| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are 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 monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Amelino-Camelia, G., et al.
(författare)
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Physics with the KLOE-2 experiment at the upgraded DA Phi NE
- 2010
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 68:3-4, s. 619-681
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Forskningsöversikt (refereegranskat)abstract
- Investigation at a f-factory can shed light on several debated issues in particle physics. We discuss: (i) recent theoretical development and experimental progress in kaon physics relevant for the Standard Model tests in the flavor sector, (ii) the sensitivity we can reach in probing CPT and Quantum Mechanics from time evolution of entangled-kaon states, (iii) the interest for improving on the present measurements of non-leptonic and radiative decays of kaons and eta/eta' mesons, (iv) the contribution to understand the nature of light scalar mesons, and (v) the opportunity to search for narrow di-lepton resonances suggested by recent models proposing a hidden dark-matter sector. We also report on the e(+)e(-) physics in the continuum with the measurements of (multi) hadronic cross sections and the study of gamma gamma processes.
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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)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.
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| 4. |
- Danesh, John, et al.
(författare)
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Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis
- 2005
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 294:14, s. 1799-1809
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Forskningsöversikt (refereegranskat)abstract
- CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.
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| 5. |
- Franks, P. W., et al.
(författare)
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Technological readiness and implementation of genomic-driven precision medicine for complex diseases
- 2021
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:3, s. 602-620
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Forskningsöversikt (refereegranskat)abstract
- The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.
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| 6. |
- Rescorla, Leslie, et al.
(författare)
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International Epidemiology of Child and Adolescent Psychopathology II: Integration and Applications of Dimensional Findings From 44 Societies
- 2012
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567. ; 51:12, s. 1273-1283
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Forskningsöversikt (refereegranskat)abstract
- Objective: To build on Achenbach, Rescorla, and Ivanova (2012) by (a) reporting new international findings for parent, teacher, and self-ratings on the Child Behavior Checklist, Youth Self-Report, and Teacher's Report Form; (b) testing the fit of syndrome models to new data from 17 societies, including previously underrepresented regions; (c) testing effects of society gender, and age in 44 societies by integrating new and previous data; (d) testing cross-society correlations between mean item ratings; (e) describing the construction of multisociety norms; (f) illustrating clinical applications. Method: Confirmatory factor analyses (CFAs) of parent, teacher, and self-ratings, performed separately for each society; tests of societal, gender, and age effects on dimensional syndrome scales, DSM-oriented scales, Internalizing, Externalizing, and Total Problems scales; tests of agreement between low, medium, and high ratings of problem items across societies. Results: CFAs supported the tested syndrome models in all societies according to the primary fit index (Root Mean Square Error of Approximation [RMSEA]), but less consistently according to other indices; effect sizes were small-to-medium for societal differences in scale scores, but very small for gender, age, and interactions with society; items received similarly low, medium, or high ratings in different societies; problem scores from 44 societies fit three sets of multisociety norms. Conclusions: Statistically derived syndrome models fit parent, teacher, and self-ratings when tested individually in all 44 societies according to RMSEAs (but less consistently according to other indices). Small to medium differences in scale scores among societies supported the use of low-, medium-, and high-scoring norms in clinical assessment of individual children. J. Am. Acad. Child Aclolesc. Psychiatry; 2012; 51(12):1273-1283.
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| 7. |
- Aguilar, Maria I., et al.
(författare)
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Treatment of warfarin-associated intracerebral hemorrhage: Literature review and expert opinion
- 2007
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Ingår i: Mayo Clinic Proceedings. - 0025-6196. ; 82:1, s. 82-92
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Forskningsöversikt (refereegranskat)abstract
- Wider use of oral anticoagulants has led to an increasing frequency of warfarin-related intracerebral hemorrhage (ICH). The high early mortality of approximately 50% has remained stable in recent decades. In contrast to spontaneous ICH, the duration of bleeding is, 12 to 24 hours in many patients, offering a longer opportunity for Intervention. Treatment varies widely, and optimal therapy has yet to be defined. An OVID search was conducted from January 1996 to January 2006, combining the terms warfarin or anticoagulation with intracranial hemorrhage or intracerebral hemorrhage. Seven experts on clinical stroke, neurologic intensive care, and hematology were provided with the available information and were asked to independently address 3 clinical scenarios about acute reversal and resumption of anticoagulation in the setting of warfarin-associated ICH. No randomized trials assessing clinical outcomes were found on management of warfarin-associated ICH. All experts agreed that anticoagulation should be urgently reversed, but how to achieve it varied from use of prothrombin complex concentrates only (3 experts) to recombinant factor Vila only (2 experts) to recombinant factor Vila along with fresh frozen plasma (1 expert) and prothrombin complex concentrates or fresh frozen plasma (1 expert). All experts favored resumption of warfarin therapy within 3 to 10 days of ICH in stable patients in whom subsequent anticoagulation is mandatory. No general agreement occurred regarding subsequent anticoagulation of patients with atrial fibrillation who survived warfarin-associated ICH. For warfarin-associated ICH, discontinuing warfarin therapy with administration of vitamin K does not reverse the hemostatic defect for many hours and is inadequate. Reasonable management based on expert opinion includes a wide range of additional measures to reverse anticoagulation in the absence of solid evidence.
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| 8. |
- Ahrén, Bo, et al.
(författare)
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Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man.
- 2011
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 13:9, s. 775-783
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Forskningsöversikt (refereegranskat)abstract
- Inhibition of dipeptidyl peptidase-4 (DPP-4) by vildagliptin prevents degradation of glucagon-like peptide-1 (GLP-1) and reduces glycemia in type 2 diabetes, with low risk for hypoglycemia and no weight gain. Vildagliptin binds covalently to the catalytic site of DPP-4, eliciting prolonged enzyme inhibition. This raises intact GLP-1 levels, both after meal ingestion and in the fasting state. Vildagliptin has been shown to stimulate insulin secretion and to inhibit glucagon secretion in a glucose-dependent manner. At hypoglycemic levels, the counterregulatory glucagon response is enhanced relative to baseline by vildagliptin. Vildagliptin also inhibits hepatic glucose production, mainly through changes in islet hormone secretion, and improves insulin sensitivity, as determined with a variety of methods. These effects underlie the improved glycemia with low risk for hypoglycemia. Vildagliptin also suppresses postprandial triglyceride-rich lipoprotein levels after ingestion of a fat-rich meal and reduces fasting lipolysis, suggesting inhibition of fat absorption and reduced triglyceride stores in non-fat tissues. The large body of knowledge on vildagliptin regarding enzyme binding, incretin and islet hormone secretion and glucose and lipid metabolism is summarized, with discussion of the integrated mechanisms and comparison with other DPP-4 inhibitors and GLP-1 receptor activators, where appropriate.
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| 9. |
- Al-Haddad, Benjamin J S, et al.
(författare)
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The fetal origins of mental illness.
- 2019
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 221:6, s. 549-562
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Forskningsöversikt (refereegranskat)abstract
- The impact of infections and inflammation during pregnancy on the developing fetal brain remains incompletely defined, with important clinical and research gaps. Although the classic infectious TORCH pathogens (ie, Toxoplasma gondii, rubella virus, cytomegalovirus [CMV], herpes simplex virus) are known to be directly teratogenic, emerging evidence suggests that these infections represent the most extreme end of a much larger spectrum of injury. We present the accumulating evidence that prenatal exposure to a wide variety of viral and bacterial infections-or simply inflammation-may subtly alter fetal brain development, leading to neuropsychiatric consequences for the child later in life. The link between influenza infections in pregnant women and an increased risk for development of schizophrenia in their children was first described more than 30 years ago. Since then, evidence suggests that a range of infections during pregnancy may also increase risk for autism spectrum disorder and depression in the child. Subsequent studies in animal models demonstrated that both pregnancy infections and inflammation can result in direct injury to neurons and neural progenitor cells or indirect injury through activation of microglia and astrocytes, which can trigger cytokine production and oxidative stress. Infectious exposures can also alter placental serotonin production, which can perturb neurotransmitter signaling in the developing brain. Clinically, detection of these subtle injuries to the fetal brain is difficult. As the neuropsychiatric impact of perinatal infections or inflammation may not be known for decades after birth, our construct for defining teratogenic infections in pregnancy (eg, TORCH) based on congenital anomalies is insufficient to capture the full adverse impact on the child. We discuss the clinical implications of this body of evidence and how we might place greater emphasis on prevention of prenatal infections. For example, increasing uptake of the seasonal influenza vaccine is a key strategy to reduce perinatal infections and the risk for fetal brain injury. An important research gap exists in understanding how antibiotic therapy during pregnancy affects the fetal inflammatory load and how to avoid inflammation-mediated injury to the fetal brain. In summary, we discuss the current evidence and mechanisms linking infections and inflammation with the increased lifelong risk of neuropsychiatric disorders in the child, and how we might improve prenatal care to protect the fetal brain.
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| 10. |
- Andersson, Bo, et al.
(författare)
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Small x phenomenology: summary and status
- 2002
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 25:1, s. 77-101
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Forskningsöversikt (refereegranskat)abstract
- The aim of this paper is to summarize the general status of our understanding of small-x physics. It is based on presentations and discussions at an informal meeting OIL this topic held in Lund, Sweden, in March 2001. This document also marks the founding of an informal collaboration between experimentalists and theoreticians with a special interest in small-x physics. This paper is dedicated to the memory of Bo Andersson. who died unexpectedly from a heart attack on March 4th, 2002.
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| 11. |
- Butcher, Ken, et al.
(författare)
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Thrombolysis in the developing world: is there a role for streptokinase?
- 2013
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4949 .- 1747-4930. ; 8:7, s. 560-565
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Forskningsöversikt (refereegranskat)abstract
- Intravenous thrombolysis with tissue plasminogen activator is the only proven acute therapy for ischemic stroke. This therapy has not been translated into clinical practice in the developing world primarily due to economic constraints. Streptokinase, a lower cost alternative thrombolytic agent, is widely available in developing countries where it is utilized to treat patients with acute coronary syndromes. Although this drug has previously been found to be ineffective in ischemic stroke, the lack of benefit may have been related to a number of factors related to trial design rather than the drug itself. Specific features of prior trial designs that may have adversely affected outcomes include a prolonged treatment window, inclusion of patients with established infarction on computed tomography scan, failure to treat excessive arterial pressures, a fixed dose of streptokinase, and concomitant use of antithrombotic medications. Given the lack of therapeutic alternatives in developing countries, a new trial of streptokinase in acute stroke, utilizing stricter inclusion criteria similar to those in more recent thrombolytic studies, appears warranted.
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| 12. |
- Cadilhac, Dominique A, et al.
(författare)
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National stroke registries for monitoring and improving the quality of hospital care: A systematic review.
- 2016
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4949 .- 1747-4930. ; 11:1, s. 28-40
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Forskningsöversikt (refereegranskat)abstract
- Routine monitoring of the quality of stroke care is becoming increasingly important since patient outcomes could be improved with better access to proven treatments. It remains unclear how many countries have established a national registry for monitoring stroke care.
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| 13. |
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| 14. |
- Eller, Nanna H, et al.
(författare)
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Work-related psychosocial factors and the development of ischemic heart disease : a systematic review.
- 2009
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Ingår i: Cardiology in review. - 1538-4683. ; 17:2, s. 83-97
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- The literature on the relationship between work-related psychosocial factors and the development of ischemic heart disease (IHD) was systematically reviewed: 33 articles presented 51 analyses of studies involving male participants, 18 analyses involving female participants, and 8 analyses with both genders. Twenty of the studies originated in the Nordic countries, and the major dimensions of the Demand-Control Model were the focus of 23 articles. A balanced evaluation of the studies indicates moderate evidence that high psychologic demands, lack of social support, and iso-strain are risk factors for IHD among men. Studies performed during recent years have not shown evidence for lack of control as a risk factor for IHD. Several studies have shown that job strain is a risk factor, but in the more recent ones, these associations can be fully explained by the association between demands and disease risk. Insufficient evidence was found for a relationship between IHD and effort-reward imbalance, injustice, job insecurity, or long working hours. Studies involving women are too few to draw any conclusion concerning women, work stress, and IHD.
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| 15. |
- Fleming, Stephen A., et al.
(författare)
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An expert panel on the adequacy of safety data and physiological roles of dietary bovine osteopontin in infancy
- 2024
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Ingår i: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 11
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Forskningsöversikt (refereegranskat)abstract
- Human milk, due to its unique composition, is the optimal standard for infant nutrition. Osteopontin (OPN) is abundant in human milk but not bovine milk. The addition of bovine milk osteopontin (bmOPN) to formula may replicate OPN’s concentration and function in human milk. To address safety concerns, we convened an expert panel to assess the adequacy of safety data and physiological roles of dietary bmOPN in infancy. The exposure of breastfed infants to human milk OPN (hmOPN) has been well-characterized and decreases markedly over the first 6 months of lactation. Dietary bmOPN is resistant to gastric and intestinal digestion, absorbed and cleared from circulation within 8–24 h, and represents a small portion (<5%) of total plasma OPN. Label studies on hmOPN suggest that after 3 h, intact or digested OPN is absorbed into carcass (62%), small intestine (23%), stomach (5%), and small intestinal perfusate (4%), with <2% each found in the cecum, liver, brain, heart, and spleen. Although the results are heterogenous with respect to bmOPN’s physiologic impact, no adverse impacts have been reported across growth, gastrointestinal, immune, or brain-related outcomes. Recombinant bovine and human forms demonstrate similar absorption in plasma as bmOPN, as well as effects on cognition and immunity. The panel recommended prioritization of trials measuring a comprehensive set of clinically relevant outcomes on immunity and cognition to confirm the safety of bmOPN over that of further research on its absorption, distribution, metabolism, and excretion. This review offers expert consensus on the adequacy of data available to assess the safety of bmOPN for use in infant formula, aiding evidence-based decisions on the formulation of infant formula.
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| 16. |
- Hachinski, Vladimir, et al.
(författare)
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Preventing dementia by preventing stroke : The Berlin Manifesto
- 2019
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:7, s. 961-984
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Forskningsöversikt (refereegranskat)abstract
- The incidence of stroke and dementia are diverging across the world, rising for those in low- and middle-income countries and falling in those in high-income countries. This suggests that whatever factors cause these trends are potentially modifiable. At the population level, neurological disorders as a group account for the largest proportion of disability-adjusted life years globally (10%). Among neurological disorders, stroke (42%) and dementia (10%) dominate. Stroke and dementia confer risks for each other and share some of the same, largely modifiable, risk and protective factors. In principle, 90% of strokes and 35% of dementias have been estimated to be preventable. Because a stroke doubles the chance of developing dementia and stroke is more common than dementia, more than a third of dementias could be prevented by preventing stroke. Developments at the pathological, pathophysiological, and clinical level also point to new directions. Growing understanding of brain pathophysiology has unveiled the reciprocal interaction of cerebrovascular disease and neurodegeneration identifying new therapeutic targets to include protection of the endothelium, the blood-brain barrier, and other components of the neurovascular unit. In addition, targeting amyloid angiopathy aspects of inflammation and genetic manipulation hold new testable promise. In the meantime, accumulating evidence suggests that whole populations experiencing improved education, and lower vascular risk factor profiles (e.g., reduced prevalence of smoking) and vascular disease, including stroke, have better cognitive function and lower dementia rates. At the individual levels, trials have demonstrated that anticoagulation of atrial fibrillation can reduce the risk of dementia by 48% and that systolic blood pressure lower than 140 mmHg may be better for the brain. Based on these considerations, the World Stroke Organization has issued a proclamation, endorsed by all the major international organizations focused on global brain and cardiovascular health, calling for the joint prevention of stroke and dementia. This article summarizes the evidence for translation into action.
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| 17. |
- Hachinski, Vladimir, et al.
(författare)
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Preventing dementia by preventing stroke : The Berlin Manifesto
- 2024
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949.
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Forskningsöversikt (refereegranskat)abstract
- The incidence of stroke and dementia are diverging across the world, rising for those in low-and middle-income countries and falling in those in high-income countries. This suggests that whatever factors cause these trends are potentially modifiable. At the population level, neurological disorders as a group account for the largest proportion of disability-adjusted life years globally (10%). Among neurological disorders, stroke (42%) and dementia (10%) dominate. Stroke and dementia confer risks for each other and share some of the same, largely modifiable, risk and protective factors. In principle, 90% of strokes and 35% of dementias have been estimated to be preventable. Because a stroke doubles the chance of developing dementia and stroke is more common than dementia, more than a third of dementias could be prevented by preventing stroke. Developments at the pathological, pathophysiological, and clinical level also point to new directions. Growing understanding of brain pathophysiology has unveiled the reciprocal interaction of cerebrovascular disease and neurodegeneration identifying new therapeutic targets to include protection of the endothelium, the blood-brain barrier, and other components of the neurovascular unit. In addition, targeting amyloid angiopathy aspects of inflammation and genetic manipulation hold new testable promise. In the meantime, accumulating evidence suggests that whole populations experiencing improved education, and lower vascular risk factor profiles (e.g., reduced prevalence of smoking) and vascular disease, including stroke, have better cognitive function and lower dementia rates. At the individual levels, trials have demonstrated that anticoagulation of atrial fibrillation can reduce the risk of dementia by 48% and that systolic blood pressure lower than 140 mmHg may be better for the brain. Based on these considerations, the World Stroke Organization has issued a proclamation, endorsed by all the major international organizations focused on global brain and cardiovascular health, calling for the joint prevention of stroke and dementia. This article summarizes the evidence for translation into action.
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| 18. |
- Hardell, Lennart, et al.
(författare)
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Secret ties to industry and conflicting interests in cancer research
- 2007
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Ingår i: American Journal of Industrial Medicine. - : Wiley-Liss Inc.. - 0271-3586 .- 1097-0274. ; 50:3, s. 227-233
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Forskningsöversikt (refereegranskat)abstract
- Background: Recently it was reported that a Swedish professor in environmental health has for decades worked as a consultant for Philip Morris without reporting his employment to his academic employer or declaring conflicts of interest in his research. The potential for distorting the epidemiological assessments of hazard and risk through paid consultants, pretending to be independent, is not exclusive to the tobacco industry.Methods: Documentation is drawn from peer reviewed publications, websites, documents from the Environmental Protection Agency, University reports, Wellcome Library Special Collections and the Washington Post.Results: Some consulting firms employ university researchers for industry work thereby disguising industry links in the income of large departments. If the industry affiliation is concealed by the scientist, biases from conflicting interests in risk assessments cannot be evaluated and dealt with properly. Furthermore, there is reason to suspect that editors and journal staff may suppress publication of scientific results that are adverse to industry owing to internal conflict of interest between editorial integrity and business needs.Conclusions: Examples of these problems from Sweden, UK, and USA are presented. The shortfalls cited in this article illustrate the need for improved transparency, regulations that will help curb abuses as well as instruments for control and enforcement against abuses.
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| 19. |
- Harris, A. J L, et al.
(författare)
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Effusive crises at Piton de la Fournaise 2014–2015: a review of a multi-national response model
- 2017
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Ingår i: Journal of Applied Volcanology. - : Springer Science and Business Media LLC. - 2191-5040. ; 6:1
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Forskningsöversikt (refereegranskat)abstract
- Many active European volcanoes and volcano observatories are island-based and located far from their administrative “mainland”. Consequently, Governments have developed multisite approaches, in which monitoring is performed by a network of individuals distributed across several national research centers. At a transnational level, multinational networks are also progressively emerging. Piton de la Fournaise (La Réunion Island, France) is one such example. Piton de la Fournaise is one of the most active volcanoes of the World, and is located at the greatest distance from its “mainland” than any other vulnerable “overseas” site, the observatory being 9365 km from its governing body in Paris. Effusive risk is high, so that a well-coordinated and rapid response involving near-real time delivery of trusted, validated and operational product for hazard assessment is critical. Here we review how near-real time assessments of lava flow propagation were developed using rapid provision, and update, of key source terms through a dynamic and open integration of near-real time remote sensing, modeling and measurement capabilities on both the national and international level. The multi-national system evolved during the five effusive crises of 2014–2015, and is now mature for Piton de la Fournaise. This review allows us to identify strong and weak points in an extended observatory system, and demonstrates that enhanced multi-national integration can have fundamental implications in scientific hazard assessment and response during an on-going effusive crisis.
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| 20. |
- Korten, W., et al.
(författare)
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Physics opportunities with the Advanced Gamma Tracking Array : AGATA
- 2020
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 56:5
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Forskningsöversikt (refereegranskat)abstract
- New physics opportunities are opening up by the Advanced Gamma Tracking Array, AGATA, as it evolves to the full 4 pi instrument. AGATA is a high-resolution gamma -ray spectrometer, solely built from highly segmented high-purity Ge detectors, capable of measuring gamma rays from a few tens of keV to beyond 10 MeV, with unprecedented efficiency, excellent position resolution for individual gamma -ray interactions, and very high count-rate capability. As a travelling detector AGATA will be employed at all major current and near-future European research facilities delivering stable and radioactive ion beams.
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| 21. |
- Kumar, R, et al.
(författare)
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Adhesives and plastics based on soy protein products
- 2002
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Ingår i: Industrial Crops and Products. - 0926-6690. ; 16:3, s. 155-172
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Forskningsöversikt (refereegranskat)abstract
- Significance of eco-friendly materials based on easily renewable natural resources, and the finite nature of petrochemical resources, has necessitated the development of polymers from agricultural processing by products such as soy proteins from oil processing. Although, considerable work was done in the early part of last century on polymers based on soy protein, there was almost no activity in this field for the last fifty years. There is a need to critically analyse the available literature on soy protein based polymeric materials. Therefore, an attempt is made to review the state-of-the-art of the polymeric materials with emphasis on adhesives and plastics derived from soy protein, a renewable resource abundantly available in nature.
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| 22. |
- Lê, A D, et al.
(författare)
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Neurobiological processes in alcohol addiction.
- 2001
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Ingår i: Alcoholism, clinical and experimental research. - 0145-6008. ; 25:5 Suppl ISBRA
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Forskningsöversikt (refereegranskat)abstract
- This article represents the proceedings of a symposium at the ISBRA Meeting in Yokohama, Japan. The chairs were A. D. Lê and K. Kiianmaa. The presentations were (1) Alcohol reward and aversion, by C. L. Cunningham; (2) The role of sensitization of neuronal mechanisms in ethanol self-administration, by J. A. Engel, M. Ericson, and B. Söderpalm; (3) Alcohol self-administration in dependent animals: Neurobiological mechanisms, by G. F. Koob, A. J. Roberts, and F. Weiss; (4) Stress and relapse to alcohol, by A. D. Lê; (5) Alcohol-preferring AA and alcohol-avoiding ANA rats differ in locomotor activation induced by repeated morphine injections, by P. Hyytiä, S. Janhunen, J. Mikkola, P. Bäckström, and K. Kiianmaa; and (6) Initial sensitivity and acute functional tolerance to the hypnotic effects of ethanol in mice genetically selected for mild and severe ethanol withdrawal convulsions, by I. Ponomarev and J. C. Crabbe.
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| 23. |
- O'Donoghue, Michelle, et al.
(författare)
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Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction : a meta-analysis
- 2008
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 300:1, s. 71-80
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Forskningsöversikt (refereegranskat)abstract
- CONTEXT: Although an invasive strategy is frequently used in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), data from some trials suggest that this strategy may not benefit women. OBJECTIVE: To conduct a meta-analysis of randomized trials to compare the effects of an invasive vs conservative strategy in women and men with NSTE ACS. DATA SOURCES: Trials were identified through a computerized literature search of the MEDLINE and Cochrane databases (1970-April 2008) using the search terms invasive strategy, conservative strategy, selective invasive strategy, acute coronary syndromes, non-ST-elevation myocardial infarction, and unstable angina. STUDY SELECTION: Randomized clinical trials comparing an invasive vs conservative treatment strategy in patients with NSTE ACS. DATA EXTRACTION: The principal investigators for each trial provided the sex-specific incidences of death, myocardial infarction (MI), and rehospitalization with ACS through 12 months of follow-up. DATA SYNTHESIS: Data were combined across 8 trials (3075 women and 7075 men). The odds ratio (OR) for the composite of death, MI, or ACS for invasive vs conservative strategy in women was 0.81 (95% confidence interval [CI], 0.65-1.01; 21.1% vs 25.0%) and in men was 0.73 (95% CI, 0.55-0.98; 21.2% vs 26.3%) without significant heterogeneity between sexes (P for interaction = .26). Among biomarker-positive women, an invasive strategy was associated with a 33% lower odds of death, MI, or ACS (OR, 0.67; 95% CI, 0.50-0.88) and a nonsignificant 23% lower odds of death or MI (OR, 0.77; 95% CI, 0.47-1.25). In contrast, an invasive strategy was not associated with a significant reduction in the triple composite end point in biomarker-negative women (OR, 0.94; 95% CI, 0.61-1.44; P for interaction = .36) and was associated with a nonsignificant 35% higher odds of death or MI (OR, 1.35; 95% CI, 0.78-2.35; P for interaction = .08). Among men, the OR for death, MI, or ACS was 0.56 (95% CI, 0.46-0.67) if biomarker-positive and 0.72 (95% CI, 0.51-1.01) if biomarker-negative (P for interaction = .09). CONCLUSIONS: In NSTE ACS, an invasive strategy has a comparable benefit in men and high-risk women for reducing the composite end point of death, MI, or rehospitalization with ACS. In contrast, our data provide evidence supporting the new guideline recommendation for a conservative strategy in low-risk women.
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| 24. |
- Petropoulos, Fotios, et al.
(författare)
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Operational Research : methods and applications
- 2024
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Ingår i: Journal of the Operational Research Society. - : Taylor & Francis Group. - 0160-5682 .- 1476-9360. ; 75:3, s. 423-617
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Forskningsöversikt (refereegranskat)abstract
- Throughout its history, Operational Research has evolved to include methods, models and algorithms that have been applied to a wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first summarises the up-to-date knowledge and provides an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion and used as a point of reference by a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order. The authors dedicate this paper to the 2023 Turkey/Syria earthquake victims. We sincerely hope that advances in OR will play a role towards minimising the pain and suffering caused by this and future catastrophes.
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| 25. |
- Post, Eric, et al.
(författare)
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Ecological Dynamics Across the Arctic Associated with Recent Climate Change
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 325:5946, s. 1355-1358
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Forskningsöversikt (refereegranskat)abstract
- At the close of the Fourth International Polar Year, we take stock of the ecological consequences of recent climate change in the Arctic, focusing on effects at population, community, and ecosystem scales. Despite the buffering effect of landscape heterogeneity, Arctic ecosystems and the trophic relationships that structure them have been severely perturbed. These rapid changes may be a bellwether of changes to come at lower latitudes and have the potential to affect ecosystem services related to natural resources, food production, climate regulation, and cultural integrity. We highlight areas of ecological research that deserve priority as the Arctic continues to warm.
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| 26. |
- Swarts, J. Douglas, et al.
(författare)
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Panel 2: Eustachian Tube, Middle Ear, and Mastoid-Anatomy, Physiology, Pathophysiology, and Pathogenesis
- 2013
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Ingår i: Otolaryngology: Head and Neck Surgery. - : Wiley. - 0194-5998 .- 1097-6817. ; 148, s. 26-36
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Forskningsöversikt (refereegranskat)abstract
- Objective. This report reviews the literature to identify the advances in our understanding of the middle ear (ME)Eustachian tube (ET) system during the past 4 years and, on that basis, to determine whether the short-term goals elaborated in the last report were achieved and propose updated goals to guide future otitis media (OM) research. Data Sources. Databases searched included PubMed, Web of Science (1945-present), Medline (1950 to present), Biosis Previews (1969-present), and the Zoological Record (1978 to present). The initial literature search covered the time interval from January 2007 to June 2011, with a supplementary search completed in February 2012. Review Methods. The panel topic was subdivided; each contributor performed a literature search and provided a preliminary report. Those reports were consolidated and discussed when the panel met on June 9, 2011. At that meeting, the progress was evaluated and new short-term goals proposed. Conclusions. Progress was made on 16 of the 19 short-term goals proposed in 2007. Significant advances were made in the characterization of ME gas exchange pathways, modeling ET function, and preliminary testing of treatments for ET dysfunction. Implications for Practice. In the future, imaging technologies should be developed to noninvasively assess ME/ET structure and physiology with respect to their role in OM pathogenesis. The new data derived from form/function experiments should be integrated into the finite element models and used to develop specific hypotheses concerning OM pathogenesis and persistence. Finally, rigorous studies of treatments, medical or surgical, of ET dysfunction should be undertaken.
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| 27. |
- Vandenplas, Yvan, et al.
(författare)
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Should Partial Hydrolysates Be Used as Starter Infant Formula? : A Working Group Consensus
- 2016
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 62:1, s. 22-35
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Forskningsöversikt (refereegranskat)abstract
- Partially hydrolyzed formulas (pHFs) are increasingly used worldwide, both in the prevention of atopic disease in at-risk infants and in the therapeutic management of infants with functional gastrointestinal manifestations. Because prevention is always preferable to treatment, we reviewed the literature aiming to find an answer for the question whether pHF may be recommended for feeding all infants if breast-feeding is not possible. PubMed and Cochrane databases were searched up to December 2014. In addition, to search for data that remained undetected by the searches, we approached authors of relevant articles and major producers of pHFs asking for unpublished data. Because few data were found, nonrandomized, controlled trials and trials in preterm infants were included as well. Overall, only limited data could be found on the efficacy and safety of pHF in healthy term infants. Available data do not indicate that pHFs are potentially harmful for healthy, term infants. With respect to long-term outcomes, particularly referring to immune, metabolic and hormonal effects, data are, however, nonexistent. From a regulatory point of view, pHFs meet the nutrient requirements to be considered as standard formula for term healthy infants. Cost, which is different from country to country, should be considered in the decision-making process. Based on limited available data, the use of pHF in healthy infants is safe with regard to growth. The lack of data, in particular for metabolic consequences and long-term outcomes, is, however, the basis for our recommendation that health authorities should develop and support long-term follow-up studies. Efficacy and long-term safety data are required before a recommendation of this type of formula for all infants can be made.
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| 28. |
- Wang, Fang, et al.
(författare)
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Emerging contaminants: A One Health perspective
- 2024
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Ingår i: Innovation. - 2666-6758. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
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| 29. |
- Wilkinson, S. Mark, et al.
(författare)
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The European baseline series and recommended additions : 2023
- 2023
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 88:2, s. 87-92
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Forskningsöversikt (refereegranskat)abstract
- The European baseline series was last updated in 2019. This article discusses the reasoning behind a further iteration of the series for 2023.
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