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Notes: The demonstration by the National Surgical Adjuvant Breast Project (NSABP) that 5 years of tamoxifen therapy is associated with an approximate 50% reduction in breast cancer incidence in high-risk women was a milestone in breast cancer prevention. Because tamoxifen is associated with increased risk of side-effects such as hot flashes, menstrual abnormalities, uterine cancer, and thromboembolic phenomena, its use will not be advisable or acceptable for all high-risk women. Women over 50 years of age appear to be at highest risk for serious adverse events, such as uterine cancer and thromboembolic phenomena. Individuals in whom tamoxifen-associated breast cancer risk reduction appears to outweigh risk of serious side-effects include women with prior in situ or estrogen receptor (ER)-positive invasive cancer, atypical hyperplasia, and/or women ages 35–49 with a calculated Gail 5-year risk of ≥1.7%, hysterectomized women aged 50 and older with a 5-year Gail risk of ≥2.5%, and nonhysterectomized women aged 50 and older with a 5-year Gail risk of 〉5.0%. It is not yet clear whether tamoxifen can reduce breast cancer incidence in women with BRCA1 and BRCA2 mutations, although preliminary evidence favors benefit for at least those with a BRCA2 mutation. Raloxifene is a selective ER modulator with less uterine estrogen agonist activity than tamoxifen, and it is hoped that it will result in fewer uterine cancers but will be equally efficacious in reducing the risk of breast cancer. The NSABP is currently conducting a randomized study of tamoxifen versus raloxifene in high-risk postmenopausal women. Approximately one third of invasive cancers are ER negative. Tamoxifen does not reduce the incidence of ER-negative cancers, nor does it appear to be effective in preventing the appearance of one third of ER-positive cancers. Priorities in prevention research are to develop (a) biomarkers to refine short-term risk assessments based on epidemiologic models, (b) biomarkers predictive of response to specific classes of preventive agents, (c) drugs with fewer side-effects and/or effective in ER-negative or ER-positive tamoxifen-resistant precancerous disease, and (d) efficient clinical trial models to assess new agent efficacy. Breast intraepithelial neoplasia (IEN) may be sampled by minimally invasive techniques and is an attractive short-term risk biomarker. Molecular abnormalities observed in IEN may be used to select potential agents for testing/therapy, and modulation of these abnormalities may be used in phase I trials to select appropriate doses and in phase II trials to assess response. Breast density volume and certain serum markers such as insulin-like growth factor-1 are also being studied as potential risk and response biomarkers. Reversal or prevention of advanced IEN as well as modulation of other risk biomarkers in randomized phase II and phase III trials is being evaluated as a means of more efficiently evaluating prevention drugs in the future. A number of agents are being developed that target molecular abnormalities in IEN, have fewer or different side effects than tamoxifen, and may be effective in ER-negative or tamoxifen-resistant disease.

Notes: Introduction: Survival in patients awaiting cardiac transplantation is poor due to the severity of left ventricular dysfunction and the susceptibility to ventricular arrhythmia. The potential role of implantable cardioverter defibrillators (ICDs) in this group of patients has been the subject of increasing interest. The aims of this study were to ascertain whether ICDs improve the survival rate of patients on the waiting list for cardiac transplantation and whether any improvement is independent of concomitant beta-blocker or amiodarone therapy. Methods and Results: Data comprised findings from 310 consecutive patients at a single center who were evaluated and deemed suitable for cardiac transplantation and placed on the waiting list. Kaplan-Meier actuarial approach was used for survival analysis. Survival analysis censored patients at time of transplantation or death. Of the 310 patients, 111 (35.8%) underwent successful cardiac transplantation and 164 (52.9%) died while waiting; 35 patients remain on the waiting list. Fifty-nine (19%) patients had ICD placement for ventricular arrhythmias prior to or after being listed. Twenty-nine (49.1%) ICD patients survived until cardiac transplantation, 13 (22%) patients died, and 17 (28.8%) remain on the waiting list. Among non-ICD patients, 82 (32.7%) received transplants, 151 (60.2%) died, and 18 (7.2%) remain on the waiting list. Survival rates at 6 months and 1, 2, 3, and 4 years were better for all ICD patients compared to non-ICD patients (log-rank x2, P = 0.0001 ). By multivariate analysis, ICD therapy and beta-blocker treatment were the strongest predictors of survival. Further, ICD treatment was associated with improved survival independent of concomitant treatment with beta-blocker or amiodarone. Among ICD and non-ICD patients treated with a beta-blocker or amiodarone, survivals at the 1 and 4 years were 93% vs 69% and 57% vs 32%, respectively (log-rank x2, P = 0.003 ). Conclusion: ICD therapy is associated with improved survival in high-risk cardiac transplant candidates, and ICD benefit appears to be independent of concomitant treatment. (J Cardiovasc Electrophysiol, Vol. 14, pp. 578-583, June 2003)

Notes: Background  The etiology of idiopathic guttate hypomelanosis (IGH) remains uncertain; however, solar exposure and heredity have been proposed as causative factors.Objective  To explore the genetic predisposition to the development of IGH.Methods   A comparative case–control study was performed at a dermatology department at a university hospital. Forty-seven subjects (22 renal transplant patients and 25 controls) were enrolled. Clinical examination and human leukocyte antigen (HLA) determination were performed.Results   In the group of subjects with HLA-DQ3 (10/13, P = 0.025), there was a statistically significant (P 〈 0.05) positive association for the presence of IGH; in the group of subjects with HLA-DR8 (6/6, P = 0.023), there was a statistically significant negative association for the presence of IGH.Conclusions   The presence of HLA-DQ3 in patients with IGH suggests a genetic basis in a group of renal transplant subjects. HLA-DR8 was found in patients without IGH, and it could play a role as a “protective factor” preventing subjects from developing IGH.

Notes: The dependence of spin–spin NMR coupling constants on the basis set and electron correlation has been investigated for the hydrogen fluoride using Hartree–Fock (HF-SCF) and multiconfigurational self-consistent field (MCSCF) wave functions. The effect of the size, contraction, and tight s-type, augmented and polarization functions in the basis sets is analyzed. MCSCF wave functions with different number of active orbitals and excited electrons were used within the frozen-core approximation and with all-electron calculations. The correlation effect associated with the core electrons is not negligible. An approximation to determine spin–spin coupling constants at high level of electron correlation and reduced computational cost is applied satisfactorily. The best calculated and estimated 1JFH couplings are 544.20 and 536.63 Hz, respectively, with all electron correlation. Both values agree with the experimental one within the error bars (525±20 Hz). © 2000 American Institute of Physics.

Notes: This paper is a survey of the recent literature devoted to the economics of private labels. After providing some statistics about the development of private labels for different products in different OECD countries, the survey outlines what the literature says about the factors that favor the development of private labels, the reasons retailers introduce private labels, and the consequences of their development for the relationship between manufacturers and retailers. Issues that are less frequently addressed in the literature are also highlighted. The survey closes with discussing the impact of the development of private labels on welfare.

Notes: Professional organizations have long been depicted as rife with conflict between professionals, who are assumed to represent the interests of their profession, and managers, who are assumed to represent the potentially competing interests of the organization. This study examines the validity of this assumption. Based on past research on both professional organizations and knowledge structure development, we predict that to the extent that professionals and managers conflict, they may do so because they interpret ‘identical’ issues differently. The results of a study of resource allocation decision preferences with 350 chief financial officers, chief medical officers, and physicians revealed strong support for our issue interpretation predictions, and virtually no support for the simple professional–manager dichotomy. Specifically, using structural equation modeling, we found that: (1) single resource allocation issues could be interpreted in multiple ways; (2) issue interpretations were strong predictors of decision preferences; (3) professionals and managers tended to interpret issues differently, although many of the differences were not consistent with past theorizing about professionals; (4) the interpretations and decision preferences of professionals who occupied management positions were like those of other professionals but different from those of managers; and (5) decision maker status (i.e., professional and/or manager) was only modestly related to decision preference. Our findings suggest that the sources and manifestations of a professional–manager dichotomy are more complex than previously reported.

Notes: The prevailing approach in density-functional theory makes use of universal functionals, valid for any number of electrons (N). In this article and following the work of Lieb [E. H. Lieb, Int. J. Quantum Chem. 24, 243 (1983)], we argue that the use of N-dependent functionals could be an equally valid approach. Size consistency (dissociation into proper fragments) puts restrictions on the form that N-dependent functionals may adopt. We propose a simple procedure for correcting the size-consistency problem of existing N-dependent functionals that also provides an original way of designing new ones. © 2001 American Institute of Physics.

Notes: In contrast to the regeneration-competent peripheral nervous system (PNS), lesions of nerve tracts within the central nervous system (CNS) lead to chronically impaired neuronal connections. We have analysed changes in gene expression patterns occurring as a consequence of postcommissural fornix transection at a time when spontaneous axonal growth has ceased at the lesion site. This was done in order to describe both extrinsic and intrinsic determinants of regeneration failure. Using a genomic approach we have identified a number of so far undetected factors such as bamacan and semaphorin 6B, which relate to chronic axonal growth arrest and therefore are promising candidates for lesion-induced axonal growth inhibitors. In addition, we observed that within the subiculum, where the fornix axons originate, neuronal Oct-6 was induced and NG2 was down-regulated, indicating that axotomized neurons as well as glial cells react at the level of gene expression to remote axotomy.

Notes: The hippocampal formation communicates with the neocortex mainly through the adjacent entorhinal cortex. Neurons projecting to the hippocampal formation are found in the superficial layers of the entorhinal cortex and are largely segregated from the neurons receiving hippocampal output, which are located in deep entorhinal layers. We studied the communication between deep and superficial entorhinal layers in the anaesthetized rat using field potential recordings, current source density analysis and single unit measurements. We found that subiculum stimulation was able to excite entorhinal neurons in deep layers. This response was followed by current sinks in superficial layers. Both responses were subject to frequency dependent facilitation, but not depression. Selective blockade of deep layer responses also abolished subsequent superficial layer responses. This clearly demonstrates a functional deep-to-superficial layer communication in the entorhinal cortex, which can be triggered by hippocampal output. This pathway may provide a means by which processed hippocampal output is integrated or compared with new incoming information in superficial entorhinal layers, and it constitutes an important link in the process of re-entrance of activity in the hippocampal–entorhinal network, which may be important for consolidation of memories or retaining information for short periods.