Pulmicort® turbohaler® once daily as initial prophylactic therapy for asthma

AbstractIn a double-blind, randomized, parallel-group clinical trial, 340 asthmatic patients aged 12–70 years received budesonide 400 μg once daily in the morning, budesonide 400 μg once daily in the evening, budesonide 200 μg twice daily or placebo, for 12 weeks in addition to inhaled short-acting β2-agonists used as required (p.r.n.). Budesonide was given as Pulmicort Turbohaler.Peak expiratory flow rate (PEFR) increased by 20 to 30 1 min−1 in each of the active treatment groups, significantly more than in the placebo group (P<0·01). There were no significant differences between the active treatment groups. Symptom improvement and decreased β2-agonist use reflected the PEFR data. Incidences of adverse events in the active treatment groups were similar to those observed in the placebo group.Budesonide 400 μg given once daily morning or evening is equieffective with the same total daily dose given twice daily in the treatment of mild to moderate stable asthmatics

Human settlement of East Polynesia earlier, incremental, and coincident with prolonged South Pacific drought

The timing of human colonization of East Polynesia, a vast area lying between Hawai‘i, Rapa Nui, and New Zealand, is much debated and the underlying causes of this great migration have been enigmatic. Our study generates evidence for human dispersal into eastern Polynesia from islands to the west from around AD 900 and contemporaneous paleoclimate data from the likely source region. Lake cores from Atiu, Southern Cook Islands (SCIs) register evidence of pig and/or human occupation on a virgin landscape at this time, followed by changes in lake carbon around AD 1000 and significant anthropogenic disturbance from c. AD 1100. The broader paleoclimate context of these early voyages of exploration are derived from the Atiu lake core and complemented by additional lake cores from Samoa (directly west) and Vanuatu (southwest) and published hydroclimate proxies from the Society Islands (northeast) and Kiribati (north). Algal lipid and leaf wax biomarkers allow for comparisons of changing hydroclimate conditions across the region before, during, and after human arrival in the SCIs. The evidence indicates a prolonged drought in the likely western source region for these colonists, lasting c. 200 to 400 y, contemporaneous with the phasing of human dispersal into the Pacific. We propose that drying climate, coupled with documented social pressures and societal developments, instigated initial eastward exploration, resulting in SCI landfall(s) and return voyaging, with colonization a century or two later. This incremental settlement process likely involved the accumulation of critical maritime knowledge over several generations

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Once-daily ciclesonide 80 or 320μg for 12 weeks is safe and effective in patients with persistent asthma

SummaryThe efficacy and safety of ciclesonide was assessed in this randomized, placebo-controlled study in patients with persistent asthma (randomized n=360) maintained on low to moderate doses of inhaled corticosteroids. Patients were randomized to receive ciclesonide 80 or 320μg (ex-actuator doses, equivalent to 100 and 400μg ex-valve, respectively) or placebo once daily in the morning via metered-dose inhaler for 12 weeks. Morning peak expiratory flow was maintained throughout the treatment period in patients treated with ciclesonide and decreased significantly in patients treated with placebo (P=0.0003). Ciclesonide (80 and 320μg) significantly increased forced expiratory volume in 1s from baseline (0.13 and 0.19L increases, respectively; P<0.01); improvements were superior versus placebo (P=0.0044 for 80μg ciclesonide; P<0.0001 for 320μg ciclesonide). The probability of losing efficacy decreased in a dose-dependent manner (55% for placebo, 38% for ciclesonide 80μg, 23% for ciclesonide 320μg). Asthma symptom scores and rescue medication use were unchanged with ciclesonide and significantly worsened with placebo. The incidence of adverse events was comparable in all treatment groups and no cortisol suppression was observed. Therefore, ciclesonide 80 and 320μg administered once daily was a safe and effective maintenance treatment for patients with persistent asthma

New insights on Late Quaternary Asian palaeomonsoon variability and the timing of the Last Glacial Maximum in southwestern China

Aw6.35 m core (06SD) was retrieved from Lake Shudu, Yunnan Province, China. The sediments spanningthe period w22.6e10.5 kcal. yr BP (6.35e1.44 m) were analysed using a combination of variablesincluding pollen, charcoal, particle size, magnetic susceptibility and loss-on-ignition. The resultingpalaeorecord provides a high-resolution reconstruction of Late Pleistocene to Early Holocene climaticand environmental changes in southwestern China. Our findings indicate that from c. 22.6 to 17.7 kcal. yrBP, vegetation assemblages were primarily aligned to sparse xerophytic grassland/tundra or cold-tolerantboreal Pinus forest, indicating that climatic conditions in southwestern China were cold and dry.However, from c. 17.7 to 17.4 kcal. yr BP, the Lake Shudu record is punctuated by marked environmentalchanges. These include the establishment of denser vegetation cover, a marked expansion of boreal Pinusforest and enhanced hydrological activity in the catchment over centennial timescales, perhaps suggestingthat stepwise variations in the Asian Monsoon were triggering fundamental environmentalchanges over sub-millennial timescales. Thereafter, the pollen record captures a period of environmentalinstability reflected in fluctuations across all of the variables, which persists until c. 17.1 kcal. yr BP. Afterc. 17.1 kcal. yr BP, the expansion of steppe vegetation cover and coldecool mixed forest consisting ofmesophilous vegetation such as Tsuga and Picea, thermophilous trees including Ulmus and deciduousQuercus inferred from the Lake Shudu pollen record point to the establishment of warmer, wetter andperhaps more seasonal conditions associated with a strengthening Asian Summer Monsoon during theshift from Pleistocene to Holocene climatic conditions

Laser-plasma interactions in high-energy density plasmas

Laser-plasma interactions (LPI) have been studied experimentally in high-temperature, high-energy density plasmas. The studies have been performed using the Omega laser at the Laboratory for Laser Energetics (LLE), Rochester, NY. Up to 10 TW of power was incident upon reduced-scale hohlraums, distributed in three laser beam cones. The hot hohlraums fill quickly with plasma. Late in the laser pulse, most of the laser energy is deposited at the laser entrance hole, where most of the LPI takes place. Due to the high electron temperature, the stimulated Raman scattering (SRS) spectrum extends well beyond ${\rm \omega}_{0}$/2, due to the Bohm-Gross shift. This high-temperature, high-energy density regime provides a unique opportunity to study LPI beyond inertial confinement fusion (ICF) conditions

New integrated molecular approaches for investigating lake settlements in north-western Europe

Lake settlements, particularly crannogs, pose several contradictions—visible yet inaccessible, widespread yet geographically restricted, persistent yet vulnerable. To further our understanding, we developed the integrated use of palaeolimnological (scanning XRF, pollen, spores, diatoms, chironomids, Cladocera, microcharcoal, biogenic silica, SEM-EDS, stable-isotopes) and biomolecular (faecal stanols, bile acids, sedaDNA) analyses of crannog cores in south-west Scotland and Ireland. Both can be effective methods sets for revealing occupation chronologies and identifying on-crannog activities and practices. Strong results from sedaDNA and lipid biomarker analyses demonstrate probable on-site animal slaughter, food storage and possible feasting, suggesting multi-period, elite site associations, and the storage and protection of valuable resources