bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological characterization of N‐[(2S)‐5‐(6‐fluoro‐3‐pyridinyl)‐2, 3‐dihydro‐1H‐inden‐2‐yl]‐2‐propanesulfonamide: a novel, clinical AMPA receptor positive allosteric modulator
Authors: Ward Simon E , Beswick Paul , Calcinaghi Novella , Dawson Lee A , Gartlon Jane , Graziani Francesca , Jones Declan N C , Lacroix Laurent , Selina Mok M H , Oliosi Beatrice , Pardoe Joanne , Starr Kathryn , Woolley Marie L , Harries Mark H 
Published: December 2016

Background and PurposeAMPA receptor positive allosteric modulators represent a potential therapeutic strategy to improve cognition in people with schizophrenia. These studies collectively constitute the preclinical pharmacology data package used to build confidence in the pharmacology of this molecule and enable a clinical trial application.Experimental Approach[N‐[(2S)‐5‐(6‐fluoro‐3‐pyridinyl)‐2,3‐dihydro 1H–inden‐2‐yl]‐2‐propanesulfonamide] (UoS12258) was profiled in a number of in vitro and in vivo studies to highlight its suitability as a novel therapeutic agent.Key ResultsWe demonstrated that UoS12258 is a selective, positive allosteric modulator of the AMPA receptor. At rat native hetero‐oligomeric AMPA receptors, UoS12258 displayed a minimum effective concentration of approximately 10 nM in vitro and enhanced AMPA receptor‐mediated synaptic transmission at an estimated free brain concentration of approximately 15 nM in vivo. UoS12258 reversed a delay‐induced deficit in novel object recognition in rats after both acute and sub‐chronic dosing. Sub‐chronic dosing reduced the minimum effective dose from 0.3 to 0.03 mg·kg−1. UoS12258 was also effective at improving performance in two other cognition models, passive avoidance in scopolamine‐impaired rats and water maze learning and retention in aged rats. In side‐effect profiling studies, UoS12258 did not produce significant changes in the maximal electroshock threshold test at doses below 10 mg·kg−1.Conclusion and ImplicationsWe conclude that UoS12258 is a potent and selective AMPA receptor modulator exhibiting cognition enhancing properties in several rat behavioural models superior to other molecules that have previously entered clinical evaluation.
miR‐15b mediates oxaliplatin‐induced chronic neuropathic pain through BACE1 down‐regulation
Authors: Ito Naomi , Sakai Atsushi , Miyake Noriko , Maruyama Motoyo , Iwasaki Hirotoshi , Miyake Koichi , Okada Takashi , Sakamoto Atsuhiro , Suzuki Hidenori 
Published: December 2016

Background and PurposeAlthough oxaliplatin is an effective anti‐cancer platinum compound, it can cause painful chronic neuropathy, and its molecular mechanisms are poorly understood. MicroRNAs (miRNAs) are small non‐coding RNAs that negatively regulate gene expression in a sequence‐specific manner. Although miRNAs have been increasingly recognized as important modulators in a variety of pain conditions, their involvement in chemotherapy‐induced neuropathic pain is unknown.Experimental ApproachOxaliplatin‐induced chronic neuropathic pain was induced in rats by i.p. injections of oxaliplatin (2 mg·kg−1) for five consecutive days. The expression levels of miR‐15b and β‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1 also known as β‐secretase 1) were examined in the dorsal root ganglion (DRG). To examine the function of miR‐15b, an adeno‐associated viral vector encoding miR‐15b was injected into the DRG in vivo.Key ResultsAmong the miRNAs examined in the DRG in the late phase of oxaliplatin‐induced neuropathic pain, miR‐15b was most robustly increased. Our in vitro assay results determined that BACE1 was a target of miR‐15b. BACE1 and miR‐15b were co‐expressed in putative myelinated and unmyelinated DRG neurons. Overexpression of miR‐15b in DRG neurons caused mechanical allodynia in association with reduced expression of BACE1. Consistent with these results, a BACE1 inhibitor dose‐dependently induced significant mechanical allodynia.Conclusions and ImplicationsThese findings suggest that miR‐15b contributes to oxaliplatin‐induced chronic neuropathic pain at least in part through the down‐regulation of BACE1.
Geological controls on the present temperature field of the western Sverdrup Basin, Canadian Arctic Archipelago
Authors: Chen Zhuoheng , Grasby Stephen E. , Dewing Keith , Osadetz Kirk G. , Brent Tom 
Published: December 2016

AbstractAnalysis of current temperature data in the Canadian Arctic Archipelago results in the recognition of two major thermal regimes. High temperature regions are observed where salt diapirs and salt cored anticlines are present. Low temperature fields are observed along the western and southern basin margins and around Cornwall‐Amund Ringnes islands, where regional Mesozoic aquifers are exposed to surface, connected to basin boundary faults, or regional unconformities. Meteoric and Holocene sub‐glacial water recharge are inferred to be responsible for the low geothermal regime and low formation water salinity. Neither exhumation associated with the Eocene “Eurekan” orogeny nor volcanic intrusion associated with opening of Amerasia Basin in late Jurassic‐early Cretaceous have been interpreted to be a significant influence on the present day temperature field, although thermal indicators show evidence of elevated thermal alteration of organic matter pointing to earlier, but now dissipated, thermal anomalies.
Getting help from abroad: The macroeconomics of foreign direct investment in infrastructure in low‐income countries
Authors: Germaschewski Yin 
Published: December 2016

AbstractInfrastructure financing needs in most low‐income countries are substantial, but funding for such needs is only partly covered by national governments and aid donors. This paper introduces foreign direct investment (FDI) through public–private partnerships as a source of infrastructure financing in low‐income countries. A two‐sector open economy model is developed to assess the macroeconomic performance of FDI in infrastructure. With efficient foreign investment, an increase in revenue‐generating infrastructure investment boosts productivity and spurs private investment while stabilizing domestic prices. A direct comparison between infrastructure financed by domestic versus foreign investment shows that foreign investment creates higher output growth and welfare gains and is preferable to domestically sourced investment, irrespective of the underlying financing instrument the domestic economy is employing. FDI in non‐revenue‐generating infrastructure is also analyzed and discussed.
High endothelial venules associated with T cell subsets in the inflamed gut of newly diagnosed inflammatory bowel disease patients
Authors: Horjus Talabur Horje C S , Smids C , Meijer J W R , Groenen M J , Rijnders M K , van Lochem E G , Wahab P J 
Published: December 2016

Summary
Naive and central memory T lymphocytes (TN and TCM) can infiltrate the inflamed gut mucosa in inflammatory bowel disease (IBD) patients. Homing of these subsets to the gut might be explained by ectopic formation of tertiary lymphoid organs (TLOs), containing high endothelial venules (HEVs). We aimed to evaluate the presence of HEVs and TLOs in inflamed intestinal mucosa of newly diagnosed, untreated IBD patients in relation to the presence of TN and TCM lymphocytes. IBD patients (n = 39) and healthy controls (n = 8) were included prospectively. Biopsy samples of inflamed and normal intestine, respectively, were analysed by immunohistochemistry for lymphocytes (CD3/CD20), blood vessels (CD31) and peripheral lymph node addressin (PNAd) expression (MECA-79). TN and TCM lymphocyte subsets were identified by flow cytometric immunophenotyping. A higher number of HEVs was found in the inflamed colon of patients with ulcerative colitis [median 3·05 HEV/mm2; interquartile range (IQR) = 0–6·39] and ileum of Crohn's disease patients (1·40; 0-4·34) compared to healthy controls (both 0; P = 0·033). A high density of colonic HEVs (HEVhigh) was associated with increased infiltration of TN and TCM in the inflamed gut (median 87%; IQR = 82–93% of T cell population), compared to HEVlow patients (58%; 38–81%; P = 0·003). The number of colonic follicles was higher in HEVhigh patients (median 0·54/mm2; IQR 0·28–0·84) compared to HEVlow patients (0·25/mm2; 0·08–0·45; P = 0·031) and controls (0·31/mm2; 0·23–0·45; P = 0·043). Increased homing of TN and TCM lymphocytes to inflamed gut tissue in IBD patients might be facilitated by ectopic formation of extrafollicular HEVs and TLOs in a subgroup of patients.
Thrombospondin-derived peptide attenuates Sjögren's syndrome-associated ocular surface inflammation in mice
Authors: Contreras Ruiz L , Mir F A , Turpie B , Masli S 
Published: December 2016

Summary
Sjögren's syndrome is the second most common rheumatic disease in which autoimmune response targets exocrine glands (salivary and lacrimal glands) result in clinical symptoms of dry mouth and dry eye. Inflammation of the lacrimal gland induces tear abnormalities that contribute to the inflammation of the ocular surface, which includes ocular mucosa. Thrombospondin-1 (TSP-1) plays a critical regulatory role in the ocular mucosa and as such TSP-1–/– mice develop spontaneously chronic ocular surface inflammation associated with Sjögren's syndrome. The autoimmune pathology is also accompanied by a peripheral imbalance in regulatory (Treg) and inflammatory Th17 effectors. In this study, we demonstrate an in-vitro effect of a CD47-binding TSP-derived peptide in the induction of transforming growth factor (TGF)-β1-secreting forkhead box protein 2 (Foxp3+) Tregs from activated CD4+CD25– T cells and the inhibition of pathogenic T helper type 17 (Th17)-promoting interleukin (IL)-23 derived from antigen-presenting cells. The in-vivo administration of this peptide promotes Foxp3+ Treg induction and inhibition of Th17 development. Consistent with these results, topical administration of CD47-binding TSP peptide, both before and after the onset of the disease, attenuates clinical symptoms of SS-associated dry eye in TSP-1–/– mice. Augmented expression of Foxp3 detected in the draining lymph nodes of TSP peptide -treated mice compared to those treated with control peptide suggests the ability of TSP peptide to restore peripheral immune imbalance. Thus, our results suggest that TSP-derived peptide attenuates Sjögren's syndrome-associated dry eye and autoimmune inflammation by preventing Th17 development while promoting the induction of Tregs. Collectively, our data identify TSP-derived peptide as a novel therapeutic option to treat autoimmune diseases.
Clinical outcome of salvage neck dissections in head and neck cancer in relation to initial treatment, extent of surgery and patient factors
Authors: van den Bovenkamp K. , Noordhuis M.G. , Oosting S.F. , van der Laan B.F.A.M. , Roodenburg J.L. , Bijl H.P. , Halmos G.B. , Plaat B.E.C. 
Published: December 2016

ObjectiveSalvage surgery has a higher complication rate compared to primary surgical treatment. We evaluated clinical outcome of salvage neck dissections in relation to initial treatment modality, extent of surgery and patient‐related factors.DesignSingle institution consecutive case series.SettingTertiary Head and Neck Cancer Centre.ParticipantsIn all, 87 patients with head and neck squamous cell carcinoma, who underwent salvage neck dissection after initial radiotherapy (n = 30), radiotherapy with carboplatin/5‐fluorouracil (n = 43) or radiotherapy with cetuximab (n = 14).Main outcome measuresIncidence of complications, disease‐specific survival.ResultsComplications occurred in 28% of the patients. Multivariate analysis identified extent of neck dissection as the only independent predictor of surgical complications (P = 0.010). Surgical complication rate was 16% after radiotherapy with systemic treatment, and 47% after radiotherapy alone (P = 0.171). The 5‐year disease‐specific survival was 55%, independent of complications, initial treatment, extent of surgery and patient‐related factors.ConclusionThe only predictor for surgical complications was extent of surgery. Survival was not influenced by complications.
The epidemic of methylisothiazolinone: a European prospective study
Authors: Schwensen Jakob F. , Uter Wolfgang , Bruze Magnus , Svedman Cecilia , Goossens An , Wilkinson Mark , Giménez Arnau Ana , Gonçalo Margarida , Andersen Klaus E. , Paulsen Evy , Agner Tove , Foti Caterina , Aalto‐Korte Kristiina , McFadden John , White Ian , Johansen Jeanne D. ,   on behalf of the European Environmental Contact Dermatitis Research Group
Published: December 2016

SummaryBackgroundThe use of methylisothiazolinone (MI) in cosmetic products has caused an unprecedented epidemic of MI contact allergy. Current data concerning exposures at a European level are required.ObjectivesTo describe demographics and MI exposures for European patients with MI contact allergy.MethodsEleven European dermatology departments from eight European countries prospectively collected data between 1 May and 31 October 2015 among consecutive patients who had positive patch test reactions to MI (2000 ppm aq.).ResultsA total of 6.0% (205/3434; range 2.6–13.0%) of patients had positive patch test reactions to MI. Dermatitis most frequently affected the hands (43.4%), face (32.7%), arms (14.6%), and eyelids (11.7%); 12.7% had widespread dermatitis. For 72.7% (149/205), MI contact allergy was currently relevant mainly because of exposure to cosmetic products (83.2%; 124/149). Of these 124 patients, 19.5% were exposed to leave‐on and rinse‐off cosmetic products, 24.8% only to leave‐on cosmetic products and 38.9% only to rinse‐off cosmetic products containing MI or methylchloroisothiazolinone/MI. The majority of these (79%) noted onset of their dermatitis between 2013 and 2015. Fifteen patients (7.3%) had previously experienced allergic reactions when they were in newly painted rooms.ConclusionClinically relevant MI contact allergy remains prevalent across European countries, mainly because of exposure to rinse‐off and leave‐on cosmetic products.
Patch testing with rubber series inEurope: a critical review and recommendation
Authors: Warburton Katharine L. , Uter Wolfgang , Geier Johannes , Spiewak Radoslaw , Mahler Vera , Crépy Marie‐Noëlle , Schuttelaar Marie Louise , Bauer Andrea , Wilkinson Mark 
Published: December 2016

SummaryBackgroundRubber additives constitute an important group of contact allergens, particularly in certain occupations.ObjectivesTo collect information regarding the current practice of using a ‘rubber series’ inEurope, and discuss this against the background of evidence concerning the prevalence of allergy in order to derive a recommendation for a ‘European rubber series’.MethodsThe following were performed: (i) a survey targeting all members of theCOSTaction ‘StanDerm’ consortium, (ii) analysis of rubber contact allergy data in the database of theEuropeanSurveillanceSystem onContactAllergies, and (iii) a literature review.ResultsInformation from 13 countries was available, from one or several departments of dermatology, and occasionally occupational health. Apart from some substances tested only in single departments, a broad overlap regarding important allergens was evident, but considerable variation existed between departments.ConclusionsAn up‐to‐date ‘European rubber series’ is recommended, with the exclusion of substances only of historical concern. A ‘supplementary rubber series’ containing allergens of less proven importance, requiring further analysis, is recommended for departments specializing in occupational contact allergy. These should be continually updated as new evidence emerges.
Relevance and Reason Relations
Authors: Skovgaard‐Olsen Niels , Singmann Henrik , Klauer Karl Christoph 
Published: December 2016

AbstractThis paper examines precursors and consequents of perceived relevance of a proposition A for a proposition C. In Experiment 1, we test Spohn's (2012) assumption that ∆P = P(C|A) − P(C|~A) is a good predictor of ratings of perceived relevance and reason relations, and we examine whether it is a better predictor than the difference measure (P(C|A) − P(C)). In Experiment 2, we examine the effects of relevance on probabilistic coherence in Cruz, Baratgin, Oaksford, and Over's (2015) uncertain “and‐to‐if” inferences. The results suggest that ∆P predicts perceived relevance and reason relations better than the difference measure and that participants are either less probabilistically coherent in “and‐to‐if” inferences than initially assumed or that they do not follow P(if A, then C) = P(C|A) (“the Equation”). Results are discussed in light of recent results suggesting that the Equation may not hold under conditions of irrelevance or negative relevance.
Evolutionary Constraints on Human Object Perception
Authors: Koopman Sarah E. , Mahon Bradford Z. , Cantlon Jessica F. 
Published: December 2016

AbstractLanguage and culture endow humans with access to conceptual information that far exceeds any which could be accessed by a non‐human animal. Yet, it is possible that, even without language or specific experiences, non‐human animals represent and infer some aspects of similarity relations between objects in the same way as humans. Here, we show that monkeys’ discrimination sensitivity when identifying images of animals is predicted by established measures of semantic similarity derived from human conceptual judgments. We used metrics from computer vision and computational neuroscience to show that monkeys’ and humans’ performance cannot be explained by low‐level visual similarity alone. The results demonstrate that at least some of the underlying structure of object representations in humans is shared with non‐human primates, at an abstract level that extends beyond low‐level visual similarity. Because the monkeys had no experience with the objects we tested, the results suggest that monkeys and humans share a primitive representation of object similarity that is independent of formal knowledge and cultural experience, and likely derived from common evolutionary constraints on object representation.
Fuzzy Models to Inform Social and Environmental Indicator Selection for Conservation Impact Monitoring
Authors: Game Edward T. , Bremer Leah L. , Calvache Alejandro , Moreno Pedro H. , Vargas Amalia , Rivera Baudelino , Rodriguez Lina M. 
Published: December 2016

AbstractConservation projects increasingly aim to deliver both environmental and social benefits. To monitor the success of these projects, it is important to pick indicators for which there is a reasonable expectation of change as a result of the project, and which resonate with project stakeholders. Results chains are widely used in conservation to describe the hypothesized pathways of causal linkages between conservation interventions and desired outcomes. We illustrate how, with limited additional information, results chains can be turned into fuzzy models of social‐ecological systems, and how these models can be used to explore the predicted social and environmental impacts of conservation actions. These predictions can then be compared with the interests of stakeholders in order to identify good indicators of project success. We illustrate this approach by using it to select indicators for a water fund, an increasingly popular and multiobjective conservation strategy.
Effects of rest intervals and training loads on metabolic stress and muscle hypertrophy
Authors: Fink Julius , Kikuchi Naoki , Nakazato Koichi 
Published: December 2016

SummaryWe investigated the effects of volume‐matched resistance training (RT) with different training loads and rest intervals on acute responses and long‐term muscle and strength gains. Ten subjects trained with short rest (30 s) combined with low load (20 RM) (SL) and ten subjects performed the same protocol with long rest (3 min) and high load (8 RM) (LH). Cross‐sectional area (CSA) of the upper arm was measured by magnetic resonance imaging before and after 8 weeks of training. Acute stress markers such as growth hormone (GH) and muscle thickness (MT) changes have been assessed pre and post a single RT session. Only the SL group demonstrated significant increases in GH (7704·20 ± 11833·49%, P<0·05) and MT (35·2 ± 16·9%, P<0·05) immediately after training. After 8 weeks, the arm CSA s in both groups significantly increased [SL: 9·93 ± 4·86% (P<0·001), LH: 4·73 ± 3·01% (P<0·05)]. No significant correlation between acute GH elevations and CSA increases could be observed. We conclude that short rest combined with low‐load training might induce a high amount of metabolic stress ultimately leading to improved muscle hypertrophy while long rest with high‐load training might lead to superior strength increases. Acute GH increases seem not to be directly correlated with muscle hypertrophy.
Inventory‐Related Compensation in Decentralized Organizations
Authors: Schöndube‐Pirchegger Barbara , Voigt Guido 
Published: December 2016

ABSTRACTWe consider a principal agent problem in a decentralized organization. The agent holds private precontracting information with respect to an uncertain demand in a single period setting. Being head of a profit center, his only task is to determine the optimal order quantity. We show that using a profit share as the only performance measure to incentivize the agent creates agency costs. In fact, offering a menu of profit‐sharing contracts to the agent to pick from, requires rent payments to motivate the agent to always choose the desired contract. This result still holds if a fixed payment is added. Using an inventory‐related component as a third measure, however, allows one to solve the agency problem and to achieve first best outcomes. Precisely, each contract needs to specify a bonus or a penalty conditioned on the inventory level at the end of the selling season combined with a profit share and a fixed pay. The paper not only demonstrates that first best can be achieved in the described setting, it also provides a theoretical explanation for the observed practice of using inventory‐related compensation elements, such as service‐level agreements, in organizations.
The Health, Functioning and Wellbeing Summary Traffic Light Communication Tool: a survey of families’ views
Authors: Ireland Peter , Horridge Karen A 
Published: December 2016

AimTo ascertain families’ views about the utility of the Health, Functioning and Wellbeing Summary (HFWS) in positively supporting communication in clinics.MethodThe HFWS was co‐developed with families and members of the multidisciplinary team. A sequential convenience sample of 60 families who attended clinics in Sunderland, UK in 2015 agreed to participate and answered eight questions about their views on the tool's usefulness. Data were recorded and analysed in Microsoft Excel.ResultsAll families agreed that they had been able to discuss everything they had wanted to discuss with the doctor. All of the serious concerns that they had recorded on the HFWS had been addressed in the consultation. Most (58 out of 60; 97%) reported that the tool was easy to understand and complete, and 57 out of 60 (95%) reported that it helped them to gather their thoughts about what they wanted to discuss. Consultations that used the tool were thought to better address the needs of 49 out of 60 families (87.1%), than those in which it was not used.InterpretationThe HFWS was acceptable to most families surveyed, improved communication from their perspective, and ensured that the issues that mattered most to them were addressed in medical consultations. The tool has been translated into a number of other languages. Its acceptability and utility in other settings requires further study.