Showing papers by "University of Gothenburg published in 2008"

Spreading Dead Zones and Consequences for Marine Ecosystems

Abstract: Dead zones in the coastal oceans have spread exponentially since the 1960s and have serious consequences for ecosystem functioning. The formation of dead zones has been exacerbated by the increase in primary production and consequent worldwide coastal eutrophication fueled by riverine runoff of fertilizers and the burning of fossil fuels. Enhanced primary production results in an accumulation of particulate organic matter, which encourages microbial activity and the consumption of dissolved oxygen in bottom waters. Dead zones have now been reported from more than 400 systems, affecting a total area of more than 245,000 square kilometers, and are probably a key stressor on marine ecosystems.

The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria

Abstract: We normally live in symbiosis with approximately 10(13) bacteria present in the colon. Among the several mechanisms maintaining the bacteria/host balance, there is limited understanding of the structure, function, and properties of intestinal mucus. We now demonstrate that the mouse colonic mucus consists of two layers extending 150 mum above the epithelial cells. Proteomics revealed that both of these layers have similar protein composition, with the large gel-forming mucin Muc2 as the major structural component. The inner layer is densely packed, firmly attached to the epithelium, and devoid of bacteria. In contrast, the outer layer is movable, has an expanded volume due to proteolytic cleavages of the Muc2 mucin, and is colonized by bacteria. Muc2(-/-) mice have bacteria in direct contact with the epithelial cells and far down in the crypts, explaining the inflammation and cancer development observed in these animals. These findings show that the Muc2 mucin can build a mucus barrier that separates bacteria from the colon epithelia and suggest that defects in this mucus can cause colon inflammation.

Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk Patients

Abstract: Background The optimal combination drug therapy for hypertension is not established, although current U.S. guidelines recommend inclusion of a diuretic. We hypothesized that treatment with the combination of an angiotensin-converting–enzyme (ACE) inhibitor and a dihydropyridine calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic. Methods In a randomized, double-blind trial, we assigned 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide. The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization. Results The baseline characteristics of the two groups were similar. The trial was terminated early after a mean follow-up of 36 months, when the boundary of the prespecified stopping rule was exceeded. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril–amlodipine group and 132.5/74.4 mm Hg in the benazepril–hydrochlorothiazide group. There were 552 primary-outcome events in the benazepril–amlodipine group (9.6%) and 679 in the benazepril–hydrochlorothiazide group (11.8%), representing an absolute risk reduction with benazepril–amlodipine therapy of 2.2% and a relative risk reduction of 19.6% (hazard ratio, 0.80, 95% confidence interval [CI], 0.72 to 0.90; P<0.001). For the secondary end point of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, the hazard ratio was 0.79 (95% CI, 0.67 to 0.92; P = 0.002). Rates of adverse events were consistent with those observed from clinical experience with the study drugs. Conclusions The benazepril–amlodipine combination was superior to the benazepril–hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. (ClinicalTrials.gov number, NCT00170950.)

Emotional responses to music: The need to consider underlying mechanisms

Abstract: Research indicates that people value music primarily because of the emotions it evokes. Yet, the notion of musical emotions remains controversial, and researchers have so far been unable to offer a satisfactory account of such emotions. We argue that the study of musical emotions has suffered from a neglect of underlying mechanisms. Specifically, researchers have studied musical emotions without regard to how they were evoked, or have assumed that the emotions must be based on the "default" mechanism for emotion induction, a cognitive appraisal. Here, we present a novel theoretical framework featuring six additional mechanisms through which music listening may induce emotions: (1) brain stem reflexes, (2) evaluative conditioning, (3) emotional contagion, (4) visual imagery, (5) episodic memory, and (6) musical expectancy. We propose that these mechanisms differ regarding such characteristics as their information focus, ontogenetic development, key brain regions, cultural impact, induction speed, degree of volitional influence, modularity, and dependence on musical structure. By synthesizing theory and findings from different domains, we are able to provide the first set of hypotheses that can help researchers to distinguish among the mechanisms. We show that failure to control for the underlying mechanism may lead to inconsistent or non-interpretable findings. Thus, we argue that the new framework may guide future research and help to resolve previous disagreements in the field. We conclude that music evokes emotions through mechanisms that are not unique to music, and that the study of musical emotions could benefit the emotion field as a whole by providing novel paradigms for emotion induction.

Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41

Abstract: The distal human intestine harbors trillions of microbes that allow us to extract calories from otherwise indigestible dietary polysaccharides. The products of polysaccharide fermentation include short-chain fatty acids that are ligands for Gpr41, a G protein-coupled receptor expressed by a subset of enteroendocrine cells in the gut epithelium. To examine the contribution of Gpr41 to energy balance, we compared Gpr41-/- and Gpr41+/+ mice that were either conventionally-raised with a complete gut microbiota or were reared germ-free and then cocolonized as young adults with two prominent members of the human distal gut microbial community: the saccharolytic bacterium, Bacteroides thetaiotaomicron and the methanogenic archaeon, Methanobrevibacter smithii. Both conventionally-raised and gnotobiotic Gpr41-/- mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (+/+) littermates, despite similar levels of chow consumption. These differences are not evident when germ-free WT and germ-free Gpr41 knockout animals are compared. Functional genomic, biochemical, and physiologic studies of germ-free and cocolonized Gpr41-/- and +/+ littermates disclosed that Gpr41-deficiency is associated with reduced expression of PYY, an enteroendocrine cell-derived hormone that normally inhibits gut motility, increased intestinal transit rate, and reduced harvest of energy (short-chain fatty acids) from the diet. These results reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota.

Peri-implant diseases: Consensus Report of the Sixth European Workshop on Periodontology

Abstract: Issues related to peri-implant disease were discussed. It was observed that the most common lesions that occur, i.e. peri-implant mucositis and peri-implantitis are caused by bacteria. While the lesion of peri-implant mucositis resides in the soft tissues, peri-implantitis also affects the supporting bone. Peri-implant mucositis occurs in about 80% of subjects (50% of sites) restored with implants, and peri-implantitis in between 28% and 56% of subjects (12-40% of sites). A number of risk indicators were identified including (i) poor oral hygiene, (ii) a history of periodontitis, (iii) diabetes and (iv) smoking. It was concluded that the treatment of peri-implant disease must include anti-infective measures. With respect to peri-implant mucositis, it appeared that non-surgical mechanical therapy caused the reduction in inflammation (bleeding on probing) but also that the adjunctive use of antimicrobial mouthrinses had a positive effect. It was agreed that the outcome of non-surgical treatment of peri-implantitis was unpredictable. The primary objective of surgical treatment in peri-implantitis is to get access to the implant surface for debridement and decontamination in order to achieve resolution of the inflammatory lesion. There was limited evidence that such treatment with the adjunctive use of systemic antibiotics could resolve a number of peri-implantitis lesions. There was no evidence that so-called regenerative procedures had additional beneficial effects on treatment outcome.

Regulation of autophagy by cytoplasmic p53

Abstract: Multiple cellular stressors, including activation of the tumour suppressor p53, can stimulate autophagy. Here we show that deletion, depletion or inhibition of p53 can induce autophagy in human, mouse and nematode cells subjected to knockout, knockdown or pharmacological inhibition of p53. Enhanced autophagy improved the survival of p53-deficient cancer cells under conditions of hypoxia and nutrient depletion, allowing them to maintain high ATP levels. Inhibition of p53 led to autophagy in enucleated cells, and cytoplasmic, not nuclear, p53 was able to repress the enhanced autophagy of p53(-/-) cells. Many different inducers of autophagy (for example, starvation, rapamycin and toxins affecting the endoplasmic reticulum) stimulated proteasome-mediated degradation of p53 through a pathway relying on the E3 ubiquitin ligase HDM2. Inhibition of p53 degradation prevented the activation of autophagy in several cell lines, in response to several distinct stimuli. These results provide evidence of a key signalling pathway that links autophagy to the cancer-associated dysregulation of p53.

Definition and prevalence of peri-implant diseases.

Abstract: OBJECTIVES: The aim of the current review was to describe the prevalence of peri-implant diseases including peri-implant mucositis and peri-implantitis. MATERIAL AND METHODS: A MEDLINE search (PubMed) until December 2007 was conducted and different keywords related to the prevalence of peri-implant diseases were used. Cross-sectional and longitudinal studies including < or =50 implant-treated subjects exhibiting a function time of < or =5 years were considered. RESULTS AND CONCLUSION: The current review revealed that only a few studies provided data on the prevalence of peri-implant diseases. Cross-sectional studies on implant-treated subjects are rare and data from only two study samples were available. Peri-implant mucositis occurred in approximately 80% of the subjects and in 50% of the implants. Peri-implantitis was found in 28% and < or =56% of subjects and in 12% and 43% of implant sites.

Who is an author

Abstract: Authorship of scientific papers is an important activity for the academic researcher, as papers provide a forum for communication of scientific results and can be used to provide references of scientific merit. Authors are responsible for the content of reports, and of course, the presentation of results should be as accurate and unbiased as possible. However, manuscripts can be written in a variety of ways using different words and expressions. In addition, each scientific author does not need to write every single word in the manuscript nor is he/she a novelist. The definition of scientific authorship is not clear-cut and is interpreted differently in various scientific communities. This issue is far from new, and during my years I have seen several commentaries on this subject. Kassirer and Angell, Editors of the New England Journal of Medicine, discussed the issue of authorship in an Editorial published in 1991. I consider this Editorial important as it emphasizes the importance of scientific input and the need to define the contribution of an author particularly in multicenter trials [1]. In order to define roles more clearly, Rennie et al. suggested using “contributors” as a more appropriate designation for some authors [2]. The scientific paper when published is open for discussion, and all authors should be able to provide input of scientific value. All submissions to the European Journal of Heart Failure must include a statement about the role of each author and a signed document defining each author's contribution. This requirement was implemented as a consequence of several reports of papers being published without the knowledge of some of the co-authors. An example is the Sudbo paper, published in the Lancet in 2005, in which several of the 13 co-authors claimed that they were not aware of the submission or the full result [3]. The European Journal of Heart Failure complies with the definitions of authorship as outlined by the International Committee of Medical Journal Editors which is available online at: http://www.icmje.org. We have no further requirement more than an author should have made a scientific contribution. In our May issue, we published an Ethics statement from the HEART network [4]. In this statement, we repeat what we have stated on our website since June last year. The purpose of the statement is to ensure transparency

Comparative analysis of human gut microbiota by barcoded pyrosequencing.

Abstract: Humans host complex microbial communities believed to contribute to health maintenance and, when in imbalance, to the development of diseases. Determining the microbial composition in patients and healthy controls may thus provide novel therapeutic targets. For this purpose, high-throughput, cost-effective methods for microbiota characterization are needed. We have employed 454-pyrosequencing of a hyper-variable region of the 16S rRNA gene in combination with sample-specific barcode sequences which enables parallel in-depth analysis of hundreds of samples with limited sample processing. In silico modeling demonstrated that the method correctly describes microbial communities down to phylotypes below the genus level. Here we applied the technique to analyze microbial communities in throat, stomach and fecal samples. Our results demonstrate the applicability of barcoded pyrosequencing as a high-throughput method for comparative microbial ecology.

What Is Quality of Government? A Theory of Impartial Government Institutions

Abstract: The recent growth in research on "good governance" and the quality of government institutions has been propelled by empirical findings that show that such institutions may hold the key to understanding economic growth and social welfare in developing and transition countries. We argue, however, that a key issue has not been addressed, namely, what quality of government (QoG) actually means at the conceptual level. Based on analyses of political theory, we propose a more coherent and specific definition of QoG: the impartiality of institutions that exercise government authority. We relate the idea of impartiality to a series of criticisms stemming from the fields of public administration, public choice, multiculturalism, and feminism. To place the theory of impartiality in a larger context, we then contrast its scope and meaning with that of a threefold set of competing concepts of quality of government: democracy, the rule of law, and efficiency/effectiveness.

The ecotoxicology and chemistry of manufactured nanoparticles

Abstract: The emerging literature on the ecotoxicity of nanoparticles and nanomaterials is summarised, then the fundamental physico-chemistry that governs particle behaviour is explained in an ecotoxicological context. Techniques for measuring nanoparticles in various biological and chemical matrices are also outlined. The emerging ecotoxicological literature shows toxic effects on fish and invertebrates, often at low mg l−1 concentrations of nanoparticles. However, data on bacteria, plants, and terrestrial species are particularly lacking at present. Initial data suggest that at least some manufactured nanoparticles may interact with other contaminants, influencing their ecotoxicity. Particle behaviour is influenced by particle size, shape, surface charge, and the presence of other materials in the environment. Nanoparticles tend to aggregate in hard water and seawater, and are greatly influenced by the specific type of organic matter or other natural particles (colloids) present in freshwater. The state of dispersion will alter ecotoxicity, but many abiotic factors that influence this, such as pH, salinity, and the presence of organic matter remain to be systematically investigated as part of ecotoxicological studies. Concentrations of manufactured nanoparticles have rarely been measured in the environment to date. Various techniques are available to characterise nanoparticles for exposure and dosimetry, although each of these methods has advantages and disadvantages for the ecotoxicologist. We conclude with a consideration of implications for environmental risk assessment of manufactured nanoparticles.

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Abstract: BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)

Intraspecific ITS Variability in the Kingdom Fungi as Expressed in the International Sequence Databases and Its Implications for Molecular Species Identification

Abstract: The internal transcribed spacer (ITS) region of the nuclear ribosomal repeat unit is the most popular locus for species identification and subgeneric phylogenetic inference in sequence-based mycological research. The region is known to show certain variability even within species, although its intraspecific variability is often held to be limited and clearly separated from interspecific variability. The existence of such a divide between intra- and interspecific variability is implicitly assumed by automated approaches to species identification, but whether intraspecific variability indeed is negligible within the fungal kingdom remains contentious. The present study estimates the intraspecific ITS variability in all fungi presently available to the mycological community through the international sequence databases. Substantial differences were found within the kingdom, and the results are not easily correlated to the taxonomic affiliation or nutritional mode of the taxa considered. No single unifying yet stringent upper limit for intraspecific variability, such as the canonical 3% threshold, appears to be applicable with the desired outcome throughout the fungi. Our results caution against simplified approaches to automated ITS-based species delimitation and reiterate the need for taxonomic expertise in the translation of sequence data into species names.

Definition, assessment and treatment of wheezing disorders in preschool children: An evidence-based approach

Abstract: There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Properties of the Glomerular Barrier and Mechanisms of Proteinuria

Abstract: This review focuses on the intricate properties of the glomerular barrier. Other reviews have focused on podocyte biology, mesangial cells, and the glomerular basement membrane (GBM). However, since all components of the glomerular membrane are important for its function, proteinuria will occur regardless of which layer is affected by disease. We review the properties of endothelial cells and their surface layer, the GBM, and podocytes, discuss various methods of studying glomerular permeability, and analyze data concerning the restriction of solutes by size, charge, and shape. We also review the physical principles of transport across biological or artificial membranes and various theoretical models used to predict the fluxes of solutes and water. The glomerular barrier is highly size and charge selective, in qualitative agreement with the classical studies performed 30 years ago. The small amounts of albumin filtered will be reabsorbed by the megalin-cubulin complex and degraded by the proximal tubular cells. At present, there is no unequivocal evidence for reuptake of intact albumin from urine. The cellular components are the key players in restricting solute transport, while the GBM is responsible for most of the resistance to water flow across the glomerular barrier.

Risk factors for myocardial infarction in women and men: insights from the INTERHEART study

Abstract: Aims Coronary heart disease (CHD) is a leading cause of death among men and women globally. Women develop CHD about 10 years later than men, yet the reasons for this are unclear. The purpose of this report is to determine if differences in risk factor distributions exist between women and men across various age categories to help explain why women develop acute MI later than men. Methods and results We used the INTERHEART global case–control study including 27 098 participants from 52 countries, 6787 of whom were women. The median age of first acute MI was higher in women than men (65 vs. 56 years; P < 0.0001). Nine modifiable risk factors were associated with MI in women and men. Hypertension [2.95(2.66 –3.28) vs. 2.32(2.16–2.48)], diabetes [4.26(3.68–4.94) vs. 2.67(2.43–2.94), physical activity [0.48(0.41–0.57) vs. 0.77(0.71–0.83)], and moderate alcohol use [0.41(0.34–0.50) vs. 0.88(0.82–0.94)] were more strongly associated with MI among women than men. The association of abnormal lipids, current smoking, abdominal obesity, high risk diet, and psychosocial stress factors with MI was similar in women and men. Risk factors associations were generally stronger among younger individuals compared to older women and men. The population attributable risk (PAR) of all nine risk factors exceeded 94%, and was similar among women and men (96 vs. 93%). Men were significantly more likely to suffer a MI prior to 60 years of age than were women, however, after adjusting for levels of risk factors, the sex difference in the probability of MI cases occurring before the age of 60 years was reduced by more than 80%. Conclusion Women experience their first acute MI on average 9 years later than men. Nine modifiable risk factors are significantly associated with acute MI in both men and women and explain greater than 90% of the PAR. The difference in age of first MI is largely explained by the higher risk factor levels at younger ages in men compared to women.

Telmisartan to prevent recurrent stroke and cardiovascular events.

Abstract: BACKGROUND: Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. METHODS: In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. RESULTS: The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10). CONCLUSIONS: Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.)

The State and Social Capital: An Institutional Theory of Generalized Trust

Abstract: The purpose of this article is to present an alternative theory on the generation of social capital. In the discussion about the sources of social capital it has been stressed that generalized trust is built up by the citizens themselves through a culture that permeates the networks and organizations of civil society. Since this approach has run into conceptual problems and has produced only mixed empirical evidence, we like to highlight instead how social capital is embedded in and linked to formal political and legal institutions. Not all political institutions matter equally, however. In fact, we argue that trust thrives most in societies with effective, impartial and fair street-level bureaucracies. The article presents the causal mechanism between these institutional characteristics and generalized trust, and illustrates its validity in a crossnational context.

Central obesity and increased risk of dementia more than three decades later

Abstract: Background: Numerous reports show that a centralized distribution of adiposity is a more dangerous risk factor for cardiovascular disease and diabetes than total body obesity. No studies have evaluated whether the same pattern exists with dementia. The objective was to evaluate the association between midlife central obesity and risk of dementia three decades later. Methods: A longitudinal analysis was conducted of 6,583 members of Kaiser Permanente of Northern California who had their sagittal abdominal diameter (SAD) measured in 1964 to 1973. Diagnoses of dementia were from medical records an average of 36 years later, January 1, 1994, to June 16, 2006. Cox proportional hazard models adjusted for age, sex, race, education, marital status, diabetes, hypertension, hyperlipidemia, stroke, heart disease, and medical utilization were conducted. Results: A total of 1,049 participants (15.9%) were diagnosed with dementia. Compared with those in the lowest quintile of SAD, those in the highest had nearly a threefold increased risk of dementia (hazard ratio, 2.72; 95% CI, 2.33–3.33), and this was only mildly attenuated after adding body mass index (BMI) to the model (hazard ratio, 1.92; 95% CI, 1.58 –2.35). Those with high SAD (25 cm) and normal BMI had an increased risk (hazard ratio, 1.89; 95% CI, 0.98 – 3.81) vs those with low SAD (25 cm) and normal BMI (18.5–24.9 kg/m 2 ), whereas those both obese (BMI 30 kg/m 2 ) and with high SAD had the highest risk of dementia (HR, 3.60; 95% CI,

Detection and characterization of engineered nanoparticles in food and the environment

Abstract: Nanotechnology is developing rapidly and, in the future, it is expected that increasingly more products will contain some sort of nanomaterial. However, to date, little is known about the occurrence, fate and toxicity of nanoparticles. The limitations in our knowledge are partly due to the lack of methodology for the detection and characterisation of engineered nanoparticles in complex matrices, i.e. water, soil or food. This review provides an overview of the characteristics of nanoparticles that could affect their behaviour and toxicity, as well as techniques available for their determination. Important properties include size, shape, surface properties, aggregation state, solubility, structure and chemical composition. Methods have been developed for natural or engineered nanomaterials in simple matrices, which could be optimized to provide the necessary information, including microscopy, chromatography, spectroscopy, centrifugation, as well as filtration and related techniques. A combination of these is often required. A number of challenges will arise when analysing environmental and food materials, including extraction challenges, the presence of analytical artifacts caused by sample preparation, problems of distinction between natural and engineered nanoparticles and lack of reference materials. Future work should focus on addressing these challenges.

Solution structure of the integral human membrane protein VDAC-1 in detergent micelles.

Abstract: The voltage-dependent anion channel (VDAC) mediates trafficking of small molecules and ions across the eukaryotic outer mitochondrial membrane VDAC also interacts with antiapoptotic proteins from the Bcl-2 family, and this interaction inhibits release of apoptogenic proteins from the mitochondrion We present the nuclear magnetic resonance (NMR) solution structure of recombinant human VDAC-1 reconstituted in detergent micelles It forms a 19-stranded beta barrel with the first and last strand parallel The hydrophobic outside perimeter of the barrel is covered by detergent molecules in a beltlike fashion In the presence of cholesterol, recombinant VDAC-1 can form voltage-gated channels in phospholipid bilayers similar to those of the native protein NMR measurements revealed the binding sites of VDAC-1 for the Bcl-2 protein Bcl-x(L), for reduced beta-nicotinamide adenine dinucleotide, and for cholesterol Bcl-x(L) interacts with the VDAC barrel laterally at strands 17 and 18

Crowding Out in Blood Donation: Was Titmuss Right?

Abstract: In his seminal 1970 book, The Gift Relationship, Richard Titmuss argued that monetary compensation for donating blood might crowd out the supply of blood donors. To test this claim we carried out a field experiment with three different treatments. In the first treatment subjects were given the opportunity to become blood donors without any compensation. In the second treatment subjects received a payment of SEK 50 (about $7) for becoming blood donors, and in the third treatment subjects could choose between a SEK 50 payment and donating SEK 50 to charity. The results differ markedly between men and women. For men the supply of blood donors is not significantly different among the three experimental groups. For women there is a significant crowding-out effect. The supply of blood donors decreases by almost half when a monetary payment is introduced. There is also a significant effect of allowing individuals to donate the payment to charity, and this effect fully counteracts the crowding-out effect. (JEL: C93, D64, I18, Z13)

Nanoparticle analysis and characterization methodologies in environmental risk assessment of engineered nanoparticles

Abstract: Environmental risk assessments of engineered nanoparticles require thorough characterization of nanoparticles and their aggregates. Furthermore, quantitative analytical methods are required to determine environmental concentrations and enable both effect and exposure assessments. Many methods still need optimization and development, especially for new types of nanoparticles in water, but extensive experience can be gained from the fields of environmental chemistry of natural nanomaterials and from fundamental colloid chemistry. This review briefly describes most methods that are being exploited in nanoecotoxicology for analysis and characterization of nanomaterials. Methodological aspects are discussed in relation to the fields of nanometrology, particle size analysis and analytical chemistry. Differences in both the type of size measures (length, radius, aspect ratio, etc.), and the type of average or distributions afforded by the specific measures are compared. The strengths of single particle methods, such as electron microscopy and atomic force microscopy, with respect to imaging, shape determinations and application to particle process studies are discussed, together with their limitations in terms of counting statistics and sample preparation. Methods based on the measurement of particle populations are discussed in terms of their quantitative analyses, but the necessity of knowing their limitations in size range and concentration range is also considered. The advantage of combining complementary methods is highlighted.

Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme.

Abstract: Aims To determine whether the risk of adverse cardiovascular (CV) outcomes associated with diabetes differs in patients with low and preserved ejection fraction (EF) heart failure (HF). Methods and results We analysed outcomes in the Candesartan in Heart failure—Assessment of Reduction in Mortality and morbidity (CHARM) programme which randomized 7599 patients with symptomatic HF and a broad range of EF. The prevalence of diabetes was 28.3% in patients with preserved EF (>40%) and 28.5% in those with low EF (≤40%). Diabetes was associated with a greater relative risk of CV death or HF hospitalization in patients with preserved EF [hazard ratio (HR) 2.0 (1.70–2.36)] than in patients with low EF [HR 1.60 (1.44–1.77); interaction test P = 0.0009]. For all-cause mortality, the risk conferred by diabetes was similar in both low and preserved EF groups. The effect of candesartan in reducing CV morbidity and mortality outcomes was not modified by having diabetes at baseline ( P = 0.09 test for interaction). Conclusion Diabetes was an independent predictor of CV morbidity and mortality in patients with HF, regardless of EF. The relative risk of CV death or HF hospitalization conferred by diabetes was significantly greater in patients with preserved when compared with those with low EF HF.

Evolutionary Conservation of Human Drug Targets in Organisms used for Environmental Risk Assessments

Abstract: Pharmaceuticals are typically found in very low concentrations in the aquatic environment. Accordingly, environmental effects clearly assigned to residual drugs are consistent with high affinity interactions with conserved targets in affected wildlife species rather than with a general toxic effect. Thus, evolutionarily well-conserved targets in a given species are associated with an increased risk. In this study orthologs for 1318 human drug targets were predicted in 16 species of which several are relevant for ecotoxicity testing. The conservation of different functional categories of targets was also analyzed. Zebrafish had orthologs to 86% of the drug targets while only 61% were conserved in Daphnia and 35% in green alga. The predicted presence and absence of orthologs agrees well with published experimental data on the potential for specific drug target interaction in various species. Based on the conservation of targets we propose that aquatic environmental risk assessments for human drugs should always include comprehensive studies on aquatic vertebrates. Furthermore, individual targets, especially enzymes, are well conserved suggesting that tests on evolutionarily distant organisms would be highly relevant for certain drugs. We propose that the results can guide environmental risk assessments by improving the possibilities to identify species sensitive to certain types of pharmaceuticals or to other contaminants that act through well defined mechanisms of action. Moreover, we suggest that the results can be used to interpret the relevance of existing ecotoxicity data.

The Playing Learning Child: Towards a pedagogy of early childhood

Abstract: From children's own perspective, play and learning are not always separate in practices during early years. The purpose of this article is, first, to scrutinise the background and character of early years education in terms of play and learning. Second, to elaborate the findings of several years of research about children's learning in preschool related to the curriculum of early years education and, finally, to propose a sustainable pedagogy for the future, which does not separate play from learning but draws upon the similarities in character in order to promote creativity in future generations. Introducing the notions of act and object of learning and play (by act we mean how children play and learn and with the object we mean what children play and learn) we will chisel out an alternative early childhood education approach, here called developmental pedagogy, based on recent research in the field of play and learning, but also related to earlier approaches to early education.