bluuebunny/crossref_metadata_2025 huggingface dataset:
Embryonic Cerebral Cortical Progenitors Are Resistant to Apoptosis, but Increase Expression of Suicide Receptor DISC‐Complex Genes and Suppress Autophagy Following Ethanol Exposure
Authors: Prock Terasa L. , Miranda Rajesh C.
Published: February 2007

Background: In utero exposure to ethanol can result in severe fetal brain defects. Previous studies showed that ethanol induces apoptosis in differentiated cortical neurons. However, we know little about ethanol's effects on proliferating embryonic cortical progenitors. This study investigated the impact of ethanol exposure on the Fas/Apo‐1/CD95 suicide receptor pathway, and on the survival of proliferating cortical neuroepithelial progenitors.

Methods: Murine embryonic‐derived primary cortical neuroepithelial cells were maintained as neurosphere cultures and exposed to a dose range of ethanol for periods ranging from 1 to 5 days. Programmed cell death was measured by 4 independent means (Annexin‐V staining, caspase activation, DNA fragmentation, and autophagic vacuole formation). Surface Fas/Apo‐1 suicide receptor expression was measured by flow cytometry. Expression of Fas/Apo‐1‐associated DISC‐complex genes was measured by quantitative polymerase chain reaction.

Results: Ethanol exposure did not substantially increase apoptosis, necrosis, or surface Fas/Apo‐1 expression. Moreover, ethanol significantly decreased caspase activation and autophagic activity. Finally, ethanol exposure induced mRNA expression of genes that constitute the death receptor complex.

Conclusions: This study provides surprising evidence that ethanol does not induce either programmed cell death or necrosis of immature progenitors during neurogenesis, although ethanol may render neural progenitors susceptible to future apoptotic insults. Furthermore, our novel observation that ethanol suppresses autophagy is consistent with a hypothesis that ethanol promotes premature neural progenitor maturation. Taken together with our previous data regarding the role of the Fas/Apo‐1 receptor in neural development, we conclude that ethanol disrupts basic proliferation and differentiation machinery rather than initiating cell death per se.
Proxies and Consent Discussions for Dementia Research
Authors: Sugarman Jeremy , Roter Debra , Cain Carole , Wallace Roberta , Schmechel Don , Welsh‐Bohmer Kathleen A.
Published: February 2007

OBJECTIVES: To better understand the nature of informed consent encounters for research involving patients with dementia that requires proxy consent.

DESIGN: Audiotaping of informed‐consent encounters for a study of genetic markers for sporadic Alzheimer's disease.

SETTING: Outpatients at an Alzheimer's disease research center.

PARTICIPANTS: Patients with dementia and their companions.

MEASUREMENTS: Audiotapes were analyzed to characterize communication style and coverage of the standard elements of informed consent and, using the Roter Interaction Analysis System, to capture the dynamics of three‐way interaction between the patient, their companion, and the physician investigator.

RESULTS: Of 26 informed consent encounters, all involved a patient, a companion, and a physician. Patients had a mean Mini‐Mental State Examination (MMSE) score of 21.8. For patients, 49% of their interactions involved agreement and approval (positive statements), 16% psychosocial information, 7% biomedical information, 7% asking questions, and 7% expressing emotion. Companion interactions involved 37% positive statements and 19% biomedical information. Physician interactions involved emotional expressiveness (30%) and positive statements (19%). Discussion length was positively related to MMSE score (Spearman rho=0.45; P<.02). Coverage of required elements of informed consent was fairly comprehensive and had no relationship to patients' MMSE scores.

CONCLUSION: These data should inform policies regarding the ethically appropriate ways of conducting research with cognitively impaired adults. For example, patients in this study were more silent than their companions and the physician, but when patients spoke, they primarily agreed with what was said. Although this might first seem to signal assent, such an interpretation should be made with caution for persons with dementia. In addition, previous work on informed consent has focused on its cognitive aspects, but these data reveal that the emotional and social dimensions warrant attention.
ROC Graphs for Assessing the Ability of a Diagnostic Marker to Detect Three Disease Classes with an Umbrella Ordering
Authors: Nakas Christos T. , Alonzo Todd A.
Published: February 2007

SummaryReceiver operating characteristic (ROC) curves and the area under these curves are commonly used to assess the ability of a continuous diagnostic marker (e.g., DNA methylation markers) to correctly classify subjects as having a particular disease or not (e.g., cancer). These approaches, however, are not applicable to settings where the gold standard yields more than two disease states or classes. ROC surfaces and the volume under the surfaces have been proposed for settings with more than two disease classes. These approaches, however, do not allow one to assess the ability of a marker to differentiate two disease classes from a third disease class without requiring a monotone order for the three disease classes under study. That is, existing approaches do not accommodate an umbrella ordering of disease classes. This article proposes the construction of an ROC graph that is applicable for an umbrella ordering. Furthermore, this article proposes that a summary measure for this umbrella ROC graph can be used to summarize the classification accuracy, and corresponding variance estimates can be obtained using U‐statistics theory or bootstrap methods. The proposed methods are illustrated using data from a study assessing the ability of a DNA methylation marker to correctly classify lung specimens into three histologic classes: squamous cell carcinoma, large cell carcinoma, and nontumor lung.
Statistical Reconstruction of Transcription Factor Activity Using Michaelis–Menten Kinetics
Authors: Khanin R. , Vinciotti V. , Mersinias V. , Smith C. P. , Wit E.
Published: February 2007

Summary The basic building block of a gene regulatory network consists of a gene encoding a transcription factor (TF) and the gene(s) it regulates. Considerable efforts have been directed recently at devising experiments and algorithms to determine TFs and their corresponding target genes using gene expression and other types of data. The underlying problem is that the expression of a gene coding for the TF provides only limited information about the activity of the TF, which can also be controlled posttranscriptionally. In the absence of a reliable technology to routinely measure the activity of regulators, it is of great importance to understand whether this activity can be inferred from gene expression data. We here develop a statistical framework to reconstruct the activity of a TF from gene expression data of the target genes in its regulatory module. The novelty of our approach is that we embed the deterministic Michaelis–Menten model of gene regulation in this statistical framework. The kinetic parameters of the gene regulation model are inferred together with the profile of the TF regulator. We also obtain a goodness‐of‐fit test to verify the fit of the model. The model is applied to a time series involving the Streptomyces coelicolor bacterium. We focus on the transcriptional activator cdaR, which is partly responsible for the production of a particular type of antibiotic. The aim is to reconstruct the activity profile of this regulator. Our approach can be extended to include more complex regulatory relationships, such as multiple regulatory factors, competition, and cooperativity.
Evaluating the impact of agricultural extension on farms' performance in Crete: a nonneutral stochastic frontier approach
Authors: Dinar Ariel , Karagiannis Giannis , Tzouvelekas Vangelis
Published: February 2007

This article attempts to integrate the production‐ and the efficiency‐based approaches for evaluating the impact of extension on farms' performance. For this purpose the nonneutral production frontier model is used, and the empirical analysis refers to a sample of farms from Crete, Greece. The empirical results support the proposed formulation instead of either the production‐ or the efficiency‐based formulations as extension was found to have a statistically significant effect on closing both the technology and management gaps. Public and private extension services were found to be competitive in the production function and complementary in the technical inefficiency effect function. In addition, farms using both public and private extension services achieved a higher degree of technical efficiency than those using either public or private extension services, and farms with no extension services were found to be the least efficient.
Coping with flood: role of institutions in Bangladesh
Authors: Khandker Shahidur R.
Published: February 2007

The article examines the coping strategies that rural households adopted during the 1998 flood in Bangladesh and assesses its impact on household welfare, including coping and vulnerability. Both vulnerability and poverty have in general declined in Bangladesh. Yet, 60% of rural households adopted a coping of one type or another and about half of rural households were both vulnerable as well as found to adopt any coping mechanism during the 1998 flood. Household‐level panel data analysis confirms that the flood reduced both consumption and asset, and forced many households to adopt some coping mechanisms to mitigate the adverse effects of flood. Consequently, natural disaster such as flooding increases households' vulnerability to poverty. However, post‐flood bumper crop production and operation of targeted programs such as microfinance helped compensate the losses of flood.
Exchange rate alignment and producer support estimates (PSEs) for India
Authors: Cheng Fuzhi , Orden David
Published: February 2007

This article examines the effects of exchange rate alignment during 1985–2002 on agricultural producer support estimates (PSEs) for India. Based on several time series techniques, the equilibrium exchange rate of the Indian rupee and the corresponding misalignment of the actual rate are estimated and applied to recent PSE calculations. Our results show that the exchange rate was substantially misaligned before a financial crisis and macroeconomic reform in the early 1990s, with subsequent indirect effects on the PSEs. We find a relatively high pass‐through of exchange rate movements to domestic agricultural prices, so that removal of the exchange rate misalignment would have improved incentives to Indian farmers during this period. More recently, this indirect exchange rate effect is smaller than the direct effect in the PSEs, indicating the dominance of sectoral‐specific policies over economy‐wide policies.
Agricultural trade liberalization and economic development: the role of downstream market power
Authors: Sexton Richard J. , Sheldon Ian , McCorriston Steve , Wang Humei
Published: February 2007

A model is developed to characterize the vertically linked and concentrated nature of developed‐country food markets. This model is then parameterized and used to simulate the effects of varying food market structures on the benefits to developing‐country exporters of agricultural commodities from trade liberalization by developed countries. Results demonstrate that even relatively modest departures from perfect competition can cause much of the benefits from trade liberalization to flow to marketing firms instead of producers in the developing country. The distributional effects under downstream market power differ significantly from the perfectly competitive case and may result, somewhat paradoxically, in developing countries receiving a lower share of the total value added within the food chain as trade reform occurs.
Influence of Ginkgo biloba on ocular blood flow
Authors: Wimpissinger Barbara , Berisha Fatmire , Garhoefer Gerhard , Polak Kaija , Schmetterer Leopold
Published: February 2007

Purpose:  To investigate the effect of Ginkgo biloba extract (EGb761) on ocular blood flow.

Methods:  This randomized, double‐masked, placebo‐controlled, two‐way crossover study included 15 healthy male volunteers. Measurements were taken with laser Doppler flowmetry, laser Doppler velocimetry, a retinal vessel analyser, laser interferometry and applanation tonometry, before and up to 3 hours after oral intake of 240 mg EGb761.

Results:  At baseline, no significant differences in ocular and systemic haemodynamic parameters were observed between the two study days. Ginkgo biloba significantly decreased retinal venous diameters (p < 0.05 versus baseline), but there was no significant difference between the two groups. Blood pressure, retinal arterial and venous diameters, choroidal blood flow, fundus pulsation amplitude, intraocular pressure and retinal blood flow remained unchanged in both groups and did not differ between groups. Optic nerve head blood flow significantly increased in response to Ginkgo biloba (p < 0.002 versus baseline), but this effect was not significant compared with that of placebo.

Conclusions:  The results of this study indicate that a single administration of Ginkgo biloba does not influence ocular blood flow to a relevant degree. Whether the drug may influence ocular blood flow in patients with ocular vascular disease after longterm treatment remains to be investigated in a randomized, placebo‐controlled clinical trial.
Mobilization of endothelial progenitor cells in patients with hematological malignancies after treatment with filgrastim and chemotherapy for autologous transplantation
Authors: Mauro Endri , Rigolin Gian Matteo , Fraulini Chiara , Sofritti Olga , Ciccone Maria , Angeli Cristiano De , Castoldi Gianluigi , Cuneo Antonio
Published: February 2007

In recent years, endothelial progenitor cells (EPCs), gave rise to increasing interest because of their possible use as a therapeutic tool in the treatment of vascular lesions in ischemic tissues or as a target for anti neoplastic therapy. It has been shown that several drugs can increase the number of EPCs into the peripheral blood (PB). However, there is insufficient data concerning the mobilization and collection of EPCs during CD34+ cell mobilization. In this study, we have evaluated EPC mobilization and collection in a series of 47 patients affected by lymphoid neoplasms [31 non Hodgkin lymphoma and 16 multiple myeloma] undergoing CD34+ cell mobilization with cyclophosphamide (4000 mg/m2) and Filgrastim (5 μg/kg). PB EPCs identified by flow cytometry as CD34+/VEGFR2+/CD133+ cells showed a peak on day +10. This peak paralleled that of PB CD34+/CD45+ cells. A direct correlation was observed between CD34+ and CD34+/VEGFR2+/CD133+ cells (r = 0.99 P < 0.0001). An average of 23.7 × 10e6 CD34+/VEGFR2+CD133+ cells have been collected (range 12.1–41.76 × 10e6). These findings showed that in hematological diseases, cyclophosphamide in combination with filgrastim allows the mobilization and collection of large numbers of EPCs which may be used for reparative medicine studies in these patients.
Gamma‐glutamylcysteine synthetase‐based selection strategy for gene therapy of chronic granulomatous disease and graft‐vs.‐host disease
Authors: Rappa Germana , Anzanello Fabio , Alexeyev Mikhail , Fodstad Oystein , Lorico Aurelio
Published: February 2007

Efficient ex vivo/in vivo selection of genetically modified hematopoietic stem/progenitor cells (HPCs) and T lymphocytes could greatly improve several gene therapy strategies. We have previously reported that primary murine HPCs, transduced with a bicistronic retroviral vector, co‐expressing the catalytic subunit of gamma‐glutamylcysteine synthetase (γ‐GCSh) and eGFP, could be selected by l‐buthionine‐S,R‐sulfoximine (BSO). Upon ex vivo transduction with a low, defined gene dosage and BSO selection, HPCs were able to repopulate the bone marrow of syngeneic myeloablated hosts, showing multi‐lineage expression [Hum Gene Ther, 16 (2005), 711]. We now provide ‘proof‐of‐principle’ that the same strategy can be applied to the gene therapy of graft‐vs.‐host disease (GVHD) subsequent to allogeneic bone marrow transplantation (ABMT), and of chromosome X‐associated chronic granulomatous disease (CGD). Transfer of the herpes simplex virus‐thymidine kinase (HSV‐Tk) ‘suicide’ gene into donor T lymphocytes is a potential method to control GVHD after ABMT. However, an efficient selection system is required to eliminate non‐HSV‐Tk‐expressing T lymphocytes before administration to the patient. We now report that, upon transduction with a retroviral vector, co‐expressing γ‐GCSh and eGFP, and subsequent selection by BSO, over 95% human T lymphocytes were found to express eGFP; moreover, upon transduction with a novel retroviral vector co‐expressing γ‐GCSh and HSV‐Tk, and subsequent BSO treatment, over 95% of T lymphocytes could be eliminated by ganciclovir. The efficacy of the γ‐GCSh‐BSO selection strategy was then tested on an in vitro model of CGD. Upon transduction of gp91 (phox)‐deficient PLBKO cells with a novel bicistronic retroviral vector co‐expressing human gp91 (phox) and γ‐GCSh, exposure to BSO for 48 h eliminated most non‐transduced cells, resulting in selection of gp91 (phox)‐expressing cells, and reconstitution of NADPH oxidase activity.
A novel fibrinogen variant – Praha I: hypofibrinogenemia associated with γ Gly351Ser substitution
Authors: Kotlín Roman , Chytilová Martina , Suttnar Jiří , Salaj Peter , Riedel Tomáš , Šantrůček Jiří , Klener Pavel , Dyr Jan Evangelista
Published: February 2007

Objectives:  A 25‐yr‐old man from Prague had abnormal bleeding after several surgical operations with low fibrinogen level and hypofibrinogenemia was suspected.

Patients and methods:  The patient, 25 yr‐old male had a low fibrinogen concentration as determined by the thrombin time and immunoturbidimetrical method. His 48‐yr‐old mother presented with normal coagulation tests, normal fibrinogen level and reported no history of bleeding. To identify the genetic mutation responsible for this hypofibrinogen, genomic DNA extracted from the blood was analyzed. Fibrin polymerization measurement, kinetics of fibrinopeptide release, fibrinogen clottability measurement, mass spectroscopy, and scanning electron microscopy were performed.

Results:  DNA sequencing showed heterogeneous fibrinogen γG351S mutation in the propositus. The mutant chain was found not to be expressed to the circulation by matrix‐assisted laser desorption/ionization time of flight mass spectrometry. Scanning electron micrographs of the patient's fibrin clot as well as kinetics of fibrinopeptide release and fibrin polymerization were found to be normal.

Conclusion:  A case of hypofibrinogenemia γG351S was found by routine coagulation testing and was genetically identified.
Histological observation of root bud formation of hairy roots in Lotus corniculatus L.
Authors: Fukuda Ken‐ichi , Daimon Hiroyuki , Mishiba Kei‐ichiro , Mii Masahiro
Published: February 2007

The anatomy of endogenous buds formation in hairy roots transformed by infection with a wild strain of Agrobacterium rhizogenes, A‐13, was studied in birdsfoot trefoil (Lotus corniculatus L.). Hairy root cultures, which had been subcultured in the dark, formed green spots (GS) spontaneously within 20 days after transfer to light conditions, and then GS developed to shoots. The GS structures were produced directly on the hairy roots showing no caulogenesis. Transverse sections at the center of GS structures showed that prominent mitotic activities existed inside of the endodermis, which consisted of a layer of spindly cells. Those proliferated regions composed the GS structures and root buds arose from these regions. Within 20 days after emergence of GS, the meristematic regions developed to shoots, and the apex had distinct single‐layered tunica with leaf primordia. The region of the root in which bud initiation occurred was the pericycle. Differentiation of root buds from the other origin of root tissues such as cortical cells and root apical cells was not found.
Asian Values and the Asia Pacific Community: Shared Interests and Common Concerns1
Authors: Levine Stephen
Published: February 2007

This article is intended as a further contribution to discussions concerning the role, if any, of “Asian Values” in the political, economic, and security relationships of nation‐states in the Asia Pacific region. More specifically, this article seeks to identify shared features of these relationships, the extent to which these can be characterized as sufficiently significant as to constitute a form of “community,” and the extent to which these relationships, and such a community, are influenced in any way by values distinctively “Asian” in character.
Management of 49 antebrachial and crural fractures in dogs using circular external fixators‡
Authors: Rovesti G. L. , Bosio A. , Marcellin‐Little D. J.
Published: February 2007

Objectives:To evaluate frame constructs, postoperative fracture reduction, postoperative care, complications, treatment duration and outcome of circular external fixation for management of 49 antebrachial and crural fractures in dogs.

Methods:Medical records of dogs that underwent surgery with circular external fixation were examined for fracture location, frame configuration, postoperative fracture reduction, treatment duration, complications and outcome.

Results:Forty‐nine fractures in 48 dogs were stabilised using circular external fixation. Frame removal occurred on average 61 days after surgery (median±sd, 52±30 days). Minor complications were observed in 35 cases (71 per cent) and major complications in seven (14 per cent). Radiographic outcome at frame removal was judged as excellent in 18 cases (37 per cent), as good in 26 (53 per cent), as fair in four (8 per cent) and poor in one (2 per cent). After frame removal, one fracture was stabilised with a plate, and eight patients were lost to follow‐up. Functional and cosmetic outcome at follow‐up was judged as excellent in 32 cases (80 per cent), good in seven (18 per cent) and fair in one (2 per cent).

ClinicalSignificance:Circular external fixation can effectively treat antebrachial and crural fractures in dogs, even geometrically complex fractures. Minor complications are frequent but easily managed in most instances. Healing time is comparable to that of other external fixation methods.
Structural Principles of Tau and the Paired Helical Filaments of Alzheimer’s Disease
Authors: Mandelkow Eckhard , Von Bergen Martin , Biernat Jacek , Mandelkow Eva‐Maria
Published: February 2007

Tau, a major microtubule‐associated protein in brain, forms abnormal fibers in Alzheimer’s disease and several other neurodegenerative diseases. Tau is highly soluble and adopts a natively unfolded structure in solution. In the paired helical filaments of Alzheimer’s disease, small segments of tau adopt a β‐conformation and interact with other tau molecules. In the filament core, the microtubule‐binding repeat region of tau has a cross‐β structure, while the rest of the protein retains its largely unfolded structure and gives rise to the fuzzy coat of the filaments.
Progressive Supranuclear Palsy: Pathology and Genetics
Authors: Dickson Dennis W. , Rademakers Rosa , Hutton Michael L.
Published: February 2007

Progressive supranuclear palsy (PSP) is an atypical Parkinsonian disorder associated with progressive axial rigidity, vertical gaze palsy, dysarthria and dysphagia. Neuropathologically, the subthalamic nucleus and brainstem, especially the midbrain tectum and the superior cerebellar peduncle, show atrophy. The substantia nigra shows loss of pigment corresponding to nigrostriatal dopaminergic degeneration. Microscopic findings include neuronal loss, gliosis and neurofibrillary tangles in basal ganglia, diencephalon and brainstem. Characteristic tau pathology is also found in glia. The major genetic risk factor for sporadic PSP is a common variant in the gene encoding microtubule‐associated protein tau (MAPT) and recent studies have suggested that this may result in the altered expression of specific tau protein isoforms. Imaging studies suggest that there may be sensitive and specific means to differentiate PSP from other parkinsonian disorders, but identification of a diagnostic biomarker is still elusive.
Frontotemporal Lobar Degeneration: Current Concepts in the Light of Recent Advances
Authors: Kumar‐Singh Samir , Van Broeckhoven Christine
Published: February 2007

Work done over the past decade has led to a molecular understanding of frontotemporal lobar degeneration (FTLD), a deadly disease that afflicts patients in mid‐life. It is a common cause of dementia, second only to Alzheimer’s disease in the population below 65 years of age. Neuroanatomical and neurobiological substrates have been identified for the three major subtypes of FTLD and these discoveries have broadened the FTLD spectrum to include amyotrophic lateral sclerosis (ALS). Mutations in MAPT were found to cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17), a familial disorder with filamentous tau inclusions in nerve cells and glial cells. FTDP‐17 can result in clinical syndromes that closely resemble progressive supranuclear palsy, corticobasal degeneration and Pick’s disease. More recently, mutations in three genes (VCP, CHMP2B and PGRN) have been found to cause FTLD with ubiquitin‐positive, tau‐negative neuronal inclusions (FTLD‐U). They explain a large proportion of inherited FTLD‐U. It remains to be seen whether dementia lacking distinctive histopathology (DLDH) constitutes a third disease category, as many of these cases are now being reclassified as FTLD‐U. Recently, TAR DNA‐binding protein‐43 (TDP‐43) has been identified as a key protein of the ubiquitin inclusions of FTLD‐U and ALS. Thus, for familial forms of FTLD and related disorders, we now know the primary etiologies and accumulating proteins. These findings are pivotal for dissecting the pathways by which different etiologies lead to the varied clinicopathological presentations of FTLD.
Alois Alzheimer: His Life and Times
Authors: Goedert Michel , Ghetti Bernardino
Published: February 2007

Between national unification and World War I, Germany was preeminent in many areas of science and medicine. Alois Alzheimer, who lived during this period, was one of the founders of the field of neuropathology. His name will always be linked with the form of dementia that he described 100 years ago. Here we mark this anniversary by discussing Alzheimer’s contributions to dementia research in the context of his life and times.
From commitment to reality: early intervention in psychosis services in England
Authors: Tiffin Paul A. , Glover Gyles
Published: February 2007

Aim:  To evaluate the extent to which Government plans for early intervention in psychosis services have been realized in England, the UK.

Methods:  Data from the Mental Health Mapping Exercise and Department of Health quarterly performance monitoring were used. Semi‐structured interviews were also conducted with the nine regional early intervention in psychosis Leads from the National Institute for Mental Health in England in order to ascertain their views and experiences regarding early intervention in psychosis service development.

Results:  By 2006 118 teams were operating. However, the staffing and skill mix of each varied considerably with only half reporting that they met all the criteria set out in the original policy guidance.

Conclusion:  Although an impressive number of services have been developed, concerns remain regarding their size, configuration and functional capacity.
Prodromal stage of major depression
Authors: Fava Giovanni A. , Tossani Eliana
Published: February 2007

Aim:  The aim of this review was to survey the available literature on prodromal symptoms of unipolar major depression.

Methods:  Both a computerized (Medline) and a manual search of the literature were performed.

Results:  In a substantial proportion of patients with depression a prodromal phase can be identified. There is a relationship between residual and prodromal symptomatology (the rollback phenomenon).

Conclusions:  Appraisal of prodromal phase of major depression has important implications as to pathophysiological models of disease and relapse prevention. It may allow a staging system of depressive illness that may yield more enduring results in the therapeutic efforts.
Early identification and treatment of eating disorders: prodrome to syndrome
Authors: Grange Daniel le , Loeb Katharine L.
Published: February 2007

The onset of eating disorder psychopathology is most common in the adolescent age group. Acute psychopathology or subsyndromal eating disorders are perhaps less intractable in these young patients. Subsyndromal eating disorders in children and adolescents are not only clinically significant in their present state, but may represent legitimate candidates for preventive efforts in light of: (i) a risk of progression from subthreshold anorexia nervosa (SAN) to AN or subthreshold bulimia nervosa (SBN) to BN; (ii) the detrimental effects on outcome of delaying treatment; and (iii) the refractory, severe nature of eating disorders once the diagnostic threshold is crossed. Moreover, children and adolescents with SAN and SBN may in fact be exhibiting early ‘caseness’ of these disorders. Given that AN is notoriously difficult to treat, and there are limited efficacy data for adolescent BN, attempts to disrupt these disorders in what is arguably their early phases is an important goal in preventing more chronic and treatment‐resistant forms of these disorders. Future research should address whether the best interventions for SAN and SBN should be derived from the prevention or intervention fields.
Early Psychosis Prevention and Intervention Centre long‐term follow‐up study of first‐episode psychosis: methodology and baseline characteristics
Authors: Henry Lisa P. , Harris Meredith G. , Amminger G. Paul , Yuen Hok Pan , Harrigan Susy M. , Lambert Martin , Conus Philippe , Schwartz Orli , Prosser Amy , Farrelly Simone , Purcell Rosemary , Herrman Helen , Jackson Henry J. , McGorry Patrick D.
Published: February 2007

Aim:  This paper reports the rationale, methodology and baseline characteristics of a large long‐term follow‐up study of first‐episode psychosis from a geographically defined catchment area.

Method:  A total of 723 first‐episode psychosis patients were recruited from a specialized early psychosis service between 1989 and 2001 and prospectively followed up at a median of 7.4 years after initial presentation. Participants’ baseline demographic, clinical and functional characteristics are described. Sampling bias at study recruitment was assessed by comparison with a more complete sample of Early Psychosis Prevention and Intervention Centre (EPPIC) cases rated directly from the medical records.

Results:  At baseline, 57% of the sample were diagnosed with schizophrenia or schizophreniform disorder, whereas the full range of psychotic disorders was represented. Statistical analysis confirmed that the sample recruited was representative of total EPPIC‐treated incident cases.

Conclusions:  The EPPIC long‐term follow‐up study is a large and epidemiologically representative first‐episode psychosis cohort that has been subsequently prospectively followed up over a long period. Such a sample provides a rare opportunity to study the course and outcome of psychotic disorders.
Beliefs about appropriate first aid for young people with mental disorders: findings from an Australian national survey of youth and parents
Authors: Jorm Anthony F. , Wright Annemarie , Morgan Amy J.
Published: February 2007

Objective:  To determine the mental health first‐aid knowledge and beliefs of young people and their parents.

Methods:  A national telephone survey was carried out with 3746 people aged 12–25 years. Interviews were also carried out with 2005 co‐resident parents. First‐aid knowledge was assessed in response to one of four randomly presented vignettes covering depression, depression with alcohol misuse, social phobia and psychosis (schizophrenia). Young people were asked about first aid in relation to a peer and parents in relation to a child.

Results:  The potential value of encouraging professional help‐seeking was not universally recognized by either young people or adults. In general, positive social interactions were endorsed as likely to be helpful and negative ones as not, but again there is considerable room for improvement. Adolescents had less sophisticated first‐aid knowledge and beliefs than young adults, but were paradoxically more confident about providing help to a peer.

Conclusions:  These findings show that there is a continuing need for further community education about the potential benefits of early professional treatment of young people developing mental disorders.
Social and symptomatic outcomes of first‐episode bipolar psychoses in an early intervention service
Authors: Macmillan Iain , Howells Lawrence , Kale Kedar , Hackmann Corinna , Taylor Gavin , Hill Katherine , Bradford Steve , Fowler David
Published: February 2007

Aim:  We aimed to establish the relative proportions of all diagnoses in people aged 14–35 years presenting to an early intervention in psychosis service, and to compare demographic variables, symptoms and outcomes between the bipolar psychoses and other psychoses at 3–6 months and 1 year post referral.

Methods:  Prospective 3‐ to 6‐month diagnostic and symptomatic assessments were carried out. Diagnoses were established using the Diagnostic Interview for Psychoses – Diagnostic Module. Symptoms and outcomes were assessed using standardized instruments at 3–6 months and 1 year. Bipolar diagnoses were grouped together in a bipolar group (n=16) and compared with all other diagnoses, in a non‐bipolar group (n=62). Parallel analysis was carried out using groups of lifetime elevated, expansive or irritable mood (n=32) and no lifetime elevated, expansive or irritable mood (n=46).

Results:  Bipolar disorders account for 20.5% of all new presentations to our service. Differences in outcomes over the range of psychotic diagnoses relate to early presence of negative symptoms. Psychoses with bipolar diagnoses or lifetime elevated, expansive or irritable mood showed lower rates of negative symptoms than other psychoses and had a higher quality of life and higher function at 3–6 months and 1 year.

Conclusions:  Planning for future early intervention services should take the high rate of affective psychoses and their need for diagnosis‐specific, evidence‐based treatments into account. Lifetime elevated, expansive or irritable mood may predict improved outcomes in early psychoses, possibly mediated by lower levels of negative symptoms.
A Study of Sootblower Erosion in Waste-Incinerating Heat
Boilers
Authors: Sciubba Enrico , Zeoli Nicola
Published: February 2007

A numerical three-dimensional (3D) simulation was performed on the flow of a particle-laden steam jet impinging on the tubes of the superheating section of a waste-burning industrial boiler: the study was conducted to investigate the causes of excessive erosion systematically detected under otherwise normal operation. Prior experimental evidence had led to the identification of the slag particles as a possible agent for such an erosion: these particles are removed from the surface of the first row of the tubes by the steam jet ejected from the sootblower, and may cause erosion if they impinge on the tubes of the following (upstream, in the direction of the gas path) rows. Three sootblower configurations were considered to analyze this presumed phenomenology of tube erosion. The (significant) effects of turbulence on the motion of the solid particles are taken into account by means of a stochastic flow model. The simulation generates a prediction of the particles trajectories, both in a geometrical sense (to locate the portions of the tube surfaces on which the individual particles may impinge) and in a statistical one (to identify the relative frequency of the impacts on each portion of surface): the erosion rate for each sootblower configuration has been calculated on the basis of the impact frequency indicated by the numerical calculations.
The Exhaust Heat Use Plan When Connecting Solar Modules to a Fuel Cell Energy Network
Authors: Obara Shin’ya
Published: February 2007

The energy supply method by distributed power supply is expected from the transportation loss of the power and a decrease in heat. The system using especially renewable energy and a fuel cell is excellent from the viewpoint of the environment. However, the efficiency of the whole system depends on the amount of utilization of exhaust heat. The system assumed in this paper installs a small fuel cell and a solar module in 12 buildings, connects each building with hot-water piping, and supplies fuel cell exhaust heat. The hot-water piping path that results in minimum heat release loss was investigated in the optimization analysis using a genetic algorithm. As a result, the optimal path of the hot-water piping considering the production of electricity of a solar module and ambient temperature was clarified.
Porosity and Permeability Effects on Centerline Temperature Distributions, Peak Flame Temperature, Flame Structure, and Preheating Mechanism for Combustion in Porous Media
Authors: F. S. R. Khatami , Safavisohi B. , Sharbati E.
Published: February 2007

The applicability and usefulness of combustion in porous media is of much interest due to its competitive combustion efficiency and lower pollutants formation. In the previous works, the focus has been on the effects of combustion and heat transfer parameters such as excess air ratio, thermal power, solid conductivity, convective heat transfer coefficient, and radiation properties on centerline temperature and pollutant formations. A premixed combustion scheme and a fixed porous medium with constant geometrical parameters have been used in these works; therefore, the effects of porous material parameters have been less considered. In this research, the effects of geometrical parameters of porous medium, namely porosity and permeability, on centerline temperature distributions, peak flame temperature, flame structure, and gas mixture preheating have been investigated by numerical methods. To this, a two-dimensional axis-symmetric physical model of porous burner is considered. As the most typical porous burners, a two stage one which has preheating porous zone (PPZ) and combustion porous zone (CPZ) is studied. The continuity, momentum, energy, turbulence, and species transport equations are solved employing a one-step chemical reaction mechanism with an eddy-dissipation model for rate of reactions. The turbulence is modeled with two transport equations which are not considered in similar works. The combustion regime is assumed to be diffusion and combustion parameters are fixed in all cases. Porosity effects on the structure and temperature characteristic of the flame are probed in a wide range for PPZ and CPZ. Critical permeability is defined and permeability effects on flame characters in both of the preheating and combustion regions are studied thoroughly.
Microgrid Viability for Small-Scale Cooling, Heating, and Power
Authors: Ribarov Lubomir A. , Liscinsky David S.
Published: February 2007

Cooling, heating, and power (CHP) energy systems provide higher fuel efficiency than conventional systems, resulting in reduced fuel consumption, reduced emissions, and other environmental benefits. Until recently the focus of CHP system development has been primarily on medium-scale commercial applications in a limited number of market segments where clear value propositions lead to short term payback. Small-scale integrated CHP systems that show promise of achieving economic viability through significant improvements in fuel utilization have received increased attention lately. In this paper the economic potential is quantified for small-scale (microgrid) integrated CHP systems suitable for groups of buildings with aggregate electric loads in the 15-120kW range. Technologies are evaluated for community building groups (CBGs) consisting of aggregation of pure residential entities and combined residential and light commercial entities. Emphasis is on determination of the minimum load size (i.e., the smallest electric and thermal load for a given CBG that is supplied with electric, heating, cooling power from a CHP) for which a microgrid CHP system is both technically and economically viable. In this paper, the operation of the CHP system is parallel with the public utility grid at all times, i.e., the grid is interconnected. Evaluations of CHP technology options using simulation studies in a “three-dimensional” space (CHP technology option, CBG load aggregation, and geographical location in the USA) were evaluated based on comparisons of net present value (NPV). The simulations indicated that as electric load increases, the viability of the CHP system (independent of the system’s size) becomes more favorable. Exceeding a system runtime (utilization) of 70% was shown to pass the break-even line in the NPV analysis. Finally, geographic location was found to have a relatively weak effect on the reported trends. These results suggest that microgrid CHP systems have the potential to be economically viable with relative independence of geographic location if adequately sized to match the specific load requirements.
Efficacy of the De Novo-Derived Antimicrobial Peptide WLBU2 against Oral Bacteria
Authors: Novak Karen F. , Diamond William J. , Kirakodu Sreenatha , Peyyala Rebecca , Anderson Kimberly W. , Montelaro Ronald C. , Mietzner Timothy A.
Published: February 2007

The efficacy of a novel synthetic antimicrobial peptide (WLBU2) was evaluated against three oral microorganisms (grown planktonically):
Streptococcus gordonii, Fusobacterium nucleatum
, and
Porphyromonas gingivali
s. WLBU2 killed all three species, with
F. nucleatum
being the most susceptible. WLBU2 also reduced the bacterial burden of
S. gordonii
and
F. nucleatum
biofilms.
Modeling the Combination of Amphotericin B, Micafungin, and Nikkomycin Z against
Aspergillus fumigatus
In Vitro Using a Novel Response Surface Paradigm
Authors: Brun Yseult F. , Dennis Carly G. , Greco William R. , Bernacki Ralph J. , Pera Paula J. , Bushey Jennifer J. , Youn Richard C. , White Donald B. , Segal Brahm H.
Published: February 2007

Response surface methods for the study of multiple-agent interaction allow one to model all of the information present in full concentration-effect data sets and to visualize and quantify local regions of synergy, additivity, and antagonism. In randomized wells of 96-well plates,
Aspergillus fumigatus
was exposed to various combinations of amphotericin B, micafungin, and nikkomycin Z. The experimental design was comprised of 91 different fixed-ratio mixtures, all performed in quintuplicate. After 24 h of drug exposure, drug effect on fungal viability was assessed using the tetrazolium salt 2,3-bis {2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2
H
-tetrazolium-hydroxide} (XTT) assay. First, we modeled each fixed-ratio combination alone using the four-parameter Hill concentration-effect model. Then, we modeled each parameter, including the 50% inhibitory concentration (IC
50
) effect, versus the proportion of each agent using constrained polynomials. Finally, we modeled the three-agent response surface overall. The overall four-dimensional response surface was complex, but it can be explained in detail both analytically and graphically. The grand model that fit the best included complex polynomial equations for the slope parameter
m
and the combination index (equivalent to the IC
50
for a fixed-ratio concentration, but with concentrations normalized by the respective IC
50
s of the drugs alone). There was a large region of synergy, mostly at the nikkomycin Z/micafungin edge of the ternary plots for equal normalized proportions of each drug and extending into the center of the plots. Applying this response surface method to a huge data set for a three-antifungal-agent combination is novel. This new paradigm has the potential to significantly advance the field of combination antifungal pharmacology.
Dissemination of an Extended-Spectrum-β-Lactamase
bla
TEM-52
Gene-Carrying IncI1 Plasmid in Various
Salmonella enterica
Serovars Isolated from Poultry and Humans in Belgium and France between 2001 and 2005
Authors: Cloeckaert Axel , Praud Karine , Doublet Benoît , Bertini Alessia , Carattoli Alessandra , Butaye Patrick , Imberechts Hein , Bertrand Sophie , Collard Jean-Marc , Arlet Guillaume , Weill François-Xavier
Published: February 2007

We report here the dissemination of a conjugative IncI1 plasmid carrying
bla
TEM-52
on a Tn
3
transposon conferring resistance to extended-spectrum cephalosporins in
Salmonella enterica
serovar Agona, Derby, Infantis, Paratyphi B dT
+
, and Typhimurium isolates from poultry and humans in Belgium and France from 2001 to 2005. The most prevalent serovar spreading this resistance was serovar Infantis.
Genetic Basis of Resistance to Fusidic Acid in Staphylococci
Authors: O'Neill A. J. , McLaws F. , Kahlmeter G. , Henriksen A. S. , Chopra I.
Published: February 2007

Resistance to fusidic acid in
Staphylococcus aureus
often results from acquisition of the
fusB
determinant or from mutations in the gene (
fusA
) that encodes the drug target (elongation factor G). We now report further studies on the genetic basis of resistance to this antibiotic in the staphylococci. Two staphylococcal genes that encode proteins exhibiting ca. 45% identity with FusB conferred resistance to fusidic acid in
S. aureus
. One of these genes (designated
fusC
) was subsequently detected in all fusidic acid-resistant clinical strains of
S. aureus
tested that did not carry
fusB
or mutations in
fusA
, and in strains of
S. intermedius
. The other gene (designated
fusD
) is carried by
S. saprophyticus
, explaining the inherent resistance of this species to fusidic acid. Fusidic acid-resistant strains of
S. lugdunensis
harbored
fusB
. Thus, resistance to fusidic acid in clinical isolates of
S. aureus
and other staphylococcal species frequently results from expression of FusB-type proteins.
Synthesis and Characterization of a Dipalmitoylated Lipopeptide Derived from Paralogous Lipoproteins of
Mycoplasma pneumoniae
Authors: Into Takeshi , Dohkan Jun-ichi , Inomata Megumi , Nakashima Misako , Shibata Ken-ichiro , Matsushita Kenji
Published: February 2007

Genomic analysis of
Mycoplasma pneumoniae
revealed the existence of a large number of putative lipoprotein genes compared with the numbers in other bacteria. However, the pathogenic roles of
M. pneumoniae
lipoproteins are still obscure. In this study, we synthesized a lipopeptide (designated
M. pneumoniae
paralogous lipoprotein 1 [MPPL-1]) in which an
S
-dipalmitoylglyceryl cysteine was coupled to a peptide with a consensus sequence of a putative paralogous lipoprotein group characteristic of
M. pneumoniae
. The cytokine-inducing activity of MPPL-1 in human monocytic cells was much weaker (∼700-fold weaker) than that of the known mycoplasmal
S
-dipalmitoylated lipopeptide FSL-1 or MALP-2. MPPL-1 required Toll-like receptor (TLR2) to activate NF-κB-dependent gene transcription in HEK293 cells, although a 1,000-fold-larger amount of MPPL-1 was needed to exert activity similar to that of FSL-1 in the cells. TLR2-mediated recognition of MPPL-1 was synergistically upregulated by TLR6 but not by TLR1 or TLR10, although the activity was still weak. In addition, MPPL-1 did not antagonize FSL-1 recognition in human monocytic cells and TLR2/TLR6-expressing HEK293 cells. Thus, these results suggest that there is preferential selective recognition of diacylated lipopeptides due to the magnitude of an affinity with TLR2 and TLR6 and the roles of increased paralogous lipoprotein genes of
M. pneumoniae
in evasion of TLR2 recognition.