High dose atorvastatin associated with increased risk of significant hepatotoxicity in comparison to simvastatin in UK GPRD cohort

Background and Aims: Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment. Methods: The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions. Results: Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4–2.6]. High dose was classified as 40–80mg daily and low dose 10–20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2–12.7] for HDA, 1.4 [0.9–2.0] for LDA and 1.5 [1.0–2.2] for HDS. Conclusions: The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small

A Geometry of the Generations

We propose a geometric theory of flavor based on the discrete group $(S_3)^3$, in the context of the minimal supersymmetric standard model. The group treats three objects symmetrically, while making fundamental distinctions between the generations. The top quark is the only heavy quark in the symmetry limit, and the first and second generation squarks are degenerate. The hierarchical nature of Yukawa matrices is a consequence of a sequential breaking of $(S_3)^3$.Comment: 10 pages, 1 EPS figure as uuencoded tar-compressed file, uses psfig.st

Operationalising a metric of nitrogen impacts on biodiversity for the UK response to a data request from the Coordination Centre for Effects

As a signatory party to the Convention on Long Range Transboundary Air Pollution (CLRTAP), the UK has been requested to provide biodiversity metrics for use in assessing impacts of atmospheric nitrogen (N) pollution. Models of soil and vegetation responses to N pollution can predict changes in habitat suitability for many plant and lichen species. Metrics are required to relate changes in a set of species to biodiversity targets. In a previous study, the suitability of the habitat for a set of positive indicator-species was found to be the measure, out of potential outputs from models currently applicable to the UK, which was most clearly related to the assessment methods of habitat specialists at the Statutory Nature Conservation Bodies (SNCBs). This report describes the calculation of values for a metric, based on this principle, for a set of example habitats under different N pollution scenarios. The examples are mainly from Natura-2000 sites, and are defined at EUNIS Level 3 (e.g. F4.1 Wet heath). Values for the biodiversity metric were shown to be greater on all sites in the “Background” scenario than in the scenario with greater N and S pollution, illustrating a positive response of biodiversity to reduced pollution. Results of the study were submitted in response to the ‘Call for Data 2012-14’ by the CLTRAP Co-ordination Centre for Effects (CCE), and presented at the 24th CCE Workshop in April 2014. Metrics calculated on a similar basis were also presented by the Netherlands, Switzerland and Denmark. Such metrics indicate biodiversity status more accurately than other types of metric such as Simpson index or similarity to a reference community, so it was decided to adopt habitat-suitability for positive indicator-species as a common basis for a biodiversity metric in this context. Further work is needed to determine the typical range of metric values in different habitats, and threshold values for damage and recovery. Requirements are likely to be specified in detail in the next CCE Call for Data. The current study shows that a biodiversity metric based on habitat-suitability for positive indicator-species is a useful and responsive method for summarising outputs of models of air pollution impacts on ecosystems

Occurrence of methicillin-resistant Staphylococcus aureus in surface waters near industrial hog operation spray fields

Industrial hog operations (IHOs) have been identified as a source of antibiotic-resistant Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). However, few studies have investigated the presence of antibiotic-resistant S. aureus in the environment near IHOs, specifically surface waters proximal to spray fields where IHO liquid lagoon waste is sprayed. Surface water samples (n = 179) were collected over the course of approximately one year from nine locations in southeastern North Carolina and analyzed for the presence of presumptive MRSA using CHROMagar MRSA media. Culture-based, biochemical, and molecular tests, as well as matrix-assisted laser desorption/ionization-time of flight mass spectrometry were used to confirm that isolates that grew on CHROMagar MRSA media were S. aureus. Confirmed S. aureus isolates were then tested for susceptibility to 16 antibiotics and screened for molecular markers of MRSA (mecA, mecC) and livestock adaptation (absence of scn). A total of 12 confirmed MRSA were detected in 9 distinct water samples. Nine of 12 MRSA isolates were also multidrug-resistant (MDRSA [i.e., resistant to ≥ 3 antibiotic classes]). All MRSA were scn-positive and most (11/12) belonged to a staphylococcal protein A (spa) type t008, which is commonly associated with humans. Additionally, 12 confirmed S. aureus that were methicillin-susceptible (MSSA) were recovered, 7 of which belonged to spa type t021 and were scn-negative (a marker of livestock-adaptation). This study demonstrated the presence of MSSA, MRSA, and MDRSA in surface waters adjacent to IHO lagoon waste spray fields in southeastern North Carolina. To our knowledge, this is the first report of waterborne S. aureus from surface waters proximal to IHOs

Flavor at the TeV Scale with Extra Dimensions

Theories where the Standard Model fields reside on a 3-brane, with a low fundamental cut-off and extra dimensions, provide alternative solutions to the gauge hierarchy problem. However, generating flavor at the TeV scale while avoiding flavor-changing difficulties appears prohibitively difficult at first sight. We argue to the contrary that this picture allows us to lower flavor physics close to the TeV scale. Small Yukawa couplings are generated by ``shining'' badly broken flavor symmetries from distant branes, and flavor and CP-violating processes are adequately suppressed by these symmetries. We further show how the extra dimensions avoid four dimensional disasters associated with light fields charged under flavor. We construct elegant and realistic theories of flavor based on the maximal U(3)^5 flavor symmetry which naturally generate the simultaneous hierarchy of masses and mixing angles. Finally, we introduce a new framework for predictive theories of flavor, where our 3-brane is embedded within highly symmetrical configurations of higher-dimensional branes.Comment: 40 pages, 8 figure

A Complete Supersymmetric SO(10) Model

A complete supersymmetric SO(10) model is constructed, which is the most general consistent with certain $R$, discrete, and $U(1)$ flavor symmetries. The desired vacuum of the theory has vevs which lie in particular directions of group space. This leads to both doublet triplet splitting and to the generation of just four operators for charged fermion masses. The model illustrates how many features of superunification become related in the context of a complete theory. The features discussed here include: the weak mixing angle prediction, the doublet-triplet splitting problem, proton decay, the generation of the $\mu$ parameter, neutrino masses and the generation of the operators which lead to charged fermion mass predictions.Comment: 18 page

Maximal Neutrino Mixing from a Minimal Flavor Symmetry

We study a number of models, based on a non-Abelian discrete group, that successfully reproduce the simple and predictive Yukawa textures usually associated with U(2) theories of flavor. These models allow for solutions to the solar and atmospheric neutrino problems that do not require altering successful predictions for the charged fermions or introducing sterile neutrinos. Although Yukawa matrices are hierarchical in the models we consider, the mixing between second- and third-generation neutrinos is naturally large. We first present a quantitative analysis of a minimal model proposed in earlier work, consisting of a global fit to fermion masses and mixing angles, including the most important renormalization group effects. We then propose two new variant models: The first reproduces all important features of the SU(5)xU(2) unified theory with neither SU(5) nor U(2). The second demonstrates that discrete subgroups of SU(2) can be used in constructing viable supersymmetric theories of flavor without scalar universality even though SU(2) by itself cannot.Comment: 34 pages LaTeX, 1 eps figure, minor revisions and references adde

U(2)-like Flavor Symmetries and Approximate Bimaximal Neutrino Mixing

Models involving a U(2) flavor symmetry, or any of a number of its non-Abelian discrete subgroups, can explain the observed hierarchy of charged fermion masses and CKM angles. It is known that a large neutrino mixing angle connecting second and third generation fields may arise via the seesaw mechanism in these models, without a fine tuning of parameters. Here we show that it is possible to obtain approximate bimaximal mixing in a class of models with U(2)-like Yukawa textures. We find a minimal form for Dirac and Majorana neutrino mass matrices that leads to two large mixing angles, and show that our result can quantitatively explain atmospheric neutrino oscillations while accommodating the favored, large angle MSW solution to the solar neutrino problem. We demonstrate that these textures can arise in models by presenting a number of explicit examples.Comment: 20 pages RevTex4, 2 figure

Identification of stingless bees (Hymenoptera: Apidae) in Kenya using Morphometrics and DNA barcoding

Stingless bees are important pollinators of wild plants and crops. The identity of stingless bee species in Africa has not been fully documented. The present study explored the utility of morphometrics and DNA barcoding for identification of African stingless bee populations, and to further employ these tools to identify potential cryptic variation within species. Stingless bee samples were collected from three ecological zones, namely Kakamega Forest, Mwingi and Arabuko-Sokoke Forest, which are geographically distant and cover high, medium and low altitudes, respectively. Forewing and hind leg morphometric characters were measured to determine the extent of morphological variation between the populations. DNA barcodes were generated from the mitochondrial cytochrome c-oxidase I (COI) gene. Principal Component Analysis (PCA) on the morphometric measurements separated the bee samples into three clusters: (1) Meliponula bocandei; (2) Meliponula lendliana + Plebeina hildebrandti; (3) Dactylurina schmidti + Meliponula ferruginea black + Meliponula ferruginea reddish brown, but Canonical Variate Analysis (CVA) separated all the species except the two morphospecies (M. ferruginea reddish brown and black). The analysis of the COI sequences showed that DNA barcoding can be used to identify all the species studied and revealed remarkable genetic distance (7.3%) between the two M. ferruginea morphs. This is the first genetic evidence that M. ferruginea black and M. ferruginea reddish brown are separate species