bluuebunny/crossref_metadata_2025 huggingface dataset:
HOW EFFECTIVE ARE STRONG INTERACTIONS
Authors: VARY J. P.
Published: March 2005

Effective interactions and transition operators have a long history in nuclear physics. From the early works of Brueckner and Bethe to the present time, microscopic approaches based on realistic nucleon–nucleon interactions, fit to phase shifts, have produced many useful results and insights. Recently, an ab initio approach has been developed that successfully weds a no-core finite basis state treatment, conserving center of mass motion, with an Hermitian effective Hamiltonian derived from realistic two-nucleon and tri-nucleon interactions. We present this approach with a sample of recent results.
RELATIVISTIC DESCRIPTION OF EXOTIC COLLECTIVE EXCITATION PHENOMENA IN ATOMIC NUCLEI
Authors: PAAR N. , NIKŠIĆ T. , VRETENAR D. , RING P.
Published: March 2005

The low-lying dipole and quadrupole states in neutron rich nuclei are studied within the fully self-consistent relativistic quasiparticle random-phase approximation (RQRPA), formulated in the canonical basis of the Relativistic Hartree–Bogoliubov model (RHB), which is extended to include the density dependent interactions. In heavier nuclei, the low-lying E1 excited state is identified as a pygmy dipole resonance (PDR), i.e. as a collective mode of excess neutrons oscillating against a proton–neutron core. Isotopic dependence of the PDR is characterized by a crossing between the PDR and one-neutron separation energies. Already at moderate proton–neutron asymmetry the PDR peak is calculated above the neutron emission threshold, indicating important implications for the observation of the PDR in (γ, γ′) scattering, and on the theoretical predictions of the radiative neutron capture rates in neutron-rich nuclei. In addition, a novel method is suggested for determining the neutron skin of nuclei, based on measurement of excitation energies of the Gamow–Teller resonance relative to the isobaric analog state.
EXACTLY SOLVABLE PAIRING MODEL USING AN EXTENSION OF THE RICHARDSON–GAUDIN APPROACH
Authors: BALANTEKIN A. B. , DERELI T. , PEHLIVAN Y.
Published: March 2005

We introduce a new class of exactly solvable boson pairing models using the technique of Richardson and Gaudin. Analytical expressions for all energy eigenvalues and the first few energy eigenstates are given. In addition, another solution to Gaudin's equation is also mentioned. A relation with the Calogero–Sutherland model is suggested.
SHORTCUTS TO NUCLEAR STRUCTURE: LESSONS IN HARTREE–FOCK, RPA, AND THE NO-CORE SHELL MODEL
Authors: JOHNSON CALVIN W. , STETCU IONEL
Published: March 2005

While the no-core shell model is a state-of-the-art microscopic approach to low-energy nuclear structure, its intense computational requirements lead us to consider time-honored approximations such as the Hartree–Fock (HF) approximation and the random phase approximation (RPA). We review RPA and point out some common misunderstandings, then apply HF + RPA to the no-core shell model. Here the main issue is appropriate treatment of contamination by spurious center-of-mass motion.
SOLVABLE MEAN-FIELD PLUS EXTENDED PAIRING MODEL
Authors: FENG PAN , GUEORGUIEV V. G. , DRAAYER J. P.
Published: March 2005

A mean-field Hamiltonian with an extended pairing interaction that includes multi-pair excitations is proposed for describing strongly-deformed nuclei. Solutions are easily obtained. The results show that even though the theory includes many-body interaction terms, the one- and two-body parts continue to dominate the dynamics for small values of the pairing strength. As the strength of the pairing interaction grows, however, the higher many-body interaction terms grow in importance. A numerical study of binding energies for the 154-181 Yb isotopes demonstrates the applicability of the theory.
AB INITIO NUCLEAR STRUCTURE AND NUCLEAR REACTIONS IN LIGHT NUCLEI
Authors: NAVRÁTIL PETR
Published: March 2005

There has been significant progress in the ab initio approaches to the structure of light nuclei. One such method is the ab initio no-core shell model (NCSM). Starting from the realistic two- and three-nucleon interactions, this method can predict the low-lying levels in p-shell nuclei. It is a challenging task to extend the ab initio methods to describe nuclear reactions. In this contribution, we present a brief overview of the NCSM with examples of recent applications as well as the first steps taken toward nuclear reaction applications.
PSEUDOSPIN SYMMETRY AND THE NUCLEON–NUCLEON INTERACTION
Authors: GINOCCHIO JOSEPH N.
Published: March 2005

Pseudospin symmetry is an approximate relativistic symmetry of the nucleus as demonstrated by experimental data. This symmetry follows from the fact that the vector and scalar potentials of nucleons moving in a relativistic mean field are approximately equal in magnitude and opposite in sign. QCD sum rules in nuclear matter support this conclusion. Such an observation suggests a fundamental reason for pseudospin symmetry. We review the status of pseudospin symmetry conservation in the nucleon–nucleon interaction.
PSEUDOSPIN, SPIN, AND COULOMB DIRAC-SYMMETRIES: DOUBLET STRUCTURE AND SUPERSYMMETRIC PATTERNS
Authors: LEVIATAN A.
Published: March 2005

Relativistic symmetries of the Dirac Hamiltonian with a mixture of spherically symmetric Lorentz scalar and vector potentials are examined from the point of view of supersymmetric quantum mechanics. The cases considered include the Coulomb, pseudospin and spin limits relevant, respectively, to atoms, nuclei and hadrons.
SYMMETRY IN NUCLEI
Authors: IACHELLO F.
Published: March 2005

Applications of the concept of symmetry in nuclei are reviewed.
EXACTLY SOLVABLE MODEL FOR THE DECAY OF SUPERDEFORMED NUCLEI
Authors: BARRETT B. R. , CARDAMONE D. M. , STAFFORD C. A.
Published: March 2005

The history and importance of superdeformation in nuclei is briefly discussed. A simple two-level model is then employed to obtain an elegant expression for the branching ratio for the decay via the E1 process in the normal-deformed band of superdeformed nuclei. From this expression, the spreading width Γ↓ for superdeformed decay is found to be determined completely by experimentally known quantities. The accuracy of the two-level approximation is verified by considering the effects of other normal-deformed states. Furthermore, by using a statistical model of the energy levels in the normal-deformed well, we can obtain a probabilistic expression for the tunneling matrix element V.
ORGANIZING INFORMATION ON THE NEXT GENERATION WEB — DESIGN AND IMPLEMENTATION OF A NEW BOOKMARK STRUCTURE
Authors: GUAN SHENG-UEI , MCMULLEN P.
Published: March 2005

The next-generation Web will increase the need for a highly organized and ever evolving method to store references to Web objects. These requirements could be realized by the development of a new bookmark structure. This paper endeavors to identify the key requirements of such a bookmark, specifically in relation to Web documents, and sets out a suggested design through which these needs may be accomplished. A prototype developed offers such features as the sharing of bookmarks between users and groups of users. Bookmarks for Web documents in this prototype allow more specific information to be stored such as: URL, the document type, the document title, keywords, a summary, user annotations, date added, date last visited and date last modified. Individuals may access the service from anywhere on the Internet, as long as they have a Java-enabled Web browser.
ADAPTIVE HIGHLIGHTING OF LINKS TO ASSIST SURFING ON THE INTERNET
Authors: PALOTAI ZSOLT , GÁBOR BÁLINT , LŐRINCZ ANDRÁS
Published: March 2005

Gathering of novel information from the WWW constitutes a real challenge for artificial intelligence (AI) methods. Large search engines do not offer a satisfactory solution, their indexing cycle is long and they may offer a huge amount of documents. An AI-based assistant agent is studied here, which sorts the availabe links by their estimated value for the user. By using this link-list the best links could be highlighted in the browser, making the user's choices easier during surfing. The method makes use of (i) "experts", i.e. pre-trained text classifiers, forming the long-term memory of the system, (ii) relative values of experts and value estimation of documents based on recent choices of the user. Value estimation adapts fast and forms the short-term memory of the system. All experiments show that surfing based filtering can efficiently highlight 10%–20% of the documents in about five steps, or less.
AUTOMATIC ABSTRACTING IMPORTANT SENTENCES
Authors: REN F. J.
Published: March 2005

Being increasingly popular, the Internet greatly changes our lives. We can conveniently receive and send information via the Internet. With the information explosion on the Web, it is becoming crucial to develop means to automatically extract important sentences from the Web articles. In this paper, we propose a method which uses both statistical and structural information for sentence extraction. In addition, following the analysis of human's extractions, several heuristic rules are added to filter out non-important sentences and to prevent similar sentences from being extracted. Our experimental results proved the effectiveness of these means. In particular, once the heuristic rules being added, a significant improvement has been observed.
HOW SHOULD "KNOWLEDGE BASES" BE ORGANISED IN MULTI-TECHNOLOGY CORPORATIONS?
Authors: SAPSED JONATHAN D.
Published: March 2005

This paper addresses a key interest in Keith Pavitt's later work; the organisational arrangements for co-ordinating technological knowledge. It also concurs with Pavitt's insistence on the constraints on managerial agency and his nihilistic amusement at frustrated plans. The paper considers Pavitt's conceptualisation of knowledge bases as technical disciplines and argues that there is an inconspicuous sub-level of specialised knowledge base associated with tools, products, project experience and requirements that may hamper the intents of higher-level organisation design.

Two contrasting case studies are analysed of organisations attempting to manage transitions that are aimed at improving co-ordination processes. The first has moved from organisation around functional disciplines to product-based, cross-functional teams, while the second has done the reverse. The paper reviews the effects of these opposing organizational solutions on the processes of knowledge integration within the firms, the effects on communities of practice and the ways in which the systems have developed and adapted in response to the reorganisations. The paper challenges some of the simplistic prescriptions offered in the literature and provides further fuel for the debates over organisation design and the knowledge integration task.
COMPLEXITY AND INTERNATIONALISATION OF INNOVATION — WHY IS CHIP DESIGN MOVING TO ASIA?
Authors: ERNST DIETER
Published: March 2005

Among Keith Pavitt's many contributions to the study of innovation is the proposition that physical proximity is advantageous for innovative activities that involve highly complex technological knowledge. But chip design, a process that creates the greatest value in the electronics industry and that requires highly complex knowledge, is experiencing a massive dispersion to leading Asian electronics exporting countries. To explain why chip design is moving to Asia, the paper draws on interviews with 60 companies and 15 research institutions that are doing leading-edge chip design in Asia.

I demonstrate that "pull" and "policy" factors explain what attracts design to particular locations. But to get to the root causes that shift the balance in favour of geographical decentralisation, I examine "push" factors, i.e., changes in design methodology ("system-on-chip design") and organisation ("vertical specialisation" within global design networks). The resultant increase in knowledge mobility explains why chip design — which in Pavitt's framework is not supposed to move — is moving from the traditional centres to a few new specialised design clusters in Asia.
Impact of continuous and pulsatile insulin delivery on net hepatic glucose uptake
Authors: Grubert Jaime M. , Lautz Margaret , Lacy D. Brooks , Moore Mary C. , Farmer Ben , Penaloza Angelina , Cherrington Alan D. , McGuinness Owen P.
Published: March 2005

The pancreas releases insulin in a pulsatile manner; however, studies assessing the liver’s response to insulin have used constant infusion rates. Our aims were to determine whether the secretion pattern of insulin [continuous (CON) vs. pulsatile] in the presence of hyperglycemia 1) influences net hepatic glucose uptake (NHGU) and 2) entrains NHGU. Chronically catheterized conscious dogs fasted for 42 h received infusions including peripheral somatostatin, portal insulin (0.25 mU·kg−1·min−1), peripheral glucagon (0.9 ng·kg−1·min−1), and peripheral glucose at a rate double the glucose load to the liver. After the basal period, insulin was infused for 210 min at either four times the basal rate (1 mU·kg−1·min−1) or an identical amount in pulses of 1 and 4 min duration, followed by intervals of 11 and 8 min (CON, 1/11, and 4/8, respectively) in which insulin was not infused. A variable peripheral glucose infusion containing [3H]glucose clamped glucose levels at twice the basal level (∼200 mg/dl) throughout each study. Hepatic metabolism was assessed by combining tracer and arteriovenous difference techniques. Arterial plasma insulin (μU/ml) either increased from basal levels of 6 ± 1 to a constant level of 22 ± 4 in CON or oscillated from 5 ± 1 to 416 ± 79 and from 6 ± 1 to 123 ± 43 in 1/11 and 4/8, respectively. NHGU (−0.8 ± 0.3, 0.4 ± 0.2, and −0.9 ± 0.4 mg·kg−1·min−1) and net hepatic fractional extraction of glucose (0.04 ± 0.01, 0.04 ± 0.01, and 0.05 ± 0.01 mg·kg−1·min−1) were similar during the experimental period. Spectral analysis was performed to assess whether a correlation existed between the insulin secretion pattern and NHGU. NHGU was not augmented by pulsatile insulin delivery, and there is no evidence of entrainment in hepatic glucose metabolism. Thus the loss of insulin pulsatility per se likely has little or no impact on the effectiveness of insulin in regulating liver glucose uptake.
Activation of proteinase-activated receptor-2 in mesothelial cells induces pleural inflammation
Authors: Lee Y.C. Gary , Knight Darryl A. , Lane Kirk B. , Cheng Dong Sheng , Koay M. Audrey , Teixeira Lisete R. , Nesbitt Jon C. , Chambers Rachel C. , Thompson Philip J. , Light Richard W.
Published: March 2005

Pleural inflammation underlies many pleural diseases, but its pathogenesis remains unclear. Proteinase-activated receptor-2 (PAR2) is a novel seven-transmembrane receptor with immunoregulatory roles. We hypothesized that PAR2is present on mesothelial cells and can induce pleural inflammation. PAR2was detected by immunohistochemistry in all (19 parietal and 11 visceral) human pleural biopsies examined. In cultured murine mesothelial cells, a specific PAR2-activating peptide (SLIGRL-NH2) at 10, 100, and 1,000 μM stimulated a 3-, 42-, and 1,330-fold increase of macrophage inflammatory protein (MIP)-2 release relative to medium control, respectively ( P < 0.05 all) and a 2-, 32-, and 75-fold rise over the control peptide (LSIGRL-NH2, P < 0.05 all). A similar pattern was seen for TNF-α release. Known physiological activators of PAR2, tryptase, trypsin, and coagulation factor Xa, also stimulated dose-dependent MIP-2 release from mesothelial cells in vitro. Dexamethasone inhibited the PAR2-mediated MIP-2 release in a dose-dependent manner. In vivo, pleural fluid MIP-2 levels in C57BL/6 mice injected intrapleurally with SLIGRL-NH2(10 mg/kg) were significantly higher than in mice injected with LSIGRL-NH2or PBS (2,710 ± 165 vs. 880 ± 357 vs. 88 ± 46 pg/ml, respectively; P < 0.001). Pleural fluid neutrophil counts were higher in SLIGRL-NH2group than in the LSIGRL-NH2and PBS groups (by 40- and 26-fold, respectively; P < 0.05). This study establishes that activation of mesothelial cell PAR2potently induces the release of inflammatory cytokines in vitro and neutrophil recruitment into the pleural cavity in vivo.
Acidic pH inhibits ATP depletion-induced tubular cell apoptosis by blocking caspase-9 activation in apoptosome
Authors: Brooks Craig , Ketsawatsomkron Pimonrat , Sui Yang , Wang Jinzhao , Wang Cong-Yi , Yu Fu-Shin , Dong Zheng
Published: March 2005

Tubular cell apoptosis has been implicated in the development of ischemic renal failure. In in vitro models, ATP depletion-induced apoptosis of tubular cells is mediated by the intrinsic pathway involving Bax translocation, cytochrome c release, and caspase activation. While the apoptotic cascade has been delineated, much less is known about its regulation. The current study has examined the regulation of ATP depletion-induced tubular cell apoptosis by acidic pH, a common feature of tissue ischemia. Cultured renal tubular cells were subjected to 3 h of ATP depletion with azide and then recovered in full culture medium. The treatment led to apoptosis in ∼40% of cells. Apoptosis was significantly reduced, if the pH of ATP depletion buffer was lowered from 7–7.4 to 6–6.5. This was accompanied by the inhibition of caspase activation. However, acidic pH did not prevent Bax translocation and oligomerization in mitochondria. Cytochrome c release from mitochondria was not blocked either, suggesting that acidic pH inhibited apoptosis at the postmitochondrial level. To determine the postmitochondrial events that were blocked by acidic pH, we conducted in vitro reconstitution experiments. Exogenous cytochrome c, when added into isolated cell cytosol, induced caspase activation. Such activation was abrogated, when pH during the reconstitution was lowered to 6 or 6.5. Nevertheless, acidic pH did not prevent the recruitment and association of caspase-9 by Apaf-1, as shown by coimmunoprecipitation. Together, this study demonstrated the inhibition of tubular cell apoptosis following ATP depletion by acidic pH. A critical step blocked by acidic pH seems to be caspase-9 activation in apoptosome.
Mapping of Stimulus Energy in Primary Visual Cortex
Authors: Mante Valerio , Carandini Matteo
Published: March 2005

A recent optical imaging study of primary visual cortex (V1) by Basole, White, and Fitzpatrick demonstrated that maps of preferred orientation depend on the choice of stimuli used to measure them. These authors measured population responses expressed as a function of the optimal orientation of long drifting bars. They then varied bar length, direction, and speed and found that stimuli of a same orientation can elicit different population responses and stimuli with different orientation can elicit similar population responses. We asked whether these results can be explained from known properties of V1 receptive fields. We implemented an “energy model” where a receptive field integrates stimulus energy over a region of three-dimensional frequency space. The population of receptive fields defines a volume of visibility, which covers all orientations and a plausible range of spatial and temporal frequencies. This energy model correctly predicts the population response to bars of different length, direction, and speed and explains the observations made with optical imaging. The model also readily explains a related phenomenon, the appearance of motion streaks for fast-moving dots. We conclude that the energy model can be applied to activation maps of V1 and predicts phenomena that may otherwise appear to be surprising. These results indicate that maps obtained with optical imaging reflect the layout of neurons selective for stimulus energy, not for isolated stimulus features such as orientation, direction, and speed.
The Making of the 2003 EU Emissions Trading Directive: An Ultra-Quick Process due to Entrepreneurial Proficiency?
Authors: Wettestad Jørgen
Published: March 2005

The EU emissions trading scheme has been characterized as one of the most farreaching and radical environmental policies for many years, and “the new grand policy experiment.” Given the EU's earlier resistance to this market-based instrument with no international track record and with US origins, the EU decision-making process, which took less than two years, can be characterized as a puzzlingly ultra-quick political “pregnancy.” In order to understand this, it is necessary to take three explanatory perspectives—and the interaction between them—into account. First, the emissions trading issue was more mature within the EU system than immediately apparent, given that emissions projections were worrying and no effective common climate policies had been adopted. Second, the Commission acted as a strong and clever policy entrepreneur, dealing with other basically positive EU bodies. Third, when the US pulled out of the Kyoto process in March 2001, it provided a window of opportunity for the EU to take the reins of global policy leadership.
The prevention of street life among young people in São Paulo, Brazil
Authors: de Moura Sérgio Luiz
Published: March 2005

English

This article reports on social environments for the implementation of interventions aimed at preventing street life among young people in Sâo Paulo, Brazil. The findings suggest the prospect of prevention of street life, which focuses on families and communities in this context, is hardly feasible. Public institutions are identified as the most suitable localities for preventive interventions.

French

Cet article explore les environnements sociaux les plus appropriés pour mener des interventions visant à empêcher la vie de rue parmi les jeunes à São Paulo, Brésil. Les résultats suggèrent qu'une perspective de prévention mettant l’accent sur les familles et les communautés est à peine appropriée dans ce contexte. Les établissements publics sont identifiés comme étant les endroits les plus appropriées pour mener des interventions préventives.

Spanish

Se informa sobre entornos sociales para la puesta en práctica de intervenciones dirigidas a prevenir el peligro de la vida callejera entre los jóvenes de San Pablo en el Brasil. Los hallazgos sugieren que las posibilidades de prevención de la vida callejera no son buenas si la prevención se enfoca en las familias y las comunidades. Se señalan las instituciones públicas como los lugares más adecuados para intervenciones preventivas.
A systematic review of stress among mental health social workers
Authors: Coyle Dave , Edwards Deborah , Hannigan Ben , Fothergill Anne , Burnard Philip
Published: March 2005

English

In the UK mental health social workers reported role conflict, role ambiguity and fulfilling statutory responsibilities as possible sources of stress. Burnout was related to workload, degree of involvement with patients, lack of social support and role conflict. Further work, which investigates coping strategies and stress management interventions, is recommended.

French

Au Royaume-Uni, les travailleurs sociaux en santé mentale signalent un problème de conflit de rôle, de l’ambiguïté de rôle et des responsabilités statutaires en tant que sources possibles de stresse. L’épuisement professionnel (burnout) a été lié à la charge de travail, au niveau d’implication auprès des patients, au manque d’appui social et aux conflits de rôle. L’article souligne la nécessité d’entreprendre d’autres études sur les stratégies employées pour gérer et maîtriser le stresse.

Spanish

En el Reino Unido, los trabajadores sociales en el área de salud mental nos informan que el conflicto y la ambigüedad de roles, así como las responsabilidades estatutarias son posibles causas de estrés. El desgaste profesional (burnout) fue relacionado con la cantidad de trabajo, el grado de envolvimiento con los pacientes, la falta de apoyo social y el conflicto de roles. Se recomienda la investigación de estrategias ‘para arreglárselas’ (‘coping strategies’) e intervenciones para controlar el estrés.
The Khrushchev Kitchen: Domesticating the Scientific-Technological Revolution
Authors: Reid Susan E.
Published: March 2005

In the Soviet Union in the late 1950s, the Khrushchev regime launched an intensive campaign to build mass housing. This period, known as The Thaw, is generally regarded as one of liberalization in comparison to the preceding Stalin era. Moreover, the proposed new housing, promising separate, one-family flats to replace the communal apartments and barracks in which most urban dwellers lived, seemed to offer the possibility of a ‘private’ home life. The Khrushchev flat, in particular its small kitchen, subsequently became mythologized as the heart of an ideology-free zone of sincerity where one could shut the door on the public realm and its values. This article proposes that, far from falling outside the domain of public discourse, the new flat — and, above all, the kitchen, along with the labour it accommodated and the lone female worker it presupposed — was a central site for the linked projects of modernization and the construction of communism. However, with its complex mixture of functions, the kitchen was also the site where the contradictions of Khrushchev-era design and centrally-planned production became most evident. Far from a paragon of rational socialist planning, the kitchen could become a microcosm of its dysfunction.
Really dealing
Authors: Vincent Steve
Published: March 2005

Concepts such as ‘relational contracting’, ‘the flexible firm’ and ‘flexible specialization’ are all associated with intense academic effort directed to understanding both contractual inter-organizational relationships and the networks that sustain them. This article adopts a Realist position and draws on case study evidence in an attempt to contribute to the literature on this subject. It argues that considering inter-organizational exchange networks in terms of three inter-related causal forces provides a useful indication of the generative mechanisms that condition the outcomes observed. The causal forces considered are, first, the type of product exchanged; second, the culture of institutional practices within the context of the exchange; and finally, the level of resource dependency apparent amongst the organizations involved.
Women’s imprisonment in Spain
Authors: Almeda Elisabet
Published: March 2005

Even though Spain has one of the highest rates for the incarceration of women in Europe - 9 per cent of the total prison population - women’s imprisonment is one of the most neglected subjects of academic study and research in Spanish universities. The purpose of this article is to contribute cross-national evidence from Spain to support the claim of researchers in other countries that the needs of women in prison are different from those of men. It is divided into four main parts covering: the increase in the size of the female prison population in Spain since the 1980s; the differences in men’s and women’s prisons and between male and female prisoners’ needs; profiles of women in prison in Spain; and myths and motherhood. Much of the argument is based on research conducted by the author into women’s imprisonment during two periods of time, namely, 1995-6 and 2000-1.
Presbyteral Ministry in the Church of England
Authors: Fisher Peter
Published: March 2005

The Church of England’s Ordination rites of the sixteenth and twentieth centuries are presented and interpreted as primary sources for the understanding of Priestly/presbyteral ministry in the Church of England today. These texts are supplemented by reference to other ‘official’ sources and to some classic nineteenth-century and more recent discussions. The article concludes with a definition of ministerial priesthood as a ‘sacred office’.
Representation and the Theology of Ministry
Authors: Hannaford Robert
Published: March 2005

The article analyses the rather promiscuous use of ‘ministry’ in recent theology and attempts to re-found ministry on a more critical ecclesiological basis. It considers recent research on the meaning of diakonia and proceeds to state a high doctrine of representative ministry as an ecclesial sign of the Kingdom inaugurated by Jesus Christ.
Differences between men with screening-detected versus clinically diagnosed prostate cancers in the USA
Authors: Hoffman Richard M , Stone S Noell , Espey David , Potosky Arnold L
Published: March 2005

Background

The advent of prostate specific antigen (PSA) testing in the United States of America (USA) has led to a dramatic increase in the incidence of prostate cancer in the United States as well as the number of men undergoing aggressive treatment with radical prostatectomy and radiation therapy. We compared patient characteristics and treatment selection between American men with screening-detected versus clinically diagnosed prostate cancers.

Methods

We evaluated 3,173 men with prostate cancer in the USA. Surveys and medical records provided information on demographics, socioeconomic status, comorbidities, symptoms, tumor characteristics, and treatment. We classified men presenting with symptoms of advanced cancer – bone pain, weight loss, or hematuria – as "clinically diagnosed"; asymptomatic men and those with only lower urinary tract symptoms were considered "screening-detected." We used multivariate analyses to determine whether screening predicted receiving aggressive treatment for a clinically localized cancer.

Results

We classified 11% of cancers as being clinically diagnosed. Men with screening-detected cancers were more often non-Hispanic white (77% vs. 65%, P < 0.01), younger (36% < 65 years vs. 25%, P ≤ 0.01), better educated (80% ≥ high school vs. 67%, P < 0.01), healthier (18% excellent health vs. 10%, P < 0.01), and diagnosed with localized disease (90% vs. 75%, P < 0.01). Men with screening-detected localized cancers more often underwent aggressive treatment, 76% vs. 70%, P = 0.05.

Conclusion

Most cancers were detected by screening in this American cohort. Appropriately, younger, healthier men were more likely to be diagnosed by screening. Minority status and lower socio-economic status appeared to be screening barriers. Screening detected earlier-stage cancers and was associated with receiving aggressive treatment.
Increased capsaicin receptor TRPV1 in skin nerve fibres and related vanilloid receptors TRPV3 and TRPV4 in keratinocytes in human breast pain
Authors: Gopinath Preethi , Wan Elaine , Holdcroft Anita , Facer Paul , Davis John B , Smith Graham D , Bountra Chas , Anand Praveen
Published: March 2005

Background

Breast pain and tenderness affects 70% of women at some time. These symptoms have been attributed to stretching of the nerves with increase in breast size, but tissue mechanisms are poorly understood.

Methods

Eighteen patients (n = 12 breast reduction and n = 6 breast reconstruction) were recruited and assessed for breast pain by clinical questionnaire. Breast skin biopsies from each patient were examined using immunohistological methods with specific antibodies to the capsaicin receptor TRPV1, related vanilloid thermoreceptors TRPV3 and TRPV4, and nerve growth factor (NGF).

Results

TRPV1-positive intra-epidermal nerve fibres were significantly increased in patients with breast pain and tenderness (TRPV1 fibres / mm epidermis, median [range] – no pain group, n = 8, 0.69 [0–1.27]; pain group, n = 10, 2.15 [0.77–4.38]; p = 0.0009). Nerve Growth Factor, which up-regulates TRPV1 and induces nerve sprouting, was present basal keratinocytes: some breast pain specimens also showed NGF staining in supra-basal keratinocytes. TRPV4-immunoreactive fibres were present in sub-epidermis but not significantly changed in painful breast tissue. Both TRPV3 and TRPV4 were significantly increased in keratinocytes in breast pain tissues; TRPV3, median [range] – no pain group, n = 6, 0.75 [0–2]; pain group, n = 11, 2 [1–3], p = 0.008; TRPV4, median [range] – no pain group, n = 6, [0–1]; pain group, n = 11, 1 [0.5–2], p = 0.014).

Conclusion

Increased TRPV1 intra-epidermal nerve fibres could represent collateral sprouts, or re-innervation following nerve stretch and damage by polymodal nociceptors. Selective TRPV1-blockers may provide new therapy in breast pain. The role of TRPV3 and TRPV4 changes in keratinocytes deserve further study.
Cerebral venous thrombosis and demyelinating diseases: report of a case in a clinically isolated syndrome suggestive of multiple sclerosis onset and review of the literature
Authors: Maurelli Maurizia , Bergamaschi Roberto , Candeloro Elisa , Todeschini Alessandra , Micieli Giuseppe
Published: March 2005

Cerebral venous thrombosis (CVT) has been described in several cases of clinically definite multiple sclerosis (MS). In the majority of these, lumbar puncture followed by intravenous corticosteroid treatment was suspected as the cause. We report what is, to our knowledge, the first case of a patient with a multifocal clinically isolated syndrome suggestive of MS onset, who developed multiple CVT after lumbar puncture and during high-dose i.v. corticosteroid treatment. We conclude that the sequence ‘lumbar puncture followed by corticosteroid treatment’ may be a contributory risk factor for the development of CVT when associated with other risk factors.
A randomized, double-blind, placebo-controlled study of oral hydrolytic enzymes in relapsing multiple sclerosis
Authors: Baumhackl U , Kappos L , Radue E W , Freitag P , Guseo A , Daumer M , Mertin J
Published: March 2005

Oral administration of hydrolytic enzymes (HE), such as bromelain, trypsin and rutosid, may have beneficial effects on the clinical course of neurological symptoms related to multiple sclerosis (MS). This is supported by a complete protection by HE from experimental allergic encephalomyelitis, an animal model related to MS. Three hundred and one patients with relapsing MS were enrolled in a double-blind, placebo-controlled trial. No treatment effect between the placebo and the HE groups was found either for clinical or MRI parameters.
Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis: a correlative study
Authors: Versijpt J , Debruyne J C , Van Laere K J , De Vos F , Keppens J , Strijckmans K , Achten E , Slegers G , Dierckx R A , Korf J , De Reuck J L
Published: March 2005

Objective: The objectives of the present study were to assess brain atrophy in multiple sclerosis (MS) patients during different disease stages and to investigate by PET and [11C]PK11195, a marker of microglial activation, the relationship between inflammation, atrophy and clinically relevant measures. Methods: Eight healthy subjects and 22 MS patients were included. Semiquantitative [11C]PK11195 uptake values, with normalization on cortical grey matter, were measured for magnetic resonance imaging T2- and T1-lesions and normal appearing white matter (NAWM). As atrophy index we used the ratio of the amount of white and grey matter divided by the ventricular size, using an optimized a priori based segmentation algorithm (SPM99). Results: Atrophy was significantly greater in MS patients compared to age-matched controls. A significant correlation was found between brain atrophy and both disease duration and disability, as measured with the Expanded Disability Status Scale. For NAWM, [11C]PK11195 uptake increased with the amount of atrophy, while T2-lesional [11C]PK11195 uptake values decreased according to increasing brain atrophy. Conclusions: The present study suggests that brain atrophy, correlating with disease duration and disability, is directly related to NAWM and T2-lesional inflammation as measured by microglial activation.
Contrast-enhanced MRI lesions during treatment with interferonβ-1b predict increase in T1 black hole volume in patients with relapsing-remitting multiple sclerosis
Authors: Morgen K , Crawford A LT , Stone R D , Martin R , Richert N D , Frank J A , McFarland H F
Published: March 2005

T1 black holes (BH) have been found to represent focal areas of substantial central nervous system tissue damage in multiple sclerosis (MS) patients. We examined the development of T1 BH over a three-year period of treatment with interferon (IFN)β-1b in a group of 20 patients with relapsing-remitting MS. The number of contrast-enhancing lesions (CEL) after one year of treatment predicted a change in the T1 BH volume in the following two years. In patients without CEL, the T1 BH volume remained stable, whereas it increased in patients with CEL. The occurrence of CEL in patients treated with IFNβ may indicate a heightened risk of accumulating T1 BH.
The relationship between self-awareness of neurobehavioral symptoms, cognitive functioning, and emotional symptoms in multiple sclerosis
Authors: Goverover Yael , Chiaravalloti Nancy , DeLuca John
Published: March 2005

Objective: To examine self-awareness of neurobehavioral symptoms in multiple sclerosis (MS) across three domains of function (apathy, disinhibition, and executive control), and examine the relationship between self-awareness and cognitive functioning. Methods: Twenty-six individuals with MS completed neuropsychological testing, measures of emotional functioning, and self-ratings of neurobehavioral symptoms using the Frontal Systems Behavior Scale (FrSBe), a 46-item questionnaire with subscales assessing frequency of symptoms in executive dysfunction, disinhibition, and apathy. Informants’ ratings of the FrSBe were also obtained. Decreasing differences between patient and informant reports on each subscale of the FrSBe (concordance) indicate higher levels of self-awareness. Results: Results showed significant positive correlations between cognitive abilities and self-awareness of executive dysfunction and disinhibition. In contrast, affect symptomatology (measures of anxiety and depression) were negatively correlated with self-awareness of executive dysfunction. Conclusions: Level of self-awareness of neurobehavioral symptoms in MS is related to level of cognitive impairment. In addition, symptoms of depression and anxiety reduced the accuracy of self-reporting. Thus, a clinician who relies on self-reports in creating an evaluation and treatment plan should consider the patient’s cognitive and emotional states.
Effects of Soy Isoflavones and Conjugated Equine Estrogens on Inflammatory Markers in Atherosclerotic, Ovariectomized Monkeys
Authors: Register Thomas C. , Cann Jennifer A. , Kaplan Jay R. , Williams J. Koudy , Adams Michael R. , Morgan Timothy M. , Anthony Mary S. , Blair Robert M. , Wagner Janice D. , Clarkson Thomas B.
Published: March 2005

The effects of dietary soy isoflavones (IF) and conjugated equine estrogens (CEE) on circulating inflammatory markers were determined at the end of a 3-yr study of ovariectomized monkeys consuming a moderately atherogenic diet. Treatments were: 1) control, receiving alcohol-extracted soy-protein-based diet with low IF content (comparable to ∼5 mg/d); 2) CEE, added to the control diet at a dose comparable to 0.625 mg/d; and 3) IF, consumed as a part of unextracted soy protein isolate at a dose comparable to 129 mg/d. Serum soluble vascular cell adhesion molecule-1 (sVCAM-1) was reduced by both IF (P < 0.006) and CEE (P < 0.0001) relative to controls. Serum monocyte chemoattractant protein (MCP)-1 was reduced by CEE (P < 0.0001) but not by IF (P = 1.00). Treatments did not affect serum IL-6 (P = 0.40), soluble E-selectin (P = 0.17), or C-reactive protein (P = 0.15). Serum MCP-1 and, to a lesser extent, IL-6 significantly correlated with atherosclerosis (plaque area) in the iliac and carotid arteries (all P < 0.05). Serum MCP-1 was also strongly associated with coronary artery atherosclerosis and with indices of plaque inflammation and matrix remodeling (matrix metalloproteinase-9) in the coronary artery intima (all P < 0.01). We conclude that, in this well-established nonhuman primate model of atherosclerosis, this dose of soy IF provided an antiinflammatory effect specific for sVCAM-1, whereas the effects of CEE extended to both sVCAM-1 and MCP1. It is possible that the atheroprotective effects of IF and CEE are mediated, at least in part, by effects on VCAM-1. The sites of IF inhibitory effects on sVCAM-1 production are not known, but likely candidates include the liver and/or the cardiovascular system.
Quantitative Assessment of Glucose Transport in Human Skeletal Muscle: Dynamic Positron Emission Tomography Imaging of [O-Methyl-11C]3-O-Methyl-d-Glucose
Authors: Bertoldo Alessandra , Price Julie , Mathis Chet , Mason Scott , Holt Daniel , Kelley Carol , Cobelli Claudio , Kelley David E.
Published: March 2005

Insulin-stimulated glucose transport in skeletal muscle is regarded as a key determinant of insulin sensitivity, yet isolation of this step for quantification in human studies is a methodological challenge. One notable approach is physiological modeling of dynamic positron emission tomography (PET) imaging using 2-[18-fluoro]2-deoxyglucose ([18F]FDG); however, this has a potential limitation in that deoxyglucose undergoes phosphorylation subsequent to transport, complicating separate estimations of these steps. In the current study we explored the use of dynamic PET imaging of [11C]3-O-methylglucose ([11C]3-OMG), a glucose analog that is limited to bidirectional glucose transport. Seventeen lean healthy volunteers with normal insulin sensitivity participated; eight had imaging during basal conditions, and nine had imaging during euglycemic insulin infusion at 30 mU/min·m2. Dynamic PET imaging of calf muscles was conducted for 90 min after the injection of [11C]3-OMG. Spectral analysis of tissue activity indicated that a model configuration of two reversible compartments gave the strongest statistical fit to the kinetic pattern. Accordingly, and consistent with the structure of a model previously used for [18F]FDG, a two-compartment model was applied. Consistent with prior [18F]FDG findings, insulin was found to have minimal effect on the rate constant for movement of [11C]3-OMG from plasma to tissue interstitium. However, during insulin infusion, a robust and highly significant increase was observed in the kinetics of inward glucose transport; this and the estimated tissue distribution volume for [11C]3-OMG increased 6-fold compared with basal conditions. We conclude that dynamic PET imaging of [11C]3-OMG offers a novel quantitative approach that is both chemically specific and tissue specific for in vivo assessment of glucose transport in human skeletal muscle.
Irregular and Frequent Cortisol Secretory Episodes with Preserved Diurnal Rhythmicity in Primary Adrenal Cushing’s Syndrome
Authors: van Aken M. O. , Pereira A. M , van Thiel S. W. , van den Berg G. , Frölich M. , Veldhuis J. D. , Romijn J. A. , Roelfsema F.
Published: March 2005

To evaluate the pathophysiology of altered cortisol secretion in patients with primary adrenal hypercortisolism, cortisol secretion was investigated in 12 patients, seven with a unilateral adenoma and five with ACTH-independent macronodular adrenal hyperplasia compared with age- and gender-matched controls and with patients with pituitary-dependent hypercortisolism. Pulsatile secretion was increased 2-fold (P = 0.04), attributable to increased event frequency (P = 0.002). All patients showed a significant diurnal rhythm with a delay in phase shift of 3 h (P = 0.01). Approximate entropy ratio, a feedback-sensitive measure, was increased compared with controls (P = 0.00003) but similar to that of pituitary-dependent hypercortisolism (P = 0.77), denoting loss of autoregulation. Cortisol burst-mass tended to be smaller in patients with ACTH-independent macronodular adrenal hyperplasia than in unilateral adenoma (P = 0.06). In conclusion, increased cortisol secretion in patients with primary adrenal Cushing’s syndrome is caused by amplified pulsatile secretion via event frequency modulation. We speculate that partial preservation of secretory regularity and diurnal rhythmicity point to incomplete autonomy of these tumors.
Experimentally Induced Androgen Depletion Accentuates Ethnicity-Related Contrasts in Luteinizing Hormone Secretion in Asian and Caucasian Men
Authors: Veldhuis Johannes D. , Bae Anthony , Swerdloff Ronald S. , Iranmanesh Ali , Wang Christina
Published: March 2005

The basis for ethnicity-related distinctions in gonadotropin secretion are unknown but may have important populational and physiological implications. In male contraceptive trials, exogenous testosterone and progestins suppress spermatogenesis to a greater degree in Asian than Caucasian men. In addition, iv infusion of testosterone inhibits LH release more in Asian than Caucasian volunteers. We test the converse postulate that experimental reduction of androgen-dependent negative feedback by way of the steroidogenic inhibitor combination ketoconazole/dexamethasone will unveil ethnicity-related mechanisms of regulated LH secretion in young men. LH release was monitored by sampling blood every 10 min for 24 h followed by immunoradiometric assay, model-free pulse detection, an entropy (regulatory) statistic, and cosine regression. Statistical comparisons revealed that healthy young Asian and Caucasian men maintain comparable baseline concentrations of LH, testosterone, estradiol, SHBG, and molar testosterone to SHBG ratios. In contrast, the two ethnic groups differ prominently in each of basal, pulsatile, entropic, and 24-h rhythmic LH adaptations to short-term androgen withdrawal. Therefore, we postulate that physiological nonuniformity of sex steroid-dependent negative feedback in particular may contribute to populational diversity in LH regulation.
Dysregulation of Cytochrome P450 17α-Hydroxylase Messenger Ribonucleic Acid Stability in Theca Cells Isolated from Women with Polycystic Ovary Syndrome
Authors: Wickenheisser Jessica K. , Nelson-DeGrave Velen L. , McAllister Jan M.
Published: March 2005

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by ovarian hyperandrogenism. Theca interna cells isolated from the ovaries of women with PCOS are characterized by increased expression of cytochrome P450 17α-hydroxylase (CYP17) [steroid 17α-hydroxylase/17,20 lyase (P450c17)], a steroidogenic enzyme obligatory for the biosynthesis of androgens. Augmented expression of the gene encoding P450c17 (CYP17) in PCOS theca has been attributed, in part, to differential transcriptional regulation of the CYP17 promoter in normal and PCOS cells. The present studies examine whether CYP17 gene expression is also posttranscriptionally regulated at the level of mRNA stability in normal and PCOS theca cells maintained in long-term culture. Determination of endogenous CYP17 mRNA half-life by pharmacological inhibition of transcription demonstrated that the half-life of CYP17 mRNA increased 2-fold in PCOS theca cells, compared with normal theca cells. Forskolin treatment also prolonged CYP17 mRNA half-life in both normal and PCOS theca cells. In vitro mRNA degradation studies demonstrated that the 5′-untranslated region confers increased stability to CYP17 mRNA in PCOS theca cells and showed that the 5′-untranslated region of CYP17 also confers forskolin-stimulated stabilization of CYP17 mRNA. These studies indicate that a slower rate of CYP17 mRNA decay contributes to increased steady-state mRNA accumulation and augmented CYP17 gene expression in PCOS theca cells.