bluuebunny/crossref_metadata_2025 huggingface dataset:
Generic, Simple Risk Stratification Model for Heart Valve Surgery
Authors: Ambler Gareth , Omar Rumana Z. , Royston Patrick , Kinsman Robin , Keogh Bruce E. , Taylor Kenneth M.
Published: July 2005

Background—

Heart valve surgery has an associated in-hospital mortality rate of 4% to 8%. This study aims to develop a simple risk model to predict the risk of in-hospital mortality for patients undergoing heart valve surgery to provide information to patients and clinicians and to facilitate institutional comparisons.

Methods and Results—

Data on 32 839 patients were obtained from the Society of Cardiothoracic Surgeons of Great Britain and Ireland on patients who underwent heart valve surgery between April 1995 and March 2003. Data from the first 5 years (n=16 679) were used to develop the model; its performance was evaluated on the remaining data (n=16 160). The risk model presented here is based on the combined data. The overall in-hospital mortality was 6.4%. The risk model included, in order of importance (all
P
<0.01), operative priority, age, renal failure, operation sequence, ejection fraction, concomitant tricuspid valve surgery, type of valve operation, concomitant CABG surgery, body mass index, preoperative arrhythmias, diabetes, gender, and hypertension. The risk model exhibited good predictive ability (Hosmer-Lemeshow test,
P
=0.78) and discriminated between high- and low-risk patients reasonably well (receiver-operating characteristics curve area, 0.77).

Conclusions—

This is the first risk model that predicts in-hospital mortality for aortic and/or mitral heart valve patients with or without concomitant CABG. Based on a large national database of heart valve patients, this model has been evaluated successfully on patients who had valve surgery during a subsequent time period. It is simple to use, includes routinely collected variables, and provides a useful tool for patient advice and institutional comparisons.
Inhibition of Polymorphonuclear Leukocyte–Mediated Graft Damage Synergizes With Short-Term Costimulatory Blockade to Prevent Cardiac Allograft Rejection
Authors: El-Sawy Tarek , Belperio John A. , Strieter Robert M. , Remick Daniel G. , Fairchild Robert L.
Published: July 2005

Background—

The early inflammatory response during reperfusion of cardiac allografts is initiated by the infiltration of polymorphonuclear leukocytes (PMNs) into the graft. The impact of early PMN infiltration on allograft rejection compared with long-term graft survival remains poorly understood.

Methods and Results—

We tested the role of CXCR2, the receptor for 2 PMN attractant chemokines, KC/CXCL1 and MIP-2/CXCL2, on intragraft inflammation and vascularized cardiac allograft rejection in a murine model. Compared with allografts retrieved from control recipients, both PMN infiltration and intragraft proinflammatory cytokine expression were significantly attenuated in allografts from CXCR2-antisera–treated wild-type or from CXCR2
−/−
recipients. Adoptive transfer of alloantigen-primed T cells rapidly infiltrated and rejected allografts in control recipients, but T-cell infiltration was significantly decreased in recipients depleted of PMNs at transplantation. The influence of early PMN-mediated inflammation on the therapeutic efficacy of costimulatory blockade to prevent allograft rejection was tested. Short-term treatment of recipients with anti-CD154 mAb or CTLA-4 Ig induced modest prolongation of cardiac allograft survival. However, CD154 mAb or CTLA-4 Ig treatment, combined with either peritransplantation PMN depletion or antibodies specific for KC/CXCL1 plus MIP-2/CXCL2, prolonged cardiac allograft survival beyond 100 days.

Conclusions—

Results suggest that strategies attenuating PMN-mediated tissue damage during reperfusion significantly improve the efficacy of short-term costimulatory blockade to prevent T-cell–mediated rejection of cardiac allografts.
Exercise Testing in Asymptomatic Adults
Authors: Lauer Michael , Froelicher Erika Sivarajan , Williams Mark , Kligfield Paul
Published: July 2005

Along with coronary artery calcium scanning, ankle-brachial index measurement, and carotid artery ultrasound, exercise electrocardiography has been proposed as a screening tool for asymptomatic subjects thought to be at intermediate risk for developing clinical coronary disease. A wealth of data indicate that exercise testing can be used to assess and refine prognosis, particularly when emphasis is placed on nonelectrocardiographic measures such as exercise capacity, chronotropic response, heart rate recovery, and ventricular ectopy. Nevertheless, randomized trial data on the clinical value of screening exercise testing are absent; that is, it is not known whether a strategy of routine screening exercise testing in selected subjects reduces the risk for premature mortality or major cardiac morbidity. The writing group believes that a large-scale randomized trial of such a strategy should be performed.
Targeted Deletion of Fgl-2/Fibroleukin in the Donor Modulates Immunologic Response and Acute Vascular Rejection in Cardiac Xenografts
Authors: Mendicino Michael , Liu MingFeng , Ghanekar Anand , He Wei , Koscik Cheryl , Shalev Itay , Javadi Mojib , Turnbull Julie , Chen Wenhao , Fung Laisum , Sakamoto Seisuke , Marsden Phillip , Waddell Thomas K. , Phillips M. James , Gorczynski Reginald , Levy Gary A. , Grant David
Published: July 2005

Background—

Xenografts ultimately fail as a result of acute vascular rejection (AVR), a process characterized by intravascular thrombosis, fibrin deposition, and endothelial cell activation.

Methods and Results—

We studied whether targeted deletion of Fgl-2, an inducible endothelial cell procoagulant, (Fgl-2
−/−
) in the donor prevents AVR in a mouse-to-rat cardiac xenotransplantation model. By 3 days after transplant, Fgl-2
+/+
grafts developed typical features of AVR associated with increased levels of donor Fgl-2 mRNA. Grafts from Fgl-2
−/−
mice had reduced fibrin deposition but developed cellular rejection. Treatment with a short course of cobra venom factor and maintenance cyclosporine resulted in long-term acceptance of both Fgl-2
+/+
and Fgl-2
−/−
grafts. On withdrawal of cyclosporine, Fgl-2
+/+
grafts developed features of AVR; in contrast, Fgl-2
−/−
grafts again developed acute cellular rejection. Rejecting Fgl-2
+/+
hearts stained positively for IgG, IgM, C3, and C5b-9, whereas rejecting Fgl-2
−/−
hearts had minimal Ig and complement deposition despite xenoantibodies in the serum. Furthermore, serum containing xenoantibodies failed to stain Fgl-2
−/−
long-term treated hearts but did stain wild-type heart tissues. Treatment of Fgl-2
−/−
xenografts with mycophenolate mofetil and tacrolimus, a clinically relevant immune suppression protocol, led to long-term graft acceptance.

Conclusions—

Deletion of Fgl-2 ameliorates AVR by downregulation of xenoantigens and may facilitate successful clinical heart xenotransplantation.
Who Is Trying to Keep What Secret from Whom and Why? MI5-FBI Relations and the Klaus Fuchs Case
Authors: Goodman Michael S.
Published: July 2005

Klaus Fuchs was one of the most infamous spies of the Cold War, whose espionage feats altered the nature of the early postwar period. Drawing on newly released archival documents and witness testimony, this article considers the events surrounding his arrest and conviction. These sources reveal that even before Fuchs was arrested, he was used as a pawn.Because of his supreme importance to the British nuclear weapons program, some British of ficials initially believed that he should remain in his position, despite his admission of guilt. Until the matter was resolved, Fuchs was used unwittingly as a wedge between the British and U.S. intelligence services.Moreover, when the United States criticized British security standards, the Fuchs case was used by MI5 to cajole and mislead Parliament and the public.
Happiness as a Belief System: Individual Differences and Priming in Emotion Judgments
Authors: Robinson Michael D. , Kirkeby Ben S.
Published: July 2005

Three studies involving 104 undergraduates sought to examine how an individual’s level of life satisfaction organizes their knowledge concerning the self’s emotions. Participants judged the self’s positive and negative emotions within a computerized task. Key results sought to determine whether judging two positive emotions in a consecutive sequence speeds the second judgment—a pattern of priming that would suggest a tighter, more interconnected structure in semantic memory related to one’s positive emotions. As expected, individual differences in life satisfaction predicted the magnitude of this priming effect (Studies 1 & 2), which appeared to be unique to judgments of the self’s emotions (Study 3). The results indicate that happy, relative to less happy, individuals organize information concerning their positive emotions in a qualitatively different and tighter semantic manner.
The Apple Does Not Fall Far From the Tree: Attachment Styles and Personality Vulnerabilities to Depression in Three Generations of Women
Authors: Besser Avi , Priel Beatriz
Published: July 2005

The intergenerational transmission of attachment insecurity was examined in a community sample of 300 participants consisting of 100 three-generation triads of women. It was hypothesized that personality vulnerabilities mediate the association between attachment insecurity and depression within each generation. Findings show significant intergenerational congruence of trait vulnerabilities and attachment styles. Moreover, the second generation’s attachment dimensions and personality vulnerabilities were found to mediate the association between first- and third-generation scores on attachment and vulnerability variables. Findings supported the following hypothesized within- and between-generation paths: Within generations, self-criticism was found to mediate the association between attachment insecurity and depression; between generations, depression, but not self-criticism, mediated the association between assessments of attachment insecurity in mothers and their daughters. This study constitutes a first approach to the delineation of the role played by self-criticism in the association between negative models of the self and depression across generations.
When Subgroups Secede: Extending and Refining the Social Psychological Model of Schism in Groups
Authors: Sani Fabio
Published: July 2005

This article is about a field study (N = 1,080) concerning the secession of a subgroup from the Church of England, and it is aimed at extending and refining the existing social psychological model of schisms in groups. It was found that the first step toward a schism is the belief that the group identity has been subverted. This belief will prompt negative emotions (i.e., dejection and agitation) and decrease both group identification and perceived group entitativity (i.e., cohesion, oneness). In turn, low group entitativity will reduce the level of group identification. Finally, low group identification and high negative emotions will increase schismatic intentions. It is also demonstrated that the negative impact of group identification, and the positive impact of negative emotions, on schismatic intentions is moderated by the perceived ability to voice dissent (i.e., the greater the perceived voice, the weaker the impact).
Do Automatic Reactions Elicited by Thoughts of Romantic Partner, Mother, and Self Relate to Adult Romantic Attachment?
Authors: Zayas Vivian , Shoda Yuichi
Published: July 2005

Three studies tested the expectation that automatic reactions elicited by the mental representation of one’s current romantic partner, mother, and self relate to adult romantic attachment. Adult romantic attachment was assessed using multiple measures, and individual differences in automatic reactions were assessed by the Implicit Association Test (IAT). Studies 1 and 2 showed that automatic reactions elicited by thoughts of current romantic partner, but not by thoughts of self, were related to adult romantic attachment assessed at a specific (i.e., within one’s current romantic relationship) and general level (i.e., across all romantic relationships). The pattern of results was stronger among individuals identified as attachment-schematic. Studies 2 and 3 showed that automatic reactions elicited by thoughts of one’s mother were related to adult romantic attachment assessed at a general level. In all three studies, results did not differ depending on how adult romantic attachment was conceptualized (four styles vs. two dimensions).
Two Distinct Emotional Experiences in Romantic Relationships: Effects of Perceptions Regarding Approach of Intimacy and Avoidance of Conflict
Authors: Laurenceau Jean-Philippe , Troy Adam B. , Carver Charles S.
Published: July 2005

This study examined how perceived position and velocity regarding approach and avoidance in romantic relationships relate to affective experiences. The authors hypothesized that perceived progress toward intimacy would predict positive affect and that perceived movement toward conflict would predict anxious affect. Ninety-two romantic couples recorded perceived levels of, and perceived changes in, both intimacy and conflict twice daily throughout 10 consecutive days using electronic palm-top devices. Multilevel modeling demonstrated that perceived increase in intimacy related to positive affect above and beyond perceptions of intimacy, conflict, and changes in conflict, for both male and female partners. Perceived increase in conflict related to anxious affect above and beyond perceptions of conflict, intimacy, and changes in intimacy, but only among male partners. Findings support a dual-process view of these feelings in romantic relationships and suggest that increases in positive feelings in close relationships depend on enhancing intimacy rather than on decreasing conflict.
Differential Relationships Between Intergroup Contact and Affective and Cognitive Dimensions of Prejudice
Authors: Tropp Linda R. , Pettigrew Thomas F.
Published: July 2005

Research on affective dimensions of intergroup relationships suggests that positive effects of intergroup contact can generalize through establishing affective ties with outgroup members. However, research on cognitive dimensions emphasizes that it is often difficult to generalize positive contact outcomes. In this research, the authors examine whether affective and cognitive dimensions of prejudice bear different relationships to intergroup contact. Using data from a larger meta-analysis of contact effects, Study 1 demonstrates that affective indicators of prejudice typically yield stronger, inverse contact-prejudice relationships than such cognitive indicators as stereotypes. Study 2 replicates these trends in a survey study using multiple indicators of affective and cognitive dimensions of prejudice. Study 2 also shows significant, inverse relationships between contact and affective prejudice when contact is assessed either as number of outgroup friends or intergroup closeness. Together, these results suggest that affective dimensions of intergroup relationships are especially critical for understanding the nature of contact-prejudice effects.
Testing the Generality of the Name Letter Effect: Name Initials and Everyday Attitudes
Authors: Hodson Gordon , Olson James M.
Published: July 2005

The name letter effect is the tendency to evaluate alphabetical letters in one’s name, especially initials, particularly favorably. Recent evidence suggests that name initials may even predict career choices. The authors investigated whether people possess favorable attitudes toward basic attitude objects beginning with name initials, both between individuals (e.g., does Judy like jam more than does Doug?) and within individuals (e.g., does Judy like jam more than honey?). Ratings of animals, foods, leisure activities (Studies 1-4) and national groups (Studies 2-4) revealed no object preference as a function of matching name initials. However, the name letter effect emerged (Studies 3-4), as did a clear preference for brand names starting with one’s name initials (Study 4). Self-esteem, narcissism, and stimuli characteristics did not reliably influence these effects. Implications for extending name letter effects to basic attitude processes are discussed.
Beliefs About Power and Its Relation to Emotional Experience: A Comparison of Japan, France, Germany, and the United States
Authors: Mondillon Laurie , Niedenthal Paula M. , Brauer Markus , Rohmann Anette , Dalle Nathalie , Uchida Yukiko
Published: July 2005

This research examined the concept of power in Japan, France, Germany, and the United States, as well as beliefs about the emotions persons in power tend to elicit in others and about powerful people’s regulation (specifically, inhibition) of certain emotions. Definitions of power were assessed by examining the importance of two main components: control over self versus other and freedom of action vis-à-vis social norms. Beliefs about both positive (pride, admiration) and negative (jealousy, contempt) emotions were measured. Analyses revealed that the concept of power differed across countries and that the definitions of power as well as country of origin significantly predicted beliefs about the emotions that are elicited in others by powerful people and also the regulation of expression of emotion by powerful people.
Gefitinib induces myeloid differentiation of acute myeloid leukemia
Authors: Stegmaier Kimberly , Corsello Steven M. , Ross Kenneth N. , Wong Jenny S. , DeAngelo Daniel J. , Golub Todd R.
Published: July 2005

Cure rates for patients with acute myeloid leukemia (AML) remain low despite ever-increasing dose intensity of cytotoxic therapy. In an effort to identify novel approaches to AML therapy, we recently reported a new method of chemical screening based on the modulation of a gene expression signature of interest. We applied this approach to the discovery of AML-differentiation-promoting compounds. Among the compounds inducing neutrophilic differentiation was DAPH1 (4,5-dianilinophthalimide), previously reported to inhibit epidermal growth factor receptor (EGFR) kinase activity. Here we report that the Food and Drug Administration (FDA)-approved EGFR inhibitor gefitinib similarly promotes the differentiation of AML cell lines and primary patient-derived AML blasts in vitro. Gefitinib induced differentiation based on morphologic assessment, nitro-blue tetrazolium reduction, cell-surface markers, genome-wide patterns of gene expression, and inhibition of proliferation at clinically achievable doses. Importantly, EGFR expression was not detected in AML cells, indicating that gefitinib functions through a previously unrecognized EGFR-independent mechanism. These studies indicate that clinical trials testing the efficacy of gefitinib in patients with AML are warranted. (Blood. 2005;106: 2841-2848)
RGS16 is a negative regulator of SDF-1–CXCR4 signaling in megakaryocytes
Authors: Berthebaud Magali , Rivière Christel , Jarrier Peggy , Foudi Adlen , Zhang Yanyan , Compagno Daniel , Galy Anne , Vainchenker William , Louache Fawzia
Published: July 2005

Regulators of G-protein signaling (RGS) constitute a family of proteins involved in the negative regulation of signaling through heterotrimeric G protein–coupled receptors (GPCRs). Several RGS proteins have been implicated in the down-regulation of chemokine signaling in hematopoietic cells. The chemokine stromal-cell–derived factor 1 (SDF-1) activates migration of hematopoietic progenitors cells but fails to activate mature megakaryocytes despite high levels of CXC chemokine receptor 4 (CXCR4) receptor expression in these cells. This prompted us to analyze RGS expression and function during megakaryocyte differentiation. We found that RGS16 and RGS18 mRNA expression was up-regulated during this process. Overexpressing RGS16 mRNA in the megakaryocytic MO7e cell line inhibited SDF-1–induced migration, mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) activation, whereas RGS18 overexpression had no effect on CXCR4 signaling. Knocking down RGS16 mRNA via lentiviral-mediated RNA interference increased CXCR4 signaling in MO7e cells and in primary megakaryocytes. Thus, our data reveal that RGS16 is a negative regulator of CXCR4 signaling in megakaryocytes. We postulate that RGS16 regulation is a mechanism that controls megakaryocyte maturation by regulating signals from the microenvironment.
Polymerization of fibrin: specificity, strength, and stability of knob-hole interactions studied at the single-molecule level
Authors: Litvinov Rustem I. , Gorkun Oleg V. , Owen Scott F. , Shuman Henry , Weisel John W.
Published: July 2005

Using laser tweezers, we measured for the first time the forces of individual knob-into-hole interactions underlying fibrin polymerization. Exposure of A-knobs in desA-fibrin or its fragment from the central part of the molecule (N-terminal disulphide knot, NDSK) resulted in strong interactions with fibrinogen or fragment D (containing only a- and b-holes), producing a binding strength of approximately 125 to 130 pN. The interactions were not present in the absence of either knobs or holes and were abrogated by a specific inhibitor of fibrin polymerization, a peptide mimic of the A-knob (GPRPam). Exposure of both the A- and B-knobs in desAB-fibrin or desAB-NDSK did not change the rupture force spectra compared with the desA molecules, and their interactions with fibrinogen remained highly sensitive to GPRPam but not to GHRPam (B-knob), suggesting that neither A:b nor B:b nor B:a contacts contributed significantly to binding strength in addition to A:a contacts. The A:a interactions had a relatively small zero-force off-rate of approximately 10–4 s–1 and tight knob-to-hole contacts characterized by a transition state distance of approximately 0.3 nm. The results demonstrate that the knob-hole binding during thrombin-induced fibrin polymerization is driven by strong, stable, and highly specific A:a bonding, whereas A:b, B:b, or B:a interactions were not detected.
Positional and functional mapping of a neuroblastoma differentiation gene on chromosome 11
Authors: De Preter Katleen , Vandesompele Jo , Menten Björn , Carr Philippa , Fiegler Heike , Edsjö Anders , Carter Nigel P , Yigit Nurten , Waelput Wim , Van Roy Nadine , Bader Scott , Påhlman Sven , Speleman Frank
Published: July 2005

Background

Loss of chromosome 11q defines a subset of high-stage aggressive neuroblastomas. Deletions are typically large and mapping efforts have thus far not lead to a well defined consensus region, which hampers the identification of positional candidate tumour suppressor genes. In a previous study, functional evidence for a neuroblastoma suppressor gene on chromosome 11 was obtained through microcell mediated chromosome transfer, indicated by differentiation of neuroblastoma cells with loss of distal 11q upon introduction of chromosome 11. Interestingly, some of these microcell hybrid clones were shown to harbour deletions in the transferred chromosome 11. We decided to further exploit this model system as a means to identify candidate tumour suppressor or differentiation genes located on chromosome 11.

Results

In a first step, we performed high-resolution arrayCGH DNA copy-number analysis in order to evaluate the chromosome 11 status in the hybrids. Several deletions in both parental and transferred chromosomes in the investigated microcell hybrids were observed. Subsequent correlation of these deletion events with the observed morphological changes lead to the delineation of three putative regions on chromosome 11: 11q25, 11p13->11p15.1 and 11p15.3, that may harbour the responsible differentiation gene.

Conclusion

Using an available model system, we were able to put forward some candidate regions that may be involved in neuroblastoma. Additional studies will be required to clarify the putative role of the genes located in these chromosomal segments in the observed differentiation phenotype specifically or in neuroblastoma pathogenesis in general.
Concurrent chemoradiotherapy with low dose weekly gemcitabine in stage III non-small cell lung cancer
Authors: Abacioglu Ufuk , Yumuk Perran F , Caglar Hale , Sengoz Meric , Turhal Nazim S
Published: July 2005

Background

Combined chemoradiotherapy (CRT) is the treatment of choice for stage III NSCLC. Gemcitabine (G) is a novel deoxycitidine analogue that has been proven to be a potent radiosensitizer. Twenty-two consecutive patients were treated with concurrent CRT to demonstrate the tolerability and efficacy of low dose G given weekly as radiosensitizer in stage III NSCLC.

Methods

Patients with KPS ≥70, adequate bone marrow reserve, with no prior radiotherapy (RT) and surgery were included. Eighteen patients had received prior induction chemotherapy (CT). G (75 mg/m2/week) was infused over 1 hour for 6 weeks. Thoracic RT was given two hours later over 6 weeks at 1.8 Gy/day fractions (total dose of 61.2 Gy). Pulmonary toxicity was evaluated with computed tomography scans in 6 weeks.

Results

Median age was 60 years (range, 48–75), median follow-up was 15 months (range, 2–40). Sixty-eight percent of patients were male and median KPS score was 90. Conformal 3D-RT planning was used in 64% of patients. G was given for a median of 5 weeks (range 1–9). Twelve patients (54.6%) received all planned CT. G was stopped because of intolerance in 6 and death in 2 patients. Seven patients (31.8%) had radiation pneumonitis. Twenty patients were evaluated for overall response, 1 patient (4.5%) had clinical CR, 81.8% had PR while 9.5% had SD. Median overall survival (OS) was 14 ± 5 months (95% CI 3–25). One- and 2-year OS rates were 55% and 38%. Sixteen patients died of disease-related events (6 with progression of primary tumor, 8 due to metastatic disease), 2 patients died of other causes. One- and 2-year progression-free survival and local control rates were 56%, 27% and 79%, 51%, respectively.

Conclusion

G might be used as radiosensitizer for patients with stage III NSCLC who could not receive full doses CT with concurrent RT.
Lung cancer symptoms and pulse oximetry in the prognostic assessment of patients with lung cancer
Authors: Martins Sandro J , Ho Nelson , Cavamura Sueli O , Harada Cecilia M , Yamamoto Crystina A , Takagaki Teresa Y
Published: July 2005

Background

Medical oncologists continue to use performance status as a proxy for quality of life (QOL) measures, as completion of QOL instruments is perceived as time consuming, may measure aspects of QOL not affected by cancer therapy, and interpretation may be unclear. The pulse oximeter is widely used in clinical practice to predict cardiopulmonary morbidity after lung resection in cancer patients, but little is known on its role outside the surgical setting. We evaluated whether the Lung Cancer Symptom Scale and pulse oximetry may contribute to the evaluation of lung cancer patients who received standard anticancer therapy.

Methods

We enrolled forty-one consecutive, newly diagnosed, patients with locally advanced or metastatic lung cancer in this study. We developed a survival model with the variables gender, age, histology, clinical stage, Karnofsky performance status, wasting, LCSS symptom scores, average symptom burden index, and pulse oximetry (SpO2).

Results

Patient and observer-rated scores were correlated, except for the fatigue subscale. The median SpO2 was 95% (range: 86 to 98), was unrelated to symptom scores, and was weakly correlated with observer cough scores. In a multivariate survival model, SpO2 > 90% and patient scores on the LCSS appetite and fatigue subscales were independent predictors of survival.

Conclusion

LCSS fatigue and appetite rating, and pulse oximetry should be studied further as prognostic factors in lung cancer patients.
Computer-aided dermoscopy for diagnosis of melanoma
Authors: Barzegari Masoomeh , Ghaninezhad Haiedeh , Mansoori Parisa , Taheri Arash , Naraghi Zahra S , Asgari Masood
Published: July 2005

Background

Computer-aided dermoscopy using artificial neural networks has been reported to be an accurate tool for the evaluation of pigmented skin lesions. We set out to determine the sensitivity and specificity of a computer-aided dermoscopy system for diagnosis of melanoma in Iranian patients.

Methods

We studied 122 pigmented skin lesions which were referred for diagnostic evaluation or cosmetic reasons. Each lesion was examined by two clinicians with naked eyes and all of their clinical diagnostic considerations were recorded. The lesions were analyzed using a microDERM® dermoscopy unit. The output value of the software for each lesion was a score between 0 and 10. All of the lesions were excised and examined histologically.

Results

Histopathological examination revealed melanoma in six lesions. Considering only the most likely clinical diagnosis, sensitivity and specificity of clinical examination for diagnosis of melanoma were 83% and 96%, respectively. Considering all clinical diagnostic considerations, the sensitivity and specificity were 100% and 89%. Choosing a cut-off point of 7.88 for dermoscopy score, the sensitivity and specificity of the score for diagnosis of melanoma were 83% and 96%, respectively. Setting the cut-off point at 7.34, the sensitivity and specificity were 100% and 90%.

Conclusion

The diagnostic accuracy of the dermoscopy system was at the level of clinical examination by dermatologists with naked eyes. This system may represent a useful tool for screening of melanoma, particularly at centers not experienced in the field of pigmented skin lesions.
Epidermal Growth Factor Receptor Gene Mutations and Increased Copy Numbers Predict Gefitinib Sensitivity in Patients With Recurrent Non–Small-Cell Lung Cancer
Authors: Takano Toshimi , Ohe Yuichiro , Sakamoto Hiromi , Tsuta Koji , Matsuno Yoshihiro , Tateishi Ukihide , Yamamoto Seiichiro , Nokihara Hiroshi , Yamamoto Noboru , Sekine Ikuo , Kunitoh Hideo , Shibata Tatsuhiro , Sakiyama Tokuki , Yoshida Teruhiko , Tamura Tomohide
Published: July 2005

Purpose

To evaluate epidermal growth factor receptor (EGFR) mutations and copy number as predictors of clinical outcome in patients with non–small-cell lung cancer (NSCLC) receiving gefitinib.

Patients and Methods

Sixty-six patients with NSCLC who experienced relapse after surgery and received gefitinib were included. Direct sequencing of exons 18 to 24 of EGFR and exons 18 to 24 of ERBB2 was performed using DNA extracted from surgical specimens. Pyrosequencing and quantitative real-time polymerase chain reaction were performed to analyze the allelic pattern and copy number of EGFR.

Results

Thirty-nine patients (59%) had EGFR mutations; 20 patients had deletional mutations in exon 19, 17 patients had missense mutations (L858R) in exon 21, and two patients had missense mutations (G719S or G719C) in exon 18. No mutations were identified in ERBB2. Response rate (82% [32 of 39 patients] v 11% [three of 27 patients]; P < .0001), time to progression (TTP; median, 12.6 v 1.7 months; P < .0001), and overall survival (median, 20.4 v 6.9 months; P = .0001) were significantly better in patients with EGFR mutations than in patients with wild-type EGFR. Increased EGFR copy numbers (≥ 3/cell) were observed in 29 patients (44%) and were significantly associated with a higher response rate (72% [21 of 29 patients] v 38% [14 of 37 patients]; P = .005) and a longer TTP (median, 9.4 v 2.6 months; P = .038). High EGFR copy numbers (≥ 6/cell) were caused by selective amplification of mutant alleles.

Conclusion

EGFR mutations and increased copy numbers were significantly associated with better clinical outcome in gefitinib-treated NSCLC patients.
Increased Epidermal Growth Factor Receptor Gene Copy Number Detected by Fluorescence In Situ Hybridization Associates With Increased Sensitivity to Gefitinib in Patients With Bronchioloalveolar Carcinoma Subtypes: A Southwest Oncology Group Study
Authors: Hirsch Fred R. , Varella-Garcia Marileila , McCoy Jason , West Howard , Xavier Ana Carolina , Gumerlock Paul , Bunn Paul A. , Franklin Wilbur A. , Crowley John , Gandara David R.
Published: July 2005

Purpose

Bronchioloalveolar carcinoma (BAC) and adenocarcinomas with BAC features seem to be increasing in incidence, particularly in younger, never-smoking women. Epidermal growth factor receptor (EGFR) inhibitors demonstrated response rates of 20% to 30% in patients with advanced BAC subtypes, but selection methods for patient therapy are not established.

Patients and Methods

EGFR and HER2 gene copy numbers were assessed by fluorescence in situ hybridization (FISH) in 81 patients treated with gefitinib 500 mg/d (Southwest Oncology Group protocol S0126) and were correlated to treatment outcome. Tumors were classified into two main strata: FISH-positive (high polysomy/gene amplification) and FISH-negative (disomy/low polysomy).

Results

In 81 patients, the median survival time for EGFR/FISH-negative patients was 8 months and not yet reached for FISH-positive patients (but approaching 18 months; hazard ratio [HR] = 2.02; P = .042). Median progression-free survival time for EGFR/FISH-positive patients was 9 months versus 4 months for the FISH-negative patients (HR = 1.67; P = .072). In multivariate analysis, EGFR copy number by FISH remained a significant predictive factor for survival after accounting for smoking status, sex, histology, and performance status. Fifty-five patients were evaluated for response using Response Evaluation Criteria in Solid Tumors Group, and 12 of 19 EGFR/FISH-positive patients (63%) demonstrated disease control versus 14 (39%) of 36 patients in the FISH-negative group (P = .087). No association was found between HER2 gene copy number and response (n = 39 patients) or survival (n = 56 patients; P > .10).

Conclusion

Increased EGFR gene copy number detected by FISH is associated with improved survival after gefitinib therapy in patients with advanced BAC, suggesting FISH methodology can be used to assess survival potential in patients treated with EGFR tyrosine kinase inhibitors.
Neoadjuvant Treatment of Postmenopausal Breast Cancer With Anastrozole, Tamoxifen, or Both in Combination: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) Multicenter Double-Blind Randomized Trial
Authors: Smith Ian E. , Dowsett Mitch , Ebbs Stephen R. , Dixon J. Michael , Skene Anthony , Blohmer J.-U. , Ashley Susan E. , Francis Stephen , Boeddinghaus Irene , Walsh Geraldine
Published: July 2005

Purpose

The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) trial was designed to test the hypothesis that the clinical and/or biologic effects of neoadjuvant tamoxifen compared with anastrozole and with the combination of tamoxifen and anastrozole before surgery in postmenopausal women with estrogen receptor (ER) –positive, invasive, nonmetastatic breast cancer might predict for outcome in the Arimidex, Tamoxifen Alone or in Combination (ATAC) adjuvant therapy trial.

Patients and Methods

Postmenopausal women with ER-positive, invasive, nonmetastatic, and operable or locally advanced potentially operable breast cancer were randomly assigned to neoadjuvant tamoxifen (20 mg daily), anastrozole (1 mg daily), or a combination of tamoxifen and anastrozole for 3 months. The tumor objective response (OR) was assessed by both caliper and ultrasound. Comparisons were also made of clinical response with ultrasound response, actual and feasible surgery with feasible surgery at baseline, OR in human epidermal growth factor receptor 2 (HER2) –positive cancers, and tolerability.

Results

There were no significant differences in OR in the intent-to-treat population between patients receiving tamoxifen, anastrozole, or the combination. In patients who were assessed as requiring mastectomy at baseline (n = 124), 44% of patients received breast-conserving surgery (BCS) after anastrozole compared with 31% of patients after tamoxifen (P = .23); this difference became significant for patients who were deemed feasible for BCS by their surgeon (46% v 22%, respectively; P = .03). The OR for patients with HER2-positive cancer (n = 34) was 58% for anastrozole compared with 22% for tamoxifen (P = .18). All treatments were well tolerated.

Conclusion

Neoadjuvant anastrozole is as effective and well tolerated as tamoxifen in ER-positive operable breast cancer in postmenopausal women, but the hypothesis that clinical outcome might predict for long-term outcome in adjuvant therapy was not fulfilled.
Phase II Trial of Temsirolimus (CCI-779) in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study
Authors: Galanis Evanthia , Buckner Jan C. , Maurer Matthew J. , Kreisberg Jeffrey I. , Ballman Karla , Boni J. , Peralba Josep M. , Jenkins Robert B. , Dakhil Shaker R. , Morton Roscoe F. , Jaeckle Kurt A. , Scheithauer Bernd W. , Dancey Janet , Hidalgo Manuel , Walsh Daniel J.
Published: July 2005

Background

Temsirolimus (CCI-779) is a small-molecule inhibitor of the mammalian target of rapamycin (mTOR) and represents a rational therapeutic target against glioblastoma multiforme (GBM).

Methods

Recurrent GBM patients with ≤ 1 chemotherapy regimen for progressive disease were eligible. Temsirolimus was administered in a 250-mg intravenous dose weekly.

Results

Sixty-five patients were treated. The incidence of grade 3 or higher nonhematologic toxicity was 51%, and consisted mostly of hypercholesterolemia (11%), hypertriglyceridemia (8%), and hyperglycemia (8%). Grade 3 hematologic toxicity was observed in 11% of patients. Temsirolimus peak concentration (Cmax), and sirolimus Cmax and area under the concentration-time curve were decreased in patients receiving p450 enzyme–inducing anticonvulsants (EIACs) by 73%, 47%, and 50%, respectively, but were still within the therapeutic range of preclinical models. Twenty patients (36%) had evidence of improvement in neuroimaging, consisting of decrease in T2 signal abnormality +/− decrease in T1 gadolinium enhancement, on stable or reduced steroid doses. Progression-free survival at 6 months was 7.8% and median overall survival was 4.4 months. Median time to progression (TTP) for all patients was 2.3 months and was significantly longer for responders (5.4 months) versus nonresponders (1.9 months). Development of grade 2 or higher hyperlipidemia in the first two treatment cycles was associated with a higher percentage of radiographic response (71% v 31%; P = .04). Significant correlation was observed between radiographic improvement and high levels of phosphorylated p70s6 kinase in baseline tumor samples (P = .04).

Conclusion

Temsirolimus is well tolerated in recurrent GBM patients. Despite the effect of EIACs on temsirolimus metabolism, therapeutic levels were achieved. Radiographic improvement was observed in 36% of temsirolimus–treated patients, and was associated with significantly longer TTP. High levels of phosphorylated p70s6 kinase in baseline tumor samples appear to predict a patient population more likely to derive benefit from treatment. These findings should be validated in other studies of mTOR inhibitors.
Cognitive Science: The Newest Science of the Artificial*
Authors: Simon Herbert A.
Published: July 2005

Cognitive science is, of course, not really a new discipline, but a recognition of a fundamental set of common concerns shared by the disciplines of psychology, computer science, linguistics, economics, epistemology, and the social sciences generally. All of these disciplines are concerned with information processing systems, and all of them are concerned with systems that are adaptive—that are what they are from being ground between the nether millstone of their physiology or hardware, as the case may be, and the upper millstone of a complex environment in which they exist. Systems that are adaptive may equally well be described as “artificial,” for as environments change, they can be expected to change too, as though they were deliberately designed to fit those environments (as indeed they sometimes are).

The task of empirical science is to discover and verify invariants in the phenomena under study. The artificiality of information processing systems creates a subtle problem in defining empirical invariants in such systems. For observed regularities are very likely invariant only within a limited range of variation in their environments, and any accurate statement of the laws of such systems must contain reference to their relativity to environmental features. It is a common experience in experimental psychology, for example, to discover that we are studying sociology—the effects of the past histories of our subjects—when we think we are studying physiology—the effects of properties of the human nervous system. Similarly, business cycle economists are only now becoming aware of the extent to which the parameters of the system they are studying are dependent on the experiences of a population with economic events over the previous generation.

In artificial sciences, the descriptive and the normative are never far apart. Thus, in economics, the “principle of rationality” is sometimes asserted as a descriptive invariant, sometimes as advice to decision makers. Similarly, in psychology, the processes of adaptation (learning) have always been a central topic, at one time a topic that dominated the whole field of research. Linguistics, too, has suffered its confusions between descriptive and normative attitudes towards its subject. But we must avoid the error, in studying information processing systems, of thinking that the adaptive processes themselves must be invariant; and we must be prepared to face the complexities of regression in the possibility that they themselves may be subject to improvement and adaptation.

It might have been necessary a decade ago to argue for the commonality of the information processes that are employed by such disparate systems as computers and human nervous systems. The evidence for that commonality is now overwhelming, and the remaining questions about the boundaries of cognitive science have more to do with whether there also exist nontrivial commonalities with information processing in genetic systems than with whether men and machines both think.
The Intentionality of Intention and Action*
Authors: Searle John R.
Published: July 2005

Cognitive Science is likely to make little progress in the study of human behavior until we have a clear account of what a human action is. The aim of this paper is to present a sketch of a theory of action. I will locate the relation of intention to action within a general theory of Intentionality. I will introduce a distinction between prior intentions and intentions in actions; the concept of the experience of acting; and the thesis that both prior intentions and intentions in action are causally selfreferential. Each of these is independently motivated, but together they enable me to suggest solutions to several outstanding problems within action theory (deviant causal chains, the accordian effect, basic actions, etc.), to show how the logical structure of intentional action is strikingly like the logical structure of perceptions, and to construct an account of simple actions. A successfully performed intentional action characteristically consists of an intention in action together with the bodily movement or state of the agent which is its condition of satisfaction and which is caused by it. The account is extended to complex actions.
Physical Symbol Systems*
Authors: Newell Allen
Published: July 2005

On the occasion of a first conference on Cognitive Science, it seems appropriate to review the basis of common understanding between the various disciplines. In my estimate, the most fundamental contribution so far of artificial intelligence and computer science to the joint enterprise of cognitive science has been the notion of a physical symbol system, i.e., the concept of a broad class of systems capable of having and manipulating symbols, yet realizable in the physical universe. The notion of symbol so defined is internal to this concept, so it becomes a hypothesis that this notion of symbols includes the symbols that we humans use every day of our lives. In this paper we attempt systematically, but plainly, to lay out the nature of physical symbol systems. Such a review is in ways familiar, but not thereby useless. Restatement of fundamentals is an important exercise.
Neurological Knowledge and Complex Behaviors
Authors: Geschwind Norman
Published: July 2005

Some scholars believe thot Cognitive Science is the attempt to achieve in artificial systems what has already been achieved in the brain. Others, by contrast, argue that the study of ideal adaptive mechanisms could go on without reference to the brain. The author points out that the brain may not be the ideal cognitive device because of biological limitotions on its capacity. Although it may not be ideal, it is still of major interest to cognitive scientists because of the great interest in the human mind, and, in addition, because at this moment the brain is the most important single reservoir of odoptive mechanisms.

The paper discusses several areas of neuroscience which are likely to shed light on mechanisms of adaptation. The study of simple nervous systems is likely to reveal important design principles of cognitive devices. The study of complex nervous systems will, of course, exert a major influence. The study of such systems leads to certain general principles concerning the neural circuits involved in complex odoptive behaviors: (1) There exist innate specialized systems for the learning of many specific behaviors that at first might appeor to be purely cultural. (2) There is no evidence for the existence of any all‐purpose computer in the brain. (3) There are many surprising dissociations manifested by the specialized systems in the brain, e.g., a special system for recognition of faces as against other visual patterns. (4) The study of the nervous system enables one to formulate more precise mechanisms for the role of emotion in cognitive function.(5) Some human behoviors con probably be understood poorly or not at all if the neural substrate is not considered. (6) The cognitive systems designed for dealing with ottentionol processes may be among the most complex neural structures which underlie behavior.

There are certain other properties of brains that should be kept in mind by the cognitive scientists who are studying human behovior: (1) Brains differ from each other in structure, and it is very likely that the strategy for the solution of certain problems differs from person to person. (2) The presence of certain innate cognitive strategies in the brain may prevent that organism from employing other strategies which might be optimal for other problems. (3) Any theory about a particular cognitive strategy will have implications as to the particular mode of breakdown that might be expected after brain lesions. The study of disordered function from brain disease may thus be a valuable way to test certain cognitive theories.
Language and Memory*
Authors: Schank Roger C.
Published: July 2005

This paper outlines some of the issues and basic philosophy that have guided my work and that of my students in the last ten years. It describes the progression of conceptual representational theories developed during that time, as well as some of the research models built to implement those theories. The paper concludes with a discussion of my most recent work in the area of modelling memory. It presents a theory of MOPs (Memory Organization Packets), which serve as both processors and organizers of information in memory. This enables effective categorization of experiences in episodic memory, which in turn enables better predictive understanding of new experiences.
Models of Competence in Solving Physics Problems*
Authors: Larkin Jill H. , McDermott John , Simon Dorothea P. , Simon Herbert A.
Published: July 2005

We describe a set of two computer‐implemented models that solve physics problems in ways characteristic of more and less competent human solvers. The main features accounting for different competences are differences in strategy for selecting physics principles, and differences in the degree of automation in the process of applying a single principle. The models provide a good account of the order in which principles are applied by human solvers working problems in kinematics and dynamics. They also are sufficiently flexible to allow easy extension to several related domains of physics problems.