bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic cocaine administration induces long‐term impairment in the drive to obtain natural reinforcers in high‐ but not low‐demanding tasks
Authors: Barnea‐Ygael Noam , Gal Ram , Zangen Abraham
Published: November 2014

Repeated drug exposure induces short‐ and long‐term neuroadaptations in brain reward circuitries that are normally involved in the regulation of motivation. Hence, repeated drug exposure has been suggested to also affect the drive to acquire natural reinforcers. Here, we tested how chronic exposure of rats to cocaine, as well as a subsequent withdrawal period, affects acquisition of natural reinforcers in high‐ and low‐demanding tasks (HD and LD tasks, respectively). We chronically administered cocaine (i.p., 15 mg/kg once daily, or saline in control) for 30 days, followed by a 30‐day withdrawal period. We tested the effect of this treatment on the acquisition of two natural appetitive reinforcers, namely self‐administering a 10% sucrose solution and mounting a receptive female, under LD and HD conditions. During the cocaine exposure period, behavioral testing took place 18 hours after cocaine injection, namely after the acute pharmacologic effect of the drug dissipated. We show that chronic i.p. cocaine exposure decreased procurement of both reinforcers in HD but not in LD tasks. The effect was observed throughout the administration period with partial recovery after withdrawal. Taken together, we present empirical evidence that chronic exposure to a constant dose of cocaine is sufficient to reduce natural reinforcement, and that this decrease can outlast drug exposure. Importantly, such effects are observed only when high demands are opposing the consumption of the natural reinforcer.
Evolution of Early Repolarization Patterns after 5 Years in a Military Population at Low Cardiovascular Risk and Practical Implications in Military Medical Expertise
Authors: Vinsonneau Ulric , Pangnarind‐Heinz Vanida , Paleiron Nicolas , Heinz Louis Marie , Rohel Guenole , Piquemal Marie , Castellant Philippe , Abalea Jerome , Mansourati Jacques , Paule Philippe
Published: November 2014

Background

The French military population is a young and athletic population with a high prevalence of early repolarization patterns (ERP) compared to the general population. Screening of military officers at risk of sudden death (SD) is a priority in military medical expertise. The aim of our study was to evaluate the prevalence of ERP and its evolution over a period of 5 years in a specific asymptomatic population, free of heart disease and cardiovascular risk factors.

Methods

From March to December 2008, we prospectively collected the electrocardiograms (ECGs) of military officers enlisted into the submarine forces of France. For 5 years (until 2012), the military officers included in the study underwent a clinical examination twice per year. A new ECG was carried out 5 years after the initial one.

Results

A total of 250 male subjects were included (mean age 22.87 ± 0.5 years). The prevalence of ERP was 19.2%. The most common appearance was an elevation of a slurring type J point (31/48 or 64.5%) in inferolateral leads (18/48 or 37.8%). After 5 years, the prevalence of ERP was identical to that of the previous period (19.2%) with no change in appearance, distribution, and amplitude in 47 subjects (97.9%). Repolarization changed in two patients (one occurrence of ERP and one disappearance). During the 5 years of follow‐up, the subjects remained asymptomatic

Conclusion

ERP is common in our population of young, athletic, and asymptomatic military officers and changes little in 5 years.
Post‐market safety warnings for drugs approved in Canada under the Notice of Compliance with conditions policy
Authors: Lexchin Joel
Published: November 2014

Aims

Health Canada has developed a pathway to approve drugs that have limited efficacy and safety data, the Notice of Compliance with conditions (NOC/c) policy. Increased safety reporting is required for these drugs but there has not been any systematic review of their post‐market safety. This study compares safety warnings for NOC/c drugs with drugs with a priority and a standard review.

Methods

A list of drugs approved between January 1 1998 and March 31 2013 was developed and serious safety warnings for these drugs were identified. Drugs were put into one of three groups based on the way that they were approved. Kaplan−Meier curves were generated to examine the likelihood of NOC/c drugs receiving a serious safety warning compared with drugs with a priority and a standard review. The time spent in the review process for each of the groups was also measured.

Results

Compared with drugs with a priority review, NOC/c drugs were not more likely to receive a serious safety warning (P = 0.5940) but were more likely than drugs with a standard review (P = 0.0113). NOC/c drugs spent less time in the review process compared with drugs with a standard review.

Conclusions

Possible reasons for the increase likelihood of a serious safety warning are the limited knowledge of the safety of NOC/c drugs when they are approved and the length of time that they spend in the review process. Health Canada should consider spending longer reviewing these drugs and monitor their post‐market safety more closely.
Combined inhibition of monoacylglycerol lipase and cyclooxygenases synergistically reduces neuropathic pain in mice
Authors: Crowe Molly S , Leishman Emma , Banks Matthew L , Gujjar Ramesh , Mahadevan Anu , Bradshaw Heather B , Kinsey Steven G
Published: November 2014

Background and Purpose

Neuropathic pain is commonly treated with GABA analogues, steroids or non‐steroidal anti‐inflammatory drugs (NSAIDs). NSAIDs inhibit one or more COX isozymes but chronic COX inhibition paradoxically increases gastrointestinal inflammation and risk of unwanted cardiovascular events. The cannabinoids also have analgesic and anti‐inflammatory properties and reduce neuropathic pain in animal models. The present study investigated the analgesic effects of inhibiting both monoacylglycerol lipase (MAGL) and COX enzymes, using low doses of both inhibitors.

Experimental Approach

Mice subjected to chronic constriction injury (CCI) were tested for mechanical and cold allodynia after administration of the MAGL inhibitor, JZL184, or the non‐selective COX inhibitor diclofenac. Then, both drugs were co‐administered at fixed dose proportions of 1:3, 1:1 and 3:1, based on their ED50 values. PGs, endocannabinoids and related lipids were quantified in lumbar spinal cord.

Key Results

Combining low doses of JZL184 and diclofenac synergistically attenuated mechanical allodynia and additively reduced cold allodynia. The cannabinoid CB1 receptor antagonist, rimonabant, but not the CB2 receptor antagonist, SR144528, blocked the analgesic effects of the JZL184 and diclofenac combination on mechanical allodynia, implying that CB1 receptors were primarily responsible for the anti‐allodynia. Diclofenac alone and with JZL184 significantly reduced PGE2 and PGF2α in lumbar spinal cord tissue, whereas JZL184 alone caused significant increases in the endocannabinoid metabolite, N‐arachidonoyl glycine.

Conclusions and Implications

Combining COX and MAGL inhibition is a promising therapeutic approach for reducing neuropathic pain with minimal side effects.
Impaired endothelial function in patients with mild primary hyperparathyroidism improves after parathyroidectomy
Authors: Tuna Mazhar M. , Doğan Berçem A. , Arduç Ayşe , Imga Narin Nasiroğlu , Tütüncü Yasemin , Berker Dilek , Güler Serdar
Published: November 2014

Background

Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity; however, data on the reversibility of cardiovascular disease in mild primary hyperparathyroidism are conflicting. The aim of this study was to assess endothelial function in patients with mild PHPT before and after parathyroidectomy (Ptx).

Methods

We prospectively evaluated 53 patients with mild PHPT (Group 1; 45 women, eight men; aged 52 ± 3·1 years) and 46 healthy control subjects (Group 2; 38 women, eight men; aged 46 ± 9·5 years). Endothelial function was measured as flow‐mediated dilation (FMD) and carotid intima‐media thickness (CIMT) using Doppler ultrasonography. Patients with diabetes mellitus, coronary heart disease, impaired renal function, hyperthyroidism, hypothyroidism and a history of smoking were excluded from the study. Patients were studied at baseline and 6–12 months after the first evaluation.

Results

There were no differences with respect to age, gender and BMI between the two groups. Hypertension prevalence was three times higher in group 1 than in controls. % FMD was lower in group 1 than in group 2 (2·6 ± 1·2 vs 14·8 ± 9·6, P < 0·001). CIMT was higher in patients with PHPT than controls (0·69 ± 0·18 vs 0·61 ± 0·12, P = 0·045). This significance remained when hypertensive patients were excluded from the analysis. While FMD and CIMT improved significantly after Ptx, there were no differences in mild PHPT patients who followed without parathyroidectomy.

Conclusion

FMD and CIMT are impaired in patients with mild PHPT compared to controls and improved significantly after a successful Ptx. Ptx improves endothelial function in patients with mild PHPT that may lead to decreased cardiovascular morbidity and mortality.
Characteristic and derived diversity: implementing the species pool concept to quantify conservation condition of habitats
Authors: Helm Aveliina , Zobel Martin , Moles Angela T. , Szava‐Kovats Robert , Pärtel Meelis
Published: November 2014

Anthropogenic environmental changes in climate, land use and disturbance regimes, as well as mass propagule transport are having dramatic effects on many ecosystems. Both conservationists and ecologists need ecologically relevant metrics to quantify the condition of plant and animal communities. However, current metrics fail to address the invasion of species native to different community types in the same region, even though these ‘native aliens’ can serve as valuable indicators of recent changes in habitat condition. We propose a novel approach to reconceptualize community biodiversity based on the composition of historically developed habitat‐specific species pools. Total observed community diversity can be divided to characteristic diversity, consisting of species belonging to habitat‐specific species pool, and derived diversity, consisting of either native or non‐native species not typical to a given community and whose presence is driven by adverse human impact. Characteristic and derived diversity in communities have different historical backgrounds; thus, the ecological patterns of these components, effects on ecosystem functioning as well as actions necessary for their conservation are likewise different. We propose the Index of Favourable Conservation Status – the log ratio of characteristic to derived diversity – as an easily quantified, ecologically relevant and universal indicator of biodiversity integrity and community condition. The Index of Favourable Conservation Status provides valuable information on habitat conservation needs and recent adverse human impact in relative terms and can be compared between regions and across a wide range of ecosystems. It can also be used to monitor restoration success or characterize biodiversity degradation. We present standardized procedure of determining habitat‐specific species pools and bring several examples of how the concept of characteristic and derived diversity can be applied in conservation and research and how expert knowledge on habitat‐specific species pool composition can expand our understanding of community biodiversity.
Laparoscopic endoscopic cooperative surgery
Authors: Hiki Naoki , Nunobe Souya , Matsuda Tatsuo , Hirasawa Toshiaki , Yamamoto Yorimasa , Yamaguchi Toshiharu
Published: November 2014

Laparoscopic and endoscopic cooperative surgery (LECS) is a newly developed concept for tumor dissection of the gastrointestinal tract that was first investigated for local resection of gastric gastrointestinal stromal tumors (GIST). The first reported version of LECS for GIST has been named ‘classical LECS’ to distinguish it from other modified LECS procedures, such as inverted LECS, a combination of laparoscopic and endoscopic approaches to neoplasia with a non‐exposure technique (CLEAN‐NET), and non‐exposed endoscopic wall‐inversion surgery (NEWS). These modified LECS procedures were developed for dissection of malignant tumors which may seed tumor cells into the abdominal cavity. While these LECS‐related procedures might prevent tumor seeding, their application is limited by several factors, such as tumor size, location and technical difficulty. Currently, classical LECS is a safe and useful procedure for gastric submucosal tumors without mucosal defects, independent of tumor location, such as proximity to the esophagogastric junction or pyloric ring. For future applications of LECS‐related procedures for other malignant diseases with mucosal lesions such as GIST with mucosal defects and gastric cancer, some improvements in the techniques are needed.
Improving postpartum glucose screening after gestational diabetes mellitus: a cohort study to evaluate the multicentre IMPACT initiative
Authors: Cosson E. , Bihan H. , Vittaz L. , Khiter C. , Carbillon L. , Faghfouri F. , Leboeuf D. , Dauphin H. , Lepagnol A. , Reach G. , Valensi P.
Published: November 2014

Aims

To evaluate a mobilization campaign, the IMPACT initiative, which included multidisciplinary meetings, provision of information and a systematic prescription of an oral glucose tolerance test to improve the rate of glucose screening in women with gestational diabetes mellitus in the four largest maternity units in our area, starting in March 2011.

Methods

We retrospectively compared the level of self‐reported screening during the first 6 months postpartum of women who gave birth after having been diagnosed with gestational diabetes before (January 2009 to December 2010) and after the IMPACT campaign (April 2011 to February 2012).

Results

We included 961 women (589 in the period before and 372 in the period after the campaign was initiated) with a mean ± sd age of 33.2 ± 5.3 years and BMI of 27.8 ± 5.3 kg/m². Multivariate analysis, stratified using a propensity score in order to limit bias caused by imbalance between both periods, showed that the postpartum screening rate was higher after the campaign began (48.9 vs 33.3%, odds ratio 1.7, 95% CI 1.1–2.5; P = 0.019) and higher in women who received insulin treatment during pregnancy (odds ratio 2.3, 95% CI 1.5–3.6; P < 0.001), consumed fruit and vegetables daily (odds ratio 1.6, 95% CI 1.1–2.4; P = 0.035) and did not smoke (smoking vs non‐smoking: odds ratio 0.3, 95% CI 0.1–0.7; P = 0.01). There was no interaction between the campaign effect and these particular conditions. The proportion of oral glucose tolerance tests performed in women who underwent screening increased from 6.3 to 33.0%.

Conclusions

The IMPACT campaign increased postpartum screening, and the use the oral glucose tolerance test in particular. The effect of this initiative might be reinforced in women who are non‐daily consumers of fruit and vegetables, smokers and those who do not receive insulin treatment during pregnancy.
Human Capital and Growth: Specification Matters
Authors: Sunde Uwe , Vischer Thomas
Published: November 2014

This paper suggests that the weak empirical effect of human capital on growth in existing cross‐country studies is partly the result of an inappropriate specification that does not account for the different channels through which human capital affects growth. A systematic replication of earlier results from the literature shows that both initial levels and changes in human capital have positive growth effects, while in isolation each channel often appears insignificant. The results suggest that the effect of human capital is likely to be underestimated in empirical specifications that do not account for both channels.
Segregated labeling of olfactory bulb projection neurons based on their birthdates
Authors: Imamura Fumiaki , Greer Charles A.
Published: November 2014

Mitral and tufted cells are the projection neurons of the olfactory bulb (OB). We previously reported that somata location and innervation patterns were different between early‐ and late‐born mitral cells (Imamura et al., 2011). Here, we introduced a plasmid that drives the expression of a GFP gene into the mouse OB using in utero electroporation, and demonstrated that we can deliver the plasmid vectors into distinct subsets of OB projection neurons by changing the timing of electroporation after fertilisation. The electroporation performed at embryonic day (E)10 preferentially labeled mitral cells in the accessory OB and main OB mitral cells in dorsomedial mitral cell layer (MCL). In contrast, the E12 electroporation introduced the plasmid vectors preferentially into main OB mitral cells in the ventrolateral MCL and tufted cells. Combining these data with BrdU injections, we confirmed that E10 and E12 electroporation preferentially labeled early‐ and late‐born projection neurons, respectively. This work introduces a novel method for segregated labeling of mouse olfactory bulb projection neurons based on their birthdates. With this technique we found that early‐ and late‐born projection neurons extend their secondary dendrites in the deep and superficial external plexiform layer (EPL), respectively. Although a similar segregation has been suggested for mitral vs. tufted cell dendrites, we found mitral cells projecting secondary dendrites into the superficial EPL in E12‐electroporated main OB. Our observations indicate that timing of neurogenesis regulates not only somata location and innervation patterns but also the laminar organisation of projection neuron dendrites in the EPL.
Increased forest carbon storage with increased atmospheric CO2 despite nitrogen limitation: a game‐theoretic allocation model for trees in competition for nitrogen and light
Authors: Dybzinski Ray , Farrior Caroline E. , Pacala Stephen W.
Published: November 2014

Changes in resource availability often cause competitively driven changes in tree allocation to foliage, wood, and fine roots, either via plastic changes within individuals or through turnover of individuals with differing strategies. Here, we investigate how optimally competitive tree allocation should change in response to elevated atmospheric CO2 along a gradient of nitrogen and light availability, together with how those changes should affect carbon storage in living biomass. We present a physiologically‐based forest model that includes the primary functions of wood and nitrogen. From a tree's perspective, wood is an offensive and defensive weapon used against neighbors in competition for light. From a biogeochemical perspective, wood is the primary living reservoir of stored carbon. Nitrogen constitutes a tree's photosynthetic machinery and the support systems for that machinery, and its limited availability thus reduces a tree's ability to fix carbon. This model has been previously successful in predicting allocation to foliage, wood, and fine roots along natural productivity gradients. Using game theory, we solve the model for competitively optimal foliage, wood, and fine root allocation strategies for trees in competition for nitrogen and light as a function of CO2 and nitrogen mineralization rate. Instead of down‐regulating under nitrogen limitation, carbon storage under elevated CO2 relative to carbon storage at ambient CO2 is approximately independent of the nitrogen mineralization rate. This surprising prediction is a consequence of both increased competition for nitrogen driving increased fine root biomass and increased competition for light driving increased allocation to wood under elevated CO2.
Use of Candida‐specific chicken egg yolk antibodies to inhibit the adhering of Candida to denture base materials: prevention of denture stomatitis
Authors: Kamikawa Yoshiaki , Fujisaki Junichi , Nagayama Tomohiro , Kawasaki Kiyotsugu , Hirabayashi Daisuke , Hamada Tomofumi , Sakamoto Ryoich , Mukai Hiroshi , Sugihara Kazumasa
Published: November 2014

Objectives

Polyclonal anti‐Candida chicken egg yolk antibodies (anti‐IgY) were used to investigate the prevention of adherence of Candida species to denture base material in vitro.

Background

Candida is a potential virulence factor that can cause systemic infection and even death in immunocompromised individuals. Because long‐term antifungal treatment may lead to the emergence of drug‐resistant strains, it is necessary to develop novel preventive measures and treatments for candidiasis.

Materials and methods

Three types of chicken egg yolk antibodies were used in this study: non‐specific antibody (control IgY), Candida albicans‐specific antibody (anti‐C.a.IgY) and Candida glabrata‐specific antibody (anti‐C.g.IgY). A mixture of different dilutions of each antibody with a suspension of Candida species and denture base material was incubated for 3 h, and then the colony‐forming units of Candida on the denture base material were counted.

Results

Compared with control IgY, anti‐C.a.IgY and anti‐C.g.IgY significantly inhibited the adherence of C. albicans, but anti‐C.a.IgY tended to be more potent than anti‐C.g.IgY. The adherence of C. glabrata was also inhibited significantly by anti‐C.a.IgY and anti‐C.g.IgY with almost equivalent potency, indicating that their actions against C. glabrata were comparable.

Conclusions

This study revealed the inhibitory effects of anti‐C.a.IgY and anti‐C.g.IgY against the adherence of C. albicans and C. glabrata to denture base material. This finding indicates the possibility of a beneficial effect of IgYs for the prevention of denture stomatitis and candidiasis in clinical settings.
Dynamics and nature of support in the personal networks of people with type 2 diabetes living in Europe: qualitative analysis of network properties
Authors: Kennedy Anne , Rogers Anne , Vassilev Ivaylo , Todorova Elka , Roukova Poli , Foss Christina , Knutsen Ingrid , Portillo Mari Carmen , Mujika Agurtzane , Serrano‐Gil Manuel , Lionis Christos , Angelaki Agapi , Ratsika Nikoleta , Koetsenruijter Jan , Wensing Michel
Published: November 2014

Background

Living with and self‐managing a long‐term condition implicates a diversity of networked relationships. This qualitative study examines the personal communities of support of people with type 2 diabetes.

Methods

We conducted 170 biographical interviews in six European countries (Bulgaria, Greece, the Netherlands, Norway, Spain and UK) to explore social support and networks. Analysis was framed with reference to three predetermined social support mechanisms: the negotiation of support enabling engagement with healthy practices, navigation to sources of support and collective efficacy. Each interview was summarized to describe navigation and negotiation of participants' networks and the degree of collective efficacy.

Results

Analysis highlighted the similarities and differences between countries and provided insights into capacities of networks to support self‐management. The network support mechanisms were identified in all interviews, and losses and gains in networks impacted on diabetes management. There were contextual differences between countries, most notably the impact of financial austerity on network dynamics. Four types of network are suggested: generative, diverse and beneficial to individuals; proxy, network members undertook diabetes management work; avoidant, support not engaged with; and struggling, diabetes management a struggle or not prioritized.

Conclusions

It is possible to differentiate types of network input to living with and managing diabetes. Recognizing the nature of active, generative aspects of networks support is likely to have relevance for self‐management support interventions either through encouraging continuing development and maintenance of these contacts or intervening to address struggling networks through introducing the means to connect people to additional sources of support.
Precocious diagnosis of glaucoma: comparison between nerve fibre analyzer and blue/yellow perimetry
Authors: Trabucco T. , Vetrugno M. , Cantatore F. , Cardia L.
Published: November 2014

The authors briefly review the tests available for precocious diagnosis of glaucomatous neuropticopathy. They present a casefile of 54 ocular hypertensive eyes examined by NFA and blue‐on‐yellow perimetry to verify the equivalence of these two different tests in the precocious diagnosis of glaucoma. The results point up a perfect correspondence in 50% of the cases. They conclude by stressing the necessity of having a screening available for the precocious diagnosis of glaucoma with the use of more tests that have standardized and reliable parameters.
Glaucomatous damage to inner retina detected by the flicker ERG second harmonic: losses as a function of temporal frequency
Authors: Colotto A. , Salgarello T. , Falsini B. , Porciatti V. , Cermola S. , Scullica L.
Published: November 2014

The electroretinogram to flicker stimulation (FERO) consists of two main components: a fundamental (1F) at the same temporal frequency (TF) as the stimulus and a second harmonic (2F) at twice the stimulation frequency. The 2F is generated in the retina more proximally than the 1F and, unlike the 1F, can be significantly altered in ocular hypertension and open angle glaucoma (OAG). This study evaluated the FERG 2F as a function of TF in OAG patients and age‐matched controls. The results show that, in patients, the 2F amplitude losses were consistently found at different TFs both in the low (8–10 Hz) and high (38–40 Hz) regions of the spectrum, with optimal sensitivity at 8–10 Hz (70% of the eyes).

These data suggest that the FERG 2F recorded at the optimal TFs may be of complementary clinical use as support to a glaucoma diagnosis in patients with optical media opacities in whom most of the current functional or morphologic tests of optic nerve integrity cannot be reliably performed.
Flowmetry of optic nerve head and visual field defect in glaucomatous eyes
Authors: Mastropasqua L. , Ciancaglini M. , Carpineto P. , Falconio G. , Zuppardi E. , Doronzo E. , Gallenga P. E.
Published: November 2014

A cross‐sectional study was undertaken to analyze the relation between the perfusion of the rim area and lamina cribrosa of the optic nerve head by means of SLDF and the mean defect of the visual field.

Forty‐two patients affected by primary open angle glaucoma were enrolled.

In the rim area, no significant relation was found between the perfusion of the tissue and the visual field defect. In the lamina cribrosa area, a significant relation was found between blood volume and mean defect (p < 0.05).
Should Fertility Treatment be State Funded?
Authors: McTernan Emily
Published: November 2014

Many states offer generous provision of fertility treatment, but this article asks whether and how such state funding can be justified. I argue that, at most, there is limited justification for state funding of fertility treatment as one good among many that could enable citizens to pursue valuable life projects, but not one that should have the privileged access to funding it is currently given. I then consider and reject reasons one might think that fertility treatment has a special claim to funding, over the other goods that might enable life projects. First, I deny that fertility treatment has a special claim to funding on the grounds that infertility is a disease or disability. Second, I argue that individuals do not have a right to assistance with the project of having a child of their own. Third, I deny that providing fertility treatment is a special case on the grounds that having children is good for society. However, there may be one exception: states have a reason to fund fertility treatment for same sex couples that does not apply to heterosexual couples.
Justice in Transnational Governance
Authors: de Bres Helena
Published: November 2014

The small portion of philosophical work on global distributive justice that directly discusses particular agents, institutions or practices in global politics tends to focus on a narrow range of the existing set. The emphasis is chiefly on bilateral diplomacy or intergovernmental organisations, to the neglect of a variety of more recent forms of transnational governance, many of which incorporate non‐state actors, have more limited membership, involve informal and dynamic structures, employ cooperative and reflexive methods for ensuring compliance, and operate largely out of the public eye. This article considers how philosophers should conceive of distributive justice in relation to these neglected sites of transnational governance, using the International Organization for Standardization (ISO) as an illustration.
Decoding polyphase migmatites using geochronology and phase equilibria modelling
Authors: Yakymchuk C. , Brown M. , Clark C. , Korhonen F. J. , Piccoli P. M. , Siddoway C. S. , Taylor R. J. M. , Vervoort J. D.
Published: November 2014

In this study, in situ U–Pb monazite ages and Lu–Hf garnet geochronology are used to distinguish mineral parageneses developed during Devonian–Carboniferous and Cretaceous events in migmatitic paragneiss and orthogneiss from the Fosdick migmatite–granite complex in West Antarctica. SHRIMP U–Pb monazite ages define two dominant populations at 365–300 Ma (from cores of polychronic grains, dominantly from deeper structural levels in the central and western sectors of the complex) and 120–96 Ma (from rims of polychronic grains, dominantly from the central and western sectors of the complex, and from monochronic grains, mostly from shallower structural levels in the eastern sector of the complex). For five paragneisses and two orthogneisses, Lu–Hf garnet ages range from 116 to 111 Ma, c. 12–17 Ma older than published Sm–Nd garnet ages of 102–99 Ma from three of the same samples. Garnet grains in the analysed samples generally have Lu‐enriched rims relative to Lu‐depleted cores. By contrast, for three of the same samples, individual garnet grains have flat Sm concentrations consistent with high‐T diffusive resetting. Lutetium enrichment of garnet rims is interpreted to record the breakdown of a Lu‐rich accessory mineral during the final stage of garnet growth immediately prior to the metamorphic peak, and/or the preferential retention of Lu in garnet during breakdown to cordierite in the presence of melt concomitant with the initial stages of exhumation. Therefore, garnet is interpreted to be part of the Cretaceous mineral paragenesis and the Lu–Hf garnet ages are interpreted to record the timing of close‐to‐peak metamorphism for this event. For the Devonian–Carboniferous event, phase equilibria modelling of the metasedimentary protoliths to the paragneiss and a diatexite migmatite restrict the peak P–T conditions to 720–800 °C at 0.45–1.0 GPa. For the Cretaceous event, using both forward and inverse phase equilibria modelling of residual paragneiss and orthogneiss compositions, the P–T conditions after decompression are estimated to have been 850–880 °C at 0.65–0.80 GPa. These P–T conditions occurred between c. 106 and c. 96 Ma, determined from Y‐enriched rims on monazite that record the timing of garnet and biotite breakdown to cordierite in the presence of melt. The effects of this younger metamorphic event are dominant throughout the Fosdick complex.
ABCD1 deletion‐induced mitochondrial dysfunction is corrected by SAHA: implication for adrenoleukodystrophy
Authors: Baarine Mauhamad , Beeson Craig , Singh Avtar , Singh Inderjit
Published: November 2014

X‐linked Adrenoleukodystrophy (X‐ALD), an inherited peroxisomal metabolic neurodegenerative disorder, is caused by mutations/deletions in the ATP‐binding cassette transporter (ABCD1) gene encoding peroxisomal ABC transporter adrenoleukodystrophy protein (ALDP). Metabolic dysfunction in X‐ALD is characterized by the accumulation of very long chain fatty acids ≥ C22:0) in the tissues and plasma of patients. Here, we investigated the mitochondrial status following deletion of ABCD1 in B12 oligodendrocytes and U87 astrocytes. This study provides evidence that silencing of peroxisomal protein ABCD1 produces structural and functional perturbations in mitochondria. Activities of electron transport chain‐related enzymes and of citric acid cycle (TCA cycle) were reduced; mitochondrial redox status was dysregulated and the mitochondrial membrane potential was disrupted following ABCD1 silencing. A greater reduction in ATP levels and citrate synthase activities was observed in oligodendrocytes as compared to astrocytes. Furthermore, most of the mitochondrial perturbations induced by ABCD1 silencing were corrected by treating cells with suberoylanilide hydroxamic acid, an Histone deacetylase inhibitor. These observations indicate a novel relationship between peroxisomes and mitochondria in cellular homeostasis and the importance of intact peroxisomes in relation to mitochondrial integrity and function in the cell types that participate in the pathobiology of X‐ALD. These observations suggest suberoylanilide hydroxamic acid as a potential therapy for X‐ALD.

image

Schematic description of the effects of loss of peroxisomal ATP‐binding cassette transporter D1 (ABCD1) gene on cellular Redox and mitochondrial activities and their correction by suberoylanilide hydroxamic acid (SAHA) treatment. Pathogenomic accumulation of very long chain fatty acids (VLCFA) as a result of loss of ABCD1 leads to dysfunctions of mitochondrial biogenesis and its activities. Treatment with SAHA corrects mitochondrial dysfunctions. These studies describe unique cooperation between mitochondria and peroxisome for cellular activities.
REAL‐TIME DATA AND FISCAL POLICY ANALYSIS: A SURVEY OF THE LITERATURE
Authors: Cimadomo Jacopo
Published: November 2014

This paper surveys the empirical research on fiscal policy analysis based on real‐time data. This literature can be broadly divided into four groups that focus on: (1) the statistical properties of revisions in fiscal data; (2) the political and institutional determinants of projection errors by governments; (3) the reaction of fiscal policies to the business cycle and (4) the use of real‐time fiscal data in structural vector autoregression (VAR) models. It emerges that, first, fiscal revisions are large and initial releases are biased estimates of final values. Secondly, strong fiscal rules and institutions lead to more accurate releases of fiscal data and smaller deviations of fiscal outcomes from government plans. Thirdly, the cyclical stance of fiscal policies is estimated to be more ‘counter‐cyclical’ when real‐time data are used instead of ex post data. Fourthly, real‐time data can be useful for the identification of fiscal shocks. Finally, it is shown that existing real‐time fiscal data sets cover only a limited number of countries and variables. For example, real‐time data for developing countries are generally unavailable. In addition, real‐time data on European countries are often missing, especially with respect to government revenues and expenditures. Therefore, more work is needed in this field.
Human Motivation in Question: Discussing Emotions, Motives, and Subjectivity from a Cultural‐Historical Standpoint
Authors: González Rey Fernando Luis
Published: November 2014

Vygotsky, at the end of his life, advanced a new representation of a psychological system that was ruled by a cognitive‐emotional unity, a theorization that remains inconclusive due to Vygotsky's early death. This article discusses the advances made by Vygotsky in the comprehension of human motivation through his concepts of sense and perezhivanie at the end of his work. Through these concepts, he further advanced the discussion of motivation, despite the fact that these concepts have only very recently been considered a relevant part of his legacy in both Russian and Western psychology. This paper discusses the departure from and the historical presentations of the concept of motive in the following two main approaches of Soviet psychology that were mistakenly equated in Western interpretations: Vygotsky's approach, mainly at the first as last moment of his work, and Leontiev's Activity Theory. Based on the final theoretical positions of Vygotsky and of other Soviet authors, and further developing this legacy, this article proposes a new definition of motivation as a specific quality of subjectively configured systems and defines motive as intrinsic to the functioning of all psychological function defines subjective functions as subjectively configured processes. This new proposal of human motivation within a new way of defining subjectivity defines new categories as subjective senses and subjective configurations on which the author bases a specific approach for advancing the topic of subjectivity and motivation within a cultural‐historical framework.
School Start Time Change: An In‐Depth Examination of School Districts in the United States
Authors: Owens Judith , Drobnich Darrel , Baylor Allison , Lewin Daniel
Published: November 2014

In response to the scientific evidence documenting both profound developmental changes in sleep and circadian biology during adolescence and the myriad of negative health, performance, and safety outcomes risks associated with chronic sleep loss, at least 70 public school districts in the United States, representing approximately 1,000 schools, have successfully implemented a delay in high school start times. However, despite the compelling evidence supporting school start time change as a key strategy in addressing the epidemic of adolescent sleep loss, many school districts across the country with early high school start times have not considered the option to implement later bell schedules for adolescents. Moreover, while the current scientific literature has clearly documented the positive outcomes associated with delayed high school start times, these studies contain limited information regarding the process by which school districts consider, approve and implement bell schedule changes. Thus, this in‐depth examination of those school districts that have been successful in changing their bell schedules is intended to support the efforts of other districts in various stages of contemplating this measure. We utilized a multi‐pronged approach (literature review, case studies, telephone interviews, online survey) to summarize the experiences of school districts across the United States in regard to challenges faced, strategies employed, and lessons learned in the hope that this information will be a useful tool for other school districts looking to chart a course forward to promote the health, safety, and academic opportunities of their students.
Geometric morphometrics for the taxonomy of 11 species of Anopheles (Nyssorhynchus) mosquitoes
Authors: JARAMILLO‐O N. , DUJARDIN J.‐P. , CALLE‐LONDOÑO D. , FONSECA‐GONZÁLEZ I.
Published: November 2014

The subgenus Anopheles (Nyssorhynchus) (Diptera: Culicidae) includes the primary vectors of Plasmodium spp. in Colombia. Most adult females of this subgenus are difficult to identify in the field using the available keys. With the objective of further investigating the discriminatory power of modern morphometrics, both landmark‐based and outline‐based approaches were explored using the wing venation geometry of 11 Anopheles (Nyssorhynchus) species. Wing shape was able to separate the closest species of the subgenus. When the 11 species were analysed together, validated classification scores on average 5.3–8.6 times higher than those expected by chance were observed. These scores computed from the total sample of 11 species were not satisfactory for the recognition of Anopheles benarrochi B, Anopheles oswaldoi s.l. and Anopheles strodei. These sibling species were captured in sympatry. To improve the identification power of the morphometric tool, it was necessary to analyse these species separately from the remaining species. The best classification scores were obtained using a combination of 12 landmarks collected not only on the intersections of wing veins, but also on spots. An outline approach also gave excellent reclassification scores. Another pair of sibling species, collected in allopatry, Anopheles nuneztovari and Anopheles rangeli, also showed high classification scores.
Regulation and Disregulation of Mammalian Nucleotide Excision Repair: A Pathway to Nongermline Breast Carcinogenesis
Authors: Latimer Jean J. , Majekwana Vongai J. , Pabón‐Padín Yashira R. , Pimpley Manasi R. , Grant Stephen G.
Published: November 2014

Nucleotide excision repair (NER) is an important modulator of disease, especially in constitutive deficiencies such as the cancer predisposition syndrome Xeroderma pigmentosum. We have found profound variation in NER capacity among normal individuals, between cell‐types and during carcinogenesis. NER is a repair system for many types of DNA damage, and therefore many types of genotoxic carcinogenic exposures, including ultraviolet light, products of organic combustion, metals and oxidative stress. Because NER is intimately related to cellular metabolism, requiring components of both the DNA replicative and transcription machinery, it has a narrow range of functional viability. Thus, genes in the NER pathway are expressed at the low levels manifested by, for example, nuclear transcription factors. As NER activity and gene expression vary by cell‐type, it is inherently epigenetically regulated. Furthermore, this epigenetic modulation is disregulated during sporadic breast carcinogenesis. Loss of NER is one basis of genomic instability, a required element in cellular transformation, and one that potentially influences response to therapy. In this study, we demonstrate differences in NER capacity in eight adult mouse tissues, and place this result into the context of our previous work on mouse extraembryonic tissues, normal human tissues and sporadic early stage human breast cancer.
Analysis of yellowish skin color from an optical image and the development of 3D Skin Chroma Diagram™
Authors: Han J. Y. , Kim E. J. , Lee H. K. , Kim M. J. , Nam G. W.
Published: November 2014

Background/purpose

This study was conducted to define yellowish skin color, which is a major concern of Asian women, and to develop a 3D skin‐pigment color model.

Methods

A total of 22 Korean females were enrolled in this study. These women were asked to use a functional cosmetic product with whitening agents for 8 weeks. We photographed the subsurface reflection of each subject's face using polarized light. The color of the subsurface reflection is a result of diffusive light transports that are attenuated by various skin pigments such as melanin, hemoglobin, and skin base colors. In this subsurface photo image, we eliminated the color effects of melanin and hemoglobin distribution by skin color analysis resulting in skin base color. Based on a variety of observed skin base colors from which the melanin and hemoglobin pigments have been removed, we defined a standard skin color for the entire subject group, and then, we gained a particular yellowish skin color by excluding the standard skin color from the skin base color again.

Results

After applying whitening cosmetic products, the amount of melanin and hemoglobin was reduced by 7.3% and 18.6%, respectively. Also, through using our new analysis method, yellowish skin color has been improved by 2.8%. We showed the improvement on 3D Skin Chroma Diagram™ three‐dimensionally.

Conclusion

It became possible to diagnose yellowish color on human skin and to analyze the improvement in skin tone both quantitatively and visually.
Clinical value and safety of liver biopsies in patients transplanted for hepatitis C virus‐related end‐stage liver disease
Authors: Brauner C. , Lankisch T.O. , Fytili P. , Jaroszewicz J. , Lehner F. , Barg‐Hock H. , Klempnauer J. , Jaeckel E. , Manns M.P. , Wedemeyer H. , Negm A.A.
Published: November 2014

Background

Hepatitis C is the leading indication for liver transplantation. Differentiation between recurrent graft hepatitis C (RGH‐C) and graft rejection (GR) is challenging. Liver biopsy is standard to diagnose both conditions; however, little information is available regarding this procedure in hepatitis C virus (HCV)‐infected liver transplant recipients.

Methods

Liver biopsies (n = 211) from all consecutive patients (n = 138) transplanted for hepatitis C at Hannover Medical School between January 2000 and October 2011 were screened, and a final cohort of 96 patients with 196 biopsies was included. Indications, histopathological findings, and biopsy‐related complications were documented. Modifications in the treatment based on the biopsy result and the biochemical outcome were analyzed.

Results

Most biopsies (196/211, 93%) were representative. Five patients (2.5%) developed non‐fatal biopsy‐related complications. Biopsy results were GR (35%), RGH‐C (31%), and other diagnoses (34%). GR was independently associated with lower albumin (P = 0.025) and higher bilirubin levels (P = 0.011). Treatment was modified based on the biopsy result in 25% of cases. Alanine aminotransferase (ALT), gamma‐glutamyl transferase (GGT), and bilirubin levels improved in 41%, 25%, and 31% of cases 4 weeks post biopsy respectively. ALT improvements were more significant in patients with GR than in those with RGH‐C.

Conclusion

Liver biopsy in HCV‐infected liver transplant recipients is safe and representative in >90% of cases. GR is independently associated with lower albumin and higher bilirubin levels.
Anti‐SSA antibodies are present in immunoglobulin preparations
Authors: van der Molen Renate G. , Hamann Dörte , Jacobs Joannes F.M. , van der Meer Arnold , de Jong Jan , Kramer Christine , Strengers Paul F.W. , van der Meer Jos W.M.
Published: November 2014

Background

Anti‐SSA autoantibodies are among the most frequently detected autoantibodies and have traditionally been associated with Sjögren's syndrome (SjS) and systemic lupus erythematosus. The unexpected finding of anti‐SSA antibodies in a patient with common variable immunodeficiency disorder (CVID) treated with intravenous immunoglobulin (IVIG), who developed discoid lupus erythematosus, prompted us to investigate the presence of anti‐SSA antibodies in IVIG preparations. Since anti‐SSA antibodies may be present in apparently healthy individuals without overt autoimmune features, IVIG preparations may also contain anti‐SSA antibodies.

Study Design and Methods

IVIG consists of polyclonal immunoglobulin G isolated from the plasma of more than 1000 blood donors. Several IVIG batches from different suppliers and serum samples of patients receiving these IVIG products were tested for the presence of anti‐nuclear antibodies (ANAs) and extractable nuclear antibodies (ENAs). In addition, we tested several plasma pools for the presence of anti‐SSA and subsequent serum samples of individual donors.

Results

Several CVID‐patients receiving IVIG tested positive for ANA and anti‐SSA. The IVIG products administered also contained clearly detectable concentrations of these antibodies. The frequency of apparently healthy blood donors with anti‐SSA positivity was 0.69% and one of 1894 donors (0.05%) showed a very high titer of anti‐SSA of more than 10,000 U/mL.

Conclusion

Anti‐SSA is present in IVIG products and in blood donors without clinical symptoms. IVIG replacement can interfere with ANA and ENA serology by passive transfer of autoantibodies. We hypothesize that such autoantibodies may be causally related to disease manifestations in some recipients.