An iterative procedure to obtain inverse response functions for thick-target correction of measured charged-particle spectra

A new method for correcting charged-particle spectra for thick target effects is described. Starting with a trial function, inverse response functions are found by an iterative procedure. The variances corresponding to the measured spectrum are treated similiarly and in parallel. Oscillations of the solution are avoided by rebinning the data to finer bins during a correction iteration and back to the original or wider binning after each iteration. This thick-target correction method has been used for data obtained with the MEDLEY facility at the The Svedberg Laboratory, Uppsala, Sweden, and is here presented in detail and demonstrated for two test cases.Comment: 14 pages, 8 figures, submitted to NIM

Impacts of Forest-Based Activities on Woodland Characteristics in a Forested Watershed of Southern Zagros, Iran

The purpose of this study was to investigate the impacts of forest-based activities on the conditions of the Ganaveh woodland in the southern Zagros, Iran, and to suggest strategies for improving the implementation of forest resource management plans. Woodland inventory data was gathered in 2003, accompanied with data from interviews in 2008, were used in this study. The results show that there is forest degradation in terms of a lack of forest regeneration and a relatively high incidence of bad quality trees. These defects in the woodland attributes reflect the effects of the traditional management on vegetation cover, and are the causes of concern regarding the sustainability and conservation of the woodland. Overgrazing, seed gathering, and drought in some years are probably the main reasons for the poor natural regeneration in the area. Forest activities over the last decades could be the main causes of the relatively high rate of bad quality oak trees and the high rate of oaks in coppice form. Some efforts to gain acceptance from the woodland users for protecting the preserved areas from animal grazing and seed gathering for a period could be a better alternative for woodland rehabilitation than seeding

Swedish social insurance officers' experiences of difficulties in assessing applications for disability pensions – an interview study

<p>Abstract</p> <p>Background</p> <p>In this study the focus is on social insurance officers judging applications for disability pensions. The number of applications for disability pension increased during the late 1990s, which has resulted in an increasing number of disability pensions in Sweden. A more restrictive attitude towards the clients has however evolved, as societal costs have increased and governmental guidelines now focus on reducing costs. As a consequence, the quantitative and qualitative demands on social insurance officers when handling applications for disability pensions may have increased. The aim of this study was therefore to describe the social insurance officers' experiences of assessing applications for disability pensions after the government's introduction of stricter regulations.</p> <p>Methods</p> <p>Qualitative methodology was employed and a total of ten social insurance officers representing different experiences and ages were chosen. Open-ended interviews were performed with the ten social insurance officers. Data was analysed with inductive content analysis.</p> <p>Results</p> <p>Three themes could be identified as problematic in the social insurance officers' descriptions of dealing with the applications in order to reach a decision on whether the issue qualified applicants for a disability pension or not: 1. Clients are heterogeneous. 2. Ineffective and time consuming waiting for medical certificates impede the decision process. 3. Perspectives on the issue of work capacity differed among different stakeholders. The backgrounds of the clients differ considerably, leading to variation in the quality and content of applications. Social insurance officers had to make rapid decisions within a limited time frame, based on limited information, mainly on the basis of medical certificates that were often insufficient to judge work capacity. The role as coordinating actor with other stakeholders in the welfare system was perceived as frustrating, since different stakeholders have different goals and demands. The social insurance officers experience lack of control over the decision process, as regulations and other stakeholders restrict their work.</p> <p>Conclusion</p> <p>A picture emerges of difficulties due to disharmonized systems, stakeholder-bound goals causing some clients to fall between two stools, or leading to unnecessary waiting times, which may limit the clients' ability to take an active part in a constructive process. Increased communication with physicians about how to elaborate the medical certificates might improve the quality of certificates and thereby reduce the clients waiting time.</p

A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma

Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine

Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms

Several studies have identified obesity as a risk factor for asthma in both children and adults. An increased prevalence of asthma in subjects with gastro-oesophageal reflux (GOR) and obstructive sleep apnoea syndrome has also been reported. The aim of this investigation was to study obesity, nocturnal GOR and snoring as independent risk factors for onset of asthma and respiratory symptoms in a Nordic population. In a 5-10 yr follow-up study of the European Community Respiratory Health Survey in Iceland, Norway, Denmark, Sweden and Estonia, a postal questionnaire was sent to previous respondents. A total of 16,191 participants responded to the questionnaire. Reported onset of asthma, wheeze and night-time symptoms as well as nocturnal GOR and habitual snoring increased in prevalence along with the increase in body mass index (BMI). After adjusting for nocturnal GOR, habitual snoring and other confounders, obesity (BMI >30) remained significantly related to the onset of asthma, wheeze and night-time symptoms. Nocturnal GOR was independently related to the onset of asthma and in addition, both nocturnal GOR and habitual snoring were independently related to onset of wheeze and night-time symptoms. This study adds evidence to an independent relationship between obesity, nocturnal gastro-oesophageal reflux and habitual snoring and the onset of asthma and respiratory symptoms in adults

COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo

Collagen XXV alpha 1 (COL25A1) is a collagenous type II transmembrane protein purified from senile plaques of Alzheimer’s disease (AD) brains. COL25A1 alleles have been associated with increased risk for AD in a Swedish population. COL25A1 is specifically expressed in neurons and binds to aggregated Aβ in vitro. However, its contribution to the pathogenesis of AD and in vivo function are unknown. Here, we report that over-expression of COL25A1 in transgenic mice increases p35/p25 and β-site APP-cleaving enzyme 1 (BACE1) levels, facilitates intracellular aggregation and extracellular matrix deposits of Aβ, and causes synaptophysin loss and astrocyte activation. COL25A1 mice displayed reduced anxiety-like behavior in elevated plus maze and open field tests and significantly slower swimming speed in Morris water maze. In stable cell lines, motifs in noncollagenous domains of COL25A1 were important for the induction of BACE1 expression. These findings demonstrate that COL25A1 leads to AD-like pathology in vivo. Modulation of COL25A1 function may represent an alternative therapeutic intervention for AD

A project for future life—Swedish women's thoughts on childbearing lacking experience of giving birth and parenthood

A lifeworld hermeneutic approach was used in order to understand Swedish women's thoughts on childbearing. Nine women were interviewed, and they ranged in age from 22 to 28 years and represented diverse socioeconomic, educational, sexual, and fertility backgrounds. All women were similar in that they lacked experience of giving birth and parenthood. The analysis showed that childbearing includes dimensions of both immanence and transcendence. Immanence, as childbearing is seen as stagnant to women's freedom in present life. Transcendence, as childbearing is thought of as a project for future life, a part of female identity, and a conscious standpoint for which the woman wants to be prepared and for which she wants to create the best conditions

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research

Marx’s "Capital"in the Information Age

This article argues that a media and communication studies perspective on reading Marx’s Capital has thus far been missing, but is needed in the age of information capitalism and digital capitalism. Two of the most popular contemporary companions to Marx’s Capital, the ones by David Harvey and Michael Heinrich, present themselves as general guidebooks on how to read Marx, but are actually biased towards particular schools of Marxist thought. A contemporary reading of Marx needs to be mediated with contemporary capitalism’s structures and the political issues of the day. Media, communications and the Internet are important issues for such a reading today. It is time to see Marx not just as a critic of capitalism but also as a critic of capitalist communications

Allergic conditions and risk of hematological malignancies in adults: a cohort study

BACKGROUND: Two contradictory hypotheses have been proposed to explain the relationship between allergic conditions and malignancies, the immune surveillance hypothesis and the antigenic stimulation hypothesis. The former advocates that allergic conditions may be protective against development of cancer, whereas the latter proposes an increased risk. This relationship has been studied in several case-control studies, but only in a few cohort studies. METHODS: The association between allergic conditions and risk of developing leukemia, Hodgkin's disease, non-Hodgkin's lymphoma and myeloma was investigated in a cohort of 16,539 Swedish twins born 1886–1925. Prospectively collected, self-reported information about allergic conditions such as asthma, hay fever or eczema was obtained through questionnaires administered in 1967. The cohort was followed 1969–99 and cancer incidence was ascertained from the Swedish Cancer Registry. RESULTS: Hives and asthma tended to increase the risk of leukemia (relative risk [RR] = 2.1, 95% Confidence Interval [CI] 1.0–4.5 and RR = 1.6, 95% CI 0.8–3.5, respectively). There was also an indication of an increased risk of non-Hodgkin's lymphoma associated with eczema during childhood (RR = 2.3, 95% CI 1.0–5.3). CONCLUSION: In contrast to most previous studies, our results do not indicate a protective effect of allergic conditions on the risk of developing hematological malignancies. Rather, they suggest that allergic conditions might increase the risk of some hematological malignancies