Case-control studies in evaluating prostate cancer screening: an overview

Objectives: Ongoing randomized controlled screening trials for prostate cancer have not shown a beneficial effect on prostate cancer mortality reduction yet. A large number of observational (non-randomized) studies on prostate cancer screening have been published with contradictory outcome. This paper reviews the current case-control studies. Methods: Seven case-control studies of screening for prostate cancer were identified in a PubMed search, published from 1991 onwards, all conducted in North America. The screening test was either digital rectal examination (DRE) alone or in combination with PSA. Results: One DRE case-control study, found a significant preventive effect, whereas two others showed no effect of DRE screening on prostate cancer mortality nor on the occurrence of metastatic disease. Conflicting results were also observed in the studies assessing the effect of PSA/DRE. Only one study showed a significant 27% mortality reduction in the White male cohort, but found no effects in Blacks. The most recent study showed that screening with PSA/DRE was not protective in reducing prostate cancer mortality. Conclusions: Our review of the case-control studies does not indicate a benefit of prostate cancer screening. An answer has to come from the ERSPC trial, in Europe, and the PLCO trial, in the US, of which the outcomes are expected in 2007–2010. # 2006 European Association of Urolog

Evidence for Hoogsteen GC Base Pairs in the Proton-Induced Transition from Right-Handed to Left-Handed Poly(dG-dC) . Poly(dG-dC)

The structure of double-helical poly(dG-dC)·poly(dG-dC) is investigated at various pH values with Raman spectroscopy, absorption spectroscopy, and circular dichroism. A comparison is made between the B-form with Watson−Crick base pairing at 1 mM [Na+] and pH 7.2, the Z-form with Watson−Crick base pairing at 4 M [Na+] and pH 7.2, and a different structure at 1 mM [Na+] and pH 4.5 as well as at 150 mM [Na+] and pH 3.1. The CD spectrum of poly(dG-dC)·poly(dG-dC) under the latter conditions does not show a negative band at 290 nm. The structure is a double-helical structure different from the B-form and the Z-form according to circular dichroism, Raman, and absorption spectroscopic studies. The Raman spectra evidence that the structure contains Hoogsteen base pairing. This can be accommodated in the double helix when the cytosine group is protonated and the sugar−guanine conformer has adopted a C2‘-endo/syn conformation. It is shown that this antiparallel-stranded Hoogsteen base paired structure can be maintained under varying conditions, balancing the decrease in pH with an increased salt concentration. It is further concluded that the proton-induced transition from a Watson−Crick to a Hoogsteen base pair is aided by a decrease of [Na+] at pH 4.5 and occurs prior to a conversion from a right-handed helix to a left-handed heli

On the Economic Foundation of the Urban Network Paradigm: Spatial Integration, Functional Integration and Economic Complementarities within the Dutch Randstad

The current debate on polycentric urban development suggests that inter-firm relations are important for the creation and sustainment of urban networks. Conceptually, the degrees of spatial and functional integration and urban complementarities in economic network relations are hypothesised to be important. However, the theoretical economic rationale has not been convincingly tested. In this paper, we use data on inter-firm relations in the Dutch Randstad to test conditions for integration and the existence of economic complementarities within this region. Contrary to the ‘polycentricity hypothesis’, we observe a clear hierarchy in the different types of spatial interdependencies in the Randstad, in which the central place model prevails. Furthermore, we do not find evidence for the functional integration of municipalities in the Randstad. We conclude that at this moment the Randstad does not function as a spatially and functionally integrated region, and that spatial economic policy can better focus on smaller regions within the Randstad when urban economic complementarities and integration are desired. This also calls into question the applicability of the urban network concept in general, as the Dutch Randstad is usually seen as a prime example of an economically successful polycentric urban system

Agglomeration and New Establishment Survival: A Mixed Hierarchical and Cross-Classified Model

Recent empirical studies in regional science and urban economics show that agglomeration economies may be one source of the uneven distribution of economic activities and economic growth across cities and regions. At the same time, the body of research into the importance of agglomeration economies for the performance of firms is still growing. Such development is necessary, as the theories that underlie agglomeration economies are microeconomic in nature, but still insufficiently understood. In this study, we focus on the determinants of survival among new establishments in the advanced producer services sector in the Netherlands. Employing a mixed hierarchical and cross-classified probit regression, we introduce a model of establishment survival that is specific to characteristics of the internal and external environment of the establishment. Controlling for firm and sector characteristics, we conclude that location accounts for about 4% of the variance in the probability of survival of new establishments. We also find that localization and urbanization economies have a positive effect on the survival of new establishments. However, new establishments with large start-up sizes appear to profit more from agglomeration economies than new establishments with small start-up sizes

Multilevel Approaches and the Firm-Agglomeration Ambiguity in Economic Growth Studies

Empirical studies in spatial economics have shown that agglomeration economies may be a source of the uneven distribution of economic activities and economic growth across cities and regions. Both localization and urbanization economies are hypothesized to foster agglomeration and growth, but recent meta-analyses of this burgeoning body of empirical research show that the results are ambiguous. Recent overviews show that this ambiguity is fuelled by measurement issues and heterogeneity in terms of scale of time and space, aggregation, growth definitions, and the functional form of the models applied. Alternatively, in this paper, we argue that ambiguity may be due to a lack of research on firm-level performance in agglomerations. This research is necessary because the theories that underlie agglomeration economies are microeconomic in nature. Hierarchical or multilevel modeling, which allows micro levels and macro levels to be modeled simultaneously, is becoming an increasingly common practice in the social sciences. As illustrated by detailed Dutch data on firm-level productivity, employment growth and firm survival, we argue that these approaches are also suitable for reducing the ambiguity surrounding the agglomeration-firm performance relationship and for addressing spatial, sectoral and cross-level heterogeneity

Slow fluctuations in enhanced Raman scattering and surface roughness relaxation

We propose an explanation for the recently measured slow fluctuations and ``blinking'' in the surface enhanced Raman scattering (SERS) spectrum of single molecules adsorbed on a silver colloidal particle. We suggest that these fluctuations may be related to the dynamic relaxation of the surface roughness on the nanometer scale and show that there are two classes of roughness with qualitatively different dynamics. The predictions agree with measurements of surface roughness relaxation. Using a theoretical model for the kinetics of surface roughness relaxation in the presence of charges and optical electrical fields, we predict that the high-frequency electromagnetic field increases both the effective surface tension and the surface diffusion constant and thus accelerates the surface smoothing kinetics and time scale of the Raman fluctuations in manner that is linear with the laser power intensity, while the addition of salt retards the surface relaxation kinetics and increases the time scale of the fluctuations. These predictions are in qualitative agreement with the Raman experiments

Predictive performance of parent-metabolite population pharmacokinetic models of (S)-ketamine in healthy volunteers

Purpose The recent repurposing of ketamine as treatment for pain and depression has increased the need for accurate population pharmacokinetic (PK) models to inform the design of new clinical trials. Therefore, the objectives of this study were to externally validate available PK models on (S)-(nor)ketamine concentrations with in-house data and to improve the best performing model when necessary. Methods Based on predefined criteria, five models were selected from literature. Data of two previously performed clinical trials on (S)-ketamine administration in healthy volunteers were available for validation. The predictive performances of the selected models were compared through visual predictive checks (VPCs) and calculation of the (root) mean (square) prediction errors (ME and RMSE). The available data was used to adapt the best performing model through alterations to the model structure and re-estimation of inter-individual variability (IIV). Results The model developed by Fanta et al. (Eur J Clin Pharmacol 71:441-447, 2015) performed best at predicting the (S)-ketamine concentration over time, but failed to capture the (S)-norketamine C-max correctly. Other models with similar population demographics and study designs had estimated relatively small distribution volumes of (S)-ketamine and thus overpredicted concentrations after start of infusion, most likely due to the influence of circulatory dynamics and sampling methodology. Model predictions were improved through a reduction in complexity of the (S)-(nor)ketamine model and re-estimation of IIV. Conclusion The modified model resulted in accurate predictions of both (S)-ketamine and (S)-norketamine and thereby provides a solid foundation for future simulation studies of (S)-(nor)ketamine PK in healthy volunteers after (S)-ketamine infusion.Stress-related psychiatric disorders across the life spa

Origin and Properties of the Gap in the Half-Ferromagnetic Heusler Alloys

We study the origin of the gap and the role of chemical composition in the half-ferromagnetic Heusler alloys using the full-potential screened KKR method. In the paramagnetic phase the C1_b compounds, like NiMnSb, present a gap. Systems with 18 valence electrons, Z_t, per unit cell, like CoTiSb, are semiconductors, but when Z_t > 18 antibonding states are also populated, thus the paramagnetic phase becomes unstable and the half-ferromagnetic one is stabilized. The minority occupied bands accommodate a total of nine electrons and the total magnetic moment per unit cell in mu_B is just the difference between Z_t and $2 \times 9$. While the substitution of the transition metal atoms may preserve the half-ferromagnetic character, substituting the $sp$ atom results in a practically rigid shift of the bands and the loss of half-metallicity. Finally we show that expanding or contracting the lattice parameter by 2% preserves the minority-spin gap.Comment: 11 pages, 7 figures New figures, revised tex

Aspectos técnico-ambientais da produção orgânica na região citrícola do Vale do Rio Caí, RS.

Há uma preocupação crescente sobre a necessidade de produção e consumo de alimentos mais saudáveis, sem uso de agrotóxicos nem fertilizantes sintético-industriais. Neste contexto se insere a prática da agricultura orgânica, que, contudo, apresenta resultados ainda pouco avaliados nos meios acadêmicos e científicos. Assim, pretendeu-se nesta pesquisa diagnosticar aspectos técnico-ambientais da produção orgânica na região citrícola do Vale do Rio Caí, no Rio Grande do Sul. Inicialmente, foram selecionadas propriedades de oito agricultores familiares, todas já convertidas ao sistema orgânico de produção, sendo aplicadas entrevistas semi-estruturadas. Os produtores mostram-se satisfeitos com o sistema orgânico de produção e revelam bom conhecimento sobre o ambiente, plantas, solos e processos agroecológicos, adquiridos através da participação em eventos técnicos e em reuniões da Cooperativa Ecocitrus. A constante troca de experiências entre esses agricultores tem melhorado sua qualificação técnica, além de melhor conscientizá-los nos aspectos políticos, econômicos e sociais

Stress response inside perturbed particle assemblies

The effect of structural disorder on the stress response inside three dimensional particle assemblies is studied using computer simulations of frictionless sphere packings. Upon applying a localised, perturbative force within the packings, the resulting {\it Green's} function response is mapped inside the different assemblies, thus providing an explicit view as to how the imposed perturbation is transmitted through the packing. In weakly disordered arrays, the resulting transmission of forces is of the double-peak variety, but with peak widths scaling linearly with distance from the source of the perturbation. This behaviour is consistent with an anisotropic elasticity response profile. Increasing the disorder distorts the response function until a single-peak response is obtained for fully disordered packings consistent with an isotropic description.Comment: 8 pages, 7 figure captions To appear in Granular Matte