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Background: The role of vitamin D supplementation as adjuvant treatment of tuberculosis (TB) has lately attracted increasing interest. Our aim was to investigate the capacity of alveolar macrophages (AMs) from patients with or without exposure to TB to control intracellular growth of virulent Mycobacterium tuberculosis (Mtb). Methods: AMs were freshly harvested from the bronchoalveolar lavage fluid of 7 patients with a history of TB (4 patients with previous TB and 3 patients with current TB) and 4 non-TB subjects. The H37Rv strain, genetically modified to express Vibrio harveyi luciferase, was used to determine the growth of Mtb by luminometry in the AMs from study subjects. Cytokine levels in culture supernatants were determined using a flow cytometry-based bead array technique. Results: AMs from patients with a TB history were less efficient in restricting Mtb growth. Stimulation with 100 nM1, 25-dihydroxyvitamin D (1,25D3) did not significantly influence the capacity of AMs from any study subjects to control the infection. Out of the cytokines evaluated (TNF-α, IL-1β, IL-10 and IL-12p40) only TNF-α demonstrated detectable levels in culture supernatants, but did not respond to stimulation with 1,25D3. Conclusions: We conclude that AMs of TB-patients show reduced ability to control mycobacterial growth in vitro, and, that AMs in this pilot study do no respond to 1, 25D3-stimulation. The former observation supports the concept that innate immunity is crucial for the control of TB infection.

A disrupted balance of reduced glutathione (GSH) and iron (Fe) and subsequent enhanced susceptibility of lysosomes of lung macrophages (LMs) to oxidants may play a role in lung fibrogenesis. We assessed cellular Fe/GSH, lysosomal membrane permeabilization (LMP), and cell death in cultures of oxidant exposed LMs. LMs from 7 lung fibrosis patients and healthy subjects were exposed to a physiologic concentration of H2O2 for 1 h. LMP was assessed with acridine orange green fluorescence, apoptosis/necrosis were estimated by apoptotic DNA and typical morphology, Fe was assessed with Prussian blue staining/atomic absorption spectrophotometry, and GSH was evaluated using a GSH assay kit. Oxidant-induced LMP and cell death were more pronounced in cultures of LMs from patients with lung fibrosis, and these cells contained less GSH and more cytochemically stained Fe. These observations indicate that LMP may be involved in fibrosis development, possibly through activation of the inflammasome complex. Further studies are warranted for a detailed understanding.

BACKGROUND:Reduced ventilation in lung regions affected by chronic obstructive pulmonary disease (COPD), reflected as inhomogeneities in the single-photon emission computed tomography (SPECT) lung image, is correlated to disease advancement. An analysis method for measuring these inhomogeneities is proposed in this work. The first aim was to develop a quantitative analysis method that could discriminate between Monte Carlo simulated normal and COPD lung SPECT images. A second aim was to evaluate the ability of the present method to discriminate between human subjects with advanced COPD and healthy volunteers. METHODS:In the simulated COPD study, different activity distributions in the lungs were created to mimic the healthy lung (normal) and different levels of COPD. Gamma camera projections were Monte Carlo simulated, representing clinically acquired projections of a patient who had inhaled 125 MBq 99mTc-Technegas followed by a 10-min SPECT examination. Reconstructions were made with iterative ordered subset expectation maximisation. The coefficient of variance (CV) was calculated for small overlapping volumes covering the 3D reconstructed activity distribution. A CV threshold value (CVT) was calculated as the modal value of the CV distribution of the simulated normal. The area under the distribution curve (AUC), for CV values greater than CVT, AUC(CVT), was then calculated. Moreover, five patients with advanced emphysema and five healthy volunteers inhaled approximately 75 MBq 99mTc-Technegas immediately before the 20-min SPECT acquisition. In the human study, CVT was based on the mean CV distribution of the five healthy volunteers. RESULTS:A significant difference (p < 0.001) was found between the Monte-Carlo simulated normal and COPD lung SPECT examinations. The present method identified a total reduction of ventilation of approximately 5%, not visible to the human eye in the reconstructed image. In humans the same method clearly discriminated between the fiv

AimsTo evaluate how recommendations of European guidelines regarding pharmacological and non-pharmacological treatments for heart failure (HF) are adopted in clinical practice.Methods and resultsThe ESC-HF Long-Term Registry is a prospective, observational study conducted in 211 Cardiology Centres of 21 European and Mediterranean countries, members of the European Society of Cardiology (ESC). From May 2011 to April 2013, a total of 12 440 patients were enrolled, 40.5% with acute HF and 59.5% with chronic HF. Intravenous treatments for acute HF were heterogeneously administered, irrespective of guideline recommendations. In chronic HF, with reduced EF, renin-angiotensin system (RAS) blockers, beta-blockers, and mineralocorticoid antagonists (MRAs) were used in 92.2, 92.7, and 67.0% of patients, respectively. When reasons for non-adherence were considered, the real rate of undertreatment accounted for 3.2, 2.3, and 5.4% of the cases, respectively. About 30% of patients received the target dosage of these drugs, but a documented reason for not achieving the target dosage was reported in almost two-thirds of them. The more relevant reasons for non-implantation of a device, when clinically indicated, were related to doctor uncertainties on the indication, patient refusal, or logistical/cost issues.ConclusionThis pan-European registry shows that, while in patients with acute HF, a large heterogeneity of treatments exists, drug treatment of chronic HF can be considered largely adherent to recommendations of current guidelines, when the reasons for non-adherence are taken into account. Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written. © 2013 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com

Understanding the European Union - where it has its roots and how it works - is not easy. Still, it is an absolutely necessary skill to acquire for the individual to navigate in today's Europe.

Previously, we have shown that TNF-alpha protects iron-exposed J774 macrophages against iron-catalyzed oxidative lysosomal disruption and cell death by increasing reduced glutathione and H-ferritin in cells. Because J774 cells are able to harbor large amounts of iron, which is potentially harmful in a redox-active state, we hypothesized that TNF-alpha-stimulated J774 macrophages will prevent iron-driven oxidative killing of alveolar epithelial A549 cells in co-culture. In the present study, iron trichloride (which is endocytosed by cells as hydrated iron-phosphate complexes) was mainly deposited inside the lysosomes of J774 macrophages, while A549 cells, equally iron exposed, accumulated much less iron. When challenged by oxidants, however, reactive lysosomal iron in A549 cells promoted lysosomal disruption and cell death, particularly in the presence of TNF-alpha. This effect resulted from an elevation in ROS generation by TNF-alpha, while a compensatory upregulation of protective molecules (H-ferritin and/or reduced glutathione) by TNF-alpha was absent. A549 cell death was particularly pronounced when iron and TNF-alpha were present in the conditioned medium during oxidant challenge; thus, iron-driven oxidative reactions in the culture medium were a much greater hazard to A549 cells than those taking place inside their lysosomes. Consequently, the iron chelator, deferoxamine, efficiently prevented A549 cell death when added to the culture medium during an oxidant challenge. In co-cultures of TNF-alpha-stimulated lung cells, J774 macrophages sequestered iron inside their lysosomes and protected A549 cells from oxidative reactions and cell death. Thus, the collective effect of TNF-alpha on co-cultured lung cells was mainly cytoprotective., Funding Agencies|County Council of Ostergotland (ALF)||Medical Research Council of Southeast Sweden (FORSS)||Swedish Medical Society||Linkoping Medical Society||Olle Engkvist, Apotekare Hedberg and LiO (Ostergotland, Sweden)

The ESC-HF Pilot survey was aimed to describe clinical epidemiology and 1-year outcomes of outpatients and inpatients with heart failure (HF). The pilot phase was also specifically aimed at validating structure, performance, and quality of the data set for continuing the survey into a permanent Registry. The ESC-HF Pilot study is a prospective, multicentre, observational survey conducted in 136 Cardiology Centres in 12 European countries selected to represent the different health systems across Europe. All outpatients with HF and patients admitted for acute HF on 1 day per week for eight consecutive months were included. From October 2009 to May 2010, 5118 patients were included: 1892 (37) admitted for acute HF and 3226 (63) patients with chronic HF. The all-cause mortality rate at 1 year was 17.4 in acute HF and 7.2 in chronic stable HF. One-year hospitalization rates were 43.9 and 31.9, respectively, in hospitalized acute and chronic HF patients. Major regional differences in 1-year mortality were observed that could be explained by differences in characteristics and treatment of the patients. The ESC-HF Pilot survey confirmed that acute HF is still associated with a very poor medium-term prognosis, while the widespread adoption of evidence-based treatments in patients with chronic HF seems to have improved their outcome profile. Differences across countries may be due to different local medical practice as well to differences in healthcare systems. This pilot study also offered the opportunity to refine the organizational structure for a long-term extended European network.

To evaluate how recommendations of European guidelines regarding pharmacological and non-pharmacological treatments for heart failure (HF) are adopted in clinical practice. less thanbrgreater than less thanbrgreater thanThe ESC-HF Long-Term Registry is a prospective, observational study conducted in 211 Cardiology Centres of 21 European and Mediterranean countries, members of the European Society of Cardiology (ESC). From May 2011 to April 2013, a total of 12 440 patients were enrolled, 40.5 with acute HF and 59.5 with chronic HF. Intravenous treatments for acute HF were heterogeneously administered, irrespective of guideline recommendations. In chronic HF, with reduced EF, reninangiotensin system (RAS) blockers, beta-blockers, and mineralocorticoid antagonists (MRAs) were used in 92.2, 92.7, and 67.0 of patients, respectively. When reasons for non-adherence were considered, the real rate of undertreatment accounted for 3.2, 2.3, and 5.4 of the cases, respectively. About 30 of patients received the target dosage of these drugs, but a documented reason for not achieving the target dosage was reported in almost two-thirds of them. The more relevant reasons for non-implantation of a device, when clinically indicated, were related to doctor uncertainties on the indication, patient refusal, or logistical/cost issues. less thanbrgreater than less thanbrgreater thanThis pan-European registry shows that, while in patients with acute HF, a large heterogeneity of treatments exists, drug treatment of chronic HF can be considered largely adherent to recommendations of current guidelines, when the reasons for non-adherence are taken into account. Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written., Funding Agencies|ESC||Abbot Vascular||Bayer Pharma||BMS/Pfizer||Boehringer Ingelheim International||Daiichi Sankyo Europe||Menarini International||Novartis Pharma||Laboratoires Servier||Amgen||Boston Scientific International||MSD/Merck Co||Sanofi-Aventis Group

Recordings of the acoustic activity of free-swimming groups of echolocating dolphins increase the likelihood of collecting overlapping click trains, originating from multiple individuals, in the same set of data. In order to evaluate the click properties of each individual based on such recordings it is necessary to identify which clicks originate from which animal. This paper suggests a computationally efficient strategy to separate overlapping click trains originating from multiple free-swimming bottlenose dolphins, enabling echolocation analysis at an individual level on several animals. This technique is based on sequential matching of the frequency spectra of successive clicks. The clicks are grouped together as individual click trains if the correlation coefficients between clicks are higher than a pre-set threshold level. The robustness of the algorithm is tested by adding artificially generated white Gaussian noise and comparing the results with other comparable commonly used methods based on inter-click intervals, centroid frequencies, and amplitude levels. The described method is applicable to a variety of experimental and observational contexts, e. g., those regarding echolocation development of calves, the hypothesized acoustic "etiquette" among dolphins when investigating the same object, and the possible occurrence of eavesdropping in large dolphin pods.

This study is investigating in what way different supportive assisting techniques or the lack of them affects the work and the workers in terms of accessibility and acceptance. The study was made in three workplaces (with no, little and much assisting techniques). In the first one there were no assisting tools at all. The second one had an ordinary simple cash register, whereas the third one had a cash register, designed for people with development disability. The participants in this study where people with development disabilities who where trainees (cashiers) and their tutors, which also worked in the environment as cashiers. By using high level of assisting technique the usability and the means of social acceptance as well as the system acceptance was high. There were only small differences between the group of tutors and the group of trainees in their perception of usability. In the case of no assisting technique both groups perceived larger difficulties in the social cooperation with the customers which become a larger social acceptance issue in accordance to their operational goal. The major finding in this study is that accessibility of the system has a major influence on both the practical and the system acceptance, QC 20120425

Principles and guidelines will become more important, due to the development of accessibility policies and the harmonization with Europe in Sweden is discussed. Public policy is the body of principles that underpin the operation of legal systems in a state, which address the social, moral, and economic values that tie a society together. Accessibility policies often start at the international level. Many countries currently have different regulations for interface accessibility. In Sweden the transparency of the public sector is one of the foundations of democracy and the development of an accessible society and is manifested by a duty to publish and promote openness. Public policy and legislation play an important role in contributing to increased accessibility. Sweden is a country of negotiation and transparency, not binding legislation. Involving groups with impairments may not only provide increased accessibility but also increase innovation., QC 20120210

Musiken spelade en betydande roll i Hjalmar Söderbergs liv och konstnärsskap. Både som privatperson och som yrkesman tycks han ha haft ett starkt musikintresse. Som recensent under några år i början av sin tidningskarriär recenserade Söderberg ett brett spektrum av sceniska alster, huvudsakligen teaterpjäser av olika kaliber, men här fanns också allt ifrån revyer till operetter. Som trägen besökare av tidens olika nöjesetablissemang och utskänkningsställen, var han också väl förtrogen med den repertoar av både seriösare och mer populärt slag som enligt tidens sed samsades på tiljorna. Denna musikaliska bakgrund gör sig om och om igen påmind i Söderbergs litterära verk. P g a den starka tidsförankringen i kultur och miljö, karakteriserades Söderberg av sin samtid som en efemär författare. Man förutspådde att hans romaner och noveller snabbt skulle bli omoderna. Tiden har emellertid visat att spådomen kommit på skam. Söderbergs författarskap är fortfarande aktuellt och fräscht trots en stark förankring i samtidens politiska och kulturella problemställningar. Talespråket "ju mer personlig desto allmängiltigare" kanske kan tillämpas även här. Ju mer fast förankrad i tid och miljö en litteratur är, desto intressantare kan den paradoxalt nog vara för senare tider att spegla sig i. Detta gäller också de musikaliska beskrivningar och referenser som förekommer i Söderbergs författarskap. Musiken utgör ofta ett slags akustisk fond mot vilken diskussioner och reflektioner förs. Denna "ljudkuliss" är inte bara av historiskt intresse som en spegel av tidens repertoar och tidens musikliv, utan ger också en förståelse för den förändring som skett i musiklivet sedan sekelskiftet 1900.

The primary objective of the new ESC-HF Pilot Survey was to describe the clinical epidemiology of outpatients and inpatients with heart failure (HF) and the diagnostic/therapeutic processes applied across 12 participating European countries. This pilot study was specifically aimed at validating the structure, performance, and quality of the data set, for continuing the survey into a permanent registry. The ESC-HF Pilot study is a prospective, multicentre, observational survey conducted in 136 cardiology centres from 12 European countries selected to represent the different health systems and care attitudes across Europe. All outpatients with HF and patients admitted for acute HF were included during the enrolment period (1 day per week for 8 consecutive months). From October 2009 to May 2010, 5118 patients were included in this pilot survey, of which 1892 (37%) were admitted for acute HF and 3226 (63%) for chronic HF. Ischaemic aetiology was reported in about half of the patients. In patients admitted for acute HF, the most frequent clinical profile was decompensated HF (75% of cases), whereas pulmonary oedema and cardiogenic shock were reported, respectively, in 13.3 and 2.3% of the cases. The total in-hospital mortality rate was 3.8% and was cardiovascular in 90.1% of the cases. Lowest and highest mortality rates were observed in hypertensive HF and in cardiogenic shock, respectively. More than 80% of patients with chronic HF were treated with renin-angiotensin-aldosterone system blockers and beta-adrenergic blockers. However, target doses of such drugs were reached in one-third to one-fourth of the patients only. The ESC-HF Pilot Survey is an example of the possibility of utilizing an observational methodology to get insights into the current clinical practice in Europe, whose picture will be completed by the 1-year follow-up. Moreover, this study offered the opportunity to refine the organizational structure of a long-term, extended European network.

A challenge to HCI-designers is to create simple, usable, and useful applications. The current paper addresses this problem and presents an innovative possibility to extract useful information from users rarely represented in contemporary participatory design approaches. The study was conducted from a Universal Access point of view. The primary result of the study is that people with well defined intellectual (e.g. understanding and logical reasoning) difficulties provided the designers of web-pages with more valuable and elaborated answers to bottlenecks in the interaction than a more representative group of web-users. With this result in mind Universal Access should not be an unreachable goal. This implies that people with intellectual difficulties can be regarded as an unexploited resource in HCI when using a participatory approach., QC 20120207

QC 20120209

This paper presents the architecture of a Hybrid Broadband Broadcast TestBed deployed in Gavle, Sweden, to conduct end user trials with Interactive TV Services. The platform offers an environment for the evaluation of Interactive TV services, technology and program formats for television., QC 20120209

Detailed echolocation behavior studies on free-swimming dolphins require a measurement system that incorporates multiple hydrophones (often andgt; 16). However, the high data flow rate of previous systems has limited their usefulness since only minute long recordings have been manageable. To address this problem, this report describes a 47-channel burst-mode recording hydrophone system that enables highly resolved full beamwidth measurements on multiple free-swimming dolphins during prolonged recording periods. The system facilitates a wide range of biosonar studies since it eliminates the need to restrict the movement of animals in order to study the fine details of their sonar beams.

Is it possible to design easy to use ITV applications for all? Well it should be, but how do we design to achieve this objective? This study is the first of five aiming at a design for all strategy where focus is to find the most difficult areas in further designactivities to concentrate the on.The ITV service in this design study is intended to bring easy and understandable information to the guests at a municipal elderly care centre and the guest's next of kin. This design should workboth on a computer and on set top boxes for TV. The elderly target group has severe difficulties due to the system of care in Sweden, where elderly people live in their own homes as long aspossible. Their difficulties can be of both psychiatric and physiological nature.Individuals with defined difficulties in this UCD study was more effective than other to point out the difficult areas of the design and at the same time give more hints to the designer of how to solve them. The consequence of the results of the study is to start to rethink of how we choose users to participate in the design process. Maybe the design process becomes more effective and at the same time lowers the need of accessibility adaptation after the design when not only choosing representative participants in the process., QC 20120514

The present study describes the development and testing of a tool for dolphin research. This tool was able to visualize the dolphin echolocation signals as well as function as an acoustically operated "touch screen." The system consisted of a matrix of hydrophones attached to a semitransparent screen, which was lowered in front of an underwater acrylic panel in a dolphin pool. When a dolphin aimed its sonar beam at the screen, the hydrophones measured the received sound pressure levels. These hydrophone signals were then transferred to a computer where they were translated into a video image that corresponds to the dynamic sound pressure variations in the sonar beam and the location of the beam axis. There was a continuous projection of the image back onto the hydrophone matrix screen, giving the dolphin an immediate visual feedback to its sonar output. The system offers a whole new experimental methodology in dolphin research and since it is software-based, many different kinds of scientific questions can be addressed. The results were promising and motivate further development of the system and studies of sonar and cognitive abilities of dolphins. © 2008 Acoustical Society of America.

QC 20120516

QC 20120528

A first testing ground for QED in the combined presence of a strong Coulomb field and a strong magnetic field is provided by the precise measurement of the hyperfine structure splitting of hydrogenlike 209Bi. We present a complete calculation of the one-loop self-energy correction to the first-order hyperfine interaction for various nuclear charges. In the low-Z regime we almost perfectly agree with the Z alpha expansion, but for medium and high Z there is a substantial deviation.

The Bollnäs’ model refers to an approach for testing, evaluating and designing information and communication technology services for all kind of users. Usually an indicator group (test group) is compared to a control group consisting of people without any obvious impairment or difficulties. This “Design-for-all” model has been developed at a recently established Institute for Humane Technology (IHT), located in Bollnäs, a town in the middle part of Sweden. In collaboration with World Internet Institute in Gävle and the National IT User Centre in Uppsala efforts are made to come to grips with digital gaps. Despite the high penetration of IT-products and IT-services in Sweden about one third of the population are directly non users for different reasons. Considering the possibilities of 24-hours services and emerging e-democracy, and high governmental ambitions this condition is totally unacceptable. Therefore, it is a well recognized challenge in Sweden and elsewhere that services have to be designed for people with special needs. The concept of normality is challenged at IHT. From time to time all potential users might face difficulties of some kind in the interaction via public networks. These difficulties are frequently due to a poor adaptation of the technology to basic human requirements. Results from work with new interfaces and adapted services at IHT demonstrate that previous non users might perform excellent with adequate and timely support, adapted redesign of interfaces, and a simplified dialogue management. Thus, several user panels have been formed in Bollnäs, with a leading test site at Höghammarskolan, a boarding school for intellectually disabled. Other target groups are people with motoric disorders, visually and auditory impaired etc. The concept also includes validation on target groups with identical or similar problems. Results from a recently finished study financed by the Swedish Post and Telecom Board will be reported., NQC

Chopin´s artistry and his illness. Did Chopin´s fateful disease, and his instinctive understanding of its poor prognosis, influence his musical artistry? Generally spoken, the relation between an artist´s life and his work has been very much discussed. Concerning Chopin, Franz Liszt wrote that he used his art to reflect on the tragedy of his life. This is, certainly, not true for all his works, but it is undeniably so, that it seems relevant for some of them. Chopin composed some works that carry a very special, dark and emotional intensity that goes far beyond the musical conventions of the time. Examples are some of the Préludes, especially those in A minor, E minor and B minor Op. 28. Another amazing example is the last movement of the Sonata in B flat minor, about which Robert Schumann said that it was not music at all. Some of these works were undoubtedly composed when Chopin was struck by an awareness of his mortal illness, for example in Majorca 1838. During the 1840s when Chopin was fighting more and more desperately against his illness, we also notice a dramatic change in his musical style. The beautiful melodies are becoming fragmented, the conception of form is more improvisatory and the harmony still more audacious. One poignant example is the Polonaise-fantasie where Chopin also is mixing two genres. Another remarkable piece, presumably from his last year, is the Mazurka in F minor Op. 68 No. 4 where the advanced harmony is built on extreme chromatics and the melody is remarkably fragmented. The other relation between Chopinís artistry and his illness is easier to demonstrate - that between the pianist and his illness. Chopin never had the great force in his playing, as for example Franz Liszt. Chopin´s dynamically weak playing became still more recognizable in the 1840s when his illness progressed. During the last years several people witness that Chopin no longer could follow his own dynamic instructions - where he had written fortissimo he played pia

It is important that congestive heart failure (CHF) patients know how to monitor and manage disease-associated signs and symptoms. CHF patients were randomised to follow-up at a nurse-based outpatient clinic (intervention group (IG); n = 103), or to follow-up in primary healthcare (control group (CG); n = 105). Patient knowledge of CHF and self-care were assessed by a questionnaire and cognitive function by a Mini Mental State Examination (MMSE) at baseline and at six months. Men knew more about CHF as compared to females at baseline (p < 0.01). However, females in the IG increased their knowledge of self-care between baseline and six months as compared to CG females (p < 0.05). Patients with cognitive dysfunction (MMSE < 24) presented lower scores on knowledge as compared to those with a MMSE of >24 at baseline (p < 0.01). These differences disappeared after the intervention. Thus, females seemed to gain more than men from a nurse-based management program and patients with in-hospital signs of cognitive dysfunction should be encouraged to participate.