Description: U-Pb ages of detrital zircons in lower Paleozoic sedimentary rocks from New England permit evaluation of the relationships between tectonic activity and provenance of foreland sediments deposited in response to the Taconian and Acadian orogenies. The Lower Cambrian Poughquag Quartzite was deposited on the Laurentian passive margin. Poughquag detrital zircons (n 5 40) are mostly concordant to slightly discordant with 207Pb*/206Pb* ages of 1.67–0.87 Ga and are consistent with a provenance from the nearby Grenville Structural Province. Two Poughquag zircon grains record 206Pb*/238U ages of about 0.64 Ga and 0.55 Ga and could have been derived from riftrelated magmatic rocks. The Middle Ordovician Austin Glen Member of the Normanskill Formation and Lower Silurian Shawangunk Formation represent clastic-wedge sedimentation in the Laurentian foreland deposited in response to the Taconian orogeny (ca. 470–430 Ma). Zircons from these units (n 5 41 for Austin Glen, n 5 29 for Shawangunk) are also predominantly of Grenville age (207Pb*/206Pb* ages of 1.46–0.94 Ga). One zircon from the Austin Glen records an age of 3.29 Ga, consistent with derivation from North American Archean terranes. No zircon from either unit (or reported in the literature) can be interpreted as recording an Ordovician (Taconian) age. Devonian Catskill ‘‘redbeds’’ represent synorogenic to postorogenic foreland sedimentation associated with the Acadian orogeny (ca. 400–360 Ma). Zircons from one sample (n 5 45) are all near concordant and have a bimodal age distribution. Approximately 60% of grains have 207Pb*/ 206Pb* ages of 1.23–1.00 Ga and the other 40% have 206Pb*/238U ages of 0.47–0.42 Ga. Very different proportions of Precambrian and Paleozoic ages are seen in the Catskill sample if zircons are selected on the basis of size or optical clarity, and this observation highlights the possibility of sampling bias if detrital zircons are not randomly selected for U-Pb analysis. The 0.47–0.42 Ga population is consistent with derivation from rocks crystallized during the Taconian orogeny. No analyzed zircon in this sample records an unambiguous Devonian (Acadian) age. Accordingly, during early Paleozoic evolution of the Laurentian foreland basins in New England, detrital zircons do not appear to record contemporaneous orogenic activity but instead are restricted to recycling of the preexisting continental margin. It is possible that substantial topography (e.g., accretionary prism) impeded sediment transport from the active orogen to the foreland basin.

Description: Trial design Cluster randomised controlled trial. Objective To compare current practice for encouraging homeless people to be screened for tuberculosis on a mobile digital X-ray unit in London, UK, with the additional use of volunteer peer educators who have direct experience of tuberculosis, homelessness or both. Participants 46 hostels took part in the study, with a total of 2342 residents eligible for screening. The study took place between February 2012 and October 2013 at homeless hostels in London, UK. Intervention At intervention sites, volunteer peer educators agreed to a work plan that involved moving around the hostel in conjunction with the hostel staff, and speaking to residents in order to encourage them to attend the screening. Randomisation Cluster randomisation (by hostel) was performed using an internet-based service to ensure allocation concealment, with minimisation by hostel size and historical screening uptake. Blinding Only the study statistician was blinded to the allocation of intervention or control arms. Primary outcome The primary outcome was the number of eligible clients at a hostel venue screened for active pulmonary tuberculosis by the mobile X-ray unit. Results A total of 59 hostels were considered for eligibility and 46 were randomised. Control sites had a total of 1192 residents, with a median uptake of 45% (IQR 33–55). Intervention sites had 1150 eligible residents with a median uptake of 40% (IQR 25–61). Using Poisson regression to account for the clustered study design, hostel size and historical screening levels, there was no evidence that peer educators increased uptake (adjusted risk ratio 0.98; 95% CIs 0.80 to 1.20). The study team noted no adverse events. Conclusions This study found no evidence that volunteer peer educators increased client uptake of mobile X-ray unit screening for tuberculosis. Further qualitative work should be undertaken to explore the possible ancillary benefits to peer volunteers. Trial registration number ISRCTN17270334.

Description: About 150 km of high-resolution, seismic-reflection (CHIRP) profiles (ca. 20 m penetration) were collected in Mono Lake in order to define the uppermost sedimentary architecture of the basin, which has been heavily impacted by recent volcanic, tectonic, and climatic processes. The study also provides important background for ongoing efforts to obtain paleoenvironmental records from sediment cores in the lake. The history of four seismic-stratigraphic units in the upper 20 m of section are inferred from the data, and the interpretations are generally consistent with previous interpretations of lake history for the past 2000 years, including a major lowstand at 1941 m. No shorelines below the previously documented major lowstand at 1941 m were found. A relatively steep slope segment, whose toe is at about 1918 m, and which occurs on the southern and western margins of the deep basin of the lake, is interpreted as the relict foreset slope of deposition from prograding western tributaries. This topography is unconformably overlain by a unit of interbedded tephra and lake sediments of variable lithology, which contains tephra of the North Mono (600–625 cal yr BP) eruption in its upper part. The tephra-rich unit is overlain by a mostly massive mudflow deposit that is locally more than 18 m thick and that is distributed in a radial pattern around Paoha Island. The evidence suggests that, within the past few hundred years, rapid uplift of Paoha Island through thick, pre-existing lake deposits led to widespread slope failures, which created a terrain of disrupted, intact blocks near the island, and a thick, fluid mudflow beyond. As is common in mudflows, the mudflow moved up the depositional slope of the lake floor, terminating against the pre-existing slopes, likely in multiple surges. Since about 1700 CE, fine-grained, well-laminated sediments have accumulated in the deep parts of the lake at anomalously rapid rates, probably driven by continued rapid, small-scale shedding of sediment from Paoha Island.

Description: Drilling at Integrated Ocean Drilling Program Site U1381 on the Cocos Ridge offshore Costa Rica recovered 67 primary Miocene (ca. 8 Ma to ca. 16.5 Ma) marine fallout ash layers. Geochemical, volcanological, and geological criteria link these ashes to Plinian eruptions that carried ash to at least 50–450 km from the Galápagos hotspot. These ash layers are the first documentation of highly explosive Miocene Galápagos hotspot volcanism. This volcanism is bimodal with two-thirds of the tephra layers generated by basaltic magmas (glass compositions 〈57 wt% SiO 2 ) and one-third by rhyolitic magmas. The temporal distribution of the tephra layers, inferred from sediment accumulation rates calibrated by 40 Ar/ 39 Ar and biostratigraphic ages, reveals a distinct increase in eruption frequency and hence increased volcanic activity of the Galápagos hotspot after 14 Ma which we interpret in the context of dynamic interaction between the Galápagos plume and spreading ridge.

Description: In this study, we examined the functional importance of EZH2 during skeletal development and homeostasis using the conditional deletion of Ezh2 ( Ezh2 fl/fl ) in early mesenchyme with the use of a Prrx-1-cre driver mouse ( Ezh2 +/+ ). Heterozygous (Ezh2 +/– ) newborn and 4-wk-old mice exhibited increased skeletal size, growth plate size, and weight when compared to the wild-type control ( Ezh2 +/+ ), whereas homozygous deletion of Ezh2 ( Ezh2 –/– ) resulted in skeletal deformities and reduced skeletal size, growth plate size, and weight in newborn and 4-wk-old mice. Ezh2 –/– mice exhibited enhanced trabecular patterning. Osteogenic cortical and trabecular bone formation was enhanced in Ezh2 +/– and Ezh2 –/– animals. Ezh2 +/– and Ezh2 –/– mice displayed thinner cortical bone and decreased mechanical strength compared to the wild-type control. Differences in cortical bone thickness were attributed to an increased number of osteoclasts, corresponding with elevated levels of the bone turnover markers cross-linked C-telopeptide-1 and tartrate-resistant acid phosphatase, detected within serum. Moreover, Ezh2 +/– mice displayed increased osteoclastogenic potential coinciding with an upregulation of Rankl and M-csf expression by mesenchymal stem cells (MSCs). MSCs isolated from Ezh2 +/– mice also exhibited increased trilineage potential compared with wild-type bone marrow stromal/stem cells (BMSCs). Gene expression studies confirmed the upregulation of known Ezh2 target genes in Ezh2 –/– bone tissue, many of which are involved in Wnt/BMP signaling as promoters of osteogenesis and inhibitors of adipogenesis. In summary, EZH2 appears to be an important orchestrator of skeletal development, postnatal bone remodelling and BMSC fate determination in vitro and in vivo .—Hemming, S., Cakouros, D., Codrington, J., Vandyke, K., Arthur, A., Zannettino, A., Gronthos, S. EZH2 deletion in early mesenchyme compromises postnatal bone microarchitecture and structural integrity and accelerates remodeling.

Description: Early to Middle Miocene sea-level oscillations of approximately 40–60 m estimated from far-field records1–3 are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth2. This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene4,5. Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes. Here we provide the earliest geological evidence proving large WAIS expansions occurred during the Early Miocene (~17.72–17.40 Ma). Geochemical and petrographic data show glacimarine sediments recovered at International Ocean Discovery Program (IODP) Site U1521 in the central Ross Sea derive from West Antarctica, requiring the presence of a WAIS covering most of the Ross Sea continental shelf. Seismic, lithological and palynological data reveal the intermittent proximity of grounded ice to Site U1521. The erosion rate calculated from this sediment package greatly exceeds the long-term mean, implying rapid erosion of West Antarctica. This interval therefore captures a key step in the genesis of a marine-based WAIS and a tipping point in Antarctic ice-sheet evolution.