bluuebunny/crossref_metadata_2025 huggingface dataset:
TomoJ: tomography software for three-dimensional reconstruction in transmission electron microscopy
Authors: MessaoudiI Cédric , Boudier Thomas , Sorzano Carlos Oscar Sanchez , Marco Sergio
Published: August 2007

Background

Transmission electron tomography is an increasingly common three-dimensional electron microscopy approach that can provide new insights into the structure of subcellular components. Transmission electron tomography fills the gap between high resolution structural methods (X-ray diffraction or nuclear magnetic resonance) and optical microscopy. We developed new software for transmission electron tomography, TomoJ. TomoJ is a plug-in for the now standard image analysis and processing software for optical microscopy, ImageJ.

Results

TomoJ provides a user-friendly interface for alignment, reconstruction, and combination of multiple tomographic volumes and includes the most recent algorithms for volume reconstructions used in three-dimensional electron microscopy (the algebraic reconstruction technique and simultaneous iterative reconstruction technique) as well as the commonly used approach of weighted back-projection.

Conclusion

The software presented in this work is specifically designed for electron tomography. It has been written in Java as a plug-in for ImageJ and is distributed as freeware.
Portraits of breast cancer progression
Authors: Dalgin Gul S , Alexe Gabriela , Scanfeld Daniel , Tamayo Pablo , Mesirov Jill P , Ganesan Shridar , DeLisi Charles , Bhanot Gyan
Published: August 2007

Background

Clustering analysis of microarray data is often criticized for giving ambiguous results because of sensitivity to data perturbation or clustering techniques used. In this paper, we describe a new method based on principal component analysis and ensemble consensus clustering that avoids these problems.

Results

We illustrate the method on a public microarray dataset from 36 breast cancer patients of whom 31 were diagnosed with at least two of three pathological stages of disease (atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). Our method identifies an optimum set of genes and divides the samples into stable clusters which correlate with clinical classification into Luminal, Basal-like and Her2+ subtypes. Our analysis reveals a hierarchical portrait of breast cancer progression and identifies genes and pathways for each stage, grade and subtype. An intriguing observation is that the disease phenotype is distinguishable in ADH and progresses along distinct pathways for each subtype. The genetic signature for disease heterogeneity across subtypes is greater than the heterogeneity of progression from DCIS to IDC within a subtype, suggesting that the disease subtypes have distinct progression pathways.

Our method identifies six disease subtype and one normal clusters. The first split separates the normal samples from the cancer samples. Next, the cancer cluster splits into low grade (pathological grades 1 and 2) and high grade (pathological grades 2 and 3) while the normal cluster is unchanged. Further, the low grade cluster splits into two subclusters and the high grade cluster into four. The final six disease clusters are mapped into one Luminal A, three Luminal B, one Basal-like and one Her2+.

Conclusion

We confirm that the cancer phenotype can be identified in early stage because the genes altered in this stage progressively alter further as the disease progresses through DCIS into IDC. We identify six subtypes of disease which have distinct genetic signatures and remain separated in the clustering hierarchy. Our findings suggest that the heterogeneity of disease across subtypes is higher than the heterogeneity of the disease progression within a subtype, indicating that the subtypes are in fact distinct diseases.
Establishment and mitotic stability of an extra-chromosomal mammalian replicon
Authors: Stehle Isa M , Postberg Jan , Rupprecht Sina , Cremer Thomas , Jackson Dean A , Lipps Hans J
Published: August 2007

Background

Basic functions of the eukaryotic nucleus, like transcription and replication, are regulated in a hierarchic fashion. It is assumed that epigenetic factors influence the efficiency and precision of these processes. In order to uncouple local and long-range epigenetic features we used an extra-chromosomal replicon to study the requirements for replication and segregation and compared its behavior to that of its integrated counterpart.

Results

The autonomous replicon replicates in all eukaryotic cells and is stably maintained in the absence of selection but, as other extra-chromosomal replicons, its establishment is very inefficient. We now show that following establishment the vector is stably associated with nuclear compartments involved in gene expression and chromosomal domains that replicate at the onset of S-phase. While the vector stays autonomous, its association with these compartments ensures the efficiency of replication and mitotic segregation in proliferating cells.

Conclusion

Using this novel minimal model system we demonstrate that relevant functions of the eukaryotic nucleus are strongly influenced by higher nuclear architecture. Furthermore our findings have relevance for the rational design of episomal vectors to be used for genetic modification of cells: in order to improve such constructs with respect to efficiency elements have to be identified which ensure that such constructs reach regions of the nucleus favorable for replication and transcription.
Analysis of the Rana catesbeiana tadpole tail fin proteome and phosphoproteome during T3-induced apoptosis: identification of a novel type I keratin
Authors: Domanski Dominik , Helbing Caren C
Published: August 2007

Background

Thyroid hormones (THs) are vital in the maintenance of homeostasis and in the control of development. One postembryonic developmental process that is principally regulated by THs is amphibian metamorphosis. This process has been intensively studied at the genomic level yet very little information at the proteomic level exists. In addition, there is increasing evidence that changes in the phosphoproteome influence TH action.

Results

Here we identify components of the proteome and phosphoproteome in the tail fin that changed within 48 h of exposure of premetamorphic Rana catesbeiana tadpoles to 10 nM 3,5,3'-triiodothyronine (T3). To this end, we developed a cell and protein fractionation method combined with two-dimensional gel electrophoresis and phosphoprotein-specific staining. Altered proteins were identified using mass spectrometry (MS). We identified and cloned a novel Rana larval type I keratin, RLK I, which may be a target for caspase-mediated proteolysis upon exposure to T3. In addition, the RLK I transcript is reduced during T3-induced and natural metamorphosis which is consistent with a larval keratin. Furthermore, GILT, a protein involved in the immune system, is changed in phosphorylation state which is linked to its activation. Using a complementary MS technique for the analysis of differentially-expressed proteins, isobaric tags for relative and absolute quantitation (iTRAQ) revealed 15 additional proteins whose levels were altered upon T3 treatment. The success of identifying proteins whose levels changed upon T3 treatment with iTRAQ was enhanced through de novo sequencing of MS data and homology database searching. These proteins are involved in apoptosis, extracellular matrix structure, immune system, metabolism, mechanical function, and oxygen transport.

Conclusion

We have demonstrated the ability to derive proteomics-based information from a model species for postembryonic development for which no genome information is currently available. The present study identifies proteins whose levels and/or phosphorylation states are altered within 48 h of the induction of tadpole tail regression prior to overt remodeling of the tail. In particular, we have identified a novel keratin that is a target for T3-mediated changes in the tail that can serve as an indicator of early response to this hormone.
Detection of "Rickettsia sp. strain Uilenbergi" and "Rickettsia sp. strain Davousti" in Amblyomma tholloni ticks from elephants in Africa
Authors: Matsumoto Kotaro , Parola Philippe , Rolain Jean-Marc , Jeffery Kathryn , Raoult Didier
Published: August 2007

Background

To date, 6 tick-borne rickettsiae pathogenic for humans are known to occur in Africa and 4 of them were first identified in ticks before being recognized as human pathogens.

Results

We examined 33 and 5Amblyomma tholloniticks from African elephants in the Central African Republic and Gabon, respectively, by PCR amplification and sequencing of a part ofgltAandompAgenes of the genusRickettsia. The partial sequences ofgltAandompAgenes detected in tick in Gabon had 99.1% similarity with those ofR. heilongjiangensisand 97.1% with those ofRickettsiasp. HL-93 strain, respectively. The partialgltAandompAgene sequences detected in tick in the Central African Republic were 98.9% and 95.1% similar to those ofRickettsiasp. DnS14 strain andR. massiliae, respectively. Phylogenetic analysis showedRickettsiasp. detected in Gabon clusters withR. japonicaandR. heilongjiangensisin a phylogenetic tree based on the partialgltAandompAgenes. The genotype of theRickettsiasp. detected in the Central African Republic is close to those ofR. massiliaegroup in the phylogenetic tree based on partialgltAgene sequences, and distantly related to other rickettsiae in the tree based on partialompAgene.

Conclusion

The degrees of similarity of partialgltAandompAgenes with recognized species indicate the rickettsiae detected in this study may be new species although we could only study the partial sequences of 2 genes regarding the amount of DNA that was available. We propose theRickettsiasp. detected in Gabon be provisionally named "Rickettsia sp. stain Davousti" andRickettsiasp. detected in the Central African Republic be named "Rickettsia sp.strain Uilenbergi".
Optimization of diagnostic imaging use in patients with acute abdominal pain (OPTIMA): Design and rationale
Authors: Laméris Wytze , van Randen Adrienne , Dijkgraaf Marcel GW , Bossuyt Patrick MM , Stoker Jaap , Boermeester Marja A
Published: August 2007

Background

The acute abdomen is a frequent entity at the Emergency Department (ED), which usually needs rapid and accurate diagnostic work-up. Diagnostic work-up with imaging can consist of plain X-ray, ultrasonography (US), computed tomography (CT) and even diagnostic laparoscopy. However, no evidence-based guidelines exist in current literature. The actual diagnostic work-up of a patient with acute abdominal pain presenting to the ED varies greatly between hospitals and physicians. The OPTIMA study was designed to provide the evidence base for constructing an optimal diagnostic imaging guideline for patients with acute abdominal pain at the ED.

Methods/design

Thousand consecutive patients with abdominal pain > 2 hours and < 5 days will be enrolled in this multicentre trial. After clinical history, physical and laboratory examination all patients will undergo a diagnostic imaging protocol, consisting of plain X-ray (upright chest and supine abdomen), US and CT. The reference standard will be a post hoc assignment of the final diagnosis by an expert panel. The focus of the analysis will be on the added value of the imaging modalities over history and clinical examination, relative to the incremental costs.

Discussion

This study aims to provide the evidence base for the development of a diagnostic algorithm that can act as a guideline for ED physicians to evaluate patients with acute abdominal pain.
Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome
Authors: Chen Ashton , Frank Rachel , Vento Suzanne , Crosby Virginia , Chandra Manju , Gauthier Bernard , Valderrama Elsa , Trachtman Howard
Published: August 2007

Background

Idiopathic membranous nephropathy (IMN) is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome.

Methods

A retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988–2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFRe), histopathology, type and duration of treatment, and clinical status at final evaluation.

Results

13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 ± 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 ± 2.5 and all patients had a normal GFRe. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications – prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 ± 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 ± 3.1. The mean GFRe was 127 ± 57 mL/min/m2. Three patients had Chronic Kidney Disease Stage 3, all of whom were also hypertensive.

Conclusion

IMN is a rare but serious glomerulopathy in pediatrics. We estimate that it accounts for approximately 3% of renal biopsies. Long-term prognosis is guarded because approximately 50% of patients may have evidence of progressive kidney disease.
The unmet need for Emergency Obstetric Care in Tanga Region, Tanzania
Authors: Prytherch Helen , Massawe Siriel , Kuelker Rainer , Hunger Claudia , Mtatifikolo Ferdinand , Jahn Albrecht
Published: August 2007

Background

Improving maternal health by reducing maternal mortality constitutes the fifth Millennium Development Goal and represents a key public health challenge in the United Republic of Tanzania. In response to the need to evaluate and monitor safe motherhood interventions, this study aims at assessing the coverage of obstetric care according to the Unmet Obstetric Need (UON) concept by obtaining information on indications for, and outcomes of, major obstetric interventions. Furthermore, we explore whether this concept can be operationalised at district level.

Methods

A two year study using the Unmet Obstetric Need concept was carried out in three districts in Tanga Region, Tanzania. Data was collected prospectively at all four hospitals in the region for every woman undergoing a major obstetric intervention, including indication and outcome. The concept was adapted to address differentials in access to emergency obstetric care between districts and between rural and urban areas. Based upon literature and expert consensus, a threshold of 2% of all deliveries was used to define the expected minimum requirement of major obstetric interventions performed for absolute maternal indications.

Results

Protocols covering 1,260 complicated deliveries were analysed. The percentage of major obstetric interventions carried out in response to an absolute maternal indication was only 71%; most major obstetric interventions (97%) were caesarean sections. The most frequent indication was cephalo-pelvic-disproportion (51%). The proportion of major obstetric interventions for absolute maternal indications performed amongst women living in urban areas was 1.8% of all deliveries, while in rural areas it was only 0.7%. The high proportion (8.3%) of negative maternal outcomes in terms of morbidity and mortality, as well as the high perinatal mortality of 9.1% (still birth 6.9%, dying within 24 hours 1.7%, dying after 24 hours 0.5%) raise concern about the quality of care being provided.

Conclusion

Based on the 2% threshold, Tanga Region – with an overall level of major obstetric interventions for absolute maternal indications of 1% and a caesarean section rate of 1.4% – has significant unmet obstetric need with a considerable rural-urban disparity. The UON concept was found to be a suitable tool for evaluating and monitoring the coverage of obstetric care at district level.
Fatal interstitial lung disease associated with oral erlotinib therapy for lung cancer
Authors: Makris Demosthenes , Scherpereel Arnaud , Copin Marie Christine , Colin Guillaume , Brun Luc , Lafitte Jean Jacques , Marquette Charles Hugo
Published: August 2007

Background

Erlotinib is a Human Epidermal Growth Factor Receptor Type 1/tyrosine kinase (EGFR) inhibitor which is used for non-small-cell lung cancer treatment. Despite that erlotinib is considered to have a favorable safety profile, adverse events such as interstitial lung disease (ILD) were reported in pivotal studies. The authors report the first histologically confirmed case of fatal ILD associated with erlotinib therapy.

Case Presentation

The medical record of a patient who developed fatal ILD after receiving erlotinib treatment was reviewed to identify the cause of death and other factors potentially contributive to this adverse outcome. A 55-year-old smoker with no evidence of pre-existing interstitial disease developed bilateral ILD and respiratory failure which could be explained only as a toxicity of erlotinib. He had a history of stage IV left upper lobe squamous-cell carcinoma for which he had received three successive regimens of chemotherapy (ifosfamide plus gemcitabine, docetaxel, mitomycin plus navelbine), followed five months later by erlotinib. At initiation of erlotinib treatment there were no radiological signs suggestive of ILD disease or apparent clinical signs of respiratory distress. While the patient completed two months with erlotinib therapy he developed bilateral interstitial infiltrates; despite discontinuation of erlotinib he was admitted with respiratory failure two weeks later. Diagnostic work up for other causes of pneumonitis including infectious diseases, congestive cardiac failure and pulmonary infraction was negative. Empiric treatment with oxygene, corticosteroids and later with cyclophosphamide was ineffective and the patient progressively deteriorated and died. The clinical and post-mortem examination findings are presented and the possible association relationship between erlotinib induced ILD and previous chemotherapy is discussed.

Conclusion

Physicians should be alert to the fact that erlotinib related ILD, although infrequent, is potential fatal. The association between selective EGFR-inhibitors and ILD should be further investigated.
Correlates of exposure to second-hand smoke in an urban Mediterranean population
Authors: Twose Jorge , Schiaffino Anna , García Montse , Borras Josep Maria , Fernández Esteve
Published: August 2007

Background

To describe the socio-demographic factors associated with exposure to second-hand smoke (SHS) in different settings (home, leisure, and workplace).

Methods

We analysed cross-sectional data on self-reported SHS exposure in 1059 non-daily smokers interviewed in the Cornellà Health Interview Survey Follow-up Study in 2002. We calculated age-adjusted prevalence rates and prevalence rate ratios of SHS exposure at home, at the workplace, during leisure time, and in any of these settings.

Results

The age-standardized prevalence rate of SHS exposure in any setting was 69.5% in men and 62.9% in women. Among men, 25.9% reported passive smoking at home, 55.1% during leisure time, and 34.0% at the workplace. Among women, prevalence rates in these settings were 34.1%, 44.3% and 30.1%, respectively. Overall exposure to SHS decreased with age in both men and women. In men, SHS exposure was related to marital status, physical activity, smoking, and alcohol intake. In women, SHS exposure was related to educational level, marital status, occupational status, self-perceived health, smoking-related illness, and alcohol intake.

Conclusion

The prevalence of SHS exposure in this population was high. The strongest association with exposure were found for age and occupational status in men, and age and educational level in women.
Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity
Authors: Ulloa-Montoya Fernando , Kidder Benjamin L , Pauwelyn Karen A , Chase Lucas G , Luttun Aernout , Crabbe Annelies , Geraerts Martine , Sharov Alexei A , Piao Yulan , Ko Minoru SH , Hu Wei-Shou , Verfaillie Catherine M
Published: August 2007

Background

Recently, several populations of postnatal stem cells, such as multipotent adult progenitor cells (MAPCs), have been described that have broader differentiation ability than classical adult stem cells. Here we compare the transcriptome of pluripotent embryonic stem cells (ESCs), MAPCs, and lineage-restricted mesenchymal stem cells (MSCs) to determine their relationship.

Results

Applying principal component analysis, non-negative matrix factorization and k-means clustering algorithms to the gene-expression data, we identified a unique gene-expression profile for MAPCs. Apart from the ESC-specific transcription factor Oct4 and other ESC transcripts, some of them associated with maintaining ESC pluripotency, MAPCs also express transcripts characteristic of early endoderm and mesoderm. MAPCs do not, however, express Nanog or Sox2, two other key transcription factors involved in maintaining ESC properties. This unique molecular signature was seen irrespective of the microarray platform used and was very similar for both mouse and rat MAPCs. As MSC-like cells isolated under MAPC conditions are virtually identical to MSCs, and MSCs cultured in MAPC conditions do not upregulate MAPC-expressed transcripts, the MAPC signature is cell-type specific and not merely the result of differing culture conditions.

Conclusion

Multivariate analysis techniques clustered stem cells on the basis of their expressed gene profile, and the genes determining this clustering reflected the stem cells' differentiation potential in vitro. This comparative transcriptome analysis should significantly aid the isolation and culture of MAPCs and MAPC-like cells, and form the basis for studies to gain insights into genes that confer on these cells their greater developmental potency.
Phase I Study of Decitabine Alone or in Combination With Valproic Acid in Acute Myeloid Leukemia
Authors: Blum William , Klisovic Rebecca B. , Hackanson Bjoern , Liu Zhongfa , Liu Shujun , Devine Hollie , Vukosavljevic Tamara , Huynh Lenguyen , Lozanski Gerard , Kefauver Cheryl , Plass Christoph , Devine Steven M. , Heerema Nyla A. , Murgo Anthony , Chan Kenneth K. , Grever Michael R. , Byrd John C. , Marcucci Guido
Published: August 2007

Purpose

To determine an optimal biologic dose (OBD) of decitabine as a single agent and then the maximum-tolerated dose (MTD) of valproic acid (VA) combined with decitabine in acute myeloid leukemia (AML).

Patients and Methods

Twenty-five patients (median age, 70 years) were enrolled; 12 were untreated and 13 had relapsed AML. To determine an OBD (based on a gene re-expression end point), 14 patients received decitabine alone for 10 days. To determine the MTD, 11 patients received decitabine (at OBD, days 1 through 10) plus dose-escalating VA (days 5 through 21).

Results

The OBD of decitabine was 20 mg/m2/d intravenously, with limited nonhematologic toxicity. In patients treated with decitabine plus VA, dose-limiting encephalopathy occurred in two of two patients at VA 25 mg/kg/d and one of six patients at VA 20 mg/kg/d. Drug-induced re-expression of estrogen receptor (ER) was associated with clinical response (P ≤ .05). ER promoter demethylation, global DNA hypomethylation, depletion of DNA methyltransferase enzyme, and histone hyperacetylation were also observed. In an intent-to-treat analysis, the response rate was 44% (11 of 25). Of 21 assessable patients, 11 (52%) responded: four with morphologic and cytogenetic complete remission (CR; each had complex karyotype), four with incomplete CR, and three with partial remission. In untreated AML, four of nine assessable patients achieved CR. Clinical responses appeared similar for decitabine alone or with VA.

Conclusion

Low-dose decitabine was safe and showed encouraging clinical and biologic activity in AML, but the addition of VA led to encephalopathy at relatively low doses. On the basis of these results, additional studies of decitabine (20 mg/m2/d for 10 days) alone or with an alternative deacetylating agent are warranted.
A Phase II Placebo-Controlled Trial of Neoadjuvant Anastrozole Alone or With Gefitinib in Early Breast Cancer
Authors: Smith Ian E. , Walsh Geraldine , Skene Anthony , Llombart Antonio , Mayordomo José Ignacio , Detre Simone , Salter Janine , Clark Emma , Magill Patrick , Dowsett Mitch
Published: August 2007

Purpose

Increased epidermal growth factor receptor (EGFR) expression may promote breast cancer resistance to endocrine therapy. We have therefore investigated whether neoadjuvant gefitinib, an EGFR inhibitor, might overcome biologic and clinical resistance to neoadjuvant anastrozole in a phase II placebo-controlled trial.

Patients and Methods

Postmenopausal women with stage I to IIIB hormone receptor–positive early breast cancer received anastrozole 1 mg daily for 16 weeks and were randomly assigned at a ratio of 2:5:5 to receive, in addition, gefitinib 250 mg/d orally for 16 weeks: placebo 1 tablet/d orally for 2 weeks and then gefitinib for 14 weeks or placebo for 16 weeks. The primary end point was biologic change in proliferation as measured by Ki67 at 2 and 16 weeks; the main secondary end point was overall objective response (OR).

Results

Two hundred six women were randomly assigned. Mean changes in Ki67 with anastrozole and gefitinib versus anastrozole alone were −77.4% and −83.6%, respectively, between baseline and 16 weeks (geometric mean ratio = 1.37; 95% CI, 0.79 to 2.39; P = .26), −80.1% and −71.3% between baseline and 2 weeks (geometric mean ratio = 0.70; 95% CI, 0.39 to 1.25; P = .22) and −19.3% and −43% (geometric mean ratio = 1.42; 95% CI, 0.86 to 2.35; P = .16) between 2 and 16 weeks. ORs in the combination and anastrozole alone groups were 48% and 61% (estimated difference = −13.1%; 95% CI, –27.3% to 1.2%), respectively, with a nonsignificant trend against the combination (P = .08) and 48% versus 72% (estimated difference = −24.1%; 95% CI, –45.3% to −2.9%) in the progesterone-receptor–positive subgroup, which was significant (P = .03) and consistent with Ki67 changes. Common treatment-related adverse events included diarrhea, rash, alopecia, dry skin, and nausea. There was no evidence of a pharmacokinetic interaction.

Conclusion

Addition of gefitinib to neoadjuvant anastrozole had no additional clinical or biologic effect, failing to support our original hypothesis.
Shifting Breast Cancer Trends in the United States
Authors: Anderson William F. , Reiner Anne S. , Matsuno Rayna K. , Pfeiffer Ruth M.
Published: August 2007

Purpose

United States breast cancer incidence rates declined during the years 1999 to 2003, and then reached a plateau. These recent trends are impressive and may indicate an end to decades of increasing incidence.

Methods

To put emerging incidence trends into a broader context, we examined age incidence patterns (frequency and rates) during five decades. We used age density plots, two-component mixture models, and age-period-cohort (APC) models to analyze changes in the United States breast cancer population over time.

Results

The National Cancer Institute's Connecticut Historical Database and Surveillance, Epidemiology, and End Results program collected 600,000+ in situ and invasive female breast cancers during the years 1950 to 2003. Before widespread screening mammography in the early 1980s, breast cancer age-at-onset distributions were bimodal, with dominant peak frequency (or mode) near age 50 years and smaller mode near age 70 years. With widespread screening mammography, bimodal age distributions shifted to predominant older ages at diagnosis. From 2000 to 2003, the bimodal age distribution returned to dominant younger ages at onset, similar to patterns before mammography screening. APC models confirmed statistically significant calendar-period (screening) effects before and after 1983 to 1987.

Conclusion

Breast cancer in the general United States population has a bimodal age at onset distribution, with modal ages near 50 and 70 years. Amid a background of previously increasing and recently decreasing incidence rates, breast cancer populations shifted from younger to older ages at diagnosis, and then back again. These dynamic fluctuations between early-onset and late-onset breast cancer types probably reflect a complex interaction between age-related biologic, risk factor, and screening phenomena.
Cardiovascular Actions of Insulin
Authors: Muniyappa Ranganath , Montagnani Monica , Koh Kwang Kon , Quon Michael J.
Published: August 2007

Insulin has important vascular actions to stimulate production of nitric oxide from endothelium. This leads to capillary recruitment, vasodilation, increased blood flow, and subsequent augmentation of glucose disposal in classical insulin target tissues (e.g., skeletal muscle). Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways regulating endothelial production of nitric oxide share striking parallels with metabolic insulin-signaling pathways. Distinct MAPK-dependent insulin-signaling pathways (largely unrelated to metabolic actions of insulin) regulate secretion of the vasoconstrictor endothelin-1 from endothelium. These and other cardiovascular actions of insulin contribute to coupling metabolic and hemodynamic homeostasis under healthy conditions. Cardiovascular diseases are the leading cause of morbidity and mortality in insulin-resistant individuals. Insulin resistance is typically defined as decreased sensitivity and/or responsiveness to metabolic actions of insulin. This cardinal feature of diabetes, obesity, and dyslipidemia is also a prominent component of hypertension, coronary heart disease, and atherosclerosis that are all characterized by endothelial dysfunction. Conversely, endothelial dysfunction is often present in metabolic diseases. Insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase-dependent signaling that in vascular endothelium contributes to a reciprocal relationship between insulin resistance and endothelial dysfunction. The clinical relevance of this coupling is highlighted by the findings that specific therapeutic interventions targeting insulin resistance often also ameliorate endothelial dysfunction (and vice versa). In this review, we discuss molecular mechanisms underlying cardiovascular actions of insulin, the reciprocal relationships between insulin resistance and endothelial dysfunction, and implications for developing beneficial therapeutic strategies that simultaneously target metabolic and cardiovascular diseases.
Tele-assistance in intellectual disability
Authors: Buono Serafino , Città Santina
Published: August 2007

We conducted a trial of multidisciplinary tele-assistance to support 20 families of patients with intellectual disability. Psychological, educational, social and medical support was provided by videoconferencing, email and on-line sharing of diagnostic and rehabilitation tools. The main topics dealt with were self-care, learning processes, adaptation skills, management of problem behaviours and health problems. A computer network was developed which connected workstations at the patients' houses and two main sites at the Oasi Institute. It was based on ISDN transmission. During the study, 840 videoconference sessions and 805 programme planning and case discussions took place. After one year of tele-assistance, most families (84%) stated that they were satisfied with the experience, underlining, among various advantages, the availability of professional and continuous support, the reduction of inconvenient travelling to specialized centres and the increase in adaptation skills of their children. Although the present study was empirical, our experience suggests that tele-assistance can satisfy some of the main needs of persons with intellectual disability and their families.
The other side of teledermatology: patient preferences
Authors: Mofid Mitra , Nesbitt Thomas , Knuttel Robin
Published: August 2007

We studied patient preferences for a real-time teledermatology consultation or a conventional dermatology consultation. Dermatology patients were given the option of being seen by a dermatologist at their outlying primary care site via telemedicine or of being examined face-to-face by the same dermatologist at the primary care site. The same dermatologist provided the teleconsultations and the conventional consultations. During a 16-month study period, 52 patients were evaluated via telemedicine and 46 patients were seen face-to-face. The demographics for both study groups were similar. Those patients who selected telemedicine were more likely to have seen a dermatologist fewer than twice during the previous year, more likely to self-describe themselves in excellent health and more likely to choose a face-to-face evaluation when presenting with a possible skin cancer or a mole. Patients aged 56 years or less tended to be more likely to be seen via telemedicine, although the association with age was not significant ( P = 0.06). This information may help providers to devise strategies to direct patients to telemedicine if and when it is appropriate.
People Skills: Marketing OR/MS—A People Problem
Authors: Levasseur Robert E.
Published: August 2007

This is another in a series of articles about some of the most effective models, methods, and processes of organization development (OD), a discipline that offers much to the OR/MS practitioner determined to help clients solve real-world problems. Because it is based on a systemic view of organizations, OD includes the whole universe of ambiguous people-related issues that increasingly determine the success or failure of efforts to implement otherwise flawless technical solutions.
Implementing Large-Scale Optimization Models in Excel Using VBA
Authors: LeBlanc Larry J. , Galbreth Michael R.
Published: August 2007

We discuss the importance of spreadsheets for optimization modeling, including a description of their limitations for large-scale problems. We then describe efficient ways to overcome these limits. Our approach makes use of Excel’s standard functionality but augments Excel with its programming language, Visual Basic for Applications (VBA), where necessary. We show how using VBA within Excel to generate and solve large linear programs (LPs) overcomes many of the problems inherent in purely spreadsheet-based models and greatly increases model usability. The techniques described were instrumental in our successful development of a large-scale procurement/distribution LP that resulted in savings of approximately $1,000,000 in the first year, with even greater annual savings expected in the future.
Static and Dynamic Order Scheduling for Recreational Rental Vehicles at Tourism Holdings Limited
Authors: Ernst Andreas T. , Horn Mark , Krishnamoorthy Mohan , Kilby Philip , Degenhardt Phil , Moran Michael
Published: August 2007

Tourism Holdings Limited (THL), with 14 locations in Australia and New Zealand, operates a fleet of approximately 4,000 recreational rental vehicles of many types. It allocates vehicles to bookings centrally. If demand for a particular vehicle type at a location exceeds supply, THL may substitute vehicles of similar types or relocate vehicles from other locations to the location that needs the vehicles. The static problem that THL faces daily is to determine a vehicle schedule that minimizes the tangible and intangible costs of such substitutions and relocations. The dynamic problem is to determine—sometimes as the customer waits—whether a vehicle will be available to cover a potential booking and to incorporate that booking into the schedule. The Commonwealth Scientific and Industrial Research Organisation (CSIRO) has researched, developed, and supplied software, VASS and D-VASS, to solve the static and dynamic aspects of THL’s schedule creation and maintenance. This paper describes the THL problem, the systems that CSIRO implemented, and how THL embedded these systems into its operations.
Indian Auto-Component Supply Chain at the Crossroads
Authors: Balakrishnan Karthik , Seshadri Sridhar , Sheopuri Anshul , Iyer Ananth
Published: August 2007

We trace the evolution of the auto-component supply chain in India beginning with the opening of the economy in 1990 by using a combination of data on firm and sector performance, customer-satisfaction surveys, and interviews with experts. During the past decade, the industry has made remarkable progress on multiple fronts. This is particularly true with regard to quality—10 firms in this industry have won the coveted Deming prize during the past six years. Surprisingly, we first observe that the financial performance of the firms that won the Deming prize (i.e., Deming firms) shows no definitive differences from the performance in the rest of the industry. We then analyze the productivity growth at the firm level across two five-year intervals using a total-factor productivity model. Our results suggest that productivity improved much more during the second period, which is the interval in which most of the firms won the Deming prize. We also analyze the impact of winning the award on profitability and suggest that new firms were able to grow faster in the improving business environment. To “externally” validate our findings, we compare the auto sector in India with that in China. Despite a 10-year disadvantage because of costs that are beyond the control of the firm, the auto sector in India seems to be competitive with that sector in China on all firm-specific factors. In summary, we suggest that firms in this sector have taken the first step by becoming competitive in the areas of cost and quality. We suggest that they are now at a crossroads and must make several choices to leverage these quality gains into a profitable, global supply chain strategy.
Incorporating randomness in the Fisher information for improving item‐exposure control in CATs
Authors: Barrada Juan Ramón , Olea Julio , Ponsoda Vicente , Abad Francisco José
Published: August 2007

The most commonly employed item selection rule in a computerized adaptive test (CAT) is that of selecting the item with the maximum Fisher information for the estimated trait level. This means a highly unbalanced distribution of item‐exposure rates, a high overlap rate among examinees and, for item bank management, strong pressure to replace items with a high discrimination parameter in the bank. An alternative for mitigating these problems involves, at the beginning of the test, basing item selection mainly on randomness. As the test progresses, the weight of information in the selection increases. In the present work we study, for two selection rules, the progressive methods (Revuelta & Ponsoda, 1998) and the proportional method (Segall, 2004a), different functions that define the weight of the random component according to the position in the test of the item to be administered. The functions were tested in simulated item banks and in an operative bank. We found that both the progressive and the proportional methods tolerate a high weight of the random component with minimal or zero loss of accuracy, while bank security and maintenance are improved.
Optional thinking ability among hospital‐treated deliberate self‐harm patients: A 1‐year follow‐up study
Authors: McAuliffe Carmel. , Corcoran Paul. , Hickey Portia. , McLeavey Breda C.
Published: August 2007

Objectives

To investigate the association between optional thinking (the ability to generate alternative solutions to interpersonal problems) in deliberate self‐harm (DSH) patients and repeated self‐harm.

Design

A prospective study of the association between optional thinking in interpersonal problem solving and repeated DSH within 12 months.

Method

A non‐consecutive sample (N = 152) of DSH patients presenting to the Accident and Emergency department of an acute hospital in Cork city, Ireland, was assessed using a structured interview schedule including the Suicide Intent Scale, the Hopelessness Scale, and the Optional Thinking Test. Repetition within 1 year was established by checking Accident and Emergency records at all three city hospitals. Participants were categorized as repeaters if they engaged in at least one further hospital‐treated DSH episode, or non‐repeaters.

Results

Approximately two‐thirds (63.1%) of the sample had engaged in at least one act of DSH prior to their index episode. During follow‐up 31 individuals (20.4%) repeated. History of self‐harm was significantly associated with prospective repetition when considered alongside all the other predictor variables. Among first evers, low scores on the optional thinking test were significantly associated with the increased risk of repetition within 12 months. Among those with previous DSH, there was no evidence of an association between optional thinking and repetition within 12 months.

Conclusions

Poor optional thinking is associated with increased risk of repeated deliberate self‐harm in those who present with a first self‐harm episode. Interventions to improve optional thinking skills, delivered soon after a first DSH presentation, may be useful in preventing repetition.
Breast Screening in Response to Gain, Loss, and Empowerment Framed Messages among Diverse, Low-Income Women
Authors: Consedine Nathan S , Horton David , Magai Carol , Kukafka Rita
Published: August 2007

Framed messaging has emerged as an important means of promoting a number of health behaviors, including breast cancer screening. However, studies of message framing have infrequently considered race and income as possible moderators of framing effects, despite their importance to screening behavior. The current study examined whether demographic characteristics moderated participant responses to message framing. In the study, 102 Black and 42 White low-income, low-screening women were randomized to a loss, gain, or empowerment frame telephone intervention and re-contacted at 6 and 12 months. Contrary to expectation, there was no main effect for framing condition, although both loss and empowerment conditions elicited superior screening than the gain condition at 12 months. Income proved an important moderator of framing effects, interacting with both condition and race to influence screening. Message frames may differ in the amount of time they require to manifest in behavioral outcomes and may lead to changes in different screening outcomes. Understanding how framing effects vary as a function of key demographic characteristics such as race and income is likely to prove important as such variables facilitate targeting of frames.
Determinants of Inadequate Prenatal Care Utilization by African American Women
Authors: Johnson Allan A , Hatcher Barbara J , El-Khorazaty M. Nabil , Milligan Renee A , Bhaskar Brinda , Rodan Margaret F , Richards Leslie , Wingrove Barbara K , Laryea Haziel A
Published: August 2007

A convenience sample of city-dwelling African American women (n=246) was interviewed during each woman's postpartum stay at one of five hospitals in Washington, D.C. to determine their perceptions of factors influencing their prenatal care utilization. The Kotelchuck Adequacy of Prenatal Care Utilization Index was used to classify prenatal care utilization as either adequate (Adequate Plus and Adequate groups combined) or inadequate (Intermediate and Inadequate groups combined). Of the 246 women studied, 40% (99) had adequate prenatal care utilization. Using Classification and Regression Trees analysis, the following risk groups for inadequate prenatal care utilization were identified: women who reported psychosocial problems as barriers and who were not participants in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) (percent adequate=8.8); women who reported psychosocial problems as barriers, were participants of the WIC program, and reported substance use (percent adequate=13.8); and women who reported psychosocial problems as barriers, were participants of the WIC program, denied substance use, and reported childcare problems as barriers (percent adequate=20.0).
Breaking the Silence: What Homeless 18- to 24-Year-Olds Say about HIV Vaccine Trials
Authors: Koniak Deborah , Nyamathi Adeline , Tallen Louise , González-Figueroa Evelyn , Dominick Ernestina
Published: August 2007

Development of a global HIV vaccine will require enrollment of a large number of adults and adolescents in clinical trials. Involvement of homeless young adults in these trials will be particularly important because they often practice high-risk behaviors and are disproportionately infected by HIV. This qualitative study explores factors that might affect future participation of homeless 18- to 24-year-olds of diverse racial/ethnic backgrounds in HIV vaccine trials (HIVVTs). Twenty males and females attended focus groups. Participants expressed concern about seroconversion, the trustworthiness of the researchers and/or government agencies conducting trials, vaccine side effects, and possible negative behavior change as a result of being vaccinated. Understanding the personal perspectives of high-risk young adults will enable researchers to tailor protocols to their individual needs and cultural values and, in so doing, potentially enhance willingness to participate in HIVVTs.
Health Professional Shortage and Health Status and Health Care Access
Authors: Liu Jiexin (Jason)
Published: August 2007

Although areas designated as Health Professional Shortage Areas (HPSAs) have fewer primary care physicians than non-HPSAs, few studies have tested whether HPSA designation is related to health status and medical service access. This study examined whether residents living in HPSAs were more likely to report worse health status and to be more likely to have difficulty in getting access medical services than residents living in non-HPSAs, with survey data of 10,940 adult West Virginians. Multiple regression results indicate that HPSA is associated with worse general health status and poor physical health, and less access to medical services (measured by had usual place for medical care, experienced not getting needed health care and had outpatient care) but not to inpatient care. These findings indicate that the current HPSA designation system does capture the significant differences between residents of HPSAs and residents of non-HPSAs in health status and medical services access.
HealthSTAT: A Student Approach to Building Skills Needed to Serve Poor Communities
Authors: Mohan Carmen Patrick , Mohan Arun
Published: August 2007

The HealthSTAT model of professional development uses team-based leadership and peer-to-peer learning to cultivate inter-professional collaboration and community partnership in service to the poor and underserved of Georgia.