bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of an autologous leukocyte and platelet‐rich fibrin patch intended for the treatment of recalcitrant wounds
Authors: Lundquist Rasmus , Holmstrøm Kim , Clausen Christian , Jørgensen Bo , Karlsmark Tonny
Published: December 2012

We have investigated the physical, biochemical, and cellular properties of an autologous leukocyte and platelet‐rich fibrin patch. This was generated in an automated device from a sample of a patient's blood at the point of care. Using microscopy, cell counting, enzyme‐linked immunosorbent assay, antibody arrays, and cell culture assays, we show that the patch is a three‐layered membrane comprising a fibrin sheet, a layer of platelets, and a layer of leukocytes. Mean recovery of platelets from the donated blood was 98% (±95%CI 0.8%). Mean levels of platelet‐derived growth factor AB, human transforming growth factor beta 1, and vascular endothelial growth factor extracted from the patch were determined as 127 ng (±95% CI 20), 92 ng (±95%CI 17), and 1.35 ng (±95%CI 0.37), respectively. We showed a continued release of PDGF‐AB over several days, the rate of which was increased by the addition of chronic wound fluid. By comparison with traditional platelet‐rich plasma, differences in immune components were found. The relevance of these findings was assessed by showing a mitogenic and migratory effect on cultured human dermal fibroblasts. Further, we showed that fibrocytes, a cell type important for acute wound healing, could be grown from the patch. The relevance of these findings in relation to the use of the patch for treating recalcitrant wounds is discussed.
Prevalence of Dysphoria after Fentanyl in Dogs Undergoing Stifle Surgery
Authors: Becker Willem M. , Mama Khursheed R. , Rao Sangeeta , Palmer Ross H. , Egger Erick L.
Published: December 2012

Objective

To describe the prevalence of dysphoria after intraoperative administration of fentanyl by infusion and identify other risk factors influencing this in dogs undergoing stifle surgery.

Study Design

Prospective, randomized clinical study.

Animals

Dogs (n = 92) that had tibial plateau leveling osteotomy (TPLO) or tibial tuberosity advancement (TTA).

Methods

Dogs were anesthetized using a standardized anesthetic protocol, and randomly assigned to receive a loading dose followed by 1 of 3 infusions of fentanyl perioperatively: 2 μg/kg/h, 10 μg/kg/h, or 20 μg/kg/h. Dog characteristics and all additional medications were recorded and included as part of the statistical analysis. Dog behavior was scored before anesthesia and during recovery using a scale of 1–4 (Appendices A and B). If no improvement in behavior was seen in 3–5 minutes postextubation, dogs with a score of 3 or 4 during recovery were administered fentanyl (2 μg/kg intravenously [IV]) in the event that the behaviors associated with the higher scores were related to pain. If they did not respond favorably to the administration of additional fentanyl and wound palpation did not elicit a response, but the untoward behaviors continued, dogs were administered either a tranquilizer, sedative, or opioid antagonist, and were considered dysphoric.

Results

Of 92 dogs, 22 (23.9%) were considered dysphoric using aforementioned criteria.

Conclusions

About one‐fourth of dogs enrolled in this study were dysphoric based on study criteria.
A Framework for Dynamic Causal Inference in Political Science
Authors: Blackwell Matthew
Published: December 2012

Dynamic strategies are an essential part of politics. In the context of campaigns, for example, candidates continuously recalibrate their campaign strategy in response to polls and opponent actions. Traditional causal inference methods, however, assume that these dynamic decisions are made all at once, an assumption that forces a choice between omitted variable bias and posttreatment bias. Thus, these kinds of “single‐shot” causal inference methods are inappropriate for dynamic processes like campaigns. I resolve this dilemma by adapting methods from biostatistics, thereby presenting a holistic framework for dynamic causal inference. I then use this method to estimate the effectiveness of an inherently dynamic process: a candidate’s decision to “go negative.” Drawing on U.S. statewide elections (2000–2006), I find, in contrast to the previous literature and alternative methods, that negative advertising is an effective strategy for nonincumbents. I also describe a set of diagnostic tools and an approach to sensitivity analysis.
Parathyroid Enlargement at Dialysis Initiation in Patients With Chronic Kidney Diseases
Authors: Nakai Kentaro , Fujii Hideki , Kono Keiji , Goto Shunsuke , Miura Shuhei , Maeda Atsuhiro , Takeda Kazuhito , Nishi Shinichi
Published: December 2012

The kidney chiefly maintains homeostasis of water, electrolytes, and other solutions. When kidney function is reduced, mineral metabolism is disrupted. Mineral and bone disorder in patients with chronic kidney disease associates with increased cardiovascular risk and mortality; however, management of chronic kidney disease–mineral and bone disorder in predialysis patients remains controversial. This study investigates the association between parathyroid enlargement at dialysis initiation and hyperparathyroidism management in dialysis patients. We enrolled 72 patients at dialysis initiation in this study. Using parathyroid sonography, we categorized patients based on presence (detected group; N = 18) or absence (undetected group; N = 54) of enlarged parathyroid glands and assessed the clinical characteristics and laboratory findings. A literature review of ultrasound evaluations of secondary hyperparathyroidism was conducted. Ultrasonography revealed enlarged parathyroid glands in 18 patients (25%). Serum intact parathyroid hormone levels were high in patients with enlarged parathyroid glands; however, of the 29 patients with intact parathyroid hormone levels <240 pg/mL, four had enlarged parathyroid glands. Eight of the 29 patients with serum phosphorus and calcium levels within the optimal range had enlarged parathyroid glands. Twenty of these 29 patients were followed up at 38 ± 17 months (at least 3 months): enlarged parathyroid glands were detected in 6. During follow‐up, serum intact parathyroid hormone levels were significantly higher in the detected group compared with the undetected. In conclusion, enlarged parathyroid glands are frequently detected at dialysis initiation, potentially predicting the persistence of secondary hyperparathyroidism and the need for strict management.
Novel Inflammatory Marker in Dialysis Patients: YKL‐40
Authors: Okyay Gülay Ulusal , Er Ramazan Erdem , Tekbudak Merve Yasemin , Paşaoğlu Özge , İnal Salih , Öneç Kürşad , Paşaoğlu Hatice , Altok Kadriye , Derici Ülver , Erten Yasemin
Published: December 2012

YKL‐40 has been introduced as a marker of inflammation in different clinical situations. The association between YKL‐40 and inflammation in chronic renal failure patients has not been researched currently. The objectives of this study were to establish serum YKL‐40 concentrations in dialysis patients with chronic renal failure compared to healthy subjects and to explore its relationships with a proinflammatory cytokine, interleukine‐6 (IL‐6) and an acute phase mediator, high sensitivity C‐reactive protein (hs‐CRP). The study population included hemodialysis patients (N = 43; mean age of 40.9 ± 14.5), peritoneal dialysis patients (N = 38; mean age of 45.8 ± 13.7) and healthy subjects (N = 37; mean age of 45.5 ± 10.6). Serum concentrations of YKL‐40, IL‐6, hs‐CRP and routine laboratory measures were evaluated. Compared to the healthy subjects, hemodialysis and peritoneal dialysis patients had higher concentrations of YKL‐40, IL‐6, hs‐CRP, as well as lower concentrations of hemoglobin, serum albumin and high density lipoprotein‐cholesterol (P < 0.001). YKL‐40 concentrations were positively correlated with serum creatinine (P < 0.001, r = 0.495), IL‐6 (P < 0.001, r = 0.306), hs‐CRP (P = 0.001, r = 0.306) levels and inversely correlated with hemoglobin (P = 0.002, r = −0.285), serum albumin (P < 0.001, r = −0.355) and high density lipoprotein‐cholesterol (P = 0.001, r = −0.306). In multivariate regression analysis YKL‐40 was associated with creatinine, serum albumin and hs‐CRP concentrations after adjustments with covariates. Dialysis patients with chronic renal failure have elevated serum YKL‐40 concentrations. Associations with standard inflammatory parameters suggest that YKL‐40 might be a novel inflammatory marker in this population.
Inflammation in aspergillosis: the good, the bad, and the therapeutic
Authors: Carvalho Agostinho , Cunha Cristina , Iannitti Rossana G. , De Luca Antonella , Giovannini Gloria , Bistoni Francesco , Romani Luigina
Published: December 2012

Aspergillosis includes a spectrum of diseases caused by different Aspergillus spp. New insights into the cellular and molecular mechanisms of resistance and immune tolerance to the fungus in infection and allergy have been obtained in experimental settings. The fact that virulence factors, traditionally viewed as fungal attributes, are contingent upon microbial adaptation to various environmental stresses encountered in the human host implies that the host and fungus are jointly responsible for pathogenicity. Ultimately, despite the occurrence of severe aspergillosis in immunocompromised patients, clinical evidence indicates that aspergillosis also occurs in the setting of a heightened inflammatory response, in which immunity occurs at the expense of host damage and pathogen eradication. Thus, targeting pathogenicity rather than microbial growth, tolerance rather than resistance mechanisms of defense may pave the way to targeted anti‐inflammatory strategies in difficult‐to‐treat patients. The challenge now is to translate promising results from experimental models to the clinic.
The diverse applications of RNA‐seq for functional genomic studies in Aspergillus fumigatus
Authors: Rokas Antonis , Gibbons John G. , Zhou Xiaofan , Beauvais Anne , Latgé Jean‐Paul
Published: December 2012

The deep sequencing of an mRNA population, RNA‐seq, is a very successful application of next‐generation sequencing technologies (NGSTs). RNA‐seq takes advantage of two key NGST features: (1) samples can be mixtures of different DNA pieces, and (2) sequencing provides both qualitative and quantitative information about each DNA piece analyzed. We recently used RNA‐seq to study the transcriptome of Aspergillus fumigatus, a deadly human fungal pathogen. Analysis of the RNA‐seq data indicates that there are likely tens of unannotated and hundreds of novel genes in the A. fumigatus transcriptome, mostly encoding for small proteins. Inspection of transcriptome‐wide variation between two isolates reveals thousands of single nucleotide polymorphisms. Finally, comparison of the transcriptome profiles of one isolate in two different growth conditions identified thousands of differentially expressed genes. These results demonstrate the utility and potential of RNA‐seq for functional genomics studies in A. fumigatus and other fungal human pathogens.
Management of chronic pulmonary aspergillosis
Authors: Izumikawa Koichi , Tashiro Masato , Kohno Shigeru
Published: December 2012

Chronic pulmonary aspergillosis (CPA) is a relatively rare, slowly progressive pulmonary syndrome caused by Aspergillus spp. The scarcity of clinical evidence for its management is an important issue. Oral azoles are recommended as the primary treatment of CPA; however, the evidence for their effectiveness is insufficient. Azole‐resistant A. fumigatus is rapidly increasing and becoming a serious concern. Because long‐term administration of azoles is the mainstay of CPA, azole resistance may pose a serious threat. Furthermore, prolonged oral administration of azoles may lead to increased azole resistance in CPA patients. Therefore, alternative management strategies for CPA must be considered, and one option may involve the use of intravenous antifungals such as echinocandins and polyens. The utility of these antifungals, however, has not been well evaluated and remains controversial because the drugs are expensive and require patients to be admitted to the hospital for their use. New antifungal drugs with novel mechanisms of action are also needed.
Evolution of modular conidiophore development in the aspergilli
Authors: Harris Steven D.
Published: December 2012

Conidiophores are reproductive structures that enable filamentous fungi to produce and disseminate large numbers of asexual spores. The diversity in conidiophore morphology is sufficiently large to serve as a basis for fungal systematics. Aspergillus and Penicillium species are members of the family Trichocomaceae that form conidiophores with characteristic architecture. Whereas the Penicillium conidiophore appears to be a modified branched hyphal structure, the Aspergillus conidiophore is seemingly more complex and includes additional cell types. Here, it is proposed that the “aspergillioid” conidiophore may have evolved from a “penicillioid” ancestor via changes in expression of key regulators of the cell cycle and the GTPase Cdc42. Because the transcriptional regulatory network that controls conidiophore development in Aspergillus is well characterized, further study of how this network links to regulators of the cell cycle and Cdc42 should provide fundamental insight into the evolution of developmental morphogenesis in fungi (i.e., fungal evo‐devo).
Protein targets for broad‐spectrum mycosis vaccines: quantitative proteomic analysis of Aspergillus and Coccidioides and comparisons with other fungal pathogens
Authors: Champer Jackson , Diaz‐Arevalo Diana , Champer Miriam , Hong Teresa B. , Wong Mayyen , Shannahoff Molly , Ito James I. , Clemons Karl V. , Stevens David A. , Kalkum Markus
Published: December 2012

Aspergillus species are responsible for most cases of fatal mold infections in immunocompromised patients, particularly in those receiving hematopoietic stem cell transplants. Experimental vaccines in mouse models have demonstrated a promising avenue of approach for the prevention of aspergillosis, as well as infections caused by other fungal pathogens, such as Coccidioides, the etiological agent of valley fever (coccidioidomycosis). Here, we investigated the hyphal proteomes of Aspergillus fumigatus and Coccidioides posadasii via quantitative MSE mass spectrometry with the objective of developing a vaccine that cross‐protects against these and other species of fungi. Several homologous proteins with highly conserved sequences were identified and quantified in A. fumigatus and C. posadasii. Many abundant proteins from the cell wall of A. fumigatus present themselves as possible cross‐protective vaccine candidates, due to the high degree of sequence homology to other medically relevant fungal proteins and low homologies to human or murine proteins.
The top three areas of basic research on Aspergillus fumigatus in 2011
Authors: Osherov Nir
Published: December 2012

Over 450 peer‐reviewed papers containing the keyword Aspergillus fumigatus were published in 2011. Although this method may be an impossible task, I have selected three clusters of papers describing exciting recent advances in research on A. fumigatus. The first is the novel approach of in vivo imagining of experimental aspergillosis by the use of 68Ga‐labeled siderophores, internalized by the fungus, and detected via positron emission tomography to image the site infection. This work may lead to improved diagnosis of aspergillosis. The second important finding is that NK lymphocytes, not thought to be involved in host resistance to aspergillosis, can kill aspergilli through direct contact, either through perforin or interferon‐γ, or both. The third area pertains to a novel first‐in‐class antifungal drug, E1210 (Eisai), which inhibits GPI anchoring of fungal‐associated cell wall proteins. Thus far, it shows promising in vitro activity against a broad range of fungi including Aspergilli, as well as those that are difficult to treat with currently available therapies. Overall, these three areas demonstrate the exciting promise, progress, and utility of basic research against A. fumigatus.
Aspergillus flavusdiversity on crops and in the environment can be exploited to reduce aflatoxin exposure and improve health
Authors: Mehl Hillary L. , Jaime Ramon , Callicott Kenneth A. , Probst Claudia , Garber Nicholas P. , Ortega‐Beltran Alejandro , Grubisha Lisa C. , Cotty Peter J.
Published: December 2012

Humans and animals are exposed to aflatoxins, toxic carcinogenic fungal metabolites, through consumption of contaminated food and feed.Aspergillus flavus, the primary causal agent of crop aflatoxin contamination, is composed of phenotypically and genotypically diverse vegetative compatibility groups (VCGs). Molecular data suggest that VCGs largely behave as clones with certain VCGs exhibiting niche preference. VCGs vary in aflatoxin‐producing ability, ranging from highly aflatoxigenic to atoxigenic. The prevalence of individual VCGs is dictated by competition during growth and reproduction under variable biotic and abiotic conditions. Agronomic practices influence structures and average aflatoxin‐producing potentials ofA. flavuspopulations and, as a result, incidences and severities of crop contamination. Application of atoxigenic strains has successfully reduced crop aflatoxin contamination across large areas in the United States. This strategy uses components of the endemic diversity to alter structures ofA. flavuspopulations and improve safety of food, feed, and the overall environment.
Invasive aspergillosis in the intensive care unit
Authors: Dimopoulos George , Frantzeskaki Frantezeska , Poulakou Garyfallia , Armaganidis Apostolos
Published: December 2012

Invasive aspergillosis is a devastating infection affecting severely immunocompromised patients, most frequently with hematologic malignancies. In recent years, a surge in the incidence of invasive aspergillosis has been reported in critically ill patients without the classical risk factors. The mortality of the disease is equally high in the group of intensive care unit (ICU) patients, while the clinical signs and symptoms are nonspecific and the diagnosis remains a challenge. New noninvasive diagnostic methods in combination with better tolerated antifungal drugs aim for early diagnosis and improved prognosis of invasive aspergillosis. In this review, we discuss the epidemiology, the diagnostic strategy and algorithms, and the therapeutic choices of this severe infection in critically ill patients.
Azole resistance in Aspergillus: global status in Europe and Asia
Authors: Arikan‐Akdagli Sevtap
Published: December 2012

Azole‐resistant strains of Aspergillus have been reported from European and Asian countries at varying frequencies. Based on the limited rates of isolation of Aspergillus from clinical samples in routine practice and the limited number of the screening studies carried out so far, the true prevalence of triazole resistance and the rate of multiazole‐resistant strains remain partly unknown. Also, available data are mostly for A. fumigatus (complex), thus the situation for non‐fumigatus Aspergilli is less clear. In general, exposure of Aspergillus to antifungal agents via medical or environmental (agricultural) use of these compounds appears to have the possible major impact on acquisition of triazole resistance. Azole resistance in Aspergillus remains to be further elucidated by continued surveillance studies. Based on the possible association with agricultural azole use, environmental sampling appears significant as well.
Activation of the neutrophil NADPH oxidase by Aspergillus fumigatus
Authors: Boyle Keith B. , Stephens Len R. , Hawkins Phillip T.
Published: December 2012

Upon infection of the respiratory system with the fungus Aspergillus fumigatus various leukoctytes, in particular neutrophils, are recruited to the lung to mount an immune response. Neutrophils respond by both phagocytosing conidia and mediating extracellular killing of germinated, invasive hyphae. Of paramount importance to an appropriate immune response is the neutrophil NADPH oxidase enzyme, which mediates the production of various reactive oxygen species (ROS). This is evidenced by the acute sensitivity of both oxidase‐deficient humans and mice to invasive aspergillosis. Herein we briefly review the mechanisms and functions of oxidase activation and discuss our recent work identifying at least some of the important players in hyphal‐induced oxidase activation and neutrophil function. Among these we define the phosphoinositide 3‐kinase enzyme and the regulatory protein Vav to be of critical importance and allude to a kinase‐independent role for Syk.
Current section and species complex concepts in Aspergillus: recommendations for routine daily practice
Authors: Alastruey‐Izquierdo Ana , Mellado Emilia , Cuenca‐Estrella Manuel
Published: December 2012

The identification of fungi by molecular techniques has generated important changes in fungal taxonomy. The use of molecular tools in taxonomic studies has led to the description of some cryptic species that were placed into a complex of morphologically similar organisms and were subsequently misidentified. There are still limited data available on the prevalence of cryptic species of Aspergillus in the clinical setting, although some studies report 10–14% of the total number of Aspergillus species. In addition, the main concern about the emergence of Aspergillus cryptic species is that they can be more resistant to antifungal agents. The rise in the incidence of fungal infections and the changing landscape of epidemiology, together with the description of new pathogens and their different susceptibility profiles, make the identification by molecular methods and/or antifungal susceptibility testing the best options available for the correct management of these infections.
Risk stratification for invasive aspergillosis in immunocompromised patients
Authors: Herbrecht Raoul , Bories Pierre , Moulin Jean‐Charles , Ledoux Marie‐Pierre , Letscher‐Bru Valérie
Published: December 2012

Severe prolonged neutropenia, allogeneic hematopoietic stem cell or solid‐organ transplantation, corticosteroids or other T cell suppressive agents, and other severe immunosuppressive factors have for many years been considered to predispose patients to invasive aspergillosis. Other conditions such as impaired innate immunity, diabetes, renal impairment, progression of the underlying malignancy, prior respiratory disease, and nosocomial or environmental exposure to fungal spores or climatic factors have recently been considered additional risk factors of invasive aspergillosis. The multiplicity of risk factors as well as the obvious synergy between them renders risk stratification difficult. An international, large‐scale, multicenter, epidemiological study is necessary to develop a risk score.
SYRACUSAN IDENTITY BETWEEN TYRANNY AND DEMOCRACY
Authors: THATCHER MARK
Published: December 2012

The city of Syracuse saw enormous social changes in the first half of the fifth century BCE, as the Deinomenid tyranny gave way to a more democratic constitution. In particular, the tyrants' extension of citizenship to some 10,000 former mercenaries was accompanied by shifting conceptions of Syracusan civic identity. The ideological program of Hieron, found in Pindar and on coinage, promoted a version of civic identity that focused on the city's Dorian ethnicity and unique topographical features (the island Ortygia and the spring Arethusa) as factors shared by all citizens. After the fall of the tyranny, however, this more inclusive conception of Syracusan identity was rejected by the ‘original’ citizens, who excluded the former mercenaries from office-holding. The resulting civil strife reveals a struggle, in the aftermath of tyranny, over the nature of Syracusan civic identity: what did it mean to be Syracusan and how would that status be defined?
FIGHTING TYRANNY IN FIFTH-CENTURY ATHENS: DEMOCRATIC CITIZENSHIP AND THE OATH OF DEMOPHANTUS
Authors: MCGLEW J.
Published: December 2012

By way of explaining why he turned to the Athenian tyrannicides while narrating the Affair of the Mysteries in 415, Thucydides asserts at 6.60.1 that the Athenian demos, ‘remembering all that they knew from report’ about their civic heroes, became ‘unmanageable and suspicious of those blamed for the affair’. Should historians believe him? Perhaps not. This paper discusses the oath of Demophantus, which the Athenians collectively recited after restoring democracy in 410/09 (And. 1.97–98) and which gives prominent place to Harmodius and Aristogeiton. The tyrannicides support the oath's obvious ideological impulse, the assimilation of oligarchy and tyranny: citizens watch for threats of the few, just as Harmodius and Aristogeiton stood against tyranny. More importantly, I argue, the oath adopts tyrannicide as a model for democratic citizenship: the oath transforms the everyday political activities of citizenship into tyrannicide: standing with Harmodius and Aristogeiton (and his real neighbours), the citizen protects democracy with confidence, not suspicion.
GREEK TYRANNY AND ROMAN EMPERORS DURING THE SEVERAN PERIOD: A CASE STUDY OF P. COL. 123 AND SEG XVII 759
Authors: TUORI KAIUS
Published: December 2012

Greek and Hellenistic models were central to the formulation of the position and capabilities in law of the Roman Emperor during the Principate. The purpose of this article is to argue that the ideological response to Greek tyranny by Roman authors and the impact of the narrative tradition on tyrants both influenced what the Emperors could do and what was expected of them. Through the narrative tradition which existed on tyranny in the ancient world, Roman Emperors were presented with modes of behaviour on how the interplay and the relationship between the ruler and the ruled took place. Through the examples of the Columbia papyrus and the Goharian inscription, I will argue that the Roman situation was quite unique in the combination of approachability and the practical administration of justice. These examples show how the Emperor was not simply a benevolent monarch but also, if necessary, a strict magistrate.
Transpiration Response of Maize Hybrids to Atmospheric Vapour Pressure Deficit
Authors: Gholipoor M. , Choudhary S. , Sinclair T. R. , Messina C. D. , Cooper M.
Published: December 2012

Maize (Zea mays L.) yield is often restricted by low soil water availability, particularly late in the growing season. To increase yields, genetic options for more effective use of available soil water are being explored. One option is to select genotypes that have restricted transpiration rate under high vapour pressure deficit (VPD) conditions so that soil water is conserved for use later in the growing season. While genetic variation for this trait has been identified within several crop species, such variation has never been explored in maize. The objective of this study was to examine transpiration rate of 35 single‐cross hybrids to determine whether hybrids can be identified that express limited transpiration under high VPD. Two sets of experiments were undertaken in which plants were exposed to a range of VPD in chambers. A two‐phase transpiration response was observed in 11 hybrids in which there was a threshold VPD above which transpiration rate was restricted. The VPD threshold varied from 1.7 to 2.5 kPa among these hybrids. Eight hybrids were included in both sets of experiments, and the same results were obtained in both experiments, indicating that expression of the trait was consistent.
Latitudinal forest advance in northernmost Norway since the early 20th century
Authors: Hofgaard Annika , Tømmervik Hans , Rees Gareth , Hanssen Frank
Published: December 2012

Aim

The arctic forest–tundra boundary is expected to advance rapidly northwards in response to climate warming. The purpose of this study was: (1) to analyse region‐wide changes in the positions of the latitudinal forest line and tree line since the early 20th century; (2) to calculate rates of northward movement and to estimate uncertainties from different sources of data; (3) to analyse how rates of advance differ between two common tree species, Betula pubescens (downy birch) and Pinus sylvestris (Scots pine); and (4) to place the results in the context of dynamic global vegetation models.

Location

The study covers Finnmark county in northern Norway, which has warmed by 1–2 °C since the early 20th century.

Methods

Historical forest maps, topographic maps, aerial photographs and satellite imagery were used to delineate region‐wide, species‐specific and time‐specific subarctic forest lines and tree lines. Rates of advance were calculated using two geometrical methods, placing different emphases on the shape and mean position of the lines, but yielding similar results.

Results

The analyses revealed an average northward advance of the birch and pine forest lines of 156 and 71 m year−1, respectively. Both showed considerable spatial and temporal variation. The birch tree line showed the most pronounced advance (340 m year−1), whereas the pine tree line showed very limited advance (10 m year−1). Data sources contributed an uncertainty of around 10 m year−1 to these rates.

Main conclusions

The analysis of historical and recent forest delineation data showed a very restricted advance rate compared to the predictions of dynamic global vegetation models. If these results are representative of the behaviour of the entire circumarctic forest–tundra zone over the present century, they suggest that the modelled prediction of the loss of 40% of the current tundra is a serious overestimate. A stronger focus on factors limiting the response of the forest–tundra ecotone to climate change is needed to refine the output from dynamic global vegetation models.
A KCNQ1 Mutation Causes a High Penetrance for Familial Atrial Fibrillation
Authors: BARTOS DANIEL C. , ANDERSON JEFFREY B. , BASTIAENEN RACHEL , JOHNSON JONATHAN N. , GOLLOB MICHAEL H. , TESTER DAVID J. , BURGESS DON E. , HOMFRAY TESSA , BEHR ELIJAH R. , ACKERMAN MICHAEL J. , GUICHENEY PASCALE , DELISLE BRIAN P.
Published: December 2012

R231H Causes a High Penetrance for Familial AF

Background

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its incidence is expected to grow. A genetic predisposition for AF has long been recognized, but its manifestation in these patients likely involves a combination of rare and common genetic variants. Identifying genetic variants that associate with a high penetrance for AF would represent a significant breakthrough for understanding the mechanisms that associate with disease.

Method and Results

Candidate gene sequencing in 5 unrelated families with familial AF identified the KCNQ1 missense mutation p.Arg231His (R231H). In addition to AF, several of the family members have abnormal QTc intervals, syncope or experienced sudden cardiac arrest or death. KCNQ1 encodes the voltage‐gated K+ channel that conducts the slowly activating delayed rectifier K+ current in the heart. Functional and computational analyses suggested that R231H increases KCNQ1 current (IKCNQ1) to shorten the atrial action potential (AP) duration. R231H is predicted to minimally affect ventricular excitability, but it prevented the increase in IKCNQ1 following PKA activation. The unique properties of R231H appeared to be caused by a loss in voltage‐dependent gating.

Conclusions

The R231H variant causes a high penetrance for interfamilial early‐onset AF. Our study indicates R231H likely shortens atrial refractoriness to promote a substrate for reentry. Additionally, R231H might cause abnormal ventricular repolarization by disrupting PKA activation of IKCNQ1. We conclude genetic variants, which increase IKs during the atrial AP, decrease the atrial AP duration, and/or shorten atrial refractoriness, present a high risk for interfamilial AF.
Quality of interaction between at‐risk infants and caregiver at 12–15 months is associated with 3‐year autism outcome
Authors: Wan Ming Wai , Green Jonathan , Elsabbagh Mayada , Johnson Mark , Charman Tony , Plummer Faye ,   the BASIS Team
Published: December 2012

Background:  Recent models of the early emergence of autism spectrum disorder (ASD) propose that infant intrinsic risk susceptibilities in behaviour may be amplified by interaction within the early social environment into an increasingly atypical developmental trajectory. This study examines whether 6‐ and 12‐month parent–infant interactions in at‐risk siblings differ from those with low‐risk and whether – in at‐risk siblings – such interactions predict later 3‐year classification of ASD or no ASD.

Method:  Within the British Autism Study of Infant Siblings (BASIS), 6‐min videotaped episodes of parent–infant free play in infants at 6–10 months (45 at‐risk siblings and 47 low‐risk siblings) and 12–15 months (43 at‐risk siblings and 48 low‐risk siblings) in a laboratory setting were rated on the Manchester Assessment of Caregiver‐Infant Interaction (MACI), blind to participant information. Standard tests were administered for concurrent behavioural signs of ASD features and developmental level. Systematic consensus diagnostic classification of ASD was made at 3 years for the at‐risk siblings.

Results:  Parent nondirectiveness and sensitive responsiveness differed in relation to ASD/risk status (at‐risk ASD, at‐risk no‐ASD and low‐risk) at both 6 and 12 months. At 6 months, infant liveliness was lower in the at‐risk groups; at 12 months, infant attentiveness to parent and positive affect were lower in the at‐risk group later diagnosed with ASD. Dyadic mutuality and intensity of engagement showed a group effect at 12 months. Dyadic mutuality, infant positive affect and infant attentiveness to parent at 12 months (but not 6 months) predicted 3‐year ASD outcome, whereas infant ASD‐related behavioural atypicality did not.

Conclusions:  This is the first prospective evidence that early dyadic interaction between at‐risk infants and their parents is associated with later diagnostic outcome in ASD. Possible explanations for these findings and their theoretical implications are considered.
Combined examination of glyceryl trinitrate‐mediated vascular dilation with flow‐mediated vascular dilation is essential for assessment of vascular function in type 2 diabetes
Authors: Furuta Machi , Ueyama Minoru , Morita Shuhei , Yamana Akiko , Sanke Tokio
Published: December 2012

Aims/Introduction

In order to characterize the impaired vascular function in type 2 diabetes (DM) patients, we evaluated the flow‐mediated vascular dilation (FMD) with glyceryl trinitrate‐mediated vascular dilation (NMD) using ultrasonography.

Materials and Methods

A total of 111 DM patients and 42 healthy control participants were studied. The maximal dilatation of FMD and NMD (%FMD and %NMD, respectively), the beginning time (T) of dilatation after stimulation and the velocity (V) of the vascular dilatation were also measured.

Results

Among DM patients, 49% had impaired %NMD, which affects the results of %FMD. In DM patients with normal %NMD, the %FMD was also significantly lower than that in control participants, although the T and the V were not impaired. In contrast, both the T and the V were disturbed in the DM patients with low %NMD. Multiple linear regression analysis showed that %NMD was independently correlated with albuminuria. Our results indicate that the impaired FMD in DM is be affected by low NMD, and impaired endothelial function already exists even in DM patients whose vascular smooth muscle function is still retained, and also albuminuria is the clinical feature of DM with low %NMD.

Conclusions

Examination of NMD, not only FMD, should be carried out as it offers the possibility of clarifying vascular function in DM patients.
Hydrological analysis for water level projections in Taihu Lake, China
Authors: Liu L. , Xu Z.X. , Reynard N.S. , Hu C.W. , Jones R.G.
Published: December 2012

Changes in precipitation can be expected to have a major influence on the frequency and severity of flooding in the Taihu Basin. As part of an integrated assessment of flood risk in the Taihu Basin, this paper addresses the hydrological conditions and the potential impacts of climate change on Taihu Lake water levels. The hydrological system is simulated by using the distributed hydrological model VIC (Variable Infiltration Capacity), with future climate scenarios generated by the regional climate model PRECIS (Providing Regional Climates for Impacts Studies). The results indicate that maximum and mean flood water levels under the A2 and B2 scenarios for 2021–2050 will be higher than the levels during the baseline period (1961–1990), with larger increases under the B2 scenario than for the A2 scenario. The storm return periods leading to extreme water levels in the Taihu Lake in the future is projected to decrease significantly in comparison to the baseline period, implying the potential for the more frequent occurrence of major floods. These results indicate the importance of planning for future flood control in the Taihu Basin.
A comparative evaluation of flood mitigation alternatives using GIS‐based river hydraulics modelling and multicriteria decision analysis
Authors: Ghanbarpour M.R. , Salimi S. , Hipel K.W.
Published: December 2012

A multicriteria framework is developed for the selection of optimal flood mitigation and river training measures in a selected reach of Zaremroud River in Northern Iran. A river model, Hydrologic Engineering Center River Analysis System, combined with geographic information system analysis is used to simulate water levels for steady, gradually varied flow and mapping inundated flood extents. The modelling is performed for four different alternatives, considering various channel modifications with different dimensions and levee construction. Flood inundation area, flood level, flow velocity and stream power on the downstream and outside of the river bend are used as decision criteria for each alternative. Economic analysis is conducted to evaluate the cost‐effectiveness of each alternative. The decision analysis method, technique for order of preference by similarity to ideal solution, is used to compare different flood hazard mitigation measures based on risk, and environmental and economic impacts criteria. The findings of the analysis are that a levee construction at the right side of the river bank adjacent to the residential area is superior to the other three alternatives, which is confirmed using a scenario analysis of different flood mitigation measures.
Pharmacological analysis of the cortical neuronal cytoskeletal protective efficacy of the calpain inhibitor SNJ‐1945 in a mouse traumatic brain injury model
Authors: Bains Mona , Cebak John E. , Gilmer Lesley K. , Barnes Colleen C. , Thompson Stephanie N. , Geddes James W. , Hall Edward D.
Published: December 2012

The efficacy of the amphipathic ketoamide calpain inhibitor SNJ‐1945 in attenuating calpain‐mediated degradation of the neuronal cytoskeletal protein α‐spectrin was examined in the controlled cortical impact (CCI) traumatic brain injury (TBI) model in male CF‐1 mice. Using a single early (15 min after CCI‐TBI) i.p. bolus administration of SNJ‐1945 (6.25, 12.5, 25, or 50‐mg/kg), we identified the most effective dose on α‐spectrin degradation in the cortical tissue of mice at its 24 h peak after severe CCI‐TBI. We then investigated the effects of a pharmacokinetically optimized regimen by examining multiple treatment paradigms that varied in dose and duration of treatment. Finally, using the most effective treatment regimen, the therapeutic window of α‐spectrin degradation attenuation was assessed by delaying treatment from 15 min to 1 or 3 h post‐injury. The effect of SNJ‐1945 on α‐spectrin degradation exhibited a U‐shaped dose–response curve when treatment was initiated 15 min post‐TBI. The most effective 12.5 mg/kg dose of SNJ‐1945 significantly reduced α‐spectrin degradation by ~60% in cortical tissue. Repeated dosing of SNJ‐1945 beginning with a 12.5 mg/kg dose did not achieve a more robust effect compared with a single bolus treatment, and the required treatment initiation was less than 1 h. Although calpain has been firmly established to play a major role in post‐traumatic secondary neurodegeneration, these data suggest that even brain and cell‐permeable calpain inhibitors, when administered alone, do not show sufficient cytoskeletal protective efficacy or a practical therapeutic window in a mouse model of severe TBI. Such conclusions need to be verified in the human clinical situation.
Nineteenth Century Wood Engravers at Work: Mass Production of Illustrated Periodicals (1840–1880)
Authors: Martin Michèle
Published: December 2012

This paper traces the labour processes and working conditions of wood engravers in France and England during the 19th century as the process of production of the illustrated periodicals became increasingly industrialized. It argues that the bulk of 19th century wood engravers should be considered as one of the first classes of proletarians in the mass media industry. The paper first looks at the general socio‐economic conditions from which 19th century wood engravers emerged as proletarians. Second, it examines wood engraving workshops, wood engravers' working conditions, their training and type of production. Lastly, it discusses the hierarchical relations between editors‐publishers and wood engravers, the wood engravers economic conditions, their socio‐cultural attitudes towards their work and the control exercised on them in the labour process. With the industrialization of the production of illustrated periodicals, wood engravers formed a class of waged workers who owned no means of production, had little autonomy or creativity in their work and sold their labour power to fabricate illustrations. Workshops operated as factories, training apprentices to mechanically reproduce fragmented segments of illustrations in an assembly‐line type of labour and based on a rigid hierarchy in which engraver‐apprentices were at the bottom.
Promiscuous Intimacies: Rethinking the History of American Casual Sex
Authors: Reay Barry
Published: December 2012

Casual sex has become a cultural commonplace since it was named in the 1960s and later became associated with the US college sex phenomenon of “hooking up”. However, contemporary accounts of this sexual practice are curiously lacking in historical perspective. This article explores this modern history, both before and after uncommitted, non‐romantic, sexual encounters – sex for sex's sake – were named as casual sex. It agues that studies that contrast the increased “sexual possibilities” of hookup sex to the assumed restrictive practices of an earlier era distort both the restrictions of the earlier period and the freedoms of the latter.
Hepatitis E: source and route of infection, clinical manifestations and new developments
Authors: Scobie L. , Dalton H. R.
Published: December 2012

Hepatitis E was previously thought to be a disease of developing countries causing significant morbidity and mortality in young adults, particularly among pregnant women and patients with pre‐existing chronic liver disease. Recent studies have shown that hepatitis E is also an issue in developed countries. In this setting, hepatitis E is a zoonotic infection and causes acute infection mainly in middle‐aged and elderly men; and chronic infection in the immunosuppressed. The scope and burden of disease are still emerging. The diagnosis of hepatitis E should be considered in any patient with hepatitis, irrespective of their age or travel history.
The role of protostellar jets in star formation and the evolution of the early solar system: Astrophysical and meteoritical perspectives
Authors: SALMERON Raquel , IRELAND Trevor
Published: December 2012

Abstract– The rock record from the early solar system indicates high‐temperature thermal processing sufficient to melt refractory oxides and silicates. The astrophysical context for the formation and evolution of our solar system, from a molecular cloud to a “clean” planetary system, is difficult to constrain tightly because of the large scales and lack of resolution of astronomical observations. Protostellar jets and winds, commonly associated with forming stars, are likely to play a role in heating and redistribution of the processed material in the solar system. We have recently proposed that disk‐winds can cause melting of small inclusions to distances out to several AU. Particularly energetic outbursts, such as the FU‐Orionis and EXor events, occur over relatively short time scales (approximately 100 and 1 yr, respectively), and are probably events related to formation of the refractory solids present in primitive meteorites.
Oxygen isotopic zoning of reversely zoned melilite crystals in a fluffy type A Ca‐Al‐rich inclusions from the Vigarano meteorite
Authors: KATAYAMA Juri , ITOH Shoichi , YURIMOTO Hisayoshi
Published: December 2012

Abstract– The oxygen isotopic microdistributions within melilite measured using in situ secondary ion mass spectrometry correspond to the chemical zoning profiles in single melilite crystals of a fluffy type A Ca‐Al‐rich inclusions (CAIs) of reduced CV3 Vigarano meteorite. The melilite crystals show chemical reverse zoning within an individual single crystal from the åkermanite‐rich core to the åkermanite‐poor rim. The composition changes continuously with the crystal growth. The zoning structures suggest that the melilite grew in a hot nebular gas by condensation with decreasing pressure. The oxygen isotopic composition of melilite also changes continuously from 16O‐poor to 16O‐rich with the crystal growth. These observations suggest that the melilite condensation proceeded with change consistent with an astrophysical setting around the inner edge of a protoplanetary disk where both 16O‐rich solar coronal gas and 16O‐poor dense protoplanetary disk gas could coexist. Fluffy type A CAIs could have been formed around the inner edge of the protoplanetary disk surrounding the early sun.
A new three‐dimensional analysis of asymmetry for patients with craniofacial syndromes
Authors: Yáñez‐Vico R‐M , Iglesias‐Linares A , Torres‐Lagares D , Gutiérrez‐Pérez J‐L , Solano‐Reina E
Published: December 2012

Objecives

The use of three‐dimensional computed tomography (3D‐CT) analyses represents a substantial improvement in planning treatment. The aim of this study is to introduce a new three‐dimensional (3D) analysis of clinical value for evaluating asymmetry in cases of craniofacial syndrome.

Subjects and methods

Virtual 3D models were reconstructed from CT images of 62 normal subjects (35 males and 27 females), more than 18 years old. Measurements of asymmetrical skeletal and dentoalveolar relationships were evaluated and standardized data obtained. The feasibility of the new 3D craniofacial analysis was then evaluated on one patient with severe maxillomandibular asymmetry in the form of hemifacial microsomia.

Results

Standardized 3D data from the analysis were obtained and classified into 6 maxillary measurements, eight mandibular measurements and seven dentoalveolar process measurements. No significant differences were found between males and females (U‐Mann–Whitney test, P > 0.05). Useful data of clinical value was provided for planning orthodontic and surgical treatment of asymmetries, as well as a diagnostic chart.

Conclusion

This method is useful for the clinical evaluation of asymmetry in craniofacial syndromes. The use of 3D analysis facilitates surgical and orthodontic treatment planning.