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Background Despite effective national immunisation programmes in Europe, some groups remain incompletely or un-vaccinated (‘under-vaccinated’), with underserved minorities and certain religious/ideological groups repeatedly being involved in outbreaks of vaccine preventable diseases (VPD). Gaining insight into factors regarding acceptance of vaccination of ‘under-vaccinated groups’ (UVGs) might give opportunities to communicate with them in a trusty and reliable manner that respects their belief system and that, maybe, increase vaccination uptake. We aimed to identify and describe UVGs in Europe and to describe beliefs, attitudes and reasons for non-vaccination in the identified UVGs. Methods We defined a UVG as a group of persons who share the same beliefs and/or live in socially close-knit communities in Europe and who have/had historically low vaccination coverage and/or experienced outbreaks of VPDs since 1950. We searched MEDLINE, EMBASE and PsycINFO databases using specific search term combinations. For the first systematic review, studies that described a group in Europe with an outbreak or low vaccination coverage for a VPD were selected and for the second systematic review, studies that described possible factors that are associated with non-vaccination in these groups were selected. Results We selected 48 articles out of 606 and 13 articles out of 406 from the first and second search, respectively. Five UVGs were identified in the literature: Orthodox Protestant communities, Anthroposophists, Roma, Irish Travellers, and Orthodox Jewish communities. The main reported factors regarding vaccination were perceived non-severity of traditional “childhood” diseases, fear of vaccine side-effects, and need for more information about for example risk of vaccination. Conclusions Within each UVG identified, there are a variety of health beliefs and objections to vaccination. In addition, similar factors are shared by several of these groups. Communication strategies regarding these similar factors such as educating people about the risks associated with being vaccinated versus not being vaccinated, addressing their concerns, and countering vaccination myths present among members of a specific UVG through a trusted source, can establish a reliable relationship with these groups and increase their vaccination uptake. Furthermore, other interventions such as improving access to health care could certainly increase vaccination uptake in Roma and Irish travellers.

Advances in synthetic biology have made microbes easier to engineer than ever before. However, synthetic biology in animals and plants has lagged behind. Since it is now known that the phenotype of higher organisms depends largely on their microbiota, we propose that this is an easier route to achieving synthetic biology applications in these organisms.

The fundamental role of p38 mitogen-activated protein kinases (MAPKs) in inflammation underlines their importance as therapeutic targets for various inflammatory medical conditions, including infectious, vascular, neurobiological and autoimmune disease. Although decades of research have yielded several p38 inhibitors, most clinical trials have failed, due to lack of selectivity and efficacy in vivo. This underlines the continuous need to screen for novel structures and chemotypes of p38 inhibitors. Here we report an optimized MK2-EGFP translocation assay in a semi-automated image based High Content Analysis (HCA) system to screen a combinatorial library of 3362 proprietary compounds with extensive variations of chemotypes. By determining the levels of redistribution of MK2-EGFP upon activation of the Rac/p38 pathway in combination with compound treatment, new candidates were identified, which modulate p38 activity in living cells. Based on integrated analysis of TNFα release from human whole blood, biochemical kinase activity assays and JNK3 selectivity testing, we show that this cell based assay reveals a high overlap and predictability for cellular efficacy, selectivity and potency of tested compounds. As a result we disclose a new comprehensive short-list of subtype inhibitors which are functional in the low nanomolar range and might provide the basis for further lead-optimization. In accordance to previous reports, we demonstrate that the MK2-EGFP translocation assay is a suitable primary screening approach for p38-MAPK drug development and provide an attractive labor- and cost saving alternative to other cell based methods including determination of cytokine release from hPBMCs or whole blood.

The aim of this study was to assess the clinical and radiological outcome of the cementless-system (CLS) femoral component designed by Spotorno with a taper design. Ninety-four patients (107 hips) were operated on from January 1987 to December 1988. The female/male ratio was 2/1, the mean age was 51 years (range 20-77 years). Clinical follow-up was obtained in 89 hips (83%). Five patients (7 hips, 6.5%) could not be traced. Nine patients (11 hips, 10%) had died before the minimum time of follow-up required for this study (10 years). All these hips still had their stem in place at the time of the last intermediate inquiry. The mean follow-up was 10.3 +/- 0.3 years. No stem required revision. According to the Harris score, 84% of hips were rated good or excellent, 14% fair, and 2% poor. The average Harris hip score was 88 at the time of the last follow-up. Fifteen patients (17%) reported occasional thigh pain. All patients reported complete relief of pain within the first 6 months after the operation. Radiologically, 95% of stems showed stable fixation by bony ingrowth, 5% by fibrous ingrowth. Seven (9%) uncemented acetabular components showed progressive migration. Three of those cups had been replaced in the meantime. Fifty-one (65%) of the CLS stems induced either no change in femoral bone density or only patchy loss of bone density localized to zone 1 or 7 according to Gruen, while 27 (35%) of the hips showed some reduction of bone density in the proximal diaphysis of the femur (zone 2 or 6). Severe progressive osteolysis of the femoral cortex underneath the lesser trochanter was found in 4 hips (5%) with coexistent loosening of the cup. In all of these hips, the Mecron cup had been used. At a mean follow-up of 10 years, the results of the CLS femoral component are comparable with those of modern techniques of cementing in primary total hip arthroplasty and with the long-term outcomes of other uncemented stems with tapered design. The long-term fixation of the cup remains an unsolved problem.

Henri Bergson's philosophy, since it is a method for identifying problems and clarifying concepts, can be a useful tool that can recast the problem of the symbolic in new terms today. He proposes a new concept of the symbolic because he doesn't conceive it as the representation of an object, in a two-strata theory of knowledge, but as a way to express and mediate experience through language, in an image of thinking as a layered reality, composed of several strata or \"plateaux.\" Keck wants to show that the virtual, the symbolic, and the actual are three degrees of experience that are intertwined in complex and productive ways, and that the symbolic is an intermediary level between the virtual and the actual that allows their inter-expression.

The purpose of this study was to evaluate the Keller Index of Nausea (KIN), a new instrument for observational assessment of nausea in children 1 through 5 years of age. The KIN and the University of Wisconsin Children's Hospital Pain Scale were used to assess children brought to a general pediatric outpatient clinic for a variety of health problems. There were statistically significant positive point biserial correlations between the KIN scores and three criteria: (a) a medical diagnosis consistent with the presence of nausea, (b) a chief complaint per parent consistent with the presence of nausea, and (c) the parent's statement that the child is experiencing nausea.

The effect of hypothyroidism on left ventricular function at rest and during exercise was studied in nine patients without demonstrable cardiovascular disease who had had total thyroidectomy and ablative radioiodine treatment for thyroid cancer. Radionuclide ventriculography and simultaneous right heart catheterisation were performed while the patients were hypothyroid two weeks after stopping triiodothyronine treatment (to permit routine screening for metastases) and while they were euthyroid on thyroxine replacement treatment. When the patients were hypothyroid, cardiac output, stroke volume, and end diastolic volume at rest were all lower and peripheral resistance was higher than when they were euthyroid. Pulmonary capillary wedge pressure, right atrial pressure, heart rate, left ventricular ejection fraction, and the systolic pressure:volume relation of the left ventricle, which was used as an estimate of the contractile state, were not significantly different when the patients were hypothyroid or euthyroid. During exercise, heart rate, cardiac output, end diastolic volume, and stroke volume were higher when the patients were euthyroid than when they were hypothyroid. Again, pulmonary capillary wedge pressure, ejection fraction, and the systolic pressure:volume relation were similar in both thyroid states. The data suggest that the alterations in cardiac performance seen in short term hypothyroidism are primarily related to changes in loading conditions and exercise heart rate; they do not suggest that acute thyroid hormone deficiency has a major effect on the contractile properties of the myocardium.

The effect of hypothyroidism on non-specific bronchial reactivity was studied in 11 patients without pulmonary disease (mean age 40 (SD 13) years) who had had a total thyroidectomy and radioiodine treatment for thyroid cancer 41 (36) months before the study. All patients when mildly hyperthyroid while having long term thyroxine replacement treatment and once when hypothyroid two weeks after stopping triiodothyronine for the purpose of screening for metastases. Bronchial reactivity was assessed by measuring specific airways conductance (sGaw) after increasing doses of inhaled carbachol (45-1260 micrograms). The dose producing a 35% decrease in sGaw (PD35) was determined from the cumulative log dose-response curve by linear regression analysis. Mean baseline sGaw values were similar when the patients were hypothyroid and when they were hyperthyroid (1.35 (0.36) and 1.41 (0.56) s-1 kPa-1). The interstudy coefficients of variation of baseline sGaw were higher in the thyroid patients than in a euthyroid control group (14% versus 8%). Geometric mean PD35 was lower when the patients were hypothyroid (97 micrograms) than when they were mildly hyperthyroid (192 micrograms). It is concluded that acute hypothyroidism increases non-specific bronchial reactivity in nonasthmatic subjects.

ABSTRACT Aspects of nursing students' clinical experiences are anxiety provoking. High anxiety may contribute to decreased learning. The purpose of this study was to identify potentially anxiety-producing clinical experiences for student nurses. Thirty-nine junior and 53 senior nursing students from a BS degree program completed the \"Clinical Experience Assessment form,\" a 16-item Likert scale. The items included communication and procedural aspects of patient care, interpersonal relationships with healthcare providers, and interactions with faculty. An open-ended question asked students to identify the most anxiety-producing aspect of their clinical practice. The students expressed the highest anxiety for the initial clinical experience on a unit and the fear of making mistakes. Faculty evaluation and observation were also anxiety-producing. The results of the student t-test indicated that juniors were significantly higher in their expression of anxiety than seniors. The main theme from the content analysis was that students' anxiety was increased in the clinical setting by their perceptions of nonsupportive faculty.