bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytoreductive radiofrequency ablation in patients with metastatic renal cell carcinoma (RCC) with small primary tumours treated with sunitinib or interferon‐α
Authors: Tsimafeyeu Ilya , Zart Janie S. , Chung Bin
Published: June 2013

Objectives

To evaluate the role of cytoreductive radiofrequency ablation (cRFA) in patients with metastatic renal cell carcinoma (RCC) with small primary tumours treated with immuno‐ or targeted therapy.

To assess the efficacy of sunitinib in patients with metastatic RCC with unresected small primary tumours.

Patients and Methods

Three parallel single‐arm prospective studies were conducted. Eligibility criteria were nearly identical for all trials and included: histopathologically confirmed RCC; metastatic measurable disease; size of primary tumour <5 cm; good or intermediate prognosis according to the Memorial Sloan‐Kettering Cancer Center model; and no previous therapy.

Study 1: Patients were treated with percutaneous cRFA under computed tomography guidance followed by interferon (IFN)‐α, 9 MIU, s.c., three times per week. Study 2: Patients received cRFA followed by sunitinib in repeated 6‐week cycles of 50 mg/day orally for 4 weeks, then 2 weeks off treatment. Study 3: Patients with unresected primary RCC received sunitinib alone. The primary endpoint was progression‐free survival (PFS).

Results

Baseline patient characteristics (age, gender, histology, Eastern Cooperative Oncology Group performance status, metastatic sites, primary tumour size) were similar in all three studies.

Efficacy data for 114 evaluable patients showed an objective response rate of 8% (95% confidence interval [CI] 4.5, 10.5) for study 1, 28.9% (95% CI 15.2, 34) for study 2, and 31.6% (95% CI 20.3, 38.9) for study 3. The median (95% CI) PFS times were 9.1 (6.9, 10.2), 13.4 (9.8, 14.4) and 12.7 (11.3, 13.5) months for studies 1, 2 and 3, respectively.

Objective response rate was significantly higher and PFS significantly longer in the sunitinib trials than in study 1 (P < 0.01 all differences); no differences were found between studies 2 and 3 (objective response rate, P = 0.1; PFS, P = 0.6). Study 1 met its primary endpoint, showing that PFS was significantly longer than the expected 5 months (P = 0.02).

The median (95% CI) overall survival (OS) times were greater in study 2 (cRFA/sunitinib) and study 3 (sunitinib‐alone) than in study 1 (IFN‐α) at 27.2 (22.6, 31.8) and 22.5 (20.7, 24.3) vs 19.5 (16.3, 22.7) months, respectively. Differences were significant (study 1 vs 2, hazard ratio [HR] = 0.55; P = 0.003; study 1 vs study 3 HR = 0.6, P = 0.01). OS was significantly longer in the cRFA/sunitinib group compared with the sunitinib‐alone group (HR = 0.71; P = 0.04).

There were no unexpected toxicities of medical treatment or complications of cRFA.

Conclusions

cRFA is a safe and effective approach for select patients with metastatic RCC treated with immunotherapy.

The cRFA technique did not improve PFS in patients treated with sunitinib; cRFA probably has impact on OS in these patients. This needs to be tested in a larger trial.

Sunitinib was effective in patients with metastatic RCC with unresected small primary tumours.
The mitogen‐inducible gene‐6 is involved in regulation of cellular senescence in normal diploid fibroblasts
Authors: Xie Bushan , Zhao Lin , Chen Hao , Jin Bo , Mao Zebin , Yao Zhi
Published: June 2013

Background information

The mitogen‐inducible gene‐6 (Mig‐6) is a non‐kinase scaffolding adaptor protein. It has been shown that Mig‐6 may play important roles in regulating stress response, maintaining homeostasis and functioning as a tumour suppressor. In this study, we investigated the role of Mig‐6 in cellular senescence.

Results

Our results showed that Mig‐6 is up‐regulated during the senescence process. Functional analysis indicated that cells over‐expressing Mig‐6 have reduced DNA synthesis and showed the signs of senescence. Knockdown of Mig‐6 delayed the initiation of Ras‐induced cellular senescence. These results suggest that the increase of Mig‐6 expression contributes to establishment of cellular senescence. Furthermore, our results showed that Mig‐6 induction of senescence is related to its inhibition of EGF receptor (EGFR)/Erb B signalling. Subsequent analysis of the mechanism responsible for the up‐regulation of its expression showed that FOXO3A transcriptionally up‐regulates Mig‐6 expression via directly binding to the FOXO response element in Mig‐6 5′‐flanking regulatory sequences.

Conclusions

Mig‐6 induces premature senescence via functioning in regulation of cellular senescence in normal diploid fibroblasts.
TAK1 Inhibition in the DFG‐Out Conformation
Authors: Kilty Iain , Green Martin P. , Bell Andrew S. , Brown David G. , Dodd Peter G. , Hewson Christopher , Hughes Samantha J. , Phillips Christopher , Ryckmans Thomas , Smith Robert T. , van Hoorn Willem P. , Cohen Philip , Jones Lyn H.
Published: June 2013

The first example of an inhibitor of the kinase TAK1 that binds in the DFG‐out conformation is disclosed. These preliminary studies used kinase‐targeted screening and structure‐based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell‐based, anti‐inflammatory assay.
High variability in baseline urinary free cortisol values in patients with Cushing's disease
Authors: Petersenn S. , Newell‐Price J. , Findling J. W. , Gu F. , Maldonado M. , Sen K. , Salgado L. R. , Colao A. , Biller B. M. K. ,   Pasireotide B2305 Study Group
Published: June 2013

Objective

Twenty‐four‐hour urinary free cortisol (UFC) sampling is commonly used to evaluate Cushing's syndrome. Because there are few data on UFC variability in patients with active Cushing's disease, we analysed baseline UFC in a large patient cohort with moderate‐to‐severe Cushing's disease and assessed whether variability correlates with hypercortisolism severity. These data will help clinicians establish the minimum number of UFC samples required to obtain reliable data.

Design

Observational study (enrolment phase of Phase III study).

Methods

Patients (n = 152) with persistent/recurrent or de novo Cushing's disease and mean UFC (mUFC) ≥1·5×ULN (normal: 30–145 nmol/24 h) were included. Mean UFC level was calculated from four 24‐h urine samples collected over 2 weeks.

Results

Over 600 24‐h UFC samples were analysed. The mUFC levels of samples 1 and 2 and samples 3 and 4 were 1000 nmol/24 h (SD 1872) and 940 nmol/24 h (SD 2148), respectively; intrapatient coefficient of variation (CV) was 38% for mUFC. The intrapatient CV using all four samples was 52% (95% CI: 48–56). The intrapatient CV was 51% (95% CI: 44–58) for samples 1 and 2, 49% (95% CI: 43–56) for samples 3 and 4 and 54% (95% CI: 49–59) for samples 1, 2 and 3. Variability in mUFC increased as UFC levels increased. There were no correlations between UFC and clinical features of hypercortisolism.

Conclusions

There is intrapatient variability of approximately 50% in 24‐h UFC measurements, which is relevant to targets set to estimate any treatment effect. Analysing more than two 24‐h collection periods in individual patients does not result in a relevant decrease in variability. Interestingly, UFC levels did not correlate with hypercortisolism severity.
Operationalizing the Resilience of Coral Reefs in an Era of Climate Change
Authors: Mumby Peter J. , Wolff Nicholas H. , Bozec Yves‐Marie , Chollett Iliana , Halloran Paul
Published: June 2013

Ecosystem management frequently aims to manage resilience yet measuring resilience has proven difficult. Here, we quantify the ecological resilience of the largest reef in the Caribbean and map potential benefits of marine reserves under two scenarios of greenhouse gas emissions. Resilience is calculated using spatial ecological models and defined as the probability of a reef remaining in its coral‐dominated basin of attraction such that it does not flip into an alternate, algal‐dominated attractor. In practice, resilience is the probability that coral populations will maintain the ability to exhibit a recovery trend after acute disturbances such as hurricanes. The inputs required to estimate resilience are a reef's initial state, physical environment, and disturbance regime. One major driver of reef resilience is herbivory by parrotfish and recent action to protect parrotfish in Belize was found to have increased resilience 6‐fold. However, the expected benefits of parrotfish protection to future coral cover were relatively modest with only a 2‐ to 2.6‐fold improvement over a business‐as‐usual scenario, demonstrating how resilience and ecosystem states are decoupled. Global action to reduce greenhouse gas emissions had little impact on average coral state unless it was accompanied by local controls of fishing. However, combined global and local action reduced the rate of reef degradation threefold. Operationalizing resilience explicitly integrates available biophysical data and accommodates the complex interactions among ecological processes and multiple types of disturbance.
Hypertension risk: exercise is medicine* for most but not all
Authors: Loenneke Jeremy P. , Fahs Christopher A. , Abe Takashi , Rossow Lindy M. , Ozaki Hayao , Pujol Thomas J. , Bemben Michael G.
Published: June 2013

Hypertension is a risk factor for heart disease, and chronic exercise is recognized as a method for reducing resting blood pressure. Recent studies report that while exercise may benefit the majority of the population, the blood pressure adaptation is not always uniform; some individuals have an adverse blood pressure response to chronic aerobic exercise programmes. The purpose of this study was to examine the individual changes in resting blood pressure in response to exercise training regimens aimed at increasing muscle mass and strength. We have also included exercise (resistance and aerobic) in combination with blood flow restriction (BFR). Of 74 individuals, 11% had an increased risk, 16% had a decreased risk and 73% had no change in risk classification following exercise. The statistical analysis found that the group that decreased risk with exercise tended to have higher baseline levels of blood pressure. However, there were little baseline differences between the group that increased risk or the group that had no change in risk, suggesting that starting values may not necessarily determine who will see a beneficial response. In conclusion, the blood pressure adaptation to resistance training and exercise with BFR is not homogeneous with some participants increasing, decreasing or staying in the same risk category following an exercise intervention. These are important findings as they would not have been noted or discussed when looking only at the group means. Future research may identify molecular predictors so that individuals at risk for adverse events can be identified prior to exercise.
Large area of walled‐off pancreatic necrosis successfully treated by endoscopic necrosectomy using a grasping‐type scissors forceps
Authors: Aso Akira , Igarashi Hisato , Matsui Noriaki , Ihara Eikichi , Takaoka Takehiro , Osoegawa Takashi , Niina Yusuke , Oono Takamasa , Akahoshi Kazuya , Nakamura Kazuhiko , Ito Tetsuhide , Takayanagi Ryoichi
Published: June 2013

Endoscopic necrosectomy (EN) for walled‐off pancreatic necrosis (WOPN) is less invasive than surgical treatment and has become the first choice for pancreatic abscess. EN is usually carried out with several devices including snares, baskets, and grasping forceps. Occasionally, we have encountered cases in which EN has not been satisfactorily carried out, and there is pressure for further innovation in EN. Here, we describe a case of a large area of WOPN that was successfully treated by EN with endoscopic submucosal dissection and associated techniques, which facilitated removal of necrotic tissues. A 60‐year‐old man was referred to our hospital for WOPN as a complication of necrotizing pancreatitis. As a result of his complicating conditions including ischemic heart disease, uncontrollable arrhythmia, chronic renalfailure, and persistent pleural effusion, he was deemed a poor surgical candidate. Although EN with conventional devices was carried out for five sessions, we could not remove the dense and massive necrotic tissues. At the sixth EN session, the Clutch Cutter device (Fujifilm, Tokyo, Japan) was used to remove the necrotic tissues, without major complications. This is believed to be the first report of EN using the Clutch Cutter for successful treatment of WOPN.
A Multiparametric Clinical and Echocardiographic Score to Risk Stratify Patients with Chronic Systolic Heart Failure: Derivation and Testing
Authors: Fontanive Paolo , Miccoli Mario , Simioniuc Anca , Angelillis Marco , Bello Vitantonio Di , Baggiani Angelo , Bongiorni Maria Grazia , Marzilli Mario , Dini Frank Lloyd
Published: June 2013

Although echo Doppler and biomarkers are the most common examinations performed worldwide in heart failure (HF), they are rarely considered in risk scores. In outpatients with chronic HF and left ventricular ejection fraction (LVEF) ≤45%, data on clinical status, echo Doppler variables, aminoterminal pro‐type B natriuretic peptide (NT‐proBNP), estimated glomerular filtration rate (eGFR), and drug therapies were combined to build up a multiparametric score. We randomly selected 250 patients to produce a derivation cohort and 388 patients were used as a testing cohort. Follow‐up lasted 29 ± 23 months. The univariable predictors that entered into the multivariable Cox model were as follows: furosemide daily dose >25 mg, inability to tolerate angiotensin converting enzyme (ACE) inhibitors, inability to tolerate β‐blockers, age >75 years, New York Heart Association (NYHA) >2, eGFR<60 mL/min, NT‐proBNP plasma levels above the median, tricuspid plane systolic excursion (TAPSE) ≤14 mm, LV end‐diastolic volume index (LVEDVi) >96 mL/m2, moderate‐to‐severe mitral regurgitation (MR) and LVEF <30%. The scores of prognostic factors were obtained with the respective odds ratio divided by the lower odd ratio: 4 points for furosemide dose, 3 points for age, NT‐proBNP, LVEDVi, TAPSE, 2 points for inability to tolerate β‐blockers, inability to tolerate ACE inhibitors, NYHA, eGFR<60 mL/min, moderate‐to‐severe MR, 1 point for LVEF. The multiparametric score predicted all‐cause mortality either in the derivation cohort (68.4% sensitivity, 79.5% specificity, area under the curve [AUC] 78.7%) or in the testing cohort (73.7% sensitivity, 71.3% specificity, AUC 77.2%). All‐cause mortality significantly increased with increasing score both in the derivation and in the testing cohort (P < 0.0001). In conclusion, this multiparametric score is able to predict mortality in chronic systolic HF.
Emerging Role of Three‐Dimensional Speckle Tracking Strain for Accurate Quantification of Left Ventricular Dyssynchrony
Authors: Tanaka Hidekazu , Tatsumi Kazuhiro , Matsumoto Kensuke , Kawai Hiroya , Hirata Ken‐ichi
Published: June 2013

A case was 53‐year‐old female with dilated‐phase hypertrophic cardiomyopathy. She was classified as New York Heart Association functional class III heart failure despite receiving optimal medical therapy. The electrocardiogram taken showed intraventricular conduction delay with a QRS width of 194 msec. The left ventricular (LV) end‐diastolic and systolic volumes, and ejection fraction (EF) were 101 mL, 68 mL, and 32%, respectively. The patient showed no significant mechanical LV dyssynchrony as evidenced by two‐dimensional (2D) speckle tracking radial strain, which is defined as the time difference between anterior‐septum and posterior wall, of 105 msec (<130 msec). Three‐dimensional (3D) speckle tracking radial strain was performed for more detailed LV mechanical dyssynchrony analysis. An especially important finding for 3D speckle tracking radial strain analysis was that the average time‐to‐peak strain of 5 septum segments at 3 different LV levels (basal‐anterior‐septum, basal‐septum, mid‐anterior‐septum, mid‐septum, apical‐septum) was significantly shorter than that of 5 posterolateral segments at 3 different LV levels (basal‐posterior, basal‐lateral, mid‐posterior, mid‐lateral, apical‐lateral). This time difference between septum and posterolateral wall was 216 msec (204 msec vs. 420 msec), which was considered to indicate significant LV mechanical dyssynchrony (≥130 msec). 12 months after cardiac resynchronization therapy (CRT), EF had improved to 47%, while end‐systolic and diastolic volumes had decreased to 88 mL and 47 mL, respectively, so that the patient was classified as a responder. In conclusions, a newly developed 3D speckle tracking strain can provide a comprehensive evaluation of “true” LV mechanical dyssynchrony from pyramidal 3D data sets acquired in the same beat, thus yielding more accurate information than previously possible with the 2D speckle tracking system.
THE ECONOMICS OF AEROBICS
Authors: MORELAND KEMPER W.
Published: June 2013

This study presents a simple model that weighs the benefits and costs of aerobic exercise to the individual. The model assumes that adding years to life serves as the primary benefit of exercise, and that hours of exercise over a lifetime serve as the cost. Given previous estimates of individual rates of time preference this study finds that people act rationally when they choose to watch a track event rather than choose to run themselves. (JEL I1)
Second and third year oral health and dental student perceptions of future professional work
Authors: Tan A. S. , Anderson V. R. , Foster Page L. A.
Published: June 2013

Objectives

To explore and compare the ways dental and oral health students characterise their future professional work (FPW) at the end of their second and third professional years.

Materials and methods

Questionnaires were given to a cohort group of 48 dental students and 31 oral health students at the end of their second and third professional years at the University of Otago. Students' characterisations of their FPW were identified using an inductive approach, and the emphasis on each characterisation was confirmed using a ‘weighted’ table.

Results

Dental student response rates were 92% (in 2010) and 85% (in 2011); and oral health student response rates were 100% (in 2011) and 97% (in 2011). Students characterised their FPW in ten broad ways: in reference to treatment‐related concerns, patient‐related concerns, oral health promotion, oral health education, disease prevention and monitoring, communication, teamwork, maintaining an ideal clinical environment, maintaining a sense of self and improving quality of life. In both years, dental students emphasised treatment‐related concerns as central to their FPW and dealing with patient‐related concerns as a primary source of difficulty. Oral health students emphasised oral health promotion, oral health education, disease prevention and monitoring and restorative tasks as central to their FPW and dealing with patient‐related concerns as a primary source of difficulty.

Conclusion

Students' broad perceptions of their FPW changed little as they progressed through their programmes; however, their responses suggested the need for greater attention within their programmes to patient management and teamwork.
Effects of background light conditions on thermoperiodic eclosion rhythm of onion fly Delia antiqua
Authors: Watari Yasuhiko , Tanaka Kazuhiro
Published: June 2013

To elucidate the effects of light on thermoperiodic regulation of adult eclosion rhythm in the onion fly, Delia antiqua, the responses to two thermoperiods, 29°C (12 h):21°C (12 h) and 25.5°C (12 h):24.5°C (12 h), with different amplitude and same average temperature, were examined in continuous darkness (DD) and continuous light (LL). Irrespective of the temperature step between warm phase (W) and cool phase (C), temperature cycles effectively entrained the adult eclosion rhythm in both DD and LL. Eclosion peaks, however, varied with light conditions and temperature step between W and C. It advanced by approximately 2–3 h in DD than in LL and at smaller temperature step. Background light conditions and temperature step also affect the amplitude of eclosion rhythm. It became lower in LL than in DD and at smaller temperature steps. On transfer to constant temperature (25°C), eclosion rhythm was elicited earliest in the pupae at 8°C temperature step in DD and latest in those at 1°C temperature step in LL. Pupae at 1°C temperature step in DD and at 8°C temperature step in LL demonstrated intermediate responses, but the eclosion rhythm was elicited 1 day earlier in the former than in the latter. This might be ascribed to the interaction between background light and temperature step under thermoperiodic conditions. The results suggest that continuous light and a smaller temperature step weaken the coupling strength between eclosion rhythm and thermoperiod, but the light effect is stronger than the temperature step effect.
Bridging the Gap: Humanitarian Protection and the Convergence of Laws in Europe
Authors: Dean Meryll
Published: June 2013

This article uses the thematic of humanitarian protection to examine the convergence of laws in Europe. It considers the heterogeneous architecture of the Refugee Convention and European Convention on Human Rights then analyses the homogenous framework of the EU's Common Asylum System and, in particular, the Qualification Directive. It argues that in an area where international, regional and national laws intersect, convergence needs to be underpinned by Member States adopting a common interpretative methodology that has international law at its core. Article 15 of the Qualification Directive (QD) is used to illustrate how this can be achieved. The article adds to the growing literature on the convergence of laws in Europe and illustrates the importance of adopting a common interpretative methodology. It suggests a paradigm for protection regimes around the world and a methodology that could be transplanted to other areas of law involving the intersection of international, regional and national laws.
Distal hindlimb kinematics of gallopingThoroughbred racehorses on dirt and synthetic racetrack surfaces
Authors: Symons J. E. , Garcia T. C. , Stover S. M.
Published: June 2013

Reasons for performing study

The effect of racetrack surface (dirt or synthetic) on distal hindlimb kinematics of racehorses running at competition speeds is not known.

Objectives

To compare distal hindlimb and hoof kinematics during stance of breezing (unrestrained gallop) racehorses between dirt and synthetic surfaces.

Study design

Two‐dimensional kinematic video analysis of 5Thoroughbred racehorses galloping at high speeds (12–17 m/s) on a dirt racetrack and a synthetic racetrack.

Methods

The positions of kinematic markers applied to the left hindlimb were recorded at 500 Hz. Position, velocity and acceleration of joint angles and hoof translation during stance were calculated in the sagittal plane. Peak translational and angular kinematic values were compared between the dirt and synthetic race surfaces using mixed model analyses of covariance.

Results

Maximum and heel‐strike metatarsophalangeal (fetlock) angles were greater (P<0.05) on the dirt surface than on the synthetic surface. Maximum fetlock angle occurred earlier during stance on the dirt surface (P<0.05). Greater horizontal displacement of the heel during slide occurred on the dirt surface (P<0.05).

Conclusions

During high‐speed gallop, hindlimb fetlock hyperextension and horizontal hoof slide are greater on a dirt surface than on a synthetic surface. Synthetic race surfaces may mitigate risk of injury to hindlimb fetlock structures by reducing fetlock hyperextension and associated strains in fetlock support structures. Differences in hoof slide may contribute to different distal hindlimb kinematics between surfaces.
Latent myostatin has significant activity and this activity is controlled more efficiently by WFIKKN1 than by WFIKKN2
Authors: Szláma György , Trexler Mária , Patthy László
Published: June 2013

Myostatin, a negative regulator of skeletal muscle growth, is produced from myostatin precursor by multiple steps of proteolytic processing. After cleavage by a furin‐type protease, the propeptide and growth factor domains remain associated, forming a noncovalent complex, the latent myostatin complex. Mature myostatin is liberated from latent myostatin by bone morphogenetic protein 1/tolloid proteases. Here, we show that, in reporter assays, latent myostatin preparations have significant myostatin activity, as the noncovalent complex dissociates at an appreciable rate, and both mature and semilatent myostatin (a complex in which the dimeric growth factor domain interacts with only one molecule of myostatin propeptide) bind to myostatin receptor. The interaction of myostatin receptor with semilatent myostatin is efficiently blocked by WAP, Kazal, immunoglobulin, Kunitz and NTR domain‐containing protein 1 or growth and differentiation factor‐associated serum protein 2 (WFIKKN1), a large extracellular multidomain protein that binds both mature myostatin and myostatin propeptide [Kondás et al. (2008) J Biol Chem 283, 23677–23684]. Interestingly, the paralogous protein WAP, Kazal, immunoglobulin, Kunitz and NTR domain‐containing protein 2 or growth and differentiation factor‐associated serum protein 1 (WFIKKN2) was less efficient than WFIKKN1 as an antagonist of the interactions of myostatin receptor with semilatent myostatin. Our studies have shown that this difference is attributable to the fact that only WFIKKN1 has affinity for the propeptide domain, and this interaction increases its potency in suppressing the receptor‐binding activity of semilatent myostatin. As the interaction of WFIKKN1 with various forms of myostatin permits tighter control of myostatin activity until myostatin is liberated from latent myostatin by bone morphogenetic protein 1/tolloid proteases, WFIKKN1 may have greater potential as an antimyostatic agent than WFIKKN2.

Structured digital abstract

Furin cleaves Promyostatin by protease assay (View interaction)

myostatin binds to PRO by surface plasmon resonance (View interaction)

BMP-1 cleaves Promyostatin by protease assay (View interaction)

ACR IIB physically interacts with Latent Myostatin by surface plasmon resonance (View interaction)

Promyostatin and Promyostatin bind by comigration in gel electrophoresis (View interaction)

WFIKKN1 binds to Latent Myostatin by pull down (View interaction)

ACR IIB binds to Mature Myostatin by surface plasmon resonance (View Interaction: 1, 2, 3)

WFIKKN1 binds to Myostatin Prodomain by surface plasmon resonance (View Interaction: 1, 2, 3)
Large‐scale variations in the vegetation growing season and annual cycle of atmospheric CO2 at high northern latitudes from 1950 to 2011
Authors: Barichivich Jonathan , Briffa Keith R. , Myneni Ranga B. , Osborn Timothy J. , Melvin Thomas M. , Ciais Philippe , Piao Shilong , Tucker Compton
Published: June 2013

We combine satellite and ground observations during 1950–2011 to study the long‐term links between multiple climate (air temperature and cryospheric dynamics) and vegetation (greenness and atmospheric CO2 concentrations) indicators of the growing season of northern ecosystems (>45°N) and their connection with the carbon cycle. During the last three decades, the thermal potential growing season has lengthened by about 10.5 days (P < 0.01, 1982–2011), which is unprecedented in the context of the past 60 years. The overall lengthening has been stronger and more significant in Eurasia (12.6 days, P < 0.01) than North America (6.2 days, P > 0.05). The photosynthetic growing season has closely tracked the pace of warming and extension of the potential growing season in spring, but not in autumn when factors such as light and moisture limitation may constrain photosynthesis. The autumnal extension of the photosynthetic growing season since 1982 appears to be about half that of the thermal potential growing season, yielding a smaller lengthening of the photosynthetic growing season (6.7 days at the circumpolar scale, P < 0.01). Nevertheless, when integrated over the growing season, photosynthetic activity has closely followed the interannual variations and warming trend in cumulative growing season temperatures. This lengthening and intensification of the photosynthetic growing season, manifested principally over Eurasia rather than North America, is associated with a long‐term increase (22.2% since 1972, P < 0.01) in the amplitude of the CO2 annual cycle at northern latitudes. The springtime extension of the photosynthetic and potential growing seasons has apparently stimulated earlier and stronger net CO2 uptake by northern ecosystems, while the autumnal extension is associated with an earlier net release of CO2 to the atmosphere. These contrasting responses may be critical in determining the impact of continued warming on northern terrestrial ecosystems and the carbon cycle.
The Principle of Objectified Circumstances (POC): Clarifying the Proximate End
Authors: Dixon Paul
Published: June 2013

This paper seeks to clarify the proximate end. A distinction is made between the definition of an act and the identification of an act. The principle of objectified circumstances (POC) is postulated which, without expanding beyond the proximate end, gives due weight to both the perspective of the acting person and the context within which an act occurs. POC is used to help discern the object contained within the proximate end. It is applied to the issues of euthanasia, lying, mutilation, and the controversy between Martin Rhonheimer and Janet Smith concerning the use of condoms for HIV protection. The challenge of angelism is addressed. The paper argues that the object, located exclusively in the proximate end, can be understood in a way that is sensitive to both traditionalist and proportionalist schools of thought. POC opens up an avenue of thought for fresh dialogue concerning the identification of the moral object.
Synthesis and characterization of a glycerol salicylate resin for bioactive root canal sealers
Authors: Portella F. F. , Santos P. D. , Lima G. B. , Leitune V. C. B. , Petzhold C. L. , Collares F. M. , Samuel S. M. W.
Published: June 2013

Aim

To develop and characterize a salicylate resin with potential use in bioactive endodontic sealers.

Methodology

Methyl salicylate, glycerol and titanium isopropoxide were added in a closed system for the transesterification reaction. The resin obtained was characterized by proton nuclear magnetic resonance spectroscopy (1H NMR) and size exclusion chromatography (SEC). To verify the applicability of the resin to the development of endodontic sealers, experimental cements were prepared by mixing glycerol salicylate resin, calcium hydroxide and methyl salicylate in the ratios of 2 : 1 : 1, 1 : 2 : 1, 1 : 1 : 2, 1 : 1 : 1, 4 : 1 : 1, 1 : 4 : 1 and 1 : 1 : 4. Setting times were measured according to ISO 6876. Features of the hardening reaction were described by micro‐RAMAN spectroscopy.

Results

The transesterification reaction had a 72% efficiency. The 1H NMR analysis revealed the presence of the expected functional groups (hydroxyls and aromatic rings), and the SEC confirmed the molar mass of the resin produced. The setting times of experimental sealers ranged from 70 min (ratio 1 : 1 : 1) to 490 min (ratio 1 : 1 : 4). The conversion of the salicylic groups (1 613 cm−1) to salicylate salt (1 543 cm−1) and the reduction in calcium hydroxide peaks (1084 and 682 cm−1) were confirmed by micro‐RAMAN spectroscopy, which showed the calcium chelation by the resin.

Conclusion

The new glycerol salicylate resin was successfully synthesized and revealed a potential application in the development of endodontic sealers.
Integration of High‐Conductivity Graphite Foam to Metallic Systems Using Ag‐Cu‐Ti and Ag‐Cu‐Pd Braze Alloys
Authors: Singh Mrityunjay , Smith Craig , Asthana Rajiv , Gyekenyesi Andrew
Published: June 2013

Graphite foams with low, medium, and high densities were joined to Cu‐clad‐Mo, 430 stainless steel, titanium, and Inconel 625 using Cusil‐ABA® and Palcusil‐5®. Copper‐clad‐molybdenum and steel were also joined to SiC‐coated foam. Well‐bonded joints with partially infiltrated foam and with carbon ligaments enriched with Ti formed in Cusil‐ABA joints of coated and uncoated foam. Low‐density foams showed greatest braze penetration and penetration distance decreased with increasing foam density. Foam/metal joints with Palcusil‐5 showed less penetration than Cusil‐ABA. The tension test on foam/Cu‐clad‐Mo and foam/430 stainless steel joints made using Cusil‐ABA revealed that the joints were always stronger than the foam.
Evaluation of registered nurses' knowledge and practice of documentation at a Jamaican hospital
Authors: Blake‐Mowatt C. , Lindo J.L.M. , Bennett J.
Published: June 2013

Background

Documentation is central to the management of patients in hospitals. Nurses are trained to follow the Ministry of Health Jamaica's policy on documentation, which is available in all public hospitals.

Aim

Audit of documentation practices by registered nurses at a referral hospital.

Methods

Ninety patient records from three medical wards were audited for documentation practices using an approved Jamaican Ministry of Health tool. Qualitative data regarding the nurses' experience with documentation were gathered from a focus group discussion of 12 nurses assigned to the audited wards.

Findings

Most nurses (98%) followed documentation guidelines for admission by recording patients' past complaints, medical history and assessment data; used authorized abbreviations only (97%); documented nursing actions taken after identification of a problem and a provided a summary of the patients' condition at the end of the shift (98%). However, only 26% of the records had nursing diagnosis, which corresponded to the current medical diagnosis and 48% had documented evidence of discharge planning. Eighty‐seven per cent had no evidence of patient teaching. The main reported factors affecting documentation practices were workload and staff/patient ratios. Participants believed that nursing documentation could be improved with better staffing, improved peer guidance and continuing education.

Conclusions

The study showed high levels of accurate documentation by nurses at a referral hospital in Western Jamaica and the nurses appeared to be familiar with the required documentation guidelines with policy manuals available on each ward. Weaknesses in discharged planning and patient teaching were identified, which should be addressed by targeted continuing nursing.
Role of fibronectin in normal wound healing
Authors: Lenselink Ellie A
Published: June 2013

Fibronectin is an adhesive molecule that plays a crucial role in wound healing, particularly in extracellular matrix (ECM) formation and also in reepithelialisation. Fibronectin plays many different roles in the wound healing process because of the presence of specific function domains and binding sites in its structure. Fibronectin interacts with different cell types, cytokines and the ECM. The main role of fibronectin is ECM formation. First, plasma fibronectin forms a provisional fibrin–fibronectin matrix, which will later be replaced by the mature ECM‐containing tissue fibronectin.
Oral microbial colonization in laryngectomized patients as a possible cofactor of biofilm formation on their voice prostheses
Authors: Bertl Kristina , Zatorska Beata , Leonhard Matthias , Rechenmacher‐Strauss Julia , Roesner Imme , Schneider‐Stickler Berit
Published: June 2013

Aim

Biofilm formation on voice prostheses, which are used for voice rehabilitation in laryngectomized patients, is a main cause of device failure. The aim of this study was to assess whether the presence of periodontal pathogens in the biofilm on voice prostheses is related to that in the oral cavity and associated with the periodontal status of the patients.

Methods

Thirty‐one laryngectomized patients were invited to participate, 13 of whom met exclusion criteria. The remaining 18 were classified according to the community periodontal index of treatment needs (community periodontal index of treatment needs (CPITN), grades 0–4). Biofilm samples from the oral cavity and voice prostheses were analysed by PCR‐based hybridization for 11 pathogens.

Results

All dentate patients required periodontal treatment (CPITN‐3: n = 4, CPITN‐4: n = 8); the remaining six were edentulous. The diversity (i.e. number of bacterial species detected) of pathogens detected on the voice prostheses correlated significantly positively with the diversity of pathogens in the oral cavity and with clinical parameters. Furthermore, the diversity of pathogens differed significantly between dentate and edentulous patients.

Conclusions

Results emphasize the oral cavity as an important source of bacteria for biofilm formation on voice prostheses. Whether these pathogens reduce the lifetime of the device by increased biofilm formation and/or increase the risk of silicone deterioration requires further study.
Framework for Applying a Complex Adaptive System Approach to Model the Operation of Eco‐Industrial Parks
Authors: Romero Elena , Ruiz M. Carmen
Published: June 2013

Models of eco‐industrial parks (EIPs) might help us transform our production systems by fostering the emergence of sustainable EIPs since such models have the potential to support the decision‐making processes of cooperative companies that participate and to decrease operational uncertainties. In this article, a conceptual framework for modeling the operation of EIPs is presented. The framework is underpinned by complex adaptive systems theory, industrial ecology, and an analysis of the experiences of existing EIPs. The proposed framework draws on the observed strengths of two types of industrial symbiosis models—planned eco‐industrial parks (PEIPs) and EIPs that developed through self‐organizing symbiosis (SOS)—as well as their observed weaknesses and the features of complex adaptive systems. From this analysis, five key properties to be modeled are deduced: functionality, reliability, life span, theoretical knowledge, and adaptability. It is proposed that the properties of functionality and theoretical knowledge are determined by the goals of the EIP and its member companies, while the property of adaptability is determined by the understanding that the companies in an EIP have of the environment surrounding the EIP, while the properties of reliability and life span are determined by the internal and external relationships of the companies that make up an EIP.
Aerobic training improved low‐grade inflammation in obese women with intellectual disability
Authors: Ordonez F. J. , Rosety M. A. , Camacho A. , Rosety I. , Diaz A. J. , Fornieles G. , Garcia N. , Rosety‐Rodriguez M.
Published: June 2013

Background

Obesity is a major health problem in people with intellectual disabilities. It is also widely accepted that low‐grade systemic inflammation associated to obesity plays a key role in the pathogenic mechanism of several disorders. Fortunately, physical activity has shown to improve inflammation in people with metabolic syndrome and type 2 diabetes. Accordingly, we assessed the influence of aerobic training on pro‐inflammatory cytokines and acute phase proteins in women with Down syndrome.

Methods

To achieve this outcome, 20 premenopausal obese young women with Down syndrome volunteered for this study. Eleven were randomly assigned to the intervention group and performed a 10‐week aerobic training programme, three sessions per week, consisting of a warm‐up then a 30‐ to 40‐min treadmill exercise at a work intensity of 55–65% of peak heart rate followed by a cooling‐down period. The control group included nine age‐, sex‐ and body mass index‐matched women with Down syndrome. Fat mass percentage and fat distribution were measured. Plasmatic levels of tumour necrosis factor (TNF)‐α, interleukin (IL)‐6 and fibrinogen were assessed by commercial enzyme‐linked immunosorbent assay kits. C‐reactive protein (CRP) was assessed by nephelometry.

Results

Plasmatic levels of TNF‐α (11.7 ± 1.6 vs. 9.2 ± 1.3 pg/ml; P = 0.022), IL‐6 (8.2 ± 1.1 vs. 6.1 ± 0.9 pg/ml; P = 0.014) and high sensitive CRP (0.62 ± 0.11 vs. 0.53 ± 0.09 mg/dl; P = 0.009) were significantly reduced in the intervention group. Further, significant correlations between plasmatic and anthropometric parameters were found.

Conclusion

A 10‐week training programme reduced pro‐inflammatory cytokines and acute phase proteins in obese young women with Down syndrome. Long‐term, well‐conducted studies are still required to determine whether correction of this low‐grade inflammation improves clinical outcomes of women with trisomy 21.
Antibodies bound to Aβ oligomers potentiate the neurotoxicity of Aβ by activating microglia
Authors: Morkuniene Ramune , Zvirbliene Aurelija , Dalgediene Indre , Cizas Paulius , Jankeviciute Silvija , Baliutyte Giedre , Jokubka Ramunas , Jankunec Marija , Valincius Gintaras , Borutaite Vilmante
Published: June 2013

Beta amyloid (Aβ) oligomers are thought to contribute to the pathogenesis of Alzheimer's disease. However, clinical trials using Aβ immunization were unsuccessful due to strong brain inflammation, the mechanisms of which are poorly understood. In this study we tested whether monoclonal antibodies to oligomeric Aβ would prevent the neurotoxicity of Aβ oligomers in primary neuronal‐glial cultures. However, surprisingly, the antibodies dramatically increased the neurotoxicity of Aβ. Antibodies bound to monomeric Aβ fragments were non‐toxic to cultured neurons, while antibodies to other oligomeric proteins: hamster polyomavirus major capsid protein, human metapneumovirus nucleocapsid protein, and measles virus nucleocapsid protein, strongly potentiated the neurotoxicity of their antigens. The neurotoxicity of antibody‐oligomeric antigen complexes was abolished by removal of the Fc region from the antibodies or by removal of microglia from cultures, and was accompanied by inflammatory activation and proliferation of the microglia in culture. In conclusion, we find that immune complexes formed by Aβ oligomers or other oligomeric/multimeric antigens and their specific antibodies can cause death and loss of neurons in primary neuronal‐glial cultures via Fc‐dependent microglial activation. The results suggest that therapies resulting in antibodies to oligomeric Aβ or oligomeric brain virus proteins should be used with caution or with suppression of microglial activation.

image

Immunization against Aβ in Alzheimer's disease carries a significant risk of neuroinflammation, the mechanisms of which are poorly understood. In this study we show that oligomeric antigens such as Aβ and viral proteins complexed with their specific antibodies can exert neurotoxic effects by Fc‐dependent microglia activation. This suggests that therapies using antibodies against oligomeric proteins should be used with caution.
Dietary supplementation and engaging in physical activity as predictors of coronary artery disease among middle‐aged women
Authors: Tsai Ching‐Ching , Hsieh Ming‐Hsiung , Li Ai‐Hsien , Chen Ping‐Ling , Jeng Chii
Published: June 2013

Aim and objectives

To explore risk factors for coronary artery disease (CAD) among middle‐aged women in Taiwan.

Background

Coronary artery disease is a leading cause of death among females. Risk factors for CAD vary due to differences in ethnicity, gender and age. However, few studies have documented risk factors among middle‐aged women.

Design

We employed a cross‐sectional, comparative study design.

Methods

Sixty‐five middle‐aged women who were suspected of having CAD and who received cardiac catheterisation were purposively sampled and divided into a CAD group (with at least one coronary artery with > 50% stenosis) and a control group, according to the results of catheterisation. Individual questionnaires regarding their medical history, blood test results, sociodemographic characteristics, metabolism, biomarkers and lifestyle risk factors were administered and quantified.

Results

The mean age of the 65 women (31 CAD and 34 controls) was 56·2 years. Within the CAD group, there was a greater incidence of women with a history of diabetes mellitus (DM), increased fasting blood glucose and increased diastolic blood pressure. Comparatively fewer women within the CAD category used dietary supplements or had a lower level of physical activity. After adjusting for other confounders, it was discovered that women who used dietary supplements (OR = 0·28; p = 0·04) and engaged in physical activities (OR = 0·16; p = 0·02) were less likely to develop CAD.

Conclusions

Use of dietary supplements and engaging in physical activities can significantly predict the incidence of CAD among middle‐aged women in Taiwan.

Relevance to clinical practice

Middle‐aged women should be encouraged to take appropriate dietary supplements and engage in physical activity in order to prevent CAD.
The End of the World Designed with Men in Mind
Authors: Glendinning Simon
Published: June 2013

According to Derrida, the European self‐understanding marking the name “Man” is governed by eschatology and teleology. Man is that being on its way towards its proper end. The times of science seemed to Kant and others to be evidence of just such progress. For Freud, by contrast, the great scientific achievements of Copernicus, Darwin and Freud have cumulatively contributed a series of de‐centring blows to our “self‐love”. This paper explores the nature of great scientific achievements, and raises the possibility of a further devastating blow to Man, this time in the twentieth century, and connected to the name of Marx.
Corporate Turnarounds: The Duality of Retrenchment and Recovery
Authors: Schmitt Achim , Raisch Sebastian
Published: June 2013

Corporate turnaround research has described retrenchment and recovery as contradictory forces that should be addressed separately. While a few scholars have argued that retrenchment and recovery are interrelated and may have to be integrated, others have contended that such arguments are flawed since they downplay the contradictions between the two activities. In this paper, we clarify the nature of the retrenchment–recovery interrelations, as well as their importance for turnaround performance. Drawing on the paradox literature, we argue that retrenchment and recovery form a duality: they are both contradictory and complementary. Integrating the two activities allows turnaround firms to create benefits that exceed the costs of their integration, which affects turnaround performance positively. We test our arguments through an empirical study of 107 Central European turnaround initiatives and find evidence for the assumed duality between retrenchment and recovery. Our main contribution is integrating the hitherto disparate theory perspectives of corporate turnaround into an overarching framework.