bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bayesian Benefit‐Risk Model Applied to the South Florida Building Code
Authors: Englehardt James D. , Peng Chengjun
Published: January 2007

A Bayesian compound Poisson benefit‐risk model is described in this paper, and used to evaluate recent revisions to the South Florida Building Code (SFBC). The model accounts for natural variability in hurricane frequency and severity, and uncertainty in the effectiveness of the revised code. Ranges of residential growth rate, code effectiveness, construction cost increase, and planning period length are assumed, to show the ranges of cost‐to‐performance ratio within which the code will make sense economically. The expected cost of residential hurricane damage over 50 years for ten South Florida counties assuming continuation of previous building practices was $93 billion, equivalent to the residential damage of 5.2 Andrews. Assuming a reduction in the growth of damageable housing in South Florida from 5.5% to 2% as a result of code revision, estimated damages under the new code were $45 billion. At a per‐house construction cost increase of 5%, the probability of at least recovering the estimated $40 billion cost of the specified wind‐resistant construction was estimated to be 47%. Expected return on investment was estimated at $7 billion over 50 years. The expected return lies between a $44 billion loss and a $47 billion gain, when growth in damageable housing is allowed to range from 1% to 4% and construction cost increases are assumed to lie between 3% and 8%. Actual monetary return for a 5% cost increase and 2% growth in damageable housing ranges from a $20 billion loss to a $100 billion gain with 95% probability, as a result of weather variability alone. Results support SFBC revisions on solely economic grounds, a conclusion strengthened considerably in light of potentially avoided deaths and hurricane traumas. The model represents one approach to evaluating economic aspects of the sustainability of new technological measures on the basis of available information.
On‐Site Storage of High Level Nuclear Waste: Attitudes and Perceptions of Local Residents
Authors: Bassett Gilbert W. , Jenkins‐Smith Hank C. , Silva Carol
Published: January 2007

No public policy issue has been as difficult as high‐level nuclear waste. Debates continue regarding Yucca Mountain as a disposal site, and—more generally—the appropriateness of geologic disposal and the need to act quickly. Previous research has focused on possible social, political, and economic consequences of a facility in Nevada. Impacts have been predicted to be potentially large and to emanate mainly from stigmatization of the region due to increased perceptions of risk. Analogous impacts from leaving waste at power plants have been either ignored or assumed to be negligible. This paper presents survey results on attitudes of residents in three counties where nuclear waste is currently stored. Topics include perceived risk, knowledge of nuclear waste and radiation, and impacts on jobs, tourism, and housing values from leaving waste on site. Results are similar to what has been reported for Nevada; the public is concerned about possible adverse effects from on‐site storage of waste.
Small Parts Aspiration, Ingestion, and Choking in Small Children: Findings of the Small Parts Research Project
Authors: Rider Gene , Wilson Cheryl L.
Published: January 2007

Obtaining information on current child injury trends and their associated issues is an important factor in developing products that meet or surpass acceptable toy safety boundaries. Understanding these boundaries helps determine safe product design characteristics that reduce the risk of product‐related injury. Inchcape Testing Services developed a Small Parts Aspiration, Ingestion, and Choking Hazards Research Project, independent of an ongoing consumer Product Safety Commission (CPSC) project. The project's purpose was to determine, independent of CPSC, whether a more stringent small parts regulatory standard was necessary and, if so, to ensure that the standard was determined objectively. This article reports on the project's findings relating to critical characteristics (size, shape, and consistency) relative to the victim's age, of objects responsible for child choking injuries and fatalities.
Environmental Agencies' Funding Sources Should Follow Their Diverse Business Models
Authors: O'Hare Michael
Published: January 2007

Environmental agencies provide a variety of regulatory, consulting, analysis, and other services that are typically funded by a mix of mechanisms including taxes, fees, contributions, and earmarked streams. Public deliberation in this area mostly attends to the levels of funding of these services, with inadequate attention to the relationship between means and funding adequacy, or between means and agency performance.

The characteristic business models of such agencies provide useful guidance regarding appropriate funding mechanisms. In particular, five different such models are commonly found, each with strong analogies to other familiar kinds of enterprise: (i) Agriculture: the Wildlife Ranch; (ii) Habitat; (iii) Maintenance: the Park; (iv) Consulting, education, and permits: the Think Tank; (v) Risk Spreading: Insurance; and (vi) Enforcement: The Police. Each of these models has strong although not usually decisive implications for the type of funding mechanism best suited to it. Budget analysis and internal accounting that incorporates these models would improve agencies' practice and their claims on appropriate funding. The analysis uses the California Department of Fish and Game as an example.
Assessing Differential Gene Expression with Small Sample Sizes in Oligonucleotide Arrays Using a Mean‐Variance Model
Authors: Hu Jianhua , Wright Fred A.
Published: January 2007

SummaryThe identification of the genes that are differentially expressed in two‐sample microarray experiments remains a difficult problem when the number of arrays is very small. We discuss the implications of using ordinaryt‐statistics and examine other commonly used variants. For oligonucleotide arrays with multiple probes per gene, we introduce a simple model relating the mean and variance of expression, possibly with gene‐specific random effects. Parameter estimates from the model have natural shrinkage properties that guard against inappropriately small variance estimates, and the model is used to obtain a differential expression statistic. A limiting value to the positive false discovery rate (pFDR) for ordinaryt‐tests provides motivation for our use of the data structure to improve variance estimates. Our approach performs well compared to other proposed approaches in terms of the false discovery rate.
Testing Goodness of Fit of a Uniform Truncation Model
Authors: Mandel Micha , Betensky Rebecca A.
Published: January 2007

SummarySeveral goodness‐of‐fit tests of a lifetime distribution have been suggested in the literature; many take into account censoring and/or truncation of event times. In some contexts, a goodness‐of‐fit test for the truncation distribution is of interest. In particular, better estimates of the lifetime distribution can be obtained when knowledge of the truncation law is exploited. In cross‐sectional sampling, for example, there are theoretical justifications for the assumption of a uniform truncation distribution, and several studies have used it to improve the efficiency of their survival estimates. The duality of lifetime and truncation in the absence of censoring enables methods for testing goodness of fit of the lifetime distribution to be used for testing goodness of fit of the truncation distribution. However, under random censoring, this duality does not hold and different tests are required. In this article, we introduce several goodness‐of‐fit tests for the truncation distribution and investigate their performance in the presence of censored event times using simulation. We demonstrate the use of our tests on two data sets.
Phylogeny of Phagotrophic Euglenids (Euglenozoa) as Inferred from Hsp90 Gene Sequences
Authors: BREGLIA SUSANA A. , SLAMOVITS CLAUDIO H. , LEANDER BRIAN S.
Published: January 2007

ABSTRACT. Molecular phylogenies of euglenids are usually based on ribosomal RNA genes that do not resolve the branching order among the deeper lineages. We addressed deep euglenid phylogeny using the cytosolic form of the heat‐shock protein 90 gene (hsp90), which has already been employed with some success in other groups of euglenozoans and eukaryotes in general. Hsp90 sequences were generated from three taxa of euglenids representing different degrees of ultrastructural complexity, namely Petalomonas cantuscygni and wild isolates of Entosiphon sulcatum, and Peranema trichophorum. The hsp90 gene sequence of P. trichophorum contained three short introns (ranging from 27 to 31 bp), two of which had non‐canonical borders GG‐GG and GG‐TG and two 10‐bp inverted repeats, suggesting a structure similar to that of the non‐canonical introns described in Euglena gracilis. Phylogenetic analyses confirmed a closer relationship between kinetoplastids and diplonemids than to euglenids, and supported previous views regarding the branching order among primarily bacteriovorous, primarily eukaryovorous, and photosynthetic euglenids. The position of P. cantuscygni within Euglenozoa, as well as the relative support for the nodes including it were strongly dependent on outgroup selection. The results were most consistent when the jakobid Reclinomonas americana was used as the outgroup. The most robust phylogenies place P. cantuscygni as the most basal branch within the euglenid clade. However, the presence of a kinetoplast‐like mitochondrial inclusion in P. cantuscygni deviates from the currently accepted apomorphy‐based definition of the kinetoplastid clade and highlights the necessity of detailed studies addressing the molecular nature of the euglenid and diplonemid mitochondrial genome.
Maternal effects on the life histories of bruchid beetles infesting Acacia raddiana in the Negev desert, Israel
Authors: Or K. , Ward D.
Published: January 2007

Acacia trees (Leguminosae) in the Negev desert of Israel are in substantial danger of extinction as a result of high mortality, caused by anthropogenically induced water stress and very low recruitment, which is highly negatively affected by bruchid beetle infestation. Intensive seed infestation (up to 97%) by bruchids on Acacia species in the Negev desert has been described. We hypothesized that water‐stressed trees would be less able to produce secondary defense compounds in their seeds to decrease seed herbivory and hence suffer higher infestation. Thus, there should be a negative correlation between the beetle's fitness and the tree's physiological state. We further hypothesized the mechanism of the correlation to be maternal effects on beetle quality. Thus, beetles whose mothers were reared on seeds of trees in a poor state should have higher fitness, regardless of the quality of the seeds in which they were reared. We reared F1 generation Caryedon palaestinicus Southgate (Coleoptera: Bruchidae) in seeds of Acacia raddiana Savi (Leguminosae) trees in good and in poor physiological state. We then conducted a reciprocal infestation experiment enabling females to lay on seeds from both sources. We found maternal effects on offspring number but not on body mass. The major effect was the limited survival of maternal beetles on trees in good physiological state. However, contrary to our prediction, C. palaestinicus developing in seeds from Acacia raddiana in good physiological state had significantly higher body mass.
Oxytocin Involvement in SSRI-Induced Delayed Ejaculation: A Review of Animal Studies
Authors: de Jong Trynke R. , Veening Jan G. , Olivier Berend , Waldinger Marcel D.
Published: January 2007

Introduction

Selective serotonin reuptake inhibitors (SSRIs) differ in the severity of induced ejaculation delay. Various studies indicate that oxytocin is involved in sexual behavior.

Aim

To review and evaluate the involvement of oxytocin in SSRI-induced ejaculation delay.

Main Outcome Measures

Oxytocine release, 5-hydroxytryptamine (5-HT) neurotransmission, and desensitization of 5-HT1A receptors.

Methods

A review and critical analysis of animal studies investigating the interaction of serotonergic and oxytocinergic neurotransmission in relation to the ejaculation process.

Results

Although acute treatment with the SSRIs fluoxetine and paroxetine immediately causes increased serotonin levels, delayed ejaculation does not occur. The increased serotonin levels induce oxytocin release via activation of 5-HT1A receptors, and this might compensate for the inhibitory actions of serotonin on sexual behavior. Chronic treatment with fluoxetine and paroxetine desensitizes 5-HT1A receptors on oxytocin neurons, and that might in part determine the onset of delayed ejaculation. Desensitization of 5-HT1A receptors is less strong following chronic treatment with the SSRIs fluvoxamine or citalopram, which may attenuate the degree of delayed ejaculation.

Conclusion

Preliminary data suggest that the severity of chronic SSRI treatment-induced delayed ejaculation and the differences between the various SSRIs in inducing ejaculation delay is related to gradual desensitization of 5-HT1A receptors on oxytocin neurons.
Sexual Counseling for Women in the Context of Physical Diseases—A Teaching Model for Physicians
Authors: Bitzer Johannes , Platano Giacomo , Tschudin S. , Alder Judith
Published: January 2007

Introduction

Chronic medical conditions are frequently associated with sexual difficulties and problems, which are often underreported and underdiagnosed. Patients may feel that sexual problems in the context of disease are not important enough to be mentioned to their physicians, and physicians may feel uncomfortable and sometimes incompetent. Furthermore, the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders-IV and International Classification of Diseases-10 are focused on the phenomenology of the sexual response without any specificity regarding diseases.

Aim

To facilitate access for patients and physicians, we wanted to develop a tool for assessment and discussion of sexual problems in the context of disease. This tool should be broadly applicable, easy to use and learn for nonmental health professionals.

Main Outcome Measures

Content analysis with respect to the integration of general sexological and disease-specific dimensions. Formulation of a diagnostic and therapeutic algorithm that can be used as a teaching tool.

Methods

Based on our experience as a liaison-consultation sexological division of the university hospital of Basel, we analyzed the sexological diagnostic workup performed with the following group of female patients: women with benign gynecologic conditions; women with incontinence; oncological patients (mammary carcinoma, genital carcinoma); neurological patients (multiple sclerosis, spine injury, Parkinson’s); patients with metabolic and endocrine disorders (diabetes, metabolic syndrome, polycystic ovarian syndrome); and patients with mental health disorders (depression, anxiety disorder, schizophrenia). We extracted the commonly used steps in the workup to construct a tool with easy-to-remember elements, which would help the physician to evaluate patients’ sexual problems and plan for referral or therapy.

Results

We could differentiate three diagnostic dimensions. The first were person-related preexisting factors, such as sexual satisfaction and function, age, body image, and general well-being. The second were the disease-specific implications, which could be summarized under the 8 Ds: Danger, Destruction, Disfigurement, Disability and pain, Dysfunction, Dysregulation, Disease load, and Drugs. The third was the patient’s and partner’s general response to the disease determined by affective response, coping style, body image impact, and changes in relationship dynamics.

Conclusion

Sexual problems are frequent in many clinical conditions, but are not yet a routine part of diagnostic workup and therapeutic planning. We have developed a tool to help physicians in different clinical settings to evaluate sexual problems of the female patients with specific clinical conditions in order to facilitate access to recognition and possible treatment.
Corpus Cavernosum Electromyography with Revised Methodology: An Explorative Study in Patients with Erectile Dysfunction and Men with Reported Normal Erectile Function
Authors: Meuleman Eric , Jiang Xiaogang , Holsheimer January , Wagner Gorm , Knipscheer Ben , Wijkstra Hessel
Published: January 2007

Introduction

A lack of standardization of the recording techniques of corpus cavernosum electromyography (CC-EMG) and objective criteria to characterize the recorded signals (CC-potentials) are the main difficulties hindering the clinical application of this method. These difficulties have been recently overcome by revising the recording and interpretation methodology of CC-EMG

Aim

To assess if CC-EMG performed with the revised methodology is discriminative for well-defined clinical conditions in patients with erectile dysfunction (ED).

Methods

Based on blinded clinical diagnosis, ED patients were catalogued into five subgroups: severe penile fibrosis, cavernous arterial insufficiency (CAI), cardio-vascular comorbidity (CVCM) without proven CAI, post-radical retropubic prostatectomy (RRP), and psychogenic ED. With four electrodes placed on the penile shaft bilaterally, CC-EMG was recorded monopolarly for 30 minutes during flaccidity. After evaluation of the recordings by visual inspection, CC-potentials were analyzed using cross- and autocorrelation techniques. The parameters evaluated were amplitude, duration, dominant frequency (DF), and maximum cross-correlation coefficient (Rmax) of CC-potentials recorded from proximal and distal parts of the CC.

Main Outcome Measures

Comparison of the values of parameters amplitude, duration, DF, and Rmax between patient and control groups.

Results

A total of 119 patients with ED and 43 men with reported normal erectile function were studied. Thirteen out of 14 patients with severe penile fibrosis did not show any distinguishable CC-potential. Patients with CAI had significantly decreased amplitude compared with the potent controls, as well as the patients with CVCM but without proven CAI. Significantly decreased amplitude and Rmax were detected in ED patients following RRP compared with the controls.

Conclusion

Corpus cavernosum electromyography performed with the revised methodology is able to discriminate ED patients with conditions that are associated with cavernous smooth muscle degeneration and/or autonomic neuropathy from men with reported normal erectile function.
Using a priori structural information from magnetic resonance imaging to investigate the feasibility of prostate diffuse optical tomography and spectroscopy: A simulation study
Authors: Li Chengyu , Liengsawangwong Raweewan , Choi Haesun , Cheung Rex
Published: January 2007

Implementation of diffuse optical tomography (DOT) for prostate cancer is challenging because the prostate is a deep‐seated organ. We investigated whether diffuse optical tomography (DOT) and spectroscopy could be applied to monitor the physiology of prostate cancer using a small probe that could be placed endorectally. We manually segmented the prostate, the intraprostatic tumor, and the rectum using data from endorectal magnetic resonance imaging. These structures were reconstructed and meshed with tetrahedral finite elements in three dimensions. A probe that has ten sources and 52 detectors were placed to face the anterior wall of the rectum in our simulation. Optical properties of the organs were obtained from the literature in the near infrared regime. Diffusion approximation was used to simulate photon migration with finite element method. Five wavelengths were used to simulate tissue absorption with realistic water, oxy‐ and deoxyhaemoglobin concentrations in the prostate. We combined a global search based on genetic algorithm with gradient‐driven local search methods to fit the simulated data. Our results suggest that the optical properties and the concentrations of the chromophores of the prostate and the prostate cancer can be reliably recovered from the measurements using an endorectal probe. Prostate DOT is worth further investigation for clinical application.
Absorption spectroscopy of EBT model film
Authors: Devic Slobodan , Tomic Nada , Pang Zhiyu , Seuntjens Jan , Podgorsak Ervin B. , Soares Christopher G.
Published: January 2007

The introduction of radiochromic films has solved some of the problems associated with conventional 2D radiation detectors. Their high spatial resolution, low energy dependence, and near‐tissue equivalence make them ideal for measurement of dose distributions in radiation fields with high dose gradients. Precise knowledge of the absorption spectra of these detectors can help to develop more suitable optical densitometers and potentially extend the use of these films to other areas such as the measurement of the radiation beam spectral information. The goal of this study is to present results of absorption spectra measurements for the new film, EBT type, exposed to photon beam in the dose range from 0 to . Spectroscopic analysis reveals that in addition to the two main absorption peaks, centered at around and , the absorption spectrum in the spectral range from to contains six more absorption bands. Comparison of the absorption spectra reveals that previous HD‐810, MD‐55, as well as HS film models, have nearly the same sensitive layer base material, whereas the new EBT model, film has a different composition of its sensitive layer. We have found that the two most prominent absorption bands in EBT model radiochromic film do not change their central wavelength position with change in a dose deposited to the film samples.
Dose response of storage phosphor plates exposed to megavoltage photon beams
Authors: Li H. Harold , Gonzalez Albin L. , Ji Huaying , Duggan Dennis M.
Published: January 2007

The storage phosphor plate (SPP) is a reusable radiation image detector, widely used in diagnostic computed radiography, x‐ray crystallography and radioactive tracer studies. When exposed to ionizing radiation, the SPP stores a latent image until it is scanned with a red reading laser which causes blue photostimulated luminescent (PSL) photons to be emitted. The mechanism of formation of the latent image is still poorly understood, especially for megavoltage photon beams. In order to gain insight into this mechanism and aid applications to high‐energy beam dosimetry, the authors have directly determined the SPP generation efficiency, , the energy required to produce one quantum of emitted PSL when it is irradiated by and photon beams. This was done in four steps: 1. The SPP, in a water‐equivalent plastic (WEP) phantom, was exposed to a or beam, which had been calibrated to give a known absorbed dose to water in a water phantom at the position of the sensitive layer of the SPP. 2. Monte Carlo simulations were used to calculate the ratio of the dose to the sensitive layer in the WEP phantom to the dose to water at the same position in a water phantom. 3. A bleaching experiment was used to determine the number of photons emitted by a plate given a known dose. 4. The generation efficiency was calculated from the number of photons and the dose. This method is much more direct than previous calculations for kilovoltage x‐ray beams based on quantum noise analysis. W was found, within experimental uncertainty, to be for and for , independent of dose. The values for kilovoltage x‐ray beams determined previously agree, within their large uncertainty, with these values for megavoltage beams.
Biological dose volume histograms during conformal hypofractionated accelerated radiotherapy for prostate cancer
Authors: Koukourakis Michael I. , Abatzoglou Ioannis , Touloupidis Stavros , Manavis Ioannis
Published: January 2007

Radiobiological data suggest that prostate cancer has a low ratio. Large radiotherapy fractions may, therefore, prove more efficacious than standard radiotherapy, while radiotherapy acceleration should further improve control rates. This study describes the radiobiology of a conformal hypofractionated accelerated radiotherapy scheme for the treatment of high risk prostate cancer. Anteroposterior fields to the pelvis deliver a daily dose of , while lateral fields confined to the prostate and seminal vesicles deliver an additional daily dose of . Radiotherapy is accomplished within (15 fractions). Dose volume histograms, calculated for tissue specific ratios and time factors, predict a high biological dose to the prostate and seminal vesicles . The biological dose to normal pelvic tissues is maintained at standard levels. Radiobiological dosimetry suggests that, using hypofractionated and accelerated radiotherapy, high biological radiation dose can be given to the prostate without overdosing normal tissues.
Validation of Laboratory Screening Criteria for Herpes Simplex Virus Testing of Cerebrospinal Fluid
Authors: Hanson Kimberly E. , Alexander Barbara D. , Woods Christopher , Petti Cathy , Reller L. Barth
Published: January 2007

Most patients with herpes simplex virus (HSV) central nervous system (CNS) infection have abnormal cerebrospinal fluid (CSF) indices. Therefore, we implemented screening criteria based on CSF values and host immune status to guide testing. All CSF samples submitted for HSV PCR analysis from January 1999 through December 2004 were included in the study. Specimens from patients with human immunodeficiency virus, a history of transplants, an age of <2 years, a CSF white blood cell count of >5 cells/mm
3
, or a protein level of >50 mg/dl were tested upon request. All other samples were rejected and frozen. To validate our screening criteria, rejected specimens were pooled and tested retrospectively. Electronic medical records were also reviewed. A total of 1,659 HSV PCR requests from 1,458 patients were screened. Of the 1,296 specimens (78.1%) accepted for testing, 1,213 were negative, 7 were positive for HSV type 1 (HSV-1), 26 were positive for HSV-2, and 50 had unavailable results. Sixteen requests were rejected because an alternative microbiologic diagnosis had been established. Of the 347 samples rejected based on criteria, 222 (64.0%) remained available for pooled testing. No HSV-1-positive samples were identified in the rejected specimens. Two rejected specimens tested positive for HSV-2 DNA, but both met acceptance criteria which had not been communicated to the laboratory. Few patients (7.8%) with rejected specimens were treated with acyclovir, which suggests a low clinical concern for HSV encephalitis. Acceptance criteria based on CSF parameters and host immune status saved time and cost and did not miss patients with HSV CNS infection. Communication between the clinician and the laboratory is imperative for a successful screening program.
Microarray-Based Identification of Tenascin C and Tenascin XB, Genes Possibly Involved in Tumorigenesis Associated with Neurofibromatosis Type 1
Authors: Lévy Pascale , Ripoche Hugues , Laurendeau Ingrid , Lazar Vladimir , Ortonne Nicolas , Parfait Béatrice , Leroy Karen , Wechsler Janine , Salmon Isabelle , Wolkenstein Pierre , Dessen Philippe , Vidaud Michel , Vidaud Dominique , Bièche Ivan
Published: January 2007

Purpose: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a complex variety of clinical manifestations. The hallmark of NF1 is the onset of heterogeneous (dermal or plexiform) benign neurofibromas. Plexiform neurofibromas can give rise to malignant peripheral nerve sheath tumors, which are resistant to conventional therapies.

Experimental Design: To identify new signaling pathways involved in the malignant transformation of plexiform neurofibromas, we applied a 22,000-oligonucleotide microarray approach to a series of plexiform neurofibromas and malignant peripheral nerve sheath tumors. Changes in the expression of selected genes were then confirmed by real-time quantitative reverse transcription-PCR.

Results: We identified two tenascin gene family members that were significantly deregulated in both human NF1-associated tumors and NF1-deficient primary cells: Tenascin C (TNC) was up-regulated whereas tenascin XB (TNXB) was down-regulated during tumor progression. TNC activation is mainly due to the up-regulation of large TNC splice variants. Immunohistochemical studies showed that TNC transcripts are translated into TNC protein in TNC-overexpressing tumors. Aberrant transcriptional activation of TNC seems to be principally mediated by activator protein transcription factor complexes.

Conclusion: TNXB and TNC may be involved in the malignant transformation of plexiform neurofibromas. Anti-TNC antibodies, already used successfully in clinical trials to treat malignant human gliomas, may be an appropriate new therapeutic strategy for NF1.
Winter-Season Climate Prediction for the U.K. Health Sector
Authors: McGregor G. R. , Cox M. , Cui Y. , Cui Z. , Davey M. K. , Graham R. F. , Brookshaw A.
Published: January 2007

The winter climate of the British Isles is characterized by considerable interannual variability, which, because of the general climate sensitivity of a number of health outcomes, places at times considerable pressure on the provision of health services. Seasonal climate forecasts potentially could improve management within the health sector and assist in hedging against the vagaries of climatic variability. For this reason, an exploratory analysis of the potential utility of seasonal climate forecasting for the health sector in the United Kingdom is presented here. Study results revealed that the general level of winter mortality at the monthly to seasonal time scale possesses a strong association with simple descriptors of winter climate such as maximum temperature and the number of days below a given temperature threshold. Because such climate indices can be derived from the output of coupled seasonal climate prediction models, predictions of general levels of mortality may be possible using simple transfer functions that describe winter climate and health associations. Despite the potential one-month-ahead and one-season-ahead predictability of winter mortality levels, the predictability of the key climate indices by coupled climate models is shown to be somewhat limited, which compromises the ability to predict general levels of winter mortality for all months except February.
Cirrus Microphysical Properties and Air Motion Statistics Using Cloud Radar Doppler Moments. Part I: Algorithm Description
Authors: Deng Min , Mace Gerald G.
Published: January 2007

The first three moments of the millimeter-wavelength radar Doppler spectrum provide valuable information regarding both cloud properties and air motion. An algorithm using these Doppler radar moments is developed to retrieve cirrus microphysical properties and the mean air vertical motion and their errors. The observed Doppler spectrum results from the convolution of a quiet-air radar reflectivity spectrum with the turbulence probability density function. Instead of expressing the convolution integral in terms of the particle fall velocity as in past studies, herein the convolution integral is integrated over the air motion so that the mean vertical velocity within the sample volume can be explicitly solved. To avoid an ill-conditioned problem, the turbulence is considered as a parameter in the algorithm and predetermined from the Doppler spectrum width and radar reflectivity based on the observation that the spread of the particle size distribution in the velocity domain dominates the Doppler spectrum width measurement for most cirrus. It is also shown that the assumed single mode functional shapes cannot reliably represent significant bimodalities. Nevertheless, the IWC can be retrieved more reliably than can the mass mean particle size. Error analysis also shows that the retrieval algorithm results are very sensitive to the power-law relationships describing the ice particle mass and the terminal velocity in terms of the particle maximum length. It is estimated that the algorithm errors will be on the order of 35%, 85%, and ±20 cm s−1 for mass mean particle size, IWC, and sample volume mean air motion, respectively. Algorithm validation with in situ data demonstrates that the algorithm can determine the cloud microphysical properties and air mean vertical velocity within the predicted theoretical error bounds.
The role of chemerin in the colocalization of NK and dendritic cell subsets into inflamed tissues
Authors: Parolini Silvia , Santoro Amerigo , Marcenaro Emanuela , Luini Walter , Massardi Luisa , Facchetti Fabio , Communi David , Parmentier Marc , Majorana Alessandra , Sironi Marina , Tabellini Giovanna , Moretta Alessandro , Sozzani Silvano
Published: January 2007

Chemerin is a chemotactic agonist recently identified as the ligand of ChemR23, a serpentine receptor expressed by mononuclear phagocytes and dendritic cells (DCs). This study shows that blood CD56lowCD16+ natural killer (NK) cells selectively express functional ChemR23 and that this receptor is coexpressed with CXCR1, the CXCL8 receptor, and the KIR receptors. In vitro culturing of NK cells with IL-2 or IL-15 induced a delayed and time-dependent down-regulation of ChemR23 that was associated with the inhibition of NK cell migration to chemerin. Biopsies obtained from patients with oral lichen planus presented an infiltration of CD94+CD3−CD56+ NK cells that coexpressed ChemR23. The same biopsies were infiltrated by myeloid, DC-SIGN+ and plasmacytoid, CD123+BDCA2+, ChemR23+ dendritic cells that were occasionally associated with NK cells. In the same histologic sections, chemerin was expressed by inflamed dermal endothelium. These findings propose a role for the ChemR23/chemerin axis in the recruitment of blood NK cells and strongly implicate chemerin as a key factor for the colocalization of NK cells and DC subsets in pathologic peripheral tissues.
Protocol for the THREAD (THREshold for AntiDepressants) study: a randomised controlled trial to determine the clinical and cost-effectiveness of antidepressants plus supportive care, versus supportive care alone, for mild to moderate depression in UK general practice
Authors: Chatwin Judy , Kendrick Tony ,   the THREAD Study Group
Published: January 2007

Background

Depression guidelines in the UK recommended a policy of watchful waiting for mild depression due to a lack of evidence for the effectiveness of antidepressant treatment for mild cases. However there has been relatively little research carried out in primary care to help establish the severity threshold at which antidepressant treatment is effective and cost-effective.

Methods/Design

The THREAD (THREshold for AntiDepressants) study is a multi-centre randomised controlled trial designed to determine the clinical and cost effectiveness of a selective serotonin reuptake inhibitor (SSRI) plus general practitioner (GP) supportive care, versus supportive care alone, for mild to moderate depression in primary care. The aim is to recruit 300 patients from three centres (Southampton, London and Liverpool). Depressive symptoms will be assessed at baseline, 12 weeks and 26 weeks, using the 17-item Hamilton Depression Rating Scale (HDRS). Two severity sub-groups of patients will be recruited, with HDRS scores of 12–15, and 16–19. Possible predictors of response will be explored including life events and difficulties and alcohol consumption. Analysis of covariance, controlling for baseline value, severity group and centre will be used to estimate the overall treatment effectiveness (difference in HDRS score) at final follow up. The primary analysis will be by 'intention to treat' using double sided tests. The interaction between severity sub-group and treatment will be tested, and if appropriate, effects within separate severity sub-groups estimated. The economic analysis will compare the two treatment groups in terms of mean costs and cost-effectiveness.

Discussion

The results of this study will give GPs important information to help them determine the severity of depression at which antidepressant treatment is likely to be cost-effective.
Hereditary chronic pancreatitis
Authors: Rosendahl Jonas , Bödeker Hans , Mössner Joachim , Teich Niels
Published: January 2007

Hereditary chronic pancreatitis (HCP) is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) have been found to be associated with chronic pancreatitis (idiopathic and hereditary) as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.
Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling
Authors: Haraguchi Ryuma , Motoyama Jun , Sasaki Hiroshi , Satoh Yoshihiko , Miyagawa Shinichi , Nakagata Naomi , Moon Anne , Yamada Gen
Published: January 2007

The urogenital and reproductive organs, including the external genitalia,bladder and urethra, develop as anatomically aligned organs. Descriptive and experimental embryology suggest that the cloaca, and its derivative, the urogenital sinus, contribute to the formation of these organs. However, it is unknown how the primary tissue lineages in, and adjacent to, the cloaca give rise to the above organs, nor is bladder formation understood. While it is known that sonic hedgehog (Shh) is expressed by the cloacal epithelia, the developmental programs that regulate and coordinate the formation of the urogenital and reproductive organs have not been elucidated. Here we report that Shh mutant embryos display hypoplasia of external genitalia, internal urethra (pelvic urethra) and bladder. The importance of Shh signaling in the development of bladder and external genitalia was confirmed by analyzing a variety of mutant mouse lines with defective hedgehog signaling. By genetically labeling hedgehog-responding tissue lineages adjacent to the cloaca and urogenital sinus, we defined the contribution of these tissues to the bladder and external genitalia. We discovered that development of smooth muscle myosin-positive embryonic bladder mesenchyme requires Shh signaling,and that the bladder mesenchyme and dorsal (upper) external genitalia derive from Shh-responsive peri-cloacal mesenchyme. Thus, the mesenchymal precursors for multiple urogenital structures derive from peri-cloacal mesenchyme and the coordination of urogenital organ formation from these precursors is orchestrated by Shh signals.
Prevention of Plasticity of Endocannabinoid Signaling Inhibits Persistent Limbic Hyperexcitability Caused by Developmental Seizures
Authors: Chen Kang , Neu Axel , Howard Allyson L. , Földy Csaba , Echegoyen Julio , Hilgenberg Lutz , Smith Martin , Mackie Ken , Soltesz Ivan
Published: January 2007

Depolarization-induced suppression of inhibition (DSI) is an endocannabinoid-mediated short-term plasticity mechanism that couples postsynaptic Ca2+rises to decreased presynaptic GABA release. Whether the gain of this retrograde synaptic mechanism is subject to long-term modulation by glutamatergic excitatory inputs is not known. Here, we demonstrate that activity-dependent long-term DSI potentiation takes place in hippocampal slices after tetanic stimulation of Schaffer collateral synapses. This activity-dependent, long-term plasticity of endocannabinoid signaling was specific to GABAergic synapses, as it occurred without increases in the depolarization-induced suppression of excitation. Induction of tetanus-induced DSI potentiationin vitrorequired a complex pathway involving AMPA/kainate and metabotropic glutamate receptor as well as CB1 receptor activation. Because DSI potentiation has been suggested to play a role in persistent limbic hyperexcitability after prolonged seizures in the developing brain, we used these mechanistic insights into activity-dependent DSI potentiation to test whether interference with the induction of DSI potentiation prevents seizure-induced long-term hyperexcitability. The results showed that thein vitro, tetanus-induced DSI potentiation was occluded by previousin vivofever-induced (febrile) seizures, indicating a common pathway. Accordingly, application of CB1 receptor antagonists during febrile seizuresin vivoblocked the seizure-induced persistent DSI potentiation, abolished the seizure-induced upregulation of CB1 receptors, and prevented the emergence of long-term limbic hyperexcitability. These results reveal a new form of activity-dependent, long-term plasticity of endocannabinoid signaling at perisomatic GABAergic synapses, and demonstrate that blocking the induction of this plasticity abolishes the long-term effects of prolonged febrile seizures in the developing brain.
Serotonin Modulates Pallidal Neuronal Activity in the Awake Monkey
Authors: Kita Hitoshi , Chiken Satomi , Tachibana Yoshihisa , Nambu Atsushi
Published: January 2007

Serotonin (5-HT)-containing neurons in the dorsal raphe project to the external and internal segments of the pallidum, which express several 5-HT receptors. Although the involvement of 5-HT in basal ganglia movement control has been suggested, little is known about the physiological action of 5-HT in the pallidum. Previous anatomical studies andin vitrophysiological studies in other brain areas have suggested the following possibilities: (1) 5-HT suppresses GABAergic inhibition through presynaptic 5-HT1Breceptors; (2) 5-HT decreases the firing of pallidal neurons through postsynaptic 5-HT1Areceptors; and (3) 5-HT postsynaptically excites pallidal neurons through activation of 5-HT2C, 5-HT4, or 5-HT7receptors. To test these possibilities, we examined the effects of locally applied agonists and antagonists of 5-HT on spontaneous neuronal firing and on excitatory and inhibitory responses of pallidal neurons to electrical stimulation of the motor cortex in awake monkeys. Althoughin vivoexperiments could not conclusively determine the receptor types or the active sites involved in the observed effects, the results suggested the following possibilities: (1) 5-HT strongly suppresses GABAergic inhibition probably through 5-HT1Breceptors; (2) in the external pallidal segment, the suppression may involve additional receptors or mechanisms; and (3) 5-HT suppresses glutamatergic excitation probably through 5-HT1A(and not 5-HT1B) receptors. The present study did not isolate or identify the existence of strong, direct postsynaptic inhibitory or excitatory effects of 5-HT. Thus, present results imply that 5-HT modulates synaptic inputs of both pallidal segments and exerts a significant role in movement control.
Hyperexcitability of Distal Dendrites in Hippocampal Pyramidal Cells after Chronic Partial Deafferentation
Authors: Cai Xiang , Wei Dong-Sheng , Gallagher Sandra E. , Bagal Ashish , Mei Yan-Ai , Kao Joseph P. Y. , Thompson Scott M. , Tang Cha-Min
Published: January 2007

Traumatic injury to the CNS results in chronic partial deafferentation of subsets of surviving neurons. Such injuries are often followed by a delayed but long-lasting period of aberrant hyperexcitability. The cellular mechanisms underlying this delayed hyperexcitability are poorly understood. We developed anin vitromodel of deafferentation and reactive hyperexcitability using organotypic hippocampal slice cultures to study the underlying cellular mechanisms. One week after transection of the Schaffer collateral and temporoammonic afferents to CA1 neurons, brief tetanic stimulation of the residual excitatory synapses produced abnormally prolonged depolarizations, compared with responses in normally innervated neurons. Responses to weak stimulation, in contrast, were unaffected after deafferentation. Direct stimulation of distal apical dendrites using focal photolysis of caged glutamate triggered abnormally prolonged plateau potentials in the deafferented neurons when strong stimulation was given, but responses to weak stimulation were not different from controls. An identical phenotype was produced by chronic “chemical deafferentation” with glutamate receptor antagonists. Responses to strong synaptic and photolytic stimulation were selectively prolonged by small-conductance (SK-type) calcium-activated potassium channel blockers in normally innervated cells but not after deafferentation. No significant changes in SK2 mRNA or protein levels, GABAergic inhibition, glutamate receptor function, input resistance, or action potential parameters were observed after chronic deafferentation. We suggest that a posttranslational downregulation of SK channel function in thin distal dendrites is a significant contributor to deafferentation-induced reactive hyperexcitability.
Nonvesicular Release of Glutamate by Glial xCT Transporters Suppresses Glutamate Receptor ClusteringIn Vivo
Authors: Augustin Hrvoje , Grosjean Yael , Chen Kaiyun , Sheng Qi , Featherstone David E.
Published: January 2007

We hypothesized that cystine/glutamate transporters (xCTs) might be critical regulators of ambient extracellular glutamate levels in the nervous system and that misregulation of this glutamate pool might have important neurophysiological and/or behavioral consequences. To test this idea, we identified and functionally characterized a novelDrosophilaxCT gene, which we subsequently named “genderblind” (gb). Genderblind is expressed in a previously overlooked subset of peripheral and central glia. Genetic elimination ofgbcauses a 50% reduction in extracellular glutamate concentration, demonstrating that xCT transporters are important regulators of extracellular glutamate. Consistent with previous studies showing that extracellular glutamate regulates postsynaptic glutamate receptor clustering,gbmutants show a large (200–300%) increase in the number of postsynaptic glutamate receptors. This increase in postsynaptic receptor abundance is not accompanied by other obvious synaptic changes and is completely rescued when synapses are cultured in wild-type levels of glutamate. Additionalin situpharmacology suggests that glutamate-mediated suppression of glutamate receptor clustering depends on receptor desensitization. Together, our results suggest that (1) xCT transporters are critical for regulation of ambient extracellular glutamatein vivo; (2) ambient extracellular glutamate maintains some receptors constitutively desensitizedin vivo; and (3) constitutive desensitization of ionotropic glutamate receptors suppresses their ability to cluster at synapses.