bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Angina in Women Versus Men
Authors: Hemingway Harry , Langenberg Claudia , Damant Jacqueline , Frost Chris , Pyörälä Kalevi , Barrett-Connor Elizabeth
Published: March 2008

Background—

In the absence of previous international comparisons, we sought to systematically evaluate, across time and participant age, the sex ratio in angina prevalence in countries that differ widely in the rate of mortality due to myocardial infarction.

Methods and Results—

We searched MEDLINE and EMBASE until February 2006 for healthy population studies published in any language that reported the prevalence of angina (Rose questionnaire) in women and men. We obtained myocardial infarction mortality rates from the World Health Organization. A total of 74 reports of 13 331 angina cases in women and 11 511 cases in men from 31 countries were included. Angina prevalence varied widely across populations, from 0.73% to 14.4% (population weighted mean 6.7%) in women and from 0.76% to 15.1% (population weighted mean 5.7%) in men, and was strongly correlated within populations between the sexes (
r
=0.80,
P
<0.0001). Angina prevalence showed a small female excess with a pooled random-effects sex ratio of 1.20 (95% CI 1.14 to 1.28,
P
<0.0001). This female excess was found across countries with widely differing myocardial infarction mortality rates in women (interquartile range 12.7 to 126.5 per 100 000), was particularly high in the American studies (1.40, 95% CI 1.28 to 1.52), and was higher among nonwhite ethnic groups than among whites. This sex ratio did not differ significantly by participant’s age, the year the survey began, or the sex ratio for mortality due to myocardial infarction.

Conclusions—

Over time and at different ages, independent of diagnostic and treatment practices, women have a similar or slightly higher prevalence of angina than men across countries with widely differing myocardial infarction mortality rates.
Vascular Remodeling and Duration of Hypertension Predict Outcome of Adrenalectomy in Primary Aldosteronism Patients
Authors: Rossi Gian Paolo , Bolognesi Massimo , Rizzoni Damiano , Seccia Teresa M. , Piva Anna , Porteri Enzo , Tiberio Guido A.M. , Giulini Stefano M. , Agabiti-Rosei Enrico , Pessina Achille C.
Published: March 2008

Remodeling of the resistance arteries is a hallmark of arterial hypertension and predicts cardiovascular events, but it was unknown whether it could also predict the blood pressure response to adrenalectomy of patients with an aldosterone-producing adenoma. Therefore, we investigated the outcome of adrenalectomy as a function of vascular remodeling in the context of the preoperative features of aldosterone-producing adenoma patients. At 2 referral centers for hypertension, we prospectively measured the media:lumen ratio of small arteries from fat tissue of 50 consecutive aldosterone-producing adenoma patients treated with adrenalectomy. The blood pressure response to adrenalectomy was assessed by considering the blood pressure values and the number and dosages of antihypertensive medications. Adrenalectomy significantly (
P
<0.001) lowered plasma aldosterone (from 27.3±4.9 ng/dL to 8.3±11.2 ng/dL), the aldosterone:renin ratio (from 117±35 to 11±2), and blood pressure (from 163±22/98±2 mm Hg to 133±2/84±1 mm Hg), even despite a reduction (from 141±14 to 100±15;
P
=0.02) of the score of antihypertensive treatment. It provided cure of hypertension in 30% of the aldosterone-producing adenoma patients, normotension with less antihypertensive therapy in 52%, and improved blood pressure control in the rest. The media:lumen ratio and the known duration of hypertension significantly predicted the blood pressure response to adrenalectomy at univariate and multivariate analyses. Because a long duration of hypertension and/or the presence of vascular remodeling imply lower chances of blood pressure normalization at long-term follow-up postadrenalectomy, these findings emphasize the importance of an early diagnosis of aldosterone-producing adenoma.
Policy Concertation in Europe
Authors: Baccaro Lucio , Simoni Marco
Published: March 2008

This article focuses on the European governments' decision to involve unions and employers in the design and implementation of public policy. Based on new measures of the phenomenon, the authors argue that between 1974 and 2003, no convergence on a pluralist model of policy formation is visible. They then use these measures to identify and analyze the clearest cases of adoption or demise of concertation, namely, the contrasting responses of the British and Irish governments to wage policy and of the Austrian and Italian governments to pension reform. They argue that governments are willing to share their policy-making prerogatives when they are politically weak and when unions, while still representing a credible threat to policy implementation, have been declining in the recent past. A combination of partisanship and policy learning reinforces the push for change.
Values, Interests, and the Capacity to Act
Authors: Detert James R. , Pollock Timothy G.
Published: March 2008

This article uses a longitudinal, multimethod, comparative case study of teachers' behavioral and cognitive reactions to the implementation of Total Quality Management (TQM) in two U.S. high schools to explore professionals' reactions to change in a highly institutionalized environment. Detailed analyses using the metathemes of teachers' values, personal interests, and capacity for change revealed that teachers held positive views about most aspects of the change initiative but that personal interests and capacity issues limited their implementation. The findings also suggest that in neither school have changes become cognitively institutionalized, or self-sustaining, despite different levels of coercion coming from multiple levels of the schools' complex institutional environments and different patterns of actual practice change across the schools. The results contribute to a variety of literatures interested in explaining stability and change in highly institutionalized settings (e.g., neoinstitutional, professions, identity).
The International Law and Politics of Climate Change
Authors: von Stein Jana
Published: March 2008

A considerable challenge for the creators of international environmental agreements is how to design mechanisms that deter defection without deterring participation. Relatively ``soft'' law often garners widespread participation, but it creates few concrete incentives for states to improve behavior. ``Harder'' commitments make shirking more difficult, but these institutional features may deter from joining the very states whose practices are least consistent with the treaty's requirements. Empirical analyses of ratification of the core agreements of the climate change regime support these propositions. Flexibility provisions provide one mechanism for states to mitigate this dilemma. The findings with regard to one flexibility mechanism strongly support this argument. The results with regard to a second flexibility mechanism, however, tend to follow an opposite pattern. The author offers a preliminary interpretation of this finding. Finally, this article provides insight into how international social networks and the strength of domestic nongovernmental organizations affect ratification.
Beyond the Numbers
Authors: Varghese Joe , Aruldas Vijay , Jeemon Panniyammakal
Published: March 2008

The last few census reports in India increasingly indicate a high male sex ratio among children in different parts of the country. A study was conducted to examine the trends in the sex ratio at birth of hospital deliveries in the state of Delhi, and their relation with various demographic and socio-economic factors. The study was based on the data available with the birth records of eight large hospitals in Delhi. Birth data of one of the hospitals was analysed in detail. Births were the unit of analysis and SRB based on hospital birth was the indicator for sex-selection practices. A 10-year study of SRB of hospitalised deliveries showed sharp increasing trends in masculinity from the beginning of the study period. Results also indicated intense son preference, resulting in sex selection, particularly if earlier children were girls. Any rigorous measures for control of population growth in India would be disastrous for the sex ratio at birth.
More sophisticated thermodynamic designs of welds between dissimilar steels
Authors: Sopoušek J. , Foret R.
Published: March 2008

In the present paper, steels that are mostly used in technical practice as base materials, filler metals and consumable electrodes in the design of dissimilar weld joints are studied. These steels differ mainly in the content of Cr, Mo, V, W and N. It is explained and emphasised in the present paper that the effect of thermodynamics, diffusion and phase transformations on the stability of dissimilar weld joints that are exposed to temperatures of over ∼500°C cannot be underrated during operation. For all the materials under study the carbon activity at 600°C is given as calculated by the CALPHAD method, and a correlation is shown to exist between the carbon activity and the total chromium content. This correlation can be used as a most general alternative in the selection of filler metals or consumable electrodes in the design of dissimilar weld joints. The primary goal of the present paper is, however, to present a more sophisticated alternative based on a mutual comparison of the temperature dependence of the carbon activities of the base alloys, filler metals and consumable electrodes under consideration. This alternative is suitable for routine engineering purposes. Attention is also drawn to the currently most advanced alternative, which enables the prediction of the redistribution of elements and phases after prolonged exposure.
Magnesium alloy weld using manganese chloride coated wire
Authors: Liu L. M. , Cai D. H. , Zhang Z. D.
Published: March 2008

Magnesium alloy was welded with normal wire and activated flux coated wire. Weld bead penetration, arc voltage, arc profiles and welding arc electronic temperature were researched. Weld bead penetration, arc voltage and welding arc electronic temperature increased when activated flux coated wire was used. It is also found that the welding arc constricted in flux coated wire weld. It is believed that deep weld penetration associated with flux coated wire in this experiment is caused by arc constriction.
Ultrasonic stress evaluation on welded plates with Lcr wave
Authors: Lu H. , Liu X. S. , Yang J. G. , Zhang S. P. , Fang H. Y.
Published: March 2008

The acoustical theory is introduced. Ultrasonic stress measurement experimental installation is established, consisted of a variable angle transducer and an oscillograph with special higher digitiser board. Acoustoelastic coefficient of longitudinal critically refracted waves propagating in Q-235 steel is calibrated by the tensile testing machine. In the present paper are discussed the longitudinal stress and transverse stress on twin wire welded plate, and a comparison is made with the result of finite element method obtained by Marc Software. The present paper also discusses the longitudinal stress distributions of multilayer welded plate and longitudinal residual stress gradient of 2219 Al alloy is obtained in the ultrasonic travel time change expression formal. Instability acoustoelasticity effect in elastic region of welding residual stress field is discovered. The sources of measurement error are pointed out. In conclusion the potential of the ultrasonic method in different industrial cases is particularised.
Effects of weld microstructure on static and impact performance of resistance spot welded joints in advanced high strength steels
Authors: Khan M.I. , Kuntz M.L. , Zhou Y.
Published: March 2008

Evaluating the impact performance of resistance spot welded joints in advanced high strength steels (AHSS) is critical for their continued integration into the automotive architecture. The effect of strain rate on the joint strength and failure mode is an important consideration in the design of welded structures. Recent results suggest that the failure mode is dependent upon the strength, chemistry, and processing of AHSS. Current literature, however, does not explain the effects of weld microstructure and a comprehensive comparison has yet to be conducted. The present study details the fracture paths within the joint microstructure of spot welded AHSS, including dual phase (DP), transformation induced plasticity (TRIP) and ferritic–bainitic (FB), in comparison to new high strength low alloy steels. Quasi-static and impact tests were conducted using a universal tensile tester and an instrumented drop tower respectively. Results for elongation, failure load and energy absorption for each material are presented. Failure modes were detailed by observing weld fracture surfaces. In addition, cross-sections of partially fractured weldments were examined to detail fracture paths during static loading. Correlations between the fracture path and mechanical properties were developed using observed microstructures in the fusion zone and heat affected zone. Results showed that good impact performance was obtained in DP780 and TRIP780 grades in relation to DP600, 590R and conventional high strength low alloy.
Fault identification in gas metal arc welding with signature images
Authors: Simpson S. W.
Published: March 2008

The present work presents a new method for classifying welding faults in real time during gas metal arc welding based on signature images. The through the arc technique classifies faults when they occur during welding. The method is generally applicable and utilises angle measures in the space of the welding signature images to recognise particular faults, accurately identifying them by comparison with the characteristics of known fault signatures in a database which can be extended as new faults appear. Overall, 10 categories representing common industrial faults are considered for pulse welding of a fillet joint. It is shown that the classification technique generalises fault categories in a reasonable way when unknown faults are encountered, and is capable of discriminating between similar faults when necessary. The method can reduce down time due to faults in production welding, as well as providing information which is useful for reducing rates of fault occurrence.
Resistance (mash) seam welding: Influence of welding conditions on tin distribution
Authors: Blom A. H. , Richardson I. M. , Elzinga E. , de Haas M.
Published: March 2008

Mash seam welding involves the rapid production of a continuous weld seam by means of overlapping resistance spot welds. The applicability of the process is known to be dependent on the properties and structure of the welded materials, and for steel can production, is almost always applied to tin coated steels. In the present work, the authors report on an experimental investigation of the influence of welding conditions on tin distribution at and close to the bond interface and discuss the role of the tin coating in the welding process. It is shown that for acceptable welding conditions, tin is either intermittently present on the bond line at lower currents in the range of acceptable welding currents and is absent at higher currents within this range; the majority of tin being extruded to the side of the joint during welding. The tin layer acts both as a protection against corrosion and as an electrical contact medium during the initial stages of the welding process. It is concluded that the displacement of the tin during welding is a sufficient but not a necessary condition for acceptable joint formation.
Phylogenetic position of the langur genera Semnopithecus and Trachypithecus among Asian colobines, and genus affiliations of their species groups
Authors: Osterholz Martin , Walter Lutz , Roos Christian
Published: March 2008

Background

The evolutionary history of the Asian colobines is less understood. Although monophyly of the odd-nosed monkeys was recently confirmed, the relationships among the langur genera Presbytis, Semnopithecus and Trachypithecus and their position among Asian colobines remained unclear. Moreover, in Trachypithecus various species groups are recognized, but their affiliations are still disputed. To address these issues, mitochondrial and Y chromosomal sequence data were phylogenetically related and combined with presence/absence analyses of retroposon integrations.

Results

The analysed 5 kb fragment of the mitochondrial genome allows no resolution of the phylogenetic relationships among langur genera, but five retroposon integrations were detected which link Trachypithecus and Semnopithecus. According to Y chromosomal data and a 573 bp fragment of the mitochondrial cytochrome b gene, a common origin of the species groups T. [cristatus], T. [obscurus] and T. [francoisi] and their reciprocal monophyly is supported, which is also underpinned by an orthologous retroposon insertion. T. [vetulus] clusters within Semnopithecus, which is confirmed by two retroposon integrations. Moreover, this species group is paraphyletic, with T. vetulus forming a clade with the Sri Lankan, and T. johnii with the South Indian form of S. entellus. Incongruence between gene trees was detected for T. [pileatus], in that Y chromosomal data link it with T. [cristatus], T. [obscurus] and T. [francoisi], whereas mitochondrial data affiliates it with the Semnopithecus clade.

Conclusion

Neither relationships among the three langur genera nor their position within Asian colobines can be settled with 5 kb mitochondrial sequence data, but retroposon integrations confirm at least a common origin of Semnopithecus and Trachypithecus. According to Y chromosomal and 573 bp mitochondrial sequence data, T. [cristatus], T. [obscurus] and T. [francoisi] represent true members of the genus Trachypithecus, whereas T. [vetulus] clusters within Semnopithecus. Due to paraphyly of T. [vetulus] and polyphyly of Semnopithecus, a split of the genus into three species groups (S. entellus - North India, S. entellus - South India + T. johnii, S. entellus - Sri Lanka + T. vetulus) seems to be appropriate. T. [pileatus] posses an intermediate position between both genera, indicating that the species group might be the result of ancestral hybridization.
The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome
Authors: Firmann Mathieu , Mayor Vladimir , Vidal Pedro Marques , Bochud Murielle , Pécoud Alain , Hayoz Daniel , Paccaud Fred , Preisig Martin , Song Kijoung S , Yuan Xin , Danoff Theodore M , Stirnadel Heide A , Waterworth Dawn , Mooser Vincent , Waeber Gérard , Vollenweider Peter
Published: March 2008

Background

Cardiovascular diseases and their associated risk factors remain the main cause of mortality in western societies. In order to assess the prevalence of cardiovascular risk factors (CVRFs) in the Caucasian population of Lausanne, Switzerland, we conducted a population-based study (Colaus Study). A secondary aim of the CoLaus study will be to determine new genetic determinants associated with CVRFs.

Methods

Single-center, cross-sectional study including a random sample of 6,188 extensively phenotyped Caucasian subjects (3,251 women and 2,937 men) aged 35 to 75 years living in Lausanne, and genotyped using the 500 K Affymetrix chip technology.

Results

Obesity (body mass index ≥ 30 kg/m2), smoking, hypertension (blood pressure ≥ 140/90 mmHg and/or treatment), dyslipidemia (high LDL-cholesterol and/or low HDL-cholesterol and/or high triglyceride levels) and diabetes (fasting plasma glucose ≥ 7 mmol/l and/or treatment) were present in 947 (15.7%), 1673 (27.0%), 2268 (36.7%), 2113 (34.2%) and 407 (6.6%) of the participants, respectively, and the prevalence was higher in men than in women. In both genders, the prevalence of obesity, hypertension and diabetes increased with age.

Conclusion

The prevalence of major CVRFs is high in the Lausanne population in particular in men. We anticipate that given its size, the depth of the phenotypic analysis and the availability of dense genome-wide genetic data, the CoLaus Study will be a unique resource to investigate not only the epidemiology of isolated, or aggregated CVRFs like the metabolic syndrome, but can also serve as a discovery set, as well as replication set, to identify novel genes associated with these conditions.
Individual case safety reports in children in commonly used drug groups – signal detection
Authors: Brunlöf Gertrud , Tukukino Carina , Wallerstedt Susanna M
Published: March 2008

Background

Due to few paediatric drug safety studies, knowledge on risks of drug treatment in children is limited. The knowledge needs to be increased to make proper risk-benefit analyses possible when treating paediatric patients with drugs. The aim of the present study was to investigate drug groups commonly used in children concerning type and frequency of individual case safety reports in children.

Methods

Number and type of individual case safety reports in the 30 groups of drugs (5th level ATC-code) most sold (number of defined daily doses) in outpatient treatment to children (<15 years old) during 2005 were obtained. Descriptive analyses of the adverse drug reactions reported in children were performed.

Results

The number of individual case safety reports per million defined daily doses in children varied in the groups of drug between 0 and 24. The largest number was found in the drug group R03DC, the leukotriene receptor antagonist montelukast; the majority of the children being <5 years old and experiencing psychiatric adverse drug reactions.

Conclusion

The number of individual case safety reports per million defined daily doses varies in different groups of drugs. A possible signal for montelukast and psychiatric adverse drug reactions was found, which should be further explored.
Increased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatment
Authors: Qin Liya , He Jun , Hanes Richard N , Pluzarev Olivera , Hong Jau-Shyong , Crews Fulton T
Published: March 2008

Background

Cytokines and alcohol share a common modulation of inflammation and hormones as well as being implicated in multiple diseases, but the mechanisms are poorly understood. The purpose of this study was to investigate the interaction of liver, serum and brain cytokines as well as whether ethanol would potentiate endotoxin (Lipopolysaccharide, LPS) responses once ethanol had cleared.

Methods

Male C57BL/6J mice were treated intragastrically with water (control) or ethanol (5 g/kg, i.g., 25% ethanol, w/v), with volumes matched, for 1 day or daily for 10 days. Mice were then injected intraperitoneally with saline (control) or LPS (3 mg/kg, i.p.) in saline 24 hrs after the last dose of ethanol. Gene expression and protein synthesis of proinflammatory cytokines and anti-inflammatory cytokine, oxidative enzymes, microglial activation and inhibition of neurogenesis were examined using real-time PCR, ELISA, and immunohistochemistry.

Results

LPS increased proinflammatory cytokines (TNFα, MCP-1, IL-1β) several fold in liver, brain and serum at 1 hr. Ethanol is known to increase liver cytokines and alter the risk of multiple chronic diseases. Ten daily doses of ethanol increased brain and liver TNFα, and pretreatment with ethanol potentiated LPS-induced increases in TNFα, MCP-1, IL-1βin liver, serum and brain. Proinflammatory cytokine levels in liver and serum returned to basal levels within a day, whereas brain proinflammatory cytokines remained elevated for long periods. IL-10, an anti-inflammatory cytokine, is reduced in brain by ethanol and LPS, while brain proinflammatory cytokines remain increased, whereas liver IL-10 is increased when proinflammatory cytokines have returned to control levels. Activation of brain microglia indicated by morphological changes, reduced neurogenesis and increased brain expression of COX-2 and gp91phoxNADPH oxidase subunit mRNA were found in the 10 daily doses of ethanol-pretreated LPS group.

Conclusion

Acute increases in serum cytokines induce long lasting increases in brain proinflammatory cytokines. Ten daily doses of ethanol exposure results in persistent alterations of cytokines and significantly increases the magnitude and duration of central and peripheral proinflammatory cytokines and microglial activation. Ethanol induced differential anti-inflammatory cytokine IL-10 responses in liver and brain could cause long lasting disruption of cytokine cascades that could contribute to protection or increased risk of multiple chronic diseases.
Complications post renal transplantation: literature focus on BK virus nephropathy and diagnostic tools actually available
Authors: Mischitelli Monica , Bellizzi Anna , Anzivino Elena , Fioriti Daniela , Boldorini Renzo , Miglio Umberto , Chiarini Fernanda , Di Monaco Franco , Pietropaolo Valeria
Published: March 2008

Clinical diagnosis of kidney transplants related illnesses is not a simple task. Several studies were conducted to define diseases and complications after renal transplantation, but there are no comprehensive guidelines about diagnostic tools for their prevention and detection.

The Authors of this review looked for the medical literature and pertinent publications in particular to understand the role of Human Polyomavirus BK (BKV) in renal failure and to recognize analytical techniques for BK virus associated nephropathy (BKVAN) detection.
Managerial and environmental determinants of clinical mastitis in Danish dairy herds
Authors: Sato Kenji , Bartlett Paul C , Alban Lis , Agger Jens F , Houe Hans
Published: March 2008

Background

Several management and environmental factors are known as contributory causes of clinical mastitis in dairy herd. The study objectives were to describe the structure of herd-specific mastitis management and environmental factors and to assess the relevance of these herd-specific indicators to mastitis incidence rate.

Methods

Disease reports from the Danish Cattle Data Base and a management questionnaire from 2,146 herds in three Danish regions were analyzed to identify and characterize risk factors of clinical mastitis. A total of 94 (18 continuous and 76 discrete) management and production variables were screened in separate bivariate regression models. Variables associated with mastitis incidence rate at a p-value < 0.10 were examined with a factor analysis to assess the construct of data. Separately, a multivariable regression model was used to estimate the association of management variables with herd mastitis rate.

Results

Three latent factors (quality of labor, region of Denmark and claw trimming, and quality of outdoor holding area) were identified from 14 variables. Daily milk production per cow, claw disease, quality of labor and region of Denmark were found to be significantly associated with mastitis incidence rate. A common multiple regression analysis with backward and forward selection procedures indicated there were 9 herd-specific risk factors.

Conclusion

Though risk factors ascertained by farmer-completed surveys explained a small percentage of the among-herd variability in crude herd-specific mastitis rates, the study suggested that farmer attitudes toward mastitis and lameness treatment were important determinants for mastitis incidence rate. Our factor analysis identified one significant latent factor, which was related to labor quality on the farm.
Molecular Characteristics of Bronchioloalveolar Carcinoma and Adenocarcinoma, Bronchioloalveolar Carcinoma Subtype, Predict Response to Erlotinib
Authors: Miller Vincent A. , Riely Gregory J. , Zakowski Maureen F. , Li Allan R. , Patel Jyoti D. , Heelan Robert T. , Kris Mark G. , Sandler Alan B. , Carbone David P. , Tsao Anne , Herbst Roy S. , Heller Glenn , Ladanyi Marc , Pao William , Johnson David H.
Published: March 2008

Purpose

We conducted this phase II trial to determine the efficacy of erlotinib in patients with bronchioloalveolar carcinoma (BAC) and adenocarcinoma, BAC subtype, and to determine molecular characteristics associated with response.

Patients and Methods

Patients (n = 101) with BAC (n = 12) or adenocarcinoma, BAC subtype (n = 89), were enrolled. All patients received erlotinib 150 mg daily. Epidermal growth factor receptor (EGFR) mutation, EGFR copy number, EGFR immunohistochemistry (IHC), and KRAS mutation status were analyzed in available tumors. The primary end point was response rate (RR).

Results

Overall RR was 22% (95% CI, 14% to 31%). In patients with pure BAC, the RR and median survival were 20% and 4 months, as compared with 23% and 19 months in those with adenocarcinoma, BAC subtype. No patient (zero of 18; 95% CI, 0% to 19%) whose tumor harbored a KRAS mutation responded to erlotinib. Patients with EGFR mutations had an 83% RR (15 of 18; 95% CI, 65% to 94%) and 23-month median OS. On univariate analysis, EGFR mutation and copy number were associated with RR and PFS. EGFR IHC was not associated with RR or progression-free survival (PFS). After multivariate analysis, only EGFR mutation was associated with RR and PFS. No molecular factors were associated with overall survival.

Conclusion

Erlotinib is active in BAC and adenocarcinoma, mixed subtype, BAC. Testing for EGFR and KRAS mutations can predict RR and PFS after treatment with erlotinib in this histologically enriched subset of patients with non–small-cell lung cancer (NSCLC). These data suggest that histologic subtype and molecular characteristics should be reported in clinical trials in NSCLC using EGFR-directed therapy.
Randomization Reveals Unexpected Acute Leukemias in Southwest Oncology Group Prostate Cancer Trial
Authors: Flaig Thomas W. , Tangen Catherine M. , Hussain Maha H.A. , Stadler Walter M. , Raghavan Derek , Crawford E. David , Glodé L. Michael
Published: March 2008

Purpose

Southwest Oncology Group (SWOG) study 9921 is a randomized, phase III, intergroup study to define the role of adjuvant chemotherapy in patients with high-risk prostate cancer.

Patients and Methods

We allocated 983 patients with prostate cancer with high-risk features to receive 2 years of androgen-deprivation therapy (ADT) with or without six cycles of mitoxantrone (12 mg/m2) after prostatectomy.

Results

In January 2007, SWOG 9921 was closed to further accrual after three cases of acute myelogenous leukemia (AML) were reported of a total of 487 patients in the mitoxantrone treatment arm. The key cytogenetic features of these cases included inv(16) in the first case, t(15;17) in the second, and del(5) in the third case. Time from the start of mitoxantrone to the detection of AML was 13, 48, and 72 months, respectively. Before SWOG 9921, there were no cases of mitoxantrone-induced AML reported in patients treated for prostate cancer.

Conclusion

The emergence of this possible pattern of secondary malignancy emphasizes the importance of randomized controlled trials in defining safety and efficacy of new approaches for patients in the adjuvant setting.
Prognostic Value of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography Imaging in Patients With Advanced-Stage Non–Small-Cell Lung Carcinoma
Authors: Hoang Jenny K. , Hoagland Luke F. , Coleman R. Edward , Coan April D. , Herndon James E. , Patz Edward F.
Published: March 2008

Purpose

To determine whether the amount of fluorine-18 fluorodeoxyglucose (FDG) uptake in the primary lung cancer on positron emission tomography (PET) imaging at the time of presentation has prognostic significance in patients with advanced-stage non–small-cell lung cancer (NSCLC).

Patients and Methods

A retrospective review identified 214 patients with advanced-stage NSCLC (stage IIIA, IIIB, and IV) who underwent FDG PET study at the time of diagnosis. Extensive clinical data, including tumor histologic cell type, pathologic stage at presentation, and treatment, were recorded. The maximum standardized uptake value (SUVmax) in the primary tumor on FDG PET on survival was examined using Cox proportional hazards regression.

Results

One hundred fifty-eight (74%) of the 214 patients died and 56 patients were reported alive at 27 months (range, 3 to 140 months) after the diagnosis of NSCLC. Using the median SUVmaxof 11.1, the patient population was subdivided. The median survival of the 106 patients with the primary tumor having an SUVmaxless than 11.1 was 16 months (95% CI, 12 to 21 months), whereas the median survival of the 108 patients with the primary tumor having an SUVmax≥ 11.1 was 12 months (95% CI, 10 to 15 months). Univariate and multivariate analysis did not provide evidence that survival for patient subgroups defined by the median SUVmaxwere significantly different (univariate P = .11; multivariate P = .45).

Conclusion

FDG uptake of the primary lesions in patients with a new diagnosis of advanced-stage NSCLC does not have a significant relationship with survival.
Phase II Trial of Pemetrexed and Gemcitabine in Chemotherapy-Naïve Malignant Pleural Mesothelioma
Authors: Jänne Pasi A. , Simon George R. , Langer Corey J. , Taub Robert N. , Dowlati Afshin , Fidias Panos , Monberg Matthew , Obasaju Coleman , Kindler Hedy
Published: March 2008

Purpose

Pemetrexed and gemcitabine have single-agent activity in malignant pleural mesothelioma (MPM). The combination of pemetrexed/gemcitabine has not previously been studied in MPM to our knowledge.

Patients and Methods

Patients with histologic or cytologic diagnosis of MPM were included. Cohort 1 received gemcitabine 1,250 mg/m2on days 1 and 8, with pemetrexed 500 mg/m2on day 8, and cohort 2 received gemcitabine 1,250 mg/m2on days 1 and 8, with pemetrexed 500 mg/m2on day 1. Cycles were repeated every 21 days; all patients were supplemented with folic acid and vitamin B12and received dexamethasone.

Results

One hundred eight patients (cohort 1, n = 56; cohort 2, n = 52) with pleural mesothelioma were enrolled. Among assessable patients, response rate was 26.0% in cohort 1 and 17.1% in cohort 2. Median time to disease progression was 4.34 months for cohort 1 and 7.43 months for cohort 2. Median survival was 8.08 months for cohort 1 (1-year survival = 31.14%) and 10.12 months for cohort 2 (1-year survival = 45.80%). In cohorts 1 and 2, incidence of grade 4 neutropenia was 25.0% and 29.4%, grade 4 thrombocytopenia was 14.3% and 3.9%, grade 3 or 4 anemia was 5.4% and 5.9%, and grade 3 or 4 fatigue was 23.2% and 15.7%, respectively.

Conclusion

The combination of pemetrexed and gemcitabine resulted in moderate clinical activity in MPM. However, the median survival times are similar to those with single-agent pemetrexed and inferior to outcomes observed with cisplatin in combination with an antifolate.
Improved Staging of Patients With Carcinoid and Islet Cell Tumors With 18F-Dihydroxy-Phenyl-Alanine and 11C-5-Hydroxy-Tryptophan Positron Emission Tomography
Authors: Koopmans Klaas P. , Neels Oliver C. , Kema Ido P. , Elsinga Philip H. , Sluiter Wim J. , Vanghillewe Koen , Brouwers Adrienne H. , Jager Pieter L. , de Vries Elisabeth G.E.
Published: March 2008

Purpose

To evaluate and compare diagnostic sensitivity of positron emission tomography (PET) scanning in carcinoid and islet cell tumor patients with a serotonin and a catecholamine precursor as tracers.

Patients and Methods

Carcinoid (n = 24) or pancreatic islet cell tumor (n = 23) patients with at least one lesion on conventional imaging including somatostatin receptor scintigraphy (SRS) and computed tomography (CT) scan underwent 11C-5-hydroxytryptophan (11C-5-HTP) PET and 6-[F-18]fluoro-L-dihydroxy-phenylalanin (18F-DOPA) PET. PET findings were compared with a composite reference standard derived from all available imaging along with clinical and cytologic/histologic information.

Results

In carcinoid tumor patients, per-patient analysis showed sensitivities for 11C-5-HTP PET, 18F-DOPA PET, SRS, and CT of 100%, 96%, 86%, 96%, respectively, and in islet cell tumors of 100%, 89%, 78%, 87%, respectively. In carcinoid patients, per-lesion analysis revealed sensitivities for 11C-5-HTP PET, 11C-5-HTP PET/CT, 18F-DOPA PET, 18F-DOPA PET/CT, SRS, SRS/CT, and CT alone of, respectively, 78%, 89%, 87%, 98%, 49%, 73%, and 63% and in islet cell tumors of 67%, 96%, 41%, 80%, 46%, 77%, and 68%, respectively. In all carcinoid patients 18F-DOPA PET and 11C-5-HTP PET detected more lesions than SRS (P < .001). 11C-5-HTP PET was superior to 18F-DOPA PET in islet cell tumors (P < .0001). In all cases, CT improved the sensitivity of the nuclear scans.

Conclusion

18F-DOPA PET/CT is the optimal imaging modality for staging in carcinoid patients and 11C-5-HTP PET/CT in islet cell tumor patients.
Complex Formation between a Nucleobase and Tetracyanoquinodimethane Derivatives: Crystal Structures and Transport Properties of Charge-Transfer Solids of Cytosine
Authors: Murata Tsuyoshi , Saito Gunzi , Nishimura Kazukuni , Enomoto Yuichiro , Honda Genki , Shimizu Yasuhito , Matsui Shogo , Sakata Masafumi , Drozdova Olga O , Yakushi Kyuya
Published: March 2008

Reaction between cytosine, a nucleobase, in methanol and several 7,7,8,8-tetracyanoquinodimethane derivatives (R-TCNQ) in acetonitrile yielded three kinds of ionic solids; (I) insulators composed of methoxy-substituted R-TCNQ anions, (II) semiconducting fully ionic R-TCNQ radical anion salts, and (III) conductive partially ionic or mixed-valent R-TCNQ radical anion salts. Electronic and chemical structures of these products were characterized by optical and magnetic measurements, and structural and elemental analyses. Cation units in all products were found to be protonated cytosine species. Crystal structures were determined for methoxy-substituted anion salts (R = F4 and H) in Group I and R-TCNQ radical anion salts (R = H and Et2) in Group II with hemiprotonated cytosine pairs formed by triple self-complementary hydrogen bonds. They established one-dimensional hemiprotonated cytosine ribbons by double complementary hydrogen bonds. Hydrogen bonds between cytosine and R-TCNQ anions exhibited high potential to regulate molecular arrangements producing a segregated layered structure and uniform arrangement of R-TCNQ radical anion columns stable down to low temperature. The partially ionic salt of MeTCNQ in Group III exhibited metallic behavior and the highest conductivity of 10+1 S cm−1 so far observed for charge-transfer complexes based on biological molecules.
Synthesis and Structural Characterization of Dinuclear Manganese(III) Complexes with Cyclam-Based Macrocyclic Ligands Having Schiff-Base Pendant Arms as Chelating Agents
Authors: Wada Shusaku , Mikuriya Masahiro
Published: March 2008

Reaction of a series of dodecadentate ligands (H4L), 1,4,8,11-tetrakis(salicylideneaminoethyl)-1,4,8,11-tetraazacyclotetradecane and its substituted derivatives, with manganese(II) salts afforded ten dinuclear manganese(III) complexes, [Mn2X2L] (X = O2CCH3, O2CC6H5, and N3), which were characterized by analyzing infrared and electronic spectra and determining the temperature dependence of magnetic susceptibilities (4.5–300 K). Single-crystal X-ray crystallography of [Mn2(O2CCH3)2(tbsaec)]·2CHCl3 (3·2CHCl3) (H4tbsaec = 1,4,8,11-tetrakis(5-bromosalicylideneaminoethyl)-1,4,8,11-tetraazacyclotetradecane), [Mn2(O2CC6H5)2(tbsaec)] (4), [Mn2(O2CC6H5)2(tcsaec)] (6) (H4tcsaec = 1,4,8,11-tetrakis(5-chlorosalicylideneaminoethyl)-1,4,8,11-tetraazacyclotetradecane), [Mn2(N3)2(tnaec)]·2CHCl3 (7·2CHCl3) (H4tnaec = 1,4,8,11-tetrakis(2-hydroxy-1-naphthylmethylideneaminoethyl)-1,4,8,11-tetraazacyclotetradecane), [Mn2(O2CCH3)2(tmsaec)] (8) (H4tmsaec = 1,4,8,11-tetrakis(3-methoxysalicylideneaminoethyl)-1,4,8,11-tetraazacyclotetradecane) showed that each manganese(III) ion is chelated by two Schiff-base pendant arms outside the central tetraazacyclotetradecane ring, forming an axially compressed octahedron (for 3, 4, 6, and 8) or trigonal bipyramid (for 7) with an intramolecular Mn–Mn distance of 9.676(4)–10.096(2) Å. In accordance with the crystal structures, the magnetic interaction between the two manganese ions was very weak with a rather significant zero-field splitting of the manganese(III) ions.
Structure of a Barium(II) Complex Sandwiched by a Schiff Base Macrocycle
Authors: Tsukuda Toshiaki , Maeda Satsuki , Yasui Masahiko , Tamane Takeshi , Tsubomura Taro
Published: March 2008

A barium complex sandwiched by an octaaza Schiff base macrocycle prepared by [2+2] condensation of diimine and phenanthroline dicarbaldehyde has been studied; the ten-coordinate structure of the complex and increase of absorption intensity on coordination has been revealed.
Silylcupration and Copper-Catalyzed Carbomagnesiation of Ynamides: Application to Aza-Claisen Rearrangement
Authors: Yasui Hiroto , Yorimitsu Hideki , Oshima Koichiro
Published: March 2008

Treatment of ynamides with silylcopper reagents resulted in silylcupration to afford (E)-β-silylenamides, after protonolysis, in good yields with high regio- and stereoselectivity. Reaction of ynamides having an allyl group on the nitrogen with Grignard reagents in the presence of a copper catalyst resulted in carbomagnesiation across the alkynyl unit and subsequent heating provided 4-pentenenitriles via aza-Claisen rearrangement.
Functionalization of Multi-Walled Carbon Nanotubes Realized by Microwave-Driven Chemistry Inducing Dispersibility in Liquid Media
Authors: Tsukahara Yasunori , Yamauchi Tomohisa , Kawamoto Tadashi , Wada Yuji
Published: March 2008

Carboxyl groups have been successfully introduced to multi-walled carbon nanotubes by oxidation with a nitric acid or sodium hypochlorite aqueous solution under microwave irradiation. The introduced functional groups have been employed as a reactive terminus for introducing long alkyl chains to the surface of the nanotubes. The dispersibility in various solvents having different polarities can be controlled by the surface functionalization.
A Close-packed, Highly Insulating Organic Thin Monolayer on Si(111)
Authors: Tanaka Kentaro , Tanaka Taishi , Hasegawa Takeshi , Shionoya Mitsuhiko
Published: March 2008

A long-chain dialkylated olefin, 2C18 was found to form a close-packed, highly insulating self-assembled monolayer (SAM) on Si(111) via Si–C bond formation. The IR absorption spectra of the 2C18-SAM show that the alkyl chains are densely packed with an all-trans conformation. The threshold voltage to initiate the scanned probe oxidation (SPO) of the 2C18-SAM-covered Si(111) was ca. 9 V, which is much higher than the previously reported voltages for organic monolayers on Si or SiO2/Si substrates.
Primary prevention of coronary heart disease in women
Authors: Rees Margaret , Stevenson John
Published: March 2008

The British Menopause Society Council is committed to provide up-to-date authoritative reviews to aid health professionals to inform and advise women about key issues in post reproductive health. Coronary heart disease (CHD) is a leading cause of death in women. Observational studies have consistently shown estrogen to help prevent CHD in postmenopausal women. The large randomized controlled Women's Health Initiative (WHI) trial did not confirm these observational findings. However, further analyses of the WHI study as well as the observational Nurses’ Health Study have now found that the timing of onset of hormone replacement therapy (HRT) use is important and that estrogen may have a protective role in CHD in women aged 50–59 years. This consensus statement will examine the evidence regarding HRT and non-estrogen therapies (lipid lowering agents, aspirin, antihypertensives, antidiabetic medications, selective estrogen receptor modulators [SERMs]) as well as diet, lifestyle and smoking cessation in the primary prevention of CHD in women.
Scientific Consensus on Climate Change?
Authors: Schulte Klaus-Martin
Published: March 2008

Fear of anthropogenic “global warming” can adversely affect patients' well-being. Accordingly, the state of the scientific consensus about climate change was studied by a review of the 539 papers on “global climate change” found on the Web of Science database from January 2004 to mid-February 2007, updating research by Oreskes, who had reported that between 1993 and 2003 none of 928 scientific papers on “global climate change” had rejected the consensus that more than half of the warming of the past 50 years was likely to have been anthropogenic. In the present review, 31 papers (6% of the sample) explicitly or implicitly reject the consensus. Though Oreskes said that 75% of the papers in her former sample endorsed the consensus, fewer than half now endorse it. Only 7% do so explicitly. Only one paper refers to “catastrophic” climate change, but without offering evidence. There appears to be little evidence in the learned journals to justify the climate-change alarm that now harms patients.
Climate Protection Policy in Germany: Facing up to the Data
Authors: Kübler Knut
Published: March 2008

The year 2006 offered us the opportunity to obtain clarity about whether, and to which extent, the German government has remained faithful to the goals of the climate policy it set at the beginning of the nineties. Present data only show a decline of energy-induced CO2 emissions in Germany's old states of some 28 million t (or 4%) from 1990 to 2005. This means that the 25% emissions reduction target set by the German government back in 1990 – before reunification – has been missed by a wide margin. Thoughts on re-orientating climate-protection policy in Germany and placing greater emphasis on promoting the research and development of modern energy technologies are presented here.
Calcitonin Receptor Plays a Physiological Role to Protect Against Hypercalcemia in Mice
Authors: Davey Rachel A , Turner Andrew G , McManus Julie F , Chiu WS Maria , Tjahyono Francisca , Moore Alison J , Atkins Gerald J , Anderson Paul H , Ma Cathy , Glatt Vaida , MacLean Helen E , Vincent Cristina , Bouxsein Mary , Morris Howard A , Findlay David M , Zajac Jeffrey D
Published: March 2008

It is well established that calcitonin is a potent inhibitor of bone resorption; however, a physiological role for calcitonin acting through its cognate receptor, the calcitonin receptor (CTR), has not been identified. Data from previous genetically modified animal models have recognized a possible role for calcitonin and the CTR in controlling bone formation; however, interpretation of these data are complicated, in part because of their mixed genetic background. Therefore, to elucidate the physiological role of the CTR in calcium and bone metabolism, we generated a viable global CTR knockout (KO) mouse model using the Cre/loxP system, in which the CTR is globally deleted by >94% but <100%. Global CTRKOs displayed normal serum ultrafiltrable calcium levels and a mild increase in bone formation in males, showing that the CTR plays a modest physiological role in the regulation of bone and calcium homeostasis in the basal state in mice. Furthermore, the peak in serum total calcium after calcitriol [1,25(OH)2D3]-induced hypercalcemia was substantially greater in global CTRKOs compared with controls. These data provide strong evidence for a biological role of the CTR in regulating calcium homeostasis in states of calcium stress.