Effects of coastal managed retreat on mercury biogeochemistry

We investigated the impact of managed retreat on mercury (Hg) biogeochemistry at a site subject to diffuse contamination with Hg. We collected sediment cores from an area of land behind a dyke one year before and one year after it was intentionally breached. These sediments were compared to those of an adjacent mudflat and a salt marsh. The concentration of total mercury (THg) in the sediment doubled after the dyke was breached due to the deposition of fresh sediment that had a smaller particle size, and higher pH. The concentration of methylmercury (MeHg) was 27% lower in the sediments after the dyke was breached. We conclude that coastal flooding during managed retreat of coastal flood defences at this site has not increased the risk of Hg methylation or bioavailability during the first year. As the sediment becomes vegetated, increased activity of Hg-methylating bacteria may accelerate Hg-methylation rate

Gaseous mercury flux from salt marshes is mediated by solar radiation and temperature

Salt marshes are ecologically sensitive ecosystems where mercury (Hg) methylation and biomagnification can occur. Understanding the mechanisms controlling gaseous Hg flux from salt marshes is important to predict the retention of Hg in coastal wetlands and project the impact of environmental change on the global Hg cycle. We monitored Hg flux from a remote salt marsh over 9 days which included three cloudless days and a 4 mm rainfall event. We observed a cyclical diel relationship between Hg flux and solar radiation. When measurements at the same irradiance intensity are considered, Hg flux was greater in the evening when the sediment was warm than in the morning when the sediment was cool. This is evidence to suggest that both solar radiation and sediment temperature directly influence the rate of Hg(II) photoreduction in salt marshes. Hg flux could be predicted from solar radiation and sediment temperature in sub-datasets collected during cloudless days (R2 = 0.99), and before (R2 = 0.97) and after (R2 = 0.95) the rainfall event, but the combined dataset could not account for the lower Hg flux observed after the rainfall event that is in contrast to greater Hg flux from soils after rainfall events

Folate-targeted amphiphilic cyclodextrin nanoparticles incorporating a fusogenic peptide deliver therapeutic siRNA and inhibit the invasive capacity of 3D prostate cancer tumours

The main barrier to the development of an effective RNA interference (RNAi) therapy is the lack of a suitable delivery vector. Modified cyclodextrins have emerged in recent years for the delivery of siRNA. In the present study, a folate-targeted amphiphilic cyclodextrin was formulated using DSPE-PEG5000-folate to target prostate cancer cells. The fusogenic peptide GALA was included in the formulation to aid in the endosomal release of siRNA. Targeted nanoparticles were less than 200 nm in size with a neutral surface charge. The complexes were able to bind siRNA and protect it from serum nucleases. Incubation with excess free folate resulted in a significant decrease in the uptake of targeted nanoparticles in LNCaP and PC3 cells, both of which have been reported to have differing pathways of folate uptake. There was a significant reduction in the therapeutic targets, ZEB1 and NRP1 at mRNA and protein level following treatment with targeted complexes. In preliminary functional assays using 3D spheroids, treatment of PC3 tumours with targeted complexes with ZEB1 and NRP1 siRNA resulted in more compact colonies relative to the untargeted controls and inhibited infiltration into the Matrigel™ layer

Mercury in the marine environment of the Canadian Arctic: Review of recent findings

AbstractThis review summarizes data and information which have been generated on mercury (Hg) in the marine environment of the Canadian Arctic since the previous Canadian Arctic Contaminants Assessment Report (CACAR) was released in 2003. Much new information has been collected on Hg concentrations in marine water, snow and ice in the Canadian Arctic. The first measurements of methylation rates in Arctic seawater indicate that the water column is an important site for Hg methylation. Arctic marine waters were also found to be a substantial source of gaseous Hg to the atmosphere during the ice-free season. High Hg concentrations have been found in marine snow as a result of deposition following atmospheric mercury depletion events, although much of this Hg is photoreduced and re-emitted back to the atmosphere. The most extensive sampling of marine sediments in the Canadian Arctic was carried out in Hudson Bay where sediment total Hg (THg) concentrations were low compared with other marine regions in the circumpolar Arctic. Mass balance models have been developed to provide quantitative estimates of THg fluxes into and out of the Arctic Ocean and Hudson Bay.Several recent studies on Hg biomagnification have improved our understanding of trophic transfer of Hg through marine food webs. Over the past several decades, Hg concentrations have increased in some marine biota, while other populations showed no temporal change. Marine biota also exhibited considerable geographic variation in Hg concentrations with ringed seals, beluga and polar bears from the Beaufort Sea region having higher Hg concentrations compared with other parts of the Canadian Arctic. The drivers of these variable patterns of Hg bioaccumulation, both regionally and temporally, within the Canadian Arctic remain unclear. Further research is needed to identify the underlying processes including the interplay between biogeochemical and food web processes and climate change

Whatever works: Uncertainty and technological hybrids in medical innovation

The persistent uncertainty that looms over the search for solutions to health problems offers important conceptual insights for the study of technological change. This paper explores the notion of hybridization, namely the embodiment of multiple competing operational principles within a single medical device, as strategy to deal with the practical shortcomings due to said uncertainty. The history of the development of the hybrid artificial disc affords the elaboration of an alternative view of hybridization and, at the same time, the articulation of a dualism between medical science as area of basic research (e.g. what disease is) and as practical knowledge (e.g. how disease can be tackled).Barberá Tomás, JD.; Consoli, D. (2012). Whatever works: Uncertainty and technological hybrids in medical innovation. Technological Forecasting and Social Change. 79(5):932-948. doi:10.1016/j.techfore.2011.12.009S93294879

Making real progress toward more sustainable societies using decision support models and tools: Introduction to the special volume

Academics, politicians, professionals and the general public are aware that without stewarding our planet’s natural resources, man is on the pathway towards a global collapse. Over the next three decades mankind is expected to consume an estimated 140 billion tons of minerals, ores, fossil fuels and biomass per year – three times current consumption. Social welfare and human wellbeing are threatened with the scarcity of natural resources; consequently, nations and their societies are also at risk of collapse. The readers of this special volume will find a compilation of scholarly research papers with real-life applications that take the challenge of proposing decision-making models and tools to address sustainability challenges in integrative ways. The main focus of this special volume is integration of sustainability dimensions (economic, social, environmental, ethical and time) into decision-support models and to identify pathways to achieve more sustainable societies. The majority of the research in this special volume, 74 percent, focuses on environmental and economic dimensions. Only 26 percent integrated social dimensions with them. Methodologically, a range of mathematical models and tools are presented to support prescriptive decision-making, with some descriptive models integrated, to support decision-makers in solving practical problems across a variety of industries and scenarios. The breadth and complexity of issues facing organizations and society requires innovative applications of these methodologies. The concerns cover a spectrum ranging from energy to solid waste management. A multitude of levels from broad-based policy concerns to strategic inter-organizational sustainable supply chain management and significantly, shop floor operational issues are also covered. The variety of problems and solutions exemplifies the potential for modelling and operations research for addressing some of our world’s most pressing concerns

Association of schizotypy with striatocortical functional connectivity and its asymmetry in healthy adults

Altered striatocortical functional connectivity has been suggested to be a trait marker of schizophrenia spectrum disorders, including schizotypal personality. In the present study, we examined the association between schizotypal personality traits and striatocortical functional connectivity in a sample of healthy adults. The German version of the Schizotypal Personality Questionnaire was obtained from N=111 participants recruited from the general public. Resting-state functional magnetic resonance imaging scans were acquired at 3T. Six striatal seed regions in each hemisphere were defined and striatocortical resting-state functional connectivity (rsFC) as well as its lateralization indices was calculated. Regression analysis showed that schizotypy scores, especially from the positive dimension, were positively correlated with rsFC between ventral striatum and frontal cortex and negatively associated with rsFC between dorsal striatum and posterior cingulate. No significant associations were found between negative dimension schizotypy and striatocortical rsFC. We also found positive correlations between schizotypy total scores and lateralization index of right dorsal caudate and right rostral putamen. In conclusion, the present study extends previous evidence of altered striatocortical rsFC in the schizophrenia spectrum. The observed associations resemble in part the alterations observed in psychotic patients and their relatives, providing support for dimensionality from schizotypal personality to the clinical disorder. Hum Brain Mapp 39:288-299, 2018. (c) 2017 Wiley Periodicals, Inc

Association of IL-4RA single nucleotide polymorphisms, HLA-DR and HLA-DQ in children with Alternaria-sensitive moderate-severe asthma

<p>Abstract</p> <p>Background</p> <p>Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked <it>Alternaria </it>sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying <it>Alternaria </it>sensitivity and asthma, in these studies we examined T cell responses to <it>Alternaria </it>antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma.</p> <p>Methods</p> <p>Sixty children with <it>Alternaria</it>-sensitive moderate-severe asthma were compared to 49 children with <it>Alternaria</it>-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in <it>Alternaria</it>-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 <it>Alternaria</it>-specific T-cells, cultures were stimulated in media alone, <it>Alternaria alternata </it>extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up-regulation of CD23 on B cells.</p> <p>Results</p> <p>Children with <it>Alternaria</it>-sensitive moderate-severe asthma trended to have increased sensitivities to <it>Cladosporium </it>(46% versus 35%), to <it>Aspergillus </it>(43% versus 28%), and significantly increased sensitivities to trees (78% versus 57%) and to weeds (68% versus 48%). The IL-4RA ile75val polymorphism was significantly increased in <it>Alternaria</it>-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency) compared to <it>Alternaria</it>-sensitive mild asthmatics, 57% (0.388 allele frequency). This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL-4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of <it>Alternaria</it>-sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in <it>Alternaria</it>-sensitive moderate-severe asthmatics compared to mild asthmatics to <it>Alternaria </it>extract and Alt a1 stimulation. The frequency of HLA-DQB1*03 allele was significantly decreased in <it>Alternaria</it>-sensitive moderate-severe asthmatics compared to mild asthmatics, 39% versus 63%, with significantly decreased allele frequency, 0.220 versus 0.398.</p> <p>Summary</p> <p>In children with <it>Alternaria</it>-sensitive moderate severe asthma, there was an increased Th2 response to <it>Alternaria </it>stimulation and increased sensitivity to IL-4 stimulation. This skewing towards a Th2 response was associated with an increased frequency of the IL-4RA ile75val polymorphism. In evaluating the HLA association, there was a decreased frequency of HLA-DQB1*03 in <it>Alternaria</it>-sensitive moderate severe asthmatic children consistent with previous studies suggest that HLA-DQB1*03 may be protective against the development of mold-sensitive severe asthma.</p

High-flow nasal cannulae for respiratory support in adult intensive care patients

Background High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adult patients experiencing acute respiratory failure in the intensive care unit (ICU). Objectives We evaluated studies that included participants 16 years of age and older who were admitted to the ICU and required treatment with HFNC. We assessed the safety and efficacy of HFNC compared with comparator interventions in terms of treatment failure, mortality, adverse events, duration of respiratory support, hospital and ICU length of stay, respiratory effects, patient-reported outcomes, and costs of treatment. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3), MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Web of Science, proceedings from four conferences, and clinical trials registries; and we handsearched reference lists of relevant studies. We conducted searches from January 2000 to March 2016 and reran the searches in December 2016. We added four new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. Selection criteria We included randomized controlled studies with a parallel or cross-over design comparing HFNC use in adult ICU patients versus other forms of non-invasive respiratory support (low-flow oxygen via nasal cannulae or mask, continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP)). Data collection and analysis Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. Main results We included 11 studies with 1972 participants. Participants in six studies had respiratory failure, and in five studies required oxygen therapy after extubation. Ten studies compared HFNC versus low-flow oxygen devices; one of these also compared HFNC versus CPAP, and another compared HFNC versus BiPAP alone. Most studies reported randomization and allocation concealment inadequately and provided inconsistent details of outcome assessor blinding. We did not combine data for CPAP and BiPAP comparisons with data for low-flow oxygen devices; study data were insufficient for separate analysis of CPAP and BiPAP for most outcomes. For the primary outcomes of treatment failure (1066 participants; six studies) and mortality (755 participants; three studies), investigators found no differences between HFNC and low-flow oxygen therapies (risk ratio (RR), Mantel-Haenszel (MH), random-effects 0.79, 95% confidence interval (CI) 0.49 to 1.27; and RR, MH, random-effects 0.63, 95% CI 0.38 to 1.06, respectively). We used the GRADE approach to downgrade the certainty of this evidence to low because of study risks of bias and different participant indications. Reported adverse events included nosocomial pneumonia, oxygen desaturation, visits to general practitioner for respiratory complications, pneumothorax, acute pseudo-obstruction, cardiac dysrhythmia, septic shock, and cardiorespiratory arrest. However, single studies reported adverse events, and we could not combine these findings; one study reported fewer episodes of oxygen desaturation with HFNC but no differences in all other reported adverse events. We downgraded the certainty of evidence for adverse events to low because of limited data. Researchers noted no differences in ICU length of stay (mean difference (MD), inverse variance (IV), random-effects 0.15, 95% CI -0.03 to 0.34; four studies; 770 participants), and we downgraded quality to low because of study risks of bias and different participant indications. We found no differences in oxygenation variables: partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) (MD, IV, random-effects 7.31, 95% CI -23.69 to 41.31; four studies; 510 participants); PaO2 (MD, IV, random-effects 2.79, 95% CI -5.47 to 11.05; three studies; 355 participants); and oxygen saturation (SpO2) up to 24 hours (MD, IV, random-effects 0.72, 95% CI -0.73 to 2.17; four studies; 512 participants). Data from two studies showed that oxygen saturation measured after 24 hours was improved among those treated with HFNC (MD, IV, random-effects 1.28, 95% CI 0.02 to 2.55; 445 participants), but this difference was small and was not clinically significant. Along with concern about risks of bias and differences in participant indications, review authors noted a high level of unexplained statistical heterogeneity in oxygenation effect estimates, and we downgraded the quality of evidence to very low. Meta-analysis of three comparable studies showed no differences in carbon dioxide clearance among those treated with HFNC (MD, IV, random-effects -0.75, 95% CI -2.04 to 0.55; three studies; 590 participants). Two studies reported no differences in atelectasis; we did not combine these findings. Data from six studies (867 participants) comparing HFNC versus low-flow oxygen showed no differences in respiratory rates up to 24 hours according to type of oxygen delivery device (MD, IV, random-effects -1.51, 95% CI -3.36 to 0.35), and no difference after 24 hours (MD, IV, random-effects -2.71, 95% CI -7.12 to 1.70; two studies; 445 participants). Improvement in respiratory rates when HFNC was compared with CPAP or BiPAP was not clinically important (MD, IV, random-effects -0.89, 95% CI -1.74 to -0.05; two studies; 834 participants). Results showed no differences in patient-reported measures of comfort according to oxygen delivery devices in the short term (MD, IV, random-effects 0.14, 95% CI -0.65 to 0.93; three studies; 462 participants) and in the long term (MD, IV, random-effects -0.36, 95% CI -3.70 to 2.98; two studies; 445 participants); we downgraded the certainty of this evidence to low. Six studies measured dyspnoea on incomparable scales, yielding inconsistent study data. No study in this review provided data on positive end-expiratory pressure measured at the pharyngeal level, work of breathing, or cost comparisons of treatment. Authors' conclusions We were unable to demonstrate whether HFNC was a more effective or safe oxygen delivery device compared with other oxygenation devices in adult ICU patients. Meta-analysis could be performed for few studies for each outcome, and data for comparisons with CPAP or BiPAP were very limited. In addition, we identified some risks of bias among included studies, differences in patient groups, and high levels of statistical heterogeneity for some outcomes, leading to uncertainty regarding the results of our analysis. Consequently, evidence is insufficient to show whether HFNC provides safe and efficacious respiratory support for adult ICU patients