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Congruent strategies for carbohydrate sequencing. 2. FragLib: an MSn spectral library.

A bottom-up approach to achieve full oligosaccharide and glycan characterization has been described that is based on an MSn fragment spectral library and associated tools. The library, identified as FragLib, was initiated with known standards and commercially available oligomers prepared as methylated derivatives. As a component of this effort a set of software tools has been written for storing, organizing, and comparing spectral files, including the identification of isobaric mixtures. These tools provide a facile and objective evaluation of structural details including interresidue linkage, monomer identification, anomeric configuration, and branching. The tools are components of a web-based data sharing interface for sample tracking, spectral searching, and structural confirmation. Applications have been detailed with unknown samples and previously characterized glycoconjugates.

Carbohydrate Sequence↗

Evaluation of a transit first-aid station providing emergency care to former Yugoslavian war victims evacuated in Ancona, Italy.

BACKGROUND: A first-aid station was implemented in Falconara Marittima airport (Ancona, Italy). It provided medical emergency care to war victims evacuated from former Yugoslavia in transit for further treatment. MATERIALS AND METHODS: A descriptive analysis of the displaced population arriving at the first-aid station was performed using three independent datasets for administrative information, of which one included medical information. The implemented resources were also evaluated. RESULTS: From August 1993 to March 1995, 2272 displaced persons were registered at the first-aid station, out of which 54.2% were accompanying family members. Among those needing medical intervention (45.8% of total), most frequent diagnoses were traumatisms and burns (59.8%), neoplasms (15.6%), and congenital malformations (13.2%). The medical care provided at the first-aid station was most often basic: a medical examination alone was performed on 77.0% of the patients, and a minor dressing on 17.3%. Median length of stay was 1 day. Patients were sent to 30 different countries and 8% were forwarded to the local regional hospital. Deployed logistical resources exceeded by far actual needs but a lack of psychological assistance was observed, mainly for children. The agencies involved did not coordinate data sharing and follow-up information. CONCLUSIONS: The medical assistance to the war victims was efficient regarding provided care and timeliness. Effectiveness of such a programme could be improved by a better coordination between partners, allowing more adequate logistics according to appropriate epidemiological information.

Adolescent↗

Distant collaboration in drug discovery: the LINK3D project.

The work describes the development of novel software supporting synchronous distant collaboration between scientists involved in drug discovery and development projects. The program allows to visualize and share data as well as to interact in real time using standard intranets and Internet resources. Direct visualization of 2D and 3D molecular structures is supported and original tools for facilitating remote discussion have been integrated. The software is multiplatform (MS-Windows, SGI-IRIX, Linux), allowing for a seamless integration of heterogeneous working environments. The project aims to support collaboration both within and between academic and industrial institutions. Since confidentiality is very important in some scenarios, special attention has been paid to security aspects. The article presents the research carried out to gather the requirements of collaborative software in the field of drug discovery and development and describes the features of the first fully functional prototype obtained. Real-world testing activities carried out on this prototype in order to guarantee its adequacy in diverse environments are also described and discussed.

Computer Graphics↗

Definition of respiratory symptoms and disease in early childhood in large prospective birth cohort studies that predict the development of asthma.

We have reviewed the prospective value of early respiratory symptoms for determining the risk of development of asthma later in life by using data from studies based on the general population, hospital population, and general practices. Although "wheezing" in infancy generally has a good prognosis, it is an important risk factor for the development of asthma later in life. The prognostic value of "coughing" and "shortness of breath" in infancy for the later development of asthma is less clear. Despite the fact that no internationally accepted criteria for the definition of asthma in early childhood are available, many studies have been performed on this topic. We also investigated the outcome variables that were used to describe respiratory symptoms and disease in early childhood in the publications of nine large prospective birth cohort studies on the development of asthma. From seven of these studies, we reviewed the original questionnaires. We found that various studies used different outcome variables, but the data actually collected were similar. This is an important observation because it implies that comparisons between studies can be markedly improved by data sharing among investigators.

Asthma↗

Will the new code help researchers to be more ethical?

A code of ethics has 2 largely incompatible objectives: to set forth enforceable minimal standards of conduct and to teach about or invoke ethical conduct. The section of the new American Psychological Association code dealing with research ethics achieves the former to some degree. However, it neither provides needed education in the ethics of research nor states where the reader might turn for such information. The code is particularly deficient in the following areas: privacy and confidentiality; institutional review boards; deception; debriefing; data sharing; and research on marginal populations, on children and adolescents, and in organizational contexts. Suggestions are offered for providing a bibliographic resource, in hard copy and on-line, that would stimulate independent interest, scholarship, education, and research on research ethics.

Behavioral Research↗

Oligonucleotide and amplification fingerprinting of wild species and cultivars of banana (Musa spp.).

DNA oligonucleotide and amplification fingerprinting have been successfully used to detect genetic polymorphisms in 15 representative species and cultivars of the genus Musa, comprising AA, AAA, AAAA, AAB, ABB, and BB genotypes. In-gel-hybridization of Hinf I-digested genomic banana DNA to the 32P-labeled synthetic oligonucleotides (GATA)4, (GTG)5, and (CA)8 revealed considerable polymorphisms between Musa species and cultivars. The fingerprint patterns proved to be somatically stable and did not show differences between individual plants of 'Grand Nain' (AAA genotype). Dendrograms based on oligonucleotide fingerprint band sharing data proved to be consistent with most of the known features of the history of banana and plantain cultivation and evolution, respectively. DNA samples from the same banana species and cultivars were also amplified by PCR using single or pairwise combinations of short oligonucleotide primers. Amplification products were separated on agarose or polyacrylamide gels and visualized by ethidium bromide or silver staining, respectively. Polymorphic patterns were obtained with some but not all primers. By using the CCCTCTGCGG primer in simplex and/or duplex PCR, the induced mutant 'GN60A' was clearly recognized from its original variety 'Grand Nain'. Both fingerprint techniques allowed the detection of bands characteristic for the A and B genome. This DNA fingerprinting technology has potential application in several areas of Musa improvement.

Base Sequence↗

ICH topic: the draft ICH S7B step 2: note for guidance on safety pharmacology studies for human pharmaceuticals.

During the last ICH Expert Working Group meeting for Safety Pharmacology in February 2002 in Brussels, the appended step 2 S7B document on QT Prolongation was signed off. This paper will now be published by the three agencies. The comment period will be 6 months. Nevertheless, the EU and EFPIA would be very appreciative of comments received before the end of May 2002, in order to start the discussion on how this step 2 document should be modified. In addition, everybody is requested to share data that could support the evaluation process of all methods addressed in this document. The EWG appreciates every support.

Animals↗

A computer-based frozen blood inventory and information system.

A computer-based, time-sharing data processing system was developed to assist in maintaining information regarding units of red blood cells frozen for eventual transfusion. An automated system has been programmed to compile and retrieve data concerning stored units, prepare shipping documents as required, and maintain transfusion records in a retrievable manner for thawed or shipped units. Requests for frozen red blood cells are processed through this system. Units are selected by the computer to meet requirements specified by the operator of a keyboard terminal. These requirements include method of cryopreservation, specific antigenic characteristics required, and the number of units requested. The computer prints out on the keyboard terminal the units meeting the requirements and the keyboard operator then indicates to the computer the name of the requesting facility, if these units are to be shipped. This input initiates a programmed routine that generates a shipping invoice and a new file for these units in a permanent transfusion record which can by acessed by either donor number or the frozen blood cell code.

Blood Banks↗

Collection and transfusion of blood and blood components in the United States, 1989.

To probe recent trends in transfusion practice and their effect on the adequacy of the national blood resource, transfusions and collections in the United States in 1989 were studied, by using data shared by the American Association of Blood Banks, the American Red Cross, and the Council of Community Blood Centers, together with results from a sample survey of the 3600 hospitals that were not members of the national organizations. Statistical methods were used to estimate national activities. The total US supply of blood in 1989 was 14,229,000 units, an increase of 1.2 percent over the supply in 1987. Red cell transfusions were 12,059,000 units. A total of 3,159,000 patients underwent transfusion with whole blood and/or red cells (mean, 3.8 units/patient). Preoperative autologous deposits of 655,000 units by 310,000 patients represented an increase of 65 percent over the level in 1987. However, only 356,000 units (54%) were transfused to the patients who preoperatively deposited them; of the remainder, 13,000 units were crossed over for transfusion to other patients, while 286,000 units were never used. Directed donations, 350,000 units, were provided for 130,000 intended recipients, but only 97,000 units (28%) were transfused to their intended recipients; of the balance, 59,000 units (17%) were crossed over and 194,000 units (55%) were never transfused. Total platelet transfusions were equivalent to 7,258,000 units in 1989, for an increase of 13.7 percent over totals in 1987.

Blood Component Transfusion↗

Retransplantation of liver: primary graft nonfunction and hepatitis C virus are associated with worse outcome.

It is not known whether the outcome of liver retransplantation (re-LT) is dependent on the indication for re-LT or cause of liver disease. In this study, our aim is to compare the outcome of re-LT in adults with that of primary liver transplantation (PLT) and determine whether the outcome of re-LT is dependent on its indication. United Network for Organ Sharing data from 1988 to 2001 were used for the study. Of 34,267 patients who met our inclusion criteria, 761 patients underwent re-LT for primary graft nonfunction (PGNF; group 1), 3,428 patients underwent re-LT for other reasons (group 2), and 30,078 patients underwent PLT (group 3). There was a greater incidence of PGNF (9.4% v 4.0%; P <.001) and regrafting (23.1% v 7.4%; P <.001) in the re-LT groups compared with the PLT group. Kaplan-Meier analysis and Cox regression analysis, after adjusting for confounding risk factors, showed significantly lower short- and long-term patient and graft survival in the re-LT groups compared with the PLT group. Kaplan-Meier survival showed lower patient and graft survival in group 1 compared with group 2. However, only graft, not patient, survival was lower in group 1 by Cox regression analysis when adjusted for other risk factors. Patients with hepatitis C virus (HCV) infection who underwent re-LT had lower patient and graft survival compared with those without HCV infection, and HCV was an independent predictor of mortality after re-LT. Re-LT was associated with a greater rate of complications and lower patient and graft survival compared with PLT. Re-LT for PGNF and HCV infection was associated with lower patient and graft survival compared with re-LT for other causes.

Adult↗

Falls Clinics in Australia: a survey of current practice, and recommendations for future development.

The aim of this study was to identify common themes and differences in structure and function of Falls Clinics in Australia, to provide a framework for planning future activity. A paper-based survey was circulated to 20 identified Falls Clinic services throughout Australia in late 2000. Fifteen responses (75%) were received, although two of the 15 Clinics were not operating at the time of the survey, and so their responses were not included. Nine of the Clinics had commenced operation since 1998. Staffing commonly included a physiotherapist, geriatrician, and an occupational therapist, with the comprehensive multidisciplinary assessment process taking an average of 130 minutes. Although standard assessment tools were used by more than half of the Clinics, there were no universally applied assessment tools. Waiting lists for initial assessments ranged up to 16 weeks (average 6 weeks). Most Clinics instituted a number of management options themselves, but also used a range of existing community services to provide some of the planned interventions. Limited formal evaluation of the effectiveness of Clinics was reported. Recommended future activity included increasing staff levels and operating times for Clinics to more adequately meet identified need, increased networking and data sharing between Clinics, and a greater emphasis on research and staff training. We conclude that the recent increase in the number of Falls Clinics around Australia has occurred in a relatively unstructured manner, with many differences in staffing, operation and evaluation. There is a need for improved communication and standardisation of core procedures and assessment tools to facilitate best practice in all Clinics, and to provide a framework for a systematic evaluation of the effectiveness of Falls Clinics in Australia.

Accidental Falls↗

Studies on the biosynthesis of taxol: the taxane carbon skeleton is not of mevalonoid origin.

A cell culture of Taxus chinensis was established to produce the diterpene 2alpha,5alpha,10beta,14beta-tetra-acetoxy4 ++ +(20),11-taxadiene (taxuyunnanine C) in 2.6% (dry weight) yield. The incorporation of [U-13C6]glucose, [1-13C]glucose, and [1,2-13C2]acetate into this diterpene was analyzed by NMR spectroscopy. Label from [1,2-13C2]acetate was diverted to the four acetyl groups of taxuyunnanine C, but not to the taxane ring system. Label from [1-13C]glucose and [U-13C6]glucose was efficiently incorporated into both the taxane ring system and the acetyl groups. The four isoprenoid moieties of the diterpene showed identical labeling patterns. The analysis of long-range 13C13C couplings in taxuyunnanine C obtained from an experiment with [U-13C6]glucose documents the involvement of an intramolecular rearrangement in the biosynthesis of the isoprenoid precursor. The labeling patterns are inconsistent with the mevalonate pathway. The taxoid data share important features with the alternative pathway of isoprenoid biosynthesis operating in certain eubacteria Rohmer, M., Knani, M., Simonin, P., Sutter, B. & Sahm, H. (1993) Biochem. J. 295, 517-524].

Cells, Cultured↗

Computer-mediated interdisciplinary teams: theory and reality.

The benefit of experience, tempered with the wisdom of hindsight and 5 years of text-based, asynchronous, computer-mediated, interdisciplinary team communications, provides the energy, insights and data shared in this article. Through the theoretical lens of group dynamics and the epistemology of interdisciplinary teaming, we analyze the interactions of a virtual interdisciplinary team to provide an understanding and appreciation of collaborative interdisciplinary communication in the context of interactive technologies. Whilst interactive technologies may require new patterns of language similar to that of learning a foreign language, what is communicated in the interdisciplinary team process does not change. Most important is the recognition that virtual teams, similar to their face-to-face counterparts, undergo the same challenges of interdisciplinary teaming and group developmental processes of formation: forming, storming, norming, performing, and transforming. After examining these dynamics of communication and collaboration in the context of the virtual team, the article concludes with guidelines facilitating interdisciplinary team computer-mediated communication.

Computer-Assisted Instruction↗

Development of an Internet Security Policy for health care establishments.

The Internet provides unprecedented opportunities for interaction and data sharing among health care providers, patients and researchers. However, the advantages provided by the Internet come with a significantly greater element of risk to the confidentiality and integrity of information. This paper defines the basic security requirements that must be addressed in order to use the Internet to safely transmit patient and/or other sensitive Health Care information. It describes a suitable Internet Security Policy for Health Care Establishments and provides the set of technical measures that are needed for its implementation. The proposed security policy and technical approaches have been based on an extensive study of the related recommendations from the security and standard groups both in EU amid USA and our related work and experience. The results have been utilized in the framework of the Intranet Health Clinic project, where the use of the Internet for the transmission of sensitive Health Care information is of vital importance.

Computer Communication Networks↗

Analysis of user-satisfaction with the use of a teleconsultation system in oncology.

There is an increasing interest in assessing telemedicine as alternative method of delivering high quality cancer treatment to patients living in rural areas. In the Province of Trento (north-east Italy) a tele-oncology system was implemented to provide non-surgical oncological consultation to district general hospitals. The aim of this study was to explore user-satisfaction with the system after 6 months of experimentation. During the on-field validation two questionnaires with open and closed-response questions were distributed to 80 physicians and nurses 6 months apart to investigate the users' expected benefits vs. perceived ones. The two questionnaires were compared to assess how perceived benefits differed from expected ones. Significant differences were found regarding improvements in: the standardization of diagnostic-therapeutic procedures using the Electronic Patient Record (EPR)]; information sharing; data updating; consultation speed; and the possibility to diminish patients' travels through the use of teleconsultation (TC). Physicians' responses showed a significant difference regarding the EPR's effects on relationship with patient, the nurses' responses with regards to its effects on care quality. Physicians felt that both modalities of teleconsultation were useful in enhancing communication with colleagues (86% for the synchronous TC, 80% for the asynchronous TC). Responses indicated that the major difficulties encountered were in the introduction of the system into the daily routine. Despite this, user expectations for its future use in clinical field were considerably high.

Attitude of Health Personnel↗

State of the evidence: current status and prospects of meta-analysis in infectious diseases.

Meta-analysis is increasingly applied in infectious diseases to summarize clinical data and to evaluate the strength, diversity, and deficiencies of evidence for medical questions of interest. We present an overview of the current status of meta-analysis in the area of infectious diseases and the lessons learnt from its applications. Recently published meta-analyses show that several important areas of research on infectious diseases lack sufficient randomized evidence. Often evidence is scattered across a large number of small trials, making meta-analysis a promising way to integrate diverse results. Quality of trials in the field is often poor. There are several examples where evidence was accumulated primarily for marketing rather than for scientific purposes. Finally, meta-analyses are also raising the problem of what constitutes clinically significant treatment benefits, as well as interesting issues about the reproducibility of clinical evidence and its evolving nature. The increasing applications of meta-analytic methods in the study of infectious diseases may enhance data sharing and international collaborations.

Anti-Bacterial Agents↗

Immunophenotypic markers and antiretroviral therapy (IMART): T cell activation and maturation help predict treatment response.

To determine whether markers of T cell activation and maturation are independently predictive of the response to potent antiretroviral therapy, the Immunophenotypic Markers and Antiretroviral Therapy study applied a novel data-sharing strategy across 5 Adult AIDS Clinical Trial Group trials that counted naive and activated CD4(+) and CD8(+) T cells in 324 subjects. Regression models--adjustment for baseline CD4 cell count, human immunodeficiency virus (HIV) RNA, and study--revealed that high pretreatment CD8(+) T cell activation predicted virologic failure (P=.046). Additional models showed the greatest increase in CD4(+) T cell counts in subjects with highest pretreatment naive CD4(+) T cell counts (P<.0001), which was enhanced by high CD4(+) and low CD8(+) T cell activation. Total lymphocyte count also predicted a subsequent CD4(+) T cell change. These results document the utility of T cell markers in predicting treatment outcome and their potential value for the study and management of HIV-1 infection.

Adult↗

Neurobiological correlates of acupuncture: November 17-18, 2005.

The "Neurobiological Correlates of Acupuncture" Conference was convened November 17-18, 2005 in Bethesda, Maryland. The conference was sponsored by the National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (NIH), U.S. Department of Health and Human Services (DHHS). Its goals were to encourage exchange of ideas regarding the direction of neuroimaging in acupuncture research as well as to discuss some of the challenges in this field. The use of neuroimaging, a relatively recent advance in the study of acupuncture, holds the promise of localizing and characterizing brain activity associated with acupuncture interventions in real time and in a minimally invasive way. Among the main challenges to research into the biological mechanisms of acupuncture are the multiple treatment variables and the difficulties of selecting appropriate experimental controls. Despite these challenges, numerous findings from acupuncture neuroimaging experiments were presented and discussed at the conference on topics related to possible signaling networks, sham acupuncture controls, acupoint specificity, acupuncture analgesia, acupuncture-associated brain response, and the potential for using neuroimaging in conjunction with translational and clinical acupuncture research. Future directions in acupuncture neuroimaging research, as recommended by conference participants, should focus on (1) continuing exploration of acupuncture signaling networks; (2) establishing standards and recommendations for performing and reporting acupuncture neuroimaging results; (3) enabling data sharing in the acupuncture neuroimaging community; (4) gaining a better understanding of placebo and control groups in acupuncture neuroimaging experiments; and (5) developing biomarkers that relate to physiologically and/or clinically relevant acupuncture responses to neuroimaging results.

Acupuncture Therapy↗