bluuebunny/crossref_metadata_2025 huggingface dataset:
Biodistribution of Evans blue in an orthotopic AY‐27 rat bladder urothelial cell carcinoma model: implication for the improved diagnosis of non‐muscle‐invasive bladder cancer (NMIBC) using dye‐guided white‐light cystoscopy
Authors: Elsen Sanne , Lerut Evelyne , Van Cleynenbreugel Ben , van der Aa Frank , van Poppel Hein , de Witte Peter A.
Published: March 2015

Objectives

To investigate the possibility of using Evans blue (EB) as a novel diagnostic tool to detect bladder tumours with white‐light (WL) cystoscopy, in this preclinical study we examine the biodistribution of EB in the different layers (urothelium, submucosa, muscle) of a normal rat bladder and a rat bladder bearing a malignant urothelium composed of syngeneic AY‐27 tumour cells.

Materials and Methods

EB was instilled into both normal as well as tumour‐bearing rat bladders. After instillation, bladders were removed and snap frozen in liquid nitrogen. The distribution of EB in the different layers was quantified using fluorescence microscopy. To gain more insight into the mechanism underlying the selective accumulation of EB in tumour tissue, bladder sections were prepared for ultrastructural investigations by means of transmission electron microscopy (TEM). In addition, we also examined the expression of E‐cadherin, claudin‐1 and desmoglein‐1 by immunohistochemistry to study the integrity of the bladder wall, as these molecules are key constituents of adherens junctions, tight junctions and desmosomes, respectively.

Results

In most cases, the accumulation of EB in malignant bladders was substantially higher than in healthy bladders, at least when 1 mm EB instillations were used. In case of a 1 mm EB instillation for 2 h, the EB‐associated fluorescence in malignant urothelial tissue was 55‐times higher than the fluorescence found in normal urothelium. Ultrastructurally, malignant tissue displayed wider intercellular spaces and a decreased number of cell junction components compared with normal tissue, pointing to defects in the urothelial barrier. There were no differences in the expression of E‐cadherin, whereas desmoglein‐1 staining was stronger in the membranes of healthy bladder urothelium compared with tumour tissue. Claudin‐1 expression was negative in all samples tested.

Conclusion

EB is selectively taken up by tumour tissue after intravesical instillations in rats bearing bladder tumours. The lower expression of desmoglein‐1 in tumour samples, together with the reduced presence of desmosomes seen with TEM, likely imply that desmosomes play an important role in the ultrastructural differences between healthy rat urothelium and tumour tissue, and secondary to that, to the differential uptake of EB in both tissues. We consider that our findings could be useful for future clinical developments in the field of diagnostics for bladder cancer.
Role of aldehyde dehydrogenase in hypoxic vasodilator effects of nitrite in rats and humans
Authors: Arif Sayqa , Borgognone Alessandra , Lin Erica Lai‐Sze , O'Sullivan Aine G , Sharma Vishal , Drury Nigel E , Menon Ashvini , Nightingale Peter , Mascaro Jorge , Bonser Robert S , Horowitz John D , Feelisch Martin , Frenneaux Michael P , Madhani Melanie
Published: March 2015

Background and Purpose

Hypoxic conditions favour the reduction of nitrite to nitric oxide (NO) to elicit vasodilatation, but the mechanism(s) responsible for bioconversion remains ill defined. In the present study, we assess the role of aldehyde dehydrogenase 2 (ALDH2) in nitrite bioactivation under normoxia and hypoxia in the rat and human vasculature.

Experimental Approach

The role of ALDH2 in vascular responses to nitrite was studied using rat thoracic aorta and gluteal subcutaneous fat resistance vessels from patients with heart failure (HF; 16 patients) in vitro and by measurement of changes in forearm blood flow (FBF) during intra‐arterial nitrite infusion (21 patients) in vivo. Specifically, we investigated the effects of (i) ALDH2 inhibition by cyanamide or propionaldehyde and the (ii) tolerance‐independent inactivation of ALDH2 by glyceryl trinitrate (GTN) on the vasodilator activity of nitrite. In each setting, nitrite effects were measured via evaluation of the concentration–response relationship under normoxic and hypoxic conditions in the absence or presence of ALDH2 inhibitors.

Key Results

Both in rat aorta and human resistance vessels, dilatation to nitrite was diminished following ALDH2 inhibition, in particular under hypoxia. In humans there was a non‐significant trend towards attenuation of nitrite‐mediated increases in FBF.

Conclusions and Implications

In human and rat vascular tissue in vitro, hypoxic nitrite‐mediated vasodilatation involves ALDH2. In patients with HF in vivo, the role of this enzyme in nitrite bioactivation is at the most, modest, suggesting the involvement of other more important mechanisms.
Supraspinal actions of nociceptin/orphanin FQ, morphine and substance P in regulating pain and itch in non‐human primates
Authors: Ding H , Hayashida K , Suto T , Sukhtankar D D , Kimura M , Mendenhall V , Ko M C
Published: March 2015

Background and Purpose

Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects of centrally administered ligands on regulating pain and itch in non‐human primates. In particular, nociceptive thresholds affected by intracisternal N/OFQ were compared with those of morphine and substance P, known to provide analgesia and mediate hyperalgesia, respectively, in humans.

Experimental Approach

Intrathecal catheters were installed to allow intracisternal and lumbar intrathecal administration in awake and unanaesthetized rhesus monkeys. Nociceptive responses were measured using the warm water tail‐withdrawal assay. Itch scratching responses were scored from videotapes recording behavioural activities of monkeys in their home cages. Antagonist studies were conducted to validate the receptor mechanisms underlying intracisternally elicited behavioural responses.

Key Results

Intracisternal morphine (100 nmol) elicited more head scratches than those after intrathecal morphine. Distinct dermatomal scratching locations between the two routes suggest a corresponding activation of supraspinal and spinal μ receptors. Unlike intracisternal substance P, which induced hyperalgesia, intracisternal N/OFQ (100 nmol) produced antinociceptive effects mediated by NOP receptors. Neither peptide increased scratching responses.

Conclusions and Implications

Taken together, these results demonstrated differential actions of ligands in the primate supraspinal region in regulating pain and itch. This study not only improves scientific understanding of the N/OFQ‐NOP receptor system in pain processing but also supports the therapeutic potential of NOP‐related ligands as analgesics.
α‐Galactosylceramide suppresses murine eosinophil production through interferon‐γ‐dependent induction ofNOsynthase andCD95
Authors: Gaspar‐Elsas Maria Ignez , Queto Túlio , Masid‐de‐Brito Daniela , Vieira Bruno Marques , de Luca Bianca , Cunha Fernando Queiroz , Xavier‐Elsas Pedro
Published: March 2015

Background and Purpose

α‐Galactosylceramide (α‐GalCer), a pleiotropic immunomodulator with therapeutic potential in neoplastic, autoimmune and allergic diseases, activates invariant natural killerT‐cells throughCD1‐restricted receptors for α‐GalCer on antigen‐presenting cells, inducing cytokine secretion. However the haemopoietic effects of α‐GalCerremain little explored.

Experimental Approach

α‐GalCer‐induced modulation of eosinophil production inIL‐5‐stimulated bone marrow cultures was examined in wild‐type (BALB/c,C57BL/6) mice and their mutants lackingCD1, inducibleNOS(iNOS),CD95 andIFN‐γ, along with the effects of lymphocytes;IFN‐γ; caspase andiNOSinhibitors; non‐steroidal anti‐inflammatory drugs (NSAIDs) andLTD4; and dexamethasone.

Key Results

α‐GalCer (10−6–10−8M) suppressedIL‐5‐stimulated eosinopoiesis by inducing apoptosis. α‐GalCer pretreatmentin vivo(100 μg·kg−1, i.v.) suppressed colony formation byGM‐CSF‐stimulated bone marrow progenitors in semi‐solid cultures. α‐GalCerand dexamethasone synergistically promoted eosinophil maturation. Suppression of eosinophil production by α‐GalCerwas prevented by aminoguanidine and was undetectable in bone marrow lackingiNOS,CD95,CD28; orCD1d. Separation on Percoll gradients and depletion ofCD3+ cells made bone marrow precursors unresponsive to α‐GalCer. Responsiveness was restored with splenic lymphocytes. Experiments with (i)IFN‐γ‐deficient bone marrow, alone or co‐cultured with spleenT‐cells from wild‐type, but not fromCD1d‐deficient, donors; (ii)IFN‐γ neutralization; and (iii) recombinantIFN‐γ, showed that these effects of α‐GalCer were mediated by IFN‐γ. Effects of α‐GalCeron eosinophil production were blocked byLTD4andNSAIDs.

Conclusions and Implications

α‐GalCeractivation ofIFN‐γ‐secreting,CD1d‐restricted lymphocytes inducediNOS‐CD95‐dependent apoptosis in developing eosinophils. This pathway is initiated by endogenous regulatory lymphocytes, antagonised byLTD4,NSAIDsand aminoguanidine, and modified by dexamethasone.
Contextual and individual determinants of dental pain in preschool children
Authors: Ferreira‐Júnior Osmar Martins , Freire Maria do Carmo Matias , Moreira Rafael da Silveira , Costa Luciane Rezende
Published: March 2015

Objectives

Despite growing interest on dental pain in children, there are very few studies on its prevalence and determinants among preschool children. The objective of this study was to assess prevalence of dental pain and associated individual and contextual factors in 5 year‐old Brazilian children.

Methods

This cross‐sectional study used primary data from the 2010 National Survey of Oral Health, carried out in capital cities and a sample of country towns. Participants were 7280 5‐year‐olds, who were examined in their homes and whose parents answered a questionnaire. Dependent variable was report of dental pain in the last 6 months. Independent variables were contextual (city level) socioeconomic factors, and individual (child) sociodemographic and oral health‐related variables. Data analysis included hierarchized Poisson regression models, using a multilevel approach and prevalence rate (PR) estimates.

Results

The prevalence of dental pain was 22.0% (95% CI 19.1–25.2). It was higher among those living in cities with lower human development index (PR 0.07; 95% CI 0.02–0.22) and with a higher percentage of their population with an incomplete primary education (PR 1.03; 95% CI 1.01–1.06). Indigenous children had prevalence of dental pain 1.97 times higher (95% CI 1.19–3.26) than those of white colour. Families with monthly incomes of U$ 218.00 or less and between U$ 219.00 and U$ 656.00 had, respectively, a prevalence of dental pain 2.67 (95% CI 1.33–5.32) and 2.11 (95% CI 1.03–4.32) times higher than families with highest income level. For each unit increase in the number of dwellers per bedroom, there was a 14% increase in the probability of having pain. Children with caries experience had a 3.45 (95% CI 2.58–4.62) higher prevalence of pain than caries‐free individuals.

Conclusion

Dental pain prevalence in Brazilian preschool children was high and influenced by contextual and individual factors.
Toll‐like receptor‐4 knockout mice are more resistant to optic nerve crush damage than wild‐type mice
Authors: Morzaev Dana , Nicholson James D , Caspi Tomm , Weiss Shirel , Hochhauser Edith , Goldenberg‐Cohen Nitza
Published: March 2015

Background

This study aims to investigate the role of the inflammatory response following optic nerve crush (ONC) in knockout mice for the toll‐like receptor‐4 gene (TLR4−/−) compared to wild‐type (WT) mice.

Methods

ONC was induced in TLR4−/− and C57BL6 WT mice. Histological sections of the retina and optic nerve were analysed on days 1, 3 or 21 after injury. Molecular analysis with real‐time quantitative polymerase chain reaction was used to study the expression of CD45, tumour necrosis‐alpha (TNF‐α) and glial fibrillary acidic protein, as well as retinal ganglion cell (RGC) markers THY‐1 and Brn3b.

Results

There was a 25.5% and 38% loss in the RGC layer of the ONC‐injured eyes of the TLR4−/− and the WT mice, respectively (with 27% and 9% of the remaining cells positive for Brn3a, respectively). Mean levels of Thy‐1 and Brn3b were higher in the TLR4−/− mice. CD45 and Iba1 staining revealed infiltration of inflammatory cells into the injured nerve and retina in both groups. Molecular analysis of the optic nerve on day 1 showed increased TNF‐α expression and reduced CD45 and GFAP expression; on day 3, CD45 reverted to baseline but GFAP remained low; on day 21, all 3 markers were at baseline in the TLR4−/− group and decreased in the WT group.

Conclusion

Inflammation plays a major role in the response to ONC injury. Reduced levels of inflammation are associated with improved RGC preservation. The increase in TNF‐α and reduction in CD45 in both TLR4−/− and WT mice may indicate the presence of an alternative pathway for induction of RGC death.
Conditioned medium from fresh and demineralized bone enhances osteoclastogenesis in murine bone marrow cultures
Authors: Caballé‐Serrano Jordi , Schuldt Filho Guenther , Bosshardt Dieter D. , Gargallo‐Albiol Jordi , Buser Daniel , Gruber Reinhard
Published: March 2015

Objectives

Osteoclasts rapidly form on the surface of bone chips at augmentation sites. The underlying molecular mechanism, however, is unclear. Soluble factors released from bone chips in vitro have a robust impact on mesenchymal cell differentiation. Whether these soluble factors change the differentiation of hematopoietic cells into osteoclasts remains unknown.

Methods

Osteoclastogenesis, the formation of tartrate‐resistant acid phosphatase‐positive multinucleated cells, was studied with murine bone marrow cultures exposed to RANKL and M‐CSF, and conditioned medium from fresh (BCM) and demineralized bone matrix (DCM). Histochemical staining, gene and protein expression, as well as viability assays were performed.

Results

This study shows that BCM had no impact on osteoclastogenesis. However, when BCM was heated to 85°C (BCMh), the number of tartrate‐resistant acid phosphatase‐positive multinucleated cells that developed in the presence of RANKL and M‐CSF approximately doubled. In line with the histochemical observations, there was a trend that BCMh increased expression of osteoclast marker genes, in particular the transcription factor c‐fos. The expression of c‐fos was significantly reduced by the TGF‐β receptor I antagonist SB431542. DCM significantly stimulated osteoclastogenesis, independent of thermal processing.

Conclusions

These data demonstrate that activated BCM by heat and DBM are able to stimulate osteoclastogenesis in vitro. These in vitro results support the notion that the resorption of autografts may be supported by as yet less defined paracrine mechanisms.
Acupoint herbal patching for allergic rhinitis: a systematic review and meta‐analysis of randomised controlled trials
Authors: Zhou F. , Yan L.‐J. , Yang G.‐Y. , Liu J.‐P.
Published: March 2015

Background

Acupoint herbal patching (AHP) is extensively used in treatment of allergic rhinitis in China. However, existing systematic review is insufficient.

Objective of review

To evaluate the effectiveness and safety of AHP in treating allergic rhinitis.

Search strategy

We searched seven electronic databases for randomised controlled trials (RCTs) from inception until August 2014.

Evaluation method

Two authors selected studies, extracted data and evaluated risk of bias independently. The Cochrane risk of bias tool was applied to assess the methodological quality of the included trials, and RevMan 5.2 software was utilised to perform data analysis.

Results

Twenty RCTs involving 2438 participants were included. Most of them were evaluated as high risk of bias. Acupoint herbal patching significantly decreased the recurrence rate at 6 months compared with Western medicine (RR 0.52; 95% CI 0.42–0.64), and similar effect was found for AHP plus Western medicine versus Western medicine (RR 0.53; 95% CI 0.44–0.65). Acupoint herbal patching appeared to be more effective than placebo in improving total clinical symptoms and signs after treatment and at 6 months, and in improving quality of life at <3 months and over 3 months. No severe adverse effects were found in the AHP groups.

Conclusions

Acupoint herbal patching alone or combined with Western medicine appears to be more effective than placebo or Western medicine, respectively. Acupoint herbal patching seems to be a safe treatment. However, the findings should be interpreted with caution. Further large‐scale, rigorously designed trials are warranted to confirm the findings.
Barriers and facilitators in the implementation of recommendations for hand eczema prevention among healthcare workers
Authors: van der Meer Esther W. C. , van der Gulden Joost W. J. , van Dongen Diana , Boot Cécile R. L. , Anema Johannes R.
Published: March 2015

Background

Evidence‐based recommendations are available for the prevention of hand eczema among healthcare workers. However, the implementation of these recommendations is not always successful.

Objectives

To identify barriers and facilitators in the implementation of recommendations for the prevention of hand eczema among healthcare workers alongside a randomized controlled trial.

Methods

A qualitative study was performed in which 19 healthcare workers were interviewed. The interview transcripts were open coded and also coded by means of a template by two researchers to identify relevant barriers and facilitators.

Results

Most barriers and facilitators reported for the recommendations were found at the level of the innovation (e.g. the recommendations), whereas for the guideline as a whole, multiple levels (socio‐political, organization, user, and facilities) were identified.

Conclusions

To enhance the implementation of recommendations for the prevention of hand eczema in a healthcare setting, having knowledge about these recommendations seems to be an important first step. In addition, maintaining the attention of the subject, testing the products beforehand and close collaboration with the infection control department might enhance implementation. Furthermore, it is important that the recommendations fit in with the work of the healthcare workers. When the implementation of the recommendations is prepared, these points should be taken into account.
Use of clinical next‐generation sequencing to identify melanomas harboring SMARCB1 mutations
Authors: Stockman David L. , Curry Jonathan L. , Torres‐Cabala Carlos A. , Watson Ian R. , Siroy Alan E. , Bassett Roland L. , Zou Lihua , Patel Keyur P. , Luthra Rajyalakshmi , Davies Michael A. , Wargo Jennifer A. , Routbort Mark A. , Broaddus Russell R. , Prieto Victor G. , Lazar Alexander J. , Tetzlaff Michael T.
Published: March 2015

Background

SMARCB1 (INI1/BAF47/SNF5) encodes a part of a multiprotein complex that regulates gene expression through chromatin remodeling. SMARCB1 expression is lost or downregulated in multiple human tumors, including epithelioid sarcoma, meningioma and rhabdoid tumors of the brain, soft tissue and kidney.

Methods

A 46‐gene or 50‐gene next‐generation sequencing AmpliSeq Cancer Panel (Life Technologies; San Francisco, CA, USA) was applied to ∼1400 primary or metastatic melanoma tissues.

Results

We identified eight cases of melanoma harboring mutations in SMARCB1. Immunohistochemistry demonstrated preservation of SMARCB1 protein expression in all cases. SMARCB1 mutations occurred together with TP53 mutations in five of the eight cases, suggesting a functional relationship between these tumor suppressors in melanoma.

Conclusions

Because single‐base substitutions in SMARCB1 occur in a small subset of melanomas and do not affect SMARCB1 protein expression, such mutations would only be discovered by sequencing approaches. Our findings highlight the potential for next‐generation sequencing platforms to identify mutations unexpected for melanoma that may contribute to its oncogenic potential. Though rare, the identification of SMARCB1 mutations adds to the growing literature regarding the role of epigenetic control mechanisms in melanoma progression and therapeutic resistance and provide a rationale for strategies targeting such alterations (via chromatin remodeling agents) in clinical trials.
Superficial fibrin thrombi … and other findings: a review of the histopathology of human scabietic infections
Authors: Elwood Hillary , Berry Ryan S. , Gardner Jerad M. , Shalin Sara C.
Published: March 2015

Background

Cutaneous infection with the mite Sarcoptes scabiei var. hominis is associated with epidermal and dermal changes. After noting superficial fibrin thrombi in two biopsies with scabies mites, we comprehensively reviewed the histopathologic findings in scabietic infections to determine the frequency of this finding.

Methods

Twenty five biopsies of scabies infection were retrieved from the archives of our institution; only cases containing scabietic mite parts or scybala were included. The microscopic features were documented.

Results

Nearly half (40%) of the cases showed fibrin thrombi within vessels of the superficial dermis. Other frequent findings included dermal eosinophils (88% of cases), epidermal spongiosis (76% of cases), lymphocyte atypia (64%), a superficial and deep infiltrate (52% of cases), dermal neutrophils (52%) and endothelial cell swelling (52%). Half of the cases contained polarizable mite elements. Less commonly encountered features included extravasated erythrocytes (44%), dermal edema (32%), pink ‘pigtails’(28%), intraepidermal pustules (24%), plasma cells (20%) and vasculitis (4%).

Conclusions

The pathologic characteristics of scabietic infection are wide‐ranging. Spongiosis, superficial and deep inflammation, and dermal eosinophils and neutrophils are seen in the majority of cases. Superficial fibrin thrombi are not uncommon in scabietic infection, and may provide a helpful diagnostic clue when mites are not visible on initial sections.
Historical summer distribution of the endangered North Atlantic right whale (Eubalaena glacialis): a hypothesis based on environmental preferences of a congeneric species
Authors: Monsarrat Sophie , Pennino Maria G. , Smith Tim D. , Reeves Randall R. , Meynard Christine N. , Kaplan David M. , Rodrigues Ana S. L.
Published: March 2015

Aim

To obtain a plausible hypothesis for the historical distribution of North Atlantic right whales (NARWs) (Eubalaena glacialis) in their summer feeding grounds. Previously widespread in the North Atlantic, after centuries of hunting, these whales survive as a small population off eastern North America. Because their exploitation began before formal records started, information about their historical distribution is fragmentary.

Location

North Atlantic and North Pacific oceans.

Methods

We linked historical records of North Pacific right whales (E. japonica; from 19th‐century American whaling logbooks) with oceanographic data to generate a species distribution model. Assuming that the two species have similar environmental preferences, the model was projected into the North Atlantic to predict environmental suitability for NARWs. The reliability of these predictions was assessed by comparing the model results with historical and recent records in the North Atlantic.

Results

The model predicts suitable environmental conditions over a wide, mostly offshore band across the North Atlantic. Predictions are well supported by historical and recent records, but discrepancies in some areas indicate lower discriminative ability in coastal, shallow‐depth areas, suggesting that this model mainly describes the summer offshore distribution of right whales.

Main conclusions

Our results suggest that the summer range of the NARW consisted of a relatively narrow band (width c. 10° in latitude), extending from the eastern coast of North America to northern Norway, over the Grand Banks of Newfoundland, south of Greenland and Iceland, north of the British Isles and in the Norwegian Sea. These results highlight possibilities for additional research both on the history of exploitation and on the current summer distribution of this species. In particular, better survey coverage of historical whaling grounds could help inform conservation efforts for this endangered species. More generally, this study illustrates the challenges and opportunities in using historical data to understand the original distribution of highly depleted species.
Invasive earthworms shape forest seed bank composition
Authors: Nuzzo Victoria , Dávalos Andrea , Blossey Bernd
Published: March 2015

Aim

To assess how non‐native earthworm and non‐native plant invasions shape soil seed bank composition in deciduous temperate forests.

Location

New York State, USA.

Methods

We recorded earthworm density, earthworm biomass and vegetation composition in 12 deciduous forests and subsequently collected soil cores and recorded emergence of plant species from the seed bank. We used path analysis to assess direct and indirect contributions of earthworms and vegetation composition (species richness and cover of native and non‐native plants) to the species richness and abundance of emergent seedlings.

Results

High earthworm populations were positively associated with increased species richness and seedling density of both native and non‐native plant species emerging from the seed bank. This relationship held for all life‐form groups, although the earthworm effect was indirect for non‐native graminoid abundance. Non‐native plants were positively correlated with earthworms and while they influenced both aboveground vegetation cover and species richness, they had no direct influence on emergent abundance or species richness.

Main conclusions

Our results suggest that forest seed bank composition is strongly influenced by the presence and abundance of non‐native earthworms, and only weakly influenced by non‐native plants. Forest understorey recovery from seed banks is possible following earthworm invasion, but resulting communities bear little similarity to standing vegetation. Recovery of the full desirable and typical complement of aboveground vegetation will require input to seed banks by (1) fostering seed production of existing vegetation and/or (2) planting seed of desired species. We suggest managing understorey vegetation to allow herbaceous species to set seed.
Do attitudes toward societal structure predict beliefs about free will and achievement? Evidence from the Indian caste system
Authors: Srinivasan Mahesh , Dunham Yarrow , Hicks Catherine M. , Barner David
Published: March 2015

Intuitive theories about the malleability of intellectual ability affect our motivation and achievement in life. But how are such theories shaped by the culture in which an individual is raised? We addressed this question by exploring how Indian children's and adults’ attitudes toward the Hindu caste system – and its deterministic worldview – are related to differences in their intuitive theories. Strikingly, we found that, beginning at least in middle school and continuing into adulthood, individuals who placed more importance on caste were more likely to adopt deterministic intuitive theories. We also found a developmental change in the scope of this relationship, such that in children, caste attitudes were linked only to abstract beliefs about personal freedom, but that by adulthood, caste attitudes were also linked to beliefs about the potential achievement of members of different castes, personal intellectual ability, and personality attributes. These results are the first to directly relate the societal structure in which a person is raised to the specific intuitive theories they adopt.
Spontaneous non‐verbal counting in toddlers
Authors: Sella Francesco , Berteletti Ilaria , Lucangeli Daniela , Zorzi Marco
Published: March 2015

A wealth of studies have investigated numerical abilities in infants and in children aged 3 or above, but research on pre‐counting toddlers is sparse. Here we devised a novel version of an imitation task that was previously used to assess spontaneous focusing on numerosity (i.e. the predisposition to grasp numerical properties of the environment) to assess whether pre‐counters would spontaneously deploy sequential (item‐by‐item) enumeration and whether this ability would rely on the object tracking system (OTS) or on the approximate number system (ANS). Two‐and‐a‐half‐year‐olds watched the experimenter performing one‐by‐one insertion of ‘food tokens’ into an opaque animal puppet and then were asked to imitate the puppet‐feeding behavior. The number of tokens varied between 1 and 6 and each numerosity was presented many times to obtain a distribution of responses during imitation. Many children demonstrated attention to the numerosity of the food tokens despite the lack of any explicit cueing to the number dimension. Most notably, the response distributions centered on the target numerosities and showed the classic variability signature that is attributed to the ANS. These results are consistent with previous studies on sequential enumeration in non‐human primates and suggest that pre‐counting children are capable of sequentially updating the numerosity of non‐visible sets through additive operations and hold it in memory for reproducing the observed behavior.
The Contribution of Regions to Aggregate Growth in the OECD
Authors: Garcilazo Enrique , Oliveira Martins Joaquim
Published: March 2015

This article investigates the contribution of regions to aggregate growth. We find a great degree of heterogeneity in the performance of Territorial Level 3 (TL3) regions of the OECD (Organization for Economic Cooperation and Development). The regional contributions to aggregate growth follow a power law, with a coefficient around 1.2 (in absolute terms). This implies that Few‐Large (FL) regions contribute disproportionately to aggregate growth whereas Many‐Small (MS) individual regions contribute only marginally. Because the large number of these smaller regions and the decay of their contribution to growth is slow (generating a fat tail distribution), their cumulated contribution is actually around two‐thirds of aggregate growth.
Living standards and plague in London, 1560–1665
Authors: Cummins Neil , Kelly Morgan , Ó Gráda Cormac
Published: March 2015

This article uses individual records of 930,000 burials and 630,000 baptisms to reconstruct the spatial and temporal patterns of birth and death in London from 1560 to 1665, a period dominated by recurrent plague. The plagues of 1563, 1603, 1625, and 1665 appear of roughly equal magnitude, with deaths running at five to six times their usual rate, but the impact on wealthier central parishes falls markedly through time. Tracking the weekly spread of plague, we find no evidence that plague emerged first in the docks, and in many cases elevated mortality emerges first in the poor northern suburbs. Looking at the seasonal pattern of mortality, we find that the characteristic autumn spike associated with plague continued into the early 1700s. Natural increase improved as smaller crises disappeared after 1590, but fewer than half of those born survived childhood.
Health, height, and the household at the turn of the twentieth century
Authors: Bailey Roy E. , Hatton Timothy J. , Inwood Kris
Published: March 2015

This article examines the health and height of men born in England and Wales in the 1890s who enlisted in the army at the time of the First World War, using a sample of recruits from the army service records. These are linked to their childhood circumstances as observed in the 1901 census. Econometric results indicate that height on enlistment was positively related to socio‐economic class, and negatively to the number of children in the household in 1901 and the proportion of household members who were earners, as well as to the degree of crowding. Adding the characteristics of the locality has little effect on the household‐level effects. However local conditions were important; in particular the industrial character of the district, local housing conditions, and the female illiteracy rate. These are interpreted as representing the negative effect on height of the local disease environment. The results suggest that changing conditions at both household and locality levels contributed to the increase in height and health in the following decades.
A practical two‐step approach for mixed model‐based kriging, with an application to the prediction of soil organic carbon concentration
Authors: Ritz C. , Putku E. , Astover A.
Published: March 2015

Soil scientists often use prediction models to obtain values at unsampled locations. The spatial variation in the soil is best captured by using the empirical best linear unbiased predictor (EBLUP) based on a restricted maximum likelihood (REML) approach that efficiently exploits available data on both mean trends and correlation structures. We proposed a practical two‐step implementation of the REML approach for model‐based kriging, exemplified by predicting soil organic carbon (SOC) concentrations in mineral soils in Estonia from the large‐scale digital soil map information and a previously established prediction model. The prediction model was a linear mixed model with soil type, physical clay content (particle size < 0.01 mm) and A‐horizon thickness as fixed effects and site, transect, plot, year, year‐transect random intercepts and site‐specific random slopes for clay content. We used only the site‐specific intercept EBLUPs for estimating spatial correlation parameters as they described most of the variation in the random effects (86.8%). Fitting an exponential correlation model to these EBLUPs resulted in an estimated range of 10.5 km and the estimated proportion of the variance from the nugget effect was 0.23. The results of a simulation study showed a downwards bias that decreased with sample size. The results were validated through an external dataset, resulting in root mean square errors (RMSE) of 1.06 and 1.07% for the two‐step approach for kriging and the model with only fixed effects (no kriging), respectively. These results indicate that using the two‐step approach for kriging may improve prediction.
No evidence of a role for cystatin B gene in juvenile myoclonic epilepsy
Authors: Mumoli Laura , Tarantino Patrizia , Michelucci Roberto , Bianchi Amedeo , Labate Angelo , Franceschetti Silvana , Marini Carla , Striano Pasquale , Gagliardi Monica , Ferlazzo Edoardo , Sofia Vito , Pennese Loredana , Annesi Grazia , Aguglia Umberto , Guerrini Renzo , Zara Federico , Gambardella Antonio ,   the Genetic Commission, Italian League Against Epilepsy
Published: March 2015

Genetic factors play a major role in the etiology of juvenile myoclonic epilepsy (JME), a common form of idiopathic generalized epilepsy, but so far, genes related to JME remain largely unknown. JME shares electroclinical features with Unverricht‐Lundborg disease (progressive myoclonic epilepsy type 1; EPM1), a form of progressive myoclonus epilepsy characterized by myoclonus, epilepsy, and gradual neurologic deterioration. EPM1 is caused by mutations in the gene that codes for cystatin B (CSTB), an inhibitor of cysteine protease. In the present study, we wished to investigate the role of the CSTB gene in patients with JME. Fifty‐seven unrelated patients (35 women; mean age ± standard deviation [SD], 24.1 ± 7.7; mean age ± SD at onset, 15.3 ± 2.4) with JME were enrolled. Twenty‐three of 57 patients were the probands of families with JME. The molecular diagnosis was carried out to identify the common dodecamer repeat expansion mutation or other disease‐causing mutations in the CSTB gene. The molecular analysis did not depict mutations in any of the 57 patients with JME. Our study did not support a role for the CSTB gene in patients with familial or sporadic JME.
Distance decay is uncommon in large‐scale population synchrony of common moths: does it promote vulnerability to climate change?
Authors: Nieminen Marko
Published: March 2015

Large‐scale spatial synchrony is common in population dynamics. In nearly all empirical data sets, population synchrony decays with distance.

Large‐scale spatial population synchrony of 20 common moth species was studied using 367 separate light‐trap time series of 3–27 years, at 13–19 localities in southern Finland. The maximum distance between trap sites wasca1075 km. The degree of spatial synchrony in three weather variables (daily mean and minimum temperature, and daily total precipitation) from 15 weather stations was also studied. Data were analysed with spatial non‐parametric correlation functions (Sncf).

Statistically significant large‐scale spatial synchrony in population fluctuations occurred in 85% of the species (Scotopteryx chenopodiata,Eulithis populata,Chloroclysta citrata,Epirrita autumnata,Perizoma alchemillata,P. didymata,Eupithecia pusillata,Macaria wauaria,Itame brunneata,Cabera pusaria,C. exanthemata,Eilema lurideola,Rusina ferruginea,Amphipoea fucosa,Orthosia gothica,Cerapteryx graminisandDiarsia mendica), as well as in all weather variables.

Spatial synchrony decreased with distance (=distance decay) in 45% of the species, and there was no indication of distance decay in the remaining species.

Climate change is likely to cause an increasing frequency of extreme weather events, and insects are strongly affected by such environmental stochasticity. In combination with the high frequency of large‐scale spatial synchrony, which did not show distance decay as a rule in these data, even currently common moth species may become threatened in the near future.
Compensatory Intracranial Arterial Dilatation in Extracranial Carotid Atherosclerosis: The Northern Manhattan Study
Authors: Gutierrez Jose , Elkind Mitchell S. V. , Gomez-Schneider Maia , DeRosa Janet T. , Cheung Ken , Bagci Ahmet , Alperin Noam , Sacco Ralph L. , Wright Clinton B. , Rundek Tatjana
Published: March 2015

Background

There is a scarcity of data supporting the association between atherosclerosis and dolichoectasia in unbiased samples.

Aims

To test the hypothesis that the association between dolichoectasia and extracranial carotid atherosclerosis depends on the degree of collateral circulation.

Methods

The Northern Manhattan Study magnetic resonance imaging substudy consists of 1290 participants who remained stroke-free at the time of magnetic resonance imaging. Arterial diameters were collected in all participants with available magnetic resonance angiography. Dolichoectasia was defined as a head-size adjusted diameter >2 standard deviation for each artery. Carotid Doppler was used to evaluate for carotid atherosclerosis (carotid plaque, maximum plaque thickness and carotid intima media thickness).

Results

We included 994 participants with available Doppler and magnetic resonance angiography data (mean age 63 years, 60% female). Any dolichoectasia was reported in 16% of participants, 54% had at least one carotid plaque and the mean carotid intima media thickness was 0·92 ± 0·09 mm. After adjusting for demographic and clinical characteristics, there was no association between markers of carotid atherosclerosis and dolichoectasia. However, stratifying by collaterals, it was observed that dolichoectasia was more likely in the anterior and posterior circulations when collaterals were available among participants with carotid atherosclerosis. These associations were confirmed by noting an increment in arterial diameters in the corresponding arteries ipsilateral and contralateral to each carotid as well as in the posterior circulation.

Conclusions

We did not find an association of extracranial carotid atherosclerosis with dolichoectasia. However, we found that dolichoectasia is more frequent when intracranial collaterals are available suggesting a compensatory process that needs further investigation.
Improvement of overactive bladder symptoms after tension‐free vaginal mesh operation in women with pelvic organ prolapse: Correlation with preoperative urodynamic findings
Authors: Tomoe Hikaru
Published: March 2015

Objectives

To further elucidate the mechanisms of overactive bladder coexisting with pelvic organ prolapse.

Methods

A total of 100 consecutive women with stage 2 or greater pelvic organ prolapse associated with cystocele were enrolled in the present prospective study. They underwent urodynamic studies and then received tension‐free vaginal mesh operation. Urodynamic studies were carried out before and after the correction of pelvic organ prolapse using a single gauze pack in the vagina in the sitting position. The overactive bladder symptom score and International Prostate Symptom Score were collected before and 3 months after surgery.

Results

In 53 of 100 cases, pelvic organ prolapse was accompanied with overactive bladder, and detrusor overactivity was observed in 28 out of 53 pelvic organ prolapse with overactive bladder cases (52.8%). Detrusor overactivity was resolved in 18 and reduced in four out of 28 cases after the correction of pelvic organ prolapse by the gauze packing method. Of 53 patients who had overactive bladder preoperatively, overactive bladder symptoms disappeared in 35 cases (66.0%) and improved in six additional cases (11.3%) after tension‐free vaginal mesh operation. A total of 20 of 25 cases whose overactive bladder symptoms disappeared or improved after surgery coincided with those who had shown either disappearance (n = 16) or improvement (n = 4) of detrusor overactivity after intravaginal gauze pack insertion in preoperative urodynamic studies. All scores in the overactive bladder symptom score decreased significantly after tension‐free vaginal mesh, as well as the International Prostate Symptom Score, except for night‐time frequency.

Conclusions

Pelvic organ prolapse‐associated overactive bladder or detrusor overactivity conditions can be reversed in most cases within a short period of time after surgical correction of pelvic organ prolapse.
A second great transformation in Europe: The rise and imminent fall of the technocrats
Authors: Stråth Bo
Published: March 2015

Bo Stråth traces the rise of the technocracy – the ‘political abandonment of politics’ – and its spread from the EU to its member states. If Europe's institutions are to survive the crisis of legitimacy, he argues, the ‘market Europe’ consensus must end and a ‘social Europe’ must emerge.
The primacy of politics: Towards a more realistic liberalism
Authors: Sleat Matt
Published: March 2015

Matt Sleat asks how liberal politics can recharge its vision and ideals for a contemporary reality marked by increased political disengagement and the rise of populism. The answer, he argues, lies in a dialled‐down sense of morality, a willingness to compromise, and an unerring eye on power in all its forms.
Including the uncountable: The realism of feminist politics
Authors: Frazer Elizabeth
Published: March 2015

Feminist politics is an exemplar of political realism, argues Elizabeth Frazer, in that it seeks to represent those who might be left out of the theoretical frameworks or empirical experiments of traditional social sciences. This is why, she says, realistic politics must focus on the margins as much as the centres of power.
Moral Enhancement and Mental Freedom
Authors: Bublitz Christoph
Published: March 2015

Promotion of pro‐social attitudes and moral behaviour is a crucial and challenging task for social orders. As traditional ways such as moral education have some, but apparently and unfortunately only limited effect, some authors have suggested employing biomedical means such as pharmaceuticals or electrical stimulation of the brain to alter individual psychologies in a more direct way — moral bioenhancement. One of the salient questions in the nascent ethical debate concerns the impact of such interventions on human freedom. Advocates argue that moral bioenhancements do not pose a serious threat to freedom. This contention, however, is based on an overly narrow, if not impoverished, sense of freedom, which comprises only freedom of action and freedom of will. Mind‐altering interventions primarily affect another sense of freedom: freedom of mind, a concept that has not received much attention although it should rank among the most important legal and political freedoms. The article introduces three senses of mental freedom potentially infringed upon by moral bioenhancement and places it in a broader perspective. Ignorance of mental freedom has far‐ranging consequences for the shape of the political and legal order at large. As many advocates are apparently not aware of the freedoms they seek to undermine, their calls for moral enhancement programmes are dangerously premature.
Chemerin‐induced mitochondrial dysfunction in skeletal muscle
Authors: Xie Qihai , Deng Yujie , Huang Chenglin , Liu Penghao , Yang Ying , Shen Weili , Gao Pingjin
Published: March 2015

Chemerin is a novel adipocyte‐derived factor that induces insulin resistance in skeletal muscle. However, the effect of chemerin on skeletal muscle mitochondrial function has received little attention. In the present study, we investigated whether mitochondrial dysfunction is involved in the pathogenesis of chemerin‐mediated insulin resistance. In this study, we used recombinant adenovirus to express murine chemerin in C57BL/6 mice. The mitochondrial function and structure were evaluated in isolated soleus muscles from mice. The oxidative mechanism of mitochondrial dysfunction in cultured C2C12 myotubes exposed to recombinant chemerin was analysed by western blotting, immunofluorescence and quantitative real‐time polymerase chain reaction. The overexpression of chemerin in mice reduced the muscle mitochondrial content and increased mitochondrial autophagy, as determined by the increased conversion of LC3‐I to LC3‐II and higher expression levels of Beclin1 and autophagy‐related protein‐5 and 7. The chemerin treatment of C2C12 myotubes increased the generation of mitochondrial reactive oxygen species, concomitant with a reduced mitochondrial membrane potential and increased the occurrence of mitochondrial protein carbonyls and mitochondrial DNA deletions. Knockdown of the expression of chemokine‐like receptor 1 or the use of mitochondria‐targeting antioxidant Mito‐TEMPO restored the mitochondrial dysfunction induced by chemerin. Furthermore, chemerin exposure in C2C12 myotubes not only reduced the insulin‐stimulated phosphorylation of protein kinase B (AKT) but also dephosphorylated forkhead box O3α (FoxO3α). Chemerin‐induced mitochondrial autophagy likely through an AKT‐FoxO3α‐dependent signalling pathway. These findings provide direct evidence that chemerin may play an important role in regulating mitochondrial remodelling and function in skeletal muscle.