The Cabrières Biota (France) provides insights into Ordovician polar ecosystems.

Early Palaeozoic sites with soft-tissue preservation are predominantly found in Cambrian rocks and tend to capture past tropical and temperate ecosystems. In this study, we describe the diversity and preservation of the Cabrières Biota, a newly discovered Early Ordovician Lagerstätte from Montagne Noire, southern France. The Cabrières Biota showcases a diverse polar assemblage of both biomineralized and soft-bodied organisms predominantly preserved in iron oxides. Echinoderms are extremely scarce, while sponges and algae are abundantly represented. Non-biomineralized arthropod fragments are also preserved, along with faunal elements reminiscent of Cambrian Burgess Shale-type ecosystems, such as armoured lobopodians. The taxonomic diversity observed in the Cabrières Biota mixes Early Ordovician Lagerstätten taxa with Cambrian forms. By potentially being the closest Lagerstätte to the South Pole, the Cabrières Biota probably served as a biotic refuge amid the high-water temperatures of the Early Ordovician, and shows comparable ecological structuring to modern polar communities.

Funeralaspis n. gen.: a new odontopleurine trilobite from the early Middle Ordovician (Dapingian) of Death Valley, eastern California, USA, and the classification of Ordovician odontopleurines.

Funeralaspis n. gen. (type species F. deathvalleyensis n. sp.) is the oldest known formally named odontopleurine trilobite species, described on the basis of abundant secondarily silicified sclerites of all sclerite types except the rostral plate, from the Dapingian of the Antelope Valley Formation, west flank of the Funeral Range, Death Valley National Park, Inyo County, California. Many Ordovician odontopleurines have been assigned to Diacanthaspis, to the point that it has become something of a taxon of convenience. All of the potential species are listed along with their provenance, preservation, and represented sclerite types. A core group of Diacanthaspis, termed Diacanthaspis (sensu stricto or s.s.) possibly represents a Laurentian clade, consisting of the type species, D. cooperi, and D. lepidus, D. orandensis, D. scitulus, D. secretus, and possibly D. elapsa and D. parvula. This group is characterized by extreme dorsal spinosity, dorsal accessory spines on the base of the genal spine, pygidial spines with lateral fringes of tiny spines, and thoracic and pygidial ring furrows with fringes of tiny spines. Funeralaspis deathvalleyensis has none of the features characteristic of Diacanthaspis and in general scarcely resembles members of this Upper Ordovician group. Remaining species that have been assigned to Diacanthaspis, some of which are very poorly known, should be reclassified as knowledge of Ordovician odontopleurines advances, but for the present are treated as Diacanthaspis (sensu lato or s.l.). A heretofore nearly unknown species described as Ceratocephala maquoketensis from the early Katian of Howard County, Iowa, has not been commented upon in the literature since it was proposed. It is an odontopleurine which in the current state of knowledge should be assigned to the Diacanthaspis (s.l.) group.

Middle Ordovician (Darriwilian) cheirurid trilobites from the Table Cove Formation, western Newfoundland, Canada.

A diverse mid-Darriwilian trilobite fauna from the Table Cove Formation, western Newfoundland, has long been known on the basis of calcareous specimens from the west coast of the Great Northern Peninsula. Discovery of silicified faunas in localities on the east coast provides additional morphological information for previously known species, and also reveals the presence of multiple new genera and species. Many of these species are important, as they represent some of the earliest Laurentian members of the diversifying Whiterock Fauna, and seem phylogenetically near to the base of their respective clades. The concept of Sphaerexochinae is restricted to the genus Sphaerexochus itself, with the possible inclusion of Newfoundlandops n. gen. (type species N. karimae n. sp.), which shares with Sphaerexochus potential synapomorphies including the structure of the hypostome and the presence of fine granular sculpture on the librigenal border and field. Most of the Early and Middle Ordovician taxa with three pygidial segments previously classified as Sphaerexochinae by many authors are reassigned to Acanthoparyphinae on the basis of multiple putative synapomorphies. Other new cheirurid genera from the Table Cove Formation are the pilekiine Harebayaspis n. gen. (type species H. plurima n. sp.), and the deiphonine Mainbrookia n. gen. (type species M. becki n. sp.). Other species revised or described include the cheirurine Laneites polydorus (Billings, 1865), and the acanthoparyphines Cydonocephalus tiffanyae n. sp., Kawina stougei n. sp., and Kawina? sp.

Towards improved migraine management: Determining potential trigger factors in individual patients.

Background Certain chronic diseases such as migraine result in episodic, debilitating attacks for which neither cause nor timing is well understood. Historically, possible triggers were identified through analysis of aggregated data from populations of patients. However, triggers common in populations may not be wholly responsible for an individual's attacks. To explore this hypothesis we developed a method to identify individual 'potential trigger' profiles and analysed the degree of inter-individual variation. Methods We applied N = 1 statistical analysis to a 326-migraine-patient database from a study in which patients used paper-based diaries for 90 days to track 33 factors (potential triggers or premonitory symptoms) associated with their migraine attacks. For each patient, univariate associations between factors and migraine events were analysed using Cox proportional hazards models. Results We generated individual factor-attack association profiles for 87% of the patients. The average number of factors associated with attacks was four per patient: Factor profiles were highly individual and were unique in 85% of patients with at least one identified association. Conclusion Accurate identification of individual factor-attack profiles is a prerequisite for testing which are true triggers and for development of trigger avoidance or desensitisation strategies. Our methodology represents a necessary development toward this goal.

Activity of aclidinium bromide, a new long-acting muscarinic antagonist: a phase I study.

AIM: Aclidinium bromide is a muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). This phase I trial in healthy subjects investigated the bronchodilator activity of aclidinium and its ability to reduce methacholine-induced bronchoconstriction. METHODS: This double-blind, partial-crossover study randomized 12 subjects to treatment with single doses of aclidinium (50, 300 or 600 microg) or placebo. Drug activity was assessed for 24 h after administration by specific airway conductance (sGaw), airways resistance (Raw) and bronchial responsiveness (PC35 sGaw methacholine). RESULTS: Aclidinium significantly increased sGaw compared with placebo at all assessments and doses (sGaw mean +/- SD AUC (l kPa(-1) h) for placebo 24.4 +/- 4.37, for 50 microg 29.0 +/- 7.08, for 300 microg 31.2 +/- 6.68 and for 600 microg 32.7 +/- 7.95) (P < 0.009), except 50 microg at 1 and 24 h. Significant decreases in Raw were observed with aclidinium 300 and 600 microg compared with placebo at all assessments (Raw mean +/- SD AUC (kPa s(-1) l(-1) h) for placebo 7.7 +/- 3.46, for 300 microg 5.8 +/- 2.33, for 600 microg 6.3 +/- 3.11) (P < 0.04) except 600 microg at 24 h. Differences between aclidinium 300 and 600 microg vs. placebo in PC35 doubling concentration were significant at all assessments (mean +/- SD AUC (mg ml(-1) h) for placebo 100.0 +/- 30.27, for 50 microg 117.2 +/- 33.33, for 300 microg 168.9 +/- 28.66 and for 600 microg 179.1 +/- 15.73 (P < 0.0001). For all endpoints, there was a significant difference between aclidinium 50 microg and the higher doses (P < 0.0001). Aclidinium was not detected in plasma and was well tolerated. CONCLUSION: Aclidinium produced statistically significant and sustained bronchodilation over 24 h, suggesting long-acting efficacy and providing a rationale for future studies in patients with COPD.

The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study.

BACKGROUND: Blonanserin is a novel atypical antipsychotic agent with potent dopamine D(2) and serotonin 5-HT(2) antagonist properties. It may potentially have a lower incidence of adverse events than other antipsychotic agents. OBJECTIVE: To determine the efficacy and safety of three doses of blonanserin compared with placebo and haloperidol in patients with acute-phase schizophrenia. METHODS: This was a 6-week, randomized, double-blind, placebo- and haloperidol-controlled, international, multicentre study. Patients with an acute exacerbation of their schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) score >/=70 and a Clinical Global Impression - Severity of Illness (CGI-S) score >/=4 ('moderately ill') [with no decrease >/=20% or >/=1 point, respectively, during the wash-out period] were randomized into one of five treatment groups (blonanserin 2.5, 5 or 10 mg, haloperidol 10 mg or placebo once daily). Patients were assessed weekly for clinical efficacy, adverse events, extrapyramidal symptoms (EPS) and drug compliance, and were assessed biweekly for other safety variables. RESULTS: All 307 randomized patients received at least one dose of study medication and 228 (74.3%) completed the study. The mean reduction in PANSS total score at week 6 was significantly greater with all active treatments compared with placebo (-12.58; p < 0.001); blonanserin 10 mg was significantly superior to blonanserin 2.5 mg (-30.18 vs -20.6; p < 0.001), but blonanserin 5 mg (-27.19) and haloperidol 10 mg (-28.16) were not. All active treatments showed greater efficacy against the positive symptoms of schizophrenia, and blonanserin (5 and 10 mg) was more effective against the negative symptoms than haloperidol. Blonanserin was well tolerated at all doses and there was no evidence of clinically important weight gain, orthostatic hypotension, corrected QT interval prolongation or clinically relevant changes in laboratory test results. Haloperidol caused persistent elevation in prolactin levels, but this was not seen with any dose of blonanserin throughout the study period. There was a lower incidence of EPS with blonanserin 10 mg (26.6%) than with haloperidol 10 mg (53.3%). CONCLUSION: Blonanserin was effective in the treatment of acute schizophrenia and showed greater efficacy in negative symptoms compared with placebo and haloperidol. Blonanserin was well tolerated and its safety profile compared favourably with haloperidol, particularly with respect to prolactin elevation and EPS frequency.

Meta-analysis of the efficacy of ebastine 20 mg compared to loratadine 10 mg and placebo in the symptomatic treatment of seasonal allergic rhinitis.

BACKGROUND: Few randomized studies have compared the efficacy of ebastine and loratadine in the symptomatic treatment of seasonal allergic rhinitis (SAR). METHODS: A meta-analysis was performed on data from four randomized, double-blind, placebo-controlled, parallel-group clinical trials comparing the efficacy of ebastine 20 mg once daily versus loratadine 10 mg once daily in the symptomatic treatment of SAR symptoms. Primary efficacy variable was the mean change in the overall mean daily reflective total symptom score (TSS), i.e. the sum of five rhinitis symptom scores: nasal discharge, nasal congestion, nasal itching, sneezing and total eye symptoms (itchy/watery eyes) over the first 2 weeks of treatment compared to baseline. RESULTS: There were 2,089 patients in the population analyzed: 749, 739 and 601 patients in the ebastine 20 mg, loratadine 10 mg and placebo groups, respectively. Compared to baseline, overall mean daily reflective TSS over the first 2 weeks of treatment was -3.61 (35.4% reduction from baseline) in the ebastine group, -3.05 (29.0% reduction) in the loratadine group and -2.30 (22.7% reduction) in the placebo group. Statistically significant differences in the mean change from baseline were found when comparing ebastine and loratadine (p<0.001), ebastine and placebo (p<0.0001), and loratadine and placebo (p<0.0001). The global effect (i.e. the difference in overall mean daily reflective TSS over the first 2 weeks of treatment) of ebastine compared with loratadine over the first 2 weeks of treatment was -0.56 (95% confidence interval, CI, -0.86 to -0.26), and it was sustained during the whole (4-week) period studied. The global effects of ebastine and loratadine compared with placebo were -1.30 (95% CI, -1.61 to -0.99) and -0.74 (95% CI, -1.05 to -0.43), respectively. Secondary variables (reflective and snapshot individual symptom scores) showed the same trend. CONCLUSIONS: This meta-analysis confirms that ebastine 20 mg has a good efficacy profile, inducing a greater decrease from baseline in mean rhinitis symptom scores than loratadine 10 mg or placebo.

Genetic analysis of SLC11A1 polymorphisms in multiple sclerosis patients.

Solute carrier 11a1 (SLC11A1; formerly NRAMP1, where NRAMP stands for natural resistance-associated macrophage protein) is a proton/bivalent cation antiporter that localizes to late endosomes/lysosomes. SLC11A1 regulates macrophage functions that are of potential importance in the induction and/or maintenance of autoimmune diseases such as rheumatoid arthritis, type I diabetes and Crohn's disease. We investigated SLC11A1 gene as a candidate gene for genetic susceptibility to multiple sclerosis (MS) in our population. Four SLC11A1 gene polymorphisms (5'GT repeat, D543N, 1729 + 55del4 and 1729 + 271del4) were analysed in a case-control study of 195 patients with MS and 125 control subjects. We found no evidence of association between SLC11A1 polymorphisms and MS susceptibility in the Spanish population.