bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel association between serum pentraxin‐2 levels and advanced fibrosis in well‐characterised patients with non‐alcoholic fatty liver disease
Authors: Verna E. C. , Patel J. , Bettencourt R. , Nguyen P. , Hernandez C. , Valasek M. A. , Kisselva T. , Brenner D. A. , Loomba R. 
Published: June 2015

SummaryBackgroundPentraxin‐2 (PTX‐2), a serum protein, inhibits inflammation and fibrosis, and recombinant PTX‐2 is being tested as an anti‐fibrotic agent.AimTo evaluate the association between serum PTX‐2 levels and fibrosis stage in patients with non‐alcoholic fatty liver disease (NAFLD).MethodsSerum pentraxin‐2 levels were compared between four groups of well‐characterised patients including NAFLD with no fibrosis, NAFLD with mild‐moderate fibrosis (stage 1–2), NAFLD with advanced fibrosis (stage 3–4), and age‐sex matched non‐NAFLD controls.ResultsSixty subjects were included in the study. The mean age was 58.9 years, 68% were male and 58% were Caucasian. In univariate analysis, serum PTX‐2 levels significantly decreased from non‐NAFLD controls to mild NAFLD with no fibrosis, to NAFLD with mild‐moderate fibrosis and were lowest in patients with NAFLD and advanced fibrosis, in a dose‐dependent manner (P < 0.0001). In multivariable‐adjusted analyses controlling for age, sex, albumin, and CRP, the results remained consistent and statistically significant. Serum PTX‐2 level had an AUROC of 0.84 (95% CI: 0.71–0.97) for the diagnosis of NAFLD, and an AUROC of 0.77 (95% CI: 0.65–0.90) for the diagnosis of advanced fibrosis in NAFLD. Serum PTX‐2 levels also decreased with increasing liver stiffness as estimated by magnetic resonance elastography (r = −0.31, P = 0.02).ConclusionsPTX‐2 levels are significantly lower in patients with NAFLD compared to non‐NAFLD controls, and decline further in patients with advanced fibrosis. PTX‐2 may therefore be both a biomarker of disease and a potential target for anti‐fibrotic therapy with the recombinant pentraxin‐2.
Developing a Competency‐based Curriculum in Basic and Clinical Pharmacology – A Delphi Study among Physicians
Authors: Midlöv Patrik , Höglund Peter , Eriksson Tommy , Diehl Annika , Edgren Gudrun 
Published: June 2015

AbstractA new curriculum is planned for the medical school at Lund University, Sweden. Pharmacology, in a broad sense, has been identified as a subject that needs to be strengthened based on needs in the healthcare system. The aim was to identify the competencies in basic and clinical pharmacology that a newly qualified physician needs. Using a modified three‐round Delphi technique, 31 physicians were invited to list necessary competencies (round 1). After content analysis, these panel members classified the list by importance on two occasions (rounds 2 and 3) using a 4‐point scale (4 = necessary, 3 = desirable, 2 = useful, 1 = not necessary). Competencies with the highest ranks based on necessity were retained. Thirty physicians accepted the invitation and 25 (83%) of them completed all three rounds. Round 1 resulted in 258 suggestions, which were subsequently reduced to 95 competencies. Of these 95 competencies, 40 were considered necessary by at least 75% of the panel members. The degree of consensus increased between round 2 and round 3. Using a modified Delphi technique, we identified 40 competencies that could be transferred to learning outcomes for a new curriculum in basic and clinical pharmacology at medical school.
Intraspecific Food‐Robbing and Neighborhood Competition: Consequences for Anti‐Robber Vigilance and Colony Productivity
Authors: Jandt Jennifer M. , Hunt Elizabeth M. , McGlynn Terrence P. 
Published: June 2015

AbstractMost social animals have mechanisms to distinguish group members from outsiders, in part to prevent the exploitation of resources reserved for members of the group. Nevertheless, specialized thieves of the Neotropical ant, Ectatomma ruidum, also known as the ‘thieving ant’, regularly enter and steal resources from distinct, neighboring colonies. Here, we examine the mechanisms and consequences of thievery in a population of E. ruidum. We show that (1) individuals from nearby colonies were accepted more often than those from farther colonies; (2) rejection rates decreased as individuals interacted more with non‐nestmates from the same source colony; and (3) colonies that were experimentally treated to reduce thievery rates had improved productivity. The boost in productivity with thievery reduction was greater in low density populations than in high density populations. We conclude that, as in other species, thievery has negative fitness costs to E. ruidum. However, greater acceptance of neighbors than non‐neighbors and increased acceptance after habituation to non‐nestmates suggest a proximate explanation for the presence of thievery. Moreover, lower fitness costs of thievery at high nesting density, combined with observations of extraordinarily high densities of E. ruidum throughout its range, suggest there is little selection pressure among these ants to guard against thieves, thus providing an ultimate explanation why thievery persists among litter‐foraging ants.
Weathering the Storm: Family Ownership, Governance, and Performance Through the Financial and Economic Crisis
Authors: Minichilli Alessandro , Brogi Marina , Calabrò Andrea 
Published: June 2015

AbstractManuscript TypeEmpiricalResearch Question/IssueConsidering the recent financial and economic crisis as a unique exogenous shock, our study investigates the financial performance of family‐controlled firms in “steady‐state” conditions as opposed to situations of severe economic distress. In addition, we focus our attentionwithinfamily firms in order to tease out the leadership (family or non‐family CEO) and family ownership (family ownership concentration or dispersion) conditions that allow some governance arrangements to perform better than others during an economic downturn.Research Findings/InsightsExamining the entire population of Italian industrial family and non‐family publicly listed companies over the period 2002–2012, we observe a significantly and consistently better performance of family‐controlled firms during the financial and economic crisis, a finding that proves to be robust to several analytical specifications, as well as to different performance measures (ROA, ROE). Then, focusing on family firms only, we find that mixed configurations (family CEOs with relatively lower family ownership concentration) produce better performance in the face of an external hazard.Theoretical/Academic ImplicationsOur study confirms the pivotal assumption of the socioemotional wealth perspective that the advantages of family firms show up exactly when ownership is at stake. Our results also add to the growing literature on the resilience of family firms, showing that they are more able than others to absorb exogenous shocks.Practitioner/Policy ImplicationsOur findings suggest the importance of crafting governance structures well in advance of a crisis. Our research speaks to policymakers, indicating the importance of family firms for national economies, and the political opportunity to sustain their growth and managerial development.
Why the ‘last drinking occasion’ approach to measuring alcohol consumption should be avoided
Authors: Østhus Ståle , Brunborg Geir Scott 
Published: June 2015

AbstractIntroduction and AimsThere has been debate about which type of measurement instrument gives the best alcohol consumption estimates. This study used alcohol consumption data for a simulated population to compare the last drinking occasion (LDO) method against the true alcohol consumption. The LDO method requires respondents to indicate the quantity consumed at the LDO, and this information is used to calculate population estimates.Design and MethodsWe simulated three hypothetical distributions of alcohol consumption, each with different underlying drinking patterns and each representing an idealised example of the distribution of alcohol consumption in Norway, Russia and France under specified conditions. We investigated the level of agreement between LDO consumption and the within‐person average consumption, and the expected bias that arises when parameters of interest such as means, percentiles, exceedance proportions, differences in group means, correlation and regression coefficients, attributable fractions, and estimated disease risk functions, are calculated from LDO consumption.ResultsSevere bias was found when LDO consumption was used to calculate common parameters of interest in alcohol and health research. The bias is caused by poor agreement between consumption at the LDO and the within‐person ‘true’ or average consumption. The asymptotically expected bias is particularly problematic because it is unpredictable in terms of direction and magnitude, it varies across groups and populations, and it is probably impossible to adjust for.Discussion and ConclusionFuture data collections should avoid relying on the LDO method as a measure of typical alcohol consumption, despite its ease of administration. [Østhus S, Brunborg GS. Why the ‘last drinking occasion’ approach to measuring alcohol consumption should be avoided. Drug Alcohol Rev 2015;34:549–58]
Alcohol outlet density and violence: A geographically weighted regression approach
Authors: Cameron Michael P. , Cochrane William , Gordon Craig , Livingston Michael 
Published: June 2015

AbstractIntroduction and AimsWe investigate the relationship between outlet density (of different types) and violence (as measured by police activity) across the North Island of New Zealand, specifically looking at whether the relationships vary spatially.Design and MethodsWe use New Zealand data at the census area unit (approximately suburb) level, on police‐attended violent incidents and outlet density (by type of outlet), controlling for population density and local social deprivation. We employed geographically weighted regression to obtain both global average and locally specific estimates of the relationships between alcohol outlet density and violence.ResultWe find that bar and night club density, and licensed club density (e.g. sports clubs) have statistically significant and positive relationships with violence, with an additional bar or night club is associated with nearly 5.3 additional violent events per year, and an additional licensed club associated with 0.8 additional violent events per year. These relationships do not show significant spatial variation. In contrast, the effects of off‐licence density and restaurant/café density do exhibit significant spatial variation. However, the non‐varying effects of bar and night club density are larger than the locally specific effects of other outlet types.Discussion and ConclusionThe relationships between outlet density and violence vary significantly across space for off‐licences and restaurants/cafés. These results suggest that in order to minimise alcohol‐related harms, such as violence, locally specific policy interventions are likely to be necessary. [Cameron MP, Cochrane W, Gordon C, Livingston M. Alcohol outlet density and violence: A geographically weighted regression approach. Drug Alcohol Rev 2016;35:280–288]
Intermittent dosing of rapamycin maintains antiepileptogenic effects in a mouse model of tuberous sclerosis complex
Authors: Rensing Nicholas , Han Lirong , Wong Michael 
Published: June 2015

SummaryObjectiveInhibitors of the mechanistic target of rapamycin (mTOR) pathway have antiepileptogenic effects in preventing epilepsy and pathologic and molecular mechanisms of epileptogenesis in mouse models of tuberous sclerosis complex (TSC). However, long‐term treatment with mTOR inhibitors may be required to maintain efficacy and potentially has chronic side effects, such as immunosuppression. Attempts to minimize drug exposure will facilitate translational efforts to develop mTOR inhibitors as antiepileptogenic agents for patients with TSC. In this study, we tested intermittent dosing paradigms of mTOR inhibitors for antiepileptogenic properties in a TSC mouse model.MethodsWestern blot analysis of phosphorylation of S6 protein was used to assess the dose‐ and time‐dependence of mTOR inhibition by rapamycin in control mice and conditional knockout mice with inactivation of the Tsc1 gene in glial fibrillary acidic protein (GFAP)–expressing cells (Tsc1GFAPCKO mice). Based on the Western blot studies, different dosing paradigms of rapamycin starting at postnatal day 21 were tested for their ability to prevent epilepsy or pathologic abnormalities in Tsc1GFAPCKO mice: 4 days of rapamycin only (4–∞), 4 days on–24 days off (4–24), and 4 days on–10 days off (4–10).ResultsmTOR activity was inhibited by rapamycin in a dose‐dependent fashion and recovered to baseline by about 10 days after the last rapamycin dose. The 4–10 and 4–24 dosing paradigms almost completely prevented epilepsy and the 4–10 paradigm inhibited glial proliferation and megalencephaly in Tsc1GFAPCKO mice.SignificanceIntermittent dosing of rapamycin, with drug holidays of more than 3 weeks, maintains significant antiepileptogenic properties in mouse models of TSC. These findings have important translational applications in developing mTOR inhibitors as antiepileptogenic agents in TSC patients by minimizing drug exposure and potential side effects.
Rapid brief feedback intracerebral stimulation based on real‐time desynchronization detection preceding seizures stops the generation of convulsive paroxysms
Authors: Salam Muhammad T. , Kassiri Hossein , Genov Roman , Perez Velazquez Jose L. 
Published: June 2015

SummaryObjectiveTo investigate the abortion of seizure generation using “minimal” intervention in hippocampi using two rat models of human temporal lobe epilepsy.MethodsThe recording or stimulation electrodes were implanted into both hippocampi (CA1 area). Using the kainic acid (chronic: experiment duration 24 days) and the 4‐aminopyridine (acute: experiment duration 2 h) models of paroxysms in rats, a real‐time feedback stimulation paradigm was implemented, which triggered a short periodic electrical stimulus (5 Hz for 5 s) upon detecting a seizure precursor. Our seizure precursor detection algorithm relied on the monitoring of the real‐time phase synchronization analysis, and detected/anticipated electrographic seizures as early as a few seconds to a few minutes before the behavioral and electrographic seizure onset, with a very low false‐positive rate of the detection.ResultsThe baseline mean seizure frequencies were 5.39 seizures per day (chronic) and 13.2 seizures per hour (acute). The phase synchrony analysis detected 88% (434 of 494) of seizures with a mean false alarm of 0.67 per day (chronic) and 83% (86 of 104) of seizures with a mean false alarm of 0.47 per hour (acute). The feedback stimulation reduced the seizure frequencies to 0.41 seizures per day (chronic) and 2.4 seizures per hour (acute). Overall, the feedback stimulation paradigm reduced seizure frequency by a minimum of 80% to a maximum of 100% in 10 rats, with 83% of the animals rendered seizure‐free.SignificanceThis approach represents a simple and efficient manner for stopping seizure development. Because of the short on‐demand stimuli, few or no associated side effects are expected in clinical application in patients with epilepsy. Abnormal synchrony patterns are common features in epilepsy and other neurologic and psychiatric syndromes; therefore, this type of feedback stimulation paradigm could be a novel therapeutic modality for use in various neurologic and psychiatric disorders.
A review of research into second intention equine wound healing using manuka honey: Current recommendations and future applications
Authors: Dart A. J. , Bischofberger A. S. , Dart C. M. , Jeffcott L. B. 
Published: June 2015

SummaryIn addition to the generic properties of honey, manuka honey has a nonperoxide antimicrobial activity largely attributed to methylglyoxal. Commercially, manuka honey is graded against a standard antiseptic, phenol, to provide a measure of antimicrobial activity referred to as the unique manuka factor (UMF). The higher the UMF, the greater the antimicrobial activity. However, more recently, there is evidence that manuka honey can also modulate the initial inflammatory response through activation of toll‐like receptor 4 on monocytes to enhance production of cytokines important in tissue repair and regeneration. Recent studies investigating the effects of manuka honey on second intention healing of lower limb wounds in horses have shown that wounds treated with UMF 20 manuka honey retracted less and healed faster than untreated wounds. Using this wound healing model, the primary effects of manuka honey appeared to be associated with the modulation of the initial inflammatory reaction rather than its antimicrobial effects. Based on the current knowledge, treatment with manuka honey should be instituted as soon as possible after injury. Where bacterial contamination is substantial, manuka honey with a UMF ≥15 should be used. While bandages will improve the contact between the honey and the wound and may be indicated in the early stages of wound healing, prolonged bandaging may lead to the production of excessive granulation tissue. If topical treatment without a bandage is to be used, more honey is not necessarily better. Using a thin film combined with regular application, contact times may be optimised. Application 2–3 times daily to open wounds may improve efficacy. Manuka honey should be applied for at least 21 days after wounding but there may be beneficial effects if it is applied until wound healing is almost complete.
Epithelial deletion of podoplanin is dispensable for re‐epithelialization of skin wounds
Authors: Baars Sebastian , Bauer Christine , Szabowski Sibylle , Hartenstein Bettina , Angel Peter 
Published: June 2015

AbstractThe mucin‐like transmembrane protein podoplanin (PDPN) is prominently represented in tumor‐associated gene expression signatures of numerous types of cancer including squamous cell carcinoma, and gain‐of‐function and knockdown approaches in tissue culture strongly suggested an important role of PDPN in cell proliferation, migration and adhesion. PDPN is absent during epidermal homeostasis but is highly expressed in basal keratinocytes during cutaneous wound healing. Enhanced motility of immortalized keratinocytes upon ectopic PDPN overexpression argues for wound healing defects upon podoplanin deficiency in keratinocytes; however, in vivo data that unequivocally define the impact of PDPN by functional studies in a physiologically relevant system are still missing. Here, we have applied an in vivo loss‐of‐function approach by generating a novel transgenic mouse line with keratinocyte‐specific podoplanin deficiency. Performing cutaneous full‐thickness excisional wounds to examine re‐epithelialization capacity, unexpectedly, no defects were observed in wound healing properties of mutant mice. Similarly, PDPN‐deficient primary keratinocytes showed no impairment in migration, adhesion or proliferation. Thus, PDPN function is not rate‐limiting for re‐epithelialization but may be functionally compensated by an as yet unknown protein. Our data also call for in vivo functional studies on PDPN in settings of skin tumor development and progression to clarify PDPN's role in skin pathology.
CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin‐10 production predominantly by regulatory B cells
Authors: Fjelbye Jonas , Antvorskov Julie C. , Buschard Karsten , Issazadeh‐Navikas Shohreh , Engkilde Kåre 
Published: June 2015

AbstractConflicting observations have been reported concerning the role of CD1d‐dependent natural killer T (NKT) cells in contact hypersensitivity (CHS), supporting either a disease‐promoting or downregulatory function. We studied the role of NKT cells in CHS by comparing the immune response in CD1d knockout (CD1d KO) and wild‐type (Wt) mice after contact allergen exposure. For induction of CHS, C57BL/6 CD1d KO mice (n = 6) and C57BL/6 Wt mice (n = 6) were sensitised with 1% (w/v) dinitrochlorobenzene (DNCB) or vehicle for three consecutive days and subsequently challenged with a single dose of 0.5% DNCB (w/v) on the ears fifteen days later. We demonstrate that CD1d KO mice, as compared with Wt littermates, have more pronounced infiltration of mononuclear cells in the skin (29.1% increase; P < 0.001), lower frequencies of interleukin‐10+ B cells (Bregs) in the spleen (53.2% decrease; P < 0.05) and peritoneal cavity (80.8% decrease; P < 0.05) and increased production of interferon‐γ (3‐fold; P < 0.05) after DNCB sensitisation and challenge, which suggests an important regulatory and protective role of CD1d‐dependent NKT cells in CHS in our model, at least in part via regulation of IL‐10 producing Bregs.
Food consumption rates of piscivorous brown trout (Salmo trutta) foraging on contrasting coregonid prey
Authors: Jensen H. , Kahilainen K. K. , Vinni M. , Gjelland K. Ø. , Malinen T. , Harrod C. , Amundsen P.‐A. 
Published: June 2015

AbstractKnowledge of predator–prey dynamics is essential to understand ecosystem functioning. Quantification of such interactions is important for fisheries management, in particular in the case of stocking programmes. Here, food consumption rates (FCR) were quantified for wild and stocked piscivorous brown trout,Salmo truttaL., in three subarctic lakes with contrasting coregonid (Coregonusspp.) prey communities, using the Wisconsin and the Elliott–Hurley bioenergetic models.FCRwas highest for stocked brown trout in lakes with the lowest predator densities, and lowest for wild brown trout. AlthoughFCRestimate may vary somewhat depending on the specific model used, such tools are imperative for the proper impact assessment of brown trout stocking programmes and for the provision of advice on optimal stocking densities.
Upstream and downstream responses of fish assemblages to an eastern Amazonian hydroelectric dam
Authors: Sá‐Oliveira Júlio C. , Hawes Joseph E. , Isaac‐Nahum Victoria J. , Peres Carlos A. 
Published: June 2015

Summary

Major hydroelectric dams are proliferating in tropical regions such as Amazonia, where extensive new hydropower developments are planned despite potentially severe ecological and social impacts. The status of freshwater biota in the vicinity of existing dams could be valuable to predict the effects of such developments, but detailed ecological monitoring before and after dam construction is frequently lacking.

In the absence of these data, we used a space‐for‐time replacement to compare a key component of the aquatic biota at upstream and downstream sites, with the latter more closely resembling river channel conditions prior to the dam. We assessed the fish assemblages upstream and downstream of the Coaracy Nunes Dam in Amapá, Brazil, the first ecological study at this site since this dam was constructed 42 years earlier. We used gillnets during eight bimonthly field campaigns, covering both wet and dry seasons, and sampled the ichthyofauna (1819 individuals, 81 species) at four sites: Downstream Channel, Reservoir, Upstream Lake and Upstream Channel.

We found clear negative impacts on the abundance, biomass, species richness, alpha diversity and species dominance upstream of the dam. The physical subdivision of the river channel and the upstream channel conversion from lentic to lotic habitats were strongly associated with differences in the composition and structure of fish communities. Notable changes include an increased contribution of small‐bodied fish in the reservoir and an absence of long‐distance migrants upstream of the dam.

Downstream channel habitats, in particular, retained their fish diversity with high conservation value typical of eastern Amazonia, yet these areas now face the threat of new hydropower development farther downstream. The long‐term impacts on aquatic biodiversity highlighted in this study are especially relevant in the face of burgeoning new hydroelectricity development plans for rivers across lowland Amazonia.