Reconstructing sea-level change in the Falkland Islands (Islas Malvinas) using salt-marsh foraminifera, diatoms and testate amoebae

Proxy records of past sea-level change provide a means of extending sea-level histories from tide gauges into the pre-industrial period. This is especially valuable in the South Atlantic region where sea-level data are limited to only a few tide-gauge records. Multi-proxy approaches to sea-level reconstruction are relatively rare but have distinct benefits when groups of micro-organisms are sparse or under-represented in modern or fossil sediments. Here, we address this challenge by utilising surface foraminifera, testate amoebae and diatoms from a salt marsh at Swan Inlet, East Falkland. All three micro-organism groups occupied distinct vertical niches in the contemporary salt-marsh. We investigated the relative performance of each group of micro-organisms in providing a sea-level reconstruction using individual (group-specific) regression models and with a multi-proxy regression model that combined all three groups. Foraminifera alone were not a suitable proxy. Surveyed sample elevations were closely matched by estimated elevations using Weighted-Average (WA) and Weighted-Average Partial-Least-Squares (WA- PLS) regressions. Relative sea-level reconstructions were derived by applying each model to microfossil assemblages recovered from a core (SI-2) from the same site. The combined transfer function yielded reconstructive precision (± 0.08 m) comparable to our best single-proxy transfer function (± 0.06 m) but only 18% of palaeo-samples were identified as having “close” or “good” analogues in the combined training data set. We highlight the benefit of a pragmatic approach to sea-level reconstructions whereby additional proxies should be employed if the use of only one proxy performs poorly across the width of the elevation gradient

Late-Holocene climate dynamics recorded in the peat bogs of Tierra del Fuego, South America

The ombrotrophic peat bogs of Tierra del Fuego are located within the southern westerly wind belt (SWWB), which dominates climate variability in this region. We have reconstructed late-Holocene water-table depths from three peat bogs and aimed to relate these records to shifts in regional climate. Water-table depths were quantified by the analysis of testate amoeba assemblages, and a regional transfer function was used to infer past water-table depths. During the last 2000 years, testate amoeba assemblages have been relatively stable, with a dominance of Difflugia pulex and Difflugia pristis type, and an increase in Assulina muscorum and other Euglyphida at the top of each section. Multivariate analyses show that water-table depth remained the main environmental variable explaining assemblages along the TiA12 core, but reconstructions were not significant for the two other cores. In line with the low variability in assemblages, water tables were relatively stable during the last 2000 years. Slightly wetter conditions were found between ~1400 and 900 cal. BP and a pronounced recent dry shift was reconstructed in all of the three peat profiles. Considering the regional climatic context, this recent shift may have been forced by a decrease in precipitation and warmer conditions linked to an increase in the importance of the SWWB. Nevertheless, we cannot exclude the influence of higher UV-B radiation resulting from the local degradation of the ozone layer since the late 1970s, which may have had an additional effect on the relative presence of A. muscorum in the southern Patagonian region

Do baseline characteristics affect depressive symptoms treatment success? Posthoc subgroup analysis from the CONEMO trials

Objective: As a secondary trial plan analysis, we aim to examine whether participant characteristics, measured before randomization, modified the effect of a digital intervention designed to improve depressive symptoms (CONEMO – Emotional Control) on recovery from depression that has presented a substantive impact on previous research.Method: Mixed logistic regression was used to explore interactions between the treatment arm and subgroups of interest, including suicidal ideation, race/color, age, gender, income, type of mobile phone, alcohol misuse, tobacco use, and diabetes/hypertension). We estimated interaction effects between the treatment group and these subgroup factors for the secondary outcomes using linear mixed regression models.Results: Increased effects of the CONEMO intervention on the primary outcome (reduction of the scores of depressive symptoms in at least 50% at three-month follow-up) were observed amongst older and wealthier participants in Lima (p-values 0.030 and 0.001, respectively). At the same time, there was no evidence of such differential effects in São Paulo or any other secondary outcomes level in both countries.Conclusions: Digital intervention used in primary care settings needs to be accessible. We conclude that the technological intervention CONEMO has no heterogeneity effects on most subgroups studied, except income and age in the Lima trial

Effectiveness of a childhood obesity prevention programme delivered through schools, targeting 6 and 7 year olds: cluster randomised controlled trial (WAVES study).

OBJECTIVE: To assess the effectiveness of a school and family based healthy lifestyle programme (WAVES intervention) compared with usual practice, in preventing childhood obesity. DESIGN: Cluster randomised controlled trial. SETTING: UK primary schools from the West Midlands. PARTICIPANTS: 200 schools were randomly selected from all state run primary schools within 35 miles of the study centre (n=980), oversampling those with high minority ethnic populations. These schools were randomly ordered and sequentially invited to participate. 144 eligible schools were approached to achieve the target recruitment of 54 schools. After baseline measurements 1467 year 1 pupils aged 5 and 6 years (control: 28 schools, 778 pupils) were randomised, using a blocked balancing algorithm. 53 schools remained in the trial and data on 1287 (87.7%) and 1169 (79.7%) pupils were available at first follow-up (15 month) and second follow-up (30 month), respectively. INTERVENTIONS: The 12 month intervention encouraged healthy eating and physical activity, including a daily additional 30 minute school time physical activity opportunity, a six week interactive skill based programme in conjunction with Aston Villa football club, signposting of local family physical activity opportunities through mail-outs every six months, and termly school led family workshops on healthy cooking skills. MAIN OUTCOME MEASURES: The protocol defined primary outcomes, assessed blind to allocation, were between arm difference in body mass index (BMI) z score at 15 and 30 months. Secondary outcomes were further anthropometric, dietary, physical activity, and psychological measurements, and difference in BMI z score at 39 months in a subset. RESULTS: Data for primary outcome analyses were: baseline, 54 schools: 1392 pupils (732 controls); first follow-up (15 months post-baseline), 53 schools: 1249 pupils (675 controls); second follow-up (30 months post-baseline), 53 schools: 1145 pupils (621 controls). The mean BMI z score was non-significantly lower in the intervention arm compared with the control arm at 15 months (mean difference -0.075 (95% confidence interval -0.183 to 0.033, P=0.18) in the baseline adjusted models. At 30 months the mean difference was -0.027 (-0.137 to 0.083, P=0.63). There was no statistically significant difference between groups for other anthropometric, dietary, physical activity, or psychological measurements (including assessment of harm). CONCLUSIONS: The primary analyses suggest that this experiential focused intervention had no statistically significant effect on BMI z score or on preventing childhood obesity. Schools are unlikely to impact on the childhood obesity epidemic by incorporating such interventions without wider support across multiple sectors and environments. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97000586.This study was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (project reference No 06/85/11)

Physical activity for antenatal and postnatal depression in women attempting to quit smoking: randomised controlled trial

Background: Antenatal depression is associated with harmful consequences for both the mother and child. One intervention that might be effective is participation in regular physical activity although data on this question in pregnant smokers is currently lacking. Methods: Women were randomised to six-weekly sessions of smoking cessation behavioural-support, or to the same support plus 14 sessions combining treadmill exercise and physical activity consultations. Results: Among 784 participants (mean gestation 16-weeks), EPDS was significantly higher in the physical activity group versus usual care at end-of-pregnancy (mean group difference (95% confidence intervals (CIs)): 0.95 (0.08 to 1.83). There was no significant difference at six-months postpartum. Conclusion: A pragmatic intervention to increase physical activity in pregnant smokers did not prevent depression at end-of-pregnancy or at six-months postpartum. More effective physical activity interventions are needed in this population. Trial registration: Current Controlled Trials ISRCTN48600346. The trial was prospectively registered on 21/07/2008

Unequal Anthropogenic Enrichment of Mercury in Earth's Northern and Southern Hemispheres

Remote Northern Hemisphere (NH) and Southern Hemisphere (SH) lake sediment and peat records of mercury (Hg) deposition have shown a ×3 to ×5 Hg enrichment since pre-industrial times (<1880 AD), leading to the perception that global atmospheric Hg enrichment is moderate and uniform across the hemispheres. Anthropogenic Hg emissions in the NH are, however, approximately 4 times higher than those in the SH. Here, we reconstruct atmospheric Hg deposition in four remote SH peatlands and review sediment and peat Hg records from both hemispheres. We observe a ×4 all-time enrichment in SH Hg deposition from pre-anthropogenic (<1450 AD) to the late 20th-century periods, which is lower than the large ×16 all-time enrichment in NH Hg deposition. We attribute this difference to lower anthropogenic Hg emissions in the SH, and higher natural atmospheric SH Hg concentrations, supported by ×2 higher natural background Hg accumulation in SH peat records. We suggest that the higher SH natural atmospheric Hg deposition reflects the SH land-ocean distribution, and is driven by important SH marine Hg emissions. Our findings indicate that atmospheric Hg background levels and anthropogenic enrichment in both hemispheres are different and should be taken into account in international Hg assessments and environmental policy

Pharmacogenomic associations of adverse drug reactions in asthma:systematic review and research prioritisation

We would like to thank the NIHR Collaboration for Leadership in Applied Health Research and Care North West Coast (CLAHRC) for funding Amanda McKenna’s internship, and Charlotte Kings MPhil, and the members of the PiCA consortia for their help in completing the survey. U. Potočnik, K. Repnik and V. Berce were supported by SysPharmPedia grant, co-financed by Ministry of Education, Science and Sport of the Republic of Slovenia Author information These authors contributed equally: Charlotte King, Amanda McKenna These authors jointly supervised this work: Ian Sinha, Daniel B. HawcuttPeer reviewedPublisher PD

Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain

BACKGROUND: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. METHODS AND FINDINGS: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. CONCLUSIONS: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma