A theorem on topologically massive gravity

We show that for three dimensional space-times admitting a hypersurface orthogonal Killing vector field Deser, Jackiw and Templeton's vacuum field equations of topologically massive gravity allow only the trivial flat space-time solution. Thus spin is necessary to support topological mass.Comment: published in Classical and Quantum Gravity 13 (1996) L2

Spinor formulation of topologically massive gravity

In the framework of real 2-component spinors in three dimensional space-time we present a description of topologically massive gravity (TMG) in terms of differential forms with triad scalar coefficients. This is essentially a real version of the Newman-Penrose formalism in general relativity. A triad formulation of TMG was considered earlier by Hall, Morgan and Perjes, however, due to an unfortunate choice of signature some of the spinors underlying the Hall-Morgan-Perjes formalism are real, while others are pure imaginary. We obtain the basic geometrical identities as well as the TMG field equations including a cosmological constant for the appropriate signature. As an application of this formalism we discuss the Bianchi Type $VIII - IX$ exact solutions of TMG and point out that they are parallelizable manifolds. We also consider various re-identifications of these homogeneous spaces that result in black hole solutions of TMG.Comment: An expanded version of paper published in Classical and Quantum Gravity 12 (1995) 291

Topologically massive gravito-electrodynamics: exact solutions

We construct two classes of exact solutions to the field equations of topologically massive electrodynamics coupled to topologically massive gravity in 2 + 1 dimensions. The self-dual stationary solutions of the first class are horizonless, asymptotic to the extreme BTZ black-hole metric, and regular for a suitable parameter domain. The diagonal solutions of the second class, which exist if the two Chern-Simons coupling constants exactly balance, include anisotropic cosmologies and static solutions with a pointlike horizon.Comment: 15 pages, LaTeX, no figure

Mass and angular momentum of asymptotically AdS or flat solutions in the topologically massive gravity

We study the conserved charges of supersymmetric solutions in the topologically massive gravity theory for both asymptotically flat and constant curvature geometries.Comment: REVTEX4, 8 pages, no figures, added 2 references and a few clarifying remark

Dynamics and energetics of the mammalian phosphatidylinositol transfer protein phospholipid exchange cycle

Phosphatidylinositol-transfer proteins (PITPs) regulate phosphoinositide signaling in eukaryotic cells. The defining feature of PITPs is their ability to exchange phosphatidylinositol (PtdIns) molecules between membranes, and this property is central to PITP-mediated regulation of lipid signaling. However, the details of the PITP-mediated lipid exchange cycle remain entirely obscure. Here, all-atom molecular dynamics simulations of the mammalian StART-like PtdIns/phosphatidylcholine (PtdCho) transfer protein PITP alpha, both on membrane bilayers and in solvated systems, informed downstream biochemical analyses that tested key aspects of the hypotheses generated by the molecular dynamics simulations. These studies provided five key insights into the PITP alpha lipid exchange cycle: (i) interaction of PITP alpha with the membrane is spontaneous and mediated by four specific protein substructures; (ii) the ability of PITP alpha to initiate closure around the PtdCho ligand is accompanied by loss of flexibility of two helix/loop regions, as well as of the C-terminal helix; (iii) the energy barrier of phospholipid extraction from the membrane is lowered by a network of hydrogen bonds between the lipid molecule and PITP alpha; (iv) the trajectory of PtdIns or PtdCho into and through the lipidbinding pocket is chaperoned by sets of PITP alpha residues conserved throughout the StART-like PITP family; and (v) conformational transitions in the C-terminal helix have specific functional involvements in PtdIns transfer activity. Taken together, these findings provide the first mechanistic description of key aspects of the PITP alpha PtdIns/PtdCho exchange cycle and offer a rationale for the high conservation of particular sets of residues across evolutionarily distant members of the metazoan StART-like PITP family.Peer reviewe

Perusopetuksen oppimisympäristöjen digitalisaation nykytilanne ja opettajien valmiudet hyödyntää digitaalisia oppimisympäristöjä

Tällä selvityksellä esitetään yleiskuva siitä, millainen on oppimisympäristöjen digitalisaation nykytilanne ja minkälaiset ovat opettajien valmiudet niiden hyödyntämiseen perusasteella. Selvitys toteutettiin verkkopohjaista Opeka-työkalua käyttäen ja saatua aineistoa täydennettiin kohderyhmien haastatteluilla. Kohdennettu haastattelu suoritettiin valituille sivistystoimenjohtajille, rehtoreille ja opettajille. Koulujen digitaalisuudessa ei ole suuria alueellisia eroja eri puolilla Suomea ja opettajat suhtautuvat pääosin (75 %) myönteisesti tieto- ja viestintäteknologian (TVT) käytön lisäämiseen omassa työssään. Opettajista noin puolet arvioi omaavansa perustason TVT:n käyttötaidot, viidenneksen kokiessa taitojensa olevan perustasoa paremmat. Selvityksen mukaan omien taitojen kehittämistäkin tarvitaan, noin 20 % vastaajista kokee osaamisessaan merkittäviä puutteita. Käytössä olevien laitteistojen tai välineistön määrä koetaan riittämättömäksi ja käytössä olevien laitteistojen laadussa nähdään olevan puutteita (60 %). Puolet vastaajista koki käytössään olevan internetyhteyden riittäväksi. Joka kolmannes vastaajista koki tyytymättömyyttä käytössään olevaan langattomaan verkkoon, osasta kouluja langaton verkko puuttuu edelleen. Uusi teknologia aiheuttaa myös stressiä lähes puolelle opettajista. Joustavat, innovatiiviset täydennyskoulutusratkaisut sekä teknisen ja pedagogisen tuen kehittäminen nousevat esiin tässäkin selvityksessä. Digitaalisuus ei ole itseisarvo, vaan väline kehittää koulutusta ja tarjota lapsille ja nuorille taitoja hyödyntää digitaalisuuden suomia mahdollisuuksia niin opiskelussa, työssä kuin vapaa-ajalla. Tätä raporttia täydentävät liite 1 haastatteluraportti sekä liite 2 raporttiin liittyviä taulukoita ja kuvioita

Statins for children with familial hypercholesterolemia

BACKGROUND: Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review. OBJECTIVES: To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia. SEARCH METHODS: Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 20 February 2017. SELECTION CRITERIA: Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion and extracted data. MAIN RESULTS: We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (moderate quality evidence). Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point (low quality evidence). The risks of myopathy (low quality evidence) and clinical adverse events (moderate quality evidence) were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery (low quality evidence), and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness (low quality evidence). AUTHORS' CONCLUSIONS: Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins

Familial hypercholesterolemia and elevated lipoprotein(a) : double heritable risk and new therapeutic opportunities

Vuorio A, Watts GF, Schneider WJ, Tsimikas S, Kovanen PT (Mehilainen Airport Health Centre, Vantaa; University of Helsinki, Helsinki, Finland; University of Western Australia, Perth, Australia; Royal Perth Hospital, Perth, Australia; Medical University of Vienna, Vienna, Austria; University of California San Diego, La Jolla, CA, USA; Wihuri Research Institute, Helsinki, Finland). Familial hypercholesterolemia and elevated lipoprotein(a): double heritable risk and new therapeutic opportunities (Review). J Intern Med 2020; 287: 2-18. There is compelling evidence that the elevated plasma lipoprotein(a) [Lp(a)] levels increase the risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. Like low-density lipoprotein (LDL) particles, Lp(a) particles contain cholesterol and promote atherosclerosis. In addition, Lp(a) particles contain strongly proinflammatory oxidized phospholipids and a unique apoprotein, apo(a), which promotes the growth of an arterial thrombus. At least one in 250 individuals worldwide suffer from the heterozygous form of familial hypercholesterolemia (HeFH), a condition in which LDL-cholesterol (LDL-C) is significantly elevated since birth. FH-causing mutations in the LDL receptor gene demonstrate a clear gene-dosage effect on Lp(a) plasma concentrations and elevated Lp(a) levels are present in 30-50% of patients with HeFH. The cumulative burden of two genetically determined pro-atherogenic lipoproteins, LDL and Lp(a), is a potent driver of ASCVD in HeFH patients. Statins are the cornerstone of treatment of HeFH, but they do not lower the plasma concentrations of Lp(a). Emerging therapies effectively lower Lp(a) by as much as 90% using RNA-based approaches that target the transcriptional product of the LPA gene. We are now approaching the dawn of an era, in which permanent and significant lowering of the high cholesterol burden of HeFH patients can be achieved. If outcome trials of novel Lp(a)-lowering therapies prove to be safe and cost-effective, they will provide additional risk reduction needed to effectively treat HeFH and potentially lower the CVD risk in these high-risk patients even more than currently achieved with LDL-C lowering alone.Peer reviewe

Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study

AIMS: To examine the changes in coronary, all-cause, and cancer mortality in patients with heterozygous familial hypercholesterolaemia (FH) before and after lipid-lowering therapy with statins. METHODS AND RESULTS: A total of 3382 patients (1650 men) aged <80 years were recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2006 for 46 580 person-years. There were 370 deaths, including 190 from coronary heart disease (CHD) and 90 from cancer. The standardized mortality ratio (compared with the population in England and Wales) was calculated before and from 1 January 1992. In patients aged 20-79 years, CHD mortality fell significantly by 37% (95% CI = 7-56) from 3.4- to 2.1-fold excess. Primary prevention resulted in a 48% reduction in CHD mortality from 2.0-fold excess to none, with a smaller reduction of nearly 25% in patients with established disease. Coronary mortality was reduced more in women than in men. In patients without known CHD at registration, all-cause mortality from 1992 was 33% (21-43), lower than in the general population, mainly due to a 37% (21-50) lower risk of fatal cancer. CONCLUSION: The results emphasize the importance of early identification of FH and treatment with statins

AdS Black Hole Solutions in the Extended New Massive Gravity

We have obtained (warped) AdS black hole solutions in the three dimensional extended new massive gravity. We investigate some properties of black holes and obtain central charges of the two dimensional dual CFT. To obtain the central charges, we use the relation between entropy and temperature according to the AdS/CFT dictionary. For AdS black holes, one can also use the central charge function formalism which leads to the same results.Comment: 24pages, some organization corrected, minor corrections, references added, final published versio