bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Utility of Anti-EBV Antibody Testing for Defining NPC Risk among Individuals from High-Risk NPC Families
Authors: Yu Kelly J. , Hsu Wan-Lun , Pfeiffer Ruth M. , Chiang Chun-Ju , Wang Cheng-Ping , Lou Pei-Jen , Cheng Yu-Juen , Gravitt Patti , Diehl Scott R. , Goldstein Alisa M. , Chen Chien-Jen , Hildesheim Allan
Published: March 2011

Purpose: Epstein–Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families.

Experimental Design: We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/specificity and receiver operating characteristic (ROC) curves were calculated.

Results: A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4–16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5–61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker.

Conclusions: Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity. Clin Cancer Res; 17(7); 1906–14. ©2011 AACR.
Predicting Accrual Achievement: Monitoring Accrual Milestones of NCI-CTEP–Sponsored Clinical Trials
Authors: Cheng Steven K. , Dietrich Mary S. , Dilts David M.
Published: March 2011

Purpose: The need to increase the number oncology clinical trials with sufficient enrollments is a well-known issue, particularly for trials targeting therapeutic applications. It is critical to identify early predictors of eventual study accrual achievement.

Experimental Design: All nonpediatric phase I, I/II, II, and III therapeutic studies supported by the National Cancer Institute Cancer Therapy Evaluation Program (NCI-CTEP) between 2000 and 2007 (n = 764) were analyzed for accrual performance. Accrual achievement is defined as those enrolling 100% or more of the stated minimum accrual goal at the time of trial closure. Two accrual milestones were analyzed per trial: time to first patient enrollment and expected time to accrual goal. Multivariate logistic regression analysis was used to calculate the OR with respect to the likelihood of clinical trial accrual achievement.

Results: A total of 81.5% (n = 623) of the trials did not achieve the projected accrual goals within the anticipated accruing period. Furthermore, 37.2% (n = 284) of trials failed to achieve the minimum projected accrual at study closure regardless of time the trial was open. Trials that accrue the first enrollment beyond 2 months (n = 379, 49.6%) are significantly less likely to achieve the accrual performance than those trials that enroll patients under 2 months (OR: 0.637, 95% CI: 0.464–0.875, P = 0.005). Of the studies that are open beyond the anticipated enrollment period (n = 603), those do not achieve at least 60.0% of the projected minimum accrual (n = 391, 64.8%) have a significantly less likelihood of achieving final accruals by study closure (OR: 0.190, 95% CI: 0.055–0.652, P = 0.008).

Conclusions: The time to first patient enrollment and expected time to accrual goal are shown to be valid measures to evaluate the likelihood of achieving the minimum projected accrual. Clin Cancer Res; 17(7); 1947–55. ©2011 AACR.
Two Drug Interaction Studies of Sirolimus in Combination with Sorafenib or Sunitinib in Patients with Advanced Malignancies
Authors: Gangadhar Tara C. , Cohen Ezra E.W. , Wu Kehua , Janisch Linda , Geary David , Kocherginsky Masha , House Larry K. , Ramirez Jackie , Undevia Samir D. , Maitland Michael L. , Fleming Gini F. , Ratain Mark J.
Published: March 2011

Purpose: Sirolimus is the prototypical mTOR inhibitor. Sorafenib and sunitinib are small molecule inhibitors of multiple kinases including VEGF receptor (VEGFR) kinases. These agents have different mechanisms of action, providing a strong rationale for combination.

Experimental Design: Patients with advanced cancer were assigned to receive either sirolimus or the VEGFR inhibitor alone for a 2-week lead-in period, followed by combination therapy. The primary end point of each trial was to determine whether a drug interaction exists between sirolimus and either sorafenib or sunitinib, as defined by a difference in Cmax for each drug alone compared with its Cmax during combination therapy.

Results: The sorafenib and sunitinib trials enrolled 34 and 23 patients, respectively. There were no clinically significant differences in Cmax for any of the drugs alone compared with the Cmax during combination therapy. Toxicity profiles were similar to those expected for each drug alone. One patient with adrenal cortical cancer had a partial response to sirolimus and sunitnib.

Conclusions: Sirolimus can be safely combined with sorafenib or sunitinib. Our trial design is feasible and informative in screening for potential drug–drug interactions, using a relatively small number of patients and limited pharmacokinetic sampling. Clin Cancer Res; 17(7); 1956–63. ©2011 AACR.
A Phase 1 Study of AS1409, a Novel Antibody-Cytokine Fusion Protein, in Patients with Malignant Melanoma or Renal Cell Carcinoma
Authors: Rudman Sarah M. , Jameson Michael B. , McKeage Mark J. , Savage Philip , Jodrell Duncan I. , Harries Mark , Acton Gary , Erlandsson Fredrik , Spicer James F.
Published: March 2011

Purpose: AS1409 is a fusion protein comprising a humanized antibody BC1 linked to interleukin-12 (IL-12). It is designed to deliver IL-12 to tumor-associated vasculature using an antibody targeting the ED-B variant of fibronectin.

Experimental Design: We conducted a phase 1 trial of weekly infusional AS1409 in renal carcinoma and malignant melanoma patients. Safety, efficacy, markers of IL-12–mediated immune response, and pharmacokinetics were evaluated.

Results: A total of 11 melanoma and 2 renal cell carcinoma patients were treated. Doses of 15 and 25 μg/kg were studied. Most drug-related adverse events were grade 2 or less, and included pyrexia, fatigue, chills, headache, vomiting, and transient liver function abnormalities. Three dose limiting toxicities of grade 3 fatigue and transaminase elevation were seen at 25 μg/kg. IFN-γ and interferon-inducible protein-10 (IP-10) were elevated in all patients, indicating activation of cell-mediated immune response; this was attenuated at subsequent cycles. Antidrug antibody responses were seen in all patients, although bioassays indicate these do not neutralize AS1409 activity. Plasma half-life was 22 hours and not dose-dependent. Five patients received 6 cycles or more and a best response of at least stable disease was seen in 6 (46%) patients. Partial response was seen in a melanoma patient, and disease shrinkage associated with metabolic response was maintained beyond 12 months in another melanoma patient despite previous rapid progression.

Conclusions: The maximum tolerated dose was established at 15 μg/kg weekly. AS1409 is well tolerated at this dose. Evidence of efficacy assessed by RECIST, functional imaging, and biomarker response warrants the planned further investigation using this dose and schedule in malignant melanoma. Clin Cancer Res; 17(7); 1998–2005. ©2011 AACR.
Knockdown of FLOT1 Impairs Cell Proliferation and Tumorigenicity in Breast Cancer through Upregulation of FOXO3a
Authors: Lin Chuyong , Wu Zhiqiang , Lin Xi , Yu Chunping , Shi Tingting , Zeng Yong , Wang Xi , Li Jun , Song Libing
Published: March 2011

Purpose: Lipid rafts, specialized domains in cell membranes, function as physical platforms for various molecules to coordinate a variety of signal transduction processes. Flotinllin-1 (FLOT1), a marker of lipid rafts, is involved in the progression of cancer, but the precise mechanism remains unclear. The aim of the present study was to examine the role of FLOT1 on the tumorigenesis of breast cancer cells and its clinical significance in progression of the disease.

Experimental Design: FLOT1 expression was analyzed in 212 paraffin-embedded, archived clinical breast cancer samples by using immunohistochemistry (IHC). The effect of FLOT1 on cell proliferation and tumorigenesis was examined in vitro and in vivo. Western blotting and luciferase reporter analyses were carried out to identify the effects of downregulating FLOT1 on expression of cell cycle regulators and transcriptional activity of FOXO3a.

Results: IHC analysis revealed high expression of FLOT1 in 129 of the 212 (60.8%) paraffin-embedded archived breast cancer specimens. The overall expression level of FLOT1 significantly correlated with clinical staging and poor patient survival of breast cancer. Strikingly, we found that silencing FLOT1 inhibited proliferation and tumorigenicity of breast cancer cells both in vitro and in vivo, which was further shown to be mechanistically associated with suppression of Akt activity, enhanced transcriptional activity of FOXO3a, upregulation of cyclin-dependent kinase inhibitor p21Cip1 and p27Kip1, and downregulation of the CDK regulator cyclin D1.

Conclusions: FLOT1 plays an important role in promoting proliferation and tumorigenesis of human breast cancer and may represent a novel prognostic biomarker and therapeutic target for the disease. Clin Cancer Res; 17(10); 3089–99. ©2011 AACR.
Activity of Sorafenib against Desmoid Tumor/Deep Fibromatosis
Authors: Gounder Mrinal M. , Lefkowitz Robert A. , Keohan Mary Louise , D'Adamo David R. , Hameed Meera , Antonescu Cristina R. , Singer Samuel , Stout Katherine , Ahn Linda , Maki Robert G.
Published: March 2011

Background: Desmoid tumors (deep fibromatoses) are clonal connective tissue malignancies that do not metastasize, but have a significant risk of local recurrence, and are associated with morbidity and occasionally mortality. Responses of desmoid patients to sorafenib on an expanded access program led us to review our experience.

Methods: After Institutional Review Board (IRB) approval, we reviewed data for 26 patients with desmoid tumors treated with sorafenib. Sorafenib was administered at 400 mg oral daily and adjusted for toxicity.

Results: Sorafenib was the first-line therapy in 11/26 patients and the remaining 15/26 had received a median of 2 prior lines of therapy. Twenty-three of 26 patients had shown evidence of progressive disease by imaging, whereas 3 patients had achieved maximum benefit or toxicity with chemotherapy. Sixteen of 22 (∼70%) patients reported significant improvement of symptoms. At a median of 6 months (2–29) of treatment, the best response evaluation criteria in solid tumors (RECIST) 1.1 response included 6/24 (25%) patients with partial response (PR), 17/24 (70%) with stable disease, and 1 with progression and death. Twelve of 13 (92%) patients evaluated by MRI had > 30% decrease in T2 signal intensity, an indirect metric for increased fibrosis and loss of cellularity. Eighty percent of patients with radiological benefit had extra-abdominal desmoids.

Discussion: Sorafenib is active against desmoid tumors. A prospective, randomized clinical trial of sorafenib against other active agents is warranted. Loss of MRI T2 signal may be a useful surrogate for defining responses, but requires validation by examination of tumor pathology. Clin Cancer Res; 17(12); 4082–90. ©2011 AACR.
Genetic and Expression Analysis of MET, MACC1, and HGF in Metastatic Colorectal Cancer: Response to Met Inhibition in Patient Xenografts and Pathologic Correlations
Authors: Galimi Francesco , Torti Davide , Sassi Francesco , Isella Claudio , Corà Davide , Gastaldi Stefania , Ribero Dario , Muratore Andrea , Massucco Paolo , Siatis Dimitrios , Paraluppi Gianluca , Gonella Federica , Maione Francesca , Pisacane Alberto , David Ezio , Torchio Bruno , Risio Mauro , Salizzoni Mauro , Capussotti Lorenzo , Perera Timothy , Medico Enzo , Di Renzo Maria Flavia , Comoglio Paolo M. , Trusolino Livio , Bertotti Andrea
Published: March 2011

Purpose: We determined the gene copy numbers for MET, for its transcriptional activator MACC1 and for its ligand hepatocyte growth factor (HGF) in liver metastases from colorectal carcinoma (mCRC). We correlated copy numbers with mRNA levels and explored whether gain and/or overexpression of MET and MACC1 predict response to anti-Met therapies. Finally, we assessed whether their genomic or transcriptional deregulation correlates with pathologic and molecular parameters of aggressive disease.

Experimental Design: One hundred three mCRCs were analyzed. Copy numbers and mRNA were determined by quantitative PCR (qPCR). Thirty nine samples were implanted and expanded in NOD (nonobese diabetic)/SCID (severe combined immunodeficient) mice to generate cohorts that were treated with the Met inhibitor JNJ-38877605. In silico analysis of MACC1 targets relied on genome-wide mapping of promoter regions and on expression data from two CRC datasets.

Results: No focal, high-grade amplifications of MET, MACC1, or HGF were detected. Chromosome 7 polysomy and gain of the p-arm were observed in 21% and 8% of cases, respectively, and significantly correlated with higher expression of both Met and MACC1. Met inhibition in patient-derived xenografts did not modify tumor growth. Copy number gain and overexpression of MACC1 correlated with unfavorable pathologic features better than overexpression of Met. Bioinformatic analysis of putative MACC1 targets identified elements besides Met, whose overexpression cosegregated with aggressive forms of colorectal cancer.

Conclusions: Experiments in patient-derived xenografts suggest that mCRCs do not rely on Met genomic gain and/or overexpression for growth. On the basis of pathologic correlations and bioinformatic analysis, MACC1 could contribute to CRC progression through mechanisms other than or additional to Met transcriptional upregulation. Clin Cancer Res; 17(10); 3146–56. ©2011 AACR.
Frequency of Virulence-Associated Genes in Enterococccus faecalis Isolated in Kuwait Hospitals
Authors: Udo Edet E. , Al-Sweih Noura
Published: March 2011

Objective: The objective of this study was to investigate the carriage of 6 virulence-associated genes in Enterococcus faecalis isolates obtained from patients in 8 hospitals in Kuwait. Materials and Methods: In total, 466 E. faecalis isolates were obtained from 313 urine samples, 68 wound swabs, 36 blood samples, 25 rectal swabs, 12 high vaginal swabs and 12 miscellaneous sources. Genes for gelatinase(gelE),aggregation substance (aggA), hemolysin activation factor (cylA), enhanced expression of pheromone (eep), enterococcal surface protein (esp), and E. faecalis endocarditis antigen A (efaA) were detected in PCR assays. Results: Of 466 isolates, 423 (90.8%) were positive for 1 and up to 5 genes. However, none of the genes was detected in all of the isolates. The prevalence of the individual genes was eep: 31.9%; esp: 31.5%; gelE: 28.5%; efaA: 27.9%; aggA: 23.4%, and cylA: 18.5%. Of the 423 positive isolates, 148 (34.9%) were positive for 2 genes and 52 (12.3%), 15 (3.5%) and 5 (0.9%) isolates were positive for 3, 4 and 5 virulence genes, respectively. The efaA and esp combination was detected in isolates from all clinical sources. Conclusion: The study showed a high prevalence of virulence genes in E. faecalis isolated in Kuwait hospitals. The absence of a dominant gene in all of the isolates suggests that infections by E. faecalis may require the involvement of multiple virulence factors.
Sequence Analysis of blaCTX-M Genes Carried by Clinically Significant Escherichia coli Isolates in Kuwait Hospitals
Authors: Al Hashem G. , Al Sweih N. , Jamal W. , Rotimi V.O.
Published: March 2011

Objective: To investigate the extent, distribution and sequence analysis of blaCTX-M genes carried by Escherichia coli isolated from patients admitted to all government hospitals in Kuwait. Methods: Extended-spectrum β-lactamase (ESBL)-producing E. coli isolates were collected from the 8 major hospitals in Kuwait. CTX-M ESBLs were analyzed by PCR and sequenced. Clonality of the positive isolates was determined for genetic relatedness using pulsed-field gel electrophoresis (PFGE) with XbaI digestion of the genomic DNA. Results: Of the 136 ESBL-positive isolates, 106 (77.9%) harbored blaCTX-M genes. Among these, blaCTX-M-15 was the most frequent with a prevalence rate of 84.1%, followed by blaCTX-M-14 (6.8%), blaCTX-M-14b (5.7%) and blaTOHO-1 (3.4%). Ninety-three (87.7%) were isolated from Kuwaiti (35.9%), Egyptian (31.1%) and Indian (20.8%) nationals; the majority of isolates positive for blaCTX-M-15 were mainly from these 3 nationalities. PFGE analysis did not demonstrate any clustering of positive isolates in any particular hospital. Conclusion: This study confirms an explosive emergence of CTX-M-15 β-lactamase among E. coli isolates in Kuwait and shows that the strains were clonally heterogeneous with no evidence of inter- or intra-hospital spread. Thus Kuwait may represent an important source of CTX-M-15-positive E. coli.
Patient-Reported Adverse Drug Reactions and Drug-Drug Interactions: A Cross-Sectional Study on Malaysian HIV/AIDS Patients
Authors: Hasan Syed S. , Keong See C. , Choong Christopher L.K. , Ahmed Syed I. , Ching Ting W. , Anwar Mudassir , Ahmadi Keivan , Babar Muneer G.
Published: March 2011

Objective: This study aimed to explore the adverse drug reactions (ADRs) reported by patients and to identify drug-drug interactions (DDIs) among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients. Subjects and Methods: This cross-sectional study was conducted at the Medication Therapy Adherence Clinic, Hospital Sungai Buloh, an HIV/AIDS referral centre. The patients were randomly selected and were encouraged to describe ADRs caused specifically by any of the prescribed antiretroviral drugs (ARDs). Sociodemographic characteristics were recorded from the patients’ medical records. In addition data on antiretroviral treatment (ART), DDIs and other conventional medication were also documented. Results: A total of 325 randomly selected HIV/AIDS patients with a mean age of 22.94 years participated in the study. The most frequently prescribed ARDs were lamivudine (64.6%), zidovudine (40.6%) and efavirenz (42.5%). Commonly reported ADRs were fatigue (54.8%), allergic reactions (41.5%), weight loss (41.5%), dry mouth (35.1%) and memory loss (35.1%). Female (87.8%), non-complementary and alternative medicine (CAM) users (87.3%) and participants below 50 years old (81.1%) were identified as having a higher prevalence of ADRs compared to males (79.6%), CAM users (78.7%) and participants aged 50 years or more (77.5%). Patient age was found to be significantly associated (p = 0.048) with the ADRs. In addition, a total of 44 cases of DDIs belonging to category D were also found in this study. Conclusions: This study enabled us to identify the most common ADRs and DDIs associated with the use of ART. Safe and effective treatment depends on the healthcare providers’ knowledge of the same.
Vascular Calcification in Patients with Chronic Kidney Disease: Types, Clinical Impact and Pathogenesis
Authors: Román-García Pablo , Rodríguez-García Minerva , Cabezas-Rodríguez Iván , López-Ongil Susana , Díaz-López Bernardino , Cannata-Andía Jorge B.
Published: March 2011

Vascular calcification plays a major role in cardiovascular disease, which is one of the main causes of mortality in chronic kidney disease patients. Vascular calcification is determined by prevalent traditional and uraemia-related (non-traditional) risk factors. It occurs mainly in the arteries, which are classified into three types according to their size and structural characteristics. In addition, vascular calcification has been associated with bone loss and fractures in chronic kidney disease patients and the general population, stressing the fact that both disorders can share pathogenetic pathways. The strategies to control vascular calcification involve several measures, chief among them the control of hyperphosphataemia. Furthermore, it has been recently described that strategies that reduce bone resorption and increase bone mineralization may decrease the risk of vascular calcifications; however, this approach still remains controversial. The mechanisms involved in vascular calcification are complex and not yet fully understood. Phosphorus plays a major role, while other factors related to bone formation have been recently identified.
Value of Three-Dimensional Optical Coherence Tomography and Fundus Photochromy in Correlating the Fluorescein Leaking Sites of Acute Central Serous Chorioretinopathy
Authors: Wang Guang-Hui , Zhang Jun , Zhang Dan , Lv Fu-Li , Wang Le-Xin
Published: March 2011

Objectives: This study was designed to investigate the value of 3-D optical coherence tomography (3-D OCT) combined with fundus photochromy in the diagnosis of acute central serous chorioretinopathy (CSCR). Subjects and Methods: 3-D OCT and fundus photochromy were performed on 30 patients (36 eyes) with acute CSCR. Fluorescein angiography (FA) was also performed to confirm the diagnosis and to obtain the fluorescein leakage sites. Results: 22 eyes presented neurosensory retinal detachment determined by 3-D OCT (28 leakage spots), 1 eye showed retinal pigment epithelium (RPE) detachment (2 leakage spots), and 13 eyes showed both neurosensory and RPE detachment (17 leakage spots). 3-D OCT showed significant changes in the RPE in 36 of 47 leakage spots (76.6%). Fundus photochromy showed white-gray changes in 22 of the 47 leakage spots (59.6%). 47 leakage spots were identified by FA in 36 eyes. The combination of 3-D OCT and fundus photochromy identified 42 of the 47 leakage spots (89.4%) spotted by FA. Conclusion: A combination of 3-D OCT and fundus photochromy offered a high identification rate of the leakage spots. The combination of the two noninvasive techniques may be used as an alternative diagnostic or evaluation tool for acute CSCR.
Associated Cutaneous Diseases in Obese Adult Patients: A Prospective Study from a Skin Referral Care Center
Authors: Al-Mutairi Nawaf
Published: March 2011

Objective: The aim of the present study was to determine the spectrum of skin diseases seen among adult obese patients referred to Farwaniya Hospital. Materials and Methods: A total of 437 overweight/obese subjects (200 men and 237 women) aged 18–74 years were enrolled in the study, which was conducted from October 2008 to November 2009. Demographic details such as age, sex, occupation, personal and family history of diabetes mellitus, hypertension, and obesity were recorded. A thorough examination was performed by an experienced dermatologist (N.A.M.). Blood investigations such as complete blood count, fasting and postprandial blood sugar levels, liver function tests, kidney function tests, lipid profile, and thyroid function tests were done for all patients in addition to hormonal assay and abdominal sonar to exclude polycystic ovary disease for indicated patients. Results: Common skin diseases found among these patients were plantar hyperkeratosis: n = 197; acanthosis nigricans: n = 144; skin tags: n = 131; striae cutis distensae: n = 102; intertrigo: n = 97; acne vulgaris: n = 94. Diabetes mellitus was diagnosed in 87 patients, polycystic ovary syndrome/hyperandrogenism in 74 female patients, and hyperlipidemia in 209 patients. Conclusion: This study shows that certain dermatoses such as plantar hyperkeratosis, acanthosis nigricans, skin tags, striae cutis distensae, and intertrigo are more common among obese persons. Some, such as plantar hyperkeratosis, could serve as markers of obesity and its severity, while the presence of acanthosis nigricans and skin tags may point to underlying internal disease such as diabetes and polycystic ovary syndrome.
In vivo Antinociceptive and Anti-inflammatory Activities of Dried and Fermented Processed Virgin Coconut Oil
Authors: Zakaria Z.A. , Somchit M.N. , Mat Jais A.M. , Teh L.K. , Salleh M.Z. , Long K.
Published: March 2011

Objective: The present study was carried out to investigate the antinociceptive and anti-inflammatory activities of virgin coconut oil (VCO) produced by theMalaysian Agriculture Research and Development Institute (MARDI) using various in vivo models. Materials and Methods: Two types of VCOs, produced via standard drying (VCOA) and fermentation (VCOB) processes were used in this study. Both VCOA and VCOB were serially diluted using 1% Tween 80 to concentrations (v/v) of 10, 50 and 100%. Antinociceptive and anti- inflammatory activities of both VCOs were examined using various in vivomodel systems. The antinociceptive activity of the VCOs were compared to those of 1% Tween 80 (used as a negative control), morphine (5 mg/kg) and/or acetylsalicylic acid (100 mg/kg). Results: Both VCOA and VCOB exhibited significant (p < 0.05) dose-dependent antinociceptive activity in the acetic acid-induced writhing test. Both VCOs also exerted significant (p < 0.05) antinociceptive activity in both phases of the formalin and hot-plate tests. Interestingly, the VCOs exhibited anti-inflammatory activity in an acute (carrageenan-induced paw edema test), but not in a chronic (cotton-pellet-induced granuloma test) model of inflammation. Conclusion: The MARDI-produced VCOs possessed antinociceptive and anti-inflammatory activities. Further studies are needed to confirm these observations.
Risk Factors and Outcomes for Retinopathy of Prematurity in Neonatal Infants with a Birth Weight of 1,501–2,000 g in a Chinese Neonatal Unit
Authors: Gu Mei-Hong , Jin Ji , Yuan Tian-Ming , Yu Hui-Min
Published: March 2011

Objective: To determine the risk factors and outcomes of retinopathy of prematurity (ROP) in infants with a birth weight of 1,501–2,000 g. Materials and Methods: Clinical characteristics and risk factors were compared and nonconditional logistic regression analysis was performed to determine independent predictors for ROP. Results: There were 54 (9.8%) cases of ROP in 553 patients with a birth weight of 1,501–2,000 g. The most common classification of ROP was in stage 1 (50/54, 92.6%; stages 2 and 3 ROP: 2 infants each). By logistic regression analysis, the following factors independently predicted ROP: gestational age at birth ≤34 weeks [odds ratio (OR): 9.01; 95% confidence interval (CI): 1.18–68.70], septicemia (OR: 2.88; 95% CI: 1.30–6.36) and perinatal asphyxia (OR: 5.74; 95% CI: 2.35–14.01). Conclusion: ROP occurred commonly among infants with a birth weight of 1,501–2,000 g. The risk factors were gestational age at birth ≤34 weeks, septicemia and perinatal asphyxia.
Recurrent High-Dose Intravenous Methylprednisolone Succinate Pulse Therapy-Induced Hepatopathy in a Patient with Multiple Sclerosis
Authors: Furutama Daisuke , Kimura Fumiharu , Shinoda Keiichi , Maeda Tamaki , Tanaka Toshifumi , Ohsawa Nakaaki
Published: March 2011

Objective: We describe recurrent and reversible hepatopathy in a girl with multiple sclerosis (MS) after glucocorticoid pulse therapy, to point out the possibility that glucocorticoid may harm the liver. Clinical Presentation and Intervention: An 11-year-old girl with MS, who was treated with high-dose methylprednisolone succinate pulse therapy, developed elevation of liver enzymes. The episodes of hepatopathy occurred 1–5 weeks after the therapy and disappeared within several weeks. The examination for antinuclear antibody and viruses which can cause hepatitis produced negative results. Conclusion: The present case emphasizes the possible effects of high-dose glucocorticoids in the induction of liver enzymes and the importance of follow-up liver tests after pulse therapy.
Factors Associated with Self-Rated Health after Kidney Transplantation: A Prospective Study
Authors: Majernikova Maria , Prihodova Lucia , Rosenberger Jaroslav , Nagyova Iveta , Roland Robert , Groothoff Johan W. , van Dijk Jitse P.
Published: March 2011

Background: This prospective study explores and compares the relationship between patients’ self-rated health (SRH) after kidney transplantation (KT) at different follow-up periods and its medical and nonmedical predictors over time. Methods: Patients (n = 128) who completed a questionnaire (the SRH question of the SF-36 and the End-Stage Renal Disease Symptom Checklist – Transplantation Module) were enrolled. Clinical data were retrieved from medical files. The sample was stratified into early (n = 89) and late (n = 39) cohorts according to time since KT at baseline. Linear regression was used to identify predictors of SRH at follow-up. Results: In both cohorts, a change in glomerular filtration rate (GFR) over time remained a predictor of SRH; in the early cohort, age was an additional predictor; in the late cohort, a change in transplantation-associated psychological distress over time and the number of late acute rejection episodes during the observation period were additional predictors. Conclusions: Improvement in GFR over time predicted better SRH at each period after KT. Decreased transplantation-associated psychological distress and fewer late acute rejection episodes seemed to predict better SRH at a later follow-up period. Despite these observations, higher SRH was associated with better clinical outcomes.
Nitrophorin 2, a factor IX(a)-directed anticoagulant, inhibits arterial thrombosis without impairing haemostasis
Authors: Mizurini Daniella M. , Francischetti Ivo M. B. , Andersen John F. , Monteiro Robson Q.
Published: March 2011

Nitrophorin 2 (NP2) is a 20 kDa lipocalin identified in the salivary gland of the blood sucking insect, Rhodnius prolixus. It functions as a potent inhibitor of the intrinsic pathway of coagulation upon binding to factor IX (FIX) or FIXa. Herein we have investigated the in vivo antithrombotic properties of NP2. Surface plasmon resonance assays demonstrated that NP2 binds to rat FIX and FIXa with high affinities (KD = 43 and 47 nM, respectively), and prolongs the aPTT without affecting the PT. In order to evaluate NP2 antithrombotic effects in vivo two distinct models of thrombosis in rats were carried out. In the rose Bengal/laser induced injury model of arterial thrombosis, NP2 increased the carotid artery occlusion time by ≈35 and ≈155%, at doses of 8 and 80 μg/kg, respectively. NP2 also inhibited thrombus formation in an arterio-venous shunt model, showing ≈60% reduction at 400 μg/kg (i.v. administration). The antithrombotic effect lasted for up to 48 hours after a single i.v. dose. Notably, effective doses of NP2 did not increase the blood loss as evaluated by tail-transection model. In conclusion, NP2 is a potent and long-lasting inhibitor of arterial thrombosis with minor effects on haemostasis. It might be regarded as a potential agent for the treatment of human cardiovascular diseases.
MOG1
Authors: Kattygnarath Darouna , Maugenre Svetlana , Neyroud Nathalie , Balse Elise , Ichai Carole , Denjoy Isabelle , Dilanian Gilles , Martins Raphaël P. , Fressart Véronique , Berthet Myriam , Schott Jean Jacques , Leenhardt Antoine , Probst Vincent , Le Marec Hervé , Hainque Bernard , Coulombe Alain , Hatem Stéphane N. , Guicheney Pascale
Published: March 2011

Background—

Brugada syndrome (BrS) is caused mainly by mutations in the
SCN5A
gene, which encodes the α-subunit of the cardiac sodium channel Na
v
1.5. However, ≈20% of probands have
SCN5A
mutations, suggesting the implication of other genes. MOG1 recently was described as a new partner of Na
v
1.5, playing a potential role in the regulation of its expression and trafficking. We investigated whether mutations in
MOG1
could cause BrS.

Methods and Results—

MOG1
was screened by direct sequencing in patients with BrS and idiopathic ventricular fibrillation. A missense mutation p.Glu83Asp (E83D) was detected in a symptomatic female patient with a type-1 BrS ECG but not in 281 controls. Wild type (WT)- and mutant E83D-MOG1 were expressed in HEK Na
v
1.5 stable cells and studied using patch-clamp assays. Overexpression of WT-MOG1 alone doubled sodium current (I
Na
) density compared to control conditions (
P
<0.01). In contrast, overexpression of mutant E83D alone or E83D+WT failed to increase I
Na
(
P
<0.05), demonstrating the dominant-negative effect of the mutant. Microscopy revealed that Na
v
1.5 channels failed to properly traffic to the cell membrane in the presence of the mutant. Silencing endogenous MOG1 demonstrated a 54% decrease in I
Na
density.

Conclusions—

Our results support the hypothesis that dominant-negative mutations in
MOG1
can impair the trafficking of Na
v
1.5 to the membrane, leading to I
Na
reduction and clinical manifestation of BrS. Moreover, silencing MOG1 reduced I
Na
, demonstrating that MOG1 is likely to be important in the surface expression of Na
v
1.5 channels. All together, our data support
MOG1
as a new susceptibility gene for BrS.
Discharge to a Skilled Nursing Facility and Subsequent Clinical Outcomes Among Older Patients Hospitalized for Heart Failure
Authors: Allen Larry A. , Hernandez Adrian F. , Peterson Eric D. , Curtis Lesley H. , Dai David , Masoudi Frederick A. , Bhatt Deepak L. , Heidenreich Paul A. , Fonarow Gregg C.
Published: March 2011

Background—

Heart failure (HF) is the leading cause of hospitalization among older Americans. Subsequent discharge to skilled nursing facilities (SNF) is not well described.

Methods and Results—

We performed an observational analysis of Medicare beneficiaries ≥65 years of age, discharged alive to SNF or home after ≥3-day hospitalization for HF in 2005 and 2006 within the Get With The Guidelines–HF Program. Among 15 459 patients from 149 hospitals, 24.1% were discharged to an SNF, 22.3% to home with home health service, and 53.6% to home with self-care. SNF use varied significantly among hospitals (median, 10.2% versus 33.9% in low versus high tertiles), with rates highest in the Northeast. Patient factors associated with discharge to SNF included longer length of stay, advanced age, female sex, hypotension, higher ejection fraction, absence of ischemic heart disease, and a variety of comorbidities. Performance measures were modestly lower for patients discharged to SNF. Unadjusted absolute event rates were higher at 30 days (death, 14.4% versus 4.1%; rehospitalization, 27.0% versus 23.5%) and 1 year (death, 53.5% versus 29.1%; rehospitalization, 76.1% versus 72.2%) after discharge to SNF versus home, respectively (
P
<0.0001 for all). After adjustment for measured patient characteristics, discharge to SNF remained associated with increased death (hazard ratio, 1.76; 95% confidence interval, 1.66 to 1.87) and rehospitalization (hazard ratio, 1.08; 95% confidence interval, 1.03 to 1.14).

Conclusions—

Discharge to SNF is common among Medicare patients hospitalized for HF, and these patients face substantial risk for adverse events, with more than half dead within 1 year. These findings highlight the need to better characterize this unique patient population and understand the SNF care they receive.
Group psychosocial interventions for adults with schizophrenia and bipolar illness: The evidence base in the light of publications between 1986 and 2006
Authors: Segredou I. , Xenitidis K. , Panagiotopoulou M. , Bochtsou V. , Antoniadou O. , Livaditis M.
Published: March 2011

Aim: The treatment of major mental disorders usually combines medical and psychosocial interventions. The present study reviews research pertaining to the efficacy of group psychosocial interventions for people with psychotic illness.

Method: An electronic search was conducted through Medline and PsychINFO to identify articles relevant to group therapy for people with schizophrenia and bipolar affective disorder. Articles published in the English language, between January 1986 and May 2006, were considered. Studies were included if they had a control group and at least 20 participants. The search resulted in 23 articles concerning patients with schizophrenia and five concerning patients with bipolar affective disorder.

Results and Conclusion: The therapeutic approach in the majority of the studies was along the lines of cognitive behaviour therapy and psychoeducation. All studies reported improvement in at least one parameter. Most of them report improvement in skills and overall functioning.
Pluralized life courses? An exploration of the life trajectories of individuals with psychiatric disorders
Authors: Müller Nicolas S. , Sapin Marlène , Jacques-Antoine Gauthier , Orita Alina , Widmer Eric D.
Published: March 2011

Background: Most of the existing research relating to the life courses of people with psychiatric symptoms focuses on the occurrence and the impact of non-normative events on the onsets of crises; it usually disregards the more regular dimensions of life, such as work, family and intimate partnerships that may be related to the timing and seriousness of psychiatric problems. An additional reason for empirically addressing life trajectories of individuals with psychiatric problems relates to recent changes of family and occupational trajectories in relation to societal trends such as individualization and pluralization of life courses.

Aim: This paper explores the life trajectories of 86 individuals under clinical supervision and proposes a typology of their occupational, co-residence and intimacy trajectories. The results are discussed in light of the life-course paradigm.

Method: A multidimensional optimal matching analysis was performed on a sample of 86 individuals under clinical supervision to create a typology of trajectories. The influence of these trajectories on psychiatric disorders, evaluated using a SCL-90-R questionnaire, was then assessed using linear regression modelling.

Results: The typologies of trajectories showed that the patients developed a diversity of life trajectories. Individuals who have developed a standard life course with few institutionalization periods reported more symptoms and distress than individuals with an institutionalized life trajectory.

Conclusion: The results of this study stress that psychiatric patients are social actors who are influenced by society at large and its ongoing process of change. Therefore, it is essential to take into account the diversity of occupational and family trajectories when dealing with individuals in therapeutic settings.
Towards a perspective of system synchronization in water governance: a synthesis of empirical lessons and complexity theories
Authors: Teisman Geert R. , Edelenbos Jurian
Published: March 2011

In this manuscript we conclude the special issue on Water Governance. We look back on the different contributions and discuss different interesting insights from the three contributions focusing on Wisconsin, California and Southern Ecuador. We place these insights into a new perspective on integration, i.e. system synchronization, which the authors consider to be an option for integration in complex governance systems, where nobody is in charge.

Points for practitioners

In this epilogue we have picked the fruits of the contributions to this symposium. We have come to another way of looking at the fragmentation—integration debate in public administration, i.e. system synchronization. By discussing different water cases from Wisconsin, California and Southern Ecuador, we have arrived at three principles of system synchronization: Synchronization means self-organization and variation; Synchronization means thinking and acting between self and the larger whole; Synchronization means operating on and beyond the boundaries of subsystems. These principles are needed to realize system synchronicity in which different subsystems largely hold their identity, but strive for coherence.
Financial Management Accountability Index (FMAI) in the Malaysian public sector: a way forward
Authors: Nur Barizah Abu Bakar  , Ismail Suhaiza
Published: March 2011

The National Audit Department (NAD) of Malaysia has introduced the Financial Management Accountability Index (FMAI) within the framework of the audit rating system. This study shares the Malaysian experience in using FMAI as an accountability medium, evaluates the FMAI scores obtained by agencies, and proposes measures to enhance the usefulness of FMAI. The study uses secondary data as provided on the NAD website. Descriptive analyses were conducted in evaluating the rating scores across agencies. It was found that majority of the agencies have a ‘good’ financial management system, with Federal agencies performing better than their counterparts at the State level. It was also found that the overall rating system and FMAI suffer from lack of proper disclosure, consequently reducing their worthiness. There are still areas of improvement that need to be addressed by the NAD to enhance the value of the overall audit rating system.

Points for practitioners

The FMAI, which has been developed and used in Malaysia, is an important initiative that can be emulated by public managers in other governments, either in its current form or with modifications. It is particularly useful for benchmarking purposes. In the context of Malaysia, this research provides important insights for public policy-makers on how the usefulness of the audit rating system can be further increased.
How well can public service motivation connect with occupational intention?
Authors: Bangcheng Liu  , Chun Hui  , Jin Hu  , Wensheng Yang  , Xinli Yu
Published: March 2011

Researchers have hypothesized that a person’s public service motivation (PSM) has a positive connection with occupational intention: the greater an individual’s PSM, the more likely he or she is to seek membership in a public organization. However, few empirical studies have tested this proposition. Based on a survey of 584 students from two prestigious universities in eastern China, this study explores how well PSM relates to students’ occupational intention. This study found that not all dimensions of PSM were consistently connected with occupational intention. The self-sacrifice dimension of PSM has a positive relationship with occupational intention, but the commitment to the public interests dimension does not. Moreover, the study found that female students who majored in social sciences and had relatives or parents in the public sector were more likely to choose employment in the public sector. The implications of this study and areas of future research are discussed.

Points for practitioners

Results of the study demonstrated that there was a significant relationship between PSM and occupational intention, but not all dimensions of PSM were consistently connected with occupational intention. The results identified several key implications: (1) For professionals in charge of recruiting and selecting public servants, PSM of a job seeker is a key criteria. (2) For job seekers, when they decide to enter public sector, the levels of their PSM should be considered. (3) Additionally, the background information on job seekers does matter to some extent when recruiting and selecting in public sector.
Deliberative governance in synergy with government: a case study of credible environmental improvements in the Dairy Gateway, USA
Authors: Metze Tamara A.P.
Published: March 2011

This article examines a case of deliberative governance in the Dairy Gateway Project in the Northeast of Wisconsin, USA. In this project government, academic researchers, farmers and environmental organizations built cooperative voluntary networks to improve the quality of water, air and soil. They introduced dialogue, learning and stewardship as alternatives to governmental ‘command and control’. At three types of meetings a broader group of participants deliberated about the interpretation of these concepts. The study of these interpretative struggles in the form of boundary work demonstrates that participants considered dialogue and learning in networks a credible new way to cooperate, and that in most cases they accepted farmers as stewards of the land. However, they all wanted government to audit this stewardship. Hence, deliberative governance emerged in synergy with government.

Point for practitioners

Reflective conversations about boundary concepts, for example ‘stewardship’, can help to overcome environmental conflicts. This concept aligns incompatible discourses. When boundary concepts are introduced, participants in networks of, for example, farmers, environmentalists and governmental actors are challenged to think about new solutions. Moreover, they are encouraged to rethink the role of government. Deliberative settings, in which facilitators pay special attention to the quality of the conversations, enable this rethinking. In these conversations adversarial actors can empathically disagree. As a result, participants start negotiating credible solutions and establish what role government has to have.
Preparing Jordanian university services to implement a quality self-assessment methodology
Authors: Tarí Juan José , Madeleine Carolina
Published: March 2011

The purpose of this article is to analyse the European Foundation for Quality Management (EFQM) self-assessment model in higher education institutions (HEIs) in Spain and in Jordan, and show what Jordanian HEIs have learnt from the Spanish experience. The article uses a case study methodology on eight administrative services provided by a public university in Spain and seven services provided by one public and one private university in Jordan. The findings show the steps that an administrative service may follow in order to apply the questionnaire approach to self-assessment in a successful manner. It provides lessons for decision-makers and managers from other public services in HEIs in Jordan, and other developing countries, who wish to perform an exercise in self-assessment using a questionnaire approach.

Points for practitioners

The article describes a practical methodology for assessing quality in public services in HEIs. It identifies the steps to implement this methodology in public services in a developed country (Spain) and in a developing country (Jordan) and the lessons learnt by the developing country. The article shows that the concept of quality awards can be adapted to different contexts, although there is a need for modification and careful implementation. The study provides lessons for decision-makers and managers from other public services in HEIs in Jordan, and other developing countries, who wish to perform an exercise in self-assessment using a questionnaire approach.