bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of P300 Reduction in South African Treatment‐Naïve Adolescents with Alcohol Dependence
Authors: Cuzen Natalie L. , Andrew Colin , Thomas Kevin G. F. , Stein Dan J. , Fein George
Published: June 2012

Background

Event‐related potential studies show reduced P300 amplitudes in alcohol use disorders (AUDs). Alcohol exposure, genetic vulnerability to alcoholism, and comorbid psychopathology may contribute to this reduction. Most previous research has studied treated adult AUD samples, which have more severe alcoholism, a greater family history of AUDs, and more comorbidity than untreated samples. Untreated AUD samples tend to have little or no P300 amplitude reduction. We compared P300 between treatment‐naïve alcohol‐dependent (TNAD) adolescents with no diagnosable substance abuse or psychiatric comorbidity and nonsubstance‐abusing control (NSAC) adolescents.

Methods

Individuals between the ages of 13 and 18 years were recruited into either TNAD (n = 45) or NSAC (n = 64) groups. Alcohol use variables, family history density of alcohol problems, and psychiatric symptom counts were assessed in a clinician‐administered evaluation. EEGs were recorded during performance of a 3‐condition visual target detection task.

Results

P300 amplitudes were of comparable size in TNAD adolescents and NSAC adolescents. Boys demonstrated larger P3a and P3b amplitudes than girls. Within TNAD, P3b amplitude was reduced in those who drank more frequently, and P3a latency was more prolonged in subjects with higher internalizing symptom counts.

Conclusions

The P300 deficit was not present in TNAD adolescents without comorbidities. In comparison to results of reduced P300 in treated adolescent AUD samples, this finding likely reflects moderate alcohol exposure, lower genetic vulnerability to alcoholism, and lack of comorbidity in our sample. Further work is needed to determine the relative contributions of these factors to changes in the P300.
International Comparison and Suggestions for Capacity Development in Industrializing Countries
Authors: Aoki‐Suzuki Chika , Bengtsson Magnus , Hotta Yasuhiko
Published: June 2012

The global consumption of natural resources is soaring, especially in rapidly industrializing economies. This increasing demand is depleting resource stocks and is a major driver of other environmental problems, including climate change and waste. With rising prices and growing concerns about resource access, these trends are increasingly attracting policy makers’ attention. Some developed countries have devised indicator systems, based on economy‐wide material flow analysis/accounting (EW‐MFA), to monitor resource consumption. This article consists of two separate but related parts: (1) a study of how EW‐MFA indicators are used in a number of developed countries, including analysis of the commonalities between countries that are actively using these indicators in policy, and (2) a survey of the current capacity for EW‐MFA in developing countries, including data availability and policy uptake. This study found that countries in which policy makers show a great interest in EW‐MFA indicators are characterized by large resource imports and large net export of manufactured goods. Many rapidly industrializing countries demonstrate similar characteristics. The study of developing countries found that many of the data for EW‐MFA exist, but collection is fragmented and access is limited. This article recommends that capacity development of EW‐MFA in rapidly industrializing economies should first coordinate a national focal point and then raise awareness among government officials, strengthen institutions collecting EW‐MFA data, and train researchers and experts in EW‐MFA techniques and effective policy interaction.
A randomized controlled trial evaluating recovery and survival of 6% dimethyl sulfoxide–frozen autologous platelets in healthy volunteers
Authors: Dumont Larry J. , Cancelas Jose A. , Dumont Deborah F. , Siegel Alan H. , Szczepiorkowski Zbigniew M. , Rugg Neeta , Pratt P. Gayle , Worsham D. Nicole , Hartman Elizabeth L. , Dunn Susan K. , O'Leary Margaret , Ransom Janet H. , Michael Rodney A. , Macdonald Victor W.
Published: June 2012

BACKGROUND: Availability of platelets (PLTs) is severely limited by shelf life in some settings. Our objective was to determine and compare to Food and Drug Administration (FDA) criteria the PLT recovery and survival of autologous PLTs cryopreserved at −65°C or less in 6% dimethyl sulfoxide (DMSO) reconstituted with a no‐wash method (cryopreserved PLTs [CPPs]) compared to autologous fresh PLTs.

STUDY DESIGN AND METHODS: This was a randomized, Phase I study analyzing PLT viability and in vitro function in consenting healthy subjects. Apheresis PLTs (APs) were collected in plasma. APs were suspended in 6% DMSO, concentrated, and placed at not more than −65°C for 7 to 13 days. Frozen CPPs were thawed at 37°C and resuspended into 25 mL of 0.9% NaCl. Control PLTs (fresh autologous) and CPPs were labeled with 111In or 51Cr, and recovery and survival after reinfusion were determined using standard methods. A panel of in vitro assays was completed on APs and CPPs.

RESULTS: After frozen storage, CPPs retained 82% of AP yield and showed increased PLT associated P‐selectin and reduced responses to agonists. CPP 24‐hour recovery (41.6 ± 9.7%) was lower than for fresh PLTs (68.4 ± 8.2%; p < 0.0001) and did not meet the current FDA criterion. CPPs had diminished survival compared to fresh PLTs (7.0 ± 2.1 days vs. 8.4 ± 1.2 days, respectively; p = 0.018), but did meet and exceed the FDA criterion for survival.

CONCLUSION: While 24‐hour recovery does not meet FDA criteria for liquid‐stored PLTs, the CPP survival of circulating PLTs was surprisingly high and exceeded the FDA criteria. These data support proceeding with additional studies to evaluate the clinical effectiveness of CPPs.
Two cases of transfusion‐transmitted hepatitis B virus (HBV) infection in a low‐endemic country before implementation of HBV nucleic acid testing
Authors: Servant‐Delmas Annabelle , Chuteau Claude , Lefort Caroline , Piquet Yves , Chevaleyre Sylvie , Betbeze Véronique , Delhoume Martine , Hantz Sébastien , Alain Sophie , Laperche Syria
Published: June 2012

BACKGROUND: The risk of hepatitis B virus (HBV) transmission by transfusion is higher than that of other blood‐borne viruses. In France, before the introduction of HBV nucleic acid testing (NAT) in 2010, blood donations were tested for hepatitis B surface antigen (HBsAg) and antibodies against hepatitis B core antigen, and the residual risk of HBV transfusion related to preseroconversion acute phase was estimated at 0.54 per million donations. The additional value of the implementation of a highly sensitive HBV NAT to prevent such transmissions is discussed.

STUDY DESIGN AND METHODS: Two lookback investigations based on HBV seroconversion of repeat donors were performed. Donors and recipients were followed up in multiple samples that were tested for HBV serologic and molecular markers.

RESULTS: The recipients have shown posttransfusion HBsAg seroconversion. The archived samples from the implicated donations were positive for HBV DNA at extremely low viral load in both cases. HBV isolates from donors and recipients of each case were organized in the same cluster with 100% identities into Genotypes A2 and B4, respectively. One recipient spontaneously recovered from infection while the second was successfully treated.

CONCLUSION: The present cases highlight the importance of introducing highly sensitive HBV NAT to prevent transmission. Moreover, the lookback studies based on appropriate molecular and serologic investigations of patients transfused with previous donations from newly identified HBV‐infected repeat donors offer the opportunity to treat a recently infected recipient.
Assessment of Right Ventricular Mechanics in Patients with Mitral Stenosis by Two‐Dimensional Deformation Imaging
Authors: Tanboga Ibrahim Halil , Kurt Mustafa , Bilen Emine , Aksakal Enbiya , Kaya Ahmet , Isik Turgay , Ekinci Mehmet , Karakoyun Süleyman , Sevimli Serdar
Published: June 2012

Background: It is well known that right ventricular (RV) dysfunction occurs early before clinical systemic congestion in patients with mitral stenosis (MS). Therefore, we aimed to evaluate the role of two‐dimensional (2D) strain imaging in the assessment of subclinical RV dysfunction. Methods: Fifty‐nine patients with isolated MS (mild and moderate) and 31 healthy control subjects constituted the study population. RV peak longitudinal strain (RV‐LS) and strain rate (RV‐LSr) measurements were obtained from apical four‐chamber view. Results: There were no significant differences in left ventricular ejection fraction (LV‐EF) and RV fractional area change between control and MS groups. RV strain (23.5 ± 7.2 vs. 18.63 ± 6.3, P = 0.001) and RV strain rate (1.72 ± 0.54 vs. 1.37 ± 0.66, P = 0.01) measurements were significantly lower in patients with MS than the control group. However, RV strain and strain rate measurements were comparable between MS subgroups. Correlation analysis revealed that there was poor correlation between RV‐LS/LSr and mean‐maximum gradients and echoscore but moderate correlation between RV‐LS and RV‐Sr in systolic pulmonary artery pressure and planimetric mitral valve area. Conclusion: We demonstrated that patients with MS had lower RV functions using 2D strain imaging and this is independent from severity of MS. In the detection of subclinical RV dysfunction in patients with MS, 2D strain imaging appears to be useful. (Echocardiography, 2012;00:1–6)
Utility of Intravascular Ultrasound Guidance in Patients Undergoing Percutaneous Coronary Intervention for Type C Lesions
Authors: WAKABAYASHI KOHEI , LINDSAY JOSEPH , LAYNEZ‐CARNICERO ANA , BEN‐DOR ITSIK , SARDI GABRIEL , TORGUSON REBECCA , XUE ZHENYI , SATLER LOWELL F. , PICHARD AUGUSTO D. , WAKSMAN RON
Published: June 2012

Background:
 Percutaneous coronary intervention (PCI) of complex lesions (i.e., American College of Cardiology/American Heart Association class type C) remains challenging and the outcome may be compromised. The use of intravascular ultrasound (IVUS) to guide PCI was suggested to improve outcome.

Methods:

A cohort of 1,984 patients who underwent PCI to type C lesions in our center from April 2000 to March 2010 was identified. Using propensity score matching with clinical and angiographic characteristics, we identified 637 patients who underwent IVUS guidance and 637 patients who had only angiographic guidance PCI. Major adverse cardiovascular events (MACE), a composite end‐point of all‐cause mortality, Q‐wave myocardial infarction and target lesion revascularization, were compared between the 2 groups.

Results:

After propensity score matching, baseline clinical and angiographic characteristics were well matched. Patients undergoing IVUS‐guided PCI had less predilatation and more postdilatation, and were treated more often with cutting balloon. Final diameter stenosis was significantly smaller in the IVUS‐guided group (3 ± 11% vs. 7 ± 19%, P < 0.001), resulting in higher angiographic success compared with the non‐IVUS‐guided group (97.9% vs. 94.8%, P < 0.001). The incidence of MACE was significantly lower in the IVUS‐guided group compared to the angiography‐guided group (11.0% vs. 15.6%, P = 0.017) as was cardiac death (1.9% vs. 4.4%, P = 0.010).

Conclusion:

IVUS‐guided PCI for complex type C lesions is associated with better outcome and should be considered for these lesions. (J Interven Cardiol 2012;25:452–459)
Vascular associated gene variants in patients with preeclampsia: results from the Danish National Birth Cohort
Authors: LYKKE JACOB A. , BARE LANCE A. , OLSEN JØRN , LAGIER ROBERT , TONG CARMEN , ARELLANO ANDRE , PAIDAS MICHAEL J. , LANGHOFF‐ROOS JENS
Published: June 2012

Objective. Preeclampsia has been linked to subsequent vascular disease with many shared predisposing factors. We investigated the association between severe preeclampsia, and its subtypes, and specific vascular‐related polymorphisms. Design. The study was a retrospective nested case‐cohort design. Setting. Pregnant Danish women participating in the Danish National Birth Cohort. Population. 263 cases of severe preeclampsia and 1851 random controls were selected from the Danish National Birth Cohort. Methods. We validated all cases of severe preeclampsia and genotyped for 108 single nucleotide polymorphisms (SNPs) that were selected based on previous publications on the association with vascular disease. Logistic models were used for statistical analyses. Main outcome measures. Maternal polymorphisms in genomic models. Results. We found 17 of 108 SNPs associated with severe preeclampsia (p < 0.05). Women homozygous for the rs1799983 in NOS3 were 1.6‐fold [95% confidence interval (CI) 1.0–2.4] more likely to develop severe preeclampsia. Women homozygous for the rs1010 SNP in VAMP8 were twofold (95%CI 1.1–3.5) more likely to deliver preterm when preeclampsia was present. Women homozygous for the rs10811661 SNP were 2.1‐fold (95%CI 1.1–3.9) more likely to develop severe preeclampsia and 3.7‐fold (95%CI 1.1–12.4) more likely to deliver a small‐for‐gestational age child when preeclampsia was present. All associations are available as Supporting Information. Conclusion. We found several vascular‐associated SNPs linked to severe preeclampsia; however, most of these associations are probably by pure chance, which warrants replication and further translational research. To date, no specific SNP has yet proven valuable in a clinical setting in predicting preeclampsia.
Lipid rafts association and anti‐apoptotic function of prohibitin in ultraviolet B light‐irradiated HaCaT keratinocytes
Authors: Wu Qiong , Wu Shiyong
Published: June 2012

Upon UVB irradiation, an alternation of major lipid raft components can lead to the recruitment/activation of rafts‐associated proteins and initiation of downstream apoptotic signalling pathways. We used two‐dimensional gel electrophoresis (2‐DE) to identify potential regulators of UVB‐induced apoptosis and mass spectrometry fingerprint analysis to identify proteins that are altered in the rafts after UVB irradiation. Our data show that levels of several proteins, including prohibitin (PHB), were changed in lipid rafts after UVB irradiation. We also demonstrate that while total PHB expression was not changed, the protein was enriched in lipid rafts after UVB irradiation. Reduced expression of PHB using siRNA knockdown resulted in an increase in cellular apoptosis after UVB irradiation. Based on these results, we propose that PHB protects keratinocytes from UVB‐induced apoptosis.
Ultraviolet B‐induced LGI3 secretion protects human keratinocytes
Authors: Lee Seung Hoon , Jeong Yun‐Mi , Kim So‐Young , Jeong Hyo‐Soon , Park Kyoung‐Chan , Baek Kwang Jin , Kwon Nyoun Soo , Yun Hye‐Young , Kim Dong‐Seok
Published: June 2012

Leucine‐rich glioma inactivated 3 (LGI3) is known to be expressed mainly in the brain. However, the expression and physiological roles of LGI3 in skin cells remain unknown. In this study, it was found for the first time that LGI3 is expressed mostly by normal human keratinocytes. Furthermore, ELISA analysis showed that HaCaT human keratinocytes increased LGI3 secretion after exposure to ultraviolet B (UVB) in a time‐ and dose‐dependent manner. We next investigated the possible role of LGI3 in keratinocytes. LGI3 (50 ng/ml) increased survival of HaCaT cells by 20% after UVB irradiation (150 mJ/cm2). It was also found that LGI3 stimulates the phosphorylation of Akt, which is involved in the cell survival‐signalling cascade. Furthermore, LGI3 led to the phosphorylation of MDM2 and subsequent p53 degradation. Taken together, the data suggest that LGI3 may regulate p53 levels and that keratinocyte‐derived LGI3 may act as a novel cytokine for skin homoeostasis.
News on microenvironmental physioxia to revisit skin cell targeting approaches
Authors: Grillon Catherine , Matejuk Agata , Nadim Mahdi , Lamerant‐Fayel Nathalie , Kieda Claudine
Published: June 2012

The skin is a multifunctional organ and a first line of defense actively protecting from environmental stress caused by injury, microbial treat, UV irradiation and environmental toxins. Diverse cutaneous cell types together with extracellular matrix elements and factors create a dynamic scene for cellular communication crucial in vital processes such as wound healing, inflammation, angiogenesis, immune response. Direct functional success of skin equilibrium depends on its microenvironment settings and particularly the local oxygen tension. Indeed, skin entire milieu is characterized by and highly dependent on its low oxygen tension called physioxia as emphasized in this review. In the context of skin physioxia, we review and propose here new approaches to minimize age‐related changes in skin state and function. We particularly emphasize carbohydrate‐mediated interactions and new 3D models of engineered skin substitutes. We highlight newly emerged tools and targets including stem cells, miRNAs, matrix metalloproteinases, mitochondria and natural antioxidants that are promising in prevention of skin ageing and disease restraint. In the era of advanced dermatology, new attempts are bringing us closer to ‘well being’ perception.
The influence of surfactants and hydrolyzed proteins on keratinocytes viability and elasticity
Authors: Kobiela Tomasz , Lelen‐Kaminska Karolina , Stepulak Michal , Lekka Malgorzata , Malejczyk Magdalena , Arct Jacek , Majewski Slawomir
Published: June 2012

Background/purpose

The knowledge how surfactants and hydrolyzed proteins influence the elastic properties of living epidermal keratinocytes is sparse. We demonstrate that the stiffness of cells measured by atomic force microscope (AFM) can be correlated with viability test.

Methods and materials

The effects of sodium lauryl sulphate (SLS) and hydrolyzed collagen (HK) of molecular weight 9 kDa were examined with respect to human keratinocytes viability and elasticity. MTT assay was applied to determine the survival fraction of keratinocytes treated with SLS and HK solutions of various molar ratios. The AFM measurements of the keratinocytes stiffness were carried out immediately after the exposure of cells to the SLS and HK, respectively.

Results

The increase of the SLS concentration resulted in the decrease of cells proliferation and this effect was inhibited by addition of HK. The strongest inhibition was observed for the SLS:HK molar ratio equals to 2:1. AFM study shows decrease in the cell stiffness for cells treated with SLS. Fluorescence microscopy reveals remodeling of actin filaments of SLS‐treated cells. SLS:HK mixture treatment results in mechanical stiffness close to untreated cells.

Conclusion

These results provide possible correlations between mechanical properties and viability of keratinocytes when the chemical stress occurs.
Understorey plant species show long‐range spatial patterns in forest patches according to distance‐to‐edge
Authors: Pellissier Vincent , Bergès Laurent , Nedeltcheva Théodora , Schmitt Marie‐Cécile , Avon Catherine , Cluzeau Catherine , Dupouey Jean‐Luc
Published: June 2012

Questions

How does the presence of understorey plant species vary with distance‐to‐edge along very large periphery‐to‐interior and forest patch size gradients? Can forest core and periphery species profiles be identified? What life‐history traits can discriminate between forest core and forest periphery species?

Location

Temperate forests in the northern half of France.

Methods

Local climate, soil, stand characteristics and landscape metrics were collected on 19 989 plots in 1801 forest patches using data from the French National Forest Inventory. Very large distance‐to‐edge (3–1096 m) and patch size gradients (327–100 000 ha) were explored. Four logistic regression models were compared to determine the response patterns of 214 species to distance‐to‐edge, while controlling for patch size and local habitat quality (soil, climate and stand). The maximum distance of correlation between species occurrence and distance‐to‐edge was assessed using response curve characteristics. The relationships between life‐history traits (habitat preference, preference for ancient forests, reproduction mode, dispersal mode, life form and autecology) and species profile according to distance‐to‐edge were tested.

Results

Of the 214 species analysed, 40 had a core profile and 38 a periphery profile. The maximum distance of correlation was on average 748 m. Core species were more often species reproducing both by seed and vegetatively, ancient forest species, anemochores, bryophytes, pteridophytes, hemicryptophytes and acidophiles, whereas peripheral species were more often species reproducing by seed only, endozoochores, phanerophytes, thermophiles, basophiles, nitrogen‐demanding and heliophiles.

Conclusions

Significant periphery‐to‐core patterns of distribution were detected over much larger ranges than hitherto recognized for common understorey plant species. Plant traits differentiated forest core from forest periphery species. This deep gradient cannot be solely explained by the usual edge‐related biotic and abiotic factors. We hypothesized that it was due to edge displacement following general reforestation since ca. 1830. This edge shift created recent forests with new habitats on former agricultural lands where dispersal‐limited core species had slowly expanded and forest edge species regressed at variable speeds. This long periphery‐to‐interior gradient of presence has important implications for forest plant species distribution, dynamics and conservation.
Changes in circulating adiponectin and metabolic hormone concentrations during periparturient and lactation periods in Holstein dairy cows
Authors: OHTANI Yoshihisa , TAKAHASHI Tatsuyuki , SATO Katsuyoshi , ARDIYANTI Astrid , SONG Sang‐Houn , SATO Reiichiro , ONDA Ken , WADA Yasunori , OBARA Yoshiaki , SUZUKI Keiichi , HAGINO Akihiko , ROH Sang‐gun , KATOH Kazuo
Published: June 2012

Although our previous report demonstrated that adiponectin and AdipoR1 gene expressions changed among different lactation stages in the bovine mammary gland, its in vivo kinetics remain unclear in ruminant animals. In this study, we investigated the changes in circulating concentrations of adiponectin, as well as other metabolic hormones and metabolites, (i) during the periparturient period and (ii) among different lactation stages, in Holstein dairy cows. In experiment 1, serum adiponectin concentrations increased after parturition. Serum insulin concentrations were lower in the postpartum than prepartum period, whereas serum growth hormone (GH) concentrations increased in the postpartum period. Serum nonesterified fatty acids (NEFA) levels were increased during the postpartum period and were dependent on the parity. In experiment 2, there was no significant difference in plasma adiponectin concentrations among lactational stages. Plasma insulin concentrations tended to be lower in early lactation while plasma GH levels tended to be higher. Plasma NEFA concentrations were significantly lower in mid‐ and late‐lactation stages than non‐lactation stages. These findings indicate that elevation of serum adiponectin might be involved in energy metabolism just around parturition, and might exert its action through regulation of receptor expression levels in target tissues in each lactational stage in Holstein dairy cows.
Factors associated with dry mouth in dependent Japanese elderly
Authors: Kakudate Naoki , Muramatsu Tsukasa , Endoh Mami , Satomura Kazuhito , Koseki Takeyoshi , Sato Yuji , Ito Kayoko , Ogasawara Tadashi , Nakamura Seiji , Kishimoto Etsuo , Kashiwazaki Haruhiko , Yamashita Yoshihisa , Uchiyama Kimio , Nishihara Tatsuji , Kiyohara Yutaka , Kakinoki Yasuaki
Published: June 2012

Objectives

To identify factors associated with dry mouth.

Background

Dry mouth adversely affects oropharyngeal health, particularly in elderly, and can lead to pneumonia. A better understanding of the epidemiology of dry mouth is therefore important in improving treatment strategies and oral health in high‐risk elderly patients.

Methods

We conducted a cross‐sectional study involving 383 dependent Japanese elderly individuals (65–84 [n = 167] and ≥85 [n = 216] years) at eight long‐term care facilities and hospitals. Thirty‐four potential factors associated with dry mouth were examined by multiple logistic regression analysis. The primary outcome was dry mouth, as diagnosed by tongue dorsum moisture.

Results

We identified that body mass index and severity of physical disability were identified as a potential factors associated with dry mouth in the super‐elderly (≥85 years) group, whereas severity of physical disability, outcome measurement time, high daily water consumption, mouth breathing, use of antidepressants and diuretics, and high frequency of daily brushing (≥2 times per day; Odds ratio: 5.56; 95% Confidence Interval: 1.52–20.00) were associated with dry mouth in the 65‐ to 84‐year‐old group.

Conclusion

To our knowledge, this is the first study to identify a link between frequency of daily brushing and dry mouth and suggests that tooth brushing should be encouraged in high‐risk dependent Japanese elderly (65–84 years), particularly those taking antidepressants and/or diuretics.
THE HAPPY AND SUFFERING STUDENT? ROUSSEAU'S EMILE AND THE PATH NOT TAKEN IN PROGRESSIVE EDUCATIONAL THOUGHT
Authors: Mintz Avi I.
Published: June 2012

One of the mantras of progressive education is that genuine learning ought to be exciting and pleasurable, rather than joyless and painful. To a significant extent, Jean‐Jacques Rousseau is associated with this mantra. In a theme of Emile that is often neglected in the educational literature, however, Rousseau stated that “to suffer is the first thing [Emile] ought to learn and the thing he will most need to know.” Through a discussion of Rousseau's argument for the importance of an education in suffering, Avi Mintz contends that the reception of Rousseau by progressives suggests a detrimental misstep in the history of educational thought, a misstep that we should recognize and correct today. We ought to revive the progressive tradition of distinguishing the valuable educational pains from the harmful ones, even if we disagree with the particular types of pain that Rousseau identified as educationally valuable.
ROUSSEAU, HAPPINESS, AND THE ECONOMIC APPROACH TO EDUCATION
Authors: Gilead Tal
Published: June 2012

Since the 1960s, the influence of economic thought on education has been steadily increasing. Taking Jean‐Jacques Rousseau's educational thought as a point of departure, Tal Gilead critically inquires into the philosophical foundations of what can be termed the economic approach to education. Gilead's focus in this essay is on happiness and the role that education should play in promoting it. The first two parts of the essay provide an introduction to Rousseau's conception of happiness, followed by an examination of the economic approach to education and the notion of human capital. In the course of this discussion, Gilead shows that increasing happiness is one of the economic approach's major aims. In the third part of the essay, he uses Rousseau's views to interrogate significant aspects of the economic approach to education. He then continues by highlighting some of the educational implications that stem from Rousseau's critique. Gilead maintains that Rousseau's ideas can provide valuable suggestions regarding how education might contribute to the promotion of happiness. The article concludes by proposing that while Rousseau's ideas on the matter should not necessarily be embraced, contemporary policymakers can learn some important lessons from them.
The Critical Need for Academic Health Centers to Assess the Training, Support, and Career Development Requirements of Clinical Research Coordinators: Recommendations from the Clinical and Translational Science Award Research Coordinator Taskforce*
Authors: Speicher Lisa A. , Fromell Gregg , Avery Sue , Brassil Donna , Carlson Lori , Stevens Erika , Toms Michele
Published: June 2012

Clinical Research Coordinators (CRCs) are a vital component of the clinical research enterprise providing a pivotal role in human subject protection through the numerous activities and responsibilities assigned to them. In 2006, the National Institutes of Health’s National Center for Research resources (NCRR) implemented the Clinical and Translational Science Awards program (CTSA) to advance biomedical research. As a part of this endeavor, many workgroups were formed among the Consortium to support translational research. The Research Coordinator Taskforce was created as part of the Regulatory Knowledge group of the Clinical Research Innovation Key Function Committee, and focuses on enhancing CTSA capabilities to provide support and training for CRCs. In the spring of 2008, this taskforce conducted two surveys of the then 24 CTSA Consortium members to better understand the current expectations and responsibilities of research coordinators in addition to the mechanism for providing education, training, and support in order for CRCs to successfully meet the study responsibilities placed upon them. The results of these surveys are summarized in this article and provide context to the recommendations of the Research Coordinator Taskforce for institutional considerations, approaches, and best practices for providing education, training, and support the expanding role of CRCs in fulfilling their responsibilities delegated to them by investigators. Clin Trans Sci 2012; Volume 5: 470–475
Recombinant Human Thyrotropin in Veterinary Medicine: Current Use and Future Perspectives
Authors: Campos M. , van Hoek I. , Peremans K. , Daminet S.
Published: June 2012

Recombinant human thyrotropin (rhTSH) was developed after bovine thyrotropin (bTSH) was no longer commercially available. It was approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) as an aid to diagnostic follow‐up of differentiated thyroid carcinoma in humans and for thyroid remnant ablation with radioiodine. In addition, rhTSH is used in human medicine to evaluate thyroid reserve capacity and to enhance radioiodine uptake in patients with metastatic thyroid cancer and multinodular goiter. Likewise, rhTSH has been used in veterinary medicine over the last decade. The most important veterinary use of rhTSH is thyroidal functional reserve testing for the diagnosis of canine hypothyroidism. Recent pilot studies performed at Ghent University in Belgium have investigated the use of rhTSH to optimize radioiodine treatment of canine thyroid carcinoma and feline hyperthyroidism. Radioiodine treatment optimization may allow a decreased therapeutic dosage of radioiodine and thus may improve radioprotection. This review outlines the current uses of rhTSH in human and veterinary medicine, emphasizing research performed in dogs and cats, as well as potential future applications.
Category count models for resource management
Authors: Fackler Paul L.
Published: June 2012

1.A category count model consists of a fixed set of objects (often sites) each of which is classified as one of a set of mutually exclusive categories. Additionally, the category membership of each object evolves over time as a Markov process. The evolution of the objects can be affected by choosing the number of objects in each category that receive alternative management actions.

2.Category count models have been used for a variety of resource management applications, including conservation of endangered species, land management and the management of pest infestations.

3.This paper provides for the first time a general framework for such models, briefly reviews existing applications that fit the general framework, discusses the non‐trivial problem of how transition probabilities can be computed as well as some of the challenges facing analysts using this framework.

4.The framework is applied to an existing application (the management of habitat for a threatened species), demonstrating the importance of modelling the stochasticity inherent in the problem.
Estimating patterns and drivers of infection prevalence and intensity when detection is imperfect and sampling error occurs
Authors: Miller David A. W. , Talley Brooke L. , Lips Karen R. , Campbell Grant Evan H.
Published: June 2012

1. Epidemiological studies are crucial for understanding the distribution and dynamics of emerging infectious diseases. To accurately assess infection states in wild populations, researchers need to account for observational uncertainty. We focus on two sources of uncertainty when estimating epidemiological parameters: nondetection of infection in sampled individuals and sampling error when quantifying infection intensity for infected individuals.

2. We developed new analytical methods to simultaneously estimate prevalence and the distribution of infection intensities based on repeated sampling of individuals in the wild. The methods are an extension of those used for occupancy estimation and address both sources of observation error. At the same time, we account for heterogeneity in detection probability that results from individual variation in infection intensity.

3. We use two estimation approaches to account for detection. The first is to use the complete likelihood in a hierarchical Bayesian model and fit using Markov chain Monte Carlo sampling. The second is to estimate the detection relationship using a mark–recapture abundance estimator and use those results to calculate weighted estimates for prevalence and mean infection intensities.

4. We use data from a field survey of Batrachochytrium dendrobatidis in Illinois amphibians to test these methods. We show that detection probability using quantitative PCR is strongly related to infection intensity, measured in zoospore equivalents. Sites in the study varied greatly in estimated prevalence and to a lesser extent in mean infection intensities of infected individuals. We did not find evidence of a relationship of snout‐vent‐length to infection intensity or prevalence. Naïve estimates of prevalence that do not account for detection were less than estimates for either of our methods, which yielded similar prevalence values for most sites.

5. Uncertainty when assessing disease state is a characteristic of most diagnostic tests. The estimators presented here account for this uncertainty and thus can improve accuracy when assessing the relationship of ecological factors to prevalence and infection intensity.
Null model tests for niche conservatism, phylogenetic assortment and habitat filtering
Authors: Ulrich Werner , Piwczyński Marcin , Maestre Fernando T. , Gotelli Nicholas J.
Published: June 2012

1. Phylogenetic and trait analyses are powerful tools for disentangling the mechanisms underlying the structure of plant and animal communities, and their use has become prominent in the last decade. However, few studies have simultaneously incorporated data on species traits or phylogeny, environment, and species co‐occurrences. Therefore, the relative importance of these factors as drivers of community assembly is largely unknown.

2. We introduce new and conceptually simple null model tests and appropriate metrics to disentangle the relationships between species co‐occurrence, traits or phylogeny and environmental factors not covered by available packages for phylogenetic analysis. We illustrate the methods with an extensive data set on understory plant assemblages sampled in three Polish forests.

3. Benchmark testing indicates that the proposed methods have good error behaviour when tested against a variety of artificial matrix sets covering a wide range of observed patterns. Test results are largely independent of matrix size and matrix fill and have adequate power to detect even weak patterns of non‐randomness. The different metrics used are uncorrelated with one another and capture different, and often divergent, patterns expressed within the same matrix.

4. Our case study revealed three distinct patterns in forest understory plant assemblages: (i) multiple patterns of species associations within meta‐communities might mask the influence of phylogeny and environmental variables on species occurrences, (ii) the strength of environmental and phylogenetic signals depend on the co‐occurrence pattern (segregated, aggregated, clumped) and might vary within a single meta‐community, and (iii) a random association of phylogeny and species co‐occurrence coupled with significant correlations between environmental factors and phylogeny might reveal species with traits that have passed through environmental filtering.
Correspondence
Authors: Curtis Simon
Published: June 2012

See also response by Ramsey et al
Chronic hypoxia‐induced upregulation of Ca2+‐activated Cl− channel in pulmonary arterial myocytes: a mechanism contributing to enhanced vasoreactivity
Authors: Sun Hui , Xia Yang , Paudel Omkar , Yang Xiao‐Ru , Sham James S. K.
Published: June 2012

Key points

A prolonged reduced oxygen level in the lungs, as occurs in patients of many chronic lung diseases and in residents living at high altitude, causes pulmonary hypertension characterized by profound structural and functional changes in pulmonary vasculature.

Many of these changes are ascribed to alterations in Ca2+ homeostasis related to cation channels of pulmonary arterial smooth muscle cells.

Here we report the increase of an anion conductance called calcium‐activated chloride channel and the expression of the channel gene TMEM16A in pulmonary arterial smooth muscle cells isolated from rats exposed to 10% oxygen for 3–4 weeks.

The upregulation of the chloride channel contributes to the hyper‐responsiveness of pulmonary arteries to serotonin associated with pulmonary hypertension.

These results help us to appreciate the importance of anion channels in the pathophysiology of pulmonary hypertension, and may lead to alternative strategies for the treatment of the disease.

Abstract  Chronic hypoxic pulmonary hypertension (CHPH) is associated with altered expression and function of cation channels in pulmonary arterial smooth muscle cells (PASMCs), but little is known for anion channels. The Ca2+‐activated Cl− channel (CaCC), recently identified as TMEM16A, plays important roles in pulmonary vascular function. The present study sought to determine the effects of chronic hypoxia (CH) on the expression and function of CaCCs in PASMCs, and their contributions to the vascular hyperreactivity in CHPH. Male Wistar rats were exposed to room air or 10% O2 for 3–4 weeks to generate CHPH. CaCC current (ICl.Ca) elicited by caffeine‐induced Ca2+ release or by depolarization at a constant high [Ca2+]i (500 or 750 nm) was significantly larger in PASMCs of CH rats compared to controls. The enhanced ICl.Ca density in CH PASMCs was unrelated to changes in amplitude of Ca2+ release, Ca2+‐dependent activation, voltage‐dependent properties or calcineurin‐dependent modulation of CaCCs, but was associated with increased TMEM16A mRNA and protein expression. Maximal contraction induced by serotonin, an important mediator of CHPH, was potentiated in endothelium‐denuded pulmonary arteries of CH rats. The enhanced contractile response was prevented by the CaCC blockers niflumic acid and T16Ainh‐A01, or by the L‐type Ca2+ channel antagonist nifedipine. The effects of niflumic acid and nifedipine were non‐additive. Our results demonstrate for the first time that CH increases ICl.Ca density, which is attributable to an upregulation of TMEM16A expression in PASMCs. The augmented CaCC activity in PASMCs may potentiate membrane depolarization and L‐type channel activation in response to vasoconstrictors and enhance pulmonary vasoreactivity in CHPH.
Experience‐dependent expression of NPAS4 regulates plasticity in adult visual cortex
Authors: Maya‐Vetencourt José Fernando , Tiraboschi Ettore , Greco Dario , Restani Laura , Cerri Chiara , Auvinen Petri , Maffei Lamberto , Castrén Eero
Published: June 2012

Key points

Transcription factors at the basis of plasticity in the adult visual system are unknown.

Enhanced levels of NPAS4 transcription factor parallel visual cortical plasticity in adult life.

Overexpression of NPAS4 restores plasticity in the adult visual cortex.

NPAS4 down‐regulation prevents the plastic outcome caused by fluoxetine (FLX) in adulthood.

NPAS4 regulates the expression of plasticity genes in the adult visual cortex.

Abstract  There is evidence that developmental‐like plasticity can be reactivated in the adult visual cortex. Although activity‐dependent transcription factors underlying the process of plasticity reactivation are currently unknown, recent studies point towards NPAS4 as a candidate gene for the occurrence of plasticity in the adult visual system. Here, we addressed whether NPAS4 is involved in the reinstatement of plasticity by using the monocular deprivation protocol and long‐term fluoxetine treatment as a pharmacological strategy that restores plasticity in adulthood. A combination of molecular assays for gene expression and epigenetic analysis, gene delivery by lentiviral infection, shRNA interference and electrophysiology as a functional read‐out, revealed a previously unknown role for the transcription factor NPAS4 in the regulation of adult visual cortical plasticity. We found that NPAS4 overexpression restores ocular dominance plasticity in adult naïve animals whereas NPAS4 down‐regulation prevents the plastic outcome caused by fluoxetine in adulthood. Our findings lead the way to the identification of novel therapeutic targets for pathological conditions where reorganization of neuronal networks would be beneficial in adult life.
Physical activity opposes coronary vascular dysfunction induced during high fat feeding in mice
Authors: Park Yoonjung , Booth Frank W. , Lee Sewon , Laye Mathew J. , Zhang Cuihua
Published: June 2012

Key points

Sedentary and high‐fat diet lifestyles are associated with greater prevalence of obesity and type 2 diabetes in humans, both of which independently increase atherosclerosis.

High‐fat diet in sedentary individuals produces endothelial dysfunction in blood vessels as a first step toward coronary arteriosclerosis.

We observed preservation of coronary arteriolar vascular function when mice began voluntary running in wheels at the start of a high‐fat diet.

We further showed that mechanisms by which running opposed the detrimental effects of high‐fat diet on vascular function included maintenance of eNOS phosphorylation, leptin sensitivity, and redox balance in mouse coronary arterioles.

The results provide evidence for how physical activity is an effective therapy to oppose the development of atherosclerosis in the first place.

Abstract  The study's purpose was to investigate if physical activity initiated with the start of high‐fat feeding would oppose development of endothelial dysfunction, and if it does, then to determine some potential mechanisms. C57BL/6 female mice were randomly divided into three groups: (1) control low‐fat diet (LF‐SED; 15% of calories from fat), (2) high‐fat diet (HF‐SED; 45% of calories from fat), and (3) HF diet given access to a voluntary running wheel (HF‐RUN). Our hypothesis was that HF‐RUN would differ in multiple markers of endothelial dysfunction from HF‐SED after 10 weeks of 45%‐fat diet, but would not differ from LF‐SED. HF‐RUN differed from HF‐SED in nine determinations in which HF‐SED either had decreases in (1) acetylcholine (ACh)‐induced and flow‐induced vasodilatations in isolated, pressurized coronary arterioles, (2) heart phosphorylated endothelial nitric oxide synthase (p‐eNOS/eNOS) protein, (3) coronary arteriole leptin (ob) receptor protein, (4) phosphorylated signal transducer and activator of transcription 3 (p‐STAT3/STAT3) protein, and (5) coronary arteriole superoxide dismutase 1 protein; or had increases in (6) percentage body fat, (7) serum leptin, (8) coronary arteriole suppressor of cytokine signalling 3 (SOCS3) protein, and (9) coronary arteriole gp91phox protein. Higher endothelium‐dependent vasodilatation by ACh or leptin was abolished with incubation of NOS inhibitor NG‐nitro‐l‐arginine‐methyl ester (l‐NAME) in LF‐SED and HF‐RUN groups. Further, impaired ACh‐induced vasodilatation in HF‐SED was normalized by apocynin or TEMPOL to LF‐SED and HF‐RUN. These findings demonstrate multiple mechanisms (eNOS, leptin and redox balance) by which voluntary running opposes the development of impaired coronary arteriolar vasodilatation during simultaneous high‐fat feeding.
Morphological, neurochemical and electrophysiological features of parvalbumin‐expressing cells: a likely source of axo‐axonic inputs in the mouse spinal dorsal horn
Authors: Hughes D. I. , Sikander S. , Kinnon C. M. , Boyle K. A. , Watanabe M. , Callister R. J. , Graham B. A.
Published: June 2012

Key points

Perception of normal bodily sensations relies on the precise regulation of sensory information entering the dorsal horn of the spinal cord.

Inhibitory, axoaxonic, synapses provide a mechanism for this regulation, but the source of these important inhibitory connections remains to be elucidated.

This study shows that a subpopulation of spinal interneurons that expresses parvalbumin and have specific morphological, connectivity and functional characteristics are a likely source of the inhibitory inputs that selectivity regulate non‐noxious tactile input in the spinal cord.

Our findings suggest that a loss of normal function in parvalbumin positive dorsal horn neurons may result in the development of tactile allodynia, where non‐painful stimuli gain the capacity to evoke the sensation of pain.

Abstract  Axo‐axonic synapses on the central terminals of primary afferent fibres modulate sensory input and are the anatomical correlate of presynaptic inhibition. Although several classes of primary afferents are under such inhibitory control, the origin of these presynaptic inputs in the dorsal horn is unknown. Here, we characterize the neurochemical, anatomical and electrophysiological properties of parvalbumin (PV)‐expressing cells in wild‐type and transgenic mice where enhanced green fluorescent protein (eGFP) is expressed under the PV promoter. We show that most PV cells have either islet or central cell‐like morphology, receive inputs from myelinated primary afferent fibres and are concentrated in laminae II inner and III. We also show that inhibitory PV terminals in lamina II inner selectively target the central terminals of myelinated afferents (∼80% of 935 PVeGFP boutons) and form axo‐axonic synapses (∼75% of 71 synapses from PV boutons). Targeted whole‐cell patch‐clamp recordings from PVeGFP positive cells in laminae II and III showed action potential discharge was restricted to the tonic firing and initial bursting patterns (67% and 33% respectively; n= 18), and virtually all express Ih subthreshold voltage‐gated currents (94%; n= 18). These neurons show higher rheobase current than non‐eGFP cells but respond with high frequency action potential discharge upon activation. Together, our findings show that PV neurons in laminae II and III are a likely source of inhibitory presynaptic input on to myelinated primary afferents. Consequently PV cells are ideally placed to play an important role in the development of central sensitization and tactile allodynia.