On your marks ... the race to read the book of life is about to start in earnest, and tensions are rising.
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A problem in forensic facial comparison of images of perpetrators and suspects is that distances between fixed anatomical points in the face, which form a good starting point for objective, anthropometric comparison, vary strongly according to the position and orientation of the camera. In case of a cooperating suspect, a 3D image may be taken using e.g. a laser scanning device. By projecting the 3D image onto a 2D image with the suspect's head in the same pose as that of the perpetrator, using the same focal length and pixel aspect ratio, numerical comparison of (ratios of) distances between fixed points becomes feasible. An experiment was performed in which, starting from two 3D scans and one 2D image of two colleagues, male and female, and using seven fixed anatomical locations in the face, comparisons were made for the matching and non-matching case. Using this method, the non-matching pair cannot be distinguished from the matching pair of faces. Facial expression and resolution of images were all more or less optimal, and the results of the study are not encouraging for the use of anthropometric arguments in the identification process. More research needs to be done though on larger sets of facial comparisons.
Arabidopsis is a crucifer weed with a small genome of about 120 Mbp which has been chosen as a model species for plant molecular genetics. Four years ago, a consortium of nine French laboratories, including ours, initiated a project aimed at mapping the transcribed regions of the genome. The strategy employed was to systematically and randomly sequence cDNA clones isolated from libraries made from different tissues and organs of plants grown under various physiological conditions. The consortium released about 7,000 expressed sequenced tags (ESTs) in the dbEST database corresponding to approximately 3,500 unique genes. In the next phase of the programme, a YAC library with average inserts of 500 kbp has been prepared. We have now started to use the EST information to map the cDNA clones on these YACs. The most recent aspect of Arabidopsis sequencing is the ESSA (European Scientists Sequencing Arabidopsis) project, in which the aim is to describe 2.5 Mbp by the end of 1996. Genomic sequencing has revealed a very high gene density. Comparison of present genomic sequencing results with the EST data suggests that up to half of the genes might already be tagged with an EST. In collaboration with Carlos Quiros' group in Davis we have also analysed the conservation of a 30 kbp locus (Em 1, a late embryogenesis abundant protein gene) on chromosome 3 between Arabidopsis and several Brassica species. Progress on these various aspects will be reviewed. We shall also present some sequence comparisons between Arabidopsis and rice ESTs. These results suggest that it should be possible in the very near future to map a pool of common genes onto many different plant genomes. This should provide a common framework to integrate maps from different species and facilitate mapbased cloning of genes of agronomical importance.
A project of group-based peer review by general practitioners is described. Attention is given to the motivation of general practitioners to participate in audits, to the threat posed by peer review and to the use of criteria. The recruitment and motivation were successful. A total of 253 general practitioners took part, divided into 23 groups. This represented approximately 30% of all general practitioners in the area and 72% of all general practitioners specifically approached by us. The threat posed by audit disappears rapidly for most physicians once they have started auditing. The use of predefined criteria developed by 'experts', representing an optimal way of work for the general practitioner, appeared to be quite feasible in this project. From the results several conclusions are drawn as regards the planning and implementation of peer review under general practitioners.
OBJECTIVE: To evaluate the safety, dose tolerance, and efficacy of topical bexarotene gel in patients with early-stage cutaneous T-cell lymphoma (CTCL). DESIGN: Phase 1 and 2, open-label, dose-escalation clinical trial of bexarotene gel. SETTING: Three university-based clinics. PARTICIPANTS: Sixty-seven adults with early-stage (TNM stages IA-IIA) CTCL. INTERVENTIONS: Bexarotene gel, 0.1%, 0.5%, and 1.0%, applied in incremental dose adjustments from 0.1% gel every day to 1.0% gel 4 times daily or the maximal tolerated dose. MAIN OUTCOME MEASURES: Patients were followed for efficacy and safety, and treatment continued as long as they benefited. Response (> or =50% improvement) was evaluated by the Physician's Global Assessment of cutaneous disease and by an overall severity assessment of cutaneous disease, including signs of CTCL and area involved. RESULTS: Most patients tolerated topical bexarotene at 1% gel twice daily for routine use. Adverse events were generally mild to moderate in severity and were confined to treatment sites. Treatment-limiting toxic effects were associated with skin irritation and increased with gel exposure. Patients achieved an overall response rate of 63% and a clinical complete response rate of 21%. Median projected time to onset of response was 20.1 weeks (range, 4.0-86.0 weeks), and the estimated median response duration from the start of therapy was 99 weeks. Patients with no previous therapy for mycosis fungoides responded at a higher rate (75%) than those who previously underwent topical therapies (67%). CONCLUSIONS: Bexarotene gel was well tolerated, was easily self-applied, and had a substantial response rate in treating patients with early-stage CTCL.
Within the framework of a pilot project on the analysis of the mouse proteome, we investigated C57BL/6 mice (Mus musculus), a standard inbred strain of the mouse, starting with the analysis of brain, liver and heart proteins. Tissue extraction and the separation of proteins were performed with techniques offering a maximum of resolution. Proteins separated were analyzed by mass spectrometry. Gene-protein identification was performed by genetic analyses using the European Collaborative Interspecific Backcross (EUCIB), established from the two mouse species Mus musculus and Mus spretus. On the basis of protein polymorphisms we mapped hundreds of genes on the mouse chromosomes, allowing us new insight into the relationship between genotype and phenotype of proteins. In particular, the results showed that protein modifications can be genetically determined, therefore representing their own class of protein phenotypes. In this context, results are discussed suggesting that phenotypes of single protein species may result from several genes. Accordingly, proteins are considered as polygenic traits. In contrast, one example demonstrates that proteins may also have pleiotropic effects: a single gene mutation (a single altered protein) may affect several other proteins. From these studies we conclude that gene-related functional proteomics will show in the future that genetic diseases, defined today by clinical symptoms and considered as etiological entireties, can be subdivided into different diseases according to different affected genes.
The major mammalian subcortical visual structures receive topographically ordered projections from both eyes. In the adult dorsal lateral geniculate nucleus (dLGN) each projection terminates in separate restricted regions of the nucleus. This pattern is different during development. Initially in ferrets the projections from each eye to the dLGN overlap throughout this structure. Although the projections do not occupy regions that are appropriate given the adult pattern, they are both retinotopically organised. Consequently, the formation of the adult pattern requires that the two retinotopic projections shift in relation to one another. The experiments undertaken here on the newborn ferret demonstrate the relationship between the two unsegregated projections in terms of their retinal origin and relative pattern of projection to the dLGN. By establishing the relationship between the projections at this stage of development it is possible to determine the relative changes that must be made between them in order to bring about the adult pattern of registration. By mapping the two unsegregated projections with a combination of retinal lesions and anterograde tracing methods it is demonstrated that at birth the ipsilateral projection arises from the temporal retina, and the contralateral projection arises from the entire retina. Because of the significant contralateral projection from the temporal retina the relatively sharp nasotemporal division found in the adult is not present at this stage. This element of the contralateral projection maps in continuity with the rest of this projection and terminates at the caudal pole of the nucleus. However, it is probably lost before the adult pattern has clearly started to develop.(ABSTRACT TRUNCATED AT 250 WORDS)
Uranium production in Brazil will be restarted in the year 2000, through exploration of the Jazida da Cachoeira, located in the uraniferous region of Lagoa Real, Bahia State, northeast Brazil. Because of the mining operations, an open cast mine of approximately 27 x 10(4) m2 will be produced and the material removed will constitute approximately 14 x 10(6) tons, occupying an estimated area of 50 x 10(4) m2. Currently, there is a new concept about project developing, where the impact assessment is addressed during the initial phases. Beside this, legislation requires an environmental impact assessment before starting mining activities. In this context purpose, it is the purpose of this work to evaluate the chemical composition of the future waste; thus, samples were collected from the rocks that surround the mineral deposits. Instrumental neutron activation analysis was used for the elemental quantification, the mean elemental concentrations were calculated, and the ratios were normalized using North American Shale Composite (NASC). In the raw material eight main mineral structures exist whose elementary composition were compared using the statistical techniques of analysis of variance, ranking ANOVA, and multivariate ANOVA.
The Netherlands Vaccine Institute (NVI) developed the micro-carrier technology for large-scale production of IPV in the late 1960s and has used this technology successfully to produce IPV as well as DTP-IPV for the national immunization program in the Netherlands. As a public sector organization, and as one of the Millennium Development Goals, NVI has supported over the years access to vaccine technology like DTP and Hib for vaccine manufacturers in developing countries. In line with this role as a resource institute, NVI has recently been approached by a number of vaccine manufacturers, predominantly from developing countries, for transfer of IPV technology to meet the anticipated increase in demand for IPV following OPV cessation. Since WHO encourages new manufacturers to use the attenuated Sabin virus instead of wild polio strains in the production of IPV, NVI decided to respond positively to this WHO policy. The existing NVI experience in large-scale production of IPV and OPV using Vero cell based micro-carrier technology and its experience with experimental Sabin-IPV is an attractive start for the development of Sabin-IPV. This paper discusses the approach followed and the experience already gained in the project, as well as factors critical to its success.
Elder mistreatment (EM) is a growing and hidden problem. Nurses have a responsibility to identify potential and actual EM victims. The purpose of this article is to describe the roles of nurses on interprofessional elder mistreatment teams. Current nursing roles in the recognition and management of EM include assessment and screening, mandatory reporting, direct care, and complaint investigation. While the efforts of individual nurses in the detection and management of cases is important, EM is a complex problem that is best approached through interprofessional collaboration. In the greater Seattle area, such collaboration is accomplished through membership on the King County Elder Abuse Project teams. Nurses give expert opinion, educate team members, and provide case consultation. University faculty experience on the teams inspired the start of a Master's pathway in Forensic Nursing, focused nursing research, and increased public policy activity and community service. Nurses on interprofessional teams gain networking opportunities as well as experience with the system that is in place to protect and serve vulnerable adults.
Health promotion interventions with marginalised groups are increasingly expected to demonstrate genuine community participation in their design and delivery. However, ideals of egalitarian democratic participation are far removed from the starting point of the hierarchical and exploitative social relations that typically characterise marginalised communities. What scope is there for health promotion projects to implement ideals of community leadership within the realities of marginalisation and inequality? We examine how the Sonagachi Project, a successful sex-worker-led HIV prevention project in India, has engaged with the unequal social relations in which it is embedded. Our ethnographic study is based on observation of the Project's participatory activities and 39 interviews with a range of its stakeholders (including sex worker employees of the Project, non-sex-worker development professionals, brothel managers, sex workers' clients). The analysis shows that the project is deeply shaped by its relationships with non-sex-worker interest groups. In order to be permitted access to the red light district, it has had to accommodate the interests of local men's clubs and brothel managers. The economic and organisational capacity to run such a project has depended upon the direct input of development professionals and funding agencies. Thus, the 'community' that leads this project is much wider than a local grouping of marginalised sex workers. We argue that, given existing power relations, the engagement with other interest groups was necessary to the project's success. Moreover, as the project has developed, sex workers' interests and leadership have gained increasing prominence. We suggest that existing optimistic expectations of participation inhibit acknowledgement of the troubling work of balancing power relations. Rather than denying such power relations, projects should be expected to plan for them.
The tissue and cell bank of the HCL (Hospices Civils de Lyon) has, since 10 June 1999, consisted of two sections with related activities: cell culture for the Skin Substitutes Laboratory (Laboratoire des Substituts Cutanés, LSC) and preservation of corneas at 31 degrees C for the Cornea Bank. As the LSC had been ISO 9001 certified since March 1997 our aim, since merger, was to raise the Cornea Bank to the same level of quality as the LSC, so as to coincide with the renewal of the LSC certificate in February 2000. The methods we used (project, quality control, analysis and process optimization) led us to receive official certification only nine months after the merger. The procedure started with a program of quality control at the Cornea Bank from February 1999 onwards, in order to list the work and equipment required, evaluate its documentation system and what was needed to incorporate this new activity into the existing system of quality assurance at the LSC. On the 7th March 2000, the Tissue and Cell Bank of the HCL obtained an ISO 9001 certificate for its combined functions. As well as achieving our objectives and the strong points highlighted by the auditor during the renewal process, this quality assessment revealed many advantages: improvements in the conservation of corneas, economies in staff replacement and reductions in both the cost of maintaining quality, the cost of the corneas themselves, etc. The decree 'Banque' no. 99-741 of 30th August 1999, which put in place the system of authorization of tissue banks in France, demands quality control. Our application for certification which started in early 1999 had anticipated this regulation. This helped us enormously when compiling the dossier accompanying the official request and was an essential element in obtaining the favourable response of the ASSAPS on 21 June 2000.
The objectives were to compare first, second and third year medical students on self-perceived sexual health knowledge, comfort in addressing sexual health problems, and attitudes towards the importance of addressing sexual health issues with patients as part of a sexual health medical curriculum enhancement project. A paper-and-pencil questionnaire survey was designed and administered to first and second year medical students at the start of the fall semester, resulting in high participation rates for both years (98% and 86%, respectively). Third year students were surveyed through an on-line version of the questionnaire yielding a lower response rate (52%). Multivariate statistical analyses were used to compare knowledge, comfort and attitudes by year in medical school. Results were as follows: As might be expected, sexual health knowledge and comfort in addressing sexual health problems increased linearly from first to third year (P<0.01) for all questions. Unexpectedly, second year students had significantly higher scores on questions assessing attitudes towards the importance of addressing sexual health issues than either first or third year students (P<0.001). Female medical students reported that addressing sexual health issues with patients was significantly more important than did male medical students; however, male students reported higher levels of self-reported knowledge and comforting related to sexual health issues than did female students in a number of areas. In conclusion, knowledge gained from this survey was used to finalize the design of an enhanced, integrated curriculum on sexual health for medical students. Further investigation of gender differences related to training medical students in this area is suggested.
OBJECTIVE: To develop an effective selection procedure for lower limb functional neurostimulation (LLFNS) for standing in paraplegia. DESIGN: The selection procedure and exclusion criteria were based on the previous experience for two clinical centres with experience of LLFNS. SETTING: Two Regional Spinal Injuries units in southern England. SUBJECTS: 254 fully rehabilitated paraplegics living in the community. INTERVENTION: Patients were invited to participate in the programme, and if suitable to subject themselves to a rigorous staged selection procedure from which they could withdraw at any time. OUTCOME MEASURE: Functionally successful home standing using closed-loop surface electrical stimulation. RESULTS: 57/254 patients were suitable on paper and were accessible. 19 of these (CI = 10-28) were interested in the project and attended one of the spinal centres for details. Twelve (CI = 5-19) of these fulfilled the selection criteria and started on the training programme; and 10 of them completed the muscle training programme successfully. Seven patients (CI = 2-12) achieved closed-loop standing in the laboratory and four patients (CI = 1-8) did so at home.
In order to understand the structural basis of charge differences among enzyme variants without undertaking purification and sequencing of the protein, an original approach was developed. The approach is applicable to any enzyme or protein provided that there is a specific staining procedure. This consists, as a first step, in the projection of electrophoretically obtained mobility values versus pI of all variants into a two-dimensional profile. In a second step, starting from the most common variant, various theoretical possibilities of substitutions are envisaged, taking into consideration the pH of the electrophoretic conditions, pI of the variants and range of variations of the pK values of several amino acid side chains. In a third step, verification of the theoretical data is obtained through comparative protein titration curves by combined isoelectrofocusing-electrophoresis of several pairs of relevant variants. The validity of this approach is tested on the highly polymorphic carboxylesterase B enzyme of Escherichia coli and is found to provide valuable information.
A method has been developed that allows reporting of the fuel consumption and carbon dioxide (CO2) emissions for in-use vehicles from a fast-pass transient (IM240) inspection. The major technical obstacle to reporting CO2 emission rate and fuel consumption is that inspection and maintenance tests do not all use a standardized test duration or test method. The method is able to project full-duration fuel consumption from IM240 tests that actually fast-passed as early as just 30 sec from starting the test. It is based on basic considerations of the work done in driving the inspection cycle, with additional empirical adjustments. The initial application examined the differences between passing and failing inspections, and this did confirm that there are significant differences.
BACKGROUND: Cyclosporine (CsA) dosing is traditionally based on trough blood levels (C0) rather than area under the concentration-time curve (AUC), although AUC correlates better with posttransplantation clinical events. For Neoral, AUC based on limited sampling correlates closely with full 12-hr AUC. The purpose of our study was to correlate C0 with AUC based on CsA levels at 0, 1, 2, 3, and 4 hr after dose (PK0-4) and to compare this AUC with C0 in predicting acute rejection (AR) and acute cyclosporine nephrotoxicity (CsANT) in de novo first kidney transplant patients. METHODS: PK0-4 was done 2-4 days after starting Neoral for 156 patients. All received CsA-based triple-drug immunosuppression without antibody induction. AUC was calculated as projected 12-hr (AUC0-12) and actual 4-hr (AUC0-4) from the PK0-4 using the parallel trapezoid rule. Neoral dosing was based on C0 not AUC. AUC was retrospectively compared with C0 as a predictor of AR and CsANT during the first 90 days. RESULTS: C0 correlated poorly with AUC0-12 and AUC0-4 (r=0.61 and r=0.42). C0 (mean+/-SEM) levels were not significantly different in 34 patients with and 109 without AR (293+/-21 vs. 294+/-11 microg/L, P=0.95). AUC0-12 and AUC0-4 were significantly lower in patients with than without AR (AUC0-12 9090+/-598 vs. 10608+/-336 microg x h/L, P=0.01; AUC0-4 3934+/-306 vs. 4802+/-166 microg.h/L, P=0.006). In stepwise regression analysis only AUC0-12 or AUC0-4 (P=0.03/P=0.02) and delayed graft function (P=0.007) predicted AR. AUC0-12, AUC0-4, and C0 were all significantly higher in patients with CsANT than without CsANT (AUC0-12 11746+/-650 vs. 10023+/-301 microg x h/L, P=0.01; AUC0-4 5270+/-358 vs. 4474+/-150 microg x h/L, P=0.01; C0 343+/-18 vs. 287+/-10 microg/L, P=0.01), but in stepwise regression analysis C0 was not an independent predictor of CsANT. Patients with AUC0-12 in the range of 9500 to 11500 microg x h/L or AUC0-4 between 4400 and 5500 microg x h/L had the lowest incidence of AR (13% and 7%, respectively) without significantly higher risk for CsANT. CONCLUSION: C0 correlates poorly with AUC based on PK0-4. Early AUC based on PK0-4 is more closely associated with AR and CsANT than is C0. Our data suggest that a target AUC0-12 of 9500-11500 or AUC0-4 of 4400-5500 microg x h/L may provide optimal Neoral immunosuppression.
A myocardial infarction (mi) register was started on May 1, 1972 in the county of North Karelia in Eastern Finland as a part of the North Karelia project. Information about all cases with a suspected acute MI among the North Karelian population are collected by the register. The principles of the register follow the recommendations of the WHO expert working group. Altogether 713 cases were registered between May 1, and Dec. 31,1972. The distribution of them into diagnostic categories was: "definite" 57%, "possible" 30%, "no acute MI" 8% and "insufficient information" 5%. Patients with no acute MI have been excluded in the results. About 47% of the male patients below 65 years had a history of previous MI. Most of the patients in the group had been heavy cigarette smokers, eating mainly butter as the fat in their diet. Overweight was rare among the male patients but not among the females. During the years preceding the attack, most of the patients had visited a physician and a pathological ECG had been recorded. The average time delay before hospital treatment was internationally relatively short. The 4 week fatality rate among patients below 65 years was 37% for males and 35% for females. These rates were slightly lower than those in the register material in Helsinki. The annual incidence rate per thousand for the age group 30-64 in North Karelia was 13.8 among males and 2.6 among females. The incidence rate increased continuously with age among males,among females it increased markedly only after the age of 60. The risk ratio between North Karelia and Helsinki for the age standardized incidence rates of males in the age group 30-64 was 1.38, and for respective mortality rates 1.21. Within North Karelia the highest incidence rate for males aged 30-64 was recorded in the rural area of Ilomantsi-Tuupovaara in the East.