Showing papers by "Linköping University published in 2008"

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Abstract: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms Recent reviews have described the range of assays that have been used for this purpose(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi) Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response

Psychotherapy for depression in adults: a meta-analysis of comparative outcome studies.

Abstract: Although the subject has been debated and examined for more than 3 decades, it is still not clear whether all psychotherapies are equally efficacious. The authors conducted 7 meta-analyses (with a total of 53 studies) in which 7 major types of psychological treatment for mild to moderate adult depression (cognitive-behavior therapy, nondirective supportive treatment, behavioral activation treatment, psychodynamic treatment, problem-solving therapy, interpersonal psychotherapy, and social skills training) were directly compared with other psychological treatments. Each major type of treatment had been examined in at least 5 randomized comparative trials. There was no indication that 1 of the treatments was more or less efficacious, with the exception of interpersonal psychotherapy (which was somewhat more efficacious; d = 0.20) and nondirective supportive treatment (which was somewhat less efficacious than the other treatments; d = -0.13). The drop-out rate was significantly higher in cognitive-behavior therapy than in the other therapies, whereas it was significantly lower in problem-solving therapy. This study suggests that there are no large differences in efficacy between the major psychotherapies for mild to moderate depression.

State of the art: using natriuretic peptide levels in clinical practice.

Abstract: Natriuretic peptide (NP) levels (B-type natriuretic peptide (BNP) and N-terminal proBNP) are now widely used in clinical practice and cardiovascular research throughout the world and have been incorporated into most national and international cardiovascular guidelines for heart failure. The role of NP levels in state-of-the-art clinical practice is evolving rapidly. This paper reviews and highlights ten key messages to clinicians: 1) NP levels are quantitative plasma biomarkers of heart failure (HF). 2) NP levels are accurate in the diagnosis of HF. 3) NP levels may help risk stratify emergency department (ED) patients with regard to the need for hospital admission or direct ED discharge. 4) NP levels help improve patient management and reduce total treatment costs in patients with acute dyspnoea. 5) NP levels at the time of admission are powerful predictors of outcome in predicting death and re-hospitalisation in HF patients. 6) NP levels at discharge aid in risk stratification of the HF patient. 7) NP-guided therapy may improve morbidity and/or mortality in chronic HF. 8) The combination of NP levels together with symptoms, signs and weight gain assists in the assessment of clinical decompensation in HF. 9) NP levels can accelerate accurate diagnosis of heart failure presenting in primary care. 10) NP levels may be helpful to screen for asymptomatic left ventricular dysfunction in high-risk patients.

A consensus approach toward the standardization of back pain definitions for use in prevalence studies

Abstract: A modified Delphi study conducted with 28 experts in back pain research from 12 countries. OBJECTIVE. To identify standardized definitions of low back pain that could be consistently used by investigators in prevalence studies to provide comparable data. SUMMARY OF BACKGROUND DATA. Differences in the definition of back pain prevalence in population studies lead to heterogeneity in study findings, and limitations or impossibilities in comparing or summarizing prevalence figures from different studies. METHODS. Back pain definitions were identified from 51 articles reporting population-based prevalence studies, and dissected into 77 items documenting 7 elements. These items were submitted to a panel of experts for rating and reduction, in 3 rounds (participation: 76%). Preliminary results were presented and discussed during the Amsterdam Forum VIII for Primary Care Research on Low Back Pain, compared with scientific evidence and confirmed and fine-tuned by the panel in a fourth round and the preparation of the current article. RESULTS. Two definitions were agreed on a minimal definition (with 1 question covering site of low back pain, symptoms observed, and time frame of the measure, and a second question on severity of low back pain) and an optimal definition that is made from the minimal definition and add-ons (covering frequency and duration of symptoms, an additional measure of severity, sciatica, and exclusions) that can be adapted to different needs. CONCLUSION. These definitions provide standards that may improve future comparisons of low back pain prevalence figures by person, place and time characteristics, and offer opportunities for statistical summaries.

Homogeneous large-area graphene layer growth on 6H-SiC(0001)

Abstract: Homogeneous large-area graphene monolayers were successfully prepared ex situ on 6H-SiC(0001). The samples have been studied systematically and the results are compared with those from a sample cut from the same wafer and prepared by in situ heating. The formation of smaller graphene flakes was found on the in situ prepared sample, which is in line with earlier observations. Distinctly different results are observed from the ex situ graphene layers of different thicknesses, which are proposed as a guideline for determining graphene growth. Recorded C 1s spectra consisted of three components: bulk SiC, graphene (G), and interface (I), the latter being a 6 root 3 layer. Extracted intensity ratios of G/I were found to give a good estimate of the thickness of graphene. Differences are also revealed in micro low energy electron diffraction images and electron reflectivity curves. The diffraction patterns were distinctly different from a monolayer thickness up to three layers. At a larger thickness only the graphitelike spot was visible. The electron reflectivity curve showed a nice oscillation behavior with kinetic energy and as a function of the number of graphene layers. The graphene sheets prepared were found to be very inert and the interface between the substrate and the layer(s) was found to be quite abrupt. No free Si could be detected in or on the graphene layers or at the interface.

Epidemiology of traumatic dental injuries – a 12 year review of the literature

Abstract: Several reports have been published during the past decades showing a lack of care of traumatic dental injuries (TDIs) as well as dentists and lay people having insufficient knowledge on how to man ...

Defining Lean Production : Some conceptual and practical issues

Abstract: Purpose - This paper aims to investigate the definition of Lean Production and the methods and goals associated with the concept as well as how it differs from other popular management concepts. Methodology/Approach - The paper is based on a review of the contemporary literature on Lean Production, both journal articles and books. Findings - It is shown in the paper that there is no consensus on a definition of Lean Production between the examined authors. The authors also seem to have different opinions on which characteristics that should be associated with the concept. Overall it can be concluded that Lean Production is not clearly defined in the reviewed literature. This divergence can cause some confusion on a theoretical level, but is probably more problematic on a practical level when organizations aim to implement the concept. This paper argues that it is important for an organization to acknowledge the different variations, and to raise the awareness of the input in the implementation process. It is further argued that the organization should not accept any random variant of Lean, but make active choices and adapt the concept to suit the organization-s needs. Through this process of adaptation, the organization will be able to increase the odds of performing a predictable and successful implementation. Originality/Value - This paper provides a critical perspective on the discourse surrounding Lean Production, and gives an input to the discussion of the implementation of management models. Keywords - Lean Production, Definition, Construct Validity, Total Quality Management Paper type - Conceptual paper

Internet-administered cognitive behavior therapy for health problems: a systematic review

Abstract: Cognitive-behavioral interventions are the most extensively researched form of psychological treatment and are increasingly offered through the Internet. Internet-based interventions may save therapist time, reduce waiting-lists, cut traveling time, and reach populations with health problems who can not easily access other more traditional forms of treatments. We conducted a systematic review of twelve randomized controlled or comparative trials. Studies were identified through systematic searches in major bibliographical databases. Three studies focused on patients suffering from pain, three on headache, and six on other health problems. The effects found for Internet interventions targeting pain were comparable to the effects found for face-to-face treatments, and the same was true for interventions aimed at headache. The other interventions also showed some effects, although effects differed across target conditions. Internet-delivered cognitive-behavioral interventions are a promising addition and complement to existing treatments. The Internet will most likely assume a major role in the future delivery of cognitive-behavioral interventions to patients with health problems.

GAD treatment and insulin secretion in recent-onset type 1 diabetes

Abstract: Background The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age. Methods We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 μg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied. Results Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (−0.21 vs. −0.27 nmol per liter [−0.62 vs. −0.81 ng per milliliter], P = 0.045), as did stimulated secretion measured as the area under the curve (−0.72 vs. −1.02 nmol per liter per 2 hours [−2.20 vs. −3.08 ng per milliliter per 2 hours], P = 0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response. Conclusions GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981.)

Cognition counts: A working memory system for ease of language understanding (ELU)

Abstract: A general working memory system for ease of language understanding (ELU, Ronnberg, 2003a) is presented. The purpose of the system is to describe and predict the dynamic interplay between explicit and implicit cognitive functions, especially in conditions of poorly perceived or poorly specified linguistic signals. In relation to speech understanding, the system based on (1) the quality and precision of phonological representations in long-term memory, (2) phonologically mediated lexical access speed, and (3) explicit, storage, and processing resources. If there is a mismatch between phonological information extracted from the speech signal and the phonological information represented in long-term memory, the system is assumed to produce a mismatch signal that invokes explicit processing resources. In the present paper, we focus on four aspects of the model which have led to the current, updated version: the language generality assumption; the mismatch assumption; chronological age; and the episodic buffer function of rapid, automatic multimodal binding of phonology (RAMBPHO). We evaluate the language generality assumption in relation to sign language and speech, and the mismatch assumption in relation to signal processing in hearing aids. Further, we discuss the effects of chronological age and the implications of RAMBPHO.

Lipids, Apolipoproteins, and Their Ratios in Relation to Cardiovascular Events With Statin Treatment

Abstract: Background— Low-density lipoprotein (LDL) cholesterol is the principal target of lipid-lowering therapy, but recent evidence has suggested more appropriate targets. We compared the relationships of on-treatment levels of LDL cholesterol, non–high-density lipoprotein (HDL) cholesterol, and apolipoprotein B, as well as ratios of total/HDL cholesterol, LDL/HDL cholesterol, and apolipoprotein B/A-I, with the occurrence of cardiovascular events in patients receiving statin therapy. Methods and Results— A post hoc analysis was performed that combined data from 2 prospective, randomized clinical trials in which 10 001 (“Treating to New Targets”) and 8888 (“Incremental Decrease in End Points through Aggressive Lipid Lowering”) patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment. In models with LDL cholesterol, non-HDL cholesterol and apolipoprotein B were positively associated with cardiovascular outcome, whereas a positive relationship with LDL cholesterol w...

Complete Characterization of the Pareto Boundary for the MISO Interference Channel

Abstract: In this correspondence, we study the achievable rate region of the multiple-input single-output (MISO) interference channel, under the assumption that all receivers treat the interference as additive Gaussian noise. Our main result is an explicit parametrization of the Pareto boundary for an arbitrary number of users and antennas. The parametrization describes the boundary in terms of a low-dimensional manifold. For the two-user case we show that a single real-valued parameter per user is sufficient to achieve all points on the Pareto boundary and that any point on the Pareto boundary corresponds to beamforming vectors that are linear combinations of the zero-forcing (ZF) and maximum-ratio transmission (MRT) beamformers. We further specialize the results to the MISO broadcast channel (BC). A numerical example illustrates the result.

Rapid magnetic resonance quantification on the brain: Optimization for clinical usage.

Abstract: A method is presented for rapid simultaneous quantification of the longitudinal T1 relaxation, the transverse T2 relaxation, the proton density (PD), and the amplitude of the local radio frequency ...

‘Legitimation’ and ‘development of positive externalities’: two key processes in the formation phase of technological innovation systems

Abstract: Responding to the climate change challenge requires a massive development and diffusion of carbon neutral technologies and, thus, emergence and growth of new socio-technical systems. This paper contributes to an improved understanding of the formative phase of new technological innovation systems (TIS) by outlining a framework for analysing TIS dynamics in terms of structural growth and key innovation-related processes (“functions”) and by discussing two of these functions at some depth: “legitimation” and “development of positive externalities”. Empirical examples are provided from case studies on renewable energy technologies. We highlight the problematic role of technology assessment studies in shaping legitimacy and the importance of early market formation for the emergence of “packs of entrepreneurs” that may contribute to legitimation, and discuss how exploitation of overlaps between different TISs may create positive externalities, opening up for a powerful “bottom-up” process of system growth. Ass...

Competition Versus Cooperation on the MISO Interference Channel

Abstract: We consider the problem of coordinating two competing multiple-antenna wireless systems (operators) that operate in the same spectral band. We formulate a rate region which is achievable by scalar coding followed by power allocation and beamforming. We show that all interesting points on the Pareto boundary correspond to transmit strategies where both systems use the maximum available power. We then argue that there is a fundamental need for base station cooperation when performing spectrum sharing with multiple transmit antennas. More precisely, we show that if the systems do not cooperate, there is a unique Nash equilibrium which is inefficient in the sense that the achievable rate is bounded by a constant, regardless of the available transmit power. An extension of this result to the case where the receivers use successive interference cancellation (SIC) is also provided. Next we model the problem of agreeing on beamforming vectors as a non-transferable utility (NTU) cooperative gametheoretic problem, with the two operators as players. Specifically we compute numerically the Nash bargaining solution, which is a likely resolution of the resource conflict assuming that the players are rational. Numerical experiments indicate that selfish but cooperating operators may achieve a performance which is close to the maximum-sum-rate bound.

Gene expression profiling of human decidual macrophages: evidence for immunosuppressive phenotype.

Abstract: Background: Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known. Methodology/Principal Findings: Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications. Conclusions/Significance: The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.

Nonoperative treatment of primary anterior shoulder dislocation in patients forty years of age and younger. a prospective twenty-five-year follow-up.

Abstract: Background: During 1978 and 1979, we initiated a prospective multicenter study to evaluate the results of nonoperative treatment of primary anterior shoulder dislocation. In the current report, we ...

Bioprocess optimization using design-of-experiments methodology.

Abstract: This review surveys recent applications of design-of-experiments (DoE) methodology in the development of biotechnological processes. Methods such as factorial design, response surface methodology, and (DoE) provide powerful and efficient ways to optimize cultivations and other unit operations and procedures using a reduced number of experiments. The multitude of interdependent parameters involved within a unit operation or between units in a bioprocess sequence may be substantially refined and improved by the use of such methods. Other bioprocess-related applications include strain screening evaluation and cultivation media balancing. In view of the emerging regulatory demands on pharmaceutical manufacturing processes, exemplified by the process analytical technology (PAT) initiative of the United States Food and Drug Administration, the use of experimental design approaches to improve process development for safer and more reproducible production is becoming increasingly important. Here, these options are highlighted and discussed with a few selected examples from antibiotic fermentation, expanded bed optimization, virus vector transfection of insect cell cultivation, feed profile adaptation, embryonic stem cell expansion protocols, and mammalian cell harvesting.

Estrogen-Dependent Signaling in a Molecularly Distinct Subclass of Aggressive Prostate Cancer

Abstract: BACKGROUND: The majority of prostate cancers harbor gene fusions of the 5'-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transfo ...

An energy efficient Swedish pulp and paper industry – exploring barriers to and driving forces for cost-effective energy efficiency investments

Abstract: Despite the need for increased industrial energy efficiency, studies indicate that cost-effective energy efficiency measures are not always implemented, which is explained by the existence of barri ...

Room-temperature spintronic effects in Alq3-based hybrid devices

Abstract: We report on efficient spin polarized injection and transport in long (102 nm) channels of Alq3 organic semiconductor. We employ vertical spin valve devices with a direct interface between the bottom manganite electrode and Alq3, while the top-electrode geometry consists of an insulating tunnel barrier placed between the “soft” organic semiconductor and the top Co electrode. This solution reduces the ubiquitous problem of the so-called ill-defined layer caused by metal penetration, which extends into the organic layer up to distances of about 50–100 nm and prevents the realization of devices with well-defined geometry. For our devices the thickness is defined with an accuracy of about 2.5 nm, which is near the Alq3 molecular size. We demonstrate efficient spin injection at both interfaces in devices with 100- and 200-nm-thick channels. We solve one of the most controversial problems of organic spintronics: the temperature limitations for spin transport in Alq3-based devices. We clarify this issue by achieving room-temperature spin valve operation through the improvement of spin injection properties of both ferromagnetic/Alq3 interfaces. In addition, we discuss the nature of the inverse sign of the spin valve effect in such devices proposing a mechanism for spin transport.