bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical effects of the use of a bipolar vessel sealing device for soft palate resection and tonsillectomy in dogs, with histological assessment of resected tonsillar tissue
Authors: Cook DA , Moses PA , Mackie JT
Published: December 2015

Objective

To investigate whether soft palate resection and tonsillectomy with a bipolar vessel sealing device (BVSD) improves clinical respiratory score. To document histopathological changes to tonsillar tissue following removal with a BVSD.

Methods & Results

Case series of 22 dogs with clinical signs of upper respiratory obstruction related to brachycephalic airway syndrome. Soft palate and tonsils were removed using a BVSD. Alarplasty and saccullectomy were also performed if indicated. A clinical respiratory score was assigned preoperatively, 24‐h postoperatively and 5 weeks postoperatively. Excised tonsillar samples were measured and then assessed histologically for depth of tissue damage deemed to be caused by the device. Depth of tissue damage was compared between two power settings of the device. Soft palate resection and tonsillectomy with a BVSD lead to a significant improvement in respiratory scores following surgery. Depth of tissue damage was significantly less for power setting 1 compared with power setting 2. Using power setting 1, median calculated depth of tonsillar tissue damage was 3.4 mm (range 1.2–8.0). One dog experienced major complications.

Conclusion

Soft palate resection and tonsillectomy with a BVSD led to significant improvement in clinical respiratory score.
Capabilities and Incapabilities of the Capabilities Approach to Health Justice
Authors: Selgelid Michael J.
Published: December 2015

This first part of this article critiques Sridhar Venkatapuram's conception of health as a capability. It argues that Venkatapuram relies on the problematic concept of dignity, implies that those who are unhealthy lack lives worthy of dignity (which seems politically incorrect), sets a low bar for health, appeals to metaphysically problematic thresholds, fails to draw clear connections between appealed‐to capabilities and health, and downplays the importance/relevance of health functioning. It concludes by questioning whether justice entitlements should pertain to the capability for health versus health achievements, challenging Venkatapuram's claims about the strength of health entitlements, and demonstrating that the capabilities approach is unnecessary to address social determinants of health.
Voluntary Informed Consent in Paediatric Oncology Research
Authors: Dekking Sara A. S. , Van Der Graaf Rieke , Van Delden Johannes J. M.
Published: December 2015

In paediatric oncology, research and treatments are often closely combined, which may compromise voluntary informed consent of parents. We identified two key scenarios in which voluntary informed consent for paediatric oncology studies is potentially compromised due to the intertwinement of research and care. The first scenario is inclusion by the treating paediatric oncologist, the second scenario concerns treatments confined to the research context. In this article we examine whether voluntary informed consent of parents for research is compromised in these two scenarios, and if so whether this is also morally problematic. For this, we employ the account of voluntary consent from Nelson and colleagues, who assert that voluntary consent requires substantial freedom from controlling influences. We argue that, in the absence of persuasion or manipulation, inclusion by the treating physician does not compromise voluntariness. However, it may function as a risk factor for controlling influence as it narrows the scope within which parents make decisions. Furthermore, physician appeal to reciprocity is not controlling as it constitutes persuasion. In addition, framing information is a form of informational manipulation and constitutes a controlling influence. In the second scenario, treatments confined to the research context qualify as controlling if the available options are restricted through manipulation of options. Although none of the influences is morally problematic in itself, a combination of influences may create morally problematic instances of involuntary informed consent. Therefore, safeguards should be implemented to establish an optimal environment for parents to provide voluntary informed consent in an integrated research‐care context.
Modeling Overdispersion Heterogeneity in Differential Expression Analysis Using Mixtures
Authors: Bonafede Elisabetta , Picard Franck , Robin Stéphane , Viroli Cinzia
Published: December 2015

Next-generation sequencing technologies now constitute a method of choice to measure gene expression. Data to analyze are read counts, commonly modeled using negative binomial distributions. A relevant issue associated with this probabilistic framework is the reliable estimation of the overdispersion parameter, reinforced by the limited number of replicates generally observable for each gene. Many strategies have been proposed to estimate this parameter, but when differential analysis is the purpose, they often result in procedures based on plug-in estimates, and we show here that this discrepancy between the estimation framework and the testing framework can lead to uncontrolled type-I errors. Instead, we propose a mixture model that allows each gene to share information with other genes that exhibit similar variability. Three consistent statistical tests are developed for differential expression analysis. We show through a wide simulation study that the proposed method improves the sensitivity of detecting differentially expressed genes with respect to the common procedures, since it reaches the nominal value for the type-I error, while keeping elevate discriminative power between differentially and not differentially expressed genes. The method is finally illustrated on prostate cancer RNA-Seq data.
Family demographic profiles and their relationship with the quality of executive functioning subcomponents in kindergarten
Authors: Vandenbroucke Loren , Verschueren Karine , Ceulemans Eva , De Smedt Bert , De Roover Kim , Baeyens Dieter
Published: December 2015

Executive functioning (EF), needed for goal‐oriented behaviour, thoughts, and emotions, is important for various life domains. This study examined the relationship between family demographics and EF subcomponents. A kindergarten sample was tested on subcomponents of working memory, inhibition, and cognitive flexibility. Parents provided information on demographic variables. For 78 children both EF and demographic data were available. First, demographic profiles were identified within the sample. Two profiles were found: A low‐risk profile of mainly two‐biological‐parent, high‐income families with a highly educated mother who did not smoke during pregnancy and a high‐risk profile of low‐income families with a young, low‐educated mother who more often smoked during pregnancy. Second, children with different demographic profiles were compared on EF subcomponents. Results indicate differential relations between family demographics and EF subcomponents: Whereas for most EF subcomponents no association with family demographics was found, high‐risk children performed better on response shifting and tended to perform worse on verbal memory than low‐risk children. Parenting stress decreased performance only for high‐risk children. Although this study found limited impact of family demographics for EF, further longitudinal research can provide nuanced insights about which factors influence specific EF subcomponents during which developmental periods and guide targeted prevention of EF difficulties.
The haematological features and transfusion management of women who required massive transfusion for major obstetric haemorrhage in the UK: a population based study
Authors: Green Laura , Knight Marian , Seeney Frances , Hopkinson Cathy , Collins Peter W. , Collis Rachel E. , Simpson Nigel A. B. , Weeks Andrew , Stanworth Simon J.
Published: December 2015

Understanding the coagulopathy of major‐obstetric‐haemorrhage (MOH) that leads to massive‐transfusion (MT) is fundamental to improving outcomes. This study reports on the haematological features and transfusion management of women experiencing MT [defined as transfusion of ≥8 units of red blood cells (RBC) within 24 h of delivery]. One hundred and eighty‐one cases [median (interquartile range; IQR) age 33 years (29–36)] were identified from all UK hospitals, using the UK Obstetric Surveillance System between July 2012 and June 2013. The median (IQR) estimated blood loss was 6 l (4·5–8). At presentation, the median platelet count was lowest for placenta accreta, compared with other causes, while the median prothrombin time and fibrinogen were <1·5 × mean normal and <3 g/l, respectively for all aetiologies. Median platelet count and fibrinogen fell to <75 × 109/l and <2 g/l, respectively for all causes during bleeding, except for trauma. The median (IQR) units of RBC, fresh‐frozen‐plasma (FFP) and cryoprecipitate transfused were 10 (8–14), 6 (4–8) and 2 (2–4), respectively. The median time from the onset of bleeding to delivery of the first RBC unit was significantly shorter for women who delivered via elective caesarean section, compared with others. The coagulopathy of MT during MOH differs significantly depending on its cause, suggesting that more targeted transfusion strategies are required.
Relative frequency of non‐Hodgkin lymphoma subtypes in selected centres in North Africa, the middle east and India: a review of 971 cases
Authors: Perry Anamarija M. , Diebold Jacques , Nathwani Bharat N. , MacLennan Kenneth A. , Müller‐Hermelink Hans K. , Bast Martin , Boilesen Eugene , Armitage James O. , Weisenburger Dennis D.
Published: December 2015

Comparative data regarding the distribution of non‐Hodgkin lymphoma (NHL) subtypes in North Africa, the Middle East and India (NAF/ME/IN) is scarce in the literature. In this study, we evaluated the relative frequencies of NHL subtypes in this region. Five expert haematopathologists classified 971 consecutive cases of newly‐diagnosed NHL from five countries in NAF/ME/IN. After review, 890 cases (91·7%) were confirmed to be NHL and compared to 399 cases from North America (NA). The male‐to‐female ratio was significantly higher in NAF/ME/IN (1·8) compared to NA (1·1; P< 0·05). The median ages of patients with low‐grade (LG) and high‐grade (HG) B‐NHL in NAF/ME/IN (56 and 52 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). In NAF/ME/IN, a significantly lower proportion of LG B‐NHL (28·4%) and a higher proportion of HG B‐NHL (58·4%) were found compared to NA (56·1% and 34·3%, respectively). Diffuse large B‐cell lymphoma was more common in NAF/ME/IN (49·4%) compared to NA (29·3%), whereas follicular lymphoma was less common in NAF/ME/IN (12·4%) than in NA (33·6%). In conclusion, we found significant differences in NHL subtypes and clinical features between NAF/ME/IN and NA. Epidemiological studies are needed to better understand the pathobiology of these differences.
New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B‐cell precursor acute lymphoblastic leukaemia
Authors: van der Velden Vincent H. J. , de Launaij Daphne , de Vries Jeltje F. , de Haas Valerie , Sonneveld Edwin , Voerman Jane S. A. , de Bie Maaike , Revesz Tamas , Avigad Smadar , Yeoh Allen E. J. , Swagemakers Sigrid M. A. , Eckert Cornelia , Pieters Rob , van Dongen Jacques J. M.
Published: December 2015

In childhood acute lymphoblastic leukaemia (ALL), central nervous system (CNS) involvement is rare at diagnosis (1–4%), but more frequent at relapse (~30%). Because of the significant late sequelae of CNS treatment, early identification of patients at risk of CNS relapse is crucial. Using microarray‐analysis, we discovered multiple differentially expressed genes between B‐cell precursor (BCP) ALL cells in bone marrow (BM) and BCP‐ALL cells in cerebrospinal fluid (CSF) at the time of isolated CNS relapse. After confirmation by real‐time quantitative polymerase chain reaction, selected genes (including SCD and SPP1) were validated at the protein level by flowcytometric analysis of BCP‐ALL cells in CSF. Further flowcytometric validation showed that a subpopulation of BCP‐ALL cells (>1%) with a ‘CNS protein profile’ (SCD positivity and increased SPP1 expression) was present in the BM at diagnosis in patients who later developed an isolated CNS relapse, whereas this subpopulation was <1% or absent in all other patients. These data indicate that the presence of a (small) subpopulation of BCP‐ALL cells with a ‘CNS protein profile’ at diagnosis (particularly SCD‐positivity) is associated with isolated CNS relapse. Such information can be used to design new diagnostic and treatment strategies that aim at prevention of CNS relapse with reduced toxicity.
68Ga‐PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment
Authors: van Leeuwen Pim J. , Stricker Phillip , Hruby George , Kneebone Andrew , Ting Francis , Thompson Ben , Nguyen Quoc , Ho Bao , Emmett Louise
Published: December 2015

Objectives

To examine the detection rates of 68Ga‐PSMA‐positron emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP), and also the impact on their management.

Materials and Methods

A total of 300 consecutive patients with prostate cancer (PCa) who underwent 68Ga‐PSMA‐PET/CT between February and July 2015 were prospectively included in the Prostate Cancer Imaging (ProCan‐I) database. For the present analysis, we included patients with BCR (prostate‐specific antigen [PSA] level ≥0.05 and <1.0 ng/mL) after RP, who were being considered for salvage radiation therapy (RT) according to the Faculty of Radiation Oncology Genito‐Urinary Group (FROGG) guidelines. Two readers assessed each 68Ga‐PSMA‐PET/CT, and all positive lesions were assigned to an anatomical location. For each patient, the clinical and pathological features were recorded, their association with pathological 68Ga‐PSMA uptake was investigated, and detection rates were determined according to PSA level.

Results

A total of 70 patients were included, and 53 positive 68Ga‐PSMA lesions were detected in 38 (54%) patients. Among patients with PSA levels 0.05–0.09 ng/mL, 8% were definitely positive; the corresponding percentages for the other PSA ranges were as follows: PSA 0.1–0.19 ng/mL, 23%; PSA 0.2–0.29 ng/mL, 58%; PSA 0.3–0.49 ng/mL, 36%; and PSA 0.5–0.99 ng/mL, 57%. Eighteen of 70 patients (27%) had pathological 68Ga‐PSMA uptake in the prostatic fossa, 11 (14.3%) in the pelvic nodes, and five (4.3%) in both the fossa and pelvic lymph nodes. Finally, there was uptake outside the pelvis with or without a lesion in the fossa or pelvic lymph nodes in four cases (8.6%). As a result of the 68Ga‐PSMA findings there was a major management change in 20 (28.6%) patients.

Conclusions

68Ga‐PSMA appears to be useful for re‐staging of PCa in patients with rising PSA levels who are being considered for salvage RT even at PSA levels <0.5 ng/mL. These results underline the need for further prospective trials to evaluate the changes in RT volume or management attributable to 68Ga‐PSMA findings.
Innovating and Exploiting Entrepreneurial Opportunities in Smart Cities: Evidence from Germany
Authors: Kraus Sascha , Richter Chris , Papagiannidis Savvas , Durst Susanne
Published: December 2015

Smart City initiatives are considered a vehicle for achieving sustainable development of urban growth. This paper explores the conditions and factors that affect innovation in Smart Cities from an entrepreneurial vantage point. Data was obtained through a series of interviews with German entrepreneurs active in Smart Cities. Beyond examining the importance of a set of factors that originate from the extant literature, our findings suggest that entrepreneurs believe that Smart City initiatives need a clear vision to drive their development and growth and that government has a key role to play in bringing the necessary resources and stakeholders together.
Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA
Authors: Kwok Albert , McCarthy David , Hart Stephen L. , Tagalakis Aristides D.
Published: December 2015

The effects of lysine peptide lengths on DNA and siRNA packaging and delivery were studied using four linear oligolysine peptides with 8 (K8), 16 (K16), 24 (K24) and 32 (K32) lysines. Oligolysine peptides with 16 lysines or longer were effective for stable monodisperse particle formation and optimal transfection efficiency with plasmid DNA (pDNA), but K8 formulations were less stable under anionic heparin challenge and consequently displayed poor transfection efficiency. However, here we show that the oligolysines were not able to package siRNA to form stable complexes, and consequently, siRNA transfection was unsuccessful. These results indicate that the physical structure and length of cationic peptides and their charge ratios are critical parameters for stable particle formation with pDNA and siRNA and that without packaging, delivery and transfection cannot be achieved.
Involvement of C‐X‐C chemokine receptor type 4 signaling in the efficiency of intercellular transmission of human T‐lymphotropic virus type I
Authors: Nakamura Tatsufumi , Satoh Katsuya , Fukushima Naomi
Published: December 2015

Objective

We investigated the relationships between the efficiency of intercellular transmission of human T‐lymphotropic virus type I (HTLV‐I) and C‐X‐C chemokine receptor type 4 (CXCR4) signaling in a comparative study of HTLV‐I‐infected T cell lines derived from an HTLV‐I‐associated myelopathy/tropical spastic paraparesis patient (HCT‐5) or an HTLV‐I carrier (TL‐Su).

Methods

After co‐cultivation of each HTLV‐I‐infected T cell line with H9/K30 luc reporter cells, relative activities of luc were calculated to measure the intercellular transmission of HTLV‐I. The level of stromal cell‐derived factor‐1α was measured using an enzyme‐linked immunoassay. Rap1 activation in HTLV‐I‐infected T cell lines was analyzed by a pull‐down assay.

Results

HCT‐5 had higher intercellular transmission efficiency of HTLV‐I compared with TL‐Su. Intercellular transmission of HTLV‐I in TL‐Su was increased significantly by stromal cell‐derived factor‐1α treatment. Pretreatment with an anti‐CXCR4 blocking antibody for H9/K30 luc reporter cells induced a significant reduction in intercellular transmission of HTLV‐I in HCT‐5, but not in TL‐Su. Stromal cell‐derived factor‐1α was not detected in the culture supernatants of HCT‐5, but existence of a humoral factor that activates CXCR4 signaling in HCT‐5 was suggested from studies with condition media. Bound Rap1‐GTP was detected in HCT‐5, but not in TL‐Su.

Conclusions

Our data suggest that CXCR4 signaling is involved in the efficiency of intercellular transmission of HTLV‐I.
Predictors of weight‐loss response with glucagon‐like peptide‐1 receptor agonist treatment among adolescents with severe obesity
Authors: Nathan B. M. , Rudser K. D. , Abuzzahab M. J. , Fox C. K. , Coombes B. J. , Bomberg E. M. , Kelly A. S.
Published: December 2015

In two previous, separate clinical trials, we demonstrated significant reductions in body mass index (BMI) with exenatide in adolescents with severe obesity. In the present study, we pooled data from these near identical trials to evaluate factors that may predict BMI reduction at 3 months. Data from 32 patients (mean age 14.3 ± 2.2 years; 69% female; mean BMI 39.8 ± 5.8 kg m−2) were included. Exenatide treatment consisted of 5 mcg twice daily for 1 month, followed by an increase to 10 mcg twice daily for 2 additional months. Predictor variables included baseline BMI, BMI percent change at 1 month, incidence of nausea or vomiting and baseline appetite and satiety measures. Treatment effects of percent change in BMI from baseline were estimated within predictor subgroups using generalized estimating equations with exchangeable working correlation and robust variance estimation for confidence intervals and P‐values to account for paired observations. The pooled data treatment effect on absolute BMI at 3 months was −3.42% (95% confidence interval: −5.41%, −1.42%) compared to placebo. Within treated participants, appetite at baseline (treatment effect in high [−4.28%] vs. low [1.02%], P = 0.028) and sex (treatment effect in female [−4.78%] vs. male [0.76%], P = 0.007) were significant predictors of change in BMI at 3 months. Baseline BMI, BMI percent change at 1 month, age, incidence of nausea, vomiting, or other gastrointestinal symptoms and satiety scores did not predict 3‐month responses. Sex and measures of appetite may serve as useful predictors of glucagon‐like peptide‐1 receptor agonist treatment response among adolescents with severe obesity.
HOW DO SPEED AND SECURITY INFLUENCE CONSUMERS' PAYMENT BEHAVIOR?
Authors: Schuh Scott , Stavins Joanna
Published: December 2015

The Federal Reserve named improvements in the speed and security of the payment system as two of its policy initiatives for 2012–2016. Using new data from the 2013 Survey of Consumer Payment Choice (SCPC) and models from earlier research, we estimate how various aspects of speed and security influence consumers' decisions to adopt and use payment instruments. Some aspects of speed and security have a statistically significant influence on the adoption and use of selected payment instruments, but not as much as other characteristics of payment instruments. Using econometric models to simulate selected policies proposed by the Fed, we show that faster speed of payment deduction for Automatic Clearing House (ACH) transactions would slightly increase consumers' adoption of ACH‐based payment methods, while enhanced security of payment cards would marginally increase the use of credit and debit cards. However, neither improvement is likely to increase consumer welfare much because consumer demand for payments is very inelastic with respect to speed and security. Our analysis focuses exclusively on consumers' behavior and does not include potential benefits of improvements to the payment system that would directly benefit businesses or financial institutions. In addition, preventing security breaches may preserve public confidence in the payment system, benefitting consumers even if they do not change their payment behavior. (JEL D12, D14, E58)
Fabrication of high‐quality silica photonic crystals on polyester fabrics by gravitational sedimentation self‐assembly
Authors: Zhou Lan , Wu Yujiang , Liu Guojin , Li Yichen , Fan Qinguo , Shao Jianzhong
Published: December 2015

A series of monodispersed silica microspheres with favourable sphericity and different diameters in the range 180–380 nm were prepared by adjusting the concentrations of tetraethylorthosilicate, ammonia, and deionised water by the Stöber method. In different self‐assembly conditions, the quality of silica photonic crystals on a polyester fabric substrate was investigated by field‐emission scanning electron microscopy for the morphology of the crystal structures and by spectrometry for their stop band intensities. High‐quality silica photonic crystals with a face‐centred cubic (fcc) array on polyester fabrics were produced at a low evaporation rate by adopting a high‐relative‐humidity controlled condition with a medium mass fraction of colloidal silica, and exhibited brilliant and variable structural colours, depending on the photonic band gap regulated by the spherical size of the silica microspheres and the viewing angles.
Interaction of Phenol Red with cetyltrimethylammonium bromide in aqueous solution
Authors: Wang Nong , Su Chengwu , Xiao Shijun
Published: December 2015

This paper studies the interaction of anionic dye Phenol Red with cationic surfactant cetyltrimethylammonium bromide in aqueous solution and its influence on the formation of cetyltrimethylammonium bromide micelles for the first time. We obtain a series of thermodynamic parameters of the interaction by establishing a reasonable physical model of the association. Moreover, an in‐depth study on the variation in the absorption spectrum finds that the value of absorbance at the maximum absorption peak changes regularly with increase in the cetyltrimethylammonium bromide concentration. By establishing the micellisation models and measuring the changes in electrical conductivity with different cetyltrimethylammonium bromide concentrations, the critical micelle concentration values are obtained, which are essentially the same as the range of concentrations of regular change in absorbance, which shows that the formation of the cetyltrimethylammonium bromide micelles have an impact on the association interaction between Phenol Red and cetyltrimethylammonium bromide. All these data and phenomena illustrate a strong interaction between Phenol Red and cetyltrimethylammonium bromide.
Tumour cell population growth inhibition and cell death induction of functionalized 6‐aminoquinolone derivatives
Authors: Franci G. , Manfroni G. , Cannalire R. , Felicetti T. , Tabarrini O. , Salvato A. , Barreca M. L. , Altucci L. , Cecchetti V.
Published: December 2015

Objectives

A number of previous studies has provided evidence that the well‐known anti‐bacterial quinolones may have potential as anti‐cancer drugs. The aim of this study was to evaluate potential anti‐tumour activity and selectivity of a set of 6‐aminoquinolones showing some chemical similarity to naphthyridone derivative CX‐5461, recently described as innovative anti‐cancer agent.

Materials and methods

In‐house quinolones 1‐8 and ad hoc synthesized derivatives 9‐13 were tested on Michigan Cancer Foundation‐7 (MCF‐7) breast cancer cells and mesenchymal progenitor (MePR2B) cell lines, analysing their effects on the cell cycle and cell death using FACS methodology. Activation of p53 was evaluated by western blotting.

Results

Benzyl esters 4, 5 and their amide counterparts 12, 13 drastically modulated MCF‐7 cell cycles inducing DNA fragmentation and cell death, thus proving to be potential anti‐tumour compounds. When assayed in non‐tumour MePR2B cells, compounds 4 and 5 were cytotoxic while 12 and 13 had a certain degree of selectivity, with compound 12 emerging as the most promising. Western blot analysis revealed that severe p53‐K382ac activation was promoted by benzylester 5. In contrast, amide 12 exerted only a moderate effect which was, however, comparable to that of suberoylanilide hydoxamic acid (SAHA).

Conclusions

Taken together, these results further reinforce evidence that quinolones have potential as anti‐cancer agents. Future work will be focused on understanding compound 12 mechanisms of action, and to obtain more potent and selective compounds.
Atopy: a risk factor of refractory mycoplasma pneumoniae pneumonia?
Authors: Bao Yi‐Xiao , Li Jing , Tian Ye , Liu Quang‐Hua , Bao Jun
Published: December 2015

Objective

To investigate the relationship of pathogen DNA copies with clinic and laboratory features among children with Mycoplasma pneumoniae (MP) pneumonia.

Methods

A total of 95 enrolled children with MP pneumonia were assigned into the high‐MP‐load group (>106/mL) and the low‐MP‐load group (≤106/mL) according to MP‐DNA copies in bronchoalveolar lavage fluid (BALF). Clinical characteristics and any allergy history were collected. Aeroallergens and food allergens were detected with a skin test. Serum IgE and eosinophil cationic protein (ECP) were assessed using enzyme immunoassay. BALF levels of IL‐4, IFN‐γ, IL‐8 and TNF‐α were assessed by ELISA.

Results

Compared with the low‐MP‐load group, 72.7% in the high‐MP‐load group developed refractory MP pneumonia who failed to respond to at least 1‐week treatment with macrolides (72.7% vs 41.9%, P = 0.005). More children in the high‐load group than those in the low‐load group presented with extrapulmonary manifestations, lung consolidation, pleural effusion and atopic conditions including any allergy history, positive findings of aeroallergen test and increased serum IgE and ECP (P < 0.05). A significant higher BALF IL‐4 level was seen in the high‐load group versus the low‐load group (23.00 ± 11.24 vs 14.68 ± 7.12; pg/mL; P < 0.01). There were no significant differences in BALF levels of IFN‐γ, IL‐8 and TNF‐α between the two groups (P > 0.05).

Conclusion

Atopy may be a risk factor for the presence and severity of refractory MP pneumonia due to the high pathogen load in airway.
Invasion debt – quantifying future biological invasions
Authors: Rouget Mathieu , Robertson Mark P. , Wilson John R. U. , Hui Cang , Essl Franz , Renteria Jorge L. , Richardson David M.
Published: December 2015

Aim

We develop a framework for quantifying invasions based on lagged trends in invasions (‘invasion debt’) with the aim of identifying appropriate metrics to quantify delayed responses at different invasion stages – from introduction to when environmental impacts occur.

Location

World‐wide; detailed case study in South Africa.

Methods

We define four components of invasion debt: the number of species not yet introduced but likely to be introduced in the future given current levels of introduction/propagule pressure; the establishment of introduced species; the potential increase in area invaded by established species (including invasive species); and the potential increase in impacts. We demonstrate the approach in terms of number of species for 21 known invasive Australian Acacia species globally and estimate three components of invasion debt for 58 Acacia species already introduced to South Africa by quantifying key invasion factors (environmental suitability, species invasion status, residence time, propagule pressure, spread rate and impacts).

Results

Current global patterns of invasive species richness reflect historical trends of introduction – most acacia species that will become invasive in southern Africa have already invaded, but there is a substantial establishment debt in South and North America. In South Africa, the likely consequence of invasion debt over the next 20 years was estimated at: four additional species becoming invasive with an average increase of 1075 km2 invaded area per invasive species. We estimate that this would require over US$ 500 million to clear.

Main conclusions

Our results indicate that invasion debt is a valuable metric for reporting on the threats attributable to biological invasions, that invasion debt must be factored into strategic plans for managing global change, and, as with other studies, they highlight the value of proactive management. Given the uncertainty associated with biological invasions, further work is required to quantify the different components of invasion debt.
Legal Pluralism and Hybrid Governance: Bridging Two Research Lines
Authors: Reyntjens Filip
Published: December 2015

Legal pluralism and hybrid governance are two lines of research that address the interactions between state (official) and non‐state (unofficial) norms. Both come to similar observations, yet they seem hardly aware of each other's existence. With very few exceptions, the one does not refer to the other. This article seeks to explore whether links can be established. It presents both lines of research, identifies common ground, explores what they can learn from each other, and seeks to find whether the distance can be bridged. It concludes that legal pluralism and hybrid governance could be mutually reinforcing if scholars in the two lines were aware of and used each other's findings and methods, and saw each other as complementary.
Toward multifactorial null models of range contraction in terrestrial vertebrates
Authors: Lucas Pablo M. , González‐Suárez Manuela , Revilla Eloy
Published: December 2015

The contraction of a species’ distribution range, which results from the extirpation of local populations, generally precedes its extinction. Therefore, understanding drivers of range contraction is important for conservation and management. Although there are many processes that can potentially lead to local extirpation and range contraction, three main null models have been proposed: demographic, contagion, and refuge. The first two models postulate that the probability of local extirpation for a given area depends on its relative position within the range; but these models generate distinct spatial predictions because they assume either a ubiquitous (demographic) or a clinal (contagion) distribution of threats. The third model (refuge) postulates that extirpations are determined by the intensity of human impacts, leading to heterogeneous spatial predictions potentially compatible with those made by the other two null models. A few previous studies have explored the generality of some of these null models, but we present here the first comprehensive evaluation of all three models. Using descriptive indices and regression analyses we contrast the predictions made by each of the null models using empirical spatial data describing range contraction in 386 terrestrial vertebrates (mammals, birds, amphibians, and reptiles) distributed across the World. Observed contraction patterns do not consistently conform to the predictions of any of the three models, suggesting that these may not be adequate null models to evaluate range contraction dynamics among terrestrial vertebrates. Instead, our results support alternative null models that account for both relative position and intensity of human impacts. These new models provide a better multifactorial baseline to describe range contraction patterns in vertebrates. This general baseline can be used to explore how additional factors influence contraction, and ultimately extinction for particular areas or species as well as to predict future changes in light of current and new threats.
Characterization of physiological phenotypes of dentate gyrus synapses of PDZ1/2 domain‐deficient PSD‐95‐knockin mice
Authors: Nagura Hitoshi , Doi Tomoko , Fujiyoshi Yoshinori
Published: December 2015

The hippocampal formation is involved in several important brain functions of animals, such as memory formation and pattern separation, and the synapses in the dentate gyrus (DG) play critical roles as the first step in the hippocampal circuit. Previous studies have reported that mice with genetic modifications of the PDZ1/2 domains of postsynaptic density (PSD)‐95 exhibit altered synaptic properties in the DG and impaired hippocampus‐dependent behaviors. Based on the involvement of the DG in the regulation of behaviors, these data suggest that the abnormal behavior of these knockin (KI) mice is due partly to altered DG function. Precise understanding of the phenotypes of these mutant mice requires characterization of the synaptic properties of the DG, and here we provide detailed studies of DG synapses. We have demonstrated global changes in the PSD membrane‐associated guanylate kinase expression pattern in the DG of mutant mice, and DG synapses in these mice exhibited increased long‐term potentiation under a wide range of stimulus intensities, although the N‐methyl‐d‐aspartic acid receptor dependence of the long‐term potentiation was unchanged. Furthermore, our data also indicate increased silent synapses in the DG of the KI mice. These findings suggest that abnormal protein expression and physiological properties disrupt the function of DG neurons in these KI mice.
Fuzzy regions in an intrinsically disordered protein impair protein–protein interactions
Authors: Gruet Antoine , Dosnon Marion , Blocquel David , Brunel Joanna , Gerlier Denis , Das Rahul K. , Bonetti Daniela , Gianni Stefano , Fuxreiter Monika , Longhi Sonia , Bignon Christophe
Published: December 2015

Despite the partial disorder‐to‐order transition that intrinsically disordered proteins often undergo upon binding to their partners, a considerable amount of residual disorder may be retained in the bound form, resulting in a fuzzy complex. Fuzzy regions flanking molecular recognition elements may enable partner fishing through non‐specific, transient contacts, thereby facilitating binding, but may also disfavor binding through various mechanisms. So far, few computational or experimental studies have addressed the effect of fuzzy appendages on partner recognition by intrinsically disordered proteins. In order to shed light onto this issue, we used the interaction between the intrinsically disordered C‐terminal domain of the measles virus (MeV) nucleoprotein (NTAIL) and the X domain (XD) of the viral phosphoprotein as model system. After binding to XD, the N‐terminal region of NTAIL remains conspicuously disordered, with α‐helical folding taking place only within a short molecular recognition element. To study the effect of the N‐terminal fuzzy region on NTAIL/XD binding, we generated N‐terminal truncation variants of NTAIL, and assessed their binding abilities towards XD. The results revealed that binding increases with shortening of the N‐terminal fuzzy region, with this also being observed with hsp70 (another MeV NTAIL binding partner), and for the homologous NTAIL/XD pairs from the Nipah and Hendra viruses. Finally, similar results were obtained when the MeV NTAIL fuzzy region was replaced with a highly dissimilar artificial disordered sequence, supporting a sequence‐independent inhibitory effect of the fuzzy region.
Satellite chlorophyll fluorescence measurements reveal large‐scale decoupling of photosynthesis and greenness dynamics in boreal evergreen forests
Authors: Walther Sophia , Voigt Maximilian , Thum Tea , Gonsamo Alemu , Zhang Yongguang , Köhler Philipp , Jung Martin , Varlagin Andrej , Guanter Luis
Published: December 2015

Mid‐to‐high latitude forests play an important role in the terrestrial carbon cycle, but the representation of photosynthesis in boreal forests by current modelling and observational methods is still challenging. In particular, the applicability of existing satellite‐based proxies of greenness to indicate photosynthetic activity is hindered by small annual changes in green biomass of the often evergreen tree population and by the confounding effects of background materials such as snow. As an alternative, satellite measurements of sun‐induced chlorophyll fluorescence (SIF) can be used as a direct proxy of photosynthetic activity. In this study, the start and end of the photosynthetically active season of the main boreal forests are analysed using spaceborne SIF measurements retrieved from the GOME‐2 instrument and compared to that of green biomass, proxied by vegetation indices including the Enhanced Vegetation Index (EVI) derived from MODIS data. We find that photosynthesis and greenness show a similar seasonality in deciduous forests. In high‐latitude evergreen needleleaf forests, however, the length of the photosynthetically active period indicated by SIF is up to 6 weeks longer than the green biomass changing period proxied by EVI, with SIF showing a start‐of‐season of approximately 1 month earlier than EVI. On average, the photosynthetic spring recovery as signalled by SIF occurs as soon as air temperatures exceed the freezing point (2–3 °C) and when the snow on the ground has not yet completely melted. These findings are supported by model data of gross primary production and a number of other studies which evaluated in situ observations of CO2 fluxes, meteorology and the physiological state of the needles. Our results demonstrate the sensitivity of space‐based SIF measurements to light‐use efficiency of boreal forests and their potential for an unbiased detection of photosynthetic activity even under the challenging conditions interposed by evergreen boreal ecosystems.
Productivity and water use efficiency ofAgave americanain the first field trial as bioenergy feedstock on arid lands
Authors: Davis Sarah C. , Kuzmick Emily R. , Niechayev Nicholas , Hunsaker Douglas J.
Published: December 2015

Agavespecies are high‐yielding crassulacean acid metabolism (CAM) plants, some of which are grown commercially and recognized as potential bioenergy species for dry regions of the world. This study is the first field trial ofAgavespecies for bioenergy in the United States, and was established to compare the production ofAgave americanawith the production ofAgave tequilanaandAgave fourcroydes, which are produced commercially in Mexico for tequila and fiber. The field trial included four experimental irrigation levels to test the response of biomass production to water inputs. After 3 years, annual production of healthyA. americanaplants reached 9.3 Mg dry mass ha−1 yr−1(including pup mass) with 530 mm of annual water inputs, including both rainfall and irrigation. Yields in the most arid conditions tested (300 mm yr−1water input) were 2.0–4.0 Mg dry mass ha−1 yr−1.Agave tequilanaandAgave fourcroydeswere severely damaged by cold in the first winter, and produced maximum yields of only 0.04 Mg ha−1 yr−1and 0.26 Mg ha−1 yr−1, respectively. The agave snout weevil (Scyphophorus acupunctatus) emerged as an important challenge forA. americanacropping, killing a greater number of plants in the higher irrigation treatments. Physiological differences inA. americanaplants across irrigation treatments were most evident in the warmest season, with gas exchange beginning up to 3 h earlier and water use efficiency declining in treatments with the greatest water input (780 mm yr−1water input). Yields were lower than previous projections forAgavespecies, but results from this study suggest thatA. americanahas potential as a bioenergy crop and would have substantially reduced irrigation requirements relative to conventional crops in the southwesternUSA. Challenges for pest management and harvesting must still be addressed before an efficient production system that usesAgavecan be realized.
Frequency of pediatric migraine with aura in a clinic‐based sample
Authors: Genizi Jacob , Khourieh Matar Amal , Zelnik Nathanel , Schertz Mitchell , Srugo Isaac
Published: December 2015

Objective

To assess the prevalence and risk factors for pediatric migraine with aura (MWA) among patients presenting to pediatric neurology clinics.

Background

Headache is a common complaint among children, and the prevalence of migraine is about 8%. Up to one third of adults with migraine report experiencing aura; however, the exact percentage in children is unknown.

Methods

Medical records of children presenting with headache to three pediatric neurology clinics in Haifa in the last 5 years were retrospectively reviewed. Inclusion criteria were a diagnosis of migraine headache at 5‐18 years of age.

Results

Of 260 children (140 female) who had migraine, 26.2% experienced aura. MWA was more common among females compared to males (32.6% vs 18.9%, P < .01) and among older children (OR: 2.50, 95% CI: 1.20‐5.20; P < .01). Among those who experienced aura, visual aura was more common in females than males (66.7% vs 33.3%, P < .04). Family history of migraine was strongly related to MWA (P < .02): the odds of MWA were 2.46 times greater in children who had a family history of migraine. (OR: 2.46, 95% CI: 1.08‐5.62; P < .03).

Conclusions

MWA is as common in children as in adults. Aura is more common in older children. Children who have MWA are more likely to have a family history of migraine.
Cytoplasmic expression of maspin predicts unfavourable prognosis in patients with squamous cell carcinoma of the lung
Authors: Matsuoka Yuki , Takagi Yuzo , Nosaka Kanae , Sakabe Tomohiko , Haruki Tomohiro , Araki Kunio , Taniguchi Yuji , Shiomi Tatsushi , Nakamura Hiroshige , Umekita Yoshihisa
Published: December 2015

Aims

Maspin is known to be a tumour suppressor protein, and its prognostic significance in patients with several types of cancer, including lung squamous cell carcinoma (SCC), has been reported. However, its prognostic impact on lung SCC has been controversial. We explored the prognostic value of maspin expression with particular reference to its subcellular localization in patients with lung SCC.

Methods and results

Paraffin‐embedded tissue samples from 101 curatively resected patients with lung SCC were analysed immunohistochemically using an antibody for maspin. Maspin positivity was defined as strong expression in only the cytoplasm and observed in 25 patients (24.6%). It correlated significantly with the presence of lymph node metastasis (P = 0.006) and higher pathological stage (P = 0.003). The patients were followed‐up for 2–119 months (median: 50 months), and the maspin‐positive group had shorter disease‐free survival (DFS) and disease‐specific survival (DSS) by log‐rank test (P = 0.002, P = 0.016, respectively). Multivariate analysis revealed that the status of maspin was the only independent prognostic factor for DFS and DSS (P = 0.017, P = 0.047, respectively).

Conclusions

Cytoplasmic expression of maspin could be an independent unfavourable prognostic indicator in patients with lung SCC.
Biological markers of fertility (inhibin‐B) in HIV‐infected men: influence of HIV infection and antiretroviral therapy
Authors: Moreno‐Pérez O , Boix V , Merino E , Picó A , Reus S , Alfayate R , Giner L , Mirete R , Sánchez‐Payá J , Portilla J
Published: December 2015

Objectives

Inhibin B (IB) levels and the IB: follicle‐stimulating hormone (FSH) ratio (IFR), biomarkers of global Sertoli cell function, show a strong relationship with male fertility. The aim of the study was to examine the prevalence of impaired fertility potential in HIV‐infected men and the influence of antiretroviral therapy (ART) on fertility biomarkers.

Methods

A cross‐sectional study with sequential sampling was carried out. A total of 169 clinically stable patients in a cohort of HIV‐infected men undergoing regular ambulatory assessment in a tertiary hospital were included. The mean [± standard deviation (SD)] age of the patients was 42.6 ± 8.1 years, all were clinically stable, 61.5% had disease classified as Centers for Disease Control and Prevention (CDC) stage A, and were na?ve to ART or had not had any changes to ART for 6 months (91.1%). Morning baseline IB and FSH concentrations were measured using an enzyme‐linked immunosorbent assay (ELISA) and an electrochemiluminescent immunoassay (ECLIA), respectively. A multivariate logistic regression model was used to identify factors associated with impaired fertility, defined as IB < 119 pg/mL or IFR < 23.5.

Results

The mean (± SD) IB level was 250 ± 103 pg/mL, the median [interquartile range (IQR)] FSH concentration was 5.1 (3.3–7.8) UI/L and the median (IQR) IFR was 46.1 (26.3–83.7). The prevalence of impaired fertility was 21.9% [95% confidence interval (CI) 16.3–20.7%]. Negative correlations of body mass index and waist: hip ratio with FSH and IB levels were observed (P < 0.01), while a sedentary lifestyle and previous nevirapine exposure were associated with a decreased risk of IB levels ≤ 25th percentile in multivariate analysis. Only older age, as a risk factor, and sedentary lifestyle, with a protective effect, were independently associated with impaired fertility in multivariate analysis.

Conclusions

Global testicular Sertoli cell function and fertility potential, assessed indirectly through serum IB levels and IB: FSH ratio, appear to be well maintained in HIV‐infected men and not damaged by ART.