bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of depression and disability on quality of life in Iranian patients with multiple sclerosis
Authors: Ayatollahi P , Nafissi S , Eshraghian MR , Kaviani H , Tarazi A
Published: February 2007

Multiple sclerosis (MS) can influence all aspects of a patient's health. This study determines the main factors affecting quality of life (QoL) in Iranian MS patients. QoL (Multiple Sclerosis Impact Scale; MSIS-29), disability (Expanded Disability Status Scale; EDSS) and depression (Beck Depression Inventory; BDI) were assessed in 106 MS patients. EDSS, clinical course and MS duration significantly correlated with physical MSIS-29. Depression highly correlated with both physical and psychological MSIS-29. Regression analyses showed that depression and EDSS predicted physical health. Psychological health was predicted by depression. These findings highlight that depression and physical disability strongly influence QoL in Iranian MS patients. Multiple Sclerosis 2007; 13: 275–277. http://msj.sagepub.com
Coping and quality of life in one hundred and thirty five subjects with multiple sclerosis
Authors: Montel S.R. , Bungener C.
Published: February 2007

Introduction and objective The aim of this study was to compare coping strategies and quality of life (QoL) in multiple sclerosis (MS), as they relate to the course of the disease (relapsing-remitting (RR), secondary progressive (SP), primary progressive (PP)), while taking depression and anxiety into account.

Methods A total of 135 MS subjects were seen for a semi-structured interview in order to collect socio-demographic and clinical information, after which there was an assessment of their mental and cognitive states (Mini International Neuropsychiatric Interview (MINI), Montgomery and Asberg Depression Rating Scale (MADRS), Depressive Mood Scale (EHD), Hamilton Anxiety (HAMA), Frontal Assessment Battery (FAB)). All subjects then completed three self-report questionnaires; two about coping strategies (Ways of Coping Checklist (WCC), Coping with Health, Injuries and Problems Scale (CHIP)) and one about QoL (SEP59).

Results The mental health (depression and anxiety) and the psychological and social dimensions of QoL were relatively unaffected. However, after controlling for age and disability, the disease course had a strong effect on both mental health and QoL, with the poorest condition for SPMS and the best condition for PPMS. The SPMS patients tend to use emotional coping strategies extensively, while the PPMS patients use more instrumental strategies.

Discussion Our study clearly demonstrated that psychological and social well-being were substantially affected by the disease course. These results encourage us to develop interventions focused on coping strategies and which are better adapted to individual patients. Multiple Sclerosis 2007; 13: 393- 401. http://msj.sagepub.com
On Gearksutite at Gingin, Western Australia
Authors: Simpson Edward S.
Published: February 2007

A description is given of the occurrence of gearksutite under novel conditions, viz. in Cretaceous greensand, at Gingin in Western Australia. Some additions are made to the previously known physical and chemical properties of the mineral and a new suggestion is put forward as to its constitution. Its genesis is discussed and theories put forward to account for its origin under the previously known and newly discovered conditions.
Transgenic and gene-targeted mice as models for chronic obstructive pulmonary disease: Fig. 1—
Authors: Shapiro S. D.
Published: February 2007

Animal models play an important role in the understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD). The applicability of findings to human COPD depends upon several factors, including the disease model, and similarities in mouse structure and function between species.

There are many examples in the literature of transgenic mice that have contributed to the understanding of COPD. Several studies demonstrate the complexity of inflammatory networks and how unexpected findings in animal models have led to the search for new potential mediators in human disease.

Gene-targeting studies into α1-antitrypsin (α1-AT) and emphysema in mice have demonstrated that the genetic locus for α1-AT in mice is very complex and that the loss of one gene is lethal in embryo lung development. This underlines the differences between mice and humans that limit the ability to translate between systems in some instances. Gene targeting has also highlighted complex roles for transforming growth factor-β in COPD and has been used to determine important molecules and pathways in COPD.

Both transgenic and gene-targeted models suffer limitations and their applicability to human chronic obstructive pulmonary disease may be dependant on several factors, some of which are still being learnt. The more that is known about similarities and differences, the better the knowledge will be that is gained to develop for chronic obstructive pulmonary disease.
Global Alliance against Chronic Respiratory Diseases
Authors: Bousquet J. , Dahl R. , Khaltaev N.
Published: February 2007

Hundreds of millions of people of all ages suffer from chronic respiratory diseases which include asthma and respiratory allergies, chronic obstructive pulmonary disease, occupational lung diseases and pulmonary hypertension. More than 500 million patients live in developing countries or in deprived populations. Chronic respiratory diseases are increasing in prevalence. Although the cost of inaction is clear and unacceptable, chronic respiratory diseases and their risk factors receive insufficient attention from the healthcare community, government officials, media, patients and families. The Fifty-Third World Health Assembly recognised the enormous human suffering caused by chronic diseases and requested the World Health Organization (WHO) Director General to give priority to the prevention and control of chronic diseases, with special emphasis on developing countries. This led to the formation of the WHO Global Alliance against Chronic Respiratory Diseases (GARD). GARD is a voluntary alliance of organisations, institutions and agencies working towards a common vision to improve global lung health according to local needs. GARD is developed in a stepwise approach using the following three planning steps: estimate population need and advocate action; formulate and adopt policy; and identify policy implementation steps.
Liver dysfunction after lung recruitment manoeuvres during pressure-controlled ventilation in experimental acute respiratory distress
Authors: Kredel Markus , Muellenbach Ralf M , Brock Robert W , Wilckens Hans-Hinrich , Brederlau Joerg , Roewer Norbert , Wunder Christian
Published: February 2007

Introduction

Consequences of lung recruitment with prolonged high positive end-expiratory pressure (PEEP) ventilation for liver function are unclear. We therefore investigated liver dysfunction during two different ventilation treatment regimens of experimental acute respiratory distress syndrome.

Methods

Sixteen anaesthetised juvenile pietrain pigs were ventilated in the pressure-controlled mode (PCV) with an inspiratory fraction of oxygen (FiO2) of 1.0, a respiratory frequency of 30 per minute, a tidal volume of 6 ml/kg, and a PEEP of 5 cm H2O. After lung injury was induced by repeated pulmonary lavage with normal saline, animals were randomly assigned into two groups (n = 8 each) for a 24-hour trial: PCV (unchanged ventilation) and PCV with recruitment (PCV+R) (starting with a sustained inflation of 50 cm H2O for 1 minute, the ventilation was continued while increasing PEEP in increments of 3 cm H2O every 15 minutes as long as arterial oxygen tension [PaO2] improved). After recruitment, FiO2 was reduced to 0.4 and the PEEP was lowered every 15 minutes until PaO2 decreased to 12.0 to 14.7 kPa (90 to 110 torr). Serum levels of hyaluronic acid (HA), routine liver serum markers, and plasma disappearance rate of indocyanine green (ICG) were tested before and after lung injury, and 6 and 18 hours after randomisation. Liver serum markers were also tested at 24 hours. Paraffin sections of liver tissue stained by haematoxylin and eosin were made after euthanisation.

Results

The PCV+R group exhibited more polymorphonuclear neutrophils and lymphocytes in the liver sinusoids: median score (interquartile range) of 1.5 (1.4 to 1.5) compared to 0.9 (0.7 to 1.1) (p = 0.01). Elevation of bilirubin, aspartate aminotransferase, and lactate dehydrogenase was more prominent in the PCV+R group. Plasma disappearance rate of ICG indicated no liver dysfunction. HA levels in the PCV+R group gradually increased and were significantly higher (p < 0.001) at 6 and 18 hours with 59 (57 to 64) and 75 (66 to 84) ng/ml, respectively, than in the PCV group with 34 (32 to 48) and 41 (38 to 42) ng/ml, respectively.

Conclusion

The PCV+R group showed a more prominent inflammatory reaction in their liver sinusoids accompanied by increased serum levels of liver enzymes and HA. Therefore, recruitment with higher PEEP levels for treatment of respiratory failure might lead to liver dysfunction.
The role of mannose receptor during experimental leishmaniasis
Authors: Akilov Oleg E , Kasuboski Rachel E , Carter Cristina R , McDowell Mary Ann
Published: February 2007

The primary host cells for Leishmania replication are macrophages (MP). Several molecules on the surface of professional phagocytic cells have been implicated in the initial process of parasite internalization and initiation of signaling pathways. These pattern recognition receptors distinguish molecular patterns on pathogen surfaces. Mannose receptor (MR), specifically, recognizes mannose residues on the surface of Leishmania parasites. We studied the role of MR in the pathogenesis of experimental cutaneous and visceral leishmaniasis using MR-deficient [MR-knockout (KO)] C57BL/6 mice. MR-deficient MP exhibied a comparable infection rate and cytokine production. In the absence of MR, the clinical course of Leishmania major and Leishmania donovani infections was similar in MR-KO and wild-type mice (MR-WT). Furthermore, immunohistochemistry of cutaneous lesions from MR-KO and MR-WT mice revealed no differences in lesion architecture or cell components. Inhibition of MP responses is a hallmark of Leishmania infection; our data demonstrate further that host MR is not essential for blocking IFN-γ/LPS-induced IL-12 production and MAPK activation by Leishmania. Thus, we conclude that the MR is not essential for host defense against Leishmania infection or regulation of IL-12 production.
Risk of hip fracture in patients with a history of
schizophrenia
Authors: Howard Louise , Kirkwood Graham , Leese Morven
Published: February 2007

Background

There is evidence of an association between decreased bone mineral
density schizophrenia, and prolactin-raising antipsychotic medication.
However, it is not known whether this is clinically significant.

Aims

To investigate whether patients with a history of schizophrenia are at
increased risk of hip fracture.

Method

In a case-control study, we compared cases of ‘hip fracture’ on the
General Practice Research Database (n=16 341) with
matched controls (n=29 889).

Results

Hip fracture was associated with schizophrenia (OR=1.73; 95% CI
1.32-2.28), and prolactin-raising antipsychotics (OR=2.6; 95% CI
2.432.78), in the univariate analysis. In the multivariate analysis,
prolactin-raising antipsychotics were independently associated with hip
fracture but schizophrenia was not. A significant interaction between
gender and antipsychotics was found in the association with hip fracture
(P=0.042); OR=2.12 (95% C11.73-2.59)for men, OR=l.93
(95% C11.78-2.10) for women.

Conclusions

The association between prolactin-raising antipsychotic medication and
hip fracture may have serious implications for public health. Mental
health service patients may require preventive measures including dietary
and lifestyle advice.
Rapid Estrogen Actions in the Cardiovascular System
Authors: SIMONCINI TOMMASO , MANNELLA PAOLO , GENAZZANI ANDREA RICCARDO
Published: February 2007

Abstract:  In the last two decades, several studies have unveiled a series of original signaling mechanisms through which so‐called “nuclear” receptors can mediate rapid actions of steroid hormones. These rapid signaling actions are independent of the synthesis of mRNA or protein, and are therefore known as “nontranscriptional” or “nongenomic” as opposed to the classical genomic mechanisms. Nongenomic signaling of estrogens plays a prominent role in nonreproductive tissues, and between these is the vascular wall. At this level, estrogen triggers rapid vasodilatation, exerts anti‐inflammatory effects, stimulates endothelial growth and migration, and protects the vessels from atherosclerotic degeneration. Nongenomic signaling mechanisms have been involved in many of these actions and are increasingly considered to be of importance for vascular function in physiological and pathophysiological conditions. Rapid actions of steroid hormones have been implicated with vascular as well as with myocardial protection in animal experimental models. Moreover, the nongenomic signaling of estrogens is tightly interconnected with the nuclear pathways, and there are several indications that, through nongenomic modulation of signaling cascades, estrogens are also able to modulate the expression of several relevant genes in endothelial cells. In conclusion, while we are still in an early phase of the investigations of the nontranscriptional actions of steroid hormone receptors, it is clear that this newly recognized category of signaling mechanisms is responsible for critical steroid actions in nonreproductive tissues.
Association between Platelet Glycoprotein Ib‐α and Myocardial Infarction
Authors: CANDORE GIUSEPPINA , PIAZZA GIUSEPPINA , CRIVELLO ANTONINO , GRIMALDI MARIA PAOLA , ORLANDO VALENTINA , CARUSO MARCO , CAIMI GREGORIO , HOFFMANN ENRICO , INCALCATERRA EGLE , LIO DOMENICO , CARUSO CALOGERO
Published: February 2007

Abstract:  Myocardial infarction (AMI) is a complex multifactorial disorder. Platelet adhesion and thrombosis are pivotal events in the development of atherosclerotic lesions. Occlusive thrombus is almost exclusively initiated by plaque rupture and adhesion of platelets to subendothelial von Willebrand factor (vWf) by its specific platelet receptor, the α‐chain of glycoprotein (GP) Ib‐IX‐V complex of the human platelet‐specific antigens (HPA). Two polymorphisms have been reported in the sequence of GPIb‐α. The first, a C/T transition at nucleotide 1018 results in an amino acid dimorphism (Thr/Met) at residue 145 of GPIb‐α, which is located within the vWF‐binding domain of the receptor. The second is a T/C polymorphism in the Kozak sequence at position −5 from the initiator ATG. This affects the receptor density on the platelet surface. We assessed 1018 C/T and −5 T/C Kozak polymorphisms to see whether they are associated with AMI in homogeneous populations of Sicilian patients with AMI. To this end, we have analyzed the distribution of 1018 C/T and −5 T/C Kozak polymorphisms in 105 young Sicilian patients (<46 years) and 110 healthy age‐related controls, by PCR–SSP and PCR–RFLP. Our results demonstrate no significant differences in the frequency of 1018 C/T and −5 T/C Kozak polymorphism between patients with AMI and controls. Stratifying by gender, there is no difference between male and female patients and control data. Thus, our results indicate that the HPA‐2 polymorphisms are not associated with an increased risk for AMI at early onset (< 46 years) both in men and in women.
A Study of Serum Immunoglobulin Levels in Elderly Persons That Provides New Insights into B Cell Immunosenescence
Authors: LISTÌ FLORINDA , CANDORE GIUSEPPINA , MODICA MARIA ASSUNTA , RUSSO MARIANGELA , LORENZO GABRIELE DI , ESPOSITO‐PELLITTERI MARIA , COLONNA‐ROMANO GIUSEPPINA , AQUINO ALESSANDRA , BULATI MATTEO , LIO DOMENICO , FRANCESCHI CLAUDIO , CARUSO CALOGERO
Published: February 2007

Abstract:  The literature on immunosenescence has focused mainly on T cell impairment. With the aim of gaining insight into B cell immunosenescence, we investigated the serum immunoglobulin levels in a cohort of 166 subjects (20–106 years). Serum IgG (and IgG subclasses) were quantified by the nephelometric technique, IgE by CAP system fluorescence enzyme immunoassay, and IgD by radial immunodiffusion (RID). There was an age‐related increase of IgG and IgA; the IgG age‐related increase was significant only in men, but IgG1 levels showed an age‐related increase both in men and women, whereas IgG3 showed an age‐related increase only in men. IgE levels remain unchanged, whereas IgD and IgM serum levels decreased with age; the IgM age‐related decrease was significant only in women, likely due to the relatively small sample of aged men. Thus, in the elderly the B cell repertoire available to respond to new antigenic challenge is decreased. A lot of memory IgD− B cells are filling immunological space and the amount of naïve IgD+ B cells is dramatically decreased. This shift away from a population of predominantly naïve B cells obviously reflects the influences of cumulative exposure to foreign pathogens over time. These age‐dependent B cell changes indicate that advanced age is a condition characterized by lack of clonotypic immune response to new extracellular pathogens. In any event, the increase of memory B cells and the loss of naïve B cells, as measured by serum IgD levels, could represent hallmarks of immunosenescence and could provide useful biomarkers possibly related to the life span of humans.
From Adult Stem Cells to Cancer Stem Cells
Authors: TROSKO JAMES E.
Published: February 2007

Abstract:  Carcinogenesis is characterized by “initiation,”“promotion,” and “progression” phases. The “stem cell theory” and “de‐differentiation” theories are used to explain the origin of cancer. Growth control for stem cells, which lack functional gap junctional intercellular communication (GJIC), involves negative soluble or niche factors, while for progenitor cells, it involves GJIC. Tumor promoters, hormones, and growth factors inhibit GJIC reversibly. Oncogenes stably inhibit GJIC. Cancer cells, which lack growth control and the ability to terminally differentiate and to apoptose, lack GJIC. The Oct3/4 gene, a POU (Pit‐Oct‐Unc) family of transcription factors was thought to be expressed only in embryonic stem cells and in tumor cells. With the availability of normal adult human stem cells, tests for the expression of Oct3/4 gene and the stem cell theory in human carcinogenesis became possible. Human breast, liver, pancreas, kidney, mesenchyme, and gastric stem cells, HeLa and MCF‐7 cells, and canine tumors were tested with antibodies and polymerase chain reaction (PCR) primers for Oct3/4. Adult human breast stem cells, immortalized nontumorigenic and tumor cell lines, but not the normal differentiated cells, expressed Oct3/4. Adult human differentiated cells lose their Oct‐4 expression. Oct3/4 is expressed in a few cells found in the basal layer of human skin epidermis. The data demonstrate that normal adult stem cells and cancer stem cells maintain expression of Oct3/4, consistent with the stem cell hypothesis of carcinogenesis. These Oct‐4 positive cells might represent the “cancer stem cells.” A strategy to target “cancer stem cells” is to suppress the Oct‐4 gene in order to cause the cells to differentiate.
The Role of Flow Cytometric Immunophenotyping in Myelodysplastic Syndromes
Authors: PAGNUCCO GUIDO , GIAMBANCO CATERINA , GERVASI FRANCESCO
Published: February 2007

Abstract:  The myelodysplastic syndromes (MDSs) are a group of heterogeneous hematological disorders characterized by bilineage or trilineage dysplastic morphology, abnormal clonal populations, progressive bone marrow failure, and a high rate of transformation to acute myeloid leukemia. A combination of morphology, to detect multilineage dysplasia in the bone marrow and peripheral blood, and cytogenetics to detect characteristic clonal abnormalities, is used in establishing a diagnosis of MDS. Although diagnostic criteria are well established, a significant number of patients have blood and bone marrow findings that make diagnosis and classification difficult. Flow cytometric immunophenotyping is an accurate and highly sensitive method for quantitative and qualitative evaluation of hematopoietic cells in the different maturative compartments, and several groups have used flow cytometry in the study of MDSs. Findings of recent studies suggest that flow cytometry immunophenotyping might provide useful information in the diagnosis and the management of MDS patients.
Timing of Dietary Estrogenic Exposures and Breast Cancer Risk
Authors: DE ASSIS SONIA , HILAKIVI‐CLARKE LEENA
Published: February 2007

Abstract:  The same dietary component, such as fat or phytochemicals in plant foods, can have an opposite effect on breast cancer risk if exposed in utero through a pregnant mother or at puberty. Dietary exposures during pregnancy often have similar effects on breast cancer risk among mothers and their female offspring. High fat intake and obesity are illustrative examples: excessive pregnancy weight gain that increases high birth weight is associated with increased breast cancer risk among mothers and daughters. High body weight during childhood is inversely linked to later breast cancer risk. The main reason why the age when dietary exposures occur determines their effect on breast cancer risk likely reflects the extensive programming of the mammary gland during fetal life and subsequent reprogramming at puberty and pregnancy. Programming is a series of epigenetic/transcriptional modifications in gene expression that can be influenced by changes in the hormonal environment induced, for example, by diet. Because epigenetic modifications are inherited by daughter cells, they can persist throughout life if they occur in mammary stem cells or uncommitted mammary myoepithelial or luminal progenitor cells. Our results indicate that the estrogen receptor (ER), mitogen‐activated protein kinase (MAPK), and the tumor suppressors BRCA1, p53, and caveolin‐1 are among the genes affected by diet‐induced alterations in programming/reprogramming
. Consequently, mammary gland morphology may be altered in a manner that increases or reduces susceptibility to malignant transformation, including an increase/reduction in cell proliferation, differentiation, and survival, or in the number of terminal end buds (TEBs) or pregnancy‐induced mammary epithelial cells (PI‐MECs) that are the sites where breast cancer is initiated. Thus, dietary exposures during pregnancy and puberty may play an important role in determining later risk by inducing epigenetic changes that modify vulnerability to breast cancer.
Catechol Quinones of Estrogens in the Initiation of Breast, Prostate, and Other Human Cancers
Authors: CAVALIERI ERCOLE , ROGAN ELEANOR
Published: February 2007

Abstract: Estrogens can be converted to electrophilic metabolites, particularly the catechol estrogen‐3,4‐quinones, estrone(estradiol)‐3,4‐quinone [E1(E2)‐3,4‐Q], which react with DNA to form depurinating adducts. These adducts are released from DNA to generate apurinic sites. Error‐prone repair of this damage leads to the mutations that initiate breast, prostate, and other types of cancer. The reaction of E1(E2)‐3,4‐Q with DNA forms the depurinating adducts 4‐hydroxyE1(E2)‐1‐N3adenine [4‐OHE1(E2)‐1‐N3Ade] and 4‐OHE1(E2)‐1‐N7guanine(Gua). These two adducts constitute >99% of the total DNA adducts formed. The E1(E2)‐2,3‐Q forms small amounts of the depurinating 2‐OHE1(E2)‐6‐N3Ade adducts. Reaction of the quinones with DNA occurs more abundantly when estrogen metabolism is unbalanced. Such an imbalance is the result of overexpression of estrogen‐activating enzymes and/or deficient expression of deactivating (protective) enzymes. Excessive formation of E1(E2)‐3,4‐Q is the result of this imbalance. Oxidation of catechols to semiquinones and quinones is a mechanism of tumor initiation not only for endogenous estrogens, but also for synthetic estrogens such as hexestrol and diethylstilbestrol, a human carcinogen. This mechanism is also involved in the initiation of leukemia by benzene, rat olfactory tumors by naphthalene, and neurodegenerative diseases such as Parkinson's disease by dopamine. In fact, dopamine quinone reacts with DNA similarly to the E1(E2)‐3,4‐Q, forming analogous depurinating N3Ade and N7Gua adducts. The depurinating adducts that migrate from cells and can be found in body fluids can also serve as biomarkers of cancer risk. In fact, a higher level of estrogen‐DNA adducts has been found in the urine of men with prostate cancer and in women with breast cancer compared to healthy controls. This unifying mechanism of the origin of cancer and other diseases suggests preventive strategies based on the level of depurinating DNA adducts that generate the first critical step in the initiation of diseases.
Bioterrorism Training in U.S. Emergency Medicine Residencies: Has It Changed since 9/11?
Authors: Moye Philip Kevin , Pesik Nicki , Terndrup Thomas , Roe Jedd , Weissman Norman , Houston Thomas K. , Kiefe Catarina
Published: February 2007

Objectives: To assess the change in prevalence of bioterrorism training among emergency medicine (EM) residencies from 1998 to 2005, to characterize current training, and to identify characteristics of programs that have implemented more intensive training methods.

Methods: This was a national cross sectional survey of the 133 U.S. EM residencies participating in the 2005 National Resident Matching Program; comparison with a baseline survey from 1998 was performed. Types of training provided were assessed, and programs using experiential methods were identified.

Results: Of 112 programs (84.2%) responding, 98% reported formal training in bioterrorism, increased from 53% (40/76) responding in 1998. In 2005, most programs with bioterrorism training (65%) used at least three methods of instruction, mostly lectures (95%) and disaster drills (80%). Fewer programs used experiential methods such as field exercises or bioterrorism‐specific rotations (35% and 13%, respectively). Compared with other programs, residency programs with more complex, experiential methods were more likely to teach bioterrorism‐related topics at least twice a year (83% vs. 59%; p = 0.018), to teach at least three topics (60% vs. 40%; p = 0.02), and to report funding for bioterrorism research and education (74% vs. 45%; p = 0.007). Experiential and nonexperiential programs were similar in program type (university or nonuniversity), length of program, number of residents, geographic location, and urban or rural setting.

Conclusions: Training of EM residents in bioterrorism preparedness has increased markedly since 1998. However, training is often of low intensity, relying mainly on nonexperiential instruction such as lectures. Although current recommendations are that training in bioterrorism include experiential learning experiences, the authors found the rate of these experiences to be low.
Randomized Phase II Trial of Paclitaxel Plus Carboplatin or Gemcitabine Plus Cisplatin in Eastern Cooperative Oncology Group Performance Status 2 Non–Small-Cell Lung Cancer Patients: ECOG 1599
Authors: Langer Corey , Li Sigui , Schiller Joan , Tester William , Rapoport Bernardo L. , Johnson David H.
Published: February 2007

Purpose

Appropriate therapy for Eastern Cooperative Oncology Group (ECOG) performance status (PS) -2 patients with advanced non–small-cell lung cancer (NSCLC) remains challenging. PS-2 patients on ECOG 1594 had a median survival (MS) of only 4.1 months and 1-year overall survival (OS) of 19%. Three percent had grade 5 toxicity.

Patients and Methods

ECOG 1599, the first PS 2–specific, US cooperative group trial for treatment-naïve advanced NSCLC, randomly assigned patients to dose-attenuated carboplatin/paclitaxel (the least toxic regimen in ECOG 1594) or gemcitabine/cisplatin (which yielded an MS of 7.9 months in PS-2 patients). Patients received either carboplatin (area under the concentration-time curve, 6) and paclitaxel 200 mg/m2 every 3 weeks (CbP) or gemcitabine 1 g/m2 days 1 and 8 and cisplatin 60 mg/m2 day 1 every 3 weeks (CG).

Results

One hundred three patients were enrolled; 100 proved eligible. Median age was 66 years; 46% had at least 5% weight loss; 88% had stage IV or recurrent disease. Median number of cycles administered was three per arm. CbP featured more grade 3 neutropathy (10% v 0%) and more grade ≥ 3 neutropenia (59% v 33%), whereas CG yielded more grade ≥ 3 thrombocytopenia (33% v 14%), more grade ≥ 3 fatigue (22% v 14%), and more grade ≥ 1 creatinine elevations (43% v 6%). One grade 5 toxicity, confined to the CbP arm, occurred. Response rate, time to progression, MS, and 1-year OS rates for CG and CbP, were 23%, 4.8 months, 6.9 months, and 25%, and 14%, 4.2 months, 6.2 months, and 19%, respectively.

Conclusion

Platinum-based combination chemotherapy for PS-2 patients with NSCLC is feasible with acceptable toxicity, but survival in these patients remains inferior to that of PS-0 to -1 patients.
Two Consecutive Phase II Window Trials of Irinotecan Alone or in Combination With Vincristine for the Treatment of Metastatic Rhabdomyosarcoma: The Children's Oncology Group
Authors: Pappo Alberto S. , Lyden Elizabeth , Breitfeld Phillip , Donaldson Sarah S. , Wiener Eugene , Parham David , Crews Kristine R. , Houghton Peter , Meyer William H.
Published: February 2007

Purpose

To estimate the antitumor activity and toxicity of irinotecan alone and in combination with vincristine when administered as window therapy and in combination with standard chemotherapy in pediatric patients with newly diagnosed metastatic rhabdomyosarcoma.

Patients and Methods

Nineteen patients younger than age 21 years with newly diagnosed metastatic rhabdomyosarcoma or undifferentiated sarcoma received window therapy with two cycles of irinotecan (20 mg/m2 daily for 5 days, repeated for 2 weeks) and 50 patients received window therapy with vincristine 1.5 mg/m2 (weeks 0, 1, 3, and 4) and two cycles of irinotecan (20 mg/m2 daily for 5 days, repeated for 2 weeks). Patients who achieved a partial response (PR) or complete response (CR) received these agents alternating with vincristine (V; 1.5/mg/m2), dactinomycin (A; 1.5 mg/m2), and cyclophosphamide (C; 2.2 g/m2) during weeks 6 through 41. Nonresponders were treated with VAC alone. Radiotherapy was administered to sites of disease at weeks 15 to 21.

Results

The window response rate (PR/CR) for patients who received irinotecan was 42% (95% CI, 38% to 80%) but the high progressive disease (PD) rate of 32% (95% CI, 11% to 52%) prompted closure of the trial. The window CR/PR rate for patients who received vincristine and irinotecan was 70% (95% CI, 57% to 83%), and the PD rate was only 8%. GI toxicities (abdominal pain, diarrhea, dehydration) were the most common adverse effects associated with the administration of irinotecan.

Conclusion

The combination of vincristine and irinotecan is highly active in metastatic rhabdomyosarcoma. The different mechanism of action and nonoverlapping toxicity profile with VAC makes this combination an attractive candidate for further testing in intermediate risk patients with rhabdomyosarcoma.
Physical Activity, Body Mass Index, and Mammographic Density in Postmenopausal Breast Cancer Survivors
Authors: Irwin Melinda L. , Aiello Erin J. , McTiernan Anne , Bernstein Leslie , Gilliland Frank D. , Baumgartner Richard N. , Baumgartner Kathy B. , Ballard-Barbash Rachel
Published: February 2007

Purpose

To investigate the association between physical activity, body mass index (BMI), and mammographic density in a racially/ethnically diverse population-based sample of 522 postmenopausal women diagnosed with stage 0-IIIA breast cancer and enrolled in the Health, Eating, Activity, and Lifestyle Study.

Methods

We collected information on BMI and physical activity during a clinic visit 2 to 3 years after diagnosis. Weight and height were measured in a standard manner. Using an interview-administered questionnaire, participants recalled the type, duration, and frequency of physical activities they had performed in the last year. We estimated dense area and percentage density as a continuous measure using a computer-assisted software program from mammograms imaged approximately 1 to 2 years after diagnosis. Analysis of covariance methods were used to obtain mean density across WHO BMI categories and physical activity tertiles adjusted for confounders.

Results

We observed a statistically significant decline in percentage density (P for trend = .0001), and mammographic dense area (P for trend = .0052), with increasing level of BMI adjusted for potential covariates. We observed a statistically significant decline in mammographic dense area (P for trend = .036) with increasing level of sports/recreational physical activity in women with a BMI of at least 30 kg/m2. Conversely, in women with a BMI less than 25 kg/m2, we observed a non–statistically significant increase in mammographic dense area and percentage density with increasing level of sports/recreational physical activity.

Conclusion

Increasing physical activity among obese postmenopausal breast cancer survivors may be a reasonable intervention approach to reduce mammographic density.
Dynamic Noun Generalization: Moment‐to‐Moment Interactions Shape Children's Naming Biases
Authors: Samuelson Larissa K. , Horst Jessica S.
Published: February 2007

Recent research on early word learning suggests that children's behavior when‐generalizing novel nouns integrates their prior vocabulary knowledge with the specifics of the task. This study examines how these factors interact on the moment‐to‐moment time scale of the training children receive and the sequence of stimuli they are shown. In ***1 condition, we used a combination of training and stimulus factors predicted to produce a bias to generalize nouns by shape similarity. We then reduced this shape bias and amplified a bias to generalize nouns by material similarity via manipulations of training and stimuli across 3 other conditions. Additional analyses suggest that children's generalizations on individual trials are influenced by what they have seen and done on previous trials. These results highlight the importance of the task and stimuli in bringing children's prior knowledge to bear in early word learning.
Design aspects and clinical performance of the thrust plate hip prosthesis
Authors: Jacob H A C , Bereiter H H , Buergi M L
Published: February 2007

The thrust plate hip prosthesis (TPP) was conceived to maintain the physiological stress distribution in the proximal femur so as to prevent bone atrophy in this region, often encountered after implantation of conventional stem-type prostheses. A thrust plate of TiAlNb is firmly fixed to the neck of the femur by means of a forged CoCrMo bolt introduced through the lateral cortex, just below the greater trochanter, and through the metaphysis. A boss that contains the bolt head rests on the lateral cortex. A proximal extension from the thrust plate terminates in the ball head of the hip joint. Bone remodelling causes the initial prestressing of the structure ( primary stability) to decline, but full integration of the thrust plate with the underlying host bone affords secondary stability. A total of 102 TPPs were implanted in the Cantonal Hospital, Chur, Switzerland, from 1992 to 1999 in 84 patients. The TPP was selected particularly for patients of the younger age group (26-76). Through its ability to load the medial cortex of the proximal femur in a physiological manner, the cortical bone in this region is preserved. The mean Harris hip score is 97 points and the survival rate 98 per cent, 144 months post-operatively.
Developments in shoulder arthroplasty
Authors: Gregory T , Hansen U , Emery R J , Augereau B , Amis A A
Published: February 2007

Indications for shoulder arthroplasty are numerous, mainly owing to glenohumeral osteoarthritis, rheumatoid arthritis, or fracture of the proximal humerus. However, the anatomy and the biomechanics of the shoulder are complex and shoulder arthroplasty has evolved significantly over the past 30 years. This paper presents the main recent evolutions in shoulder replacement, the questions not answered yet, and the main future areas of research. The review focuses firstly on the design, positioning, and fixation of the humeral component, secondly on the design, positioning, and fixation of the glenoid implant, and thirdly on other concepts of shoulder arthroplasty such as the reversed prosthesis, the cementless surface replacement arthroplasty, and the bipolar arthroplasty. This review demonstrates that more research is needed. Although, in the long term, large randomized trials are needed to settle the fundamental questions of what type of replacement and which kind of fixation should be used, biomechanical research in the laboratory should be focused primarily on the comprehension of glenoid loosening, which is a major cause of total shoulder arthroplasty failure, and the significance of radiolucent lines which are often seen but with no clear understanding about their relation with failure.
Wear and biological activity of highly crosslinked polyethylene in the hip under low serum protein concentrations
Authors: Galvin A L , Tipper J L , Jennings L M , Stone M H , Jin Z M , Ingham E , Fisher J
Published: February 2007

Crosslinked ultra-high molecular weight polyethylene (UHMWPE) has been developed and introduced into clinical practice in order to reduce wear in the hip. Zero wear of highly crosslinked UHMWPE in vitro has been reported by some groups using lubricants with high concentrations of serum proteins in hip simulators. In contrast, some clinical studies have reported finite wear rates. The aim of this study was to compare the wear rates, wear surfaces, and wear debris produced by UHMWPE with different levels of crosslinking in a hip joint simulator, with lower, more physiologically relevant concentrations of protein in the lubricant.

The UHMWPEs were tested in the Leeds ProSim hip joint simulator against cobalt-chromium (CoCr) femoral heads. The wear particles were isolated and imaged using a field emission gun scanning electron microscope (FEGSEM) at high resolution. The highly crosslinked UHMWPEs had significantly lower wear volumes than the non-crosslinked UHMWPEs. No significant difference was found in the percentage number and percentage volume of the particles in different size ranges from any of the materials. They had similar values of specific biological activity. The functional biological activity (FBA), which takes into account the wear volume and specific biological activity, showed that the highly crosslinked UHMWPEs had lower FBAs due to their lower wear volume.
Fluorescent Calix[4]arene-appended Silica Nanotubes as Selective Chemosensor and Adsorbent for Pb2+ Ion
Authors: Kim Tae Ho , Jung Jong Hwa , Choi Jung Kyu , Choi Yun Hee , Lee Soo Jin , Seo Moo Lyong , Kim Jong Seung
Published: February 2007

Functionalized silica nanotube (FSNT) possessing a calix[4]arene moiety as a fluorescent receptor is fabricated by sol–gel reaction. The FSNT suspension in water selectively adsorbs 98% of Pb2+ over other metal ions (Li+, Na+, K+, Cs+, Mg2+, Ca2+, Ba2+, Zn2+, and Ag+) and shows quenched fluorescence emission in both pyrene monomer and excimer bands.
Past Success and Creativity over Time: A Study of Inventors in the Hard Disk Drive Industry
Authors: Audia Pino G. , Goncalo Jack A.
Published: February 2007

We integrate psychological theories of individual creativity with organizational theories of exploration versus exploitation to examine the relationship between past success and creativity over time. A key prediction derived from this theoretical integration is that successful people should be more likely to generate new ideas, but these ideas will tend to be less divergent as they favor the exploitation of familiar knowledge at the expense of the exploration of new domains. This prediction departs from the often-held view that people who generate more ideas will also generate ideas that are more divergent. Analyses of patenting in the hard disk drive industry support our prediction and indicate that collaboration with other inventors and organizational norms for exploration attenuate the tendency for successful individuals to generate increasingly incremental ideas.
Equivalent Information for Multiobjective Interactive Procedures
Authors: Luque Mariano , Caballero Rafael , Molina Julian , Ruiz Francisco
Published: February 2007

Despite the mathematical properties and algorithmic features of an interactive method, that method’s success usually lies in the kind of information it requires from the decision maker. In some cases, this information constrains the decision maker. If she does not find it easy and comfortable to answer the questions posed by the algorithm, then she will very likely give inconsistent answers, and the method will fail to find her most preferred solution. Therefore, it is of interest to find relations among the different kinds of information (local weights, local trade-offs, reference points, etc.) to allow the decision maker to choose what kind of questions he wants to answer, and to provide him with enough information to give such answers. In this paper, we define equivalent information—that is, different kinds of information—that produces the same solution when used in their corresponding interactive schemes.
Research Note—The Role of Production Lead Time and Demand Uncertainty in Marketing Durable Goods
Authors: Desai Preyas S. , Koenigsberg Oded , Purohit Devavrat
Published: February 2007

Firms often have to make their production decisions under conditions of demand uncertainty. This is especially true for product categories such as automobiles and technology goods where the lead time needed for manufacturing forces firms to make production decisions well in advance of the selling season. Once the firm has produced the goods, the available production volume affects the firm’s subsequent marketing decisions. In this paper, we study the relationship between the firm’s production and marketing decisions for a durable goods manufacturer. We develop a dynamic model of a durable product market in which the demand functions are developed from a micromodeling of consumer utility functions and an equilibrium analysis of consumer strategies. After taking into account the demand uncertainty as well as the potential for cannibalization of future sales, the manufacturer makes its production and sales decisions. We find that the firm’s optimal inventory level is U-shaped in the durability of the product and that the firm suffers a larger loss due to uncertainty when it is leases rather than sells its products. Furthermore, unlike the case for nondurables, for durable goods we find that the effect of uncertainty persists even after the uncertainty has been resolved.
The Economics of Remanufacturing Under Limited Component Durability and Finite Product Life Cycles
Authors: Geyer Roland , Van Wassenhove Luk N. , Atasu Atalay
Published: February 2007

This paper models and quantifies the cost-savings potential of production systems that collect, remanufacture, and remarket end-of-use products as perfect substitutes while facing the fundamental supply-loop constraints of limited component durability and finite product life cycles. The results demonstrate the need to carefully coordinate production cost structure, collection rate, product life cycle, and component durability to create or maximize production cost savings from remanufacturing.
A Good Sign for Multivariate Risk Taking
Authors: Eeckhoudt Louis , Rey Béatrice , Schlesinger Harris
Published: February 2007

Decisions under risk are often multidimensional, where the preferences of the decision maker depend on several attributes. For example, an individual might be concerned about both her level of wealth and the condition of her health. Many times the signs of successive cross-derivatives of a utility function play an important role in these models. However, there has not been a simple and intuitive interpretation for the meaning of such derivatives. The purpose of this paper is to give such an interpretation. In particular, we provide an equivalence between the signs of these cross-derivatives and individual preference within a particular class of simple lotteries.
Vicarious Learning in New Product Introductions in the Early Years of a Converging Market
Authors: Srinivasan Raji , Haunschild Pamela , Grewal Rajdeep
Published: February 2007

Technological developments combine previously distinct technologies that result in converging markets. In converging markets, firms from different industries compete against each other, often for the first time. We propose that firms introducing new products in converging markets will learn vicariously from other firms in the market. Further, we propose that this learning will vary across the dual-technology frontier (DTF), where the high-technology frontier (HTF) and low-technology frontier (LTF) map onto innovative activities driven by technological opportunity and user needs. We propose that at the HTF, local search will dominate and firms will be influenced by HTF product introductions of similarly sized, successful firms. At the LTF, learning will occur across the DTF, vary by origin industry of the firm, and be affected by complementarities in routines and capabilities and market competition among firms. We test the proposed model of vicarious learning using panel data on new product introductions of 67 firms in the U.S. digital camera market in the 1990s. Findings generally support our proposed model of vicarious learning in this market. They show heterogeneity in vicarious learning across the technology frontier and firm characteristics—including the origin industry of target firms. Our results show that vicarious learning in new product introductions in converging markets—which includes both mimetic and nonmimetic learning—is similar in some ways, but different from more traditional markets. We conclude with a discussion of the implications of our findings for theories of organizational learning, new product development, and converging markets.
Population‐Scale Movement of Coastal Cutthroat Trout in a Naturally Isolated Stream Network
Authors: Gresswell Robert E. , Hendricks Steven R.
Published: February 2007

To identify population‐scale patterns of movement, coastal cutthroat trout Oncorhynchus clarkii clarkii tagged and marked (35 radio‐tagged, 749 passive integrated transponder [PIT]‐tagged, and 3,025 fin‐clipped) were monitored from June 1999 to August 2000. The study watershed, located in western Oregon, was above a natural barrier to upstream movement. Emigration out of the watershed was estimated with a rotating fish trap. Approximately 70% of recaptured coastal cutthroat trout with PIT tags and 86% of those with radio tags moved predominantly at the channel‐unit scale (2–95 m); fewer tagged fish moved at the reach scale (66–734 m) and segment scale (229–3,479 m). In general, movement was greatest in April as spawning peaked and lowest in October, when discharge was at its lowest. Only 63 (<1% of tagged and marked fish) coastal cutthroat trout were captured in the fish trap. Trap efficiency was about 33%, and the expanded estimate of emigrants between February and June was 173 fish. These results suggest that unit‐scale movement is common throughout the year and that reach‐ and segment‐scale movements are important during the winter and spring. Although movement in headwater streams is most common at the channel‐unit scale, restoration of individual channel units of stream may not benefit the population at the watershed scale unless these activities are undertaken in the context of the greater whole. Individual coastal cutthroat trout move great distances, even within the small watersheds in the Oregon Coast Range, and although these movements may be infrequent, they may contribute substantially to recolonization after stochastic extirpation events (e.g., landslides and debris flows). Management strategies that focus on maintaining and restoring connectivity in a watershed represent an important step toward protecting the evolutionary capacity of stream salmonids.