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

Effects of adding Tiotropium or Aclidinium as triple therapy using impulse oscillometry in COPD

INTRODUCTION: Long-acting muscarinic antagonists confer improvements in spirometry when used in addition to inhaled corticosteroids and long-acting beta-agonists (ICS/LABA) in COPD. The dual objectives of this proof of concept study were to evaluate trough effects of tiotropium (TIO) or aclidinium (ACL) when used as triple therapy and to assess if impulse oscillometry (IOS) might be more sensitive than spirometry in detecting subtle differences in bronchodilator response. METHODS: Patients with moderate to severe COPD already taking ICS/LABA were randomized to receive add-on therapy in cross-over fashion with either TIO 18 µg od or ACL 322 µg bid for 2–3 weeks each. Measurements of IOS, spirometry, 6-min walk test, St George’s Respiratory Questionnaire (SGRQ) and Baseline/Transition Dyspnoea Index (TDI) were made at baseline and after chronic dosing at trough (12 h for ACL and 24 h for TIO), in addition to domiciliary diurnal spirometry. RESULTS: 13 patients were completed: mean age 69 years, FEV(1) 52 % predicted, FEV(1)/FVC 0.48, and R5 202 % predicted. There were no differences in any visit-based trough IOS or spirometry outcomes comparing TIO versus ACL. Resonant frequency but not total airway resistance at 5 Hz (R5) significantly improved from baseline with both treatments while peripheral airway resistance (R5–R20) significantly improved with ACL. Visit-based FEV(1), and forced and relaxed vital capacity were also significantly improved from baseline with both treatments. There were no significant differences in diurnal FEV(1) and FEV(6) profiles between treatments. 6-min walk distance and post-walk fatigue significantly improved from baseline with ACL, while post-walk dyspnea improved with TIO. SGRQ symptom score significantly improved to a similar degree with both treatments. TDI significantly improved with ACL versus TIO by 1.54 units. CONCLUSION: We observed comparable bronchodilator efficacy at trough with TIO and ACL when used as triple therapy in COPD, while IOS was no more sensitive than spirometry

Climate change implications for tidal marshes and food web linkages to estuarine and coastal nekton

Climate change is altering naturally fluctuating environmental conditions in coastal and estuarine ecosystems across the globe. Departures from long-term averages and ranges of environmental variables are increasingly being observed as directional changes [e.g., rising sea levels, sea surface temperatures (SST)] and less predictable periodic cycles (e.g., Atlantic or Pacific decadal oscillations) and extremes (e.g., coastal flooding, marine heatwaves). Quantifying the short- and long-term impacts of climate change on tidal marsh seascape structure and function for nekton is a critical step toward fisheries conservation and management. The multiple stressor framework provides a promising approach for advancing integrative, cross-disciplinary research on tidal marshes and food web dynamics. It can be used to quantify climate change effects on and interactions between coastal oceans (e.g., SST, ocean currents, waves) and watersheds (e.g., precipitation, river flows), tidal marsh geomorphology (e.g., vegetation structure, elevation capital, sedimentation), and estuarine and coastal nekton (e.g., species distributions, life history adaptations, predator-prey dynamics). However, disentangling the cumulative impacts of multiple interacting stressors on tidal marshes, whether the effects are additive, synergistic, or antagonistic, and the time scales at which they occur, poses a significant research challenge. This perspective highlights the key physical and ecological processes affecting tidal marshes, with an emphasis on the trophic linkages between marsh production and estuarine and coastal nekton, recommended for consideration in future climate change studies. Such studies are urgently needed to understand climate change effects on tidal marshes now and into the future

C9orf72 intermediate expansions of 24–30 repeats are associated with ALS

The expansion of a hexanucleotide repeat GGGGCC in C9orf72 is the most common known cause of ALS accounting for ~ 40% familial cases and ~ 7% sporadic cases in the European population. In most people, the repeat length is 2, but in people with ALS, hundreds to thousands of repeats may be observed. A small proportion of people have an intermediate expansion, of the order of 20 to 30 repeats in size, and it remains unknown whether intermediate expansions confer risk of ALS in the same way that massive expansions do. We investigated the association of this intermediate repeat with ALS by performing a meta-analysis of four previously published studies and a new British/Alzheimer’s Disease Neuroimaging Initiative dataset of 1295 cases and 613 controls. The final dataset comprised 5071 cases and 3747 controls. Our meta-analysis showed association between ALS and intermediate C9orf72 repeats of 24 to 30 repeats in size (random-effects model OR = 4.2, 95% CI = 1.23–14.35, p-value = 0.02). Furthermore, we showed a different frequency of the repeat between the northern and southern European populations (Fisher’s exact test p-value = 5 × 10− 3). Our findings provide evidence for the association between intermediate repeats and ALS (p-value = 2 × 10− 4) with direct relevance for research and clinical practice by showing that an expansion of 24 or more repeats should be considered pathogenic

A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of motor neurons. About 25 genes have been verified as relevant to the disease process, with rare and common variation implicated. We used next generation sequencing and repeat sizing to comprehensively assay genetic variation in a panel of known amyotrophic lateral sclerosis genes in 1126 patient samples and 613 controls. About 10% of patients were predicted to carry a pathological expansion of the C9orf72 gene. We found an increased burden of rare variants in patients within the untranslated regions of known disease-causing genes, driven by SOD1, TARDBP, FUS, VCP, OPTN and UBQLN2. We found 11 patients (1%) carried more than one pathogenic variant (P = 0.001) consistent with an oligogenic basis of amyotrophic lateral sclerosis. These findings show that the genetic architecture of amyotrophic lateral sclerosis is complex and that variation in the regulatory regions of associated genes may be important in disease pathogenesis

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN