The environmental impact of climate change adaptation on land use and water quality

Encouraging adaptation is an essential aspect of the policy response to climate change1. Adaptation seeks to reduce the harmful consequences and harness any beneficial opportunities arising from the changing climate. However, given that human activities are the main cause of environmental transformations worldwide2, it follows that adaptation itself also has the potential to generate further pressures, creating new threats for both local and global ecosystems. From this perspective, policies designed to encourage adaptation may conflict with regulation aimed at preserving or enhancing environmental quality. This aspect of adaptation has received relatively little consideration in either policy design or academic debate. To highlight this issue, we analyse the trade-offs between two fundamental ecosystem services that will be impacted by climate change: provisioning services derived from agriculture and regulating services in the form of freshwater quality. Results indicate that climate adaptation in the farming sector will generate fundamental changes in river water quality. In some areas, policies that encourage adaptation are expected to be in conflict with existing regulations aimed at improving freshwater ecosystems. These findings illustrate the importance of anticipating the wider impacts of human adaptation to climate change when designing environmental policies

Clinically Relevant Interactions between Newer Antidepressants and Second-Generation Antipsychotics

INTRODUCTION: Combinations of newer antidepressants and second-generation antipsychotics (SGAs) are frequently used by clinicians. Pharmacokinetic drug interaction (PK DI) and poorly understood pharmacodynamic (PD) drug interaction (PD DI) can occur between them. AREAS COVERED: This paper comprehensively reviews PD DI and PK DI studies. EXPERT OPINION: More PK DI studies are needed to better establish dose correction factors after adding fluoxetine and paroxetine to aripiprazole, iloperidone and risperidone. Further PK DI studies and case reports are also needed to better establish the need for dose correction factors after adding i) fluoxetine to clozapine, lurasidone, quetiapine and olanzapine; ii) paroxetine to olanzapine; iii) fluvoxamine to asenapine, aripiprazole, iloperidone, lurasidone, olanzapine, quetiapine and risperidone; iv) high sertraline doses to aripiprazole, clozapine, iloperidone and risperidone: v) bupropion and duloxetine to aripiprazole, clozapine, iloperidone and risperidone; and vi) asenapine to paroxetine and venlafaxine. Possible beneficial PD DI effects occur after adding SGAs to newer antidepressants for treatment-resistant major depressive and obsessive-compulsive disorders. The lack of studies combining newer antidepressants and SGAs in psychotic depression is worrisome. PD DIs between newer antidepressants and SGAs may be more likely for mirtazapine and bupropion. Adding selective serotonin reuptake inhibitors and SGAs may increase QTc interval and may very rarely contribute to torsades de pointes

Where the Sidewalk Ends: Jets and Missing Energy Search Strategies for the 7 TeV LHC

This work explores the potential reach of the 7 TeV LHC to new colored states in the context of simplified models and addresses the issue of which search regions are necessary to cover an extensive set of event topologies and kinematic regimes. This article demonstrates that if searches are designed to focus on specific regions of phase space, then new physics may be missed if it lies in unexpected corners. Simple multiregion search strategies can be designed to cover all of kinematic possibilities. A set of benchmark models are created that cover the qualitatively different signatures and a benchmark multiregion search strategy is presented that covers these models.Comment: 30 pages, 8 Figures, 3 Tables. Version accepted at JHEP. Minor changes. Added figur

SNAREs Interact with Retinal Degeneration Slow and Rod Outer Segment Membrane Protein-1 during Conventional and Unconventional Outer Segment Targeting

The authors would like to thank Mr. Marc Banworth, Mr. Justin Burnett, and Ms. Jamie Watson for their technical assistance, Drs. Muayyad Al-Ubaidi and David Sherry for their comments on the manuscript, and Drs. Roger Janz, Roderick McInnes, Neeraj Agarwal, Vadim Arshavsky, Robert Molday and Anand Swaroop for the provision of reagents as indicated in the text.Mutations in the photoreceptor protein peripherin-2 (also known as RDS) cause severe retinal degeneration. RDS and its homolog ROM-1 (rod outer segment protein 1) are synthesized in the inner segment and then trafficked into the outer segment where they function in tetramers and covalently linked larger complexes. Our goal is to identify binding partners of RDS and ROM-1 that may be involved in their biosynthetic pathway or in their function in the photoreceptor outer segment (OS). Here we utilize several methods including mass spectrometry after affinity purification, in vitro co-expression followed by pull-down, in vivo pull-down from mouse retinas, and proximity ligation assay to identify and confirm the SNARE proteins Syntaxin 3B and SNAP-25 as novel binding partners of RDS and ROM-1. We show that both covalently linked and non-covalently linked RDS complexes interact with Syntaxin 3B. RDS in the mouse is trafficked from the inner segment to the outer segment by both conventional (i.e., Golgi dependent) and unconventional secretory pathways, and RDS from both pathways interacts with Syntaxin3B. Syntaxin 3B and SNAP-25 are enriched in the inner segment (compared to the outer segment) suggesting that the interaction with RDS/ROM-1 occurs in the inner segment. Syntaxin 3B and SNAP-25 are involved in mediating fusion of vesicles carrying other outer segment proteins during outer segment targeting, so could be involved in the trafficking of RDS/ROM-1.Yeshttp://www.plosone.org/static/editorial#pee

Spectrofluorimetric determination of sertraline in dosage forms and human plasma through derivatization with 9-fluorenylmethyl chloroformate

<p>Abstract</p> <p>Background</p> <p>Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive-compulsive, panic and social anxiety disorders in both adults and children. A survey of the literature reveals that most of the reported methods are either insufficiently sensitive or tedious and require highly sophisticated and dedicated instrumentation. The proposed method is considered to be specific for determination of SER in presence of its metabolite (deaminated form).</p> <p>Results</p> <p>A sensitive, simple and specific spectrofluorimetric method was developed for the determination of sertraline (SER) in pharmaceutical formulations and biological fluids. The method is based on its reaction with 9-fluorenylmethyl chloroformate (FMOC-Cl) in borate buffer of pH 8.0 to yield a highly fluorescent derivative peaking at 315 nm after excitation at 265 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence concentration plot was rectilinear over the range of 0.05-1.0 μg mL^-1with a lower detection limit of 5.34 × 10^-3μg mL^-1and limit of quantitation of 0.016 μg mL^-1.</p> <p>Conclusions</p> <p>The proposed method was successfully applied to the analysis of commercial tablets and the results obtained were in good agreement with those obtained using the reference method. Furthermore, the method was applied for the determination of SER in spiked and real human plasma. The mean % recovery (n = 3) was 94.33 ± 1.53 and 92.00 ± 2.65, respectively. A proposal of the reaction pathway was postulated.</p

Reproducible, Ultra High-Throughput Formation of Multicellular Organization from Single Cell Suspension-Derived Human Embryonic Stem Cell Aggregates

Background: Human embryonic stem cells (hESC) should enable novel insights into early human development and provide a renewable source of cells for regenerative medicine. However, because the three-dimensional hESC aggregates [embryoid bodies (hEB)] typically employed to reveal hESC developmental potential are heterogeneous and exhibit disorganized differentiation, progress in hESC technology development has been hindered. Methodology/Principal Findings: Using a centrifugal forced-aggregation strategy in combination with a novel centrifugalextraction approach as a foundation, we demonstrated that hESC input composition and inductive environment could be manipulated to form large numbers of well-defined aggregates exhibiting multi-lineage differentiation and substantially improved self-organization from single-cell suspensions. These aggregates exhibited coordinated bi-domain structures including contiguous regions of extraembryonic endoderm- and epiblast-like tissue. A silicon wafer-based microfabrication technology was used to generate surfaces that permit the production of hundreds to thousands of hEB per cm 2. Conclusions/Significance: The mechanisms of early human embryogenesis are poorly understood. We report an ultra high throughput (UHTP) approach for generating spatially and temporally synchronised hEB. Aggregates generated in this manner exhibited aspects of peri-implantation tissue-level morphogenesis. These results should advance fundamental studies into early human developmental processes, enable high-throughput screening strategies to identify conditions tha

Maintenance of response with atypical antipsychotics in the treatment of schizophrenia: a post-hoc analysis of 5 double-blind, randomized clinical trials

<p>Abstract</p> <p>Background</p> <p>How long an antipsychotic is effective in maintaining response is important in choosing the correct treatment for people with schizophrenia. This post-hoc analysis describes maintenance of response over 24 or 28 weeks in people treated for schizophrenia with olanzapine, risperidone, quetiapine, ziprasidone, or aripiprazole.</p> <p>Methods</p> <p>This was a post-hoc analysis using data from 5 double-blind, randomized, comparative trials of 24 or 28 weeks duration in which olanzapine was compared to risperidone (1 study; N = 339), quetiapine (1 study; N = 346), ziprasidone (2 studies; N = 548 and 394) or aripiprazole (1 study; N = 566) for treatment of schizophrenia. For each study, time to loss of response in patients who met criteria for response at Week 8 and the proportion of patients who lost response following Week 8 were compared by treatment group. The number needed to treat (NNT) with olanzapine rather than comparator to avoid loss of one additional responder over 24 or 28 weeks of treatment was calculated for each study.</p> <p>Results</p> <p>Time maintained in response was significantly longer (p < .05) for olanzapine compared to risperidone, quetiapine, and ziprasidone. Olanzapine did not significantly differ from aripiprazole. The proportion of patients who lost response was significantly lower for olanzapine versus risperidone, quetiapine, and ziprasidone (p < .05). NNTs to avoid one additional patient with loss of response with olanzapine versus risperidone, quetiapine and ziprasidone were favourable, ranging from 5 to 9.</p> <p>Conclusion</p> <p>During 24 and 28 weeks of treatment, the antipsychotics studied differed in the time that treated patients with schizophrenia remained in response and the proportion of patients who lost response. Olanzapine treatment resulted in a consistent and statistically significant advantage in maintenance of response compared to treatment with risperidone, quetiapine and ziprasidone; but not compared to treatment with aripiprazole.</p

Bright excitons in monolayer transition metal dichalcogenides: from Dirac cones to Dirac saddle points

In monolayer transition metal dichalcogenides, tightly bound excitons have been discovered with a valley pseudospin that can be optically addressed through polarization selection rules. Here, we show that this valley pseudospin is strongly coupled to the exciton center-of-mass motion through electron-hole exchange. This coupling realizes a massless Dirac cone with chirality index I=2 for excitons inside the light cone, i.e. bright excitons. Under moderate strain, the I=2 Dirac cone splits into two degenerate I=1 Dirac cones, and saddle points with a linear Dirac spectrum emerge in the bright exciton dispersion. Interestingly, after binding an extra electron, the charged exciton becomes a massive Dirac particle associated with a large valley Hall effect protected from intervalley scattering. Our results point to unique opportunities to study Dirac physics, with exciton's optical addressability at specifiable momentum, energy and pseudospin. The strain-tunable valley-orbit coupling also implies new structures of exciton condensates, new functionalities of excitonic circuits, and possibilities for mechanical control of valley pseudospin

Measuring diversity in medical reports based on categorized attributes and international classification systems

<p>Abstract</p> <p>Background</p> <p>Narrative medical reports do not use standardized terminology and often bring insufficient information for statistical processing and medical decision making. Objectives of the paper are to propose a method for measuring diversity in medical reports written in any language, to compare diversities in narrative and structured medical reports and to map attributes and terms to selected classification systems.</p> <p>Methods</p> <p>A new method based on a general concept of f-diversity is proposed for measuring diversity of medical reports in any language. The method is based on categorized attributes recorded in narrative or structured medical reports and on international classification systems. Values of categories are expressed by terms. Using SNOMED CT and ICD 10 we are mapping attributes and terms to predefined codes. We use f-diversities of Gini-Simpson and Number of Categories types to compare diversities of narrative and structured medical reports. The comparison is based on attributes selected from the Minimal Data Model for Cardiology (MDMC).</p> <p>Results</p> <p>We compared diversities of 110 Czech narrative medical reports and 1119 Czech structured medical reports. Selected categorized attributes of MDMC had mostly different numbers of categories and used different terms in narrative and structured reports. We found more than 60% of MDMC attributes in SNOMED CT. We showed that attributes in narrative medical reports had greater diversity than the same attributes in structured medical reports. Further, we replaced each value of category (term) used for attributes in narrative medical reports by the closest term and the category used in MDMC for structured medical reports. We found that relative Gini-Simpson diversities in structured medical reports were significantly smaller than those in narrative medical reports except the "Allergy" attribute.</p> <p>Conclusions</p> <p>Terminology in narrative medical reports is not standardized. Therefore it is nearly impossible to map values of attributes (terms) to codes of known classification systems. A high diversity in narrative medical reports terminology leads to more difficult computer processing than in structured medical reports and some information may be lost during this process. Setting a standardized terminology would help healthcare providers to have complete and easily accessible information about patients that would result in better healthcare.</p

Ice sheets as a missing source of silica to the polar oceans

Ice sheets play a more important role in the global silicon cycle than previously appreciated. Input of dissolved and amorphous particulate silica into natural waters stimulates the growth of diatoms. Here we measure dissolved and amorphous silica in Greenland Ice Sheet meltwaters and icebergs, demonstrating the potential for high ice sheet export. Our dissolved and amorphous silica flux is 0.20 (0.06-0.79) Tmol year(-1), ∼50% of the input from Arctic rivers. Amorphous silica comprises >95% of this flux and is highly soluble in sea water, as indicated by a significant increase in dissolved silica across a fjord salinity gradient. Retreating palaeo ice sheets were therefore likely responsible for high dissolved and amorphous silica fluxes into the ocean during the last deglaciation, reaching values of ∼5.5 Tmol year(-1), similar to the estimated export from palaeo rivers. These elevated silica fluxes may explain high diatom productivity observed during the last glacial-interglacial period