Stratigraphic control of landscape response to base-level fall, Young Womans Creek, Pennsylvania, USA

Landscapes are thought to respond to changes in relative base level through the upstream propagation of a boundary that delineates relict from adjusting topography. However, spatially-variable rock strength can influence the topographic expression of such transient landscapes, especially in layered rocks, where strength variations can mask topographic signals expected due to changes in climate or tectonics. Here, we analyze the landscape response to base-level fall in Young Womans Creek, a 220 km2 catchment on the Appalachian Plateau, USA underlain by gently folded Paleozoic sedimentary rocks. We measured in situ 10Be concentrations in stream sands from 17 nested watersheds, and used a spatially-distributed model of sediment and 10Be production to constrain a threefold increase in the rate of base-level fall propagating upstream from the catchment outlet. Using lidar topography and a nearby detailed stratigraphic section, we map the extent of continuous, blocky, resistant sandstone strata that act as a caprock overlying more easily erodible sandstones and siltstones. The caprock influences landscape response in two ways. First, it serves as a boundary between slowly eroding (11.5 m Myr−1), low-sloping (3–5°) areas of relict topography and lower, steeper portions of the landscape adjusting to base-level fall. Second, hillslopes supported by the overlying caprock are armored with coarse sediment and are significantly steeper (20–30°) than hillslopes where the caprock has been eroded (10°), despite having similar erosion rates (36 m Myr−1) and bedrock substrate. Our results illustrate how gently dipping, layered rocks engender complicated relationships between lithology, topography and erosion rate, highlighting the importance of understanding how rock material properties influence surface processes and landscape evolution

Cobalt ions recruit inflammatory cells in vitro through human Toll-like receptor 4

AbstractMetal-on-metal (MoM) hip replacements, often manufactured from a cobalt-chrome alloy, are associated with adverse reactions including soft tissue necrosis and osteolysis. Histopathological analysis of MoM peri-implant tissues reveals an inflammatory cell infiltrate that includes macrophages, monocytes and neutrophils.Toll-like receptor 4 (TLR4) is an innate immune receptor activated by bacterial lipopolysaccharide. Recent studies have demonstrated that cobalt ions from metal-on-metal joints also activate human TLR4, increasing cellular secretion of inflammatory chemokines including interleukin-8 (IL-8, CXCL8) and CCL2. Chemokines recruit immune cells to the site of inflammation, and their overall effect depends on the chemokine profile produced.This study investigated the effect of cobalt on the secretion of inflammatory cytokines CCL20 and IL-6. The chemotactic potential of conditioned media from a cobalt-stimulated human monocyte cell line on primary monocytes and neutrophils was investigated using an in vitro transwell migration assay. The role of TLR4 in observed effects was studied using a small molecule TLR4-specific antagonist.Cobalt ions significantly increased release of CCL2 and IL-6 by MonoMac 6 cells (P<0.001). Conditioned media from cobalt-stimulated cells significantly increased monocyte and neutrophil chemotaxis in vitro (P<0.001). These effects were abrogated by the TLR4 antagonist (P<0.001) suggesting that they occur through cobalt activation of TLR4.This study demonstrates the role of TLR4 in cobalt-mediated immune cell chemotaxis and provides a potential mechanism by which cobalt ions may contribute to the immune cell infiltrate surrounding failed metal hip replacements. It also highlights the TLR4 signalling pathway as a potential therapeutic target in preventing cobalt-mediated inflammation

Impact of the COVID‐19 pandemic on Creutzfeldt–Jakob disease surveillance and patient care in the United Kingdom

BACKGROUND AND PURPOSE: Creutzfeldt–Jakob disease (CJD) is lethal and transmissible. We assessed the impact of the COVID‐19 pandemic on UK CJD surveillance. We hypothesized that (i) disruptions prolonged diagnostic latency; (ii) autopsy rates declined; and (iii) COVID‐19 infection negatively affected diagnosis, care, and survival. METHODS: We retrospectively investigated the first year of the pandemic, using the preceding year as a comparator, quantifying numbers of individuals assessed by the UK National CJD Research & Surveillance Unit for suspected CJD, time to diagnosis, disease duration, and autopsy rates. We evaluated the impact of COVID‐19 status on diagnosis, care, and survival in CJD. RESULTS: A total of 148 individuals were diagnosed with CJD in the pandemic (from a total of 166 individuals assessed) compared to 141 in the comparator (from 145 assessed). No differences were identified in disease duration or time to diagnosis. Autopsy rates were unchanged. Twenty individuals had COVID‐19; 60% were symptomatic, and 10% had severe disease. Disruptions in diagnosis and care were frequently identified. Forty percent of COVID‐19‐positive individuals died; however, COVID‐19 status did not significantly alter survival duration in CJD. CONCLUSIONS: The COVID‐19 pandemic has not impacted UK CJD case ascertainment or survival, but diagnostic evaluation and clinical care of individuals have been affected

Improving Delivery of Secondary Prophylaxis for Rheumatic Heart Disease in a High-Burden Setting: Outcome of a Stepped-Wedge, Community, Randomized Trial

BACKGROUND Health system strengthening is needed to improve delivery of secondary prophylaxis against rheumatic heart disease. METHODS AND RESULTS We undertook a stepped-wedge, randomized trial in northern Australia. Five pairs of Indigenous community clinics entered the study at 3-month steps. Study phases comprised a 12 month baseline phase, 3 month transition phase, 12 month intensive phase and a 3- to 12-month maintenance phase. Clinics received a multicomponent intervention supporting activities to improve penicillin delivery, aligned with the chronic care model, with continuous quality-improvement feedback on adherence. The primary outcome was the proportion receiving ≥80% of scheduled penicillin injections. Secondary outcomes included "days at risk" of acute rheumatic fever recurrence related to late penicillin and acute rheumatic fever recurrence rates. Overall, 304 patients requiring prophylaxis were eligible. The proportion receiving ≥80% of scheduled injections during baseline was 141 of 304 (46%)-higher than anticipated. No effect attributable to the study was evident: in the intensive phase, 126 of 304 (41%) received ≥80% of scheduled injections (odds ratio compared with baseline: 0.78; 95% confidence interval, 0.54-1.11). There was modest improvement in the maintenance phase among high-adhering patients (43% received ≥90% of injections versus 30% [baseline] and 28% [intensive], P<0.001). Also, the proportion of days at risk in the whole cohort decreased in the maintenance phase (0.28 versus 0.32 [baseline] and 0.34 [intensive], P=0.001). Acute rheumatic fever recurrence rates did not differ between study sites during the intensive phase and the whole jurisdiction (3.0 versus 3.5 recurrences per 100 patient-years, P=0.65). CONCLUSIONS This strategy did not improve adherence to rheumatic heart disease secondary prophylaxis within the study time frame. Longer term primary care strengthening strategies are needed. CLINICAL TRIAL REGISTRATION URL: www.anzctr.org.au. Unique identifier: ACTRN12613000223730

The DEEP2 Galaxy Redshift Survey: Design, Observations, Data Reduction, and Redshifts

We describe the design and data sample from the DEEP2 Galaxy Redshift Survey, the densest and largest precision-redshift survey of galaxies at z ~ 1 completed to date. The survey has conducted a comprehensive census of massive galaxies, their properties, environments, and large-scale structure down to absolute magnitude M_B = -20 at z ~ 1 via ~90 nights of observation on the DEIMOS spectrograph at Keck Observatory. DEEP2 covers an area of 2.8 deg^2 divided into four separate fields, observed to a limiting apparent magnitude of R_AB=24.1. Objects with z < 0.7 are rejected based on BRI photometry in three of the four DEEP2 fields, allowing galaxies with z > 0.7 to be targeted ~2.5 times more efficiently than in a purely magnitude-limited sample. Approximately sixty percent of eligible targets are chosen for spectroscopy, yielding nearly 53,000 spectra and more than 38,000 reliable redshift measurements. Most of the targets which fail to yield secure redshifts are blue objects that lie beyond z ~ 1.45. The DEIMOS 1200-line/mm grating used for the survey delivers high spectral resolution (R~6000), accurate and secure redshifts, and unique internal kinematic information. Extensive ancillary data are available in the DEEP2 fields, particularly in the Extended Groth Strip, which has evolved into one of the richest multiwavelength regions on the sky. DEEP2 surpasses other deep precision-redshift surveys at z ~ 1 in terms of galaxy numbers, redshift accuracy, sample number density, and amount of spectral information. We also provide an overview of the scientific highlights of the DEEP2 survey thus far. This paper is intended as a handbook for users of the DEEP2 Data Release 4, which includes all DEEP2 spectra and redshifts, as well as for the publicly-available DEEP2 DEIMOS data reduction pipelines. [Abridged]Comment: submitted to ApJS; data products available for download at http://deep.berkeley.edu/DR4

Expression of mutant exon 1 huntingtin fragments in human neural stem cells and neurons causes inclusion formation and mitochondrial dysfunction.

Robust cellular models are key in determining pathological mechanisms that lead to neurotoxicity in Huntington's disease (HD) and for high throughput pre‐clinical screening of potential therapeutic compounds. Such models exist but mostly comprise non‐human or non‐neuronal cells that may not recapitulate the correct biochemical milieu involved in pathology. We have developed a new human neuronal cell model of HD, using neural stem cells (ReNcell VM NSCs) stably transduced to express exon 1 huntingtin (HTT) fragments with variable length polyglutamine (polyQ) tracts. Using a system with matched expression levels of exon 1 HTT fragments, we investigated the effect of increasing polyQ repeat length on HTT inclusion formation, location, neuronal survival, and mitochondrial function with a view to creating an in vitro screening platform for therapeutic screening. We found that expression of exon 1 HTT fragments with longer polyQ tracts led to the formation of intra‐nuclear inclusions in a polyQ length‐dependent manner during neurogenesis. There was no overt effect on neuronal viability, but defects of mitochondrial function were found in the pathogenic lines. Thus, we have a human neuronal cell model of HD that may recapitulate some of the earliest stages of HD pathogenesis, namely inclusion formation and mitochondrial dysfunction

Non-destructive determination of floral staging in cereals using X-ray micro computed tomography (µCT)

Background Accurate floral staging is required to aid research into pollen and flower development, in particular male development. Pollen development is highly sensitive to stress and is critical for crop yields. Research into male development under environmental change is important to help target increased yields. This is hindered in monocots as the flower develops internally in the pseudostem. Floral staging studies therefore typically rely on destructive analysis, such as removal from the plant, fixation, staining and sectioning. This time-consuming analysis therefore prevents follow up studies and analysis past the point of the floral staging. Results This study focuses on using X-ray µCT scanning to allow quick and detailed non-destructive internal 3D phenotypic information to allow accurate staging of Arabidopsis thaliana L. and Barley (Hordeum vulgare L.) flowers. X-ray µCT has previously relied on fixation methods for above ground tissue, therefore two contrast agents (Lugol’s iodine and Bismuth) were observed in Arabidopsis and Barley in planta to circumvent this step. 3D models and 2D slices were generated from the X-ray µCT images providing insightful information normally only available through destructive time-consuming processes such as sectioning and microscopy. Barley growth and development was also monitored over three weeks by X-ray µCT to observe flower development in situ. By measuring spike size in the developing tillers accurate non-destructive staging at the flower and anther stages could be performed; this staging was confirmed using traditional destructive microscopic analysis. Conclusion The use of X-ray micro computed tomography (µCT) scanning of living plant tissue offers immense benefits for plant phenotyping, for successive developmental measurements and for accurate developmental timing for scientific measurements. Nevertheless, X-ray µCT remains underused in plant sciences, especially in above-ground organs, despite its unique potential in delivering detailed non-destructive internal 3D phenotypic information. This work represents a novel application of X-ray µCT that could enhance research undertaken in monocot species to enable effective non-destructive staging and developmental analysis for molecular genetic studies and to determine effects of stresses at particular growth stages

Key conservation issues for migratory landand waterbird species on the world’s major flyways

Summary An estimated 19% of the world&apos;s 9,856 extant bird species are migratory, including some 1,600 species of land-and waterbirds. In 2008, 11% of migratory land-and waterbirds were classed by BirdLife International as threatened or near-threatened on the IUCN Red List. Red List indices show that these migrants have become more threatened since 1988, with 33 species deteriorating and just six improving in status. There is also increasing evidence of regional declines. Population trend data show that more Nearctic-Neotropical migrants have declined than increased in North America since the 1980s, and more Palearctic-Afrotropical migrants breeding in Europe declined than increased during 1970-2000. Reviews of the status of migratory raptors show unfavourable conservation status for 51% of species in the African-Eurasian region (in 2005), and 33% of species in Central, South and East Asia (in 2007). Land-use change owing to agriculture is the most frequently cited threat affecting nearly 80% of all threatened and nearthreatened species. However, while agricultural intensification on the breeding grounds is often proposed as the major driver of declines in Palearctic-Afrotropical migrants, some species appear to be limited by the quantity and quality of available habitat in non-breeding areas, notably the drylands of tropical Africa. Forest fragmentation in breeding areas has contributed to the declines of Nearctic-Neotropical migrants with deforestation in non-breeding areas another possible factor. Infrastructure development including wind turbines, cables, towers and masts can also be a threat. Over-harvesting and persecution remain serious threats, particularly at key migration locations. Climate change is affecting birds already, is expected to exacerbate all these pressures, and may also increase competition between migratory and non-migratory species. The conservation of migratory birds thus requires a multitude of approaches. Many migratory birds require effective management of their critical sites, and Important Bird Areas (IBAs) provide an important foundation for such action; however to function effectively in conserving migratory species, IBAs need to be protected and the coherence of the network requires regular review. Since many migratory species (c. 55%) are widely dispersed across their breeding or nonbreeding ranges, it is essential to address the human-induced changes at the wider landscape scale, a very considerable challenge. Efforts to conserve migratory birds in one part of the range are less effective if unaddressed threats are reducing these species&apos; populations and habitats elsewhere. International collaboration and coordinated action along migration flyways as a whole are thus key elements in any strategy for the conservation of migratory birds

Evaluation of knowledge levels amongst village AIDS committees after undergoing HIV educational sessions: results from a pilot study in rural Tanzania

ABSTRACT: BACKGROUND: Village AIDS committees (VAC) were formed by the Tanzanian government in 2003 to provide HIV education to their communities. However, their potential has not been realised due to their limited knowledge and misconceptions surrounding HIV, which could be addressed through training of VAC members. In an attempt to increase HIV knowledge levels and address common misconceptions amongst the VACs, an HIV curriculum was delivered to members in rural north western Tanzania. METHODS: An evaluation of HIV knowledge was conducted prior to and post-delivery of HIV training sessions, within members of three VACs in Kisesa ward. Quantitative surveys were used with several open-ended questions to identify local misconceptions and evaluate HIV knowledge levels. Short educational training sessions covering HIV transmission, prevention and treatment were conducted, with each VAC using quizzes, role-plays and participatory learning and action tools. Post-training surveys occurred up to seven days after the final training session. RESULTS: Before the training, "good" HIV knowledge was higher amongst men than women (p = 0.041), and among those with previous HIV education (p = 0.002). The trade-centre had a faster turn-over of VAC members, and proximity to the trade-centre was associated with a shorter time on the committee.Training improved HIV knowledge levels with more members achieving a "good" score in the post-training survey compared with the baseline survey (p = < 0.001). The training programme was popular, with 100% of participants requesting further HIV training in the future and 51.7% requesting training at three-monthly intervals. CONCLUSIONS: In this setting, a series of HIV training sessions for VACs demonstrated encouraging results, with increased HIV knowledge levels following short educational sessions. Further work is required to assess the success of VAC members in disseminating this HIV education to their communities, as well as up-scaling this pilot study to other regions in Tanzania with different misconceptions

Lockerbie AcademyNeolithic and Early Historic timber halls, a Bronze Age cemetery, an undated enclosure and a post-medieval corn-drying kiln in south-west Scotland

Trial trenching carried out by CFA Archaeology Ltd in 2006 to the north of Lockerbie Academy identified four areas of archaeological significance covering a timescale from early Neolithic to post-medieval periods. The earliest site identified was the remains of a Neolithic timber hall, which was situated on top of the flat plateau towards the northwest end of the site (Area A). Pottery recovered from the Neolithic structure was of the Carinated Bowl ceramic tradition.At the summit of the rounded knoll in the centre of the area (Area D) a Bronze Age phase consisting of a cremation and inhumation cemetery enclosed by a possible ring-cairn was identified. The Bronze Age cemetery included a Collared Urn and a copper alloy dagger of Butterwick type.At the base of the rounded knoll, the remains of an Early Historic timber hall were identified (Area C). This Anglian timber hall reoccupied the site of a post-built structure, which was interpreted as a timber hall, possibly belonging to an earlier British tradition. Radiocarbon dates taken from the primary fill of two of the post-holes of the earlier structure gave dates which are broadly contemporary with the dates obtained for the Anglian hall, suggesting that the post-built structure immediately preceded it.A corn-drying kiln was identified cut into the same knoll as the Bronze Age cemetery (Area D) and has been dated to the late medieval or early post-medieval period.A segmented ditched enclosure was located towards the north-east end of the site (Area B), but the poor survival of this feature combined with a lack of finds and palaeobotanical evidence means that it remains undated and poorly understood