/ml.
Giardia lamblia Infection and Its Implications for Vitamin A Liver Stores in School Children
Authors: Astiazaran-Garcia Humberto , Lopez-Teros Veronica , Valencia Mauro E. , Vazquez-Ortiz Francisco , Sotelo-Cruz Norberto , Quihui-Cota Luis
Published: December 2010

Background: Vitamin A deficiency (VAD) is a nutritional problem affecting the health of people in developing countries because VAD compromises innate and adaptive immunity, increasing a person’s predisposition toward infectious diseases. In addition, a high prevalence of infectious diseases continues to be a problem in developing countries, including Giardia lamblia. G. lamblia may be related to VAD because of its ability to change the intestinal architecture, thereby compromising the absorption of vitamin A. The aim of this study was to evaluate the effect of giardiasis on serum retinol levels and vitamin A liver stores in school children. Methods: Thirty Giardia-infected school children participated in this study. Vitamin A liver stores were evaluated with the modified relative dose response (MRDR) technique, and antiparasitic treatment was administered. In addition, anthropometric and dietary data were collected. Results: According to anthropometric indicators (age-appropriate Z scores for weight, height and body mass index) and daily vitamin A intake, the children had a normal nutritional status. Although the mean serum retinol levels did not change significantly after treatment for Giardia (p > 0.05), the MRDR values showed significant improvement (p < 0.002). Conclusion: Giardiasis not only compromises the vitamin A status through intestinal malabsorption, it also causes profound mobilization of liver retinol stores.
Clinical and Cytological Effects of Pimecrolimus Cream 1% after Resolution of Active Atopic Dermatitis Lesions by Topical Corticosteroids: A Randomized Controlled Trial
Authors: Bangert Christine , Strober Bruce E. , Cork Michael , Ortonne Jean-Paul , Luger Thomas , Bieber Thomas , Ferguson Adam , Ecker Rupert C. , Kopp Tamara , Weise-Riccardi Sophia , Guettner Achim , Stingl Georg
Published: December 2010

Background: Topical pimecrolimus may maintain remissions of atopic dermatitis (AD) by inhibiting subclinical inflammation. Objective: To evaluate clinical and cytological effects of pimecrolimus in topical corticosteroid-treated and resolved AD lesions. Methods: Patients (n = 67) with resolved AD lesions were randomized to 3-week double-blind treatment with either pimecrolimus cream 1% or vehicle cream. Outcome measures were reduction in Eczema Area and Severity Index (EASI) and number of leukocytes in skin biopsies in all randomized patients who were evaluable at the end of study. Results: The proportion of patients with a localized EASI <2 at the end of study was higher with pimecrolimus cream 1% than with vehicle cream (73.5 vs. 39.4%, respectively). There was a significant decrease in the number of infiltrating CD45+ cells in pimecrolimus cream 1% compared with placebo cream (–88.2 vs. 43.2 cells/mm2, respectively, p = 0.047) and a slight but nonsignificant reduction in the number of dermal dendritic cells, Langerhans cells, T cells and macrophages with pimecrolimus versus vehicle cream. Limitations: This was an exploratory study. Conclusion: Topical pimecrolimus was effective at maintaining betamethasone-17α-valerate-induced AD remission by inhibiting recurrences of the inflammatory infiltrate in the skin.
Total Pancreatectomy: Porcine Model for Inducing Diabetes – Anatomical Assessment and Surgical Aspects
Authors: Chaib E. , Galvão F.H.F. , Rocha-Filho J.A. , Silveira B.L. , Chen L. , de C. Carvalho M.P.D. , Pariz C.E. , de Almeida F.S. , Waisberg D.R. , de Souza Y.E.D.M. , Machado M.C.C. , D’Albuquerque L.A.C.
Published: December 2010

Background: The swine is an essential model for carrying out preclinical research and for teaching complex surgical procedures. There is a lack of experimental models describing anatomical and surgical aspects of total pancreatectomy in the pig. Materials and Methods: The experiments were performed on 10 white male swine weighing 27–33 kg. The animals were premedicated with midazolam (0.4 mg/kg, i.m.) and ketamine (4 mg/kg, i.m.). Anesthesia was induced with propofol (1–2 mg/kg, i.v.) and was maintained with propofol and fentanyl (0.3 mg and 0.1 µg/kg/min, respectively, i.v.). The surgical period ranged from 44 to 77 min. The pancreas anatomy, and the main arterial, venous and pancreatic duct anatomy were assessed. Results: The pancreas anatomy was composed of 3 lobes, the ‘splenic’, ‘duodenal’ and ‘connecting’ lobe which is attached to the anterior portion of the portal vein. The splenic artery and the junction of the splenic vein and portal vein were divided. The left gastric artery was dissected and separated from its origin at the splenic artery. The head of the pancreas is disposed in a C shape. The pancreas was dissected and liberated from the right portion of the portal vein and the infrahepatic vena cava. The pancreas was separated from the duodenum preserving the pancreaticoduodenal artery, then we performed the total pancreatectomy preserving the duodenum, common bile duct and spleen. Conclusion: Total pancreatectomy with duodenum, bile duct and spleen preservation in the pig is feasible and an important instrument for research purposes and teaching surgical technique.
The Meaning of Interaction
Authors: Wang Xuefeng , Elston Robert C. , Zhu Xiaofeng
Published: December 2010

Although recent studies have attempted to dispel the confusion that exists in regard to the definition, analysis and interpretation of interaction in genetics, there still remain aspects that are poorly understood by non-statisticians. After a brief discussion of the definition of gene-gene interaction, the main part of this study addresses the fundamental meaning of statistical interaction and its relationship to measurement scale, disproportionate sample sizes in the cells of a two-way table and gametic phase disequilibrium.
Rechallenge with Platinum plus Fluoropyrimidine +/– Epirubicin in Patients with Oesophagogastric Cancer
Authors: Okines A.F.C. , Asghar U. , Cunningham D. , Ashley S. , Ashton J. , Jackson K. , Hawkes E. , Chau I.
Published: December 2010

Purpose: There is no standard second-line therapy for patients with oesophagogastric cancer who progress following first-line chemotherapy for advanced disease or relapse following radical multi-modality therapy. The aim of this retrospective study was to evaluate survival following rechallenge with platinum plus fluoropyrimidine (PF) +/– epirubicin. Methods: Patients treated with PF +/– epirubicin for oesophagogastric cancer at our institution were identified from the electronic prescribing database. Patients rechallenged with PF +/– epirubicin >3 months after completing initial chemotherapy were eligible. Primary endpoint was survival, calculated from day 1 of rechallenge treatment to date of death or last follow-up. Secondary endpoints were progression-free survival and response rate to PF-based re-challenge. Results: Between 2000 and 2008, 950 patients treated with PF +/– epirubicin for oesophagogastric cancer were identified. 298 patients progressed or relapsed >3 months after completing chemotherapy, of whom 106 patients were rechallenged with PF-based chemotherapy. Median progression-free survival and overall survival were 5.1 and 10 months, respectively, from date of rechallenge for patients treated with initial radical intent and 3.9 and 6.6 months, respectively, in patients treated with palliative intent from diagnosis. In a survival analysis, no significant prognostic factors were identified. Conclusion: Selected patients with oesophagogastric cancer who relapse or progress >3 months after initial treatment with PF +/– epirubicin may benefit from re-introduction of PF-based chemotherapy.
Methylprednisolone Applied Directly to the Round Window Reduces Dizziness after Cochlear Implantation: A Randomized Clinical Trial
Authors: Enticott J.C. , Eastwood H.T. , Briggs R.J. , Dowell R.C. , O’Leary S.J.
Published: December 2010

This prospective, double-blind controlled, randomized clinical trial of 43 adults showed that topical methylprednisolone applied to the round window during cochlear implantation was effective in protecting inner ear function. Postoperative vestibular disturbance was significantly lower in the steroid group (5%) than the control group (29%). Electrode impedances from the middle portion of the electrode array (electrodes 10–13) were significantly reduced in steroid-treated recipients compared to controls. Hearing and vestibular function analyses were under-powered to detect any drug changes due to limited participant data.
Inhibition of Dental Erosion by Casein and Casein-Derived Proteins
Authors: White A.J. , Gracia L.H. , Barbour M.E.
Published: December 2010

The application of milk-derived proteins such as casein as anti-erosion agents in oral healthcare products is of current interest. The aim of this study was to investigate the potential of 3 commercially available, milk-derived proteins as agents to inhibit enamel erosion. Aqueous solutions of 0.5% w/v casein, casein phosphopeptide (CPP) or glycomacropeptide (GMP) with and without 300 ppm fluoride (F, as NaF) were investigated with regard to enamel softening and tissue loss, in comparison with a deionised water (DIW) negative control and 300 ppm F positive control. Casein and F reduced enamel surface softening compared to DIW, but CPP and GMP did not (DIW: 58.2% reduction in hardness; F: 13.3%; casein: 21.8%; CPP: 50.8%; GMP: 62.4%). Similar results were obtained with solutions containing protein and F, and the effects were statistically indistinguishable from protein alone (casein + F: 19.1%; CPP + F: 48.2%; GMP + F: 66.1%). By contrast, all protein solutions and F significantly reduced tissue loss (p < 0.050; DIW: 25.8 µm tissue loss; F: 21.6 µm; casein: 20.3 µm; CPP: 20.5 µm; GMP: 20.0 µm). Solutions containing protein and F reduced erosion more than protein alone, but this difference was only significant from protein alone for casein (casein + F: 12.2 µm; CPP + F: 17.3 µm; GMP + F: 18.2 µm). Casein and casein-derived proteins may therefore have the potential to act as agents to reduce or prevent enamel erosion. Furthermore, the erosion-reducing efficacy is not reduced by F, and is in some cases enhanced.
Long-Term Functional Outcome after Unilateral Cordectomy
Authors: Keilmann Annerose , Napiontek Ulrike , Engel Christiane , Nakarat Todsaporn , Schneider Astrid , Mann Wolf
Published: December 2010

Purpose of the Study: Our aim was to longitudinally analyze the vocal outcome after endoscopic CO2 laser resection of early glottic carcinoma. Procedures: Sixteen patients treated with laser surgery for T1 or T2 tumors of the vocal cords received voice therapy and were examined 1, 2, 3, 4.5, 6 and 12 months postoperatively. Besides videolaryngostroboscopy, each examination included history, phonetogram of the speaking and the singing voice, language-specific hoarseness diagram and a questionnaire (Voice Handicap Index 12 in German). Results: Objective parameters demonstrated a broad variability with a slight tendency of improvement over time. For the maximal phonation time a nearly constant improvement was seen. After an initial improvement deterioration for subjective assessment in the Voice Handicap Index was noted in most patients 3–6 months postoperatively. Conclusions: The functional outcome after cordectomy is variable. Message of the Paper: Discrepancies between objective findings and patient satisfaction over time have to be considered after cordectomy.
Lowering Corticosterone Levels Reinstates Hippocampal Brain-Derived Neurotropic Factor and Trkb Expression without Influencing Deficits in Hypothalamic Brain-Derived Neurotropic Factor Expression in Leptin Receptor-Deficient Mice
Authors: Stranahan Alexis M. , Arumugam Thiruma V. , Mattson Mark P.
Published: December 2010

Background/Aims: Changes in the glucocorticoid milieu contribute to alterations in neurotropic factor expression across multiple brain regions. Insulin-resistant diabetes is often accompanied by dysregulation of adrenal steroid production in humans and animal models. Leptin receptor-deficient mice (db/db) show reduced expression of brain-derived neurotropic factor (BDNF) in the hippocampus and increases in circulating corticosterone levels, but the extent to which elevated corticosterone levels mediate deficits in BDNF expression has not been determined. Methods: Using in situ hybridization, we measured the expression of BDNF, its receptor TrkB, and neurotropin-3 (NT-3) in the hippocampus and hypothalamus of db/db mice and wild-type controls following adrenalectomy and low-dose corticosterone replacement (ADX+CORT) or sham operation. Results: Lowering corticosterone levels restored BDNF and TrkB expression in the hippocampus of db/db mice. However, deficits in hypothalamic BDNF expression were not reversed following ADX+CORT. There was no effect of genotype or adrenalectomy on NT-3 expression in any brain region examined. Conclusion: Leptin receptor-deficient mice exhibit reduced BDNF expression in the hippocampus and hypothalamus. In the db/db mouse hippocampus, suppression of BDNF occurs in a glucocorticoid-dependent fashion, while hypothalamic BDNF expression is reduced via glucocorticoid-independent mechanisms. Region-specific signals therefore play a role in the interaction between corticosteroids and neurotropic factor expression.
Ethical and Practical Guidelines for Reporting Genetic Research Results to Study Participants
Authors: Fabsitz Richard R. , McGuire Amy , Sharp Richard R. , Puggal Mona , Beskow Laura M. , Biesecker Leslie G. , Bookman Ebony , Burke Wylie , Burchard Esteban Gonzalez , Church George , Clayton Ellen Wright , Eckfeldt John H. , Fernandez Conrad V. , Fisher Rebecca , Fullerton Stephanie M. , Gabriel Stacey , Gachupin Francine , James Cynthia , Jarvik Gail P. , Kittles Rick , Leib Jennifer R. , O'Donnell Christopher , O'Rourke P. Pearl , Rodriguez Laura Lyman , Schully Sheri D. , Shuldiner Alan R. , Sze Rebecca K.F. , Thakuria Joseph V. , Wolf Susan M. , Burke Gregory L.
Published: December 2010

In January 2009, the National Heart, Lung, and Blood Institute convened a 28-member multidisciplinary Working Group to update the recommendations of a 2004 National Heart, Lung, and Blood Institute Working Group focused on Guidelines to the Return of Genetic Research Results. Changes in the genetic and societal landscape over the intervening 5 years raise multiple questions and challenges. The group noted the complex issues arising from the fact that technological and bioinformatic progress has made it possible to obtain considerable information on individuals that would not have been possible a decade ago. Although unable to reach consensus on a number of issues, the working group produced 5 recommendations. The working group offers 2 recommendations addressing the criteria necessary to determine when genetic results
should
and
may
be returned to study participants, respectively. In addition, it suggests that a time limit be established to limit the duration of obligation of investigators to return genetic research results. The group recommends the creation of a central body, or bodies, to provide guidance on when genetic research results are associated with sufficient risk and have established clinical utility to justify their return to study participants. The final recommendation urges investigators to engage the broader community when dealing with identifiable communities to advise them on the return of aggregate and individual research results. Creation of an entity charged to provide guidance to institutional review boards, investigators, research institutions, and research sponsors would provide rigorous review of available data, promote standardization of study policies regarding return of genetic research results, and enable investigators and study participants to clarify and share expectations for the handling of this increasingly valuable information with appropriate respect for the rights and needs of participants.
Improvements in Shortwave Bulk Scattering and Absorption Models for the Remote Sensing of Ice Clouds
Authors: Baum Bryan A. , Yang Ping , Heymsfield Andrew J. , Schmitt Carl G. , Xie Yu , Bansemer Aaron , Hu Yong-Xiang , Zhang Zhibo
Published: December 2010

This study summarizes recent improvements in the development of bulk scattering/absorption models at solar wavelengths. The approach combines microphysical measurements from various field campaigns with single-scattering properties for nine habits including droxtals, plates, solid/hollow columns, solid/hollow bullet rosettes, and several types of aggregates. Microphysical measurements are incorporated from a number of recent field campaigns in both the Northern and Southern Hemisphere. A set of 12 815 particle size distributions is used for which Tcld ≤ −40°C. The ice water content in the microphysical data spans six orders of magnitude. For evaluation, a library of ice-particle single-scattering properties is employed for 101 wavelengths between 0.4 and 2.24 μm. The library includes the full phase matrix as well as properties for smooth, moderately roughened, and severely roughened particles. Habit mixtures are developed for generalized cirrus, midlatitude cirrus, and deep tropical convection. The single-scattering properties are integrated over particle size and wavelength using an assumed habit mixture to develop bulk scattering and absorption properties. In comparison with global Cloud Aerosol Lidar with Orthogonal Polarization (CALIOP) data, models built with severely roughened particles compare best for all habit mixtures. The assumption of smooth particles provided the largest departure from CALIOP measurements. The use of roughened rather than smooth particles to infer optical thickness and effective diameter from satellite imagery such as the Moderate Resolution Imaging Spectroradiometer (MODIS) will result in a decrease in optical thickness and an increase in particle size.
MIH Supplementation Strategies
Authors: Baroni C. , Marchionni S.
Published: December 2010

The use of calcium-phosphate casein on hypomineralized molars (molar incisor hypomineralization, MIH) has been proposed but not clinically investigated. Qualitative and quantitative effects of supplementation with a calcium-phosphate casein product on MIH molars were monitored over a period of three years. Molar replicas, minimally invasive biopsies and their SEM microphotographs, plus ESEM/EDX semi-quantitative peaks of elements present in affected enamel were evaluated. Mineralization, morphology, and porosity appeared markedly improved, with calcium and phosphate levels reaching almost normal levels at three years’ follow-up. The hypothesis tested was rejected, since calcium-phosphate casein improved enamel morphology in vivo.
Is the ‘New Deal for Communities’ a New Deal for Equality? Getting Women on Board in Neighbourhood Governance
Authors: Beebeejaun Yasminah , Grimshaw Lucy
Published: December 2010

Across the EU, neighbourhoods have been the focus for achieving social cohesion and reducing social exclusion. Neighbourhood renewal and community involvement were central themes in the UK Labour government’s urban policy. This article focuses on the challenge of community engagement given the heterogeneity of individuals and neighbourhoods. It uses the case study of a New Deal for Communities (NDC) partnership to explore the experiences of different women on an NDC board, including those from minority ethnic groups. The NDC in the case study provides optimism about the possibility of including diverse groups and people in neighbourhood governance, yet too little attention is still given at both national policy and neighbourhood levels to working politically and productively with concepts of ethnicity and gender.
Assessing the Accessibility of the Homeownership Market
Authors: Neuteboom Peter , Brounen Dirk
Published: December 2010

In this paper, an examination is made of the accessibility of the homeownership market using measures that include both supply and demand characteristics of regional housing markets. These measures are applied empirically on an extensive dataset that covers the Dutch housing market. The analysis quantifies the extent to which the position of first-time buyers on the homeownership market has weakened over time and identifies the driving factors of this change. It is found that smaller portions of the housing market are becoming affordable due to financial constraints of young households. However, more importantly, first-time buyers today need to contend with a much larger group of competing bidders on every house that suits their financial situation, than ever before.
Globalization, Emerging Powers, and the Future of Capitalism
Authors: dos Santos Theotônio
Published: December 2010

Central capitalism and its supporting institutions have lost their dynamism and are no longer capable of regulating the world economy without a substantial change in the world order including cooperation with regional powers in a much broader geopolitical paradigm. What is needed is a change from U.S. hegemony to joint hegemony (with the United States still at the center), a revised conception of development in more social, sustainable, and human terms, a stronger role for the state in the organization of the local, national, and world economies, and a stronger system of South-South relations based on a rebirth of Third World institutions and a civilizational, philosophical, and political framework that transcends the Eurocentric view of the world. The emergence of Brazil, Russia, India, and China in the international structure of power is very important for this change. The economic crisis of 2008—2010 is driving international developments in this direction.
Intellectuals in a Network
Authors: Dowbor Ladislau
Published: December 2010

Brazilian social thought draws on the inspiration of past masters the common denominator of whose work is probably a deep humanism. Confronting the challenges of a fluid, ever-changing reality is now a matter of survival. The idea of climate change has made the environment, long relegated to second place, a matter of much wider interest and concern. The other great problem is poverty, and here, while there have been undeniable advances, much remains to be done. The main challenge is producing forms of social organization that will allow ordinary citizens to have an impact on what really matters. Developing policy in these areas has engaged the efforts of a wide range of experts from a variety of fields. Whereas university-educated intellectuals once formed an intelligentsia, today they are engaged in practical politics and much more often function as agents who link social actors together than as mere elaborators of theories.
Social Care in Adult Education
Authors: Taber Nancy
Published: December 2010

This article describes a research study about the experiences of adult educators in which the stories of three of the participants were central in exploring the issue of social care in adult education. It proposes that the adult educators with a social care orientation in this study acknowledge the importance of, and work to provide for, human needs (e.g., food, shelter, and belonging), care (working from an ethical affective orientation as opposed to a rational justice orientation), and social justice (a power analysis focusing on marginalization and oppression in a capitalist society).
Participation and Performance of Students With Emotional Disturbance on a Statewide Accountability Assessment in Math
Authors: Temple-Harvey Kimberly K. , Vannest Kimberly J.
Published: December 2010

The participation and performance of students in statewide accountability and assessment systems are measures of student and school success. These accountability systems theoretically reflect performance for all students, including students receiving special education. Yet few examine the participation and performance of students in special education by disability category, instead reporting on “special education” as a homogeneous population, when in fact it is not. Students with emotional disturbance (ED) demonstrate some of the most challenging academic and behavior problems and present low performances in school. The participation and performance of students with ED on a statewide accountability assessment in math were investigated in this article. Only 34% of students with ED participated and met at least minimum proficiency standards. Factors predictive of student participation and performance were identified through logistic regression. One primary finding is that instructional setting predicted participation, though not performance, and intuitively intelligence predicted both participation and performance.
The Impact of Community Service Learning Upon the Expected Political Voice of Participating College Students
Authors: Seider Scott C. , Gillmor Susan , Rabinowicz Samantha
Published: December 2010

This study considered the impact of the SERVE Program at Ignatius University upon participating students’ expected political involvement. The SERVE Program is a community service learning program sponsored jointly by Ignatius University’s philosophy and theology departments. Through a mixed methods research design, the authors found that Ignatius University students participating in the SERVE Program demonstrated statistically significant increases in their expected political voice in comparison with peers in a control group. Qualitative interviews with SERVE participants revealed that the program increased students’ awareness of political and social issues; heightened their commitment to philanthropy; fostered their interest in pursuing socially responsible work; and strengthened their commitment to working for social change.
A statistical picture of popularization activities and their evolutions in France
Authors: Jensen Pablo
Published: December 2010

This paper provides a detailed statistical picture of French scientists involved in public outreach. This is achieved by analysing the popularization practices of 7000 scientists in all major disciplines over a six-year period (2004 to 2009). I analyse the influence of discipline, position, age and academic productivity. Thanks to a temporal analysis, I show that scientists can be split into three distinct populations with radically different popularization practices. Finally, this analysis suggests that the recent increase in public engagement is the result of heightened social interest which pulls more outreach from particular disciplines.
Management of hyponatraemia in older people: old threats and new opportunities
Authors: Soiza Roy L. , Talbot Hannah S.C.
Published: December 2010

Hyponatraemia is the commonest electrolyte abnormality seen in clinical practice, and is especially prevalent in frail, older people. However, the serious implications of hyponatraemia in this age group are seldom recognized by clinicians. Hyponatraemia is associated with osteoporosis, impaired balance, falls, hip fractures and cognitive dysfunction. Even mild, apparently asymptomatic hyponatraemia is associated with prolonged stays in hospital, institutionalization and increased risk of death. Emerging evidence of the potential benefits of improved treatment of hyponatraemia is slowly generating renewed clinical interest in this area. The development of specific vasopressin-2 receptor antagonists (vaptans) has the potential to revolutionize the management of hyponatraemia, in particular for the syndrome of inappropriate antidiuretic hormone. However, challenges remain for the attending physician. Diagnosing the cause or causes of hyponatraemia in older people is difficult, and incorrect diagnosis can lead to treatment that worsens the electrolyte imbalance. Established treatments are often poorly tolerated and patient outcomes remain poor, and the role of vaptans in the treatment of older people is unclear. This review summarizes the existing evidence base and highlights areas of controversy. It includes practical guidance for overcoming some common pitfalls in the management of the elderly patient with hyponatraemia.
Response-Guided Induction Therapy in Pediatric Acute Myeloid Leukemia With Excellent Remission Rate
Authors: Abrahamsson Jonas , Forestier Erik , Heldrup Jesper , Jahnukainen Kirsi , Jónsson Ólafur G. , Lausen Birgitte , Palle Josefine , Zeller Bernward , Hasle Henrik
Published: December 2010

Purpose

To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course.

Patients and Methods

All Nordic children with AML younger than 15 years (n = 151) were treated on the Nordic Society for Pediatric Hematology and Oncology (NOPHO) AML 2004 protocol. After the first course of idarubicin, cytarabine, etoposide, and 6-thioguanin, patients with good response were allowed hematologic recovery before the second course, whereas patients with a poor (≥ 15% blasts) or intermediate (5% to 14.9% blasts) were recommended to proceed immediately with therapy. Patients not in remission after the second course received fludarabine, cytarabine, and granulocyte colony-stimulating factor. Poor responders received allogeneic stem-cell transplantation (SCT) as consolidation.

Results

Seventy-four percent of patients had good response, 17% had intermediate response, and 7% had poor response after the first course. The overall remission frequency was 97.4%, with 92% in remission after the second course. The rate of induction death was 1.3%. Patients with an intermediate response had a lower event-free survival of 35% compared with good (61%) and poor responders (82%).

Conclusion

The NOPHO-AML 2004 induction strategy gives an excellent remission rate with low toxic mortality in an unselected population. Outcome is worse in patients with intermediate response but may be improved by intensifying consolidation in this group using SCT.
Phase III Randomized Study Comparing Docetaxel Plus Trastuzumab With Vinorelbine Plus Trastuzumab As First-Line Therapy of Metastatic or Locally Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: The HERNATA Study
Authors: Andersson Michael , Lidbrink Elisabeth , Bjerre Karsten , Wist Erik , Enevoldsen Kristin , Jensen Anders B. , Karlsson Per , Tange Ulla B. , Sørensen Peter G. , Møller Susanne , Bergh Jonas , Langkjer Sven T.
Published: December 2010

Purpose

To evaluate docetaxel or vinorelbine, both with trastuzumab, as first-line therapy of human epidermal growth factor receptor 2–positive advanced breast cancer.

Patients and Methods

Patients naive to chemotherapy for advanced disease were randomly assigned to docetaxel 100 mg/m2 day 1 or vinorelbine 30 to 35 mg/m2 on days 1 and 8, both combined with trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance dose) on day 1 every 3 weeks. The primary end point was time to progression (TTP).

Results

A total of 143 patients were randomly allocated to docetaxel, and 141 patients were assigned to vinorelbine. The median TTP for docetaxel and vinorelbine respectively was 12.4 months versus 15.3 months (hazard ratio [HR] = 0.94; 95% CI, 0.71 to 1.25; P = .67), median overall survival was 35.7 months versus 38.8 months (HR = 1.01; 95% CI, 0.71 to 1.42; P = .98), and the 1-year survival rate was 88% in both arms. Median time to treatment failure for study chemotherapy was 5.6 months versus 7.7 months (HR = 0.50; 95% CI, 0.38 to 0.64; P < .0001). The investigator-assessed overall response rate among 241 patients with measurable disease were 59.3% in both arms. More patients in the docetaxel arm discontinued therapy due to toxicity (P < .001). Significantly more treatment-related grade 3 to 4 febrile neutropenia (36.0% v 10.1%), leucopenia (40.3% v 21.0%), infection 25.1% v 13.0%), fever (4.3% v 0%), neuropathy (30.9% v 3.6%), nail changes (7.9% v 0.7%), and edema (6.5% v 0%) were reported with docetaxel.

Conclusion

The study failed to demonstrate superiority of any drug in terms of efficacy, but the vinorelbine combination had significantly fewer adverse effects and should be considered as an alternative first-line option.
Immunosuppressive Therapy for Patients With Myelodysplastic Syndrome: A Prospective Randomized Multicenter Phase III Trial Comparing Antithymocyte Globulin Plus Cyclosporine With Best Supportive Care—SAKK 33/99
Authors: Passweg Jakob R. , Giagounidis Aristoteles A.N. , Simcock Mathew , Aul Carlo , Dobbelstein Christiane , Stadler Michael , Ossenkoppele Gert , Hofmann Wolf-Karsten , Schilling Kristina , Tichelli André , Ganser Arnold
Published: December 2010

Purpose

Immunosuppressive treatment is reported to improve cytopenia in some patients with myelodysplastic syndrome (MDS). Combined antithymocyte globulin (ATG) and cyclosporine (CSA) is most effective in patients with immune-mediated marrow failure.

Patients and Methods

This trial was designed to assess the impact of immunosuppression on hematopoiesis, transfusion requirements, transformation, and survival in patients with MDS randomly assigned to 15 mg/kg of horse ATG for 5 days and oral CSA for 180 days (ATG+CSA) or best supportive care (BSC), stratified by treatment center and International Prognostic Scoring System (IPSS) risk score. Primary end point was best hematologic response at 6 months. Eligible patients had an Eastern Cooperative Oncology Group performance status of ≤ 2 and transfusion dependency of less than 2 years in duration.

Results

Between 2000 and 2006, 45 patients received ATG+CSA (median age, 62 years; range, 23 to 75 years; 56% men) and 43 patients received BSC (median age, 65 years; range, 24 to 76 years; 81% men). IPSS score was low, intermediate-1, intermediate-2, high, and not evaluable in eight, 24, seven, one, and five patients on ATG+CSA, respectively, and eight, 25, five, zero, and five patients on BSC, respectively. Refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess of blasts (RAEB) -I, RAEB-II, and hypoplastic disease were present in 21, six, nine, zero, and nine patients on ATG+CSA, respectively, and 18, eight, 11, two, and four patients on BSC, respectively. By month 6, 13 of 45 patients on ATG+CSA had a hematologic response compared with four of 43 patients on BSC (P = .0156). Two-year transformation-free survival (TFS) rates were 46% (95% CI, 28% to 62%) and 55% (95% CI, 34% to 70%) for ATG+CSA and BSC patients, respectively (P = .730), whereas overall survival (OS) estimates were 49% (95% CI, 31% to 66%) and 63% (95% CI, 42% to 78%), respectively (P = .828).

Conclusion

This open-label randomized phase III trial demonstrates that ATG+CSA treatment seems to be associated with hematologic response in a subset of patients without apparent impact on TFS and OS.
THE “BEACHED WHALE”
Authors: Holland Sharon P.
Published: December 2010

This article briefly traces the fraught relationship between feminism, sexuality studies, and black feminism. I argue that as sexuality studies, through “Thinking Sex” in particular, began to follow feminism's lead—yoking blackness to a history separate from that of feminism's historical grounding—we have moved further from an exploration of blackness's centrality in queer studies discourse about the body and its erotic desires.