196 research outputs found

    Relativistic calculations of the lifetimes and hyperfine structure constants in 67^{67}Zn+^{+}

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    This work presents accurate {\it ab initio} determination of the magnetic dipole (M1) and electric quadrupole (E2) hyperfine structure constants for the ground and a few low-lying excited states in 67^{67}Zn+^{+}, which is one of the interesting systems in fundamental physics. The coupled-cluster (CC) theory within the relativistic framework has been used here in this calculations. Long standing demands for a relativistic and highly correlated calculations like CC can be able to resolve the disagreements among the lifetime estimations reported previously for a few low-lying states of Zn+^{+}. The role of different electron correlation effects in the determination of these quantities are discussed and their contributions are presented.Comment: 9 pages, 1 figure. submitted to J. Phys. B Fast Trac

    Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

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    Rabies kills many people throughout the developing world every year. The murine monoclonal antibody (mAb) 62-71-3 was recently identified for its potential application in rabies postexposure prophylaxis (PEP). The purpose here was to establish a plant-based production system for a chimeric mouse-human version of mAb 62-71-3, to characterize the recombinant antibody and investigate at a molecular level its interaction with rabies virus glycoprotein. Chimeric 62-71-3 was successfully expressed in Nicotiana benthamiana. Glycosylation was analyzed by mass spectroscopy; functionality was confirmed by antigen ELISA, as well as rabies and pseudotype virus neutralization. Epitope characterization was performed using pseudotype virus expressing mutagenized rabies glycoproteins. Purified mAb demonstrated potent viral neutralization at 500 IU/mg. A critical role for antigenic site I of the glycoprotein, as well as for two specific amino acid residues (K226 and G229) within site I, was identified with regard to mAb 62-71-3 neutralization. Pseudotype viruses expressing glycoprotein from lyssaviruses known not to be neutralized by this antibody were the controls. The results provide the molecular rationale for developing 62-71-3 mAb for rabies PEP; they also establish the basis for developing an inexpensive plant-based antibody product to benefit low-income families in developing countries.—Both, L., van Dolleweerd, C., Wright, E., Banyard, A. C., Bulmer-Thomas, B., Selden, D., Altmann, F., Fooks, A. R., Ma, J. K.-C. Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

    Double helix of research and practice—developing a practice model for crisis resolution and home treatment through participatory action research

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    Over the last five years Crisis Resolution/Home Treatment (CR/HT) teams have been established in Norway. These teams provide an alternative to in-patient acute care services offering assessment as well as direct care. This paper addresses a method of examining the nature of practice models that are being developed in a CR/HT team incorporating the philosophy of open dialogue and the open lifeworld approach. The overall design of this research is action research applying a cooperative inquiry perspective. Multistage focus group interviews are used as a method for generating data, followed by phenomenological–hermeneutic approach in analyzing the data. Three themes were identified: (a) “keeping the dialogue open” referring to the emphasis of openness in dialogues and opening up for a variety of perspectives on what's going on; (b) “tolerance of uncertainty” referring to the need to accept and deal with uncertainty and multiplicity; and (c) “nurturing everyday life issues” referring to the emphasis on illustrating clinical situations in detail through remaking of stories. The on-going co-processes of research and practice was a double helix that links the happenings in the practice with the findings in the research revealing the knowledge in practice and further developing that knowledge

    Homocysteine Levels in Chronic Gastritis and Other Conditions: Relations to Incident Cardiovascular Disease and Dementia

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    Background Homocysteine levels in circulation are determined by several factors and hyperhomocysteinemia is reportedly associated with cardiovascular diseases and dementia. The aim of this study is to determine the relation of chronic gastritis and other conditions to homocysteine levels and their relation to incident cardiovascular diseases and dementia. Methods An adult population-based cohort (N = 488) was screened for H. pylori infection, gastro-duodenitis (endoscopic biopsies), disease history, and lifestyle factors. Blood samples were analyzed for pepsinogen I and II (gastric function), vitamin B12, folate, homocysteine, and cystatin C (renal function). The methylenetetrahydrofolate reductase C677T polymorphism reportedly associated with hyperhomocysteinemia was analyzed by pyrosequencing. Incident cardiovascular diseases and dementia were monitored during a median follow-up interval of 10 years. Results At baseline, there was a positive relation of S-homocysteine to male gender, age, S-cystatin C, methylenetetrahydrofolate reductase 677TT genotype and atrophic gastritis. During follow-up, cardiovascular diseases occurred in 101/438 and dementia in 25/488 participants, respectively. Logistic regression analysis (adjusting for gender, age at baseline, follow-up interval, BMI, smoking, alcohol consumption, NSAID use, P-cholesterol, and P-triglycerides) showed an association of S-homocysteine higher than 14.5 μmol/l to cardiovascular diseases (OR 2.05 [95% c.i. 1.14–3.70]), but not to dementia overall. Conclusions Gender, age, vitamin B12, folate, renal function, atrophic gastritis and the methylenetetrahydrofolate 677TT genotype were significant determinants of homocysteine levels, which were positively related to incident cardiovascular diseases

    Pollen-based quantitative reconstructions of Holocene regional vegetation cover (plant-functional types and land-cover types) in Europe suitable for climate modelling

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    We present quantitative reconstructions of regional vegetation cover in north-western Europe, western Europe north of the Alps, and eastern Europe for five time windows in the Holocene [around 6k, 3k, 0.5k, 0.2k, and 0.05k calendar years before present (bp)] at a 1 degrees x1 degrees spatial scale with the objective of producing vegetation descriptions suitable for climate modelling. The REVEALS model was applied on 636 pollen records from lakes and bogs to reconstruct the past cover of 25 plant taxa grouped into 10 plant-functional types and three land-cover types [evergreen trees, summer-green (deciduous) trees, and open land]. The model corrects for some of the biases in pollen percentages by using pollen productivity estimates and fall speeds of pollen, and by applying simple but robust models of pollen dispersal and deposition. The emerging patterns of tree migration and deforestation between 6k bp and modern time in the REVEALS estimates agree with our general understanding of the vegetation history of Europe based on pollen percentages. However, the degree of anthropogenic deforestation (i.e. cover of cultivated and grazing land) at 3k, 0.5k, and 0.2k bp is significantly higher than deduced from pollen percentages. This is also the case at 6k in some parts of Europe, in particular Britain and Ireland. Furthermore, the relationship between summer-green and evergreen trees, and between individual tree taxa, differs significantly when expressed as pollen percentages or as REVEALS estimates of tree cover. For instance, when Pinus is dominant over Picea as pollen percentages, Picea is dominant over Pinus as REVEALS estimates. These differences play a major role in the reconstruction of European landscapes and for the study of land cover-climate interactions, biodiversity and human resources.Peer reviewe

    Experiences of the implementation of a tool for lifestyle intervention in primary health care: a qualitative study among managers and professional groups

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    <p>Abstract</p> <p>Background</p> <p>In recent years there has been increasing interest in transferring new knowledge into health care practices, a process often referred to as implementation. The various subcultures that exist among health care workers may be an obstacle in this process. The aim of this study was to explore how professional groups and managers experienced the implementation of a new tool for lifestyle intervention in primary health care (PHC). The computer-based tool was introduced with the intention of facilitating the delivery of preventive services.</p> <p>Methods</p> <p>Focus group interviews with staff and individual interviews with managers at six PHC units in the southeast of Sweden were performed 9 months after the introduction of the new working tool. Staff interviews were conducted in groups according to profession, and were analysed using manifest content analysis. Experiences and opinions from the different staff groups and from managers were analysed.</p> <p>Results</p> <p>Implementation preconditions, opinions about the lifestyle test, and opinions about usage were the main areas identified. In each of the groups, managers and professionals, factors related to the existing subcultures seemed to influence their experiences of the implementation. Managers were visionary, GPs were reluctant, nurses were open, and nurse assistants were indifferent.</p> <p>Conclusion</p> <p>This study indicates that the existing subcultures in PHC influence how the implementation of an innovation is perceived by managers and the different professionals. In PHC, an organization with several subcultures and an established hierarchical structure, an implementation strategy aimed at all groups did not seem to result in a successful uptake of the new method.</p

    Single domain antibody multimers confer protection against rabies infection

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    Post-exposure prophylactic (PEP) neutralizing antibodies against Rabies are the most effective way to prevent infection-related fatality. The outer envelope glycoprotein of the Rabies virus (RABV) is the most significant surface antigen for generating virus-neutralizing antibodies. The small size and uncompromised functional specificity of single domain antibodies (sdAbs) can be exploited in the fields of experimental therapeutic applications for infectious diseases through formatting flexibilities to increase their avidity towards target antigens. In this study, we used phage display technique to select and identify sdAbs that were specific for the RABV glycoprotein from a naïve llama-derived antibody library. To increase their neutralizing potencies, the sdAbs were fused with a coiled-coil peptide derived from the human cartilage oligomeric matrix protein (COMP48) to form homogenous pentavalent multimers, known as combodies. Compared to monovalent sdAbs, the combodies, namely 26424 and 26434, exhibited high avidity and were able to neutralize 85-fold higher input of RABV (CVS-11 strain) pseudotypes in vitro, as a result of multimerization, while retaining their specificities for target antigen. 26424 and 26434 were capable of neutralizing CVS-11 pseudotypes in vitro by 90–95% as compared to human rabies immunoglobulin (HRIG), currently used for PEP in Rabies. The multimeric sdAbs were also demonstrated to be partially protective for mice that were infected with lethal doses of rabies virus in vivo. The results demonstrate that the combodies could be valuable tools in understanding viral mechanisms, diagnosis and possible anti-viral candidate for RABV infection

    S100B and homocysteine in the acute alcohol withdrawal syndrome

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    Elevations of serum homocysteine levels are a consistent finding in alcohol addiction. Serum S100B levels are altered in different neuropsychiatric disorders but not well investigated in alcohol withdrawal syndromes. Because of the close connection of S100B to ACTH and glutamate secretion that both are involved in neurodegeneration and symptoms of alcoholism the relationship of S100B and homocysteine to acute withdrawal variables has been examined. A total of 22 male and 9 female inpatients (mean age 46.9 ± 9.7 years) with an ICD-10 diagnosis of alcohol addiction without relevant affective comorbidity were examined on admission and after 24, 48, and 120 h during withdrawal. S100B and homocysteine levels in serum were collected, and severity of withdrawal symptoms (AWS-scale), applied withdrawal medication, initial serum ethanol levels and duration of addiction were recorded. Serum S100B and homocysteine levels declined significantly (P < .05) over time. Both levels declined with withdrawal syndrome severity. Females showed a trend to a more intense decline in serum S100B levels compared to males at day 5 (P = .06). Homocysteine levels displayed a negative relationship to applied amount of clomethiazole (P < .05) and correlated with age of onset of addiction. No withdrawal seizures were recorded during the trial. As it is known for homocysteine, S100B revealed to decline rapidly over withdrawal treatment in alcoholism. This effect is more pronounced in female patients. S100B could be of relevance in the neurobiology of alcohol withdrawal syndromes. It may be indirectly related to the level of stress level or glutamatergic activity during alcohol withdrawal

    Financing intersectoral action for health: a systematic review of co-financing models.

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    BACKGROUND: Addressing the social and other non-biological determinants of health largely depends on policies and programmes implemented outside the health sector. While there is growing evidence on the effectiveness of interventions that tackle these upstream determinants, the health sector does not typically prioritise them. From a health perspective, they may not be cost-effective because their non-health outcomes tend to be ignored. Non-health sectors may, in turn, undervalue interventions with important co-benefits for population health, given their focus on their own sectoral objectives. The societal value of win-win interventions with impacts on multiple development goals may, therefore, be under-valued and under-resourced, as a result of siloed resource allocation mechanisms. Pooling budgets across sectors could ensure the total multi-sectoral value of these interventions is captured, and sectors' shared goals are achieved more efficiently. Under such a co-financing approach, the cost of interventions with multi-sectoral outcomes would be shared by benefiting sectors, stimulating mutually beneficial cross-sectoral investments. Leveraging funding in other sectors could off-set flat-lining global development assistance for health and optimise public spending. Although there have been experiments with such cross-sectoral co-financing in several settings, there has been limited analysis to examine these models, their performance and their institutional feasibility. AIM: This study aimed to identify and characterise cross-sectoral co-financing models, their operational modalities, effectiveness, and institutional enablers and barriers. METHODS: We conducted a systematic review of peer-reviewed and grey literature, following PRISMA guidelines. Studies were included if data was provided on interventions funded across two or more sectors, or multiple budgets. Extracted data were categorised and qualitatively coded. RESULTS: Of 2751 publications screened, 81 cases of co-financing were identified. Most were from high-income countries (93%), but six innovative models were found in Uganda, Brazil, El Salvador, Mozambique, Zambia, and Kenya that also included non-public and international payers. The highest number of cases involved the health (93%), social care (64%) and education (22%) sectors. Co-financing models were most often implemented with the intention of integrating services across sectors for defined target populations, although models were also found aimed at health promotion activities outside the health sector and cross-sectoral financial rewards. Interventions were either implemented and governed by a single sector or delivered in an integrated manner with cross-sectoral accountability. Resource constraints and political relevance emerged as key enablers of co-financing, while lack of clarity around the roles of different sectoral players and the objectives of the pooling were found to be barriers to success. Although rigorous impact or economic evaluations were scarce, positive process measures were frequently reported with some evidence suggesting co-financing contributed to improved outcomes. CONCLUSION: Co-financing remains in an exploratory phase, with diverse models having been implemented across sectors and settings. By incentivising intersectoral action on structural inequities and barriers to health interventions, such a novel financing mechanism could contribute to more effective engagement of non-health sectors; to efficiency gains in the financing of universal health coverage; and to simultaneously achieving health and other well-being related sustainable development goals
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