bluuebunny/crossref_metadata_2025 huggingface dataset:
The conservation “myths” we live by: Reimagining human–nature relationships within the Scottish marine policy context
Authors: Brennan Ruth E.
Published: April 2018

There are growing calls for the articulation and consideration of different value systems and emotions in shaping conservation and natural resource management decisions and participatory resource governance. This requires recognition of the socio‐cultural relations attached to landscape and seascape in marine conservation policy. Taking into account the relationship between the socio‐natural environment and socio‐political institutions and processes complicates conservation. Making human values and assumptions explicit within the conservation discourse reveals the inadequacy of conservation that is focused on a biodiversity that is framed only as other‐than‐human nature. This paper considers how the perceived separation between nature and culture underpinning conservation policy and practice exacerbated a conflict between members of a small Scottish island community and the Scottish Government around the creation of a marine protected area (MPA) off the coast of the island. A rich maritime heritage and a distinctive way of knowing the sea suggested the presence of embedded values that appeared to be colliding with values driving the MPA designation process. Social, historical and cultural forces have shaped the perceptions of landscape and seascape of many of the islanders and can help to explain the local resistance to the MPA. Visual participatory methods were used to explore local understandings of the meaning of conservation. The case‐study offers insights into different ways in which marine spaces are conceptualised and how this relates to marine resource governance. It contributes to a more complete understanding of human relations with the marine environment in the context of a marine conservation conflict.
Temporal distribution of 5BrdU‐labelled cells suggests that most injured tissues contribute proliferating cells for the regeneration of the tail and limb in lizard
Authors: Alibardi Lorenzo
Published: April 2018

After tail and limb amputation in lizard, injection of 5BrdU for 6 days produces immunolabelled cells in most tissues of tail and limb stumps. After further 8 and 16 days, and 14 and 22 days of regeneration, numerous 5BrdU‐labelled cells are detected in regenerating tail and limb, derived from most stump tissues. In tail blastema cone at 14 days, sparse‐labelled cells remain in proximal dermis, muscles, cartilaginous tube and external layers of wound epidermis but are numerous in the blastema. In apical regions at 22 days of regeneration, labelled mesenchymal cells are sparse, while the apical wound epidermis contains numerous labelled cells in suprabasal and external layers, indicating cell accumulation from more proximal epidermis. Cell proliferation dilutes the label, and keratinocytes take 8 days to migrate into corneous layers. In healing limbs, labelled cells remain sparse from 14 to 22 days of regeneration in wound epidermis and repairing tissues and little labelling dilution occurs indicating low cell proliferation for local tissue repair but not distal growth. Labelled cells are present in epidermis, intermuscle and peri‐nerve connectives, bone periosteum, cartilaginous callus and sparse fibroblasts, leading to the formation of a scarring outgrowth. Resident stem cells and dedifferentiation occur when stump tissues are damaged.
A randomised, placebo‐controlled, multicentre, Phase 2 clinical trial to evaluate the efficacy and safety of GV1001 in patients with benign prostatic hyperplasia
Authors: Moon Kyong Tae , Yoo Tag Keun , Kwon Se Yun , Ha Ji Yong , Byun Seok Soo , Kim Jang Hwan , Chung Jae Il , Kim Tae Hyoung , Moon Hong Sang , Kim Sang Jae , Lee Kyung Seop
Published: April 2018

Objectives

To evaluate the efficacy and safety of three dosing schemes of GV1001 in patients with benign prostatic hyperplasia (BPH).

Patients and methods

Eligible patients were men aged ≥50 years, with an International Prostate Symptom Score (IPSS) of ≥13, maximum urinary flow rate (Qmax) of 5–15 mL/s, post‐void residual urine volume (PVR) of ≤200 mL, and prostate volume of ≥30 mL. After a 4 week run‐in period, patients were randomly assigned to one of three treatment schedules: Group 1, GV1001 0.4 mg, 2‐week interval; Group 2, GV1001 0.56 mg, 2‐week interval; Group 3, GV1001 0.56 mg, 4‐week interval) or placebo (Group 4). The eligible patients were administered GV1001 or placebo, for a total of seven intradermal injections that were administered at 2‐week intervals at weeks 0, 2, 4, 6, 8, 10, and 12. Treatment continued for 12 weeks, and efficacy was evaluated at weeks 4, 8, 12, 13, and 16. Safety was evaluated throughout the 16‐week period. The primary efficacy variable was change from baseline (CFB) in total IPSS. Secondary endpoints were CFB in Qmax, PVR, prostate volume, International Index of Erectile Function score, plasma testosterone level, dihydrotestosterone level, and prostate‐specific antigen level.

Results

A total of 161 patients were included (Group 1, n = 41; Groups 2–4, n = 40). Most patients (88.8%) received all planned doses of the study treatment. At week 13, a statistically significant difference in the mean CFB in IPSS was seen in GV1001 treatment Groups 1 and 2 vs the control group for the full analysis population (−3.5 [control] vs −7.2 and −6.8 in Groups 1 and 2, respectively; both P < 0.05). There were also statistically significant differences in CFB at weeks 8, 12, 13, and 16 in treatment Groups 1 and 2 vs control in the per‐protocol population. There was a statistically significant reduction in prostate gland volume at week 16 vs control in all treatment groups (0.8 [control] vs −4.6, −2.5, and −4.2 mL in Groups 1–3, respectively; all P < 0.05). There were no statistically significant differences found in other secondary outcome measures. Adverse event (AE) reporting was similar across all four groups. No treatment‐emergent AEs were considered to be related to the study drug.

Conclusions

The results indicate that GV1001 was effective and well tolerated, and may provide potential beneficial effects in patients with BPH. Compared with medical therapies that require daily dosing, the convenient dosing regimen of GV1001 may provide greater patient adherence. Further investigation of these observations will require large‐scale clinical evaluation.
Guideline of guidelines: primary monotherapies for localised or locally advanced prostate cancer
Authors: Lancee Michelle , Tikkinen Kari A.O. , de Reijke Theo M. , Kataja Vesa V. , Aben Katja K.H. , Vernooij Robin W.M.
Published: April 2018

Decisions regarding the primary treatment of prostate cancer depend on several patient‐ and disease‐specific factors. Several international guidelines regarding the primary treatment of prostate cancer exist; however, they have not been formally compared. As guidelines often contradict each other, we aimed to systematically compare recommendations regarding the different primary treatment modalities of prostate cancer between guidelines. We searched Medline, the National Guidelines Clearinghouse, the library of the Guidelines International Network, and the websites of major urological associations for prostate cancer treatment guidelines. In total, 14 guidelines from 12 organisations were included in the present article. One of the main discrepancies concerned the definition of ‘localised’ prostate cancer. Localised prostate cancer was defined as cT1–cT3 in most guidelines; however, this disease stage was defined in other guidelines as cT1–cT2, or as any T‐stage as long as there is no lymph node involvement (N0) or metastases (M0). In addition, the risk stratification of localised cancer differed considerably between guidelines. Recommendations regarding radical prostatectomy and hormonal therapy were largely consistent between the guidelines. However, recommendations regarding active surveillance, brachytherapy, and external beam radiotherapy varied, mainly as a result of the inconsistencies in the risk stratification. The differences in year of publication and the methodology (i.e. consensus‐based or evidence‐based) for developing the guidelines might partly explain the differences in recommendations. It can be assumed that the observed variation in international clinical practice regarding the primary treatment of prostate cancer might be partly due to the inconsistent recommendations in different guidelines.
Intermittent vs continuous docetaxel therapy in patients with metastatic castration‐resistant prostate cancer – a phase III study (PRINCE)
Authors: Cash Hannes , Steiner Ursula , Heidenreich Axel , Klotz Theodor , Albers Peter , Melchior Sebastian , Martus Peter , Fuller Florian , Magheli Ahmed , Hinz Stefan , Kempkensteffen Carsten , Miller Kurt ,   the PRINCE investigators
Published: April 2018

Objective

To investigate non‐inferiority of intermittent docetaxel compared to continuous docetaxel in patients with metastatic castration‐resistant prostate cancer (mCRPC).

Patient and Methods

The investigator initiated randomised phase III study included 187 chemotherapy‐naïve patients with mCRPC who were allocated to two treatment arms: intermittent docetaxel and continuous docetaxel. Docetaxel was applied in both arms as weekly (35 mg/m2) or 3‐weekly (75 mg/m2). The primary endpoint was 1‐year survival, which was tested for non‐inferiority (margin δ = 0.125). The secondary endpoints were: overall survival (OS), progression‐free survival (PFS), median time to treatment failure (TTF), and toxicity.

Results

Of 156 eligible patients, 78 were allocated to each arm. The intermittent treatment met the non‐inferiority criteria for 1‐year survival (two‐sided 95% confidence interval, −0.12, 18, P = 0.022), but not for OS, according to the result of a post hoc analysis. The differences between the study arms in PFS and TTF were not significant. The median (range) treatment holiday in the intermittent arm was 110 (13–486) days, or 38% of the overall treatment duration. Safety profiles of both study arms were comparable. The main limitation of this study was that the planned number of patients could not be recruited.

Conclusion

Intermittent docetaxel chemotherapy was non‐inferior to continuous therapy for 1‐year survival; non‐inferiority in regard to OS was not reached.
Affinity propagation: An exemplar‐based tool for clustering in psychological research
Authors: Brusco Michael J. , Steinley Douglas , Stevens Jordan , Cradit J. Dennis
Published: April 2018

Affinity propagation is a message‐passing‐based clustering procedure that has received widespread attention in domains such as biological science, physics, and computer science. However, its implementation in psychology and related areas of social science is comparatively scant. In this paper, we describe the basic principles of affinity propagation, its relationship to other clustering problems, and the types of data for which it can be used for cluster analysis. More importantly, we identify the strengths and weaknesses of affinity propagation as a clustering tool in general and highlight potential opportunities for its use in psychological research. Numerical examples are provided to illustrate the method.
Ice‐marginal forced regressive deltas in glacial lake basins: geomorphology, facies variability and large‐scale depositional architecture
Authors: Winsemann Jutta , Lang Jörg , Polom Ulrich , Loewer Markus , Igel Jan , Pollok Lukas , Brandes Christian
Published: April 2018

This study presents a synthesis of the geomorphology, facies variability and depositional architecture of ice‐marginal deltas affected by rapid lake‐level change. The integration of digital elevation models, outcrop, borehole, ground‐penetrating radar and high‐resolution shear‐wave seismic data allows for a comprehensive analysis of these delta systems and provides information about the distinct types of deltaic facies and geometries generated under different lake‐level trends. The exposed delta sediments record mainly the phase of maximum lake level and subsequent lake drainage. The stair‐stepped profiles of the delta systems reflect the progressive basinward lobe deposition during forced regression when the lakes successively drained. Depending on the rate and magnitude of lake‐level fall, fan‐shaped, lobate or more digitate tongue‐like delta morphologies developed. Deposits of the stair‐stepped transgressive delta bodies are buried, downlapped and onlapped by the younger forced regressive deposits. The delta styles comprise both Gilbert‐type deltas and shoal‐water deltas. The sedimentary facies of the steep Gilbert‐type delta foresets include a wide range of gravity‐flow deposits. Delta deposits of the forced‐regressive phase are commonly dominated by coarse‐grained debrisflow deposits, indicating strong upslope erosion and cannibalization of older delta deposits. Deposits of supercritical turbidity currents are particularly common in sand‐rich Gilbert‐type deltas that formed during slow rises in lake level and during highstands. Foreset beds consist typically of laterally and vertically stacked deposits of antidunes and cyclic steps. The trigger mechanisms for these supercritical turbidity currents were both hyperpycnal meltwater flows and slope‐failure events. Shoal‐water deltas formed at low water depths during both low rates of lake‐level rise and forced regression. Deposition occurred from tractional flows. Transgressive mouthbars form laterally extensive sand‐rich delta bodies with a digitate, multi‐tongue morphology. In contrast, forced regressive gravelly shoal‐water deltas show a high dispersion of flow directions and form laterally overlapping delta lobes. Deformation structures in the forced‐regressive ice‐marginal deltas are mainly extensional features, including normal faults, small graben or half‐graben structures and shear‐deformation bands, which are related to gravitational delta tectonics, postglacial faulting during glacial‐isostatic adjustment, and crestal collapse above salt domes. A neotectonic component cannot be ruled out in some cases.
Welfare analysis when people are different
Authors: Pendakur Krishna
Published: April 2018

Inequality and poverty estimation (indeed, all welfare analysis) must deal with the fact that people are heterogeneous. Equivalence scales and indifference scales are tools that may be used for this. An equivalence scale gives the relative costs faced by different people; an indifference scale gives the relative cost of living for people in different types of households. Equivalence scales and indifference scales can be estimated using off‐the‐shelf household‐level consumer expenditure data and standard econometric techniques for nonlinear equation systems. I offer a short introduction to the identification, estimation and use of equivalence scales and indifference scales and argue that these are complementary tools in the analysis of inequality and poverty. The methods are illustrated with Canadian household expenditure data from the Surveys of Household Spending 2004–2009. Estimated equivalence scales for disability are presented, along with estimated household model parameters and an analysis of consumption poverty.

Analyse du niveau de bien‐être quand les gens sont différents.Les mesures d’inégalité et de pauvreté (en fait toutes les mesures et analyses du niveau de bien‐être) doivent prendre en compte le fait que les gens sont hétérogènes. Les échelles d’équivalence et les échelles d’indifférence sont des outils qu’on peut utiliser pour ce faire. Une échelle d’équivalence établit les coûts relatifs auxquels les différentes personnes doivent faire face; une échelle d’indifférence établit le coût relatif différent de gens qui font partie de différents types de ménages. Les échelles d’équivalence et les échelles d’indifférence peuvent être estimées à l’aide de données sur les dépenses de consommation des ménages pour les produits et services disponibles sur le marché, et des techniques économétriques conventionnelles pour calibrer les systèmes d’équations non‐linéaires. L’auteur présente une courte introduction aux problèmes d’identification, d’estimation, et d’usage des échelles d’équivalence et des échelles d’indifférence, et propose que ce sont des outils complémentaires dans l’analyse de l’inégalité et de la pauvreté. Les méthodes sont illustrées à l’aide de données sur les dépenses des ménages canadiens fournies par les Enquêtes sur les dépenses des ménages 2004‐2009. Les échelles d’équivalence sont estimées pour l’incapacité, ainsi que les paramètres estimés du modèle des ménages et une analyse de la pauvreté en termes de consommation.
Relationship to parents in adulthood with a background of out‐of‐home care in childhood
Authors: Andersson Gunvor
Published: April 2018

The longitudinal study started with children aged up to 4 who had been taken into care because of unacceptable living conditions and deficient parental care. After their initial stay in a children's home, the 26 children in the research group went on to have diverse placement histories throughout their childhood (up to age 18). The children have been divided into 4 subgroups in accordance with the length of time they lived with 1 of their parents or with foster parents. Relationships were 1 of the themes in the primary study as well as in all 8 rounds of follow‐up. This article is based on the 2 most recent rounds when the children had reached the ages of 25 to 30 and 35 to 39. A few of the interviewees talked about a close relationship to 1 of their parents, some had occasional contact, and many more had no contact at all, felt abandoned, or had decided to keep their parent(s) at a distance, not least out of consideration for their own children. The interviews showed that their adult relationship to and/or feelings for parents were still problematic and negatively affected their own well‐being, even if their parent(s) had died.
Allergic contact dermatitis caused by isobornyl acrylate in OmniPod, an innovative tubeless insulin pump
Authors: Raison‐Peyron Nadia , Mowitz Martin , Bonardel Nathalie , Aerts Olivier , Bruze Magnus
Published: April 2018

Background

The frequency of allergic contact dermatitis caused by (meth)acrylates is increasing worldwide, and isobornyl acrylate (IBOA) has been identified as a culprit sensitizer in FreeStyle Libre, a medical device used by diabetic patients.

Objectives

To report on 4 patients sensitized to IBOA contained in OmniPod, a new, tubeless insulin pump, and to describe the clinical and chemical analytical work‐up.

Method

Four patients with eczematous skin eruptions after using OmniPod, including 2 with previous adverse skin reactions to FreeStyle Libre, were patch tested with a baseline series and additional (meth)acrylates, including IBOA in several concentrations and/or vehicles. Gas chromatography‐mass spectrometry (GC‐MS) was used to identify the presence of IBOA in OmniPod.

Results

All patients were shown to be sensitized to IBOA. GC‐MS identified IBOA in OmniPod, with the highest concentrations being found in the unit itself and not in the adhesive patch.

Conclusions

The OmniPod tubeless insulin pump is another source of IBOA, and its use may lead to primary sensitization to this acrylate, or may provoke elicitation of allergic contact dermatitis in previously sensitized patients. Our cases highlight the need to obtain satisfactory cooperation from pharmaceutical companies involved in the manufacture of these widely used medical devices.
Use of drug intoxicated donors for lung transplant: Impact on survival outcomes
Authors: Whited William M. , Ising Mickey S. , Trivedi Jaimin R. , Fox Matthew P. , van Berkel Victor
Published: April 2018

Introduction

The number of increasing deaths due to the opioid epidemic has led to a potential greater supply of organ donors. There is hesitancy to use drug intoxicated donors, and we evaluated their impact on post‐transplant survival.

Background

Patients ≥18 years of age undergoing lung transplantation and donors from whom at least one organ was donated between January 2005 and March 2015 were selected from the United Network of Organ Sharing database. Baseline characteristics and post‐transplant survival were compared between drug intoxicated and all other donors.

Results

The utilization of drug intoxicated donors increased from 1.86% in 2005 to 6.23% in 2014. The 2 study groups had similar characteristics including age, gender, and Lung Allocation Score. As compared to all other donors, drug intoxicated donors were younger (29.1 ± 9.4 vs 34.6 ± 13.4 years, P < .0001), less likely to be male (52% vs 61%, P < .0001), and had a greater smoking history (14% vs 11%, P .04). There was no difference in post–lung transplant survival at 1, 3, and 5 years between drug intoxicated donors (85%, 64%, and 47%) and non‐drug intoxicated donors (83%, 65%, and 51%).

Conclusion

Transplantation utilizing drug intoxicated donor lungs has significantly increased over the past decade without significantly impacting post‐transplant survival.
Dermatologic toxicity from immune checkpoint blockade therapy with an interstitial granulomatous pattern
Authors: Trinidad Celestine , Nelson Kelly C. , Glitza Oliva Isabella C. , Torres‐Cabala Carlos A. , Nagarajan Priyadharsini , Tetzlaff Michael T. , Ivan Doina , Hwu Wen‐Jen , Prieto Victor G. , Curry Jonathan L. , Aung Phyu P.
Published: April 2018

Immunotherapies targeting cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and the programmed cell death 1 (PD‐1) receptor and its ligand (PD‐L1) have showed significant therapeutic benefit in patients with clinically advanced solid malignancies, including melanoma. However, immune‐related adverse events (irAE) are common, and novel dermatologic toxicities continue to emerge as more patients are treated with immunotherapy. Here we describe a patient treated with combination immunotherapy of ipilimumab and pembrolizumab, who developed asymptomatic erythematous patches on both legs. Histopathologic examination revealed a cutaneous interstitial granulomatous dermatitis. Notably, our patient did not require cessation of immunotherapy for these lesions, which subsequently remained stable, while the patient's melanoma remained controlled. This case expands the dermatologic toxicity profile of immune checkpoint blockade, as recognition of such toxicities is critical to optimal patient management.
Diagnosis of anaplastic large cell lymphoma on late peri‐implant breast seroma: Management of cytological sample by an integrated approach
Authors: Ronchi A. , Montella M. , Argenzio V. , Lucia A. , De Renzo A. , Alfano R. , Franco R. , Cozzolino I.
Published: April 2018

Introduction

Peri‐implant breast seroma is a late clinical presentation of reconstructive surgery or augmentation mammoplasty with breast implants. Pre‐operative cytological evaluation of the peri‐implant breast seroma is a common clinical approach, showing mainly an inflammatory reaction or more rarely a breast implant‐associated anaplastic large cell lymphoma. Herein, we reported the role of cytology in the evaluation of peri‐implant breast seroma and its critical pre‐operative implications.

Methods

Eight cases of peri‐implant breast seroma from files at Luigi Vanvitelli University were identified between January and December 2017. In all cases, seroma was aspirated; cytospins were performed and stained by Papanicolaou stain; finally, in all cases, a cell block was obtained for immunocytochemical evaluation and, in one case, for FISH to detect ALK1‐gene translocation.

Results

The median age of patients was 48 years and the mean time between the implant placement and the occurrence of peri‐implant breast seroma was 18 months. Microscopic examination showed breast implant‐associated anaplastic large cell lymphoma in one case, aspecific inflammatory reaction in six cases and silicon‐associated reaction in one case.

Conclusions

Peri‐implant breast seroma may be caused by several pathological conditions with different clinical behaviour. A proper cytological approach to peri‐implant breast seroma allows a correct differential diagnosis between inflammatory conditions and breast implant‐associated anaplastic large cell lymphoma and an appropriate management of the patient.
Fishing pressure and species traits affect stream fish invasions both directly and indirectly
Authors: Peoples Brandon K. , Midway Stephen R.
Published: April 2018

Aim

We sought to identify direct and indirect effects of factors contributing to establishment and spread of 272 stream fish species.

Location

Two hundred and ninety‐seven watersheds in the eastern United States.

Methods

We modelled two variables: (1) whether a species had become established outside its native range (establishment) and (2) the number of watersheds in which species established outside their native range (spread). We estimated these variables by comparing historical distributions to a rich data set of contemporary sampling. We calculated metrics of human use (indexing propagule pressure), and gathered species trait data from an open‐access database. We then used piecewise path analysis to estimate direct and indirect effects of human use, native range size and species traits on the two metrics of species introductions.

Results

We identified a hierarchical causal structure in which native range size and fishing pressure were important direct determinants of introductions. Species traits had some direct effects, but played a more indirect role. Native range size was significantly affected by thermal tolerance and diet breadth. Likewise, fishing pressure was significantly affected by life history strategy: larger‐bodied, longer‐living and more fecund species were positively associated with fishing pressure.

Main conclusions

Functional traits can confer an advantage to some species during the establishment phase, but human use is important for subsequent dispersal throughout the non‐native range. However, human use is non‐random, and is largely a function of species traits. Considering both direct and indirect effects of traits across stages of the invasion process can help to elucidate the full role of traits in species invasions.
Land use legacy effects on woody vegetation in agricultural landscapes of south‐western Ethiopia
Authors: Shumi Girma , Schultner Jannik , Dorresteijn Ine , Rodrigues Patrícia , Hanspach Jan , Hylander Kristoffer , Senbeta Feyera , Fischer Joern
Published: April 2018

Aim

Past land use legacy effects—extinction debts and immigration credits—might be particularly pronounced in regions characterized by complex and dynamic landscape change. The aim of this study was to evaluate how current woody plant species distribution, composition and richness related to historical and present land uses.

Location

A smallholder farming landscape in south‐western Ethiopia.

Methods

We surveyed woody plants in 72 randomly selected 1‐ha sites in farmland and grouped them into forest specialist, generalist and pioneer species. First, we investigated woody plant composition and distribution using non‐metric multidimensional scaling. Second, we modelled species richness in response to historical and current distance from the forest edge. Third, we examined diameter class distributions of trees in recently converted vs. permanent farmland.

Results

Historical distance was a primary driver of woody plant composition and distribution. Generalist and pioneer species richness increased with historical distance. Forest specialists, however, did not respond to historical distance. Only few old individuals of forest specialist species remained in both recently converted and permanent farmlands.

Main conclusions

Our findings suggest that any possible extinction debt for forest specialist species in farmland at the landscape scale was rapidly paid off, possibly because farmers cleared large remnant trees. In contrast, we found substantial evidence of immigration credits in farmland for generalist and pioneer species. This suggests that long‐established farmland may have unrecognized conservation values, although apparently not for forest specialist species. We suggest that conservation policies in south‐western Ethiopia should recognize not only forests, but also the complementary value of the agricultural mosaic—similar to the case of European cultural landscapes. A possible future priority could be to better reintegrate forest species in the farmland mosaic.
Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (CIMT) trial
Authors: Safai N. , Suvitaival T. , Ali A. , Spégel P. , Al‐Majdoub M. , Carstensen B. , Vestergaard H. , Ridderstråle M. ,   the CIMT Trial Group
Published: April 2018

Aim

Metformin is the first‐line treatment for Type 2 diabetes. However, not all people benefit from this drug. Our aim was to investigate the effects of metformin on the plasma metabolome and whether the pretreatment metabolite profile can predict HbA1c outcome.

Methods

Post hoc analysis of the Copenhagen Insulin and Metformin Therapy (CIMT) trial, a multicentre study from May 2008 to December 2012, was carried out. We used a non‐target method to analyse 87 plasma metabolites in participants with Type 2 diabetes (n = 370) who were randomized in a 1 : 1 ratio to 18 months of metformin or placebo treatment. Metabolites were measured by liquid chromatography–mass spectrometry at baseline and at 18‐month follow‐up and the data were analysed using a linear mixed‐effect model.

Results

At baseline, participants who were on metformin before the trial (n = 312) had higher levels of leucine/isoleucine and five lysophosphatidylethanolamines (LPEs), and lower levels of carnitine and valine compared with metformin‐naïve participants (n = 58). At follow‐up, participants randomized to metformin (n = 188) had elevated levels of leucine/isoleucine and reduced carnitine, tyrosine and valine compared with placebo (n = 182). At baseline, participants on metformin treatment with the highest levels of carnitine C10:1 and leucine/isoleucine had the lowest HbA1c (P‐interaction = 0.02 and 0.03, respectively). This association was not significant with HbA1c at follow‐up.

Conclusions

Metformin treatment is associated with decreased levels of valine, tyrosine and carnitine, and increased levels of leucine/isoleucine. None of the identified metabolites can predict the HbA1c‐lowering effect of metformin. Further studies of the association between metformin, carnitine and leucine/isoleucine are warranted.
Association between left atrial stiffness and aortic plaque thickness in hypertensive patients with stroke
Authors: Mahfouz Ragab A. , Galal Islam , Ghareb Mohamed S. , Abdelghafar Adel S.
Published: April 2018

Objective

Our aim was to investigate the relation between left atrial stiffness (LASt) and thoracic aortic plaque thickness in hypertensive patients with stroke.

Method

A total of 97 hypertensive patients were recruited (age: 59.2 ± 7.5 years), including 56 consecutive patients with undefined stroke and 41 age‐matched hypertensive patients without stroke. Left atrial strain and stiffness were measured using speckle tracking echo. Thoracic aortic plaque detection and evaluation was performed using transesophageal echocardiography.

Results

Hypertensive patients with stroke, when compared with those without stroke, had a significantly higher LASt value (P < .001). The percentage of plaque 1–4 mm thickness were comparable in both groups (23.2% vs 21.9%; P > .05). While the percentage of plaque ≥4 mm thickness was much higher in hypertensive patients with stroke (71.4% vs 4.9%; P < .001). LASt was considerably increased in hypertensive group with paroxysmal atrial fibrillation (PAF) when compared to hypertensive group without PAF (P < .01). A significant positive correlation was found between the LASt and plaque thickness (P < .001). Multivariate analysis showed that LASt was the strongest independent predictor for ≥4 mm aortic plaque thickness (Hazard ratio = 6.153; P < .001). With receiver operating characteristic (ROC) curve analysis, LASt > 0.63 was the best cutoff value in predicting aortic plaque thickness ≥ 4 mm.

Conclusion

Left atrial stiffness was significantly associated with aortic plaque thickness ≥ 4 mm, in hypertensive patients with stroke. These finding prevailed the importance of LASt in risk stratification of hypertension.
Co‐occurrence of defensive traits in the potato aphid Macrosiphum euphorbiae
Authors: Clarke Hannah V. , Foster Stephen P. , Oliphant Linda , Waters Ewan W. , Karley Alison J.
Published: April 2018

1. Insecticide usage selects strongly for resistance in aphid populations, but this could entail fitness costs in other resistance traits. The potato aphid Macrosiphum euphorbiae Thomas exhibits intraspecific variation in susceptibility to parasitism by braconid wasps and provides a suitable species to study the relation between the defensive traits of parasitism and insecticide resistance.

2. Clonal lines (23 in total) of M. euphorbiae were established from aphids collected in 2013 from geographically separate populations in the U.K. Clonal lines belonged to five aphid genotypes, but one genotype predominated (78% of samples), and the facultative endosymbiont Hamiltonella defensa was detected in c. 40% of lines.

3. Total esterase activity in aphid tissues varied significantly between aphid genotypes and collection areas, but there was no clear pattern in relation to H. defensa infection or between collection sites likely to differ in insecticide pressures.

4. Five clonal lines representing low to moderate levels of enzyme activity, which included different aphid genotypes and presence/absence of H. defensa infection, were assayed for their susceptibility to the parasitoid wasp Aphidius ervi Haliday. Aphid mummification varied significantly between aphid genotypes, with low values in one genotype of aphids irrespective of H. defensa presence.

5. The results revealed that aphid lines belonging to the parasitism‐resistant genotype exhibited moderate levels of total esterase activity, indicating a competitve advantage for this genotype of M. euphorbiae when exposed to chemical and biological control factors in agroecosystems.
Big floods, big knowledge gap: Food web dynamics in a variable river system
Authors: Davis Aaron M. , Pusey Brad J. , Pearson Richard G.
Published: April 2018

While flow regime is widely recognised as an over‐arching feature structuring aquatic ecosystems, the influence of flood events on feeding habits in fish assemblages inhabiting variable environments remains largely unknown. In this study, we investigated how diets of a fish assemblage changed in response to fluctuations in hydrology in a highly variable, wet‐dry tropical Australian river. We compared dietary habits, trophic guilds and intra‐ and interspecific dietary overlap and diet breadth across different seasons. Wet‐season floods acted as major geomorphic and ecological perturbations that exerted substantial effects on the trophic dynamics of the terapontid assemblage, particularly through the removal of in‐stream plant production and detritus. Forced by major shifts in food source availability due to seasonal flooding, fishes responded to these perturbations by marked changes in diet, with significant guild switching following wet‐season floods. Rather than the predictable, gradual, changes in consumer–resource interactions associated with the gentler seasonal flood pulse evident in other tropical river systems, study results instead emphasised rapid and profound changes to species' diets and trophic interactions following abrupt flood pulses. These sudden shifts in food sources may also explain some of the lack of clarity in discrimination of specific carbon sources or species' trophic levels evident in isotopic food web studies from the region. Results indicate that the effects of flood pulses on assemblage trophic interactions may differ among ecosystem types and across the broad potential scale of hydrological disturbance mediated by flood events.
Genomewide identification and development of microsatellite markers for Marssonina brunnea and their applications in two populations
Authors: Zhang Y. , He W. , Yan D.‐H.
Published: April 2018

Marssonina brunnea is an important pathogen that causes Marssonina leaf spot disease of poplar (MLDP) in various poplar species. Resistance breeding is considered as the main method for preventing this disease and requires information on genetic diversity and population structure. However, molecular markers that may be utilized in the identification of this fungus are limited. This study investigated the distribution of microsatellites in the M. brunnea genome. A total of 15,356 microsatellite markers (excluding mononucleotide repeats) were isolated from 50.1 Mb of genomic sequence. Eight M. brunnea isolates were evaluated in terms of 102 loci, followed by the selection of markers that could be utilized in investigating the population structure of 47 M. brunnea isolates from two populations. Twenty‐four polymorphic microsatellite markers were developed for M. brunnea. The number of alleles per locus ranged from two to eight (average: 3.75). The polymorphism information content (PIC) of these loci ranged from 0.0408 to 0.6492. The average Shannon's information index of these loci in the two populations was 0.3819 and 0.5351, respectively. Using these markers, M. brunnea isolates were mainly divided into two distinct clusters based on the relatedness of the sampling sites. These results indicate that the selected markers could be effectively utilized in investigating the population genetic structure of M. brunnea. This is the first report on microsatellite markers in M. brunnea.
Nietzsche on guilt: Dependency, debt, and imperfection
Authors: Morrisson Iain
Published: April 2018

In this paper, I offer a new way of reading Nietzsche's second essay inOn the Genealogy of Morality. At the heart of my account is the claim that Nietzsche is primarily interested in a persistent or existential form of guilt in this essay and only concerned with locally reactive cases of guilt as a function of this deeper phenomenon. I argue that, for Nietzsche, this persistent form of guilt develops out of a deep feeling of indebtedness or owing that accompanies a fearful sense of dependency on the gods. When this sense of dependent indebtedness mixes with bad conscience, which arises through the shift from prehistoric tribes to state‐like communities, it becomes a moral problem; vast numbers of “slaves and serfs” (GM II.20) start to feel like they are not sufficiently honoring their dependent relationship with the gods. It is this feeling of persistent guilt that Nietzsche thinks metastasizes into Christian guilt.
Ictal connectivity in childhood absence epilepsy: Associations with outcome
Authors: Tenney Jeffrey R. , Kadis Darren S. , Agler William , Rozhkov Leonid , Altaye Mekibib , Xiang Jing , Vannest Jennifer , Glauser Tracy A.
Published: April 2018

Objective

The understanding of childhood absence epilepsy (CAE) has been revolutionized over the past decade, but the biological mechanisms responsible for variable treatment outcomes are unknown. Our purpose in this prospective observational study was to determine how pretreatment ictal network pathways, defined using a combined electroencephalography (EEG)–functional magnetic resonance imaging (EEG‐fMRI) and magnetoencephalography (MEG) effective connectivity analysis, were related to treatment response.

Methods

Sixteen children with newly diagnosed and drug‐naive CAE had 31 typical absence seizures during EEG‐fMRI and 74 during MEG. The spatial extent of the pretreatment ictal network was defined using fMRI hemodynamic response with an event‐related independent component analysis (eICA). This spatially defined pretreatment ictal network supplied prior information for MEG‐effective connectivity analysis calculated using phase slope index (PSI). Treatment outcome was assessed 2 years following diagnosis and dichotomized to ethosuximide (ETX)–treatment responders (N = 11) or nonresponders (N = 5). Effective connectivity of the pretreatment ictal network was compared to the treatment response.

Results

Patterns of pretreatment connectivity demonstrated strongest connections in the thalamus and posterior brain regions (parietal, posterior cingulate, angular gyrus, precuneus, and occipital) at delta frequencies and the frontal cortices at gamma frequencies (P < .05). ETX treatment nonresponders had pretreatment connectivity, which was decreased in the precuneus region and increased in the frontal cortex compared to ETX responders (P < .05).

Significance

Pretreatment ictal connectivity differences in children with CAE were associated with response to antiepileptic treatment. This is a possible mechanism for the variable treatment response seen in patients sharing the same epilepsy syndrome.
Dawn singing of the Brownish‐flanked Bush Warbler influences dawn chorusing in a bird community
Authors: Xia Canwei , Lloyd Huw , Shi Jie , Wei Chentao , Zhang Yanyun
Published: April 2018

Despite numerous studies on the function of the avian dawn chorus, few studies have examined whether dawn singing may influence the singing of other species. Here, we built on our previous study which found male Brownish‐flanked Bush Warblers (Horornis fortipes) increase their dawn singing intensity after conspecific playback on the previous day. We reanalyzed those recordings to quantify the start of dawn singing in other nine sympatric songbird species. Ranking‐scaling analyses identified a distinctive sequential pattern of dawn singing among these bird species between the first and the second dawn chorus, and meta‐analysis showed a significant trend to singing earlier in the bird community accompanied by the increase in dawn singing intensity in Brownish‐flanked Bush Warbler. Species with songs most similar to that of the Brownish‐flanked Bush Warbler and species that were phylogenetically distantly related to the Brownish‐flanked Bush Warbler showed a greater shift in the onset of dawn singing. Our study is one of the few studies showing how bird song influences heterospecific singing, and this may influence the temporal organization of song activity in the community, and result in synchronization in singing activities among different species, such as singing in dawn and dusk chorus.
Concentration‐dependent chemosensory responses towards pheromones are influenced by receiver attributes in Asian elephants
Authors: LaDue Chase A. , Goodwin Thomas E. , Schulte Bruce A.
Published: April 2018

The physical structure of a signal is not sufficient to determine its meaning. For chemical signals between conspecifics, this concept is termed “pheromonal parsimony.” The function of a compound depends not only on its molecular structure but also on its context, which can include signal concentration and various receiver attributes. We sought to investigate the contextual flexibility of chemosensory responses through bioassays with Asian elephant (Elephas maximus) sex pheromones of various concentrations (frontalin, from males, and (Z)‐7‐dodecenyl acetate [Z7‐12:Ac], from females). We hypothesized that elephants would respond stronger to higher concentrations, especially towards the opposite‐sex pheromone, and that receiver age and sexual experience would modify responses. We examined responses of 73 captive elephants to both compounds. Pheromone concentration impacted the rate of chemosensory response, which was further modified by the sex, age and/or sexual experience of the receiver. Response rates increased with concentration for each compound across both sexes. Experience shaped male responses with older, physiologically primed males responding more often. The interaction between experience and age affected female response to frontalin, but not toZ7‐12:Ac. Furthermore, response thresholds were modified by sexual experience in most cases: experienced animals generally had lower thresholds than inexperienced animals. Elephants responded to each solution according to its perceived relevance, including concentration. These results also indicate that receiver attributes (e.g., sex, age and sexual experience) may modify seemingly fixed chemosensory responses and further emphasize the flexibility of vertebrate communication systems.
The Ubiquitous Family Environment: Examining Emotional Insecurity in the Family and Adjustment in School
Authors: Bergman Kathleen N. , Choe Grace E. , Cummings E. Mark , Davies Patrick T.
Published: April 2018

The present study examines adolescents' emotional insecurity and problem behaviors at school. Adolescents (n = 280; 136 boys, 144 girls, Median age = 13) and their parents reported on adolescents' emotional security and adjustment problems. Adolescents' teachers (n = 240) also reported on adolescents' school adjustment. Results support that emotional insecurity is related to adjustment problems in the home and at school. Emotional insecurity in the family system was a better predictor of adolescents' adjustment problems than emotional insecurity in the interparental relationship. Findings have implications for teachers, parents, school administrators and policy‐makers, as adolescents' problem behaviors at school can be explained by their emotional insecurity.
Evaluating the effects of climate change in the southern Benguela upwelling system using the Atlantis modelling framework
Authors: Ortega‐Cisneros Kelly , Cochrane Kevern L. , Fulton Elizabeth A. , Gorton Rebecca , Popova Ekaterina
Published: April 2018

The ocean is affected by multiple anthropogenic stressors including climate change, the effects of which are already evident in many ocean ecosystems. The ABACuS v2 end‐to‐end model together with climate projections from the NEMO‐MEDUSA 2.0 model were used to evaluate the effects of fishing, warming and horizontal and vertical mixing on the southern Benguela upwelling system. Of the drivers examined in this study, warming had the greatest effect on species biomass, with mainly negative effects. The magnitude of the impacts of warming intensified from the RCP 2.6 to the 8.5 emission scenario. Fishing negatively affected demersal and large pelagic fish, which in turn resulted in a biomass increase of forage fish due to a decrease in predation pressure. Water mixing was found to have minor indirect effects on zooplankton biomass and fish. The responses of species and species groups to the combined effects of fishing and warming were approximately equally divided between additive, synergistic and antagonistic. Interpretation of our model results suggests that the southern Benguela system is likely to be affected by climate change, including substantial changes in the abundance of some species important to the region's fisheries. Future planning for fisheries needs to take this into account, including through management that strives to maintain the resilience of key species and the system as a whole. In line with previous studies on the southern Benguela, the results reinforce the importance of including consideration of the indirect and combined impacts of climate change and fishing in management and planning.