bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Hormone Replacement Therapy and the Risk of Colorectal Cancer
Authors: Rennert Gad , Rennert Hedy S. , Pinchev Mila , Lavie Ofer , Gruber Stephen B.
Published: August 2009

Purpose

Estrogen/progestin replacement therapy is prescribed to women in menopause for purposes of postmenopausal symptom control or prevention of hormone deficiency–related diseases such as osteoporosis. Such treatments have formerly been shown to be associated with lower colorectal cancer risk in an as yet unknown mechanism.

Patients and Methods

The Molecular Epidemiology of Colorectal Cancer study was a population-based case-control study in northern Israel of patients with colorectal cancer who were diagnosed between 1998 and 2006, and age-, sex-, clinic-, and ethnicity-matched population controls. Use of hormone replacement therapy (HRT) was assessed using a structured interview and validated by studying prescription records in a subset of patients for whom they were available.

Results

Two thousand four hundred sixty peri/postmenopausal women were studied from among 2,648 patients with colorectal cancer and 2,566 controls. The self-reported use of HRT was associated with a significantly reduced relative risk of colorectal cancer (odds ratio [OR], 0.67; 95% CI, 0.51 to 0.89). This association remained significant after adjustment for age, sex, use of aspirin and statins, sports activity, family history of colorectal cancer, ethnic group, and level of vegetable consumption (OR, 0.37; 95% CI, 0.22 to 0.62). Statistically significant interactions were seen between use of HRT and use of aspirin and involvement in sports activity. Using pharmacy data, only users of combined oral preparations demonstrated a significant negative association with colorectal cancer.

Conclusion

The use of oral HRT was associated with a 63% relative reduction in the risk of colorectal cancer in postmenopausal women after adjustment for other known risk factors. This effect was not found in aspirin users and women with intensive sports participation.
Thrombotic Events in Patients With Cancer Receiving Antiangiogenesis Agents
Authors: Zangari Maurizio , Fink Louis M. , Elice Francesca , Zhan Fenghuang , Adcock Dorothy M. , Tricot Guido J.
Published: August 2009

Tumor-associated neoangiogenesis has recently become a suitable target for antineoplastic drug development. In this overview, we discuss specific drug-associated hemostatic complications, the already known pathogenetic mechanisms involved, and the effect of varying antithrombotic strategies. Multiple agents with angiogenic inhibitory capacity (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib, and sirolimus) have obtained US Food and Drug Administration approval, and many others have entered clinical trials. Arterial and venous thromboembolism and hemorrhage have emerged as significant toxicities associated with the use of angiogenesis inhibitors. We present a detailed analysis of the literature on thrombotic complication of antiangiogenic drugs. Close attention to hemostatic complications during antiangiogenic treatment is warranted. Further studies are required to better understand the pathophysiologic mechanisms involved and to define a safe prophylactic strategy.
Randomized Phase II Trial of Docetaxel Plus Cetuximab or Docetaxel Plus Bortezomib in Patients With Advanced Non–Small-Cell Lung Cancer and a Performance Status of 2: CALGB 30402
Authors: Lilenbaum Rogerio , Wang Xiaofei , Gu Lin , Kirshner Jeffrey , Lerro Keith , Vokes Everett
Published: August 2009

Purpose

A randomized phase II trial of two novel treatment strategies in the first-line management of advanced non–small-cell lung cancer patients with performance status (PS) 2.

Patients and Methods

Patients were assigned to docetaxel 30 mg/m2 on days 1, 8, and 15 every 28 days in combination with either cetuximab 400 mg/m2 loading dose followed by 250 mg/m2 weekly (D + C) or bortezomib 1.6 mg/m2 on days 1, 8, and 15 every 28 days (D + B) for up to 4 cycles. Patients with responding or stable disease continued cetuximab or bortezomib until progression. The primary end point was progression-free survival (PFS) rate at 6 months.

Results

Sixty-four patients were enrolled and 59 were included in this analysis. Complete or partial response rates were 13.3% and 10.3% for D + C and D + B, respectively. Median PFS was 3.4 months in the D + C arm and 1.9 months in the D + B arm. Corresponding figures for 6-month PFS were 27.8% and 13.8% and 5.0 and 3.9 months for median survival, respectively. Grade 3/4 hematologic toxicity was 16% for D + C and 21% for D + B, whereas nonhematologic toxicities were observed in 63% and 44% of patients, respectively. There was one treatment-related death in each arm.

Conclusion

These results confirm the poor prognosis associated with a PS of 2 and the difficulty in translating recent advances in targeted therapy to this subset of patients. While the results in the D + C arm are numerically superior, neither combination met the prespecified PFS end point to justify further research in this setting.
Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group
Authors: Rinke Anja , Müller Hans-Helge , Schade-Brittinger Carmen , Klose Klaus-Jochen , Barth Peter , Wied Matthias , Mayer Christina , Aminossadati Behnaz , Pape Ulrich-Frank , Bläker Michael , Harder Jan , Arnold Christian , Gress Thomas , Arnold Rudolf
Published: August 2009

Purpose

Somatostatin analogs are indicated for symptom control in patients with gastroenteropancreatic neuroendocrine tumors (NETs). The ability of somatostatin analogs to control the growth of well-differentiated metastatic NETs is a matter of debate. We performed a placebo-controlled, double-blind, phase IIIB study in patients with well-differentiated metastatic midgut NETs. The hypothesis was that octreotide LAR prolongs time to tumor progression and survival.

Patients and Methods

Treatment-naive patients were randomly assigned to either placebo or octreotide LAR 30 mg intramuscularly in monthly intervals until tumor progression or death. The primary efficacy end point was time to tumor progression. Secondary end points were survival time and tumor response. This report is based on 67 tumor progressions and 16 observed deaths in 85 patients at the time of the planned interim analysis.

Results

Median time to tumor progression in the octreotide LAR and placebo groups was 14.3 and 6 months, respectively (hazard ratio [HR] = 0.34; 95% CI, 0.20 to 0.59; P = .000072). After 6 months of treatment, stable disease was observed in 66.7% of patients in the octreotide LAR group and 37.2% of patients in the placebo group. Functionally active and inactive tumors responded similarly. The most favorable effect was observed in patients with low hepatic tumor load and resected primary tumor. Seven and nine deaths were observed in the octreotide LAR and placebo groups, respectively. The HR for overall survival was 0.81 (95% CI, 0.30 to 2.18).

Conclusion

Octreotide LAR significantly lengthens time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs. Because of the low number of observed deaths, survival analysis was not confirmatory.
VEGF and inhibitors of TGFβ type-I receptor kinase synergistically promote blood-vessel formation by inducing α5-integrin expression
Authors: Liu Zhen , Kobayashi Kazuki , van Dinther Maarten , van Heiningen Sandra H. , Valdimarsdottir Gudrun , van Laar Theo , Scharpfenecker Marion , Löwik Clemens W. G. M. , Goumans Marie-José , Dijke Peter ten , Pardali Evangelia
Published: August 2009

Vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGFβ) are potent regulators of angiogenesis. How VEGF and TGFβ signaling pathways crosstalk is not well understood. Therefore, we analyzed the effects of the TGFβ type-I-receptor inhibitors (SB-431542 and LY-2157299) and VEGF on endothelial cell (EC) function and angiogenesis. We show that SB-431542 dramatically enhances VEGF-induced formation of EC sheets from fetal mouse metatarsals. Sub-optimal doses of VEGF and SB-431542 synergistically induced EC migration and sprouting of EC spheroids, whereas overexpression of a constitutively active form of TGFβ type-I receptor had opposite effects. Using quantitative PCR, we demonstrated that VEGF and SB-431542 synergistically upregulated the mRNA expression of genes involved in angiogenesis, including the integrins α5 and β3. Specific downregulation of α5-integrin expression or functional blocking of α5 integrin with a specific neutralizing antibody inhibited the cooperative effect of VEGF and SB-431542 on EC sprouting. In vivo, LY-2157299 induced angiogenesis and enhanced VEGF- and basic-fibroblast-growth-factor-induced angiogenesis in a Matrigel-plug assay, whereas adding an α5-integrin-neutralizing antibody to the Matrigel selectively inhibited this enhanced response. Thus, induction of α5-integrin expression is a key determinant by which inhibitors of TGFβ type-I receptor kinase and VEGF synergistically promote angiogenesis.
VEGFR2-PLCγ1 axis is essential for endothelial specification of VEGFR2+ vascular progenitor cells
Authors: Sase Hitoshi , Watabe Tetsuro , Kawasaki Kyoko , Miyazono Kohei , Miyazawa Keiji
Published: August 2009

Vascular endothelial growth factor receptor 2 (VEGFR2) plays crucial roles in vasculogenesis, a process involving cell proliferation, migration and differentiation. However, the molecular mechanism by which VEGFR2 signaling directs vascular endothelial differentiation of VEGFR2+ mesodermal progenitors is not well understood. In this study, we examined the signal transduction pathway downstream of VEGFR2 for endothelial differentiation using an in vitro differentiation system of mouse embryonic stem-cell-derived VEGFR2+ cells. Using chimeric receptors composed of VEGFR2 and VEGFR3, the third member of the VEGFR family, we found that signaling through tyrosine 1175 (Y1175, corresponding to mouse Y1173) of VEGFR2 is crucial for two processes of endothelial differentiation: endothelial specification of VEGFR2+ progenitors, and subsequent survival of endothelial cells (ECs). Furthermore, we found that phospholipase Cγ1 (PLCγ1), which interacts with VEGFR2 through phosphorylated Y1175, is an inducer of endothelial specification. In contrast to VEGFR2, VEGFR3 does not transmit a signal for endothelial differentiation of VEGFR2+ cells. We found that VEGFR3 does not activate PLCγ1, although VEGFR3 has the ability to support endothelial cell survival. Taken together, these findings indicate that VEGFR2-PLCγ1 signal relay gives rise to the unique function of VEGFR2, thus enabling endothelial differentiation from vascular progenitors.
Dopamine regulates phosphorylation of VEGF receptor 2 by engaging Src-homology-2-domain-containing protein tyrosine phosphatase 2
Authors: Sinha Sutapa , Vohra Pawan Kumar , Bhattacharya Resham , Dutta Shamit , Sinha Shirshendu , Mukhopadhyay Debabrata
Published: August 2009

Vascular endothelial growth factor (VEGF)-induced receptor phosphorylation is the crucial step for initiating downstream signaling pathways that lead to angiogenesis or related pathophysiological outcomes. Our previous studies have shown that the neurotransmitter dopamine could inhibit VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR-2), endothelial cell proliferation, migration, microvascular permeability, and thus, angiogenesis. In this study, we address the mechanism by which VEGFR-2 phosphorylation is regulated by dopamine. Here, we demonstrate that D2 dopamine receptor (D2DR) colocalizes with VEGFR-2 at the cell surface. Dopamine pretreatment increases the translocation and colocalization of Src-homology-2-domain-containing protein tyrosine phosphatase (SHP-2) with D2DR at the cell surface. Dopamine administration leads to increased VEGF-induced phosphorylation of SHP-2 and this increased phosphorylation parallels the increased phosphatase activity of SHP-2. Active SHP-2 then dephosphorylates VEGFR-2 at Y951, Y996 and Y1059, but not Y1175. We also observe that SHP-2 knockdown impairs the dopamine-regulated inhibition of VEGF-induced phosphorylation of VEGFR-2 and, subsequently, Src phosphorylation and migration. Our data establish a novel role for SHP-2 phosphatase in the dopamine-mediated regulation of VEGFR-2 phosphorylation.
Ligand-independent signaling by disulfide-crosslinked dimers of the p75 neurotrophin receptor
Authors: Vilar Marçal , Charalampopoulos Ioannis , Kenchappa Rajappa S. , Reversi Alessandra , Klos-Applequist Joanna M. , Karaca Esra , Simi Anastasia , Spuch Carlos , Choi Soyoung , Friedman Wilma J. , Ericson Johan , Schiavo Giampietro , Carter Bruce D. , Ibáñez Carlos F.
Published: August 2009

Dimerization is recognized as a crucial step in the activation of many plasma membrane receptors. However, a growing number of receptors pre-exist as dimers in the absence of ligand, indicating that, although necessary, dimerization is not always sufficient for signaling. The p75 neurotrophin receptor (p75NTR) forms disulfide-linked dimers at the cell surface independently of ligand binding through Cys257 in its transmembrane domain. Here, we show that crosslinking of p75NTR dimers by cysteine-scanning mutagenesis results in constitutive, ligand-independent activity in several pathways that are normally engaged upon neurotrophin stimulation of native receptors. The activity profiles of different disulfide-crosslinked p75NTR mutants were similar but not identical, suggesting that different configurations of p75NTR dimers might be endowed with different functions. Interestingly, crosslinked p75NTR mutants did not mimic the effects of the myelin inhibitors Nogo or MAG, suggesting the existence of ligand-specific activation mechanisms. Together, these results support a conformational model of p75NTR activation by neurotrophins, and reveal a genetic approach to generate gain-of-function receptor variants with distinct functional profiles.
The effects of interfacial debonding on the elastoplastic response of unidirectional silicon carbide—titanium composites
Authors: Mahmoodi M J , Aghdam M M , Shakeri M
Published: August 2009

A three-dimensional micromechanics-based analytical model is presented to investigate the effects of initiation and propagation of interface damage on the elastoplastic behaviour of unidirectional SiC—Ti metal matrix composites (MMCs) subjected to off-axis loading. Temperature-dependent properties are considered for the matrix. Manufacturing process thermal residual stress (RS) is also included in the model. The selected representative volume element consists of r× c unit cells in which a quarter of the fibre is surrounded by matrix sub-cells. The constant compliance interface model is used to model interfacial debonding and the successive approximation method together with von Mises yield criterion is used to obtain elastoplastic behaviour. Dominance mode of damage including fibre fracture, interfacial debonding, and matrix yielding and ultimate tensile strength of the SiC—Ti MMC are predicted for various loading directions. The effects of thermal RS and fibre volume fraction on the stress—strain response of the SiC—Ti MMC are studied. Results revealed that for more realistic predictions, both interface damage and thermal RS effects should be considered in the analysis. The contribution of interfacial debonding and thermal RS in the overall behaviour of the material is also investigated. Comparison between results of the presented model shows very good agreement with the finite-element micromechanical analysis and experiment for various off-axis angles.
Experimental analysis of a dimensionless number in the cathode channels of a polymer electrolyte membrane fuel cell with different head losses
Authors: Han S H , Kim K R , Ahn D K , Choi Y D
Published: August 2009

This study investigates the effects of stoichiometry, humidity, cell temperature, and pressure on the performance and the flooding of the proton exchange membrane fuel cell. Values of stoichiometry are 1.5, 2.0, and 2.5 at cell temperatures of 50, 55, and 60 °C, respectively. This study shows that the dimensionless flooding value (FV) is a function of the stoichiometry, humidity, temperature, and pressure. The FV is calculated by using the measured values of temperature, humidity, pressure, and flowrate of the cathode. The effect of the dimensionless number on the flooding of the cathode in the proton exchange membrane fuel cell is analysed in this study. The effects of air stoichiometry, cell temperature, and air humidity are also discussed in this article.
HIV seropositive status disclosure to prospective sex partners and criminal laws that require it: perspectives of persons living with HIV
Authors: Galletly C L , Dickson-Gomez J
Published: August 2009

Thirty-one HIV-positive persons living in Michigan took part in focus group discussions about Michigan's HIV disclosure law. Discussion themes included perceived responsibility to prevent infection, concern about unwanted secondary disclosure of HIV-positive status, fear of being falsely accused of violating Michigan's HIV disclosure law and perceived vulnerability of HIV-positive persons within the US legal system. Although participants strongly agreed with the ostensible purpose of Michigan's criminal HIV disclosure law, there was considerable concern about the negative impact of the law on persons living with HIV.
Sexual behaviour, drugs and alcohol use of international students at a British university: a cross-sectional survey
Authors: Vivancos R , Abubakar I , Hunter P R
Published: August 2009

The aim of the study was to determine whether international students have greater risk-taking behaviours that could lead to importing novel and resistant strains of sexually transmitted infections (STIs). We conducted a cross-sectional web-based survey of university students' sexual behaviour, alcohol and drug use, and self-reported diagnosis of STIs and compared these between British and international students. In all, 827 students completed the survey, of whom 123 (15%) were international students. International students were less likely to have ever drunk alcohol (95.4% versus 87.8%, P = 0.002) and used drugs (56.4% versus 41.5%, P = 0.002). International students were on average almost two years older at first intercourse (18.7 versus 17 years; P < 0.001). There were no differences in the number of sexual partners between national and international students. On a discriminant analysis model, international students were characterized by being older and from a non-white background, less likely to use cocaine, they drank alcohol less frequently and were more likely to have had unprotected intercourse with two or more partners in the previous year. In conclusion, international students tend to drink more moderately and use fewer recreational drugs than British students. However, they exhibit higher sexual risk behaviours that could lead to importing novel and resistant strains of STIs.
Value of targeting at-risk populations at outreach venues: findings from a local sauna
Authors: Arumainayagam J , Grimshaw R , Acharya S , Chandramani S , Morrall I A , Pugh R N
Published: August 2009

An assessment of the need to increase access to an outreach venue, the local sauna in Walsall, UK, frequented only by men who have sex with men, was undertaken. A case-notes review of the clients who attended the monthly outreach sessions at the sauna in the year 2007 was performed. Among the 287 men seen at the 12 outreach sessions, 37% had a sexually transmitted infection (STI). Of those tested positive, 88% had never had a previous STI. Twenty-one men had syphilis and a further six tested positive for HIV. Hepatitis B vaccination was completed for 41% of the clients seen. Those who tested positive for an STI said they would not have attended a conventional setting but accepted screening at the sauna. This confirmed the need to increase access at this outreach venue, and further funding has now been provided to have outreach sessions twice a month.
Current issues in care and support for HIV-positive gay men in Sydney
Authors: Zablotska I , Frankland A , Imrie J , Adam P , Westacott R , Canavan P , Prestage G
Published: August 2009

We explored current access to care among HIV-positive people in Australia. In 2006, 270 HIV-positive gay men from a community-based Positive Health cohort in Sydney were asked about their health (including medical and social) service needs and, subsequently, about difficulty in accessing services. We report the prevalence of specific needs, barriers and associated factors. Participants most commonly used general practitioners (64%) for HIV management and needed at least one HIV-related medical service (usually several: doctors experienced in HIV management, dentists and hospital pharmacies). Most participants were able to access them. Barriers in accessing services were related to their convenience rather than lack or quality. Cost emerged as a substantial barrier to dental care and psychological counselling (91% and 48% respectively of those in need). Need for an HIV-related social service was reported by 46% of respondents. Difficulties in accessing these related to poor services and staff attitudes. Income was associated with limited access to multiple services. In Australia, HIV-related medical service needs outweigh those for social services. Complex health services remain essential to HIV-positive people, but some services are currently not meeting their needs. To remain adequate, services need to understand and constantly adapt to the changing needs of HIV-positive people.
Outcome from treatment of Pneumocystis jirovecii pneumonia with co-trimoxazole
Authors: Fisk M , Sage E K , Edwards S G , Cartledge J D , Miller R F
Published: August 2009

A retrospective case-notes audit of 359 HIV-1-infected adult patients with first-episode laboratory-confirmed Pneumocystis jirovecii pneumonia treated with co-trimoxazole (from 1987 adjuvant steroids were used if PaO2 <9.3 kPa) showed that only 230/359 (64%) patients completed treatment; 104 (29%) patients had treatment-limiting toxicity; rash occurred in 4/60 (6.7%) patients in 1985–1988 and in 15/47 (31.9%) in 2005–2008. Twenty-five patients (7%) failed co-trimoxazole treatment. Overall mortality was 13.6% (49/359); mortality among patients who failed co-trimoxazole treatment was 48% (12/25) and by contrast mortality was 4.8% (5/104) among patients with treatment-limiting toxicity.
Hepatitis B vaccination in HIV-infected adults: current evidence, recommendations and practical considerations
Authors: Kim H N , Harrington R D , Crane H M , Dhanireddy S , Dellit T H , Spach D H
Published: August 2009

Immunization with hepatitis B (HBV) vaccine is recommended for all HIV-infected individuals without immunity to HBV. This patient population, however, has relatively poor HBV vaccine responses. Factors associated with this impaired HBV vaccine response in HIV-infected individuals may include older age, uncontrolled HIV replication, and low nadir CD4 cell count. Postvaccination testing for HBV surface antibody is recommended and vaccine non-responders should undergo repeat immunization with a full series. The benefit of double dosage, the appropriate strategy for HIV-infected patients with isolated HBV core antibody and the timing and number of vaccinations in persons with advanced immunosuppression on highly active antiretroviral therapy remain controversial areas.
Improved RNA secondary structure prediction by maximizing expected pair accuracy
Authors: Lu Zhi John , Gloor Jason W. , Mathews David H.
Published: August 2009

Free energy minimization has been the most popular method for RNA secondary structure prediction for decades. It is based on a set of empirical free energy change parameters derived from experiments using a nearest-neighbor model. In this study, a program, MaxExpect, that predicts RNA secondary structure by maximizing the expected base-pair accuracy, is reported. This approach was first pioneered in the program CONTRAfold, using pair probabilities predicted with a statistical learning method. Here, a partition function calculation that utilizes the free energy change nearest-neighbor parameters is used to predict base-pair probabilities as well as probabilities of nucleotides being single-stranded. MaxExpect predicts both the optimal structure (having highest expected pair accuracy) and suboptimal structures to serve as alternative hypotheses for the structure. Tested on a large database of different types of RNA, the maximum expected accuracy structures are, on average, of higher accuracy than minimum free energy structures. Accuracy is measured by sensitivity, the percentage of known base pairs correctly predicted, and positive predictive value (PPV), the percentage of predicted pairs that are in the known structure. By favoring double-strandedness or single-strandedness, a higher sensitivity or PPV of prediction can be favored, respectively. Using MaxExpect, the average PPV of optimal structure is improved from 66% to 68% at the same sensitivity level (73%) compared with free energy minimization.
Microarray analysis of cytoplasmic versus whole cell RNA reveals a considerable number of missed and false positive mRNAs
Authors: Trask Heidi W. , Cowper-Sal-lari Richard , Sartor Maureen A. , Gui Jiang , Heath Catherine V. , Renuka Janhavi , Higgins Azara-Jane , Andrews Peter , Korc Murray , Moore Jason H. , Tomlinson Craig R.
Published: August 2009

With no known exceptions, every published microarray study to determine differential mRNA levels in eukaryotes used RNA extracted from whole cells. It is assumed that the use of whole cell RNA in microarray gene expression analysis provides a legitimate profile of steady-state mRNA. Standard labeling methods and the prevailing dogma that mRNA resides almost exclusively in the cytoplasm has led to the long-standing belief that the nuclear RNA contribution is negligible. We report that unadulterated cytoplasmic RNA uncovers differentially expressed mRNAs that otherwise would not have been detected when using whole cell RNA and that the inclusion of nuclear RNA has a large impact on whole cell gene expression microarray results by distorting the mRNA profile to the extent that a substantial number of false positives are generated. We conclude that to produce a valid profile of the steady-state mRNA population, the nuclear component must be excluded, and to arrive at a more realistic view of a cell's gene expression profile, the nuclear and cytoplasmic RNA fractions should be analyzed separately.
Formation of an active site in trans by interaction of two complete Varkud Satellite ribozymes
Authors: Ouellet Jonathan , Byrne Max , Lilley David M.J.
Published: August 2009

The complete VS ribozyme comprises seven helical segments, connected by three three-way RNA junctions. In the presence of Mg2+ ions, cleavage occurs within the internal loop of helix I. This requires the participation of a guanine (G638) within the helix I loop, and a remote adenine (A756) within an internal loop of helix VI. Previous structural studies have suggested that helix I docks into the fold of the remaining part of the ribozyme, bringing A756 and G638 close to the scissile phosphate to allow the cleavage reaction to proceed. We show here that while either A756C or G638A individually exhibit very low cleavage activity, a mixture of the two variants leads to cleavage of the A756C RNA, but not the G638A RNA. The rate of cleavage depends on the concentration of the VS G638A RNA, as expected for a bimolecular interaction. This regaining of cleavage activity by complementation indicates that helix I of one VS RNA can interact with another VS RNA molecule to generate a functional active site in trans.
A Qualitative Investigation of Long-Term Zopiclone Use and Sleep Quality Among Vietnam War Veterans with PTSD
Authors: Alderman Christopher P , Gilbert Andrew L
Published: August 2009

Background:

Self-reported sleep difficulties are common among patients with posttraumatic stress disorder (PTSD), but the routine use of hypnosedatives over extended periods is not generally recommended.

Objective:

To examine the effects of the extended use of zopiclone among a cohort of patients with combat-related PTSD.

Methods:

We conducted a 6-month follow-up cohort study of zopiclone usage characteristics for 26 combat veterans with PTSD. Psychometric and sleep assessments were also conducted at baseline and 6 months.

Results:

The mean baseline score obtained on the tranquilizer dependence questionnaire was 20.4 ± 13.4, below the cutoff score proposed as indicative of a high likelihood of dependence (23 points). Eight (30.7%) subjects exceeded the proposed cutoff score for dependence at baseline. Most (n = 24) subjects reported poor sleep quality at baseline. Actigraphy revealed that the mean sleep efficiency score was 71.2 ± 13.7% at baseline. A cohort of 13 men was available for inclusion in the follow-up phase of the study. The tranquilizer dependence questionnaire score at follow-up was broadly similar to the baseline score after a further 6 months of zopiclone use (18.9 at baseline compared with 19.9 ±2.6 at follow-up). Individual analysis revealed that the tranquilizer dependence scale score increased for 5 subjects and decreased for 8 subjects at follow-up. Four (30.7%) subjects in the follow-up cohort exceeded the proposed cutoff score for dependence at baseline and 6 (46.1%) subjects exceeded it at follow-up. Actigraphy data were consistent across measurements for individual subjects at baseline and follow-up, with similar mean sleep efficiency scores at baseline and after 6 months of treatment with zopiclone (69.6 ± 12.7% at baseline; 71.33 ± 19.0% at follow-up). The proportion of relatively poor sleepers (5/13 at baseline and 4/13 at follow-up) remained essentially unchanged.

Conclusions:

Overall, the results of this study suggest that, although the subjects in the follow-up phase of the research continued to use zopiclone on a regular basis for an extended period, the efficacy of this intervention for addressing PTSD-related sleep disturbance was low. Extended treatment with zopiclone may not necessarily be associated with increased risk for dependence. Further robust research to examine the consequences of long-term zopiclone therapy for PTSD-related sleep disturbance is warranted.
Improving Control of a Quenching Process by Coupling Analysis Methods
Authors: Banka Andrew , Franklin Jeff , Li Zhichao , Ferguson Blake L. , Freborg Andrew , Aronov Michael
Published: August 2009

Intensive quenching is a fast transient thermal process where an austenitized part is cooled rapidly by contact with a stream of high velocity water. As in all quenching processes, the quenchant flow condition has a primary effect on material response, including the final microstructural phase distribution, hardness, residual stress, and distortion. Therefore, characterization of the quenchant flow is important for understanding the quenching process and the relationships between quenchant flow rate, part cooling rate, material phase transformations, and residual stress. With the development of high-speed computer and computational fluid dynamics (CFD) technologies, the quenchant flow pattern around a complex part during quenching can be calculated. This allows the local heat transfer between the quench media and the part to be calculated. The transient heat transfer coefficients predicted from such a CFD model can then be used in a finite element based thermal-stress calculation to predict the final residual stress state of the part, as well as the microstructural phase distribution, hardness distribution, and dimensional change due to quenching. In this paper, transient CFD analyses using FLUENT are applied to characterize the water flow and thermal boundary conditions around a spur gear made of carburized Pyrowear 53 during intensive quenching. The calculated heat transfer coefficients are imported to DANTE heat treatment models, and the gear’s response to intensive quenching is predicted. The results include hardness, phase transformation, stress, and distortion. The relationships between temperature field, phase transformation, residual stress, and distortion during quenching are explained using the modeling histories. The combination of FLUENT and DANTE models provides efficient and effective solutions to the quenching fixture and water flow designs. The predicted gear distortion and residual stresses are validated using experiments.
Concrete Hygrothermal Properties and the Influence of their Variability on Moisture Movement in Concrete Walls
Authors: Onmura Sadayuki , Hokoi Shuichi , Matsushita Takayuki , Ogura Daisuke , Kominami Kazuya , Yasui Yoshitaka
Published: August 2009

The vapor permeability, equilibrium moisture content, hydraulic conductivity, and thermal conductivity of concrete specimens with three different strengths were measured under various conditions of temperature and relative humidity. Based on the measured results, the relationship between hygrothermal properties and strength, and the relationship between hygrothermal properties, water content, and temperature were considered. The variability of measured hygrothermal properties was clarified. Then, to evaluate the influence that the variability of hygrothermal properties has on the hygrothermal behaviors of a concrete wall, a water absorption experiment using a small-scale concrete wall with tile finishing was carried out under constant temperature. The experimental result shows a significantly difference between three specimens in the hygrothermal behaviors, which is partly because of the variability of the hygrothermal properties.
Appendix D: The Mean
Authors: Rothman Lori
Published: August 2009

The objective of the mean analysis is to determine if, on average, the product scores “Just About Right,” or whether there is a skew of “Too Much” or “Not Enough” of an attribute. This method of analysis uses only the JAR data. While calculation of the JAR means is completed individually for each product, these means can be compared (see Appendixes I and J). Determining whether the mean is statistically different from the scale midpoint is discussed in Appendix F.
Appendix H: A Proportional Odds/Hazards Approach to JAR Data
Authors: Xiong Rui , Meullenet Jean-Francois
Published: August 2009

t-tests, ANOVA, and linear regression all assume that the response is measured on an interval scale, so that the differences between adjacent values have the same meaning across the scale. This assumption is often violated in practice, which can lead to inaccurate conclusions. The proportional odds and proportional hazards models are ordinal regression models that are only sensitive to the order of the observations, not the specific values assigned to the categories. They are used to compare the distributions of JAR scores among products and are performed simultaneously. The proportional odds model (POM) is skew-symmetric, so that reversing the order of the scale simply changes the sign of the mean, while the proportional hazards model (PHM) is asymmetric, so that reversing the order of the scale changes both the order and the sign of the estimate.
Appendix I: Student's t-Test—Analysis of Variance of Two Samples
Authors: Parker Merry Jo
Published: August 2009

The Student's t-test is a statistical method for comparing the mean JAR scores of two product samples. The results of the t-test determine whether or not the means of two samples of data are significantly different.
Appendix J: Analysis of Variance (ANOVA)
Authors: Parker Merry Jo
Published: August 2009

Analysis of Variance (ANOVA) is a statistical method for studying differences between the mean scores of samples. ANOVA takes into account variance from different sources. When used to analyze “Just About Right” (JAR) scales, the source of variance is most often treatments and judges, so a two-way ANOVA is used.
Appendix K: Thurstonian Ideal Point Modeling
Authors: Delwiche Jeannine
Published: August 2009

Thurstonian ideal point modeling allows one to compare the JAR ratings of multiple products to a theoretical ideal product. It compares the probabilistic distribution of a product against the probabilistic distribution of the ideal.
Appendix L: Penalty Analysis or Mean Drop Analysis
Authors: Schraidt Mary
Published: August 2009

Penalty analysis or Mean drop analysis is a method for determining if respondents' “Just About Right” ratings for a specific attribute are associated with a drop in some hedonic or choice measure, most commonly Overall Liking. Penalty/Mean drop analysis is conducted on “Just About Right” data to determine if those who do not find a particular attribute “Just About Right” rate it lower for Overall Liking on that attribute than those who find the same attribute JAR. Penalty/Mean drop analysis is not a formal method for determining drivers of liking, but is an effective tool for linking attribute performance to Overall Liking.
Appendix O: Bootstrapping Penalty Analysis
Authors: Xiong Rui , Meullenet Jean-Francois
Published: August 2009

Bootstrapping penalty analysis is a method that allows you to perform statistical testing on the results of a penalty analysis, using a technique called bootstrapping to estimate variances and covariances. Recall that the purpose of penalty analysis is to identify attributes that appear to have a strong impact on Overall Liking, on a product-by-product basis.. However, there are no significance procedures to test the significance of each attribute's effect on Overall Liking. The bootstrap method, is a well-established computer-based Monte Carlo technique for determining an estimate for the standard errors, confidence intervals, biases, and prediction errors.
Appendix R: Chi-Square
Authors: Templeton Lynn
Published: August 2009

The chi-square approach looks at the relationship between “Just Right” and hedonic ratings for each product, using only the data from the “Not Just Right” sections of the scale. The objective of using a chi-square analysis is to determine if there are significant differences in liking between respondents that have rated the product differently on the JAR scales, i.e., to test the null hypothesis that there is no association between the JAR group and overall liking. For example, one could use the chi-square approach to determine whether respondents that rated the product as “Not Sweet Enough” differed from those respondents who rated the product as “Too Sweet.”
Appendix T: Correlation
Authors: Takkunen Amy
Published: August 2009

Correlation analyses can be used to measure the linear association of JAR scale data to data measured using other types of scales, e.g., liking scales. The goal of these analyses is to assess the strength and direction of the relationship between the JAR scale and the other scale(s) of interest for each product and, possibly, across products.
Appendix U: Regression
Authors: Herskovic Joseph E.
Published: August 2009

Many of the other techniques in this guideline treat the effect of JAR scales on the overall rating one scale at a time. Regression analysis allows the researcher to evaluate the joint effects of the scales levels on overall response. The stronger the relationship between a JAR scale and the overall response, the more important that “Just-Right” attribute is in explaining the liking attribute, even after controlling for the other attributes. The regression can be either non-parametric (ordinal) or parametric (ordinary regression) and the JAR scales can have either a linear or non-linear effect on the response. The examples below use linear regression because of ease of use and widespread availability in many statistical packages. The more general approaches require more statistical sophistication. Regression analysis can be done for the entire data set (all samples combined) or for each individual sample. Conducting the analysis on all samples combined gives a general overview of how the “Just Right” attributes work together to explain liking. This analysis can be conducted using either the individual respondent data or product mean scores.
Just-About-Right (JAR) Scales: Design, Usage, Benefits, and Risks
Authors: Rothman Lori , Parker Merry Jo
Published: August 2009

Description

This new ASTM manual is a comprehensive guide on the use of JAR scales in consumer testing, including their application, construction, analysis, and interpretation. It also identifies the risks associated with the use of JAR scales and ways to reduce those risks.

JAR scales measure levels of a product's attribute relative to a respondent's theoretical ideal level. These scales have an anchored midpoint of "just-about-right" or "just right", and endpoints anchored to represent intensity levels of the attributes that are higher and lower than ideal.

Manual 63 also includes numerous case studies for the analysis of JAR scale data and alternatives to JAR scales.

This is a "must have" reference for professionals who use JAR scales when conducting consumer research.
Introduction
Authors: Shackman Norman
Published: August 2009

The ASTM Bibliography on Thermostat Metals covers the period 1806–1959 and consists of 519 references. This bibliography is based largely upon one published by the American Society of Mechanical Engineers which in turn was based upon a much smaller bibliography prepared by ASTM Committee B-4 on Metallic Materials for Thermostats and for Electric Resistance, Heating, and Contacts. The ASME Bibliography on Thermostatic Bimetals, Low-Expansion Alloys, and Their Application contained 320 references and covered the years from 1806–1947. In compiling the present ASTM bibliography, most of the ASME references were used intact, additions being made to the references prior to 1947 and new references obtained for the years 1947 through 1959. The ASME was very gracious in allowing us to use their bibliography. Another valuable source of references was the Engineering Index who also kindly permitted reprinting of references taken from their publication. The bulk of the references used in the bibliography were not read by the compiler and in most cases, the annotations were obtained from sources such as the ASME Bibliography and the Engineering Index. Those taken from the American Society of Mechanical Engineers are identified by (ASME) while those taken from the Engineering Index are identified (Engineering Index).
Lacquer Marring by Plasticizer Migration from Vinyl Chloride Plastics
Authors: DeCoste J. B.
Published: August 2009

Nonrigid vinyl chloride plastics may on prolonged contact mar lacquer finishes through plasticizer migration. One example where this reaction may interfere with serviceability is in the use of these plastics as coatings on electrical cords and wires. A series of experimental vinyl chloride plastics compounded with various monomeric and polymeric plasticizers have been evaluated using the Sward rocker method. The relation of the chemical structure of plasticizers with respect to marring is discussed. The results of the study show that plasticizers that are the most attractive from a nonmarring standpoint produce compounds with the least resilience. The relationship is such, however, that compromises with satisfactory serviceability may be achieved.
In-Line Gasoline Blending Trends, Economics, and the Use of Continuous Analyzers for Quality Control
Authors: Crane B. G.
Published: August 2009

Gasoline in-line blending systems offer refiners substantial savings over batch blending methods, and their use is increasing steadily. The full potential savings cannot be realized, however, until approval by ASTM and others of continuous test methods for verification of quality where custody transfer is involved. This paper discusses the principles and economics of in-line blending and the importance of continuous analytical methods.
Clean Oil Systems for Heavy Duty Gas Turbines
Authors: Smith A. N.
Published: August 2009

Dirt can and has caused failures in gas turbine lubricating oil and fuel oil systems. How clean must these systems be? This can be determined, and, by proper construction, processes, control, and filtration, clean systems can be obtained and measured. Particle counts with no more than 12,000 particles over 5 μm in 100-ml sample are regularly obtained in heavy duty gas turbine oil systems.
Infrared Testing of Bonds Between Graphite and Protective Coatings
Authors: Green D. R. , Day C. K.
Published: August 2009

A nondestructive infrared method has been developed for testing bonds between coatings and graphite. Application of a special digital dual-scan technique makes the test independent of the specimen surface emittance (often called emissivity). In addition, this method does not require contact with the specimen, and can be automated for production testing. Heat was applied during tests by projecting a hot jet of helium onto the specimen surface. A commercial infrared radiometer was used to sense the resulting surface temperatures. This paper describes the theory and equipment, and some of the experimental results from tests on bonds between graphite and thin columbium carbide coatings.
Application of Alcohol Penetrant for Evaluation of Surface Porosity of Graphite Inserts for Rocket Nozzles
Authors: Hendron J. A.
Published: August 2009

Detection of defect conditions in rocket nozzle graphite components, using clear alcohol as a penetrant, is described as an inspection method. Procedure and acceptance criteria used for graphite with densities of 1.60 to 1.80 are given. Porosity and density evaluation using standard test blocks is discussed relative to rocket test firing results. It is concluded that this method is the most valuable single inspection technique for graphite in this density range when the technique is compared to other common nondestructive tests.
Introduction
Authors: Hardrath Herbert F.
Published: August 2009

One of the most challenging aspects of aircraft structural design is the prevention of fatigue failure. For this reason ASTM Committee E-9 on Fatigue established a subcommittee to deal especially with fatigue problems facing aircraft designers and operators. This subcommittee sponsored the present symposium to discuss recent advances and the current state of development of solutions to various phases of the aircraft fatigue problem. The symposium was held during the Third Pacific Area National Meeting of the Society to continue a precedent set three years previously when a similar symposium was held during the Second Pacific Area Meeting. The papers presented cover a broad range of individual topics from general design philosophies to rather basic considerations. Twelve papers were presented in three sessions. Nine of these papers are included in this Special Technical Publication; two will be published along with other papers at a later date and the third paper by E. H. Schuette, Dow Chemical Co., on “Fatigue-Strength Comparisons of Forged Magnesium Alloys,” has been withdrawn. The first two papers present, respectively, a method for handling fatigue data in a practical design case, and a review of probable loading conditions encountered by aircraft. An interesting description of a method for conducting sonic fatigue tests and a rather basic treatment of fatigue behavior under high biaxial stresses are the subjects of the remaining papers in the first session. In the second session, one paper deals with problems peculiar to helicopters, one with methods for improving fatigue behavior in structures, and one with methods for predicting rates of fatigue crack propagation. The two published papers from the third session discuss cumulative damage due to variable-amplitude loading.