bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal trends and predictors of pelvic lymph node dissection in open or minimally invasive radical prostatectomy
Authors: Feifer Andrew H. , Elkin Elena B. , Lowrance William T. , Denton Brian , Jacks Lindsay , Yee David S. , Coleman Jonathan A. , Laudone Vincent P. , Scardino Peter T. , Eastham James A.
Published: March 2011

BACKGROUND:

Pelvic lymph node dissection (PLND) is an important component of prostate cancer staging and treatment, especially for surgical patients who have high‐risk tumor features. It is not clear how the shift from open radical prostatectomy (ORP) to minimally invasive radical prostatectomy (MIRP) has affected the use of PLND. The objectives of this study were to identify predictors of PLND and to assess the impact of surgical technique in a contemporary, population‐based cohort.

METHODS:

In Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked with Medicare claims, the authors identified men who underwent ORP or MIRP for prostate cancer during 2003 to 2007. The impact of surgical approach on PLND was evaluated, and interactions were examined between surgical procedure, prostate‐specific antigen (PSA), and Gleason score with the analysis controlled for patient and tumor characteristics.

RESULTS:

Of 6608 men who underwent ORP or MIRP, 70% (n = 4600) underwent PLND. The use of PLND declined over time both overall and within subgroups defined by procedure type. PLND was 5 times more likely in men who underwent ORP than in men who underwent MIRP when the analysis was controlled for patient and tumor characteristics. Elevated PSA and biopsy Gleason score, but not clinical stage, were associated with a greater odds of PLND in both the ORP group and the MIRP group. However, the magnitude of the association between these factors and PLND was significantly greater for patients in the ORP group.

CONCLUSIONS:

PLND was less common among men who underwent MIRP, independent of tumor risk factors. A decline in PLND rates was not fully explained by an increase in MIRP. The authors concluded that these trends may signal a surgical approach‐dependent disparity in prostate cancer staging and therapy. Cancer 2011;. © 2011 American Cancer Society.
Secondary malignancies among nonseminomatous germ cell tumor cancer survivors
Authors: Chamie Karim , Kurzrock Eric A. , Evans Christopher P. , Litwin Mark S. , Koppie Theresa M. , Wootton‐Gorges Sandra L. , Boone John M. , Lara Primo N. , deVere White Ralph W.
Published: March 2011

BACKGROUND:

Men on active surveillance for clinical stage I nonseminomatous germ cell tumor (NSGCT) undergo frequent computed tomography imaging to avoid delayed detection of disease. Irradiation from frequent imaging and chemotherapy upon progression may place patients at increased risk of a second malignancy. In this study, the authors sought to identify such an increased risk among men who chose initial surveillance for NSGCT.

METHODS:

The authors utilized data from the Surveillance, Epidemiology and End Results Program and stratified the cohort based on whether they underwent retroperitoneal lymph node dissection (RPLND). A propensity‐score model was used to adjust for covariates, and a competing‐risks regression analysis was performed to estimate cumulative incidence rates of second malignancy. Incidence risk ratios were predicted by using the cumulative incidence rates per 10,000 patients.

RESULTS:

There was no statistically significant increase in the incidence of a secondary malignancy for the entire cohort of testicular cancer survivors. However, when the analysis was restricted to patients with clinical stage I NSGCT, nonsurgical management only in those aged >45 years was an independent predictor of developing a second malignancy. For every 10,000 patients with stage I NSGCT who chose to forego RPLND, an absolute excess incidence of 22, 52, and 73 secondary malignancies would be diagnosed at 5 years, 10 years, and 15 years, respectively.

CONCLUSIONS:

The current results indicated that patients aged >45 years who forego RPLND for T1 or T2 clinical stage I NSGCT are more likely to develop a second malignancy than those who do undergo RPLND. Nonsurgical management of NSGCT may be associated with more long‐term health risks than primary RPLND. Cancer 2011;. © 2011 American Cancer Society.
A survey of stereotactic body radiotherapy use in the United States
Authors: Pan Hubert , Simpson Daniel R. , Mell Loren K. , Mundt Arno J. , Lawson Joshua D.
Published: March 2011

BACKGROUND:

Stereotactic body radiotherapy (SBRT) is a technique used to deliver high, ablative doses of radiation in a limited number of fractions to ≥1 extracranial target(s). To the authors' knowledge, the prevalence of SBRT use among radiation oncologists in the United States is unknown.

METHODS:

A random sample of 1600 American radiation oncologists was surveyed via e‐mail and facsimile (fax) regarding SBRT usage, including year of adoption, motivations, disease sites treated, and common prescriptions used.

RESULTS:

Of 1373 contactable physicians, 551 responses (40.1%) were received. The percentage of physicians using SBRT was 63.9% (95% confidence interval, 60%‐68%), of whom nearly half adopted it in 2008 or later. The most commonly cited reasons for adopting SBRT were to allow the delivery of higher than conventional radiation doses (90.3%) and to allow retreatment (73.9%) in select patients. Academic physicians were more likely to report research as a motivation for SBRT adoption, whereas physicians in private practice were more likely to list competitive reasons. Among SBRT users, the most common disease sites treated were lung (89.3%), spine (67.5%), and liver (54.5%) tumors. Overall, 76.0% of current SBRT users planned to increase their use, whereas 66.5% of nonusers planned to adopt the technology in the future.

CONCLUSIONS:

SBRT has rapidly become a widely adopted treatment approach among American radiation oncologists. Further research and prospective trials are necessary to assess the benefits and risks of this novel technology. Cancer 2011;. © 2011 American Cancer Society.
Second‐line chemotherapy for recurrent carcinoma of the ovary
Authors: Thigpen J. Tate , Vance Ralph B. , Khansur Tawfig
Published: March 2011

Despite relatively high response rates to chemotherapy for ovarian carcinoma, most patients eventually will have progressive disease that will require additional therapy. Most efforts to study such second‐line or “salvage” chemotherapy have been single‐arm trials of small numbers of patients, which report widely variable response rates, relatively short response durations, and short survival times. Only recently have certain critical patient characteristics been recognized as important in determining appropriate therapy as follows: (1) the extent and volume of disease at recurrence and (2) the type and duration of response to prior chemotherapy. Patients with small‐volume disease confined to the peritoneal cavity have a far better chance of achieving a response to second‐line chemotherapy with subsequent prolonged survival than do those with bulky disease or disease outside the abdomen. Perhaps even more critical is the distinction between those patients whose neoplasm is still “clinically sensitive” to the platinum‐containing compounds (initial response to platinum‐based therapy and relapse more than 6 months after cessation of treatment) and those with “clinically resistant” disease (progression during or within 6 months of front‐line platinum‐based therapy). Those considered clinically sensitive to platinum‐based therapy should be retreated with a platinum‐containing regimen at the time of recurrence. Those with evidence for resistance should receive alternative treatment with one or more drugs capable of inducing responses in such patients. These drugs currently include: taxol, ifosfamide, and hexamethylmelamine.
Paradigms for Sustainable Development: Implications of Management Theory
Authors: Dutta Saurav , Lawson Raef , Marcinko David
Published: March 2011

We provide a framework for examining the trade‐offs between socio‐environmental, organizational, and managerial goals. Using this framework we examine management choices under agency and stewardship theories. We advance a theory of social stewardship to explain behavior inconsistent with both agency and stewardship. We illustrate that social stewardship behavior by managers and principals, while best from a societal perspective, is not a viable management approach under current business and regulatory conditions. This conclusion is vital to public policymakers who seek to foster socially desirable behavior by publicly traded companies. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment.
A novel scoring system combining expression of CD23, CD20, and CD38 with platelet count predicts for the presence of the t(11;14) translocation of mantle cell lymphoma
Authors: Medd Patrick G. , Clark Nithiya , Leyden Kevin , Turner Susan , Strefford Jennifer A. , Butler Caroline , Collins Graham P. , Roberts David J. , Atoyebi Wale , Hatton Chris S. R.
Published: March 2011

Background:

Both chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are CD5/19 positive. The t(11;14) MCL translocation is identified by fluorescent in situ hybridization (FISH) and can distinguish the two disorders. We attempted to identify flow cytometric and other markers predictive of a positive FISH test.

Methods:

We examined 100 atypical CLL/MCL cases for demographic, hematological, and cytometric variables, 96 were FISH tested for t(11;14) and four were known MCL.

Results:

Twenty‐two cases were confirmed as MCL. Multivariate analysis identified four variables associated with MCL: Thrombocytopenia (taken as Plt < 150 × 109/L), CD23 negative, CD20 strong, and CD38 positive, with these variables a four‐point score was devised. By ROC analysis, the MCL score was superior in differentiating MCL to the Marsden CLL score (AUC 0.95 vs. 0.78). MCL score ≥2 showed sensitivity 1, specificity 0.66, positive predictive value (PPV) 0.49, and negative predictive value (NPV) 1 for MCL. The score was then prospectively validated on an independent cohort of 44 cases of atypical CLL/MCL. No MCL had a score <3. Validation PPV/NPV of score ≥3 were 0.5/1. Overall survival in MCL was shorter compared to t(11;14) negative patients (median 3.3 vs. 4.2 years, HR 2.2, 95% CI 0.87–5.5, P = 0.1).

Conclusions:

The score described can be used to identify cases of CD5/19 positive lymphoproliferative disorders likely to be t(11;14) positive MCL. © 2011 International Clinical Cytometry Society
Methodological comparison of two anti‐ZAP‐70 antibodies
Authors: Degheidy Heba A. , Venzon David J. , Farooqui Mohammed Z. H. , Abbasi Fatima , Arthur Diane C. , Wilson Wyndham H. , Wiestner Adrian , Stetler‐Stevenson M. A. , Marti Gerald E.
Published: March 2011

Background:

ZAP‐70 expression is a stage independent prognostic marker in CLL. However, interlaboratory variation is large, and there is neither a consensus nor a regulatory approved methodology.

Methods:

Two anti‐ZAP70 clones (1E7.2 and SBZAP) were compared in 45 untreated CLL patients. Nine different methods for ZAP‐70 expression analysis were evaluated: M1, isotype control to determine negative; M2, internal residual T‐cell to determine positive; M3, normal donor (ND) T‐cell to determine positive; M4, internal T‐cell/clone ratio; M5, ND residual T‐cell/clone ratio; M6, clone/normal remaining B‐cell ratio; M7, clone/ND B‐ cell ratio; M8, CLL‐Z score; M9, modified CLL‐Z score. A scoring system was designed integrating both 1E7.2 and SBZAP clones to assign ZAP‐70 expression.

Results:

The correlation coefficients for the four selected highest statistically significant methods were as follows (M1 = 0.71, M3 = 0.72, M7 = 0.67, and M9 = 0.64). These four methods were used to generate a combined score. The two reagents showed agreement using the designed scoring system for 37/45 samples (82%), and 8/45 (18%) showed equivocal result with one of the two clones. Seven of the eight equivocal samples were resolved using the scoring system.

Conclusions:

Four of the nine methods of analysis were compared for each reagent. The use of two independent ZAP‐70 reagents increases analytical certitude and the scoring method aids in the resolution of equivocal results. The combined use of two reagents, four methods of analysis, and a scoring method allowed for assignment of ZAP‐70 expression in 44/45 samples (98%) tested and improved performance of this important prognostic assay. Published 2011 Wiley‐Liss, Inc.
Expression and actions of transcription factors in adult hippocampal neurogenesis
Authors: Hodge Rebecca D. , Hevner Robert F.
Published: March 2011

Neurogenesis in the adult brain, a process once thought to be essentially absent, has now been demonstrated to occur throughout adult mammalian life within several brain regions. Adult neurogenesis normally occurs only within the subventricular zone (SVZ) bordering the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). Neurogenic progenitors within these regions produce distinct neuron types, with progenitors in the SGZ giving rise to glutamatergic neurons that populate the DG granule cell layer and those within the SVZ producing neurons destined for the olfactory bulb. In this review, we highlight recent research on transcription factor expression and function during adult hippocampal neurogenesis. In this regard, recent evidence indicates that adult neurogenesis replicates important aspects of progenitor cell development in the embryonic brain. Specifically, work from our laboratory and others indicates that transcription factor cascades active in progenitor cells during neurogenesis in the embryonic cerebral cortex are also activated in adult hippocampal progenitor cells, where they play an important role in determining neuronal fate and regulating progenitor cell proliferation and maintenance. These findings suggest thatconserved transcription factor cascades regulate genetic programs that delineate progenitor cell lineages and control progenitor cell proliferation and differentiation. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 71:680–689, 2011
Covalent Functionalization of Silicon Surfaces with a Cavitand‐Modified Salen
Authors: Tudisco Cristina , Sfrazzetto Giuseppe Trusso , Pappalardo Andrea , Motta Alessandro , Tomaselli Gaetano A. , Fragalà Ignazio L. , Ballistreri Francesco P. , Condorelli Guglielmo G.
Published: March 2011

Si(100) and porous silicon substrates have been engineered with cavitand modified salen molecules. A salen derivative, specifically designed for covalently anchoring on silicon, was grafted onto Si(100) surfaces by photochemical hydrosilylation, and onto porous silicon by thermal hydrosilylation. These hybrid systems have been studied by different analytic techniques. Monochromatized X‐ray photoelectron spectroscopy (XPS) was used to characterize both flat and porous samples. Atomic force microscopy (AFM) and, in particular, atomic force lithography (AFL) were used to evaluate the monolayer structure and morphology of the flat silicon surface, while Fourier transform infrared spectroscopy (FTIR) was adopted to probe the hydrosilylation process involving porous samples. The uranyl complex of the salen derivative was directly synthesized on the silicon surface by the reaction between Si‐anchored salen and uranyl acetate. This surface‐based synthesis suggests that the salen molecules are intact and keep their specific properties after silicon anchoring.
Total Synthesis of (–)‐Corynantheidine by Nickel‐Catalyzed Carboxylative Cyclization of Enynes
Authors: Mizuno Takashi , Oonishi Yoshihiro , Takimoto Masanori , Sato Yoshihiro
Published: March 2011

The total synthesis of (–)‐corynantheidine has been achieved through Ni0‐mediated carboxylative cyclization as the key reaction step with incorporation of CO2, and this cyclization was also successfully expanded to the catalytic reaction by using Et2Zn in the presence of an excess amount of DBU.
Compulsory project‐level involvement and the use of program‐level evaluations: Evaluating the Local Systemic Change for Teacher Enhancement program
Authors: Johnson Kelli , Weiss Iris R.
Published: March 2011

In 1995, the National Science Foundation (NSF) contracted with principal investigator Iris Weiss and an evaluation team at Horizon Research, Inc. (HRI) to conduct a national evaluation of the Local Systemic Change for Teacher Enhancement program (LSC). HRI conducted the core evaluation under a $6.25 million contract with NSF. This program evaluation project, called the LSC core evaluation, had an overarching program‐wide focus that included all 88 local LSC projects. The LSC core evaluation was a large, multisite program evaluation that included multiple data‐collection and information‐dissemination activities. Each local LSC project was required to have a project‐level evaluator, to collect information by using predesigned data‐collection instruments developed by HRI, and to report findings to the core evaluation on a regular basis. This case study describes the relationship between project‐level involvement in the LSC core evaluation and the use of the core evaluation by project leaders and evaluators. © Wiley Periodicals Inc., and the American Evaluation Association.
Congenital anomalies and rhabdoid tumor associated with 22q11 germline deletion and somatic inactivation of the SMARCB1 tumor suppressor
Authors: Toth George , Zraly Claudia B. , Thomson Tricia L. , Jones Carolyn , Lapetino Shawn , Muraskas Jonathan , Zhang Jiwang , Dingwall Andrew K.
Published: March 2011

The most common microdeletion in humans involves the 22q11 region. Congenital anomalies associated with 22q11 loss include cardiac and facial defects. Less frequent is the co‐presentation of malignant rhabdoid tumors that are highly aggressive childhood malignancies typically found in renal or extra‐renal soft tissues and central nervous system. A newborn patient presented with multiple congenital anomalies consistent with 22q11 deletion syndrome including cleft lip and palate, ear tags and ventricular septal defects co‐presenting with an axillary rhabdoid tumor. Comparative genomic hybridization revealed a 2.8 Mb germline deletion in the 22q11.2 region containing genes required for normal fetal development and the SMARCB1 tumor suppressor gene. Analysis of tumor DNA revealed a somatic deletion of exon 7 in the second allele of SMARCB1. Expression of SMARCB1 was absent, while tumor markers including MYC, GFAP, and CLAUDIN‐6 were upregulated. The presence of tandem oriented BCRL modules located within interspersed low copy repeat elements throughout the 22q11 distal region may predispose this area for microdeletions through nonalleleic homologous recombination. © 2011 Wiley‐Liss, Inc.
High‐resolution array CGH identifies common mechanisms that drive embryonal rhabdomyosarcoma pathogenesis
Authors: Paulson Vera , Chandler Garvin , Rakheja Dinesh , Galindo Rene L. , Wilson Kathleen , Amatruda James F. , Cameron Scott
Published: March 2011

Pediatric rhabdomyosarcoma occurs as two biologically distinct histological variants, embryonal (ERMS) and alveolar (ARMS). To identify genomic changes that drive ERMS pathogenesis, we used a new array comparative genomic hybridization (aCGH) platform to examine a specific subset of ERMS tumors, those occurring in children with clinically defined intermediate‐risk disease. The aCGH platform used has an average probe spacing ∼1 kb, and can identify genomic changes with single gene resolution. Our data suggest that these tumors share a common genomic program that includes inactivation of a master regulator of the p53 and Rb pathways, CDKN2A/B, and activation of FGFR4, Ras, and Hedgehog (Hh) signaling. The CDKN2A/B tumor suppressor is deleted in most patient samples. FGFR4, which encodes a receptor tyrosine kinase, is activated in 20% of tumors, predominantly by amplification of mutant, activating FGFR4 alleles. Over 50% of patients had low‐level gains of a region containing the Hh‐pathway transcription factor GLI1, and a gene expression pattern consistent with Hh‐pathway activation. We also identified intragenic deletions affecting NF1, a tumor suppressor and inhibitor of Ras, in 15% of tumor samples. Deletion of NF1 and the presence of activating Ras mutations (in 42% of patients) were mutually exclusive, suggesting NF1 loss is an alternative and potentially common mechanism of Ras activation in ERMS. Our data suggest that intermediate‐risk ERMS is driven by a common set of genomic defects, a finding that has important implications for the application of targeted therapies to improve the treatment of children diagnosed with this disease. © 2011 Wiley‐Liss, Inc.
The Nrf2‐inducible antioxidant defense in astrocytes can be both up‐ and down‐regulated by activated microglia:Involvement of p38 MAPK
Authors: Correa Fernando , Ljunggren Elin , Mallard Carina , Nilsson Michael , Weber Stephen G. , Sandberg Mats
Published: March 2011

The effects of microglia‐conditioned medium (MCM) on the inducible Nrf2 system in astrocyte‐rich cultures were investigated by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the modulatory subunit of γGCL (γGCL‐M) and activated MAP kinases (ERK1/2, JNK and p38). Microglia were either cultured for 24 h in serum‐free culture medium to achieve microglia‐conditioned medium from non‐activated cells (MCM0), used as control condition, or activated with different concentrations (0.1–1,000 ng mL−1) of lipopolysaccharide (LPS) to produce MCM0.1–1,000. Acute exposure (24 h) to MCM100 increased GSH, γGCL activity, the protein levels of γGCL‐M, Nrf2, and activated JNK and ERK1/2 in astrocyte‐rich cultures. In contrast, treatment with MCM10 for 24 h decreased components of the Nrf2 system in parallel with activation of p38 MAPK. Stimulation of the Nrf2 system by tBHQ was partly intact after 24 h but blocked after 72 h treatment with MCM10 and MCM100. This down‐regulation after 72 h correlated with activation of p38 MAPK and lack of ERK1/2 and JNK activation. The negative effects were partly reversed by an inhibitor of p38 which restored tBHQ mediated protection against oxidative stress. In conclusion, the study showed a negative effect of MCM10 on the inducible anti‐oxidant defense in astrocyte‐rich cultures at both 24 and 72 h that correlated with activation of p38 and was partly reversed by a p38 inhibitor. A transient protective effect of MCM100 on astrocyte‐rich cultures against H2O2 toxicity was observed at 24 h which coincided with activation of JNK and ERK1/2. © 2011 Wiley‐Liss, Inc.
Influence of intensity‐modulated radiation therapy technique on xerostomia and related quality of life in patients treated with intensity‐modulated radiation therapy for nasopharyngeal cancer
Authors: Marucci Laura , Marzi Simona , Sperduti Isabella , Giovinazzo Giuseppe , Pinnarò Paola , Benassi Marcello , Strigari Lidia
Published: March 2011

Background

The purpose of this study was to compare 5‐field and 7‐field intensity‐modulated radiation therapy (IMRT) techniques in terms of xerostomia and related quality of life in patients with nasopharyngeal cancer.

Methods

Eight and 23 patients were treated with 5‐field (group I) and 7‐field (group II) techniques, respectively. The xerostomia was evaluated using the Radiation Therapy Oncology Group (RTOG) scale, stimulated and unstimulated salivary flow (SSF/USF), and xerostomia‐related questionnaires (XQs). The assessments were done before and at 3, 6, 12, 18, and 24 months after radiotherapy.

Results

The mean parotid dose was 45.7 Gy and 29.9 Gy and the ≥G3 toxicity at 24 months was 25% and 19% in group I and II, respectively. Sixty‐three percent and 93% of patients recovered at least 25% of SSF pretherapy values. The XQ scores of both groups improved over time but more so in group II.

Conclusion

The 7‐field technique decreases the mean parotid dose, reducing xerostomia assessed by the RTOG/XQ score. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Pancreatic-derived factor promotes lipogenesis in the mouse liver: Role of the Forkhead box 1 signaling pathway
Authors: Li Jing , Chi Yujing , Wang Chunjiong , Wu Jing , Yang Hang , Zhang Dongjuan , Zhu Yi , Wang Nanping , Yang Jichun , Guan Youfei
Published: March 2011

Pancreatic-derived factor (PANDER) is a pancreatic islet-specific cytokine that cosecretes with insulin and is important for β cell function. Here, we show that PANDER is constitutively expressed in hepatocytes, and its expression is significantly increased in steatotic livers of diabetic insulin-resistant db/db mice and mice fed a high-fat diet. Overexpression of PANDER in the livers of C57Bl/6 mice promoted lipogenesis, with increased Forkhead box 1 (FOXO1) expression, whereas small interfering RNA–mediated knockdown of hepatic PANDER significantly attenuated steatosis, with reduced FOXO1 expression in db/db mice. Hepatic PANDER silencing also attenuated insulin resistance and hyperglycemia in db/db mice. In cultured hepatocytes, PANDER overexpression induced lipid deposition, increased FOXO1 expression, and suppressed insulin-stimulated Akt activation and FOXO1 inactivation. Moreover, FOXO1 overexpression increased PANDER expression in cultured hepatocytes and mouse livers.

Conclusion:

PANDER promotes lipogenesis and compromises insulin signaling in the liver by increasing FOXO1 activity. PANDER may represent a potential therapeutic target for the treatment of fatty liver and insulin resistance. (HEPATOLOGY 2011;)
Geriatric drug utilisation of psychotropics in Belgian nursing homes
Authors: Azermai Majda , Elseviers Monique , Petrovic Mirko , Van Bortel Luc , Stichele Robert Vander
Published: March 2011

Objective

To determine the prevalence of psychotropic drug use in Belgian nursing homes, in relation to residents' and institutional characteristics.

Methods

The PHEBE project (Prescribing in Homes for the Elderly in Belgium, 2005) was a cross‐sectional study, investigating drug use in 76 nursing homes. Psychotropics were categorised into antidepressants, antipsychotics, benzodiazepines and anti‐dementia drugs using the ATC classification.

Results

Residents' mean age (n = 1730) was 85 (SD: 8) years and 78% were female. The overall prevalence of psychotropic drug use among nursing home residents was 79%. Benzodiazepines were used by 54% and antipsychotics by 33% of all residents. Residents received a higher number of antipsychotics (p < 0.001) but fewer antidepressants (and other medicines) with increasing severity of dementia. Antidepressants were prescribed in 40% of which 2/3 was indicated for depression and 1/3 for insomnia. Anti‐dementia drugs were used by 8%. Institutional characteristics showed no relationship with psychotropic drug use, except for a lower use when medication was dispensed by a hospital pharmacist (p = 0.001).

Conclusion

As in other European countries, the prevalence of psychotropic utilisation in Belgian nursing homes is exceedingly high, with excessive duplicate use. Guidelines, education and clinical practice recommendations focusing on initiation, reassessment and withdrawal of psychotropic therapy, are needed. Copyright © 2011 John Wiley & Sons, Ltd.
Flood seasonality‐based regionalization methods: a data‐based comparison
Authors: Sarhadi Ali , Modarres Reza
Published: March 2011

Improving techniques of flood frequency estimation at ungauged catchments is one of the major challenges for hydrologists, especially in arid and semi‐arid regions with insufficient information. Recently, popularity of flood seasonality‐based descriptors has increased among hydrologists for delineating of hydrologically homogenous regions.

This study presents a data‐based comparison of three well‐known flood seasonality‐based regionalization methods in Halilrud basin in southeastern Iran. A Jack‐knife procedure is used to assess the performance of the methods for flood quantile estimation at ungauged sites. The results of these three seasonality‐based methods are compared to those results obtained from two alternative methods: a traditional regionalization method based on catchment's hydrogeomorphic characteristics similarity and a scenario that uses all available information without subdividing area.

The results indicate that although peak over threshold (POT) approach which uses all flood events during year leads to better performance than other methods, but applying POT data series in a specific season (critical season) based on POT‐CS approach leads to better homogenous region and improves flood quantile estimation at ungauged sites. Copyright © 2011 John Wiley & Sons, Ltd.
Spatial and temporal variability of surface water repellency in sandy loam soils of NW Spain under Pinus pinaster and Eucalyptus globulus plantations
Authors: Rodríguez‐Alleres M. , Benito E.
Published: March 2011

This work was undertaken for two main purposes. One was to examine spatial and temporal variability in surface water repellency under field conditions in sandy loam forest soils of NW Spain, and its relationship to weather and soil moisture conditions. The other purpose was to get further inside in the dynamics of soil water repellency by studying a wetting–drying cycle under controlled laboratory conditions. Both for the field and laboratory study, water repellency was determined using the Water Drop Penetration Time test. Soil water repellency under field conditions was found to exhibit a seasonal pattern, i.e. it peaked during the summer and was absent between November and May. The time required for repellency to become re‐established during the spring was shorter under eucalyptus than under pine. Spatial variability peaked at an early stage of soil drying and was minimal during the wet period when soils were hydrophilic as well as at the end of the summer, when repellency was strongest. Spatial and temporal variability in water repellency was found to be negatively correlated with soil moisture and, to a lesser extent, with antecedent rainfall. The moisture range of the so‐called transition zone (below which the soil is hydrophobic and also above which it is hydrophobic) differed for the pine (21–50%) and eucalyptus plantations (17–36%). The lower and upper bounds of the transition zone agreed well with the soil moisture contents at the permanent wilting point and at field capacity, respectively. The laboratory results with samples in the wetting phase confirmed those of the field tests. Water repellency increased slightly during the drying phase, but not so much as in the field. Copyright © 2011 John Wiley & Sons, Ltd.
Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location
Authors: Leufkens Anke M. , Van Duijnhoven Fränzel J.B. , Boshuizen Hendriek C. , Siersema Peter D. , Kunst Anton E. , Mouw Traci , Tjønneland Anne , Olsen Anja , Overvad Kim , Boutron‐Ruault Marie‐Christine , Clavel‐Chapelon Françoise , Morois Sophie , Krogh Vittorio , Tumino Rosario , Panico Salvatore , Polidoro Silvia , Palli Domenico , Kaaks Rudolf , Teucher Birgit , Pischon Tobias , Trichopoulou Antonia , Orfanos Philippos , Goufa Ioulia , Peeters Petra H.M. , Skeie Guri , Braaten Tonje , Rodríguez Laudina , Lujan‐Barroso Leila , Sánchez‐Pérez Maria‐José , Navarro Carmen , Barricarte Aurelio , Zackrisson Sophia , Almquist Martin , Hallmans Goran , Palmqvist Richard , Tsilidis Konstantinos K. , Khaw Kay‐Tee , Wareham Nick , Gallo Valentina , Jenab Mazda , Riboli Elio , Bueno‐de‐Mesquita H. Bas
Published: March 2011

Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational level and CRC. We studied data from 400,510 participants in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,447 developed CRC (colon: 1,551, rectum: 896, mean follow‐up 8.3 years). Cox proportional hazard regression analysis stratified by age, gender and center, and adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Relative indices of inequality (RII) for education were estimated using Cox regression models. We conducted separate analyses for tumor location, gender and geographical region. Compared with participants with college/university education, participants with vocational secondary education or less had a nonsignificantly lower risk of developing CRC. When further stratified for tumor location, adjusted risk estimates for the proximal colon were statistically significant for primary education or less (HR 0.73, 95%CI 0.57–0.94) and for vocational secondary education (HR 0.76, 95%CI 0.58–0.98). The inverse association between low education and CRC risk was particularly found in women and Southern Europe. These associations were statistically significant for CRC, for colon cancer and for proximal colon cancer. In conclusion, CRC risk, especially in the proximal colon, is lower in subjects with a lower educational level compared to those with a higher educational level. This association is most pronounced in women and Southern Europe.
Evaluation of 14 triage strategies for HPV DNA‐positive women in population‐based cervical screening
Authors: Rijkaart Dorien C. , Berkhof Johannes , van Kemenade Folkert J. , Coupe Veerle M.H. , Hesselink Albertus T. , Rozendaal Lawrence , Heideman Danielle A.M. , Verheijen Ren H. , Bulk Saskia , Verweij Wim M. , Snijders Peter J.F. , Meijer Chris J.L.M.
Published: March 2011

High‐risk human papillomavirus (hrHPV) testing has a higher sensitivity but lower specificity than cytology for detection of high‐grade intraepithelial neoplasia (CIN). To avoid over‐referral to colposcopy and overtreatment, hrHPV‐positive women require triage testing and/or followup. A total of 25,658 women (30–60 years) enrolled in a population‐based cohort study had an adequate baseline Pap smear and hrHPV test. The end‐point was cumulative two‐year risk of CIN grade 3 or worse (CIN3+). In a post‐hoc analysis, fourteen triage/followup strategies for hrHPV‐positive women (n = 1,303) were evaluated for colposcopy referral rate, positive (PPV) and negative predictive value (NPV). Five strategies involved triage testing without a repeat test and nine strategies involved triage testing followed by one repeat testing. The tests were cytology, hrHPV, HPV16/18 genotyping and HPV16/18/31/33/45 genotyping. Results were adjusted for women in the cohort study who did not attend repeat testing. Of the strategies without repeat testing, combined cytology and HPV16/18/31/33/45 genotyping gave the highest NPV of 98.9% (95%CI 97.6–99.5%). The corresponding colposcopy referral rate was 58.1% (95%CI 55.4–60.8%). Eight of the nine strategies with retesting had an estimated NPV of at least 98%. Of those, cytology triage followed by cytology at 12 months had a markedly lower colposcopy referral rate of 33.4% (95%CI 30.2–36.7%) than the other strategies. The NPV of the latter strategy was 99.3% (95%CI 98.1–99.8%). Triage hrHPV‐positive women with cytology, followed by repeat cytology testing yielded a high NPV and modest colposcopy referral rate and appear to be the most feasible management strategy.
Oncogenetic tree modeling of human hepatocarcinogenesis
Authors: Longerich Thomas , Mueller Michael Martin , Breuhahn Kai , Schirmacher Peter , Benner Axel , Heiss Christiane
Published: March 2011

Classical comparative genomic hybridization (CGH) has been used to identify recurrent genomic alterations in human HCC. As hepatocarcinogenesis is considered as a stepwise process, we applied oncogenetic tree modeling on all available classical CGH data to determine occurrence of genetic alterations over time. Nine losses (1p, 4q, 6q, 8p, 9p, 13q, 16p, 16q and 17p) and ten gains (1q, 5p, 6p, 7p, 7q, 8q, 17q, 20p, 20q and Xq) of genomic information were used to build the oncogenetic tree model. Whereas gains of 1q and 8q together with losses of 8p formed a cluster that represents early etiology‐independent alterations, the associations of gains at 6q and 17q as well as losses of 6p and 9p were observed during tumor progression. HBV‐induced HCCs had significantly more chromosomal aberrations compared to HBV‐negative tumors. Losses of 1p, 4q and 13q were associated with HBV‐induced HCCs, whereas virus‐negative HCCs showed an association of gains at 5p, 7, 20q and Xq. Using five aberrations that were significantly associated with tumor dedifferentiation a robust progression model of stepwise human hepatocarcinogensis (gain 1q → gain 8q → loss 4q → loss 16q → loss 13q) was developed. In silico analysis revealed that protumorigenic candidate genes have been identified for each recurrently altered hotspot. Thus, oncogenic candidate genes that are coded on chromosome arms 1q and 8q are promising targets for the prevention of malignant transformation and the development of biomarkers for the early diagnosis of human HCC that may significantly improve the treatment options and thus prognosis of HCC patients.
The Reduction of Dioxygen by Keggin Heteropolytungstates
Authors: Snir Ophir , Wang Yifeng , Weinstock Ira A.
Published: March 2011

Reversible redox chemistries are an inherent feature of numerous metal oxide cluster anions (POMs). Moreover, as discrete molecular structures with well‐defined and controllable solution chemistries, POMs can be deployed as physicochemical probes for studying inorganic reaction mechanisms. In the past decade, we have used an iso‐structural series of α‐Keggin heteropolytungstate cluster anions to systematically investigate a number of fundamental topics, including electron transfer to dioxygen. The iso‐structural series of cluster anions is obtained by varying the heteroatom, Xn+, in the plenary, Td‐symmetry α‐Keggin ion, Xn+W12O40(8−n)−, from Al3+ to Si4+ to P5+. This results in a stepwise and linear modulation of ion charge and reduction potential, whose concerted effects on reaction rates can be used to better understand electron‐transfer processes. Starting from the acquisition of activation parameters associated with electron self‐exchange between the POMs themselves, the studies discussed in this review provide a detailed account of electron transfer from reduced α‐Keggin heteropolytungstate anions to dioxygen, culminating in the recent discovery of a fundamentally new mechanism for electron transfer to O2 in water.
Underlying mechanisms for LTF inactivation and its functional analysis in nasopharyngeal carcinoma cell lines
Authors: Zhang Hejun , Feng Xiangling , Liu Weidong , Jiang Xingjun , Shan Wenjiao , Huang Chengan , Yi Hongmei , Zhu Bin , Zhou Wen , Wang Lei , Liu Chunmei , Zhang Lihua , Jia Wenting , Huang Wei , Li Guifei , Shi Jia , Wanggou Siyi , Yao Kaitai , Ren Caiping
Published: March 2011

The lactoferrin (LTF) gene, located at 3p21.3, behaves like a tumor suppressor gene in diverse tumors. To elucidate the exact role of LTF in NPC, we first detected its expression level in seven NPC cell lines by semi‐quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). The results showed the mRNA level of LTF was nearly undetectable in all the seven NPC cell lines, while it could be detected in chronic nasopharyngitis tissues. Subsequently, we used methylation‐specific PCR (MSP), microsatellite assay, PCR‐single‐strand conformation polymorphism (PCR‐SSCP) and sequencing methods to examine the promoter methylation, loss of heterozygosity (LOH) and gene mutation of LTF in NPC cell lines respectively. Consequently, we found that 100% (7 of 7) of NPC cell lines were methylated in LTF promoter, only one cell line (14%, 1 of 7) had LOH and gene mutation of LTF, respectively, while LTF exhibited re‐expression in all cell lines after 5‐aza‐dC treatment, indicating promoter methylation should be the key mechanism causing LTF downregulation in NPC cell lines. Furthermore, patched methylation assay confirmed that promoter methylation could down‐regulate LTF gene expression in NPC cells. Finally, we investigated the function of LTF in NPC cell lines by gene transfection. Restoration of LTF expression in NPC cells resulted in blockage of cell cycle progression, significant inhibition of cell growth and a reduced colony‐formation capacity in vitro and obviously weaker tumor formation potential in vivo. In conclusion, our data indicate LTF may participate in NPC carcinogenesis as a negative effector, that is, a tumor suppressor gene. J. Cell. Biochem. 112: 1832–1843, 2011. © 2011 Wiley‐Liss, Inc.
An automated image analysis system can be beneficial in preclassification of leucocytes in children with hematological disease
Authors: Portakal Oytun , Tavil Betul , Kuşkonmaz Barış , Aytaç Selin , Hasçelik Gülşen
Published: March 2011

This study was aimed to evaluate the analytical performance of an automated image analysis system (a pilot model of Diff Master™ Octavia) for the preclassification of leucocytes in children with hematological disease. Manual microscopy performed by pediatric hematologists was used as the reference method. Five mature cell class and blasts were evaluated. Diff Master Octavia correctly preclassified 87.4% of all leucocytes with a high reproducibility. The overall accuracy was found to be 93.0%. Clinical sensitivity was 97.7% and specificity was 76.0%. The average time per slide for Diff Master™ Octavia was 2.3 min lower than that of manual method. Our results indicated that the Diff Master™ Octavia can detect and preclassify leucocytes accurately; therefore, it can be used as an efficient and fast method in pediatric hematology routine. J. Clin. Lab. Anal. 25:71–75, 2011. © 2011 Wiley‐Liss, Inc.
A PCR‐based strategy for Dombrock screening in Brazilian blood donors reveals a novel allele: the DO*A‐WL
Authors: Baleotti Wilson , Suzuki Rodrigo Buzinaro , Polotto Milena , Ruiz Marcelo Ortega , Fabron Antonio , Castilho Lilian
Published: March 2011

Background: Determination of the molecular basis underlying the antigens in the Dombrock blood group system has shown various rearrangements between the alleles associated with DO*A and DO*B. Based on this, we employed a PCR‐based strategy to screen DO alleles (DO*A, DO*B, HY*1, HY*2 and JO) in Brazilians. Methods: We tested DNA of 278 Brazilian blood donors by PCR‐RFLP on plates of 96 wells to determine the 793A/G (DO*A/DO*B), 323G/T (HY), 350C/T (JO) and 898C/G (HY*1/HY*2) single nucletide polymorphisms. In order to confirm the results sequence analysis was also performed. Results: When samples of these donors were analyzed, a novel allele combination, the DO*A allele (793A and 323G) associated with 898G was identified and designated as DO*A‐WL allele. This new allele encoding 300Val is the same as HY*1 at nucleotide 898 on the molecular background of DO*A. Among the 556 alleles analyzed by PCR‐RFLP, 3 were DO*A‐WL and 78 were DO*B‐WL. This represents an overall frequency of 0.5% for DO*A‐WL and 14% for DO*B‐WL across the population studied. Conclusion: Molecular screening of Brazilians revealed one novel allele, the DO*A‐WL. Our data highlight the importance of testing a cohort of different populations to determine DO haplotypes and to establish reliable genotyping tests for predicting Doa/Dob status. J. Clin. Lab. Anal. 25:79–82, 2011. © 2011 Wiley‐Liss, Inc.
Allowable Total Error and Limits for Erroneous Results (ATE/LER) zones for agreement measurement
Authors: Zhou Yu‐Hao , Zang Jia‐Jie , Wu Mei‐Jing , Xu Jin‐Fang , He Jia
Published: March 2011

Background: When assessing the agreement of two methods, the simple correlation coefficient, the most frequently used but easy to cause misleading interpretation of results, is still comprehensively adopted in journals of clinical chemistry or diagnostic laboratory. This study is aimed at comparing the correlation coefficient with the alternative method, which came from FDA recommended guidance for waiver assays—Allowable Total Error (ATE)/Limits for Erroneous Results (LER) zones, and fully addressing the applicable conditions of the later one. Methods: The data we use were both real and simulated data to calculate correlation coefficient and ATE/LER zones, respectively, when assessing the agreement. And a modified ATE/LER zones method was brought forward to assess the agreement of repeated measurements and the repeatability of each single method. Results: The high correlation can only indicate that the two methods are linearly related rather than in agreement with each other. However, the ATE/LER zones can avoid this shortcoming by using certain statistical strategies considering the clinical judgment. The modified method is suitable to evaluate the repeatability of single method and the agreement of repeated measurement by two measuring methods. Conclusion: The ATE/LER zones method is a relatively reasonable and widely considering method for assessing the agreement. J. Clin. Lab. Anal. 25:83–89, 2011. © 2011 Wiley‐Liss, Inc.
Comparison of the automated fluorescence microscopic viability test with the conventional and flow cytometry methods
Authors: Kim Jang Su , Nam Myung Hyun , An Seong Soo A. , Lim Chae Seung , Hur Dae Sung , Chung Chanil , Chang Jun Koon
Published: March 2011

The cell viability test is an essential tool in any laboratory, performing cell‐based studies and clinical laboratory tests. The trypan blue exclusion method is the most popular assay for its simple concept among various diagnostic tools. However, several disadvantages include time‐consuming and labor‐intensive steps with low precision. In this study, we evaluated a new technique for the automatic cell viability measurement with microscopic cell counter and microchip. Upon blood draw from 11 healthy volunteers, Mononuclear cells were separated immediately from the heparinized whole blood, and the viable cells were diluted from 100 to 1%. The cell viability tests were performed simultaneously with following three methods: the conventional manual trypan blue exclusion method; the flow cytometry measurement with propidium iodide stain; and the newly developed microscopic cell counter with microchip. Linearities, precisions, and correlations from three methods were analyzed and compared. The correlations data from the microscopic cell counter were in good agreement with both the conventional trypan blue method (r=0.99, P<0.05) and the flow cytometry (r=0.99, P<0.05), respectively. The precision (2.0–6.2%) and linearity from the microscopic cell counter method with microchip were superior in comparison with the conventional method. The microscopic cell counter with microchip performed well with high precision, linearity, and efficient running time than both the manual trypan blue and the flow cytometry methods. J. Clin. Lab. Anal. 25:90–94, 2011. © 2011 Wiley‐Liss, Inc.