bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Christianity Save Civilisation?: Liberal Protestant Anti‐Secularism in Interwar America
Authors: Edwards Mark
Published: July 2014

This article explores the geopolitics of liberal evangelicalism, Christian Realism, and the ecumenical movement as collective responses to the rise of “secularism” after World War I. Alternatively, it considers how liberal Protestants looked to Roman Catholicism for support in their defence of the Christian identity of the United States and the West more generally. The long history of Christian anti‐secularism in America complicates familiar portraits of liberal Protestants as agents of secularisation.
An Investigation of Red Fox (Vulpes vulpes) and Eurasian Badger (Meles meles) Scavenging, Scattering, and Removal of Deer Remains: Forensic Implications and Applications
Authors: Young Alexandria , Márquez‐Grant Nicholas , Stillman Richard , Smith Martin J. , Korstjens Amanda H.
Published: July 2014

Within northwest Europe, especially the United Kingdom, the red fox (Vulpes vulpes) and the Eurasian Badger (Meles meles) are the largest wild scavengers capable of modifying a set of remains through scavenging. Knowledge of region‐specific and species‐typical scavenging behaviors of scavengers within the crime scene area and surroundings can aid in more efficient and accurate interpretations. The scavenging behaviors of captive and wild foxes and badgers were recorded and compared through actualistic methods and direct observation. The scavenging by wild foxes and badgers of surface‐deposited baits and whole deer (Cervus nippon; Capreolus capreolus) in a woodland was observed and analyzed. Wild foxes were found to scavenge deer more frequently than badgers. The scavenging of deer remains by foxes was also compared with forensic cases. The scavenging pattern and recovery distances of deer and human remains scavenged by foxes were similar but were potentially affected by the condition and deposition of a body, and the presence of clothing.
The Analysis of a World War I U.S. Service Member's Dental Remains Recovered in France
Authors: Shiroma Calvin Y.
Published: July 2014

In October 2009, the grave of an unknown World War I (WWI) U.S. service member was exhumed in Rembercourt‐Sur‐Mad Village, in the Lorraine Region of France. The skeletal remains and material evidence were accessioned into the Joint POW/MIA Accounting Command's (JPAC) Central Identification Laboratory (CIL). The personnel records for the associated casualty were requested, received, and reviewed. A dental profile was present among the service member's personal information. There were multiple points of concordance between the dental records of the associated casualty, and the recovered dental remains to include eight restored teeth, 15 unrestored teeth, and three antemortem missing teeth. Distinctive restorations which compared favorably included a porcelain crown and multiple gold foil fillings. All lines of evidence (historical, material evidence/personal effects, anthropological, and dental) and the circumstances of loss compared positively with the associated casualty. On April 1, 2010, the previously unaccounted‐for U.S. service member was positively identified and on June 23, 2010, was buried with full military honors at Arlington National Cemetery.
Surface Modification for the Collection and Identification of Fingerprints and Colorimetric Detection of Urea Nitrate
Authors: Cross Shoronia N. , Quinteros Elliot , Roberts Marcel
Published: July 2014

Glass surfaces were modified with a combination of dyes and reagents to allow for the potential simultaneous recording of a detailed fingerprint and the detection of the explosive urea nitrate (UN), as a proof of principle of surface modification for simultaneous linking of identity to manipulation of explosives. By coating microscope slides with 9,10‐diphenylanthracene (DPA), p‐dimethylaminobenzaldehyde (p‐DMAB) and p‐dimethylaminocinnamaldehyde (p‐DMAC), a colorimetric change was observed in the presence of UN, while revealing a fingerprint with enough resolution to isolate at least 10 minutiae. This is the first step in creating point‐of‐care devices capable of detecting low concentrations of explosives and drug metabolites and connecting them to a fingerprint.
Establishing Tobacco Origin from Pollen Identification: An Approach to Resolving the Debate
Authors: Williams Shane , Hubbard Shelby , Reinhard Karl J. , Chaves Sergio Miranda
Published: July 2014

Previous research into pollen content of tobacco resulted in a debate. We address this debate and determine that pollen analysis may be able to assist with identifying geographical origin of tobacco. However, the value of any results should be assessed on a case‐by‐case regional basis until sufficient database information is available for an objective interpretation to be undertaken on a global basis. As a first step toward developing comparative data for South America, we analyzed a tobacco sample from Brazil in an effort to identify signature taxa from the state of Minas Gerais. We also assessed the role of honey additives to tobacco to assess this issue. Comparing the data to previously published data, we conclude that pollen signatures can distinguish broad geographic areas. We conclude that this forensic interpretation framework needs to be developed in context of the National Academy of Sciences recommendations for tightening methods in forensic science.
Mid‐level providers and emergency care: Let's not lose the force
Authors: Tintinalli Judith E
Published: July 2014

The progressive rise of ED visits globally, and insufficient numbers of emergency physicians, has resulted in the use of mid‐level providers as adjuncts for the provision of emergency care, especially in the US and Canada. Military medics, midwives, aeromedical paramedics, EMT‐Ps, flight nurses, forensic nurses, sexual assault nurse examiner nurses ‐ are some examples of well‐established mid‐level provider professionals who achieve their clinical credentials through accredited training programmes and formal certification. In emergency medicine, however, mid‐level providers are trained for general care, and typically acquire emergency medicine skills through on‐the‐job experience. There are very few training programmes for NPs and PAs in emergency care. The manpower gap for physicians in general, and emergency physicians specifically, will not be eliminated in the reasonable future. Mid‐level providers – ENTs, paramedics, NPs, PAs – are an excellent addition to the emergency medicine workforce. However, the specialty of emergency medicine developed because specific and focused training was needed for physicians to practice safe and qualify emergency care. This same principle applies to mid‐level providers. Emergency Medicine needs to develop a vision and a plan to train emergency medicine specialist NPs and PAs, and explore other innovations to expand our emergency care workforce.
Review article: Maxillofacial emergencies: Oral pain and odontogenic infections
Authors: DeAngelis Adrian F , Barrowman Roland A , Harrod Richard , Nastri Alf L
Published: July 2014

Oral pain and odontogenic infections are common reasons for patients to present to EDs and general medical practice in Australia. Although most odontogenic infections can be managed on an outpatient basis, because of their proximity to the airway, infections in this region can be life threatening, requiring urgent surgical intervention and ICU management. This article focuses on the emergency assessment, triage and non‐specialist management of oral pain and odontogenic infections.
Suburban Toxicity: A Political Ecology of Asbestos in Australian Cities
Authors: HOUSTON DONNA , RUMING KRISTIAN
Published: July 2014

This paper explores the toxic legacy of asbestos in Australian suburbs and cities. During the post‐war period, Australia had one of the highest per capita rates of asbestos use in the developed world. As a consequence of this indiscriminate use, Australia also has one of the highest rates of asbestos dust disease in the world. Drawing on feminist approaches to urban political ecology (UPE) and the materialities of waste, we trace the entanglement of asbestos within the everyday spaces of homes and suburbs and through urban governance structures and processes of urban regeneration. We argue that UPE provides an important framework for putting asbestos stories and practices in the city together. UPE highlights the relational entanglements and injustices of asbestos, which render it as matter that circulates through bodies, homes, infrastructures, working‐class histories and suburban imaginaries. This approach challenges the construction of asbestos in terms of its hazardous obsolescence and resituates it as complex matter that continues to be lived with and practiced.
Erythropoietin treatment in patients with myelodysplastic syndromes and type 2 diabetes 促红细胞生成素治疗骨髓增生异常综合征合并2型糖尿病的患者
Authors: Latagliata Roberto , Alati Caterina , Carmosino Ida , Montagna Chiara , Romano Angela , Finsinger Paola , Vozella Federico , Volpicelli Paola , Breccia Massimo , Alimena Giuliana , Oliva Esther Natalie
Published: July 2014

Background

The aim of the present study was to assess the role of a concomitant type 2 diabetes as a potentially negative factor in the management of low‐risk myelodysplastic syndrome (MDS) patients treated with high‐dose (40 000 UI s.c. 2 times/week) recombinant human erythropoietin (EPO) alpha (rHuEPO alpha).

Methods

One hundred and forty patients (M/F 69/71, median age 76, interquartile range [IR] 68–81) were included in the analysis: 27/140 (19.2%) had a concomitant type 2 diabetes.

Results

No difference was reported between patients with and without diabetes as to the grade of anemia, the EPO endogenous levels and the need for transfusional requirement at baseline. Erythroid response was achieved in 79/140 patients (56.4%): factors associated with response were lower EPO levels (P < 0.0001), higher baseline Hb levels (P < 0.0001) and transfusion independence (P < 0.0001). Diabetes was not predictive of response: 17/27 (62.9%) patients with diabetes were responsive to high‐dose EPO compared with 62/113 (54.8%) patients without diabetes (P = 0.446). This was confirmed in multivariate analysis, controlling for the effects of Hb levels, transfusion‐dependence and serum EPO levels. No difference was observed in relapse rate, response duration and OS between patients with and without diabetes.

Conclusions

Concomitant type 2 diabetes was not a major concern in the management of MDS patients.
Synergy of bone marrow transplantation and curcumin ensue protective effects at early onset of diabetes in mice 在早期发病的糖尿病小鼠中使用骨髓移植和姜黄素联合治疗具有协同保护作用
Authors: Arivazhagan Arivarasan , Krishna Soni , Yadav Shivangi , Shah Harshit Rajesh , Kumar Pravir , Ambasta Rashmi Kumar
Published: July 2014

Background

The aim of this study was to investigate the early onset effects of diabetes on pro‐angiogenic signaling pathway, total number of bone marrow cells, organs (pancreas and kidney) damage and the reversal effect of diabetes by combinatorial treatment of curcumin and bone marrow transplantation in streptozotocin (STZ) induced diabetic mice.

Methods

In the present study, Streptozotocin induced diabetic mice were transplanted with bone marrow cells (2 × 106) followed by the administration of curcumin (80 mg/kg bodyweight). Effect of diabetes on the different organs was studied by H&E, Western blotting and immunofluorescence using vascular endothelial growth factor (VEGF), platelet/endothelial cell adhesion molecule (PECAM), insulin, Caspase‐9 and Caspase‐3 antibodies.

Results

The effect of diabetes results in the reduction of the total cell number and viability of the bone marrow cells, organ degeneration and lower VEGF/PECAM expression. However, transplantation with normal bone marrow cells significantly reduced the blood glucose levels (above normal range) and initiated the organ regeneration via the VEGF/PECAM mediated manner. Curcumin treatment further reduced the blood glucose level (near normal); and accelerated the organ regeneration, enhanced VEGF/PECAM expression and decreased caspase expression level in the organs. Curcumin also had a protective role against the glucotoxicity test performed on the bone marrow cells.

Conclusion

This study suggests that bone marrow transplantation and curcumin administration is an effective treatment in reversing the early onset effects of diabetes via the VEGF/PECAM signaling pathway.
Phylogenetic exploration of commonly used medicinal plants in South Africa
Authors: Yessoufou Kowiyou , Daru Barnabas H. , Muasya Abraham Muthama
Published: July 2014

The rapid growth rate of human population, along with the public health crisis encountered in many regions, particularly in developing world, creates an urgent need for the discovery of alternative drugs. Because medicinal plants are not distributed randomly across lineages, it has been suggested that phylogeny along with traditional knowledge of plant uses can guide the identification of new medicinally useful plants. In this study, we combined different statistical approaches to test for phylogenetic signal in 33 categories of plant uses in South Africa. Depending on the null models considered, we found evidence for signal in up to 45% of plant use categories, indicating the need for multiple tests combination to maximize the chance of discovering new medicinal plants when applying a phylogenetic comparative approach. Furthermore, although there was no signal in the diversity of medicinal uses—that is, total number of medicinal uses recorded for each plant—our results indicate that taxa that are evolutionarily closely related have significantly more uses than those that are evolutionarily isolated. Our study therefore provides additional support to the body of the literature that advocates for the inclusion of phylogeny in bioscreening medicinal flora for the discovery of alternative medicines.
Incentives, wages, employment, and the division of labor in teams
Authors: Rauh Michael T.
Published: July 2014

We develop a theory of incentives, wages, and employment in the context of team production. A central insight is that specialization and division of labor not only improve productivity but also increase effort and the sensitivity of effort to incentives under moral hazard. We show that employment and incentives are complements for the principal when the positive effects of specialization and division of labor outweigh the increase in risk associated with additional employment and are substitutes otherwise. We provide new characterizations of the partnership, the firm, and the role of the budget‐breaker that are quite different from the classical literature.
A systematic review and meta‐analysis of ketamine for the prevention of persistent post‐surgical pain
Authors: MCNICOL E. D. , SCHUMANN R. , HAROUTOUNIAN S.
Published: July 2014

While post‐operative pain routinely resolves, persistent post‐surgical pain (PPSP) is common in certain surgeries; it causes disability, lowers quality of life and has economic consequences. The objectives of this systematic review and meta‐analysis were to evaluate the effectiveness of ketamine in reducing the prevalence and severity of PPSP and to assess safety associated with its use.

We searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE through December 2012 for articles in any language. We included randomized, controlled trials in adults in which ketamine was administered perioperatively via any route.

Seventeen studies, the majority of which administered ketamine intravenously, met all inclusion criteria. The overall risk of developing PPSP was not significantly reduced at any time point in the ketamine group vs. placebo, nor did comparisons of pain severity scores reach statistical significance. Sensitivity analysis of exclusively intravenous ketamine studies included in this meta‐analysis demonstrated statistically significant reductions in risk of developing PPSP at 3 and 6 months (P = 0.01 and P = 0.04, respectively). Adverse event rates were similar between ketamine and placebo groups.

The study data from our review are heterogeneous and demonstrate efficacy of intravenously administered ketamine only in comparison with placebo. Highly variable timing and dosing of ketamine in these studies suggest that no unifying effective regimen has emerged. Future research should focus on clinically relevant outcomes, should stratify patients with pre‐existing pain and possible central sensitization and should enroll sufficiently large numbers to account for loss to follow‐up in long‐term studies.
RNA‐seq of the aging brain in the short‐lived fish N. furzeri – conserved pathways and novel genes associated with neurogenesis
Authors: Baumgart Mario , Groth Marco , Priebe Steffen , Savino Aurora , Testa Giovanna , Dix Andreas , Ripa Roberto , Spallotta Francesco , Gaetano Carlo , Ori Michela , Terzibasi Tozzini Eva , Guthke Reinhard , Platzer Matthias , Cellerino Alessandro
Published: July 2014

The brains of teleost fish show extensive adult neurogenesis and neuronal regeneration. The patterns of gene regulation during fish brain aging are unknown. The short‐lived teleost fish Nothobranchius furzeri shows markers of brain aging including reduced learning performances, gliosis, and reduced adult neurogenesis. We used RNA‐seq to quantify genome‐wide transcript regulation and sampled five different time points to characterize whole‐genome transcript regulation during brain aging of N. furzeri. Comparison with human datasets revealed conserved up‐regulation of ribosome, lysosome, and complement activation and conserved down‐regulation of synapse, mitochondrion, proteasome, and spliceosome. Down‐regulated genes differ in their temporal profiles: neurogenesis and extracellular matrix genes showed rapid decay, synaptic and axonal genes a progressive decay. A substantial proportion of differentially expressed genes (~40%) showed inversion of their temporal profiles in the last time point: spliceosome and proteasome showed initial down‐regulation and stress‐response genes initial up‐regulation. Extensive regulation was detected for chromatin remodelers of the DNMT and CBX families as well as members of the polycomb complex and was mirrored by an up‐regulation of the H3K27me3 epigenetic mark. Network analysis showed extensive coregulation of cell cycle/DNA synthesis genes with the uncharacterized zinc‐finger protein ZNF367 as central hub. In situ hybridization showed that ZNF367 is expressed in neuronal stem cell niches of both embryonic zebrafish and adult N. furzeri. Other genes down‐regulated with age, not previously associated with adult neurogenesis and with similar patterns of expression are AGR2, DNMT3A, KRCP, MEX3A, SCML4, and CBX1. CBX7, on the other hand, was up‐regulated with age.
Nicotine enhances modulation of food‐cue reactivity by leptin and ghrelin in the ventromedial prefrontal cortex
Authors: Kroemer Nils B. , Wuttig Franziska , Bidlingmaier Martin , Zimmermann Ulrich S. , Smolka Michael N.
Published: July 2014

Endocrine signals such as ghrelin and leptin are known to modulate the mesocorticolimbic dopaminergic system and, consequently, show associations with food and drug reward. In animal models, nicotine was demonstrated to reduce body weight by attenuating food intake and effects of leptin and ghrelin are partly modulated by nicotinic acetylcholine receptors which hint at potential interactions. However, the neuropharmacological modulation of endocrine signals by nicotine in healthy humans remains to be tested experimentally. We used functional magnetic resonance imaging to investigate food‐cue reactivity after an overnight fast and following a caloric load (oral glucose tolerance test, OGTT) in 26 healthy normal‐weight never‐smokers. Moreover, we administered either nicotine (2 mg) or placebo gums using a randomized cross‐over design and assessed blood plasma levels of ghrelin and leptin. During fasting, nicotine administration decreased correlations with ghrelin levels in the mesocorticolimbic system whereas correlations with leptin were increased. After the OGTT, nicotine increased the modulatory effects of ghrelin and leptin on food‐cue reactivity, particularly in the ventromedial prefrontal cortex (vmPFC) and the amygdala. Critically, this led to an indirect modulation of the behavioral ‘appetizer effect’ (i.e. cue‐induced increases in subjective appetite) by homeostatic feedback signals via food‐cue reactivity in vmPFC. We conclude that nicotine enhances the effect of ghrelin and leptin in the valuation and relevance network which might, in turn, reduce appetite. This highlights that amplifying the impact of homeostatic signals such as ghrelin and leptin in normal‐weight individuals might hint at a mechanism contributing to nicotine's anorexic potential.
Blood sugar levels are higher in obese young children in Sweden than in Poland
Authors: Hagman Emilia , Ighani Arani Perna , Fischer Manjula , Danielsson Pernilla , Marcinkiewicz Katarzyna , Petriczko Elzbieta , Marcus Claude
Published: July 2014

Aim

An elevated fasting glucose level is an early sign of metabolic dysfunction in obese children. This study compared fasting glucose levels in obese young children in Poland and Sweden.

Methods

We identified 109 obese children aged between two and 10 years from a Polish obesity register, with a mean BMI SDS (SD) of 3.72 (0.86). Each Polish child was matched by gender, age and degree of obesity, with ten children (n = 1090) from BORIS, the Swedish national childhood obesity treatment register. A group of 86 Swedish nonobese children served as controls.

Results

The mean fasting glucose values of the Polish, Swedish and nonobese cohorts were 4.73 (0.51) mmol/L, 4.92 (0.50) mmol/L and 4.56 (0.39) mmol/L, respectively. After adjusting for variables affecting fasting glucose, the mean glucose value of the Swedish obese children was 0.20 mmol/L higher than that of Polish obese children (p < 0.0001) and 0.41 mmol/L higher than in nonobese controls (p < 0.0001).

Conclusion

Swedish obese young children had higher glucose levels than Polish obese young children. This suggests that Swedish obese children face a higher risk of the prediabetic stage impaired fasting glycaemia.
The severity of circulating neutrophil dysfunction in patients with cirrhosis is associated with 90‐day and 1‐year mortality
Authors: Taylor N. J. , Manakkat Vijay G. K. , Abeles R. D. , Auzinger G. , Bernal W. , Ma Y. , Wendon J. A. , Shawcross D. L.
Published: July 2014

Background

Patients with cirrhosis are susceptible to sepsis, pre‐disposing to the development of encephalopathy, bleeding and organ dysfunction with associated high mortality.

Aim

To characterise circulating neutrophil function in a cirrhotic cohort as a determinant of 90‐day and 1‐year mortality.

Methods

Sixty‐two patients with cirrhosis [49 stable (Child–Pugh A/B/C = 24%/39%/37%); 13 acute‐on‐chronic liver failure] were prospectively studied and compared with 11 healthy controls. Neutrophil function was evaluated at baseline and repeated at critical points during the course of the patient's illness until death/transplantation. Neutrophil phenotype was determined using fluorochrome‐labelled antibodies to CD16/CD11b and assessed by flow cytometry. Neutrophil phagocytic activity (NPA) and capacity (NPC) were determined using FITC‐labelled opsonised Escherichia coli. Oxidative burst (OB) was quantified by the percentage of neutrophils producing reactive oxygen species (ROS) and mean fluorescence intensity at rest, and after stimulation with E. coli. Physiological variables, biochemistry, microbiology and outcomes were collected. Plasma pro‐ and anti‐inflammatory cytokine profiles were performed by ELISA.

Results

NPA/NPC was impaired in cirrhosis with the most significant dysfunction being observed in those with advanced disease and in those treated with propranolol. NPC predicted survival in stable cirrhosis [AUROC 0.83 (95% CI 0.68–0.97); P = 0.021] and differentiated survivors from nonsurvivors (90‐day P = 0.01; 1 year P < 0.001). Resting OB ≥12% predicted 90‐day mortality with 80% sensitivity and 71% specificity [AUROC 0.81 (95% CI 0.64–0.97); P = 0.026 and differentiated survivors from nonsurvivors; P = 0.015].

Conclusion

Circulating neutrophils in patients with cirrhosis are dysfunctional and predict the development of infection, organ dysfunction and survival at 90 days and 1 year.
Systematic review with meta‐analysis: the I148M variant of patatin‐like phospholipase domain‐containing 3 gene (PNPLA3) is significantly associated with alcoholic liver cirrhosis
Authors: Chamorro A.‐J. , Torres J.‐L. , Mirón‐Canelo J.‐A. , González‐Sarmiento R. , Laso F.‐J. , Marcos M.
Published: July 2014

Background

Several studies have reported an association between alcoholic liver cirrhosis (ALC) or other forms of alcoholic liver disease (ALD) and the genetic variant rs738409 (C>G) in adiponutrin/patatin‐like phospholipase domain‐containing 3 gene (PNPLA3).

Aim

To evaluate the influence of this variant on ALC and other forms of ALD.

Methods

We performed a systematic review of previous studies on the relationship between rs738409 of PNPLA3 and ALD and meta‐analysis was conducted in a random‐effects model. Calculations of the odds ratios (ORs) and their confidence intervals (CIs), tests for heterogeneity and sensitivity analyses were performed.

Results

Database search identified 11 previous studies available for inclusion with a total of 3495 patients with ALD (2087 with ALC) and 5038 controls (4007 healthy subjects and 1031 alcoholics without ALD). Patients with ALC compared to controls had a significantly higher prevalence of the G allele when comparing GG vs. CC (OR 4.30, 95% CI 3.25–5.69; P < 0.00001) or GC vs. CC genotypes (GC vs. CC: OR 1.91, 95% CI 1.67–2.17) or under a recessive or dominant model. Similar results were found when comparing separately patients with ALC vs. alcoholics without ALD or healthy subjects. An association of the G allele with ALD emerged when comparing ALD patients vs. alcoholics without ALD and/or healthy subjects although moderate to large heterogeneity was observed. Our data suggested an additive genetic model for this variant in ALD.

Conclusion

Our meta‐analysis shows that the rs738409 variant of PNPLA3 is clearly associated with alcoholic liver cirrhosis.
Disease‐specific death and metastasis do not occur in patients with Gleason score ≤6 at radical prostatectomy
Authors: Kweldam Charlotte F. , Wildhagen Mark F. , Bangma Chris H. , van Leenders Geert J.L.H.
Published: July 2014

Objectives

To assess the metastasis‐free survival (MFS) and disease‐specific survival (DSS) in men with Gleason score ≤6 prostate cancer at radical prostatectomy (RP).

Patients and Methods

We included 1101 consecutive RP patients operated between March 1985 to July 2013 at a single institution. The outcome variables were MFS and DSS. The postoperative survival was estimated by the Kaplan–Meier method.

Results

The Gleason score distribution of the study population (1101 patients) was Gleason score ≤6 (449, 41%), Gleason score 3 + 4 = 7 (436, 40%), Gleason score 4 + 3 = 7 (99, 9%) and Gleason score 8–10 (117, 11%). The median (interquartile range) postoperative follow‐up was 100 (48–150) months. During follow‐up 197 men (18%) died, of whom 42 (3.8%) died from prostate cancer‐related causes. In all, 19/1101 patients (1.7%) had documented lymph node metastasis at the time of RP: none with Gleason score ≤6, seven with Gleason score 3 + 4 = 7 (1.6%), six with Gleason score 4 + 3 = 7 (6.1%) and six with Gleason score 8–10 (5.1%). Distant metastasis occurred in 56/1101 patients (5.1%): none with Gleason score ≤6, 23 with Gleason score 3 + 4 = 7 (5.3%), 17 with Gleason score 4 + 3 = 7 (17%) and 16 with Gleason score 8–10 (14%). Disease‐specific death, stratified per Gleason‐score group was: none in ≤6, 16 (3.7%) in 3 + 4 = 7, 16 (16%) in 4 + 3 = 7 and 10 (8.5%) in 8–10 group.

Conclusion

No metastasis or disease‐specific death were seen in men with Gleason score ≤6 prostate cancer at RP, showing the negligible potential to metastasise in this large subgroup of patients with prostate cancer.
Intracystic interferon therapy in childhood craniopharyngioma: who, when and how?
Authors: Bailey Simon , Parkes Jeannette
Published: July 2014

A 13‐year‐old male presents with fluctuating visual disturbance and headaches. Imaging reveals a significant predominantly cystic suprasellar tumour, typical of a craniopharyngioma. The patient has growth hormone deficiency but the rest of the hypothalamic/pituitary axis is intact. What are the options for therapy in 2014? Specifically, is there a role for local treatment with interferon injected into the cyst cavity? The aim of management in children with craniopharyngiomas is to reduce the impact of the tumour as much as possible, while minimising the morbidity associated with treatment. There are a number of therapeutic options available: surgery, radiotherapy and the insertion of therapeutic agents directly into the tumour cyst. The role of intracystic therapy in the form of interferon is discussed; including when to use this therapeutic option and practical details of its use.
From the era of genome analysis to the era of genomic drug discovery: a pioneering example of rheumatoid arthritis
Authors: Okada Y.
Published: July 2014

Although we have obtained comprehensive catalogs of genetic risk loci that are linked to human diseases, little is known regarding how to devise a systematic strategy to integrate genetic study results with diverse biological resources. Such strategies will be crucial for providing novel insights into disease biology and for aiding drug discovery as an ultimate goal. Here we describe the current progress in this field using a pioneering example of large‐scale genetic association studies on rheumatoid arthritis (RA), an autoimmune disease characterized by inflammation and destruction of joints. Through functional and bioinformatic annotations of risk single nucleotide polymorphisms (SNPs) and genes from >100 RA risk loci identified by genome‐wide association study (GWAS) meta‐analysis, we found novel biological insights into RA pathogenicity. Further, by integrating RA genetic findings with the complete catalog of approved drugs for RA and other diseases, we provide empirical data to indicate that human genetic‐based approaches may be useful for supporting ‘genetics‐driven genomic drug discovery’ efforts in complex human traits and suggest that further development of integrative approaches should be undertaken.
Evaluating multispecies landscape connectivity in a threatened tropical mammal community
Authors: Brodie Jedediah F. , Giordano Anthony J. , Dickson Brett , Hebblewhite Mark , Bernard Henry , Mohd‐Azlan Jayasilan , Anderson Jesse , Ambu Laurentius
Published: July 2014

Habitat corridors are important tools for maintaining connectivity in increasingly fragmented landscapes, but generally they have been considered in single‐species approaches. Corridors intended to facilitate the movement of multiple species could increase persistence of entire communities, but at the likely cost of being less efficient for any given species than a corridor intended specifically for that species. There have been few tests of the trade‐offs between single‐ and multispecies corridor approaches. We assessed single‐species and multispecies habitat corridors for 5 threatened mammal species in tropical forests of Borneo. We generated maps of the cost of movement across the landscape for each species based on the species’ local abundance as estimated through hierarchical modeling of camera‐trap data with biophysical and anthropogenic covariates. Elevation influenced local abundance of banded civets (Hemigalus derbyanus) and sun bears (Helarctos malayanus). Increased road density was associated with lower local abundance of Sunda clouded leopards (Neofelis diardi) and higher local abundance of sambar deer (Rusa unicolor). Pig‐tailed macaque (Macaca nemestrina) local abundance was lower in recently logged areas. An all‐species‐combined connectivity scenario with least‐cost paths and 1 km buffers generated total movement costs that were 27% and 23% higher for banded civets and clouded leopards, respectively, than the connectivity scenarios for those species individually. A carnivore multispecies connectivity scenario, however, increased movement cost by 2% for banded civets and clouded leopards. Likewise, an herbivore multispecies scenario provided more effective connectivity than the all‐species‐combined scenario for sambar and macaques. We suggest that multispecies habitat connectivity plans be tailored to groups of ecologically similar, disturbance‐sensitive species to maximize their effectiveness.

Evaluación de la Conectividad de Terrenos Multiespecie en una Comunidad Tropical de Mamíferos
Substance use and risk of death in young offenders: A prospective data linkage study
Authors: Kinner Stuart A. , Degenhardt Louisa , Coffey Carolyn , Hearps Stephen , Spittal Matthew , Sawyer Susan M. , Patton George C.
Published: July 2014

Introduction and Aims

Young offenders are at increased risk of preventable death after release from custody, but risk factors for death in this population are poorly understood. Despite their poor health profiles, no studies have examined mortality outcomes in young people who have served community‐based orders. The aims of this study were to describe the causes and identify risk factors for death in a cohort of young offenders in Victoria, Australia.

Design and Methods

We interviewed young people serving a custodial (n = 273) or community‐based order (n = 242) in Victoria, Australia in 2002–2003. Measures included demographics and family history, offence history, experience of victimisation, mental illness, self‐harm and substance use. Deaths up to 31 December 2011 were identified through a probabilistic linkage with the National Death Index.

Results

The all‐cause crude mortality rate was 4.2 (95% confidence interval 2.7–6.8) per 1000 person years and was not significantly different for those who had served custodial and community‐based orders. Most deaths were due to drug overdose, traffic accidents or suicide. Adjusting for age, sex and order type, risk factors for death from the baseline interview included weekly use of opioids, sleeping pills or painkillers, polydrug use and injecting drug use.

Discussion and Conclusions

Young people who have served community‐based and custodial orders are at an increased risk of preventable death. Those engaging in risky substance use, particularly injecting drug use and use of multiple central nervous system depressants, are at greatest risk. There is an urgent need to develop and rigorously evaluate preventive interventions. [Kinner SA, Degenhardt L, Coffey C, Hearps S, Spittal M, Sawyer SM, Patton GC. Substance use and risk of death in young offenders: A prospective data linkage study. Drug Alcohol Rev 2015;34:46–50]
Generalized “avatar” niche shifts improve distribution models for invasive species
Authors: Larson Eric R. , Gallagher Rachael V. , Beaumont Linda J. , Olden Julian D.
Published: July 2014

Aim

Species distribution models are an invaluable tool for anticipating the potential range of invasive species. These models often improve when both native and non‐native occurrences are available for model development and validation. Therefore, how might ecologists anticipate the potential distributions for emerging invasive species that lack any or abundant non‐native range occurrences? Here, we evaluate the recent suggestion of transferring niche shifts from well‐established ‘avatar’ invaders to emerging invaders by testing if ensemble niche shifts from a group of globally invasive plants improve model predictions when each of these species is iteratively treated as an ‘emerging’ invader.

Location

Global.

Methods

We built species distribution models using Mahalanobis distance and four climatic predictors (maximum and minimum temperature and precipitation) for 26 invasive terrestrial plants from an Australian priority list of weeds. Models using only native range occurrences for each species were modified with avatar niche shifts from the remaining ensemble of 25 species based on both a typical (median) niche shift and a large (extreme) niche shift (or niche expansion). Native range and both median and extreme avatar models were then compared with total range models (developed with both native and non‐native occurrences) for performance by measures of discrimination and an approximation of calibration.

Results

Avatar niche shifts reduced errors of omission for known non‐native occurrences relative to native range models, with a trade‐off of increased errors of commission of lesser magnitude. Further, our approximation of model calibration measured relative to total range models improved with avatar niche shifts. Differences between native range and avatar models were most pronounced for the larger ‘extreme’ avatar niche shifts (or expansion) based on increased niche size and decreased (towards 0) covariance among climatic axes.

Main conclusions

We suggest that researchers and managers evaluating risk of invasion of their jurisdiction by emerging data‐poor invaders modify native range models with observed avatar niche shifts from ensembles of well‐studied invaders. Alternative implementations of the avatar invader concept are discussed and research needs for methodological improvements proposed. Despite these opportunities for improved implementation of avatar niche shifts, ample evidence now supports that researchers should expect models based on only native ranges to underestimate or misrepresent the total range for data‐poor emerging invaders. Avatar niche shifts (and specifically expansion) from well‐studied species offer a precautionary means to anticipate the extent to which native range models may underestimate total ranges.
Clinical course of gastrointestinal stromal tumor diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration
Authors: Sekine Masanari , Imaoka Hiroshi , Mizuno Nobumasa , Hara Kazuo , Hijioka Susumu , Niwa Yasumasa , Tajika Masahiro , Tanaka Tsutomu , Ishihara Makoto , Ito Seiji , Misawa Kazunari , Ito Yuichi , Shimizu Yasuhiro , Yatabe Yasushi , Ohnishi Hirohide , Yamao Kenji
Published: July 2014

Background and Aim

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of the gastrointestinal tract. However, little is known about the clinical presentation of GIST, especially small lesions. The purpose of the present study was to clarify the efficacy of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) for the diagnosis of GIST and to determine its clinical course.

Methods

Pathological and clinical records of GIST extracted from our institutional database between 1996 and 2012 were reviewed. All GIST cases were diagnosed pathologically by surgical specimen or EUS‐FNA. To examine the efficacy of EUS‐FNA for the diagnosis of GIST, the pathological findings of EUS‐FNA were compared with the surgical findings from resected cases. Next, to clarify the clinical presentation of GIST, imaging findings and changes in tumor size over time were evaluated in follow up.

Results

Of 84 cases of GIST, 67 were resected surgically after EUS‐FNA; tumor size was <20 mm in 19 patients, and ≥20 mm in 48 patients. For the diagnosis of small GIST<20 mm, sensitivity and positive predictive value of EUS‐FNA were 81.3% and 100%, respectively. A total of 27 patients with GIST was follow up for more than 1 year. Tumor size increased significantly during follow up. However, generalized linear analysis showed that there was no significant relationship between tumor size and follow up period.

Conclusions

The present results showed that even small GIST can be correctly identified by EUS‐FNA. Moreover, size of small GIST increased significantly during follow up.
Role of γ‐aminobutyric acid signalling in the attenuation of counter‐regulatory hormonal responses after antecedent hypoglycaemia in healthy men
Authors: Klement J. , Mergelkuhl B. , Born J. , Lehnert H. , Hallschmid M.
Published: July 2014

The attenuated counter‐regulatory response to hypoglycaemia after antecedent hypoglycaemic episodes has been observed in animals to be associated with an increase in γ‐aminobutyric acid (GABA) signalling. We therefore tested the hypothesis that the pharmacological suppression of GABAergic activity during a repeated hypoglycaemic episode enhances counter‐regulatory responses. Fourteen healthy men participated in two experimental sessions each comprising three insulin‐induced hypoglycaemic episodes. Before the third hypoglycaemic episode, participants received the GABA‐antagonistic drug modafinil (200 mg orally) and placebo, respectively. In the placebo condition, the secretion of norepinephrine, adrenocorticotropic hormone, cortisol and growth hormone, and the perception of neuroglycopenic symptoms were attenuated during the third as compared with the first hypoglycaemic episode (each p < 0.05). Modafinil reversed this effect for the noradrenergic response (p < 0.05), while not significantly altering the attenuation of other hormonal responses and symptom perception (p > 0.3). Our findings indicate that increased GABAergic transmission could contribute to aspects of the attenuated counter‐regulatory response after recurrent hypoglycaemia in humans.
Effect of sitagliptin therapy on triglyceride‐rich lipoprotein kinetics in patients with type 2 diabetes
Authors: Tremblay A. J. , Lamarche B. , Kelly I. , Charest A. , Lépine M.‐C. , Droit A. , Couture P.
Published: July 2014

Aim

To investigate the effects of sitagliptin therapy on the kinetics of triglyceride‐rich lipoprotein (TRL) apolipoprotein (apo)B‐48, VLDL apoB‐100, apoE and apoC‐III in patients with type 2 diabetes.

Methods

Twenty‐two subjects with type 2 diabetes were recruited in this double‐blind crossover study, during which the subjects received sitagliptin (100 mg/day) or placebo for a 6‐week period each. At the end of each phase of treatment, the in vivo kinetics of the different apolipoproteins were assessed using a primed‐constant infusion of l‐[5,5,5‐D3]leucine for 12 h, with the participants in a constantly fed state.

Results

Sitagliptin therapy significantly reduced fasting plasma triglyceride (−15.4%, p = 0.03), apoB‐48 (−16.3%, p = 0.03) and free fatty acid concentrations (−9.5%, p = 0.04), as well as plasma HbA1c (placebo: 7.0% ± 0.8 vs. sitagliptin: 6.6% ± 0.7, p < 0.0001) and plasma glucose levels (−13.5%, p = 0.001), without any significant effect on insulin levels. Kinetic results showed that treatment with sitagliptin significantly reduced the pool size of TRL apoB‐48 by −20.8% (p = 0.03), paralleled by a reduction in the production rate of these particles (−16.0%, p = 0.03). The VLDL apoB‐100 pool size was also significantly decreased by sitagliptin therapy (−9.3%, p = 0.03), mainly because of a reduction in the hepatic secretion of these lipoproteins, although this difference did not reach statistical significance (−9.2%, p = 0.06).

Conclusions

Treatment with sitagliptin for 6 weeks reduced triglyceride‐rich apoB‐containing lipoprotein levels by reducing the synthesis of these particles.
Trade openness and government size of small developing countries
Authors: Lin Faqin , Li Bing , Sim Nicholas C. S.
Published: July 2014

This paper examines the causal effect that trade openness has on government size in small developing countries (SDCs). We use the construction of the trade cost variables based on Baltic Dry Index in primary goods as instruments of trade openness to address the endogeneity issue. We find that the increase in trade openness leads to an increase in government size: a 1 percent expansion in trade openness (trade GDP ratio) raises government consumption over GDP ratio by approximately 0.1–0.2 percentage points on average. Its quantitative significance emphasizes the importance of rethinking the costs and benefits of trade openness for SDCs.
Impact of deferred grazing and fertilizer on herbage production, soil seed reserve and nutritive value of native pastures in steep hill country of southern Australia
Authors: Nie Z. N. , Zollinger R. P. , Behrendt R.
Published: July 2014

Developing sustainable grazing management systems based on perennial species is critical to preventing land degradation in marginal land classes. A field study was conducted from 2002 to 2006 to identify the impacts of deferred grazing (no defoliation of pastures for a period generally from spring to autumn) and fertilizer application on herbage accumulation, soil seed reserve and nutritive value in a hill pasture in western Victoria, Australia. Three deferred grazing strategies were used: short‐term deferred grazing (no defoliation between October and January), long‐term deferred grazing (no defoliation from October to the autumn break) and optimized deferred grazing (withholding time from grazing commenced between annual grass stem elongation and seed head emergence and concluded in February/March). These treatments were applied with two fertilizer levels (with or without fertilizer at 50 kg phosphorus ha−1 and 2000 kg lime ha−1 applied in year 1 only) in a factorial arrangement and two additional treatments: continuous grazing (CG) and no grazing (NG) in year 1. The deferred grazing treatments on average produced herbage dry matter of 4773 kg ha−1, the NG produced 4583 kg ha−1 and the CG produced 3183 kg ha−1 in year 4 (2005–06) of the experiment. Deferred grazing treatments with and without fertilizer application produced an average of 5135 and 4411 kg DM ha−1 respectively. Averaged over 4 years, deferred grazing increased the germinable seed pool of perennial grasses by 200% and annual grasses by 50% (except optimized deferred grazing that considerably decreased the annual grass seed pool) compared with the CG. The best of the deferred grazing strategies increased the digestibility of pastures by 7% compared with the CG. The results demonstrated that deferred grazing from spring to autumn followed by rotational grazing could be an effective tool to increase herbage production and soil seed pool and improve the digestibility of native pastures in the steep hill country of southern Australia.
Association between nutritional screening via the Controlling Nutritional Status index and bone mineral density in chronic liver disease of various etiologies
Authors: López‐Larramona Germán , Lucendo Alfredo J. , Tenías José María
Published: July 2014

Aim

Bone density disorders are prevalent in patients with chronic liver disease (CLD), who commonly present with hepatic osteodystrophy. However, the relationship between nutritional status and bone mineral density (BMD) has been scarcely studied in CLD.

Methods

This single‐center, cross‐sectional study included outpatients consecutively diagnosed with CLD during a 1.5‐year period. The nutritional status was assessed with the Controlling Nutritional Status (CONUT) index; dual‐energy X‐ray absorptiometry scans and parameters of bone mineral metabolism were carried out. Bone fracture risk was estimated with the World Health Organization FRAX tool.

Results

Among the 126 patients recruited (58.7% male), osteopenia and osteoporosis were present in 31.1% and 10.7%, respectively. The 10‐year fracture risk was significantly higher among women. Malnutrition estimated with the CONUT index was present in 29.9% of patients and was significantly more frequent in cirrhotic patients, 63.4% of whom were malnourished. Malnutrition stage directly correlated with hepatic function as expressed by the Model for End‐Stage Liver Disease index. A non‐significant relationship between CONUT‐assessed nutritional status and BMD was documented. 25‐Hydroxyvitamin‐D3 (25[OH]‐D3) and fracture risk correlated positively with the CONUT stage, and total cholesterol had an inverse relationship with BMD.

Conclusion

Malnutrition assessed by the CONUT was very frequent in patients with liver cirrhosis. The CONUT score inversely correlated with liver function, while malnutrition stage directly correlated with BMD, fracture risk and 25(OH)‐D3. Total cholesterol showed a negative association with BMD in this population.