bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti‐tumour efficacy on glioma models of PHA‐848125, a multi‐kinase inhibitor able to cross the blood–brain barrier
Authors: Albanese C , Alzani R , Amboldi N , Degrassi A , Festuccia C , Fiorentini F , Gravina GL , Mercurio C , Pastori W , Brasca MG , Pesenti E , Galvani A , Ciomei M
Published: January 2013

Background and Purpose

Malignant gliomas, the most common primary brain tumours, are highly invasive and neurologically destructive neoplasms with a very bad prognosis due to the difficulty in removing the mass completely by surgery and the limited activity of current therapeutic agents. PHA‐848125 is a multi‐kinase inhibitor with broad anti‐tumour activity in pre‐clinical studies and good tolerability in phase 1 studies, which could affect two main pathways involved in glioma pathogenesis, the G1‐S phase progression control pathway through the inhibition of cyclin‐dependent kinases and the signalling pathways mediated by tyrosine kinase growth factor receptors, such as tropomyosin receptors. For this reason, we tested PHA‐848125 in glioma models.

Experimental Approach

PHA‐848125 was tested on a panel of glioma cell lines in vitro to evaluate inhibition of proliferation and mechanism of action. In vivo efficacy was evaluated on two glioma models both as single agent and in combination with standard therapy.

Key Results

When tested on a subset of representative glioma cell lines, PHA‐848125 blocked cell proliferation, DNA synthesis and inhibited both cell cycle and signal transduction markers. Relevantly, PHA‐848125 was also able to induce cell death through autophagy in all cell lines. Good anti‐tumour efficacy was observed by oral route in different glioma models both with s.c. and intracranial implantation. Indeed, we demonstrate that the drug is able to cross the blood–brain barrier. Moreover, the combination of PHA‐848125 with temozolomide resulted in a synergistic effect, and a clear therapeutic gain was also observed with a triple treatment adding PHA‐848125 to radiotherapy and temozolomide.

Conclusions and Implications

All the pre‐clinical data obtained so far suggest that PHA‐848125 may become a useful agent in chemotherapy regimens for glioma patients and support its evaluation in phase 2 trials for this indication.
The β‐catenin pathway contributes to the effects of leptin on SREBP‐1c expression in rat hepatic stellate cells and liver fibrosis
Authors: Zhai Xuguang , Yan Kunfeng , Fan Jiye , Niu Minghui , Zhou Qian , Zhou Yan , Chen Hongshan , Zhou Yajun
Published: January 2013

Background and Purpose

Liver fibrosis is commonly associated with obesity and most obese patients develop hyperleptinaemia. The adipocytokine leptin has a unique role in the development of liver fibrosis. Activation of hepatic stellate cells (HSCs) is a key step in hepatic fibrogenesis and sterol regulatory element‐binding protein‐1c (SREBP‐1c) can inhibit HSC activation. We have shown that leptin strongly inhibits SREBP‐1c expression in rat HSCs. Hence, we aimed to clarify whether the β‐catenin pathway, the crucial negative regulator of adipocyte differentiation, mediates the effects of leptin on SREBP‐1c expression in HSCs and in mouse liver fibrosis.

Experimental Approach

HSCs were prepared from rats and mice. Gene expressions were analysed by real‐time PCR, Western blot analysis, immunostaining and transient transfection assays.

Key Results

Leptin increased β‐catenin protein but not mRNA levels in cultured HSCs. Leptin induced phosphorylation of glycogen synthase kinase‐3β at Ser9 and subsequent stabilization of β‐catenin protein was mediated, at least in part, by ERK and p38 MAPK pathways. The leptin‐induced β‐catenin pathway reduced SREBP‐1c expression and activity but did not affect protein levels of key regulators controlling SREBP‐1c activity, and was not involved in leptin inhibition of liver X receptor α. In a mouse model of liver injury, the β‐catenin pathway was shown to be involved in leptin‐induced liver fibrosis.

Conclusions and Implications

The β‐catenin pathway contributes to leptin regulation of SREBP‐1c expression in HSCs and leptin‐induced liver fibrosis in mice. These results have potential implications for clarifying the mechanisms of liver fibrogenesis associated with elevated leptin levels.
Integrating genetic and imaging investigations into the clinical management of congenital hyperinsulinism
Authors: Banerjee I. , Avatapalle B. , Padidela R. , Stevens A. , Cosgrove K. E. , Clayton P. E. , Dunne M. J.
Published: January 2013

Congenital Hyperinsulinism (CHI) is a rare but important cause of hypoglycaemia in infancy. CHI is a heterogeneous disease, but has a strong genetic basis; a number of genetic causes have been identified with CHI in about a third of individuals, chiefly in the genes that code for the ATP sensitive K+ channels (KATP) in the pancreatic β‐cells. Rapid KATP channel gene testing is a critical early step in the diagnostic algorithm of CHI, with paternal heterozygosity correlating with the occurrence of focal lesions. Imaging investigations to diagnose and localize solitary pancreatic foci have evolved over the last decade with (18)F‐DOPA PET‐CT scanning as the current diagnostic tool of choice. Although clinical management of CHI has improved significantly with the application of genetic screening and imaging investigations, much remains to be uncovered. This includes a better understanding of the molecular mechanisms for dysregulated insulin release in those patients without known genetic mutations, and the development of biomarkers that could characterize CHI, including long‐term prognosis and targeted treatment planning, i.e. ‘personalised medicine’. From the perspective of pancreatic imaging, it would be important to achieve greater specificity of diagnosis not only for focal lesions but also for diffuse and atypical forms of the disease.
Endoscopic resection (endoscopic mucosal resection/ endoscopic submucosal dissection) for early gastric cancer
Authors: Gotoda Takuji , Jung Hwoon‐Yong
Published: January 2013

Endoscopic resection of early gastric cancer is a well‐established standard therapy in Japan and Korea, and is increasingly used in other countries. Endoscopic resection should be curative for patients, and safe, easy and effective not only for patients, but also for endoscopists. Endoscopic submucosal dissection (ESD) is superior to standard endoscopic mucosal resection (EMR) as it is designed to provide en bloc R0 resection regardless of size and/or location. Correct pathological assessment of en bloc resected specimens is crucial for accurate diagnosis and patient stratification for the risk of metastasis. Outcome studies in Japan and Korea, countries with the highest incidence of gastric cancer, have shown that ESD is efficacious in leading to a good long‐term outcome; however, ESD requires an experienced endoscopist with a high skill level. Expanded indications for endoscopic resection have been proposed, especially after large en bloc resection have been accomplished using ESD. The use of ESD could be of huge benefit for the management of gastrointestinal superficial neoplasms. However, for ESD to become a viable therapeutic option, it requires close and supportive working relationships between endoscopists, pathologists and surgeons.
Beyond Market Signals: Negotiating Marketplace Politics and Corporate Responsibilities
Authors: Hamilton Trina
Published: January 2013

In the face of stiff resistance to their legislative efforts in national and multilateral arenas, nongovernmental organizations, unions, and others are engaging in marketplace politics to press their social and environmental concerns. While important criticisms of market‐based regulation abound, recent research has suggested that this form of politics is not restricted to simple market signals or a singular market logic, so the question of what drives corporate responsiveness remains. Drawing on a statistical analysis of a large data set of marketplace campaigns and in‐depth interviews with campaign proponents, consultants, and targeted executives, this article proposes a relational framework for understanding marketplace politics, situating campaign strategies in relation to targeted firms' brand vulnerabilities and corporate social responsibility (CSR) “absorptive capacity,” on the one hand, and parallel actions of key intermediaries—including investment advisory firms and pioneering competitors—on the other hand. I argue that it is influential minorities of consumers, investors, and intermediaries—often in dialogue with targeted executives—who create change, rather than majority, arm's length market movements. Overall, this research enhances the multiplicity of recent case studies by identifying common opportunities and barriers for marketplace politics and contributes to the burgeoning literature within economic geography that is redrawing the boundaries of corporate CSR decision making and capacity building.
Three‐Dimensional Echocardiography in the Evaluation of Global and Regional Function in Patients with Recent Myocardial Infarction: A Comparison with Magnetic Resonance Imaging
Authors: Thorstensen Anders , Dalen Håvard , Hala Pavel , Kiss Gabriel , D'hooge Jan , Torp Hans , Støylen Asbjørn , Amundsen Brage
Published: January 2013

We aimed to compare three‐dimensional (3D) and two‐dimensional (2D) echocardiography in the evaluation of patients with recent myocardial infarction (MI), using late‐enhancement magnetic resonance imaging (LE‐MRI) as a reference method. Echocardiography and LE‐MRI were performed approximately 1 month after first‐time MI in 58 patients. Echocardiography was also performed on 35 healthy controls. Left ventricular (LV) ejection fraction by 3D echocardiography (3D‐LVEF), 3D wall‐motion score (WMS), 2D‐WMS, 3D speckle tracking–based longitudinal, circumferential, transmural and area strain, and 2D speckle tracking–based longitudinal strain (LS) were measured. The global correlations to infarct size by LE‐MRI were significantly higher (P < 0.03) for 3D‐WMS and 2D‐WMS compared with 3D‐LVEF and the 4 different measurements of 3D strain, and 2D global longitudinal strain (GLS) was more closely correlated to LE‐MRI than 3D GLS (P < 0.03). The segmental correlations to infarct size by LE‐MRI were also significantly higher (P < 0.04) for 3D‐WMS, 2D‐WMS, and 2D LS compared with the other indices. Three‐dimensional WMS showed a sensitivity of 76% and a specificity of 72% for identification of LV infarct size >12%, and a sensitivity of 73% and a specificity of 95% for identification of segments with transmural infarct extension. Three‐dimensional WMS and 2D gray‐scale echocardiography showed the strongest correlations to LE‐MRI. The tested 3D strain method suffers from low temporal and spatial resolution in 3D acquisitions and added diagnostic value could not be proven.
Is basic self‐disturbance in ultra‐high risk for psychosis (‘prodromal’) patients associated with borderline personality pathology?
Authors: Nelson Barnaby , Thompson Andrew , Chanen Andrew M. , Amminger Günther Paul , Yung Alison R.
Published: January 2013

Aim

Research in the phenomenological tradition suggests that the schizophrenia spectrum is characterized by disturbance of the ‘basic’ self, whereas borderline personality disorder involves disturbance of the ‘narrative’ self. The current study investigated this proposal in an ultra‐high risk for psychosis sample.

Methods

The sample consisted of 42 ultra‐high‐risk participants with a mean age of 19.22 years. Basic self‐disturbance was measured using the Examination of Anomalous Self‐Experience. Borderline personality pathology was measured using the borderline personality disorder items from the Structured Clinical Interview for DSM‐IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) Axis II Personality Questionnaire.

Results

No correlation was found between the measures of basic self‐disturbance and borderline personality pathology.

Conclusions

The finding is consistent with the proposal that different (although not mutually exclusive) types of self‐disturbance characterize the schizophrenia spectrum and borderline personality disorder. Further research should further examine the question of basic self‐disturbance in patients with established borderline personality disorder.
Early traumatic experiences in those at clinical high risk for psychosis
Authors: Addington Jean , Stowkowy Jacqueline , Cadenhead Kristin S. , Cornblatt Barbara A. , McGlashan Thomas H. , Perkins Diana O. , Seidman Larry J. , Tsuang Ming T. , Walker Elaine F. , Woods Scott W. , Cannon Tyrone D.
Published: January 2013

Aim

Several lines of evidence suggest a possible association between a history of trauma in childhood and later psychosis or psychotic‐like experiences. The purpose of this study was to determine the extent of childhood trauma and bullying in young people at clinical high risk (CHR) of developing psychosis.

Methods

The sample consisted of 360 individuals who were at CHR of developing psychosis and 180 age‐ and gender‐matched healthy controls. All participants were assessed on past trauma and bullying. The CHR participants were also assessed on a range of psychopathology and functioning.

Results

Individuals at CHR reported significantly more trauma and bullying than healthy controls. Those who had experienced past trauma and bullying were more likely to have increased levels of depression and anxiety and a poorer sense of self.

Conclusions

These results offer preliminary support for an association between a history of trauma and later subthreshold symptoms.
Differential effects of site‐specific knockdown of estrogen receptor α in the medial amygdala, medial pre‐optic area, and ventromedial nucleus of the hypothalamus on sexual and aggressive behavior of male mice
Authors: Sano Kazuhiro , Tsuda Mumeko C. , Musatov Sergei , Sakamoto Toshiro , Ogawa Sonoko
Published: January 2013

Testosterone is known to play an important role in the regulation of male‐type sexual and aggressive behavior. As an aromatised metabolite of testosterone, estradiol‐induced activation of estrogen receptor α (ERα) may be crucial for the induction of these behaviors in male mice. However, the importance of ERα expressed in different nuclei for this facilitatory action of testosterone has not been determined. To investigate this issue, we generated an adeno‐associated virus vector expressing a small hairpin RNA targeting ERα to site‐specifically knockdown ERα expression. We stereotaxically injected either a control or ERα targeting vector into the medial amygdala, medial pre‐optic area (MPOA), or ventromedial nucleus of the hypothalamus (VMN) in gonadally intact male mice. Two weeks after injection, all mice were tested biweekly for sexual and aggressive behavior, alternating between behavior tests each week. We found that suppressing ERα in the MPOA reduced sexual but not aggressive behavior, whereas in the VMN it reduced both behaviors. Knockdown of ERα in the medial amygdala did not alter either behavior. Additionally, it was found that ERα knockdown in the MPOA caused a parallel reduction in the number of neuronal nitric oxide synthase‐expressing cells. Taken together, these results indicate that the testosterone facilitatory action on male sexual behavior requires the expression of ERα in both the MPOA and VMN, whereas the testosterone facilitatory action on aggression requires the expression of ERα in only the VMN.
Life‐history constraints in grassland plant species: a growth‐defence trade‐off is the norm
Authors: Lind Eric M. , Borer Elizabeth , Seabloom Eric , Adler Peter , Bakker Jonathan D. , Blumenthal Dana M. , Crawley Mick , Davies Kendi , Firn Jennifer , Gruner Daniel S. , Stanley Harpole W. , Hautier Yann , Hillebrand Helmut , Knops Johannes , Melbourne Brett , Mortensen Brent , Risch Anita C. , Schuetz Martin , Stevens Carly , Wragg Peter D.
Published: January 2013

Plant growth can be limited by resource acquisition and defence against consumers, leading to contrasting trade‐off possibilities. The competition‐defence hypothesis posits a trade‐off between competitive ability and defence against enemies (e.g. herbivores and pathogens). The growth‐defence hypothesis suggests that strong competitors for nutrients are also defended against enemies, at a cost to growth rate. We tested these hypotheses using observations of 706 plant populations of over 500 species before and following identical fertilisation and fencing treatments at 39 grassland sites worldwide. Strong positive covariance in species responses to both treatments provided support for a growth‐defence trade‐off: populations that increased with the removal of nutrient limitation (poor competitors) also increased following removal of consumers. This result held globally across 4 years within plant life‐history groups and within the majority of individual sites. Thus, a growth‐defence trade‐off appears to be the norm, and mechanisms maintaining grassland biodiversity may operate within this constraint.
Effects of spawning Pacific salmon on the isotopic composition of biota differ among southeast Alaska streams
Authors: REISINGER ALEXANDER J. , CHALONER DOMINIC T. , RÜEGG JANINE , TIEGS SCOTT D. , LAMBERTI GARY A.
Published: January 2013

1. Adult Pacific salmon (Oncorhynchusspp.) transport marine nutrients to fresh waters and disturb sediments during spawning. The relative importance of nutrient fertilisation and benthic disturbance by salmon spawners can be modulated by environmental conditions (e.g. biological, chemical and physical conditions in the catchment, including human land use).

2. To determine the importance of the environmental context in modifying the uptake and incorporation of salmon‐derived material into stream biota, we measured the nitrogen (δ15N) and carbon (δ13C) isotopic composition of benthic algae (i.e. epilithon) and juvenile coho salmon (Oncorhynchus kisutch) in seven streams across a timber‐harvest gradient (8–69% catchment area harvested), both before and during the salmon run. Conditional bootstrap modelling simulations were used to assess variability in the response of epilithon and juvenile coho salmon to spawning salmon.

3. In response to spawning salmon, epilithon exhibited enrichment in both δ15N (mean: 1.5‰) and δ13C (2.3‰). Juvenile coho were also enriched in both δ15N (0.7‰) and δ13C (1.4‰). Conditional bootstrap models indicate decreased variation in data as spatial replication increases, suggesting that the number of study sites can influence the results of Pacific salmon isotope studies.

4. Epilithon isotopic enrichment was predicted by environmental conditions, with δ15N enrichment predicted by stream temperature and timber harvest (R2 = 0.87) and δ13C enrichment by discharge, sediment size, timber harvest and spawner density (R2 = 0.96). Furthermore, we found evidence for a legacy effect of salmon spawners, with pre‐spawner δ15N and δ13C of both epilithon and juvenile coho predicted by salmon run size in the previous year.

5. Our results show that the degree of incorporation of salmon‐derived nitrogen and carbon differs among streams. Furthermore, the environmental context, including putative legacy effects of spawning salmon, can influence background isotopic concentrations and utilisation of salmon‐derived materials in southeast Alaska salmon streams. Future studies should consider the variation in isotopic composition of stream biota when deciding on the number of study sites and samples needed to generate meaningful results.
African Colonial Economies: Land, Labor, and Livelihoods
Authors: Ochonu Moses
Published: January 2013

In what ways and through what mechanisms and policy instruments did colonial regimes seek to draw Africans into the colonial economy as laborers, wage earners, taxpayers, and consumers of foreign manufactured goods? How successful were colonial efforts to reform access to agricultural land as a way of establishing a foundation for colonial agriculture, undermining preexisting but disfavored African land tenure practices, compelling taxation, and mobilizing African labor? This essay responds to these and related questions, surveying the main debates, key conceptual turns, and points of discussion on a critical aspect of colonial economic management in Africa: the commoditization of land and labor by colonial regimes and its consequences. The essay discusses the intertwinements of land and labor mobilization regimes, and the ways in which African maneuvers, initiatives, and strategies of self‐preservation produced outcomes that confounded and at times defeated colonial intentions in matters of land and labor.
Validation of the prognostic grouping of the seventh edition of the tumor‐nodes‐metastasis classification using a large‐scale prospective cohort study database of prostate cancer treated with primary androgen deprivation therapy
Authors: Kimura Tomokazu , Onozawa Mizuki , Miyazaki Jun , Kawai Koji , Nishiyama Hiroyuki , Hinotsu Shiro , Akaza Hideyuki
Published: January 2013

Objective

In the TNM seventh edition, a prognostic grouping for prostate cancer incorporating prostate‐specific antigen and Gleason score was advocated. The present study was carried out to evaluate and validate prognostic grouping in prostate cancer patients.

Methods

The 15 259 study patients treated with primary androgen deprivation therapy were enrolled in the Japan Study Group of Prostate Cancer. Overall survival was stratified by tumor–nodes–metastasis, Gleason score and prostate‐specific antigen, and extensively analyzed. The accuracy of grouping systems was evaluated by the concordance index.

Results

The 5‐year overall survival in prognostic grouping‐I, IIA, IIB, III and IV was 90.0%, 88.3%, 84.8%, 80.6% and 57.1%, respectively. When considering subgroup stratification, the 5‐year overall survival of subgroups prognostic grouping‐IIA, IIB, III and IV was 80.9∼90.5%, 75.4∼91.8%, 75.7∼89.0% and 46.9∼86.2%, respectively. When prognostic grouping‐IIB was subclassified into IIB1 (except IIB2) and IIB2 (T1–2b, prostate‐specific antigen >20, Gleason score ≥8, and T2c, Gleason score ≥8), the 5‐year overall survival of IIB2 was significantly lower than that of IIB1 (79.4% and 87.3%, P < 0.0001). Also, when prognostic grouping‐IV was subclassified into IV1 (except IV2) and IV2 (M1, prostate‐specific antigen >100 or Gleason score ≥8), the 5‐year overall survival of prognostic grouping‐IV1 was superior to that of IV2 (72.9% and 49.5%, P < 0.0001). Prognostic groupings were reclassified into modified prognostic groupings, divided into modified prognostic grouping‐A (prognostic grouping‐I, IIA, and IIB1), modified prognostic grouping‐B (prognostic grouping‐IIB2 and III), modified prognostic grouping‐C (prognostic grouping‐IV1) and modified prognostic grouping‐D (prognostic grouping‐IV2). The concordance index of prognostic grouping and modified prognostic grouping for overall survival was 0.670 and 0.685, respectively.

Conclusion

Prognostic grouping could stratify the prognosis of prostate cancer patients. However, there is considerable variation among the prognostic grouping subgroups. Thus, the use of a modified prognostic grouping for patients treated with primary androgen deprivation therapy is advisable.
Role of mammalian target of rapamycin inhibitor in the treatment of metastatic epithelioid angiomyolipoma: A case report
Authors: Kohno Jin , Matsui Yoshiyuki , Yamasaki Toshinari , Shibasaki Noboru , Kamba Tomomi , Yoshimura Koji , Sumiyoshi Shinji , Mikami Yoshiki , Ogawa Osamu
Published: January 2013

Epithelioid angiomyolipoma has malignant potential; however, no effective therapy has been established for advanced cases. A 50‐year‐old woman with a history of right nephrectomy for epithelioid angiomyolipoma was referred to our institution. Computed tomography and magnetic resonance imaging showed multiple tumors in her lung, liver and pelvic cavity. The liver and pelvic tumor specimens obtained by needle biopsy confirmed the diagnosis of epithelioid angiomyolipoma recurrence. The patient was treated with everolimus (10 mg/day). Three months later, pulmonary lesions disappeared; liver and pelvic tumors significantly shrank in size, but the pelvic tumor gradually enlarged again. We carried out surgical resection of the residual liver and pelvic cavity tumors. Although the mammalian target of rapamycin inhibitor seems to be effective for treating epithelioid angiomyolipoma, its long‐term effects remain unknown. Thus, aggressive administration of a multidisciplinary treatment including molecular target therapy and surgical resection is required to improve the prognosis of epithelioid angiomyolipoma.
The MYSTerious MOZ, a histone acetyltransferase with a key role in haematopoiesis
Authors: Perez‐Campo Flor M. , Costa Guilherme , Lie‐a‐Ling Michael , Kouskoff Valerie , Lacaud Georges
Published: January 2013

The MOnocytic leukaemia Zing finger (MOZ; MYST3 or KAT6A1) gene is frequently found translocated in acute myeloid leukaemia. MOZ encodes a large multidomain protein that contains, besides others, a histone acetyl transferase catalytic domain. Several studies have now established the critical function of MOZ in haematopoiesis. In this review we summarize the recent findings that underscore the relevance of the different biological activities of MOZ in the regulation of haematopoiesis.
SMAD regulatory networks construct a balanced immune system
Authors: Malhotra Nidhi , Kang Joonsoo
Published: January 2013

A balanced immune response requires combating infectious assaults while striving to maintain quiescence towards the self. One of the central players in this process is the pleiotropic cytokine transforming growth factor‐β (TGF‐β), whose deficiency results in spontaneous systemic autoimmunity in mice. The dominant function of TGF‐β is to regulate the peripheral immune homeostasis, particularly in the microbe‐rich and antigen‐rich environment of the gut. To maintain intestinal integrity, the epithelial cells, myeloid cells and lymphocytes that inhabit the gut secrete TGF‐β, which acts in both paracrine and autocrine fashions to activate its signal transducers, the SMAD transcription factors. The SMAD pathway regulates the production of IgA by B cells, maintains the protective mucosal barrier and promotes the balanced differentiation of CD4+ T cells into inflammatory T helper type 17 cells and suppressive FOXP3+ T regulatory cells. While encounters with pathogenic microbes activate SMAD proteins to evoke a protective inflammatory immune response, SMAD activation and synergism with immunoregulatory factors such as the vitamin A metabolite retinoic acid enforce immunosuppression toward commensal microbes and innocuous food antigens. Such complementary context‐dependent functions of TGF‐β are achieved by the co‐operation of SMAD proteins with distinct dominant transcription activators and accessory chromatin modifiers. This review highlights recent advances in unravelling the molecular basis for the multi‐faceted functions of TGF‐β in the gut that are dictacted by fluid orchestrations of SMADs and their myriad partners.
Indirect pulp treatment vs antibiotic sterilization of deep caries in mandibular primary molars
Authors: Trairatvorakul Chutima , Sastararuji Treesa
Published: January 2013

Background

Calcium hydroxide indirect pulp treatment (CH‐IPT) and antibiotic sterilization using a mixture of three antibiotics (3Mix‐MP) of deep caries are similar non‐invasive vital pulp treatments. No studies have compared their clinical and radiographic success rates in primary molars.

Aim

To compare the clinical and radiographic success rates of CH‐IPT and 3Mix‐MP in carious lesions approaching the pulp of mandibular primary molars.

Design

Eighty‐two mandibular primary molars from 50 children, aged 3–8 years, with carious lesions approaching the pulp, and meeting the inclusion criteria, were randomly assigned for either treatment. After treatment, blinded clinical/radiographic evaluation was performed at 6–11 and 12–29 month recalls.

Results

At 6–11 months, the overall success rates of CH‐IPT and 3Mix‐MP were 82% and 81% (P = 0.91), respectively. At 12–29 months, the success rates were 94% and 78% (P = 0.08), respectively. The most frequently observed failure at the 12–29 month recall was internal resorption (one CH‐IPT tooth and three 3Mix‐MP teeth).

Conclusion

There was no statistically significant difference in overall success rates between CH‐IPT and 3Mix‐MP in treating deep caries approaching the pulp in mandibular primary molars at either 6–11 month or 12–29 month follow‐up.
WHAT DETERMINES RELIGIOUS SCHOOL CHOICE? THEORY AND EVIDENCE FROM RURAL BANGLADESH
Authors: Asadullah M. Niaz , Chakrabarti Rupa , Chaudhury Nazmul
Published: January 2013

This paper looks at the determinants of school selection in rural Bangladesh, focusing on the choice between registered Islamic and non‐religious schools. Using a unique dataset on secondary school‐age children from rural Bangladesh, we find that madrasah enrolment falls as household income increases. At the same time, more religious households, and those that live further away from a non‐religious school are more likely to send their children to madrasahs. However, in contrast to the theory, we find that Islamic school demand does not respond to the average quality of schools in the locality.
Spatial and environmental impacts on adverse birth outcomes in Ontario
Authors: Meng Gang , Hall G. Brent , Thompson Mary E. , Seliske Patrick
Published: January 2013

This study assesses the overall spatial variations and neighbourhood‐level “hot spots” of low birth weight and preterm birth incidence within three public health units in Ontario, Canada. The analysis uses a stepwise approach of intra‐class correlation analysis, a spatial scan statistic, and multilevel spatial modeling. Results show that neighbourhood level variation accounts for only 2–3 percent of the total variation of adverse birth outcomes in the study area. However, strong spatial autocorrelation is observed at the neighbourhood level, and spatial clusters of relatively high adverse birth outcome rates exist in areas that are associated with environmental risks, including pollution sources and proximity to highways. Thus, although estimated neighbourhood impacts on adverse birth outcomes are small compared with those of individual‐level risks, local high potential environmental risk areas are identifiable. Environmental surveillance and spatial statistical analysis should be conducted regularly by local health authorities to identify and monitor the impact of environmental changes on health in general and on birth outcomes in particular. Specific community‐oriented health interventions may be required to reduce observed local health impacts.
Problems with using large‐scale oceanic climate indices to compare climatic sensitivities across populations and species
Authors: van de Pol Martijn , Brouwer Lyanne , Brooker Lesley C. , Brooker Michael G. , Colombelli‐Négrel Diane , Hall Michelle L. , Langmore Naomi E. , Peters Anne , Pruett‐Jones Stephen , Russell Eleanor M. , Webster Michael S. , Cockburn Andrew
Published: January 2013

To understand which populations and species are most sensitive to climate change, studies correlate time series of climate variables with those of traits important for population dynamics, and subsequently compare which aspects of a species’ ecology or life‐history best explain variation in climate sensitivity. Often large‐scale oceanic climate indices (LOCIs) are used as a proxy for local climatic drivers, with many studies reporting geographic gradients in climate sensitivity to LOCIs (e.g. suggesting that species living further from the equator are relatively climate sensitive). However, the relationship between LOCIs and local weather variables also varies geographically, raising the possibility that apparent intra‐ and inter‐specific differences in climate sensitivity to LOCIs could also reflect geographic variation in how well LOCIs function as a proxy for local climatic drivers. This hypothesis is rarely tested due to lack of knowledge about the specific local climatic drivers. Here we show, using reproductive and climate data from 16 long‐term population studies of 7 Australian fairy‐wren species (Malurus genus), that the use of LOCIs can result in 1) strong overestimation of the amount of inter‐specific variation in climate sensitivity and 2) spurious patterns, particularly geographic gradients. Consequently a paradox emerges: LOCIs often explain much of the temporal variation in traits important for population dynamics, but the common usage of LOCIs may prevent meaningful intra‐ and inter‐specific comparisons of climate sensitivities over large spatial scales. Our results thus may offer an alternative interpretation of the widely reported geographic gradients in sensitivity to LOCIs. Future progress will likely require better knowledge about the identity and temporal features of local environmental drivers of population dynamics.
Comparison of alternating pressure mattresses and overlays for prevention of pressure ulcers in ventilated intensive care patients: a quasi‐experimental study
Authors: Manzano Francisco , Pérez Ana‐María , Colmenero Manuel , Aguilar María‐Mar , Sánchez‐Cantalejo Emilio , Reche Ana‐María , Talavera Juan , López Francisca , Barco Sonia Frías‐Del , Fernández‐Mondejar Enrique
Published: January 2013

Aim

To compare the effectiveness of alternating pressure air mattresses vs. overlays to prevent pressure ulcers in mechanically ventilated patients in intensive care units.

Background

Pressure ulcers prevention is an important issue in the nursing of critically ill patients. It is not clear whether alternating pressure air mattresses are more effective than overlays to prevent pressure ulcers.

Design

Prospective quasi‐experimental study.

Methods

A prospective quasi‐experimental study was conducted among patients in the medical–surgery intensive care unit of a university hospital on mechanical ventilation ≥24 hours during two time periods (2001 and 2006). Overlays were used in 2001 and mattresses in 2006. Primary outcome was the incidence of pressure ulcers grade ≥II (according to the European Pressure Ulcer Advisory Panel) during intensive care unit stay.

Results

The study included 221 patients (116 in 2001 and 105 in 2006). Baseline characteristics were similar between groups except for a higher Acute Physiology and Chronic Health Evaluation III score, total and first‐day respiratory Sequential Organ Failure Assessment Score on day 1 in overlay group. There was significantly lower incidence density in the mattress vs. overlay group (12·41 cases/1000 days vs. 18·67 cases/1000 days of stay). The multivariate analyses showed the use of the mattress to be a protective factor against pressure ulcer onset.

Conclusion

This quasi‐experiment study that alternative pressure air mattresses were more effective than alternating pressure air overlays in preventing pressure ulcers in mechanically ventilated critical care patients.
Detection of emamectin benzoate tolerance emergence in different life stages of sea lice, Lepeophtheirus salmonis, on farmed Atlantic salmon, Salmo salar L
Authors: Jones P G , Hammell K L , Gettinby G , Revie C W
Published: January 2013

Emamectin benzoate has been used to treat sea lice, Lepeophtheirus salmonis, infestations on farmed Atlantic salmon, Salmo salar. Recent evidence suggests a reduction in effectiveness in some locations. A major challenge in the detection of tolerance emergence can be the typically low proportion of resistant individuals in a population during the early phases. The objectives of this study were to develop a method for determining differences in temporal development of tolerance between sea lice life stages and to explore how these differences might be used to improve the monitoring of treatment effectiveness in a clinical setting. This study examined two data sets based on records of sea lice abundance following emamectin benzoate treatments from the west coast of Scotland (2002–2006) and from New Brunswick, Canada (2004–2008). Life stages were categorized into two groups (adult females and the remaining mobile stages) to examine the trends in mean abundance and treatment effectiveness. Differences in emamectin benzoate effectiveness were found between the two groups by year and location, suggesting that an important part of monitoring drug resistance development in aquatic ectoparasites may be the need to focus on key life stages.
Co‐infection patterns of infectious salmon anaemia and sea lice in farmed Atlantic salmon, Salmo salar L., in southern Chile (2007–2009)
Authors: Valdes‐Donoso P , Mardones F O , Jarpa M , Ulloa M , Carpenter T E , Perez A M
Published: January 2013

Infectious salmon anaemia virus (ISAV) caused a large epidemic in farmed Atlantic salmon in Chile in 2007–2009. Here, we assessed co‐infection patterns of ISAV and sea lice (SL) based on surveillance data collected by the fish health authority. ISAV status and SL counts in all Atlantic salmon farms located in the 10th region of Chile were registered monthly from July 2007 through December 2009. Each farm was categorized monthly according to its ISAV and SL status. A multinomial time‐space scan test using a circular window was applied to identify disease clusters, and a multivariate regression model was fitted to quantify the association between disease‐clustering and farm‐management factors. Most of the identified clusters (9/13) were associated with high SL burdens. There were significant associations (P < 0.05) between management factors and ISAV/SL status. Areas in which good management practices were associated with a reduced disease risk were identified. The findings of this study suggest that certain management practices can effectively reduce the risk of SL and ISAV in the face of an epidemic and will be helpful towards creating an effective disease control programme in Chile.
Antibody screening identifies 78 putative host proteins involved in Cyprinid herpesvirus 3 infection or propagation in common carp, Cyprinus carpio L
Authors: Gotesman M , Soliman H , El‐Matbouli M
Published: January 2013

Cyprinid herpesvirus 3 (CyHV‐3) is the aetiological agent of a serious and notifiable disease afflicting common and koi carp, Cyprinus carpio L., termed koi herpesvirus disease (KHVD). Significant progress has been achieved in the last 15 years, since the initial reports surfaced from Germany, USA and Israel of the CyHV‐3 virus, in terms of pathology and detection. However, relatively few studies have been carried out in understanding viral replication and propagation. Antibody‐based affinity has been used for detection of CyHV‐3 in enzyme‐linked immunosorbent assay and PCR‐based techniques, and immunohistological assays have been used to describe a CyHV‐3 membrane protein, termed ORF81. In this study, monoclonal antibodies linked to N‐hydroxysuccinimide (NHS)‐activated spin columns were used to purify CyHV‐3 and host proteins from tissue samples originating in either CyHV‐3 symptomatic or asymptomatic fish. The samples were next analysed either by polyacrylamide gel electrophoresis (PAGE) and subsequently by electrospray ionization coupled to mass spectrometry (ESI‐MS) or by ESI‐MS analysis directly after purification. A total of 78 host proteins and five CyHV‐3 proteins were identified in the two analyses. These data can be used to develop novel control methods for CyHV‐3, based on pathways or proteins identified in this study.
Effects of channel shape on propagation characteristics of flood flows through a valley
Authors: Takemura Y. , Fukuoka S.
Published: January 2013

Understanding the effects of the planar, longitudinal, and cross‐sectional form (channel shape) of a river channel on the propagation of a flood flow is important for proper river improvement and management. This paper shows that the propagation characteristics of a discharge hydrograph of a flood flow are closely related to temporal changes in the mean velocity. We defined the storage volume of a flood flow produced by a decrease in the mean velocity as the ‘retarding storage volume of a flood flow’. By using observed data and unsteady two‐dimensional flow analysis of a flood of the Go River valley in June 1999, the propagation mechanics of the discharge hydrograph is described in relation to the channel shape, storage volume, and retarding storage volume.
Food label usage and reported difficulty with following a gluten‐free diet among individuals in the USA with coeliac disease and those with noncoeliac gluten sensitivity
Authors: Verrill L. , Zhang Y. , Kane R.
Published: January 2013

Background

Individuals with coeliac disease (CD) and those with noncoeliac gluten sensitivity (GS) have reported difficulty following a gluten‐free diet (GFD); however, few studies have explored the link between the food label, gluten‐free (GF) claims and the difficulty associated with following a GFD.

Methods

The present study surveyed adults with CD (n = 1,583) and adults with GS (n = 797) about their reported difficulty following a GFD, including assessing the role of food labels and GF claims, as well as other factors known to contribute to this difficulty. A two‐sample t‐test and chi‐squared tests for equality of means or proportions were used for the descriptive data and ordinal logistic regression (OLR) was used to model associations.

Results

On average, individuals with GS reported slightly more difficulty following the GFD than did participants with CD. According to the OLR results, reading the food label often was significantly associated with less reported difficulty following a GFD, whereas consuming packaged processed foods and looking for GF claims more often were significantly associated with more reported difficulty for both respondent groups.

Conclusions

Individuals with GS may rely more heavily on the GF claim for information about a product's gluten content. Individuals with CD, on the other hand, may be more experienced food label readers and may rely more on the ingredient list for finding GF foods. More studies are needed aiming to understand the role of the food label in facilitating consumers' ability to follow a GFD.
An automated method for the calculation of P–T paths from garnet zoning, with application to metapelitic schist from the Kootenay Arc, British Columbia, Canada
Authors: Moynihan D. P. , Pattison D. R. M.
Published: January 2013

An automated method for the calculation of P–T paths based on garnet zoning is presented and used to interpret zoning in metapelitic schist from the southern Canadian Cordillera. The approach adopted to reconstruct the P–T path is to match garnet compositions along a radial transect with predictions from thermodynamic forward models, while iteratively modifying the composition to account for fractional crystallization. The method is applied to a representative sample of garnet‐ and staurolite‐bearing schist from an amphibolite facies Barrovian belt in the southern Canadian Omineca belt. Garnet zoning in these schists is concentric and largely continuous from core to rim. Three zones are present, the first two of which coincide with sector‐zoned cores of garnet crystals. Similar zoning is developed in rocks that contain or lack staurolite, respectively, suggesting garnet growth was restricted to the initial part of the prograde P–T path prior to the development of staurolite. Growth zoning in large garnet crystals has not been significantly modified by diffusion. This interpretation is based on zoning characteristics of garnet crystals and is further supported by results of a forward model incorporating the effects of simultaneous fractional crystallization and intracrystalline diffusion. The P–T path calculated for this rock includes an initial, linear stage with a high dP/dT, and a later stage dominated by heating. The approach adopted in this study may have application to other garnet‐bearing rocks in which growth zoning is preserved.
Nurse practitioner prescribing practices: the most frequently prescribed medications
Authors: Buckley Thomas , Cashin Andrew , Stuart Meg , Browne Graeme , Dunn Sandra V
Published: January 2013

Aims and objectives

To explore which medications Australian nurse practitioners most frequently prescribe.

Background

Although nurse practitioners in Australia have prescriptive authority, little is known about which specific medications nurse practitioners are prescribing and how frequently they do so.

Design

Descriptive electronic survey.

Methods

A total of 209 nurse practitioners reported current prescribing practices. Medications reported were categorised according to the Australian Medicines Handbook major drug classifications and frequencies presented.

Results

Seventy‐eight per cent of respondents reported prescribing medications as part of their Nurse Practitioner practice. In total, participants reported prescribing 234 separate medications from most Australian Medicines Handbook major drug classifications. Medications from the classification anti‐infective drugs were most frequently prescribed followed by medications from analgesic, psychotropic, cardiovascular, musculoskeletal, genitourinary and gastrointestinal classifications.

Conclusion

The majority of nurse practitioners in Australia prescribe medications in their clinical practice, although the proportion of nurse practitioners prescribing has not changed significantly in the past four years. The medications prescribed are comparable with those most frequently prescribed by all prescribers in Australia and highlight the diversity in scope of practice among nurse practitioners.

Relevance to clinical practice

Findings highlight the importance of Nurse Practitioner's a capacity to prescribe wide variety of medications, especially in practice areas such acute, primary and emergency care. The unique role nurse practitioners in relation to management of patients with infective processes and patients requiring pain relief is highlighted. Insight into current Nurse Practitioner prescribing trends informs future Nurse Practitioner curricular and future continuing education programmes. Findings give unique insight for future service planning, especially service providers considering introducing nurse practitioners to their service. The finding that nurse practitioners prescribing patterns are similar to other non‐nurse practitioner prescribers in Australia highlights the potential for service providers to introduce new models of care that are Nurse Practitioner lead.