bluuebunny/crossref_metadata_2025 huggingface dataset:
A network biology model of micronutrient related health
Authors: van Ommen Ben , Fairweather-Tait Susan , Freidig Andreas , Kardinaal Alwine , Scalbert Augustin , Wopereis Suzan
Published: July 2008

Micronutrients are involved in specific biochemical pathways and have dedicated functions in the body, but they are also interconnected in complex metabolic networks, such as oxidative-reductive and inflammatory pathways and hormonal regulation, in which the overarching function is to optimise health. Post-genomic technologies, in particular metabolomics and proteomics, both of which are appropriate for plasma samples, provide a new opportunity to study the metabolic effects of micronutrients in relation to optimal health. The study of micronutrient-related health status requires a combination of data on markers of dietary exposure, markers of target function and biological response, health status metabolites, and disease parameters. When these nutrient-centred and physiology/health-centred parameters are combined and studied using a systems biology approach with bioinformatics and multivariate statistical tools, it should be possible to generate a micronutrient phenotype database. From this we can explore external factors that define the phenotype, such as lifestage and lifestyle, and the impact of genotype, and the results can also be used to define micronutrient requirements and provide dietary advice. New mechanistic insights have already been developed using biological network models, for example genes and protein-protein interactions in the aetiology of type 2 diabetes mellitus. It is hoped that the challenge of applying this approach to micronutrients will, in time, result in a change from micronutrient oriented to a health oriented views and provide a more holistic understanding of the role played by multiple micronutrients in the maintenance of homeostasis and prevention of chronic disease, for example through their involvement in oxidation and inflammation.
Comparison of multi-criteria decision models to approach the trade-off between environmental sustainability and economical viability – a case of nitrogen balance in dairy farming systems in Reunion Island
Authors: ALARY V. , GOUSSEFF M. , NIDUMOLU U. B.
Published: July 2008

In the context of market liberalization and in order to avoid trade distortions, European farmers risk experiencing a restriction of subsidies for market products. Moreover, policy makers cannot underestimate the public concerns about the non-productive functions of agriculture, such as environmental management. The current study illustrates different ways of modelling the trade-offs between environmental sustainability and economic viability for dairy farming systems in Reunion Island. Nitrogen (N) balance at the farm level is the result of complex interactions between pasture and animal management and between bio-technical and socio-economic management. Therefore, different multi-criteria models were tested using a common dynamic bio-economical model that integrated the different sub-systems of the farm and their interactions. Nitrogen excess mitigation in Reunion Island dairy farming systems was used as an illustration of a non-productive objective taken into account in the decision process modelling.

The simulations highlighted the necessity to adapt the nitrogen mitigation objective to the technical level of local territories in order to adopt environmentally friendly practices, without jeopardizing the local dairy sector. Moreover, the models generated a different set of solutions that varied according to how non-production functions are integrated in farmers' decision-making processes. This constitutes a relevant basis for discussions between farmers and decision makers.
Mapping of the conserved antigenic domains shared between potato apyrase and parasite ATP diphosphohydrolases: potential application in human parasitic diseases
Authors: FARIA-PINTO P. , REZENDE-SOARES F. A. , MOLICA A. M. , MONTESANO M. A. , MARQUES M. J. , ROCHA M. O. C. , GOMES J. A. S. , ENK M. J. , CORREA-OLIVEIRA R. , COELHO P. M. Z. , NETO S. M. , FRANCO O. L. , VASCONCELOS E. G.
Published: July 2008

Evolutionary and closer structural relationships are demonstrated by phylogenetic analysis, peptide prediction and molecular modelling betweenSolanum tuberosumapyrase,Schistosoma mansoniSmATPase 2 andLeishmania braziliensisNDPase. Specific protein domains are suggested to be potentially involved in the immune response, and also seem to be conserved during host and parasite co-evolution. Significant IgG antibody reactivity was observed in sera from patients with American cutaneous leishmaniasis (ACL) and schistosomiasis using potato apyrase as antigen in ELISA.S. mansoniadult worm or egg,L. braziliensispromastigote (Lb) andTrypanosoma cruziepimastigote (EPI) have ATP diphosphohydrolases, and antigenic preparations of them were evaluated. In ACL patients, IgG seropositivity was about 43% and 90% for Lb and potato apyrase, respectively, while IgM was lower (<19%) for both. In schistosomiasis patients IgM (>40%) or IgG (100%) seropositivity for both soluble egg (SEA) and adult worm (SWAP) antigens was higher than that found for potato apyrase (IgM=10%; IgG=39%). In Chagas disease, IgG seropositivity for EPI and potato apyrase was 97% and 17%, respectively, while the IgM was low (3%) for both antigens. The study of the conserved domains from both parasite proteins and potato apyrase could lead to the development of new drug targets or molecular markers.
Lipid content and fatty acid composition of the monogeneanNeobenedenia girellaeand comparison between the parasite and host fish species
Authors: SATO S. , HIRAYAMA T. , HIRAZAWA N.
Published: July 2008

Neobenedenia girellae, a capsalid monogenean, is a destructive fish parasite. We studied the lipid content and fatty acid composition ofN. girellaeand the skin and cutaneous mucus of a host fish, the amberjackSeriola dumerili(Carangidae). The lipid content of adultN. girellaewas less than one-fourth that of both the skin and cutaneous mucus of its host. AdultN. girellae,S. dumeriliskin and mucus had a relatively high weight-percentage of C16:0, C18:1(n-9), C18:0 and C22:6(n-3) fatty acids. WhenS. dumeriliwere fed a diet supplemented with [13C] fatty acids, [13C] fatty acids were detected inS. dumeriliskin and adultN. girellaeonS. dumerili, but no [13C] fatty acids were detected in theS. dumerilicutaneous mucus. In addition, the epidermis ofS. dumerili, attached withN. girellae, was markedly thin. These results suggest thatN. girellaefeeds primarily on host epithelial cells. We then infected 2 host fishes,S. dumeriliand the spotted halibutVerasper variegatus(Pleuronectidae; a host less susceptible toN. girellaeinfection), and compared the fatty acid composition ofN. girellaewith that of the skin and cutaneous mucus of the hosts. The fatty acid profiles from all samples were qualitatively and quantitatively similar. Thus, the fatty acid composition of the host may not contribute to the difference in susceptibility betweenS. dumeriliandV. variegatus. These results may serve to develop new strategies for the control ofN. girellaeinfections.
GUITAR COMPOSER LEO BROUWER: THE CONCEPT OF A ‘UNIVERSAL LANGUAGE’
Authors: Kronenberg Clive
Published: July 2008

In the realm of art music, Leo Brouwer (1939-) is widely considered as the most significant living composer for the guitar. Since the latter part of the 20th century, students of the guitar at most, if not all, recognized music institutions have increasingly sought to perform Brouwer's works. Correspondingly, at the South African College of Music (University of Cape Town) respected instructors like Elspeth Jack, Neefa van der Schyff, and others, have over many years consistently and devotedly incorporated Brouwer's guitar literature into their teaching programmes. Cape Town's prized composer-conductor Alan Stephenson has similarly developed a keen interest in Brouwer's large-scale works, inspiring in 1998 a memorable rendition of Brouwer's acclaimed Elegiaco Concerto, performed by the talented soloist Christiaan Van der Vyver and the University of Cape Town Orchestra. In line with this, one of Brouwer's underlying goals has been to create works that are accessible to players of varying standards of performance. As a consequence, young, inexperienced, moderate, advanced as well as top internationally-acclaimed virtuosic players have all found some measure of contentment in performing Brouwer's guitar works.
BE FRUITFUL AND MULTIPLY: A THEORETICAL EXPLANATION OF COPLAND'S ‘IN THE BEGINNING’
Authors: Sieck Stephen
Published: July 2008

The really important question is: ‘What does the composer start with; where does he begin?’ The answer to that is, Every composer begins with a musical idea – a musical idea, you understand, not a mental, literary, or extramusical idea. Suddenly a theme comes to him. (Theme is used as synonymous with musical idea.) The composer starts with this theme; and the theme is a gift from Heaven. Aaron Copland, What to Listen for in Music (1939)
Key principles for the improved conduct of health technology assessments for resource allocation decisions
Authors: Drummond Michael F. , Schwartz J. Sanford , Jönsson Bengt , Luce Bryan R. , Neumann Peter J. , Siebert Uwe , Sullivan Sean D.
Published: July 2008

Health technology assessment (HTA) is a dynamic, rapidly evolving process, embracing different types of assessments that inform real-world decisions about the value (i.e., benefits, risks, and costs) of new and existing technologies. Historically, most HTA agencies have focused on producing high quality assessment reports that can be used by a range of decision makers. However, increasingly organizations are undertaking or commissioning HTAs to inform a particular resource allocation decision, such as listing a drug on a national or local formulary, defining the range of coverage under insurance plans, or issuing mandatory guidance on the use of health technologies in a particular healthcare system. A set of fifteen principles that can be used in assessing existing or establishing new HTA activities is proposed, providing examples from existing HTA programs. The principal focus is on those HTA activities that are linked to, or include, a particular resource allocation decision. In these HTAs, the consideration of both costs and benefits, in an economic evaluation, is critical. It is also important to consider the link between the HTA and the decision that will follow. The principles are organized into four sections: (i) “Structure” of HTA programs; (ii) “Methods” of HTA; (iii) “Processes for Conduct” of HTA; and (iv) “Use of HTAs in Decision Making.”
Assessing the impact of health technology assessment in the Netherlands
Authors: Oortwijn Wija J. , Hanney Stephen R. , Ligtvoet Andreas , Hoorens Stijn , Wooding Steven , Grant Jonathan , Buxton Martin J. , Bouter Lex M.
Published: July 2008

Objectives:Investments in health research should lead to improvements in health and health care. This is also the remit of the main HTA program in the Netherlands. The aims of this study were to assess whether the results of this program have led to such improvements and to analyze how best to assess the impact from health research.

Methods:We assessed the impact of individual HTA projects by adapting the “payback framework” developed in the United Kingdom. We conducted dossier reviews and sent a survey to principal investigators of forty-three projects awarded between 2000 and 2003. We then provided an overview of documented output and outcome that was assessed by ten HTA experts using a scoring method. Finally, we conducted five case studies using information from additional dossier review and semistructured key informant interviews.

Results:The findings confirm that the payback framework is a useful approach to assess the impact of HTA projects. We identified over 101 peer reviewed papers, more than twenty-five PhDs, citations of research in guidelines (six projects), and implementation of new treatment strategies (eleven projects). The case studies provided greater depth and understanding about the levels of impact that arise and why and how they have been achieved.

Conclusions:It is generally too early to determine whether the HTA program led to actual changes in healthcare policy and practice. However, the results can be used as a baseline measurement for future evaluation and can help funding organizations or HTA agencies consider how to assess impact, possibly routinely. This, in turn, could help inform research strategies and justify expenditure for health research.
Policies of screening for colorectal cancer in European countries
Authors: Gutiérrez-Ibarluzea Iñaki , Asua José , Latorre Kepa
Published: July 2008

Objectives:The aim of this study was to analyze the current status of population screening for colon/rectum cancer in Europe to compare the different strategies, the coverage, the existence of pilot experiences, regional coverages, and the risk factors considered in each strategy.

Methods:A comprehensive, systematic search was performed in the literature for documents addressing population screening for colon/rectum cancer in Europe. An ad hoc questionnaire was prepared including questions considered relevant. The questionnaire was reviewed by experts in the area. To identify key informants, colleague members of the International Network of Agencies for Health Technology Assessment (INAHTA), participants in the EUnetHTA project, or representatives of the ministries of health of the different European countries were contacted. The information provided by key informants was checked with information directly obtained from the ministries of health, gray literature, and research documents.

Results:An 88 percent response rate was obtained. In countries for which no questionnaire data were collected, information was directly retrieved from the Web sites of the corresponding ministries. Four countries were found to perform population screenings: Austria, France, Germany, and the United Kingdom. However, they used different strategies. Five countries had begun regional or local strategies: Denmark, Finland, Italy, Spain, and Switzerland, and two additional countries (the Netherlands and Norway) reported ongoing research studies intended to determine the best strategy to implement a population-based screening program. Differences were found in age range, procedure chosen, and follow-up period.

Conclusions:Even though the European Council recommended a wider implementation of population screening for colon/rectum cancer, our results suggest that this recommendation continues to be valid. The differences found in screening strategies (in terms of age range, procedures, risk factors considered, and follow-up periods) are not warranted by the results obtained in research studies or regional-national cancer registries.
Cost-effectiveness of a new combined immunosuppressive and anti-infectious regimen in kidney transplantation
Authors: Wasserfallen Jean-Blaise , Kast-Brückner Mira , Manuel Oriol , Venetz Jean-Pierre , Meylan Pascal R. A. , Pascual Manuel
Published: July 2008

Objectives:The aims of this study were to assess the 1-year cost-effectiveness of a new combined immunosuppressive and anti-infectious regimen in kidney transplantation to prevent both rejection and infectious complications.

Methods:Patients (pts) transplanted from January 2000 to March 2003 (Group A) and treated with a conventional protocol were compared with pts submitted to a combined regimen including universal cytomegalovirus (CMV) prophylaxis between April 2003 and July 2005 (Group B). Costs were computed from the hospital accounting system for hospital stays, and official tariffs for outpatient visits. Patients with incomplete costs data were excluded from analysis.

Results:Fifty-three patients were analyzed in Group A, and 60 in Group B. Baseline characteristics including CMV serostatus were not significantly different between the two groups. Over 12 months after transplantation, acute rejections decreased from 41.5 percent in Group A to 6.7 percent in Group B (p< .001), and CMV infections from 47 percent to 15 percent (p< .001). Overall, readmissions decreased from 68 percent to 55 percent (p= .160), and average hospital days from 28 ± 19 to 20 ± 11 days (p< .007). The average number of outpatient visits decreased from 49 ± 10 to 39 ± 8 (p< .001). Average 1-year immunosuppressive and CMV prophylaxis costs (per patient) increased from CHF20,402 ± 7,273 to 27,375 ± 6,063 (p< .001), graft rejection costs decreased from CHF4,595 ± 10,182 to 650 ± 3,167 (p= .005), CMV treatment costs from CHF2,270 ± 6,161 to 101 ± 326 (p= .008), and outpatient visits costs from CHF8,466 ± 1’721 to 6,749 ± 1,159 (p< .001). Altogether, 1-year treatment costs decreased from CHF39’957 ± 16,573 to 36,204 ± 6,901 (p= .115).

Conclusions: The new combined regimen administered in Group B was significantly more effective, and its additional costs were more than offset by savings associated with complications avoidance.
Comparison of three instruments assessing the quality of economic evaluations: A practical exercise on economic evaluations of the surgical treatment of obesity
Authors: Gerkens Sophie , Crott Ralph , Cleemput Irina , Thissen Jean-Paul , Closon Marie-Christine , Horsmans Yves , Beguin Claire
Published: July 2008

Objectives:The increasing use of full economic evaluations has led to the development of various instruments to assess their quality. The purpose of this study was to compare the frequently usedBritish Medical Journal(BMJ) check-list and two new instruments: the Consensus Health Economic Criteria (CHEC) list and the Quality of Health Economic Studies (QHES) instrument. The analysis was based on a practical exercise on economic evaluations of the surgical treatment of obesity.

Methods:The quality of nine selected studies was assessed independently by two health economists. To compare instruments, the Spearman rank correlation coefficient was calculated for each assessor. Moreover, the test–retest reliability for each instrument was assessed with the intraclass correlation coefficient (ICC) (3,1). Finally, the inter-rater agreement for each instrument was estimated at two levels: comparison of the total score of each article by the ICC(2,1) and comparison of results per item by kappa values.

Results:The Spearman's rank correlation coefficient between instruments was usually high (rho > 0.70). Furthermore, test–retest reliability was good for every instruments, that is, 0.98 (95 percent CI, 0.86–0.99) for the BMJ check-list, 0.97 (95 percent CI, 0.73–0.98) for the CHEC list, and 0.95 (95 percent CI, 0.75–0.99) for the QHES instrument. However, inter-rater agreement was poor (kappa < 0.40 for most items and ICC(2,1) ≤ 0.5).

Conclusions:The study shows that the results of the quality assessment of economic evaluations are not so much influenced by the instrument used but more by the assessor. Therefore, quality assessments should be performed by at least two independent experts and final scoring based on consensus.
Analysis of the quality of clinical practice guidelines on established ischemic stroke
Authors: Navarro Puerto Ma Asunción , Ibarluzea Iñaki Gutiérrez , Ruiz Oscar Guzmán , Alvarez Francisco Moniche , Herreros Rocío Gómez , Pintiado Ruth Engelhardt , Dominguez Antonio Reyes , León Ignacio Marín
Published: July 2008

Objectives:To catalogue and comparatively assess the quality of Clinical Practice Guidelines (CPG) for ischemic stroke taking into account format and development methodology.

Methods:We performed a comprehensive, systematic bibliographic search of CPGs addressing the management of ischemic stroke. We designed a sensitive strategy, using methodological filters in the following databases: Medline, IME and Lilacs, National Guidelines Clearinghouse, National electronic Library for Health, NICE, Guidelines International Network (GIN), Canadian Medical Association Infobase, development groups such as Scottish Intercollegiate Guidelines Network (SIGN), New Zealand Guidelines Group (NZGG), Agency for Healthcare Research and Quality (AHRQ), Ministry of Health Singapore, Institute for Clinical Systems Improvement (ICSI); and scientific societies: American Heart Association, American Medical Association, Royal College of Physicians London. We included all CPGs published in English, French, Italian, Portuguese, or Spanish from 1999 to 2005 and excluded those CPGs whose scope was primary prevention and rehabilitation from ischemic stroke. Four researchers independently assessed the structure and methodologies followed in drafting the CPGs using the Changing Professional Practice (CPP) and Appraisal of Guidelines Research & Evaluation (AGREE) instruments.

Results:We retrieved 117 documents; following application of exclusion criteria, twenty-seven CPGs were appraised. With regard to methodological quality (using the AGREE instrument), the domains that scored highest were “Scope and purpose” and “Clarity and presentation.” The lowest scoring domains were “Stakeholder involvement,” “Rigor of development,” and “Applicability.” Most guidelines received an overall score of “would not recommend” (77.8 percent). Finally, based on the CPP instrument, most of the CPGs evaluated were aimed at secondary care and did not provide updating procedures.

Conclusions:The overall quality of the CPGs published for ischemic stroke management did not have minimum methodological quality. Quality improvement has been observed in more recent CPGs and may be due to the publication of new tools such as the AGREE or CPP instruments, as well as international initiatives for CPG improvement.
Appropriateness of healthcare interventions: Concepts and scoping of the published literature
Authors: Sanmartin Claudia , Murphy Kellie , Choptain Nicole , Conner-Spady Barbara , McLaren Lindsay , Bohm Eric , Dunbar Michael J. , Sanmugasunderam Suren , De Coster Carolyn , McGurran John , Lorenzetti Diane L. , Noseworthy Tom
Published: July 2008

Objectives:This report is a scoping review of the literature with the objective of identifying definitions, conceptual models and frameworks, as well as the methods and range of perspectives, for determining appropriateness in the context of healthcare delivery.

Methods:To lay groundwork for future, intervention-specific research on appropriateness, this work was carried out as a scoping review of published literature since 1966. Two reviewers, with two screens using inclusion/exclusion criteria based on the objective, focused the research and articles chosen for review.

Results:The first screen examined 2,829 abstracts/titles, with the second screen examining 124 full articles, leaving 37 articles deemed highly relevant for data extraction and interpretation. Appropriateness is defined largely in terms of net clinical benefit to the average patient and varies by service and setting. The most widely used method to assess appropriateness of healthcare services is the RAND/UCLA Model. There are many related concepts such as medical necessity and small-areas variation.

Conclusions:A broader approach to determining appropriateness for healthcare interventions is possible and would involve clinical, patient and societal perspectives.
Empirical comparison of subgroup effects in conventional and individual patient data meta-analyses
Authors: Koopman Laura , van der Heijden Geert J. M. G. , Hoes Arno W. , Grobbee Diederick E. , Rovers Maroeska M.
Published: July 2008

Objectives:Individual patient data (IPD) meta-analyses have been proposed as a major improvement in meta-analytic methods to study subgroup effects. Subgroup effects of conventional and IPD meta-analyses using identical data have not been compared. Our objective is to compare such subgroup effects using the data of six trials (n= 1,643) on the effectiveness of antibiotics in children with acute otitis media (AOM).

Methods:Effects (relative risks, risk differences [RD], and their confidence intervals [CI]) of antibiotics in subgroups of children with AOM resulting from (i) conventional meta-analysis using summary statistics derived from published data (CMA), (ii) two-stage approach to IPD meta-analysis using summary statistics derived from IPD (IPDMA-2), and (iii) one-stage approach to IPD meta-analysis where IPD is pooled into a single data set (IPDMA-1) were compared.

Results:In the conventional meta-analysis, only two of the six studies were included, because only these reported on relevant subgroup effects. The conventional meta-analysis showed larger (age < 2 years) or smaller (age ≥ 2 years) subgroup effects and wider CIs than both IPD meta-analyses (age < 2 years: RDCMA-21 percent, RDIPDMA-1-16 percent, RDIPDMA-2-15 percent; age ≥2 years: RDCMA-5 percent, RDIPDMA-1-11 percent, RDIPDMA-2-11 percent). The most important reason for these discrepant results is that the two studies included in the conventional meta-analysis reported outcomes that were different both from each other and from the IPD meta-analyses.

Conclusions:This empirical example shows that conventional meta-analyses do not allow proper subgroup analyses, whereas IPD meta-analyses produce more accurate subgroup effects. We also found no differences between the one- and two-stage meta-analytic approaches.
Rapid reviews versus full systematic reviews: An inventory of current methods and practice in health technology assessment: Corrigendum
Authors: Watt Amber , Cameron Alun , Sturm Lana , Lathlean Timothy , Babidge Wendy , Blamey Stephen , Facey Karen , Hailey David , Norderhaug Inger , Maddern Guy
Published: July 2008

In the article entitled “Rapid reviews versus full systematic reviews: An inventory of current methods and practice in health technology assessment,” by Watt et al. in volume 24 number 2 (Spring 2008) ofInternational Journal of Technology Assessment in Health Care, the affiliation of Stephen Blamey is incorrectly listed as Department of Health & Ageing. Dr. Blamey is the current Chair of the Medical Services Advisory Committee (MSAC). MSAC is an independent scientific committee comprising individuals with expertise in clinical medicine, health economics, and consumer matters. The Department of Health & Ageing administers funding and operations for MSAC. However, members of MSAC act independently of the Department. As Chair of MSAC, Dr. Blamey can be contacted through the Department. Dr. Blamey is not affiliated with the Department of Health and Ageing and his contribution to the above-mentioned article does not reflect its policy. Dr. Blamey wishes to apologize for this misunderstanding.
Commentary on the article “Key principles for the improved conduct of health technology assessments for resource allocation decisions”
Authors: Banta H. David
Published: July 2008

The article “Key principles for the improved conduct of health technology assessments for resource allocation decisions” presents fifteen principles for health technology assessment. Many of these cannot be disputed, and application of the principles as stated would undoubtedly improve HTA as it is developing in the world at large. My question is, are these the most important principles? The document does not really try to answer this question.
A criterion for a monomial in P(3) to be hit
Authors: JANFADA A. S.
Published: July 2008

Let P(n) = [x1, . . ., xn] = ⊕d≥0Pd(n) be the polynomial algebra viewed as a graded left module over the Steenrod algebra at the prime 2. The grading is by the degree of the homogeneous polynomials Pd(n) of degree d in the n variables x1, . . ., xn. The algebra P(n) realizes the cohomology of the product of n copies of infinite real projective space. We recall that a homogeneous element f of grading d in a graded left -module M is hit if there is a finite sum f = ΣiSqi(hi), called a hit equation, where the pre-images hi ∈ M have grading strictly less than d and the Sqi, called the Steenrod squares, generate . One of the important parts of the hit problem is to check whether a given polynomial in M is hit or not. In this article we study this problem in the 3-variable case.
Incorporating hypothalamic–pituitary–adrenal axis measures into preventive interventions for adolescent depression: Are we there yet?
Authors: Adam Emma K. , Sutton Jonathan M. , Doane Leah D. , Mineka Susan
Published: July 2008

Altered functioning of the hypothalamic–pituitary–adrenal (HPA) axis is a robust correlate of major depression in adults, and to a lesser extent, in adolescents. Premorbid differences in HPA axis function have been found to prospectively predict the onset of adolescent depression. To what extent might our knowledge of HPA axis function in adolescents with, or at risk for, depression, help guide efforts to prevent depression in this age group? We review evidence regarding the role of the HPA axis in the development of adolescent depression, and examine whether and which HPA axis measures might be useful in guiding prevention efforts as (a) as a criterion by which to select youth at risk for depression, (b) as a predictor of which youth will be most responsive to prevention efforts, and (c) as an indicator of whether prevention/intervention efforts are working. We conclude that our current understanding of the HPA axis, and its measurement, in adolescent depression are not sufficiently precise to be of immediate practical use in improving prevention efforts. Incorporating HPA axis measures into prevention studies, however, would be immensely useful in clarifying the role of the HPA axis in adolescent depression, such that future prevention efforts might more confidently rely on HPA axis information.
Confocal/TEM Overlay Microscopy: A Simple Method for Correlating Confocal and Electron Microscopy of Cells Expressing GFP/YFP Fusion Proteins
Authors: Keene Douglas R. , Tufa Sara F. , Lunstrum Gregory P. , Holden Paul , Horton William A.
Published: July 2008

Genetic manipulation allows simultaneous expression of green fluorescent protein (GFP) and its derivatives with a wide variety of cellular proteins in a variety of living systems. Epifluorescent and confocal laser scanning microscopy (confocal) localization of GFP constructs within living tissue and cell cultures has become routine, but correlation of light microscopy and high resolution transmission electron microscopy (TEM) on components within identical cells has been problematic. In this study, we describe an approach that specifically localizes the position of GFP/yellow fluorescent protein (YFP) constructs within the same cultured cell imaged in the confocal and transmission electron microscopes. We present a simplified method for delivering cell cultures expressing fluorescent fusion proteins into LR White embedding media, which allows excellent GFP/YFP detection and also high-resolution imaging in the TEM. Confocal images from 0.5-μm-thick sections are overlaid atop TEM images of the same cells collected from the next serial ultrathin section. The overlay is achieved in Adobe Photoshop by making the confocal image somewhat transparent, then carefully aligning features within the confocal image over the same features visible in the TEM image. The method requires no specialized specimen preparation equipment; specimens are taken from live cultures to embedding within 8 h, and confocal transmission overlay microscopy can be completed within a few hours.
A Novel Technique for Observing the Internal Ultrastructure of Human Chromosomes with Known Karyotype
Authors: Ghazizadeh Mohammad , Sasaki Yoshihiro , Oguro Tatsuo , Sato Shigeru , Egawa Seiko , Inoue Kyoko , Adachi Akiko , Shimizu Hajime , Kawanami Oichi
Published: July 2008

Observation of the internal ultrastructure of human chromosomes by transmission electron microscopy (TEM) has frequently been attempted in spite of the difficulties in detaching metaphase chromosome spreads from the glass slide for further processing. In this study we have used a method in which metaphase chromosome spreads were prepared on a flexible thermoplastic membrane (ACLAR) film. To assess chromosome identity, a diamidino-phenylindole staining and karyotying was first done using a conventional cytogenetic system. The chromosome spreads were then fixed with 1% osmium tetroxide, stained with freshly prepared 2% tannic acid, dehydrated, and flat-embedded in epoxy resin. The resin sheet was easily detachable and carried whole chromosome spreads. By this method, TEM observation of chromosomes from normal human lymphocytes allowed a thorough examination of the ultrastructure of centromeres, telomeres, fragile sites, and other chromosomal regions. Various ultrastructural patterns including thick electron dense boundaries, less dense internal regions, and extended chromatin loops at the periphery of the chromosomes were discernible. Application of the present method to chromosome research is expected to provide comprehensive information on the internal ultrastructure of different chromosomal regions in relation to function.
Gallium-Induced Milling of Silicon: A Computational Investigation of Focused Ion Beams
Authors: Russo Michael F. , Maazouz Mostafa , Giannuzzi Lucille A. , Chandler Clive , Utlaut Mark , Garrison Barbara J.
Published: July 2008

Molecular dynamics simulations are performed to model milling via a focused ion beam (FIB). The goal of this investigation is to examine the fundamental dynamics associated with the use of FIBs, as well as the phenomena that govern the early stages of trench formation during the milling process. Using a gallium beam to bombard a silicon surface, the extent of lateral damage (atomic displacement) caused by the beam at incident energies of both 2 and 30 keV is examined. These simulations indicate that the lateral damage is several times larger than the beam itself and that the mechanism responsible for the formation of a V-shaped trench is due to both the removal of surface material, and the lateral and horizontal migration of subsurface silicon atoms toward the vacuum/crater interface. The results presented here provide complementary information to experimental images of trenches created during milling with FIBs.
Synthesis of Lead Pyrophosphate, Pb2P2O7, in Water
Authors: Lytle Darren A. , White Colin , Schock Michael R.
Published: July 2008

Polyphosphates are used in drinking water to prevent the precipitation of cations such as calcium and iron. The possible negative impact of using polyphosphates is the undesirable complexation of lead that could result in elevated lead levels in consumers' tap water. Although the water industry has focused on complexation, lead polyphosphate solids such as lead pyrophosphate, Pb2P2O7, have been considered in other fields and not been shown to form in water. The ability to form lead pyrophosphate in water could have a potential impact on the strategies used to reduce lead levels in drinking water distribution systems. The objective of this work was to determine whether lead pyrophosphate could form under simulated potable drinking water conditions. Lead pyrophosphate was synthesized in water (pH 8.2, 10 mg C/L, 2.7 mg Cl2/L) after 13 days of aging. The formation of lead pyrophosphate was confirmed by X-ray diffraction and microscopy analysis. Synthesis did not require elevated temperatures or microwave assisted approaches used by past researchers. The findings suggest that lead (and possibly other metal) pyrophosphates could conceivably form in real drinking water systems, although much more work is necessary to determine the chemistry and kinetic boundaries.
Nondestructive Spectrometric Study on a Radioactive Particle Embedded in a Marine Sediment
Authors: Bielewski Marek , Himbert Jerome , Niagolova Nedialka , Falkenberg Gerald , Eriksson Mats , Betti Maria
Published: July 2008

A radioactive particle embedded in a sediment collected from the Irish Sea was examined with spectrometric methods to understand the potential bioavailability of its constituents. Images of the particle surface were acquired in the backscattering mode by scanning electron microscopy. The elemental composition of the particle surface layer was measured using energy dispersive (SEM-EDX) and wavelength dispersive (SEM-WDX) X-ray spectrometers. The investigation showed that the sample consists of a calcite matrix in which uranium is present in the form of separate inclusions. The diameter of U inclusions was less than 10 μm. Synchrotron radiation based X-ray fluorescence in confocal geometry (confocal μ-XRF) was used to determine the spatial distribution of elements in the particle. Three-dimensional reconstructions of the Ca, Cr, Mn, Fe, Zn, Sr, Ba, Pb, and U distributions were performed. The oxidation state of uranium in the different inclusions was determined by synchrotron radiation based X-ray absorption in confocal geometry (confocal μ-XANES). The isotopic composition of uranium was measured by secondary ion mass spectrometry. The results revealed that uranium was depleted in 235U. Pu and other actinides were not detected.
CD1d-restricted glycolipid antigens: presentation principles, recognition logic and functional consequences
Authors: Florence William C. , Bhat Rakesh K. , Joyce Sebastian
Published: July 2008

Invariant natural killer T (iNKT) cells are innate lymphocytes whose functions are regulated by self and foreign glycolipid antigens presented by the antigen-presenting molecule CD1d. Activation of iNKT cells in vivo results in rapid release of copious amounts of effector cytokines and chemokines with which they regulate innate and adaptive immune responses to pathogens, certain types of cancers and self-antigens. The nature of CD1d-restricted antigens, the manner in which they are recognised and the unique effector functions of iNKT cells suggest an innate immunoregulatory role for this subset of T cells. Their ability to respond fast and our ability to steer iNKT cell cytokine response to altered lipid antigens make them an important target for vaccine design and immunotherapies against autoimmune diseases. This review summarises our current understanding of CD1d-restricted antigen presentation, the recognition of such antigens by an invariant T-cell receptor on iNKT cells, and the functional consequences of these interactions.
Adenosine dysfunction in astrogliosis: cause for seizure generation?
Authors: Li Tianfu , Quan Lan Jing , Fredholm Bertil B. , Simon Roger P. , Boison Detlev
Published: July 2008

Epilepsy is characterized by both neuronal and astroglial dysfunction. The endogenous anticonvulsant adenosine, the level of which is largely controlled by astrocytes, might provide a crucial link between astrocyte and neuron dysfunction in epilepsy. Here we have studied astrogliosis, a hallmark of the epileptic brain, adenosine dysfunction and the emergence of spontaneous seizures in a comprehensive approach that includes a new mouse model of focal epileptogenesis, mutant mice with altered brain levels of adenosine, and mice lacking adenosine A1 receptors. In wild-type mice, following a focal epileptogenesis-precipitating injury, astrogliosis, upregulation of the adenosine-removing astrocytic enzyme adenosine kinase (ADK), and spontaneous seizures coincide in a spatio-temporally restricted manner. Importantly, these spontaneous seizures are mimicked by untreated transgenic mice that either overexpress ADK in brain or lack A1 receptors. Conversely, mice with reduced ADK in the forebrain do not develop either astrogliosis or spontaneous seizures. Our studies define ADK as a crucial upstream regulator of A1 receptor-mediated modulation of neuronal excitability, and support the ADK hypothesis of epileptogenesis in which upregulation of ADK during astrogliosis provides a crucial link between astrocyte and neuron dysfunction in epilepsy. These findings define ADK as rational target for therapeutic intervention.
Technology, complexity and change in agricultural production systems
Authors: Sassenrath G.F. , Heilman P. , Luschei E. , Bennett G.L. , Fitzgerald G. , Klesius P. , Tracy W. , Williford J.R. , Zimba P.V.
Published: July 2008

Technological advances have contributed to impressive yield gains and have greatly altered US agriculture. Selective breeding and directed molecular techniques address biological shortcomings of plants and animals and overcome environmental limitations. Improvements in mechanization, particularly of power sources and harvest equipment, reduce labor requirements and increase productivity and worker safety. Conservation systems, often designed to overcome problems introduced from other technologies, reduce negative impacts on soil and water and improve the environmental sustainability of production systems. Advances in information systems, largely developed in other disciplines and adapted to agriculture, are only beginning to impact US production practices. This paper is the fourth in the series of manuscripts exploring drivers of US agricultural systems. While development of technology is still largely driven by a need to address a problem, adoption is closely linked with other drivers of agricultural systems, most notably social, political and economic. Here, we explore the processes of innovation and adoption of technologies and how they have shaped agriculture. Technologies have increased yield and net output, and have also resulted in decreased control by producers, increased intensification, specialization and complexity of production, greater dependence on non-renewable resources, increased production inputs and hence decreased return, and an enhanced reliance on future technology. Future technologies will need to address emerging issues in land use, decline in work force and societal support of farming, global competition, changing social values in both taste and convenience of food, and increasing concerns for food safety and the environment. The challenge for farmers and researchers is to address these issues and develop technologies that balance the needs of producers with the expectations of society and create economically and environmentally sustainable production systems.
How to form bulges/ellipticals in dark halos as fast as central black holes?
Authors: Zhao Hong Sheng , Xu Bing-Xiao , Wu Xue-Bing
Published: July 2008

Gravity is nearly a universal constant in the cusp of an NFW galaxy halo. Inside this external field an isothermal gas sphere will collapse and trigger a starburst if above a critical central pressure. Thus formed spheroidal stellar systems have Sersic-profile and satisfy the Faber-Jackson relation. The process is consistent with observed starbursts. We also recover the MBH − σ* relation, if the gas collapse is regulated or resisted by the feedback from radiation from the central BH.
Chemical evolution of bulges at high redshift
Authors: Pipino Antonio , Matteucci Francesca , D'Ercole Annibale
Published: July 2008

We present a new class of hydrodynamical models for the formation of bulges (either massive elliptical galaxies or classical bulges in spirals) in which we implement detailed prescriptions for the chemical evolution of H, He, O and Fe. Our results hint toward an outside-in formation in the context of the supernovae-driven wind scenario. The build-up of the chemical properties of the stellar populations inhabiting the galactic core is very fast. Therefore we predict a non significant evolution of both the mass-metallicity and the mass-[α/Fe] relations after the first 0.5 − 1 Gyr. In this framework we explain how the observed slopes, either positive or negative, in the radial gradient of the mean stellar [α/Fe], and their apparent lack of any correlation with all the other observables, can arise as a consequence of the interplay between star formation and metal-enhanced internal gas flows.
Chemodynamical evolution of galaxies with hypernovae
Authors: Kobayashi Chiaki
Published: July 2008

We simulate the formation and evolution of galaxies with a hydrodynamical model including supernova and hypernova feedback. The large contribution of hypernovae is required from the observed abundance ratios in the Milky Way Galaxy. The hypernova feedback suppress star formation efficiently, which results in the cosmic star formation rate history peaked at z ~ 4. It also drives galactic outflows efficiently in low mass galaxies, and these winds eject heavy elements into the intergalactic medium. The ejected baryon and metal fraction is larger for less massive galaxies, which results in the mass-metallicity relation of galaxies. We also simulate the chemodynamical evolution of the Milky Way Galaxy, and show the difference of the stellar populations in the bulge and disk.
AGN feedback from jet-ISM/IGM interactions
Authors: Antonuccio-Delogu V. , Silk J.
Published: July 2008

We study the propagation of relativistic jets originating from AGNs within the Interstellar/Intergalactic Medium of their host galaxies, and use it to build a model for the inihibition of stellar formation within the expanding cocoon.
SPH simulations of the chemical evolution of bulges
Authors: Martínez-Serrano F. J. , Domínguez-Tenreiro R. , Mollá M.
Published: July 2008

We have implemented a chemical evolution model on the parallel AP3M+SPH DEVA code which we use to perform high resolution simulations of spiral galaxy formation. It includes feedback by SNII and SNIa using the Qij matrix formalism. We also include a diffusion mechanism that spreads newly introduced metals. The gas cooling rate depends on its specific composition. We study the stellar populations of the resulting bulges finding a potential scenario where they seem to be composed of two populations: an old, metal poor, α-enriched population, formed in a multiclump scenario at the beginning of the simulation and a younger one, formed by slow accretion of satellites or gas, possibly from the disk due to instabilities.
The morphology-density relation: a constant of nature
Authors: van der Wel Arjen
Published: July 2008

The Sloan Digital Sky Survey (SDSS) and photometric/spectroscopic surveys of two z ~ 0.8 massive clusters of galaxies and the Chandra Deep Field-South (CDFS) are used to construct volume-limited, stellar mass-selected samples of galaxies at redshifts 0 < z < 1 in a large range of environments. Morphologies are determined visually and with an automated method, using the Sérsic parameter n and a measure of the residual from the Sérsic model fits, called “bumpiness”, to distinguish different morphologies. The agreement between the visual and automated methods is excellent. The fraction of E+S0 galaxies with masses larger than ~ 0.5 M* is 40 − 50% in the field, and > 80% in the clusters, without significant changes with redshift. Therefore, we find that the morphology-density relation (MDR) for galaxies more massive than ~ 0.5 M* has remained constant since at least z ~ 0.8. This implies that galaxy evolution (in terms of mass, star formation, color, morphology, etc.) must happen such that the MDR does not change.