bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereotactic body radiotherapy using a radiobiology‐based regimen for stage I nonsmall cell lung cancer
Authors: Shibamoto Yuta , Hashizume Chisa , Baba Fumiya , Ayakawa Shiho , Manabe Yoshihiko , Nagai Aiko , Miyakawa Akifumi , Murai Taro , Iwata, Hiromitsu , Mori Yoshimasa , Mimura Mikio , Ishikura Satoshi
Published: September 2011

BACKGROUND:

The most common regimen of stereotactic body radiotherapy (SBRT) for stage I nonsmall cell lung cancer in Japan is 48 grays (Gy) in 4 fractions over 4 days. Radiobiologically, however, higher doses are necessary to control larger tumors, and interfraction intervals should be >24 hours to take advantage of reoxygenation. In this study, the authors tested the following regimen: For tumors that measured <1.5 cm, 1.5 to 3.0 cm, and >3.0 cm in greatest dimension, radiation doses of 44 Gy, 48 Gy, and 52 Gy, respectively, were given in 4 fractions with interfraction intervals of ≥3 days.

METHODS:

Among 180 patients with histologically proven disease who entered the study, 120 were medically inoperable, and 60 were operable. The median patient age was 77 years (range, 29‐92 years). SBRT was performed with 6‐megavolt photons using 4 noncoplanar beams and 3 coplanar beams. Isocenter doses of 44 Gy, 48 Gy, and 52 Gy were received by 4 patients, 124 patients, and 52 patients, respectively.

RESULTS:

The overall survival rate for all 180 patients was 69% at 3 years and 52% at 5 years. The 3‐year survival rate was 74% for operable patients and 59% for medically inoperable patients (P = .080). The 3‐year local control rate was 86% for tumors ≤3 cm (44/48 Gy) and 73% for tumors >3 cm (52 Gy; P = .050). Grade ≥2 radiation pneumonitis developed in 13% of patients (10% of the 44‐Gy/48‐Gy group and 21% of the 52‐Gy group; P = .056). All other grade 2 toxicities developed in <4% of patients.

CONCLUSIONS:

The SBRT protocol used in this study yielded reasonable local control and overall survival rates and acceptable toxicity. Dose escalation is being investigated. Cancer 2012;. © 2011 American Cancer Society.
Cancer‐testis antigens expressed in osteosarcoma identified by gene microarray correlate with a poor patient prognosis
Authors: Zou Changye , Shen Jingnan , Tang Qinglian , Yang Zheng , Yin Junqiang , Li Zhibin , Xie Xianbiao , Huang Gang , Lev Dina , Wang Jin
Published: September 2011

BACKGROUND:

From 30% to 40% patients with osteosarcoma eventually experience medical failure; and few biomarkers of prognostic significance have been established. High‐throughput methods like gene microarray analysis can help to identify molecular biomarkers that are useful for diagnosing osteosarcoma and targeting its treatment.

METHODS:

Oligonucleotide microarrays were used to compare expression profiles of osteosarcoma cell lines and osteoblasts. Differentially expressed genes were confirmed by real‐time polymerase chain reaction (PCR) analysis. Corresponding proteins were evaluated by flow cytometry and Western blot analysis in osteosarcoma cell lines and by immunohistochemistry in osteosarcoma tissues. The association between staining intensity and clinical outcome was analyzed further.

RESULTS:

Cancer‐testis antigens, including melanoma antigen family A (MAGEA), chondrosarcoma‐associated gene family, member 2 (CSAG2), and preferentially expressed antigen in melanoma (PRAME), were increased significantly in all osteosarcoma cell lines that were analyzed. Real‐time PCR examinations indicated that cancer‐testis antigen expression was frequent and coordinated in patients with osteosarcoma. The expression of MAGEA was confirmed by Western blot and flow cytometry analyses in osteosarcoma cell lines. Furthermore, immunohistochemical staining analysis suggested that MAGEA expression may be used to predict distant metastasis and poor survival. The adjusted relative risk for lung metastasis was 2.79 (95% confidence interval, 1.12‐6.93; P = .028) for MAGEA‐positive patients. Five‐year survival rates for patients with and without MAGEA expression were 39.6% ± 8.4% and 80% ± 8.9%, respectively (log‐rank test; P = .01).

CONCLUSIONS:

The combined use of an oligonucleotide microarray, a clinical database, and a tissue bank was useful for identifying molecular tumor markers. The frequent expression of MAGEA and other cancer‐testis antigens in osteosarcoma indicates that they may be useful as diagnostic markers and targets of immunotherapy that warrant further investigation. Cancer 2012. © 2011 American Cancer Society.
Optical fiber‐based in vivo quantification of growth factor receptors
Authors: Thomas Thommey P. , Chang Yu‐Chung , Ye Jing Yong , Kotlyar Alina , Cao Zhengyi , Shukla Rameshwer , Qin Suyang , Norris Theodore B. , Baker James R.
Published: September 2011

BACKGROUND:

Growth factor receptors such as epidermal growth factor receptor 1 and human epidermal growth receptor 2 (HER2) are overexpressed in certain cancer cells. Antibodies against these receptors (eg. cetuximab and transtuzumab [Herceptin]) have shown therapeutic value in cancer treatment. The existing methods for the quantification of these receptors in tumors involve immunohistochemistry or DNA quantification, both in extracted tissue samples. The goal of the study was to evaluate whether an optical fiber‐based technique can be used to quantify the expression of multiple growth factor receptors simultaneously.

METHODS:

The authors examined HER2 expression using the monoclonal antibody trastuzumab as a targeting ligand to test their system. They conjugated trastuzumab to 2 different Alexa Fluor dyes with different excitation and emission wavelengths. Two of the dye conjugates were subsequently injected intravenously into mice bearing HER2‐expressing subcutaneous tumors. An optical fiber was then inserted into the tumor through a 30‐gauge needle, and using a single laser beam as the excitation source, the fluorescence emitted by the 2 conjugates was identified and quantified by 2‐photon optical fiber fluorescence.

RESULTS:

The 2 conjugates bound to the HER2‐expressing tumor competitively in a receptor‐specific fashion, but they failed to bind to a similar cell tumor that did not express HER2. The concentration of the conjugate present in the tumor as determined by 2‐photon optical fiber fluorescence was shown to serve as an index of the HER2 expression levels.

CONCLUSIONS:

These studies offer a minimally invasive technique for the quantification of tumor receptors simultaneously. Cancer 2012;. © 2011 American Cancer Society.
The association of the BRAFV600E mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer
Authors: Kim Tae Hyuk , Park Young Joo , Lim Jung Ah , Ahn Hwa Young , Lee Eun Kyung , Lee You Jin , Kim Kyung Won , Hahn Seo Kyung , Youn Yeo Kyu , Kim Kwang Hyun , Cho Bo Youn , Park Do Joon
Published: September 2011

BACKGROUND:

The effects of the BRAFV600E mutation on prognostic factors and poor clinical outcomes in papillary thyroid cancer (PTC) have not been fully quantified. The authors performed comprehensive meta‐analysis to assess the strength of associations between these conditions and the BRAFV600E mutation.

METHODS:

The authors identified the clinical studies that examined the association of the BRAFV600E mutation in surgical specimens with clinicopathologic outcomes between January 2003 and October 2010 using the Medline database. One hundred thirty‐one relevant studies were hand‐searched. The authors selected 27 studies that included 5655 PTC patients. They calculated the pooled odds ratios (ORs) or risk ratios with 95% confidence intervals (CIs) for each study using a random effect model.

RESULTS:

The average prevalence rate of the BRAFV600E mutation was 49.4%. In 26 studies, compared with the patients who had the wild‐type BRAF genes, the PTC patients with the BRAFV600E mutation had increased ORs of an extrathyroidal invasion (OR, 2.14; 95% CI, 1.68‐2.73), a lymph node metastasis (OR, 1.54; 95% CI, 1.21‐1.97), and an advanced TNM stage (OR, 2.00; 95% CI, 1.61‐2.49). In 8 studies, patients with the mutation had 2.14‐fold increased risk of recurrent and persistent disease (95% CI, 1.67‐2.74). The associations were generally consistent across the different study populations.

CONCLUSIONS:

This meta‐analysis demonstrates that the BRAFV600E mutation is closely related to the high‐risk clinicopathological factors and poorer outcome of PTC. The results obtained here suggest that the BRAFV600E mutation should be considered as a poor prognostic marker in PTC and may lead to better management for individual patients. Cancer 2012;. © 2011 American Cancer Society.
A meta‐analysis evaluating stereotactic radiosurgery, whole‐brain radiotherapy, or both for patients presenting with a limited number of brain metastases
Authors: Tsao May , Xu Wei , Sahgal Arjun
Published: September 2011

BACKGROUND:

To perform a meta‐analysis on newly diagnosed brain metastases patients treated with whole‐brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) boost versus WBRT alone, or in patients treated with SRS alone versus WBRT and SRS boost.

METHODS:

The meta‐analysis primary outcomes were overall survival (OS), local control (LC), and distant brain control (DBC). Secondary outcomes were neurocognition, quality of life (QOL), and toxicity. Using published Kaplan‐Meier curves, results were pooled using hazard ratios (HR).

RESULTS:

Two RCTs reported on WBRT and SRS boost versus WBRT alone. For multiple brain metastases (2‐4 tumors) we conclude no difference in OS, and LC significantly favored WBRT plus SRS boost. Three RCTs reported on SRS alone versus WBRT plus SRS boost (1‐4 tumors). There was no difference in OS despite both LC and DBC significantly favoring WBRT plus SRS boost. Although secondary endpoints could not be pooled for meta‐analysis, those RCTs evaluating SRS alone conclude better neurocognition using the validated Hopkins Verbal Learning Test, no adverse risk in deteriorating Mini‐Mental Status Exam scores or in maintaining performance status, and fewer late toxicities. We conclude insufficient data for QOL outcomes.

CONCLUSIONS:

For selected patients, we conclude no OS benefit for WBRT plus SRS boost compared with SRS alone. Although additional WBRT improves DBC and LC, SRS alone should be considered a routine treatment option due to favorable neurocognitive outcomes, less risk of late side effects, and does not adversely affect the patients performance status. Cancer 2012. © 2011 American Cancer Society.
Theoretical Study of the Photochemistry of a Reversible Three‐State Bis‐Thiaxanthylidene Molecular Switch
Authors: Filatov Michael
Published: September 2011

The ground‐ and the lowest singlet excited‐state potential energy surfaces of the bis‐thiaxanthylidene (3) molecular switch are investigated using a density functional method specifically designed to treat molecular systems typified by strong non‐dynamic electron correlation. The results of the theoretical calculations suggest that the unique ability of substituted bis‐thiaxanthylidenes to switch between three states of luminescence—non‐fluorescent state, blue fluorescent state, and red fluorescent state—can be explained by specific features on the excited state potential energy surface: the potential barrier around the Franck–Condon point of the anti‐folded conformer and the existence of conical intersection in the vicinity of the syn‐folded conformer. It is suggested that the twisted conformer, if made more stable via chemical modification, should fluoresce in the near‐infrared region (λ≈740–760 nm), thus offering a possibility for a four‐state switching of luminescence in a single‐component molecular system.
Distinguishing benign from malignant mesothelial cells in effusions by Glut‐1, EMA, and Desmin expression: An evidence‐based approach
Authors: Kuperman Michael , Florence Roxanne R. , Pantanowitz Liron , Visintainer Paul F. , Cibas Edmund S. , Otis Christopher N.
Published: September 2011

Distinguishing malignant mesothelioma (MM) from reactive mesothelial hyperplasia (RM) may be difficult in effusions. This study tested the hypothesis that immunocytochemistry (IC) in effusion cell blocks (CB) can distinguish MM from RM and that the results may be applied to individual specimens. External validation of a risk score (RS) model associating sensitivity and specificity was applied to an external set of MM and RM specimens from a separate institution.

Forty three effusion cytology CBs of 25 confirmed malignant mesotheliomas were compared to CBs of 23 benign mesothelial effusions without inflammation and 13 reactive mesothelial proliferations associated with inflammation. Glut‐1, EMA, and Desmin expression were evaluated by immunocytochemistry on CBs. Each antibody was compared using ROC values, where the area under the curve (AUC) was 0.90, 0.82, and 0.84 for Glut‐1, EMA, and Desmin, respectively. Logistic regression (LR) analysis was applied to a combination of Glut‐1 and EMA. A combined ROC curve was modeled for Glut‐1 and EMA (AUC = 0.93). A RS = 2 × (Glut‐1%) + 1 × (EMA%) was created from this ROC curve. When applied to an external set of MM and RM, the RS resulted in an ROC with AUC = 0.91.

In conclusion, a RS derived from a LR of Glut‐1 and EMA IC greatly improves the distinction between MM from RM cells in individual effusions. The study illustrates principles of evidence‐based pathology concerning internal and external test performance in the differential diagnosis of MM versus RM. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc
Ancestral network module regulating prdm1 expression in the lamprey neural plate border
Authors: Nikitina Natalya , Tong Leslie , Bronner Marianne E.
Published: September 2011

prdm1 is an important transcriptional regulator that plays diverse roles during development of a wide variety of vertebrate and invertebrate species. prdm1 is required for neural crest specification in zebrafish, but not in mouse embryos. The role of this gene in neural crest formation in other species has not been examined, and its regulation during embryonic development is poorly understood. Here, we investigate the expression pattern, function, and the upstream regulatory inputs into prdm1 during lamprey neural crest development. prdm1 is strongly expressed in the lamprey neural plate border, suggesting a conserved ancestral role of this gene in the neural crest formation. We found that lamprey neural plate border expression of prdm1 is activated by Ap‐2 and Msx, but is independent of Pax3/7 and Zic. Developmental Dynamics 240:2265–2271, 2011. © 2011 Wiley‐Liss, Inc.
Use of a Drosophila genome‐wide conserved sequence database to identify functionally related cis‐regulatory enhancers
Authors: Brody Thomas , Yavatkar Amarendra S. , Kuzin Alexander , Kundu Mukta , Tyson Leonard J. , Ross Jermaine , Lin Tzu‐Yang , Lee Chi‐Hon , Awasaki Takeshi , Lee Tzumin , Odenwald Ward F.
Published: September 2011

Background: Phylogenetic footprinting has revealed that cis‐regulatory enhancers consist of conserved DNA sequence clusters (CSCs). Currently, there is no systematic approach for enhancer discovery and analysis that takes full‐advantage of the sequence information within enhancer CSCs. Results: We have generated a Drosophila genome‐wide database of conserved DNA consisting of >100,000 CSCs derived from EvoPrints spanning over 90% of the genome. cis‐Decoder database search and alignment algorithms enable the discovery of functionally related enhancers. The program first identifies conserved repeat elements within an input enhancer and then searches the database for CSCs that score highly against the input CSC. Scoring is based on shared repeats as well as uniquely shared matches, and includes measures of the balance of shared elements, a diagnostic that has proven to be useful in predicting cis‐regulatory function. To demonstrate the utility of these tools, a temporally‐restricted CNS neuroblast enhancer was used to identify other functionally related enhancers and analyze their structural organization. Conclusions: cis‐Decoder reveals that co‐regulating enhancers consist of combinations of overlapping shared sequence elements, providing insights into the mode of integration of multiple regulating transcription factors. The database and accompanying algorithms should prove useful in the discovery and analysis of enhancers involved in any developmental process. Developmental Dynamics 241:169–189, 2012. © 2011 Wiley Periodicals, Inc.
A Monte Carlo investigation of factors influencing latent class analysis: An application to eating disorder research
Authors: Swanson Sonja A. , Lindenberg Katajun , Bauer Stephanie , Crosby Ross D.
Published: September 2011

Objective:

Latent class analysis (LCA) has frequently been used to identify qualitatively distinct phenotypes of disordered eating. However, little consideration has been given to methodological factors that may influence the accuracy of these results.

Method:

Monte Carlo simulations were used to evaluate methodological factors that may influence the accuracy of LCA under scenarios similar to those seen in previous eating disorder research.

Results:

Under these scenarios, the aBIC provided the best overall performance as an information criterion, requiring sample sizes of 300 in both balanced and unbalanced structures to achieve accuracy proportions of at least 80%. The BIC and cAIC required larger samples to achieve comparable performance, while the AIC performed poorly universally in comparison. Accuracy generally was lower with unbalanced classes, fewer indicators, greater or nonrandom missing data, conditional independence assumption violations, and lower base rates of indicator endorsement.

Discussion:

These results provide critical information for interpreting previous LCA research and designing future classification studies. © 2011 by Wiley Periodicals, Inc. (Int J Eat Disord 2011)
Real‐time cell electrophysiology using a multi‐channel dielectrophoretic‐dot microelectrode array
Authors: Fatoyinbo Henry O. , Kadri Nahrizul A. , Gould David H. , Hoettges Kai F. , Labeed Fatima H.
Published: September 2011

Dielectrophoresis (DEP) has been used for many years for the analysis of the electrophysiological properties of cells. However, such analyses have in the past been time‐consuming, such that it can take 30 min or more to collect sufficient data to make valid interpretations from a single DEP spectrum. This has limited the application of the technology to a rapid tool for non‐invasive, label‐free research in areas from drug discovery to diagnostics. In this paper we present the development of a programmable, multi‐channel DEP system for rapid biophysical assessment of populations of biological cells. A new assay format has been developed for continuous near‐real‐time monitoring, using simultaneous application of up to eight alternating current electrical signals to independently addressable dot microelectrodes in an array format, allowing a DEP spectrum to be measured in 20 s, with a total cycle time between measurements of 90 s. To demonstrate the system, human leukaemic K562 cells were monitored after exposure to staurosporine and valinomycin. The DEP response curves showed the timing and manner in which the membrane properties changed for the actions of these two drugs at the early phase of induction. This technology shows the great potential for increasing our understanding of the role of electrophysiology in drug action, by observing the changes in electrical characteristics as they occur.
Subtyping Children and Adolescents Who Are Overweight Based on Eating Pathology and Psychopathology
Authors: Braet Caroline , Beyers Wim , Goossens Lien , Verbeken Sandra , Moens Ellen
Published: September 2011

Children and adolescents who are overweight can differ on dimensions measuring dietary restraint and psychopathology. Classifying clinical obese children and adolescents based on these psychological characteristics is shown to be useful in making differential prognoses. The present study aimed to research the validity of subtyping children and adolescents with overweight (N = 138) in a non‐clinical sample. Using cluster analysis, results revealed three subtypes: a dietary restraint/internalizing group (DR + IN; n = 41), a pure internalizing group (IN; n = 20) and a non‐symptomatic group (NS; n = 77). The DR + IN group outscored both other groups on measures of eating pathology, whereas the IN group outscored both other groups on measures of negative offect. Interestingly, the three groups did not differ on degree of overweight. The results seem to suggest that different psychological mechanisms can be observed in subgroups of young overweight adolescents. Further research should explore how individual psychological characteristics can be helpful when stipulating weight loss treatment programmes. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.
Photodegradation of lambda-cyhalothrin and cypermethrin in aqueous solution as affected by humic acid and/or copper: Intermediates and degradation pathways
Authors: Xie Jimin , Wang Pingli , Liu Jun , Lv Xiaomeng , Jiang Deli , Sun Cheng
Published: September 2011

The influence of coexisting humic acids (HA) or Cu2+ on the photodegradation of pesticides lambda-cyhalothrin (λ-CHT) and cypermethrin (CPM) in aqueous solution was studied under xenon lamp irradiation. The removal efficiency of pesticides λ-CHT and CPM were enhanced in the presence of either Cu2+ or HA but restrained in the presence of both Cu2+ and HA. The photodegradation of λ-CHT and CPM followed first-order reaction kinetics. The photodegradation intermediates of λ-CHT and CPM were determined using gas chromatography/mass spectrometry. Possible photodegradation pathways included decarboxylation, ester bond cleavage, dechlorination, and phenyl group removal. Environ. Toxicol. Chem. 2011;30:2440–2448. © 2011 SETAC
T‐cell lymphoblastic lymphoma shows differences and similarities with T‐cell acute lymphoblastic leukemia by genomic and gene expression analyses
Authors: Basso Katia , Mussolin Lara , Lettieri Antonella , Brahmachary Manisha , Lim Wei Keat , Califano Andrea , Basso Giuseppe , Biondi Andrea , Cazzaniga Giovanni , Rosolen Angelo
Published: September 2011

T‐cell acute lymphoblastic leukemia (T‐ALL) and lymphoma (T‐LBL) share common morphological and immunophenotypic features and are treated with similar therapeutic approaches. Nonetheless, they show distinct clinical presentations, suggesting that they may represent two different biological entities. To investigate the genetic characteristics of T‐LBL and T‐ALL, we used genomic and transcriptional profiling approaches. Genome‐wide gene expression profiling, performed on 20 T‐LBL and 10 T‐ALL diagnostic specimens, revealed that the two malignancies shared a large fraction of their transcriptional profile while a subset of genes appeared to be differentially expressed in T‐LBL versus T‐ALL. This signature included genes involved in chemotactic responses and angiogenesis, which may play a role in tumor cell localization. Genome‐wide copy number alteration analysis was performed on a subset of the samples analyzed by gene expression profiling and detected 41 recurrently altered genetic loci. Although most aberrations were found in both entities, several were selectively identified in T‐LBL or T‐ALL. In addition, NOTCH1 mutational status was found to correlate with a subset of genetic aberrations. Taken together, these results suggest that T‐LBL and T‐ALL are indeed two distinct diseases with unique transcriptional and genetic characteristics. © 2011 Wiley Periodicals, Inc.
Reduction in expression of the astrocyte glutamate transporter, GLT1, worsens functional and histological outcomes following traumatic spinal cord injury
Authors: Lepore Angelo C. , O'donnell John , Kim Andrew S. , Yang Eun Ju , Tuteja Alisha , Haidet‐Phillips Amanda , O'Banion Colin P. , Maragakis Nicholas J.
Published: September 2011

The astrocyte glutamate transporter, GLT1, is responsible for the vast majority of glutamate uptake in the adult central nervous system (CNS), thereby regulating extracellular glutamate homeostasis and preventing excitotoxicity. Glutamate dysregulation plays a central role in outcome following traumatic spinal cord injury (SCI). To determine the role of GLT1 in secondary cell loss following SCI, mice heterozygous for the GLT1 astrocyte glutamate transporter (GLT1+/−) and wild‐type mice received thoracic crush SCI. Compared with wild‐type controls, GLT1+/− mice had an attenuated recovery in hindlimb motor function, increased lesion size, and decreased tissue sparing. GLT1+/− mice showed a decrease in intraspinal GLT1 protein and functional glutamate uptake compared with wild‐type mice, accompanied by increased apoptosis and neuronal loss following crush injury. These results suggest that astrocyte GLT1 plays a role in limiting secondary cell death following SCI, and also show that compromise of key astrocyte functions has significant effects on outcome following traumatic CNS injury. These findings also suggest that increasing intraspinal GLT1 expression may represent a therapeutically relevant target for SCI treatment. © 2011 Wiley‐Liss, Inc.
Evaluating and reducing the impact of white matter lesions on brain volume measurements
Authors: Battaglini Marco , Jenkinson Mark , De Stefano Nicola
Published: September 2011

MR‐based measurements of brain volumes may be affected by the presence of white matter (WM) lesions. Here, we assessed how and to what extent this may happen for WM lesions of various sizes and intensities. After inserting WM lesions of different sizes and intensities into T1‐W brain images of healthy subjects, we assessed the effect on two widely used automatic methods for brain volume measurement such as SIENAX (segmentation‐based) and SIENA (registration‐based). To explore the relevance of partial volume (PV) estimation, we performed the experiments with two different PV models, implemented by the same segmentation algorithm (FAST) of SIENAX and SIENA. Finally, we tested potential solutions to this issue. The presence of WM lesions did not bias measurements for registration‐based method such as SIENA. By contrast, the presence of WM lesions affected segmentation‐based brain volume measurements such as SIENAx. The misclassification of both gray matter (GM) and WM volumes varied considerably with lesion size and intensity, especially when the lesion intensity was similar to that of the GM/WM interface. The extent to which the presence of WM lesions could affect tissue‐class measures was clearly driven by the PV modeling used, with the mixel‐type PV model giving a lower error in the presence of WM lesions. The tissue misclassification due to WM lesions was still present when they were masked out. By contrast, refilling the lesions with intensities matching the surrounding normal‐appearing WM ensured accurate tissue‐class measurements and thus represents a promising approach for accurate tissue classification and brain volume measurements. Hum Brain Mapp 33:2062–2071, 2012. © 2011 Wiley Periodicals, Inc.
MEASURING THE EFFECT OF POLICY INTERVENTIONS AT THE POPULATION LEVEL: SOME METHODOLOGICAL CONCERNS
Authors: D. Huesch Marco , Østbye Truls , K. Ong Michael
Published: September 2011

Health policy evaluations estimate the response of population aggregate outcomes to interventions. However, clarity on the form of the expected causal relationship, the parameter identification strategy, and the mode of hypothesis testing is required to overcome a number of conceptual and methodological problems. We use the New Jersey statewide smoking ban as an example. We examine statewide admission rates for acute myocardial infarctions, strokes and lower limb fractures, and emergency room encounter rates for asthma exacerbations before and after the smoking ban. We discuss the identification options and show the sensitivity of estimates of the response function to different specifications of the stochastic and intervention components and to different modes of inference. Model misspecification is demonstrated by rolling Chow tests for structural breaks in repeated observations. Copyright © 2011 John Wiley & Sons, Ltd.
Vanderbilt head and neck symptom survey version 2.0: Report of the development and initial testing of a subscale for assessment of oral health
Authors: Cooperstein Emily , Gilbert Jill , Epstein Joel B. , Dietrich Mary S. , Bond Stewart M. , Ridner Sheila H. , Wells Nancy , Cmelak Anthony , Murphy Barbara A.
Published: September 2011

Background

The prevalence, severity, and functional implications of adverse oral health outcomes attributed to head and neck cancer therapy are largely undefined. We report development of an oral health outcome subscale for the Vanderbilt Head and Neck Symptom Survey (VHNSS).

Methods

Oral health outcome questions were formulated through literature review and consultation with an expert panel. Questions were incorporated into the VHNSS resulting in a 50‐item survey, scored 0 (none) to 10 (severe). The tool was administered to 70 subjects who completed radiation to assess for feasibility.

Results

Patient acceptance was high with a completion time <10 minutes. A full range of scores was noted for 46 of 50 questions. Oral health symptom burden was high early and late posttreatment.

Conclusions

The VHNSS version 2.0 was feasible and could be completed in a timely manner. Validation studies are ongoing. The high prevalence of adverse oral health outcomes warrants further study. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Two‐dimensional flow patterns near contour grass hedges
Authors: Vieira Dalmo A. N. , Dabney Seth M.
Published: September 2011

Grass hedges are narrow strips of stiff‐stemmed vegetation used to control erosion and sediment delivery. When planted on the contour, the hydraulic resistance of the vegetation slows runoff, creates ponding, and promotes sediment deposition. When tillage is performed between grass hedges, soil may be thrown against the vegetation, where it settles to form a berm within the hedge. Tillage‐induced berms divert part of runoff, causing it to flow alongside the hedge without crossing it. Such flow partitioning created by grass hedges was measured on experimental plots located on silt loam loess soil near Holly Springs, Mississippi, USA, where hedges planted at the bottom of 5%, 22.1‐m‐long slopes evolved berms averaging 0.13 m in height. They diverted about 80% of the runoff for events smaller than 5 mm and about 50% for large events. A two‐dimensional model was developed to determine overland flow patterns over complex terrains, accounting for oriented roughness created by tillage corrugations, crop rows, and larger features such as berms and vegetative barriers. The model was used to reproduce the flow partition observed in the field experiments and to determine how berm height and slope steepness and length affected runoff redistribution. Numerical simulations indicated that for most runoff events, ponded runoff depths were not high enough to overtop the berm but rather crossed the berms through cracks and gaps, represented in the model as small triangular weirs. The model also was applied to a 6.0‐ha watershed in Western Iowa, USA, where nine grass hedges were planted across 12–16% slopes. Computed dynamic flow properties showed that berms increased the amount of runoff flowing laterally upslope of the hedges and that a large portion of the runoff crossed the vegetative strips at a few locations and with high flow depths, increasing the risk of development of ephemeral gullies. Copyright © 2011 John Wiley & Sons, Ltd.
Abrupt changes in the discharge and sediment load of the Pearl River, China
Authors: Zhang Qiang , Xu Chong‐Yu , Chen Xiaohong , Lu Xixi
Published: September 2011

The abrupt changes in the streamflow and sediment load at nine hydrological stations of the Pearl River basin were systematically analysed by using the simple two‐phase linear regression scheme and the coherency analysis technique. Possible underlying causes were also discussed. Our study results indicated that abrupt changes in the streamflow occurred mainly in the early 1990s. The change points were followed by significant decreasing streamflow. Multiscale abrupt behaviour of the sediment load classified the hydrological stations into two groups: (1) Xiaolongtan, Nanning and Liuzhou; and (2) Qianjiang, Dahuangjiangkou, Wuzhou, Gaoyao, Shijiao and Boluo. The grouped categories implied obvious influences of water reservoirs on the hydrological processes of the Pearl River. On the basis of analysis of the locations and the construction time of the water reservoirs, and also the time when the change points occurred, we figured out different ways the water reservoirs impacted the hydrological processes within the Pearl River basin. As for the hydrological variation along the mainstream of the Pearl River, the water reservoirs have considerable influences on both the streamflow and sediment load variations; however, more influences seemed to be exerted on the sediment load transport. In the North River, the hydrological processes seemed to be influenced mainly by climate changes. In the East River, the hydrological variations tended to be impacted by the water reservoirs. The study results also indicated no fixed modes when we address the influences of water reservoirs on hydrological processes. Drainage area and regulation behaviour of the water reservoirs should be taken into account. The results of this study will be of considerable importance for the effective water resources management of the Pearl River basin under the changing environment. Copyright © 2011 John Wiley & Sons, Ltd.
Attribution of human papillomavirus types to cervical intraepithelial neoplasia and invasive cancers in Southern China
Authors: Chan Paul K.S. , Cheung Tak‐Hong , Li Wai‐Hon , Yu Mei Y. , Chan May Y.M. , Yim So‐Fan , Ho Wendy C.S. , Yeung Apple C.M. , Ho King‐Man , Ng H.K.
Published: September 2011

The attribution of individual human papillomavirus (HPV) types to cervical neoplasia, especially intraepithelial lesions, varies ethnogeographically. Population‐specific data are required for vaccine cost‐effectiveness assessment and type replacement monitoring. HPV was detected from 2,790 Chinese women (444 invasive cervical cancers [ICC], 772 cervical intraepithelial neoplasia [CIN] grade 3, 805 CIN2 and 769 CIN1. The attribution of each HPV type found in multiple‐type infections was approximated by the fractional contribution approach. Multiple‐type infection was common and correlated inversely with lesion severity (54.7% for CIN1, 48.7% for CIN2, 46.2% for CIN3, 27.5% for ICC). Vaccine‐covered high‐risk types (HPV16/18) attributed to 59.5% of squamous cell carcinoma, 78.6% of adenocarcinoma, 35.9% of CIN3, 18.4% of CIN2 and 7.4% of CIN1. Distinct features compared to worldwide were a higher attribution of HPV52 and HPV58, and a much lower attribution of HPV45. Inclusion of HPV52 and HPV58 in future vaccines would provide the highest marginal increase in coverage with 11.7% for squamous cell carcinoma, 14.4% for CIN3, 22.6% for CIN2 and 17.7% for CIN1. The attribution of HPV types in southern China is different from elsewhere, which should be considered in prioritizing HPV types for vaccine and screening assay development.
Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease
Authors: Selth Luke A. , Townley Scott , Gillis Joanna L. , Ochnik Aleksandra M. , Murti Krisna , Macfarlane Robyn J. , Chi Kim N. , Marshall Villis R. , Tilley Wayne D. , Butler Lisa M.
Published: September 2011

Circulating microRNAs (miRNAs) are emerging as useful non‐invasive markers of disease. The objective of this study was to use a mouse model of prostate cancer as a tool to discover serum miRNAs that could be assessed in a clinical setting. Global miRNA profiling identified 46 miRNAs at significantly altered levels (p ≤ 0.05) in the serum of TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice with advanced prostate cancer compared to healthy controls. A subset of these miRNAs with known human homologues were validated in an independent cohort of mice and then measured in serum from men with metastatic castration‐resistant prostate cancer (mCRPC; n = 25) or healthy men (n = 25). Four miRNAs altered in mice, mmu‐miR‐141, mmu‐miR‐298, mmu‐miR‐346 and mmu‐miR‐375, were also found to be at differential levels in the serum of men with mCRPC. Three of these (hsa‐miR‐141, hsa‐miR‐298 and hsa‐miR‐375) were upregulated in prostate tumors compared with normal prostate tissue, suggesting that they are released into the blood as disease progresses. Moreover, the intra‐tumoral expression of hsa‐miR‐141 and hsa‐miR‐375 were predictors of biochemical relapse after surgery. This study is the first to demonstrate that specific serum miRNAs are common between human prostate cancer and a mouse model of the disease, highlighting the potential of such models for the discovery of novel biomarkers.
Apheresis medicine state of the art in 2010: American Society for Apheresis fifth special edition of the Journal of Clinical Apheresis
Authors: Winters Jeffrey L.
Published: September 2011

The quality of evidence supporting the use of apheresis in the treatment of individual diseases and disorders is often limited. For most diseases and disorders, randomized controlled trials of the use of apheresis have not been performed and for many, due to rarity of the condition, it is unlikely that they will ever be performed. In keeping with its vision, the American Society for Apheresis (ASFA) has created and regularly updated guidelines on the use of apheresis in the treatment of disease. These guidelines seek to summarize the literature on the use of apheresis in treating diseases, provide a critical review of this literature, and give practical guidance to apheresis practitioners. The most recent ASFA guidelines were published in 2010. This article reviews the history of the ASFA guidelines, the changes that were made in the 2010 guidelines, and future directions and plans for these guidelines. The 2010 ASFA guidelines on the use of therapeutic apheresis in clinical practice represent the state of the art in apheresis medicine in 2010. © 2011 Wiley‐Liss, Inc.
Forkhead box A1 (FOXA1) is a key mediator of insulin‐like growth factor I (IGF‐I) activity
Authors: Potter Adam S. , Casa Angelo J. , Lee Adrian V.
Published: September 2011

The insulin‐like growth factor receptor (IGF‐IR) has been implicated in a number of human tumors, including breast cancer. Data from human breast tumors has demonstrated that IGF‐IR is over‐expressed and hyper‐phosphorylated. Additionally, microarray analysis has shown that IGF‐I treatment of MCF7 cells leads to a gene signature comprised of induced and repressed genes, which correlated with luminal B tumors. FOXA1, a forkhead family transcription factor, has been shown to be crucial for mammary ductal morphogenesis, similar to IGF‐IR, and expressed at high levels in luminal subtype B breast tumors. Here, we investigated the relationship between FOXA1 and IGF‐I action in breast cancer cells. We show that genes regulated by IGF‐I are enriched for FOXA1 binding sites, and knock down of FOXA1 blocked the ability of IGF‐I to regulate gene expression. IGF‐I treatment of MCF7 cells increased the half‐life of FOXA1 protein and this increase in half‐life appeared to be dependent on canonical IGF‐I signal transduction through both MAPK and AKT pathways. Finally, knock down of FOXA1 led to a decreased ability of IGF‐I to induce proliferation and protect against apoptosis. Together, these results demonstrate that IGF‐I can increase the stability of FOXA1 protein expression and place it as a critical mediator of IGF‐I regulation of gene expression and IGF‐I‐mediated biological responses. J. Cell. Biochem. 113: 110–121, 2012. © 2011 Wiley Periodicals, Inc.
Recovery of ΔF508‐CFTR function by analogs of hyaluronan disaccharide
Authors: Nowakowska Ewa , Schulz Tobias , Molenda Natalia , Schillers Hermann , Prehm Peter
Published: September 2011

We recently discovered that hyaluronan was exported from fibroblasts by MRP5 and from epithelial cells by cystic fibrosis (CF) transmembrane conductance regulator (CFTR) that was known as a chloride channel. On this basis we developed membrane permeable analogs of hyaluronan disaccharide as new class of compounds to modify their efflux. We found substances that activated hyaluronan export from human breast cancer cells. The most active compound 2‐(2‐acetamido‐3,5‐dihydroxyphenoxy)‐5‐aminobenzoic acid (Hylout4) was tested for its influence on the activity of epithelial cells. It activated the ion efflux by normal and defective ΔF508‐CFTR. It also enhanced the plasma membrane concentration of the ΔF508‐CFTR protein and reduced the transepithelial resistance of epithelial cells. In human trials of healthy persons, it caused an opening of CFTR in the nasal epithelium. Thus compound Hylout4 is a corrector that recovered ΔF508‐CFTR from intracellular degradation and activated its export function. J. Cell. Biochem. 113: 156–164, 2012. © 2011 Wiley Periodicals, Inc.
Effects of stress, depression, and their interaction on heart rate, skin conductance, finger temperature, and respiratory rate: sympathetic‐parasympathetic hypothesis of stress and depression
Authors: Lin Hsiao‐Pei , Lin Hung‐Yu , Lin Wei‐Lun , Huang Andrew Chih‐Wei
Published: September 2011

We examined effects of stress, depression, and their interaction on sympathetic‐parasympathetic responses, including percentage heart rate (PHR), percentage skin conductance (PSC), percentage finger temperature (PTEMP), and percentage respiratory rate (PRESPR). Participants were categorized into normal, low‐risk, and high‐risk depression groups under stress or no‐stress by measuring psychophysiological responses. Stress increased PHR and PSC and decreased PTEMP. Depression negatively correlated with PHR and PTEMP. PSC and PTEMP were significantly dependent on and positively correlated with depression. PTEMP was significantly affected by the stress and depression interaction. Stress affects sympathetic, rather than parasympathetic, activity. Depression and the interaction between stress and depression initially associated with the sympathetic division and are then correlated with parasympathetic activity. A sympathetic‐parasympathetic hypothesis and its clinical implications are discussed. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–12, 2011.
The future of dry and wet spells in Europe: a comprehensive study based on the ENSEMBLES regional climate models
Authors: Heinrich Georg , Gobiet Andreas
Published: September 2011

Under the aspect of future climate change, it is important for decision makers to know how drought conditions might change on the regional scale in order to map out adequate adaptation and mitigation strategies. Recent RCM simulations provided by the ENSEMBLES project are used to analyse changes in dry and wet conditions in Europe by the mid of the 21st century under the A1B emission scenario. Eight RCMs are selected to capture the uncertainties of the projected changes. An empirical statistical error correction approach is applied to modelled daily mean air temperature and precipitation amount to account for RCM errors, and commonly used drought indices—the Standardized Precipitation Index (SPI), the self calibrated Palmer Z‐Index (scZI) and Palmer Drought Severity Index (scPDSI)—are calculated. Changes in the mean, in interannual variability, and in frequency, length, distance, magnitude, and area of dry and wet events are investigated. The statistical significance of the projected multi‐model mean changes and the according uncertainties are analysed for nine European subregions. Furthermore, distributional changes of the dry and wet spell characteristics are assessed. Changes in the mean, and in dry and wet event characteristics show the most pronounced changes towards drier and wetter conditions in the southern‐ and northernmost European subregions, respectively. Here, the changes are highly significant and confident, while the projected changes are more dissonant for the other subregions. Severe changes in the extremes of event length, distance, magnitude, and area particularly arise in the southern‐ and northernmost European subregions. The projected changes in interannual variability are less significant and confident. However, significantly increasing interannual variability is projected in regions with pronounced changes in the mean towards wetter as well as towards drier conditions. Copyright © 2011 Royal Meteorological Society
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for patients with peritoneal carcinomatosis secondary to urachal adenocarcinoma
Authors: Krane L. Spencer , Kader A. Karim , Levine Edward A.
Published: September 2011

Background and Objectives

Urachal adenocarcinoma with peritoneal dissemination is an unusual presentation of a rare disease. It is associated with patients experiencing significant pain, poor outcomes, and historical median survival times between 12 and 24 months. We describe our 18‐year experience in managing these patients with cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

Five patients who underwent six CRS with HIPEC for disseminated urachal cancer were identified. Demographics, perioperative data, and oncologic results were reviewed.

Results

All patients successfully completed CRS followed by HIPEC with Mitomycin C. Three patients had prior urachal mass excision and one had previous cystoprostatectomy with ileal conduit. At time of surgery, complete resection of all visible disease was only achieved in two patients. All patients developed local or distant disease recurrence at a median of 13 months postoperatively (range 7–31). The majority of patients (3/5) underwent postoperative intravenous chemotherapy for recurrence (2) or residual disease (1). All patients died of their disease, with median survival following date of surgery of 27 months (range 21–87). Symptomatic control of peritoneal disease was achieved in 2/5 (40%) of the cases.

Conclusions

Urachal adenocarcinoma with peritoneal dissemination is an aggressive, rare disease, which is uniformly fatal. In our experience, CRS followed by HIPEC with Mitomycin C may increase patient survival and palliation, although further treatment improvements are clearly required. J. Surg. Oncol. 2012; 105:258–260. © 2011 Wiley Periodicals, Inc.
Shared traumatic stress and the long‐term impact of 9/11 on Manhattan clinicians
Authors: Tosone Carol , McTighe John P. , Bauwens Jennifer , Naturale April
Published: September 2011

A sample of 481 social workers from Manhattan participated in a study of the impact of the September 11, 2001 (9/11) World Trade Center (WTC) attacks. A variety of risk factors associated with posttraumatic stress and secondary trauma were examined in relation to shared traumatic stress (STS), a supraordinate construct reflecting the dual nature of exposure to traumatic events. Risk factors included attachment style, exposure to potentially traumatic life events, and enduring distress attributed to the WTC attacks. It was expected that clinicians' resilience would mediate the relationship between these risk factors and STS. Using path analytic modeling, the findings support the study's hypotheses that insecure attachment, greater exposure to potentially traumatic life events in general, and the events of 9/11 in particular are predictive of higher levels of STS. Contrary to expectation, enduring distress attributed to 9/11 was not associated with resilience. Resilience, however, was found to be a mediator of the relationships between insecure attachment, exposure to potentially traumatic life events, and STS but did not mediate the relationship between enduring distress attributed to 9/11 and STS. Implications for theory, research, and practice are discussed.