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PubMed2004

The multiple orthogonal tools approach to define molecular causation in the validation of druggable targets.

Many genetic (gene deletion, interruption or mutation), epigenetic (such as antisense or small interfering RNA) and immunological methods are being applied in 'high-throughput target validation' studies of the novel potential targets arising from whole genome sequencing. Such applications often focus on 'loss of function' approaches. However, target validation is most reliable when multiple orthogonal approaches are used. Initiating a target-based discovery project based on correlative evidence is faster than awaiting causative evidence. Indeed, the multiple tools needed to generate firm proof usually include methods and reagents only generated after starting a discovery project with little evidence beyond correlations. Robust and rigorous tests of whether a drug candidate is efficacious in vivo because of its effects on a specific molecular particular target are best made by simultaneously applying multiple orthogonal tools. Examples of the orthogonal tools approach will be discussed.

Animals↗
PubMed1994

Integrated quality control project: relationships between pathological findings detected at the slaughterhouse and information gathered in a veterinary health scheme at pig farms.

In September 1986 an Integrated Quality Control Project (IQC) was started in the Netherlands. Over a period of 2 years a veterinary herd health scheme was applied to 21 growing and finishing pig herds. Information was collected concerning medical treatment, classified as group treatment and individual treatment, clinical observations, and housing factors. The main purpose of this project was to investigate relationships between pathological findings detected at the slaughterhouse and information gathered on the farm. Medical group treatments, clinical observations and housing did not reliably predict pathological findings. Individual medical treatment for respiratory disorders, started in the last 30 days before slaughter, proved to be positively related to the pathological findings 'pneumonia' and 'pleuritis' detected at the slaughterhouse. This may be useful for selecting pigs at the slaughterhouse that will require special treatment for the removal of the pleura parietalis. During the first year of the project the average daily gain (ADG) was 27.2 g. more than during the preceding 2 years (P < 0.0001). Coughing was negatively related with the ADG. More than 75 coughs per compartment during 10 minutes, recorded more than 50 days before slaughter, was positively related to a depression of the ADG (20 g; P < 0.05). Relationships between group medical treatments and ADG were statistically significant, when the group medical treatment was started more than 20 days before slaughter. Negative influences on the ADG were higher if the treatment was started closer to the slaughter date.(ABSTRACT TRUNCATED AT 250 WORDS)

Abattoirs↗
PubMed1999

By the numbers.

Any statement about the ability of the specialty to meet the future demand for orthodontic care based merely on a ratio of the projected number of orthodontists to the projected population is an oversimplification. Still, some inferences can be drawn from the data presented in this article. To be as prudent as possible, we will limit the scope of the discussion to the next 10 years. 1. It seems likely that the annual number of orthodontic graduates will remain about the same. 2. Considering the slow increase in the average age of orthodontists, the death rate will increase slightly, but not significantly. 3. The average annual number of retirees will be somewhere between 125 (the current rate) and 359 (the maximum projected by the JCO Retirement Survey). 4. The above assumptions would leave no less than 7,500 practicing orthodontists in the United States in 10 years. 5. The number of children age 9-17 will increase by 5-10%. In a worst-case scenario, could 7,500 orthodontists meet the orthodontic demand 10 years from now? The 1997 JCO Orthodontic Practice Study reported the annual median number of case starts to be 180. Multiplied by 9,000 orthodontists, that would equal 1,620,000 case starts. If we project a 10% increase in demand, there could be 1,782,000 case starts 10 years from now--an average of 238 starts per year for 7,500 orthodontists. Respondents to the Practice Studies have consistently indicated that they could handle 50 additional case starts with no increase in staff or facilities, which would mean current orthodontists could accommodate an average of 230 case starts. Moreover, orthodontic productivity is likely to increase due to delegation and improved technology. In conclusion, even if the sharp increase in the number of annual retirements anticipated in the JCO Retirement Survey turns out to be correct, it seems unlikely that it will affect the ability of the specialty to accomplish its mission in the foreseeable future.

Dentists↗
PubMed1995

Evaluation of a community-based youth violence prevention project.

PURPOSE: To investigate the association of exposure to a community-based youth violence prevention project with adolescents' knowledge and attitudes about violence. METHODS: Two samples of 400 teens each from Boston neighborhoods were surveyed by random-digit dialed telephone techniques: one at the start of the project and one after 1 year of implementation. Regression analyses were used to investigate associations between exposure to different educational formats and outcome measures. RESULTS: Only self-reported exposure to the mass media campaign was significantly associated with higher scores in both knowledge and attitudes. An independent interaction between gender and exposure to the mass media campaign was found among males. Analyses using a historic control group support a program effect and not recall bias. Exposure to workshops or one-on-one discussions about violence prevention were not significantly associated with outcome scores. CONCLUSION: The measurable effect of the mass media may be somewhat related to the strength of that stimulus over the study period and suggests that 12 months is too short a time frame for evaluating community-based educational efforts.

Adolescent↗
PubMed2003

Developing capacity for integrated trauma-related behavioral health services for women: start-up costs from five community sites.

Violence against women is a growing public health concern. Many community agencies are interested in expanding their service delivery capacity to better meet these needs, but little information is currently available about the costs of implementing comprehensive services for women who have experienced various types of trauma. This article responds to this need by presenting findings from a study of start-up costs incurred by five regionally-diverse sites in the Women, Co-Occurring Disorders, and Violence Study (Women's Study) during the initial two years of a 5-year federal demonstration grant. Using a cost-finding approach that included project-related expenditures without regard to the source of funding, information was obtained with a structured data collection instrument that was completed during in-person interviews with local project staff. Phase 1 start-up project costs ranged from 0.6 million dollars to almost 1.2 million dollars per site. Of the five sites, start-up costs were lowest in the two mixed urban/suburban settings, and highest in the two rural settings, where few of the project-related services had been in place prior to grant funding. Implications for public health interventions are highlighted.

Delivery of Health Care, Integrated↗
PubMed2004

Nitrogen removal from sludge water with SBR process: start-up of a full-scale plant in the municipal wastewater treatment plant at Ingolstadt, Germany.

The sludge water obtained from the dewatering processes following anaerobic sludge digestion contains high levels of ammonia. This sludge water is generally returned to the beginning of the waste water treatment plant process, thereby significantly increasing the nitrogen load on the biological process. In this project, the start-up of a full-scale sequencing batch reactor (SBR) process to separately treat the aforementioned sludge water is studied. Two parallel SBRs were operated over 8 hour cycles. The duration of the start-up was approximately 100 days until a hydraulic load of 225 m3/d was reached for each SBR. This paper presents the results of the start-up, highlighting the change in nitrogen concentration with time and the effect of other parameters such as temperature and suspended solids in that period. Following the project period of operation, the ammonium concentration was reduced by more than 95% on average.

Biofilms↗
PubMed2003

Neuroinformatics Research for Vision Science: NRV project.

The NRV project (Neuroinformatics Research for Vision Science) is the first project in Japan started in 1999 under the Science and Technology Agency of Japan, aimed at building the foundation of neuroinformatics research. Because of the wealth of data on the visual system, the NRV project will use vision research to promote experimental, theoretical and technical research as a pilot study on neuroinformatics. Details can be found at: http://www.neuroinformatics.gr.jp/.

Animals↗
PubMedDate not supplied

Study on integration of the National Leprosy Eradication Programme into primary health care services: a pilot project.

The Central Leprosy Training and Research Institute, Chengalpattu, Tamil Nadu, undertook an interventional study, as a pilot project, on integration of the National Leprosy Eradication Programme (NLEP) vertical activities into the PHC system in two selected districts of Visakhapatnam and Krishna of Andhra Pradesh, between September 1997 and March 1999. The objective of the study was to assess the various operational aspects and implications of integrated implementation of the activities of the NLEP through the PHC system. 1,304,163 people (239,142 in the study group and 1,065,020 in the control group) were enrolled in the study. The methodology employed in carrying out the pilot project in the two selected districts is described. MDT was in operation for more than 5 years in these two districts through vertical approach. Prevalence has declined from >50/10000 at the start of MDT to about 3/10000 at the start of the project. During the implementation phase, 1459 new leprosy cases were detected (NCDR 5.39/10000 person-years) and 1458 cases were released from treatment (RFT rate: 93.04%) and towards the end of the project 450 cases were under treatment (PR 1.66/10000). Simple rates, ratios and proportions were used in the analysis of data and results were compared. The interventional study was designed to assess the implications and impact of implementation of NLEP activities through PHC staff. The study design, rationale, data collection, data processing, quality control methods employed in the study project and the results are discussed. The results of the study indicate that integrated implementation of the NLEP by PHC staff is feasible, if proper support is provided.

Child↗
PubMed1999

[Promoting health in health care organizations and hospitals? A survey of the French community in Belgium].

Health promotion concept and practices have brought many significant changes even in disease management and care settings. In the Ottawa charter, health promotion is defined as "the process of enabling people to increase control over, and to improve, their health". However, care settings are in contradiction with this process on several levels (focus on disease and not enough on health, concern more on cure than on care, etc.). The emergence of health promotion practices has been deeply questioning these features. Care institutions start to reconsider their role and missions. However, changes are slow and there has been much resistance. What is the current situation of health promotion in French speaking Belgian care institutions in 1998? The WHO EUROPE HEALTH PROMOTING HOSPITALS' (HPH) project, which officially started in 1991, aims at "promoting positive health and well-being in hospitals and beyond that, in the community". For each participating hospital, the implications of membership have an important influence on the institution and care project, because it implies adherence to the principles of the Ottawa charter on health promotion, and to the philosophy and objectives of HPH. Belgium joined the WHO project and the HPH network in 1996. It was necessary to review the situation of health care institutions in the French speaking community of Belgium in order to understand the evolution over the last years, to assess health professionals expectations and the feasibility of some actions, and to provide political decision makers with information likely to influence future decisions and choices in a positive way. This article presents the descriptive results of a survey carried out on nursing and patient education departments in health care institutions. Half of 105 hospitals answered the questionnaires sent. Out of these answers, 150 projects and actions were identified and briefly described by the institutions, which had the possibility to present a maximum of five actions. The main topics addressed were chronic diseases, psychology (conflict management, aggressiveness, ill-treatment), maternity, screening, prevention and vaccination. Regarding perspectives, 78% of actions concern disease and/or risks of disease (therapeutic or preventive perspectives) and 22% concern the maintenance or improvement of health. 90% of listed and described actions are permanent, and only 10% are selective (limited), which suggests an evolution of projects and their integration in practices. Concerning the number of projects, two aspects were analysed: the number by institution and the evolution over the last twenty years. On average, there are 3.2 actions per institution. As for the evolution, 7% of hospitals said they had at least one education action/project in 1980, 60% in 1990 and 98% in 1998. This amazing and remarkable evolution occurred simultaneously to the development of education committees, of patient education co-ordinators and/or resource persons. In this field, there was also a remarkable evolution since the creation of the first committees in 1983. Amongst the elements encouraging the development of information and health education initiatives and actions mentioned by hospital managers, the first one is a demand from the public (and patients). It is the first time, since the existence of such surveys that this factor is mentioned as the most important.

Attitude of Health Personnel↗
PubMedDate not supplied

Healthy Start: a comprehensive health education program for preschool children.

BACKGROUND: Healthy Start is a 3-year demonstration and education research project designed to evaluate the effectiveness of a multidimensional cardiovascular (CV) risk reduction intervention in preschool centers over a 3-year period of time. METHODS: Two primary interventions are employed. The first is the preschool food service intervention program designed to reduce the total fat in preschool meals and snacks to less than 30% of calories and reduce the saturated fat to less than 10% of calories. The second major intervention is a comprehensive preschool health education curriculum, focused heavily on nutrition. RESULTS: Effectiveness of the intervention will be determined through evaluation of changes in dietary intake of preschool children at school meals and snacks, especially with respect to intake of total and saturated fat. Evaluation of the education component will include assessment of program implementation by teachers, assessment of changes in nutrition knowledge by preschool children, and assessment of changes in home meals that children consume (total and saturated fat content). Blood cholesterol will be evaluated semiannually to evaluate changes that may be due to modification of dietary intake. Growth and body fatness will also be assessed. CONCLUSIONS: While substantial efforts have targeted CV risk reduction and health education for elementary school children, similar efforts aimed at preschool children have been lacking. The rationale for beginning CV risk reduction programs for preschool children is based upon the premise that risk factors for heart disease are prevalent by 3 years of age and tend to track over time, most commonly hypercholesterolemia and obesity, both related to nutrition. Since the behavioral antecedents for nutritional risk factors begin to be established very early in life, it is important to develop and evaluate new educational initiatives such as Healthy Start, aimed at the primary prevention of cardiovascular risk factors in preschool children. The purpose of this publication is to describe the rationale and methods for the Healthy Start project.

Cardiovascular Diseases↗
PubMed1993

Red Cross spinal injury project in Bucharest, Romania.

Inadequate medical facilities with lack of specialised drugs and other essential medical items, scientific isolation of medical staff, unavailability of orthoses and wheelchairs: such were a few of the problems identified in Bucharest in July 1991. The aim of the federation at the start of the project was to launch an action in many directions using two basic principles: using local means including human resources, and improving the existing facilities instead of erecting new buildings. Training of the staff goes side by side with the practice of total initial care. The family is taught to position and turn patients, practice chest physiotherapy and has become a major psychological and emotional support. An orthopaedic workshop has been set up to provide orthoses and to supervise the construction of wheelchairs in a local factory. The social situation of patients is assessed to initiate social integration in the community. Home visits are organised to offer advice for adaptations. The implementation of these actions is difficult in a country which has to solve many economic problems.

Home Care Services↗
PubMed2006

Real-time respiration monitoring using the radiotherapy treatment beam and four-dimensional computed tomography (4DCT)--a conceptual study.

Real-time knowledge of intra-fraction motion, such as respiration, is essential for four-dimensional (4D) radiotherapy. Surrogate-based and internal-fiducial-based methods may suffer from one or many drawbacks such as false correlation, being invasive, delivering extra patient radiation, and requiring complicated hardware and software development and implementation. In this paper we develop a simple non-surrogate, non-invasive method to monitor respiratory motion during radiotherapy treatments in real time. This method directly utilizes the treatment beam and thus imposes no additional radiation to the patient. The method requires a pre-treatment 4DCT and a real-time detector system. The method combines off-line processes with on-line processes. The off-line processes include 4DCT imaging and pre-calculating detector signals at each phase of the 4DCT based on the planned fluence map and the detector response function. The on-line processes include measuring detector signal from the treatment beam, and correlating the measured detector signal with the pre-calculated signals. The respiration phase is determined as the position of peak correlation. We tested our method with extensive simulations based on a TomoTherapy machine and a 4DCT of a lung cancer patient. Three types of simulations were implemented to mimic the clinical situations. Each type of simulation used three different TomoTherapy delivery sinograms, each with 800 to 1000 projections, as input fluences. Three arbitrary breathing patterns were simulated and two dose levels, 2 Gy/fraction and 2 cGy/fraction, were used for simulations to study the robustness of this method against detector quantum noise. The algorithm was used to determine the breathing phases and this result was compared with the simulated breathing patterns. For the 2 Gy/fraction simulations, the respiration phases were accurately determined within one phase error in real time for most projections of the treatment, except for a few projections at the start and end of the treatment in which beam intensities were extremely low. At 2 cGy/fraction dose level, the method can still determine the respiration phase very well with less than 10% of projections having more than two phases (approximately 1 s) error. This technique can also be applied in other delivery systems such as orthogonal x-ray systems, although in those cases it would entail the delivery of additional non-treatment radiation.

Algorithms↗
PubMed1978

A first Volunteer Case Aid programme in a mental hospital. Revealing the voluntary helper's role of reality testing between staff and patients.

A pilot Voluntary Case Aid programme in an English Mental Hospital using National Health Service resources is described. The selection of ten volunteers and ten patients and the preparation of all personnel was followed by regular contacts for at least a year. Subsequent evaluation suggested high motivation with both Case Aids and patients. Changes towards improved social functioning were evident in most cases by the end of the project. A relationship starting, continuing and finishing is reported in detail and from this study it is clear that the volunteer was a reality tester for staff and patient alike, constructively disturbing and modifying their mutual projections. This was true of most of the Case Aid interventions and the implications are discussed. A method of group supervision for Case Aids is reported.

Adult↗
PubMed1983

Evaluating community-based preventive cardiovascular programs: problems and experiences from the North Karelia project.

Among the different approaches to the study of cardiovascular disease prevention are community-based programs. This type of program concerns a whole community and the intervention takes advantage of the existing service structure and community organization. The evaluation assesses the feasibility, effects on risk factor and disease reduction, costs, process, and other consequences associated with the program. Several such programs have recently been launched in the United States and some other countries. The first major community-based control program was the North Karelia project in Finland, started in 1972 and recently evaluated for its first five-year period. This paper discusses the problems in evaluating community-based CVD control programs on the experiences obtained in the North Karelia project.

Adult↗
PubMed1999

Integrating intensive psychosocial therapy and low dose medical treatment in a total material of first episode psychotic patients compared to "treatment as usual" a 3 year follow-up.

UNLABELLED: Every first episode functional psychosis patient (DSM-IV), age 18-45, with no dominating abuse, and living in an inner city area of 95,000 inhabitants have been treated as far as possible in accordance with the concept of "need adapted treatment" as formulated by Alanen et al 1991. Today about 70 patients have been treated and followed up with different clinical, psychological, and medical methods. The project group to be considered here consists of the first 32 patients, followed up during approximately 3 years. A retrospective comparison group was collected from the same area and from 2 more areas, with the same inclusion criteria. Their first psychotic episode was actualized 1-2 years before the project group was started and 72 cases were collected via records, personal questioning and databases. The outcome regarding in patient care and neuroleptic consumption, work and sickness data could be assessed for this group. RESULTS: In the project group 7/18 patients with schizophrenia diagnoses were free of positive or negative symptoms at follow up. In the non-schizophrenia psychosis group 11/14 had no psychotic symptoms. The mean in patient care consumption was considerably lower than that of the comparison group. 45% of the patients in the project group were on a neuroleptic prescription at the 3-year follow up vs. 71% of the comparison group. For those on a neuroleptic prescription the mean dosage at follow-up was 62 mgm chlorpromazine-eqv/day, vs. 192 mgm for comparison group. All the differences are significant. One conclusion to be made is that, provided a psychosocial support, neuroleptic consumption and in patient care can be considerably lowered with no detrimental effects. This is a pilot study lying behind the so-called "Parachute project", a Swedish multicenter study, which aims at deepening and broadening the clinical and methodological issues for the care of first episode psychosis patients.

Adolescent↗
PubMed1990

Axonal abnormalities in cerebellar Purkinje cells of the 'hyperspiny Purkinje cell' mutant mouse.

The hyperspiny Purkinje cell (hpc) is a murine, autosomal recessive mutation affecting cerebellar Purkinje cells. Axonal abnormalities in these neurons have been revealed by selective silver impregnation, specific immunohistochemical staining and electron microscopy. The main pathological feature consists of a massive axonal degeneration in the terminal domains of the Purkinje cell projection. This process starts approximately ten days postnatally, simultaneously with the onset of cerebellar symptoms, and evolves very rapidly. By 21 days, the vast majority of the terminal arbors have degenerated, resulting in an almost complete disruption of the corticonuclear projection. Axonal degeneration, although proceeding in a dying-back fashion, only provokes retrograde death in a small percentage of Purkinje cells (less than 15%). Purkinje cells exhibit other signs of axonal damage and axonal reaction: (a) Almost all of them bear gigantic varicosities (spheroids or torpedoes) along their transit through the granular layer. (b) In a small percentage of cases, a dendritic segment is inserted between the axon hillock and the initial segment (meganeurite). These ectopic dendrites receive a normal contingent of synaptic inputs, and are transient structures observed in four- to six-week-old mice. (c) The infra- and supraganglionic plexuses, formed by recurrent collaterals of Purkinje cell axons, have increased density and terminal domains. (d) In mice aged over 50 days, many Purkinje cells have developed 'arciform' axons, which is evidence of a compensatory reaction. The definite axonal pathology of hpc Purkinje cells confers to this mutation its own specificity, which differs from all other known mutations primarily affecting this neuronal population. Therefore, the hpc mutation offers a valuable tool to analyse some of the genetic factors involved in the differentiation and maintenance of cerebellar Purkinje cells.

Animals↗
PubMed2006

A web-based tool for the Comprehensive Unit-based Safety Program (CUSP).

BACKGROUND: An organization's ability to change is driven by its culture, which in turn has a significant impact on safety. The six-step Comprehensive Unit-Based Safety Program (CUSP) is intended to improve local culture and safety. A Web-based project management tool for CUSP was developed and then pilot tested at two hospitals. HOW ECUSP WORKS: Once a patient safety concern is identified (step 3), a unit-level interdisciplinary safety committee determines issue criticality and starts up the projects (step 4), which are managed using project management tools within eCUSP (step 5). On a project's completion, the results are disseminated through a shared story (step 6). CASE STUDIES: OSF St. Joseph's Medical Center-The Medical Birthing Center (Bloomington, Illinois), identified 11 safety issues, implemented 11 projects, and created 9 shared stories--including one for its Armband Project. The Johns Hopkins Hospital (Baltimore) Medical Progressive Care (MPC4) Unit identified 5 safety issues and implemented 4 ongoing projects, including the intravenous (IV) Tubing Compliance Project. DISCUSSION: The eCUSP tool's success depends on an organizational commitment to creating a culture of safety.

Health Facilities↗
PubMed2001

Flexible work hours, health and well-being in the European Union: preliminary data from a SALTSA project.

Demand for flexible work hours (FWH) is increasing in Europe aimed at increasing the number of production hours on one hand, and, on the other, reducing individual working hours and/or increasing autonomy and control on them. In view of the lack of knowledge of the effects of FWH on health and safety, we started a pilot project, funded by the Joint Programme for Working Life Research in Europe (SALTSA), aimed at: a) comparing the most relevant national legislation and how the EU Directive 93/104 "concerning certain aspects of working time" has been implemented in the member States; b) reporting prevalence and trend of FWH in Europe according to the three EU Surveys on Working Conditions carried out in the last decade; c) collecting practical examples of innovative FWH; d) evaluating their impact on health and safety in relation to work sectors, job demands, social life, aging and gender. Consequent actions are going to include information and consultancy for pertinent authorities and social parties involved, as well as training programmes for Union officials and similar groups concerning the organisation of FWH according to ergonomic principles.

Choice Behavior↗