bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel keratin preparation supports growth and differentiation of odontoblast‐like cells
Authors: Ajay Sharma L. , Ali M. A. , Love R. M. , Wilson M. J. , Dias G. J.
Published: May 2015

Aim

To fabricate a keratin hydrogel, characterize its functionality as a biomaterial and investigate the effects of keratin on growth and differentiation of odontoblast‐like cells.

Methodology

Keratins were extracted from sheep wool using a well‐established technique. The extracted proteins were purified by dialysis, quantified by gel electrophoresis, mass spectrometry, amino acid analysis and inductively coupled mass spectrometry. The microstructure of the fabricated keratin hydrogels was studied by scanning electron microscopy, flow characteristics by rheometer, hydrolytic stability and cytocompatibility by Live/Dead® cell assay. Furthermore, the influence of keratin on odontoblast‐like cells (MDPC‐23) was assessed to confirm their bioactivity at different dilutions. Cell proliferation was studied using alamarBlue® assay and differentiation by alkaline phosphatase enzyme activity, alizarin red staining and calcium quantification, reverse transcription polymerase chain reaction (rt‐PCR) and immunocytochemical staining for dentine matrix protein‐ 1 (DMP‐1) expression. anova with Tukey's tests was performed for statistical comparison.

Results

The characterized hydrogel was injectable with a highly porous architecture that underwent slow degradation, and its cytocompatibility was statistically equivalent to collagen hydrogel (P > 0.05). Cell proliferation and differentiation were enhanced at the optimal keratin concentration of 0.1 mg mL−1. At this concentration, the influence of keratin on cell differentiation was demonstrated by marked elevation in alkaline phosphatase activity (P < 0.05), calcium deposition (P < 0.01), gene expression (P < 0.01) and positive immunostaining for DMP‐1.

Conclusion

The presence of keratin enhanced odontoblast cell behaviour. Keratin hydrogels may be a potential scaffold for pulp–dentine regen‐eration.
Effect of the cultivation mode on red pigments production from Monascus ruber
Authors: Hajjaj Hassan , Goma Gerard , François Jean M.
Published: May 2015

In submerged cultures performed in chemically defined fermentation medium containing glucose and glutamate, the growth and production of water‐soluble red pigments and citrinin by the filamentous fungus Monascus ruber were studied under various carbon/nitrogen (C/N) ratios. The specific production of the red pigments was optimal at a glucose/glutamate ratio of about 10 and then steadily decreased at higher C/N ratio. In contrast, the production of the mycotoxin increased with increased C/N with an optimum in the range of 30–45. In a fed‐batch mode, it was also found that the production of pigments was not favoured in fed‐batch mode by feeding the medium with glucose while keeping the C/N ratio lower than 10. This low production likely resulted from concurrent high accumulation of L‐malic acid that was reported to inhibit this production. In contrast, this mode of cultivation was rather favourable for the production of the mycotoxin.
Creatinine as predictor value of mortality and acute kidney injury in rhabdomyolysis
Authors: Baeza‐Trinidad R. , Brea‐Hernando A. , Morera‐Rodriguez S. , Brito‐Diaz Y. , Sanchez‐Hernandez S. , El Bikri L. , Ramalle‐Gomara E. , Garcia‐Alvarez J. L.
Published: May 2015

Background

Rhabdomyolysis (RB) is a syndrome characterised by decomposition of skeletal muscle that could be life threatening, so the identification of biomarkers of its severity could help us in its treatment. Creatine kinase (CK) is usually taken as a reference in patients with RB in order to stratify prognosis, however that is not probably the most effective parameter.

Aims

The present study was designed to analyse the specific features and mortality of patients with RB and the relation between creatinine, CK and mortality.

Methods

Retrospective cohort analysis among patients admitted to San Pedro Hospital in Logroño (Spain) with RB (CK levels higher than 2000 U/L) diagnosed since 1 January 2009 until 31 December 2; 013 522 patients with RB patients diagnosed of RB were collected. The aetiology and the analytical feature (creatinine, CK, calcium, phosphorus, pH and bicarbonate), as well as 30‐year mortality, were investigated.

Results

Among the 522 patients, there were 138 deaths. Four patients required renal replacement therapy. The most common cause of RB was trauma (29%). Infectious aetiology had the highest mortality (41.2%). The median CK was 3451 u/L (interquartile range 3348), and the mean creatinine at admission was 132.6 umol/L (±110.5). Initial CK levels do not have predictive ability on mortality or renal dysfunction in contrast to initial creatinine values. Each state of acute kidney injury (AKI) increased mortality compared with those who have not presented this renal dysfunction (P < 0.0001). Age, calcium, phosphorus, bicarbonate and pH are associated with AKI.

Conclusion

Despite being a diagnostic marker for RB, initial CK levels do not predict mortality. However, creatinine initial levels are related to progression to acute renal injury and mortality at 30 days.
Pre‐treatment with dual antiplatelet therapy in patients with non‐ST‐segment elevation acute coronary syndromes undergoing percutaneous coronary intervention
Authors: Yudi M. B. , Eccleston D. , Andrianopoulos N. , Farouque O. , Duffy S. J. , Brennan A. , Reid C. , Clark D. J. , Ajani A. E. ,   Melbourne Interventional Group
Published: May 2015

Background

Although dual antiplatelet therapy is the standard of care in non‐ST‐segment elevation acute coronary syndromes (NSTEACS), it remains unclear when a second antiplatelet agent should be initiated. We sought to assess the safety and efficacy of pre‐treatment with clopidogrel in patients with NSTEACS undergoing percutaneous coronary intervention (PCI).

Methods

We analysed baseline clinical and procedural characteristics of 6817 patients with NSTEACS who underwent PCI from the Melbourne Interventional Group registry from 2005 to 2012. Patients were included in the pre‐treatment group if clopidogrel was administered prior to cardiac catheterisation. We assessed 30‐day mortality, myocardial infarction (MI) and major adverse cardiovascular events. The safety endpoint was in‐hospital bleeding.

Results

Of the 6817 patients, only 2951 (43%) received pre‐treatment with clopidogrel. Patients in the pre‐treatment group were more likely to present with unstable angina (70.8% vs 68.2%, P = 0.02) and have a history of MI (35.6% vs 23.6%, P < 0.01) but were less likely to have PCI within 24 h of admission (17.2% vs 25.2%, P < 0.01). There was no difference between the groups in 30‐day mortality (0.9% vs 1.4%, P = 0.06), MI (2.0% vs 2.2%, P = 0.52) or major adverse cardiovascular event (3.7% vs 4.2%, P = 0.25). There was no difference in bleeding complications (1.9% vs 1.9%, P = 0.94).

Conclusions

Pre‐treatment with dual antiplatelet therapy in NSTEACS is not routine clinical practice in Australia. Pre‐treatment appears safe but is not associated with improved short‐term clinical outcomes.
Workplace bullying prevention: a critical discourse analysis
Authors: Johnson Susan L.
Published: May 2015

Aim

The aim of this study was to analyse the discourses of workplace bullying prevention of hospital nursing unit managers and in the official documents of the organizations where they worked.

Background

Workplace bullying can be a self‐perpetuating problem in nursing units. As such, efforts to prevent this behaviour may be more effective than efforts to stop ongoing bullying. There is limited research on how healthcare organizations characterize their efforts to prevent workplace bullying.

Design

This was a qualitative study.

Method

Critical discourse analysis and Foucault's writings on governmentality and discipline were used to analyse data from interviews with hospital nursing unit managers (n = 15) and organizational documents (n = 22). Data were collected in 2012.

Findings

The discourse of workplace bullying prevention centred around three themes: prevention of workplace bullying through managerial presence, normalizing behaviours and controlling behaviours. All three are individual level discourses of workplace bullying prevention.

Conclusion

Current research indicates that workplace bullying is a complex issue with antecedents at the individual, departmental and organizational level. However, the discourse of the participants in this study only focused on prevention of bullying by moulding the behaviours of individuals. The effective prevention of workplace bullying will require departmental and organizational initiatives. Leaders in all types of organizations can use the results of this study to examine their organizations’ discourses of workplace bullying prevention to determine where change is needed.
The climate space of fire regimes in north‐western North America
Authors: Whitman Ellen , Batllori Enric , Parisien Marc‐André , Miller Carol , Coop Jonathan D. , Krawchuk Meg A. , Chong Geneva W. , Haire Sandra L.
Published: May 2015

Aim

Studies of fire activity along environmental gradients have been undertaken, but the results of such studies have yet to be integrated with fire‐regime analysis. We characterize fire‐regime components along climate gradients and a gradient of human influence.

Location

We focus on a climatically diverse region of north‐western North America extending from northern British Columbia, Canada, to northern Utah and Colorado, USA.

Methods

We used a multivariate framework to collapse 12 climatic variables into two major climate gradients and binned them into 73 discrete climate domains. We examined variation in fire‐regime components (frequency, size, severity, seasonality and cause) across climate domains. Fire‐regime attributes were compiled from existing databases and Landsat imagery for 1897 large fires. Relationships among the fire‐regime components, climate gradients and human influence were examined through bivariate regressions. The unique contribution of human influence was also assessed.

Results

A primary climate gradient of temperature and summer precipitation and a secondary gradient of continentality and winter precipitation in the study area were identified. Fire occupied a distinct central region of such climate space, within which fire‐regime components varied considerably. We identified significant interrelations between fire‐regime components of fire size, frequency, burn severity and cause. The influence of humans was apparent in patterns of burn severity and ignition cause.

Main conclusions

Wildfire activity is highest where thermal and moisture gradients converge to promote fuel production, flammability and ignitions. Having linked fire‐regime components to large‐scale climate gradients, we show that fire regimes – like the climate that controls them – are a part of a continuum, expanding on models of varying constraints on fire activity. The observed relationships between fire‐regime components, together with the distinct role of climatic and human influences, generate variation in biotic communities. Thus, future changes to climate may lead to ecological changes through altered fire regimes.
Uncovering spatial patterns in the natural and human history of Brazil nut (Bertholletia excelsa) across the Amazon Basin
Authors: Thomas Evert , Alcázar Caicedo Carolina , McMichael Crystal H. , Corvera Ronald , Loo Judy
Published: May 2015

Aim

Our goal was to test the hypothesis that ancient humans substantially contributed to shaping the current distribution of Brazil nut (Bertholletia excelsa), an Amazonian tree species that has been important for human livelihoods since pre‐Columbian times. We scrutinized the putative association between Brazil nut and Amazonian Dark Earth soils (ADE) and geometric earthworks called geoglyphs, and examined the existence of continental patterns in human footprints on Brazil nut stands.

Location

Amazon Basin.

Methods

We carried out a spatially explicit meta‐analysis of the variation of Brazil nut stand metrics across the Amazon Basin based on 87,617 density estimates and 488 average stand diameter assessments, and related these to previously published datasets and suitability maps of Brazil nut,ADEand geoglyphs.

Results

We found consistently higher Brazil nut suitability scores, stand densities and average stand diameters in the vicinities ofADEthan at larger distances, regardless of their position along a gradient from south‐western to north‐eastern Amazonia. For geoglyph sites such a pattern was only found for Brazil nut habitat suitability scores. The available data further revealed an accumulation of Brazil nut stands with increasing densities and average diameters from south‐western to central and eastern Amazonia.

Main conclusions

Our findings suggest that the chance of encountering Brazil nut stands bearing the marks of past human influences increases from south‐western to central and eastern Amazonia. In south‐western Amazonia, the regeneration of Brazil nut seems to have been controlled predominantly by natural processes, whereas in central and eastern Amazonia, anthropogenic disturbance has been more important since pre‐Columbian times. However, it remains challenging to disentangle human influences on the distribution and abundance of Brazil nut from existing environmental gradients across the Amazon Basin. In general, the results of this meta‐analysis bode well for the future coexistence of Brazil nut with different forms of contemporary human land use.
Cascading costs of reproduction in female house wrens induced to lay larger clutches
Authors: Hodges C. J. , Bowers E. K. , Thompson C. F. , Sakaluk S. K.
Published: May 2015

In many species, females produce fewer offspring than they are capable of rearing, possibly because increases in current reproductive effort come at the expense of a female's own survival and future reproduction. To test this, we induced female house wrens (Troglodytes aedon) to lay more eggs than they normally would and assessed the potential costs of increasing cumulative investment in the three main components of the avian breeding cycle – egg laying, incubation and nestling provisioning. Females with increased clutch sizes reared more offspring in the first brood than controls, but fledged a lower proportion of nestlings. Moreover, nestlings of experimental females were lighter than those of control females as brood size and prefledging mass were negatively correlated. In second broods of the season, when females were not manipulated, experimental females laid the same number of eggs as controls, but experienced an intraseasonal cost through reduced hatchling survival and a lower number of young fledged. Offspring of control and experimental females were equally likely to recruit to the breeding population, although control females produced more recruits per egg laid. The reproductive success of recruits from broods of experimental and control females did not differ. The manipulation also induced interseasonal costs to future reproduction, as experimental females had lower fecundity than controls when breeding at least 2 years after having their reproductive effort experimentally increased. Finally, females producing the modal clutch size of seven eggs in their first broods had the highest lifetime number of fledglings.
Design and implementation of a combined influenza immunization and tuberculosis screening campaign with simulation modelling
Authors: Heim Joseph A. , Huang Hao , Zabinsky Zelda B. , Dickerson Jane , Wellner Monica , Astion Michael , Cruz Doris , Vincent Jeanne , Jack Rhona
Published: May 2015

Rationale, aims and objectives

Design and implement a concurrent campaign of influenza immunization and tuberculosis (TB) screening for health care workers (HCWs) that can reduce the number of clinic visits for each HCW.

Method

A discrete‐event simulation model was developed to support issues of resource allocation decisions in planning and operations phases.

Results

The campaign was compressed to100 days in 2010 and further compressed to 75 days in 2012 and 2013. With more than 5000 HCW arrivals in 2011, 2012 and 2013, the 14‐day goal of TB results was achieved for each year and reduced to about 4 days in 2012 and 2013.

Conclusion

Implementing a concurrent campaign allows less number of visiting clinics and the compressing of campaign length allows earlier immunization. The support of simulation modelling can provide useful evaluations of different configurations.
Validity of self‐reported sleep bruxism among myofascial temporomandibular disorder patients and controls
Authors: Raphael K. G. , Janal M. N. , Sirois D. A. , Dubrovsky B. , Klausner J. J. , Krieger A. C. , Lavigne G. J.
Published: May 2015

Sleep bruxism (SB), primarily involving rhythmic grinding of the teeth during sleep, has been advanced as a causal or maintenance factor for a variety of oro‐facial problems, including temporomandibular disorders (TMD). As laboratory polysomnographic (PSG) assessment is extremely expensive and time‐consuming, most research testing this belief has relied on patient self‐report of SB. The current case–control study examined the accuracy of those self‐reports relative to laboratory‐based PSG assessment of SB in a large sample of women suffering from chronic myofascial TMD (n = 124) and a demographically matched control group without TMD (n = 46). A clinical research coordinator administered a structured questionnaire to assess self‐reported SB. Participants then spent two consecutive nights in a sleep laboratory. Audiovisual and electromyographic data from the second night were scored to assess whether participants met criteria for the presence of 2 or more (2+) rhythmic masticatory muscle activity episodes accompanied by grinding sounds, moderate SB, or severe SB, using previously validated research scoring standards. Contingency tables were constructed to assess positive and negative predictive values, sensitivity and specificity, and 95% confidence intervals surrounding the point estimates. Results showed that self‐report significantly predicted 2+ grinding sounds during sleep for TMD cases. However, self‐reported SB failed to significantly predict the presence or absence of either moderate or severe SB as assessed by PSG, for both cases and controls. These data show that self‐report of tooth grinding awareness is highly unlikely to be a valid indicator of true SB. Studies relying on self‐report to assess SB must be viewed with extreme caution.
Dietary forage concentration and particle size affect sorting, feeding behaviour, intake and growth of Chinese holstein male calves
Authors: Muhammad A. U. R. , Xia C. Q. , Cao B. H.
Published: May 2015

The objective of study was to evaluate the effect of forage concentration (F:C) and forage particle length (FPL) on sorting, feeding behaviour, intake, growth and body measurements of growing calves. Twenty‐eight weaned calves of body weight 156.79 ± 33.44 (mean ± SD) were used in 2 × 2 factorial arrangements with the factors FPL of hay grass (full and short) and hay grass concentrations (low, 50% and high, 65%). The treatments were as follows: full length (FL) with low F:C (50:50), FL with high F:C(65:35), short length (SL) with low F:C (50:50) and SL with high F:C (65:35). Increasing F:C and decreasing FPL enhanced sorting for short and fine particle and sorting against long particle (p < 0.05). Dry matter intake (DMI) was decreased by decreasing the FPL (p < 0.05). Increasing F:C (65:35) increased the DMI (p < 0.05). A positive interaction between FPL and F:C was found for (daily weight gain) DWG, weight gain (WG) and feed conversation ratio (FCR) (p < 0.05). In case of feeding behaviour, interaction for eating time and eating time per kilogram DM was present. Increasing the F:C increased the eating time in both FL and SL (p < 0.05). Chopping of hay had decreased the chewing time (p < 0.05). Increasing F:C increased chewing time per kilogram DMI. High F:C decreased the lying time (p < 0.05) in FL and SL treatments (p < 0.05). Increasing F:C reduced the overall abnormal behaviour (p < 0.05). These results suggested that animals performed better at higher F:C at SL diet. Intensity of sorting for short and fine particle and against long particle increased at higher F:C and SL diets. Eating time and eating time per kilogram DMI increased by increasing F:C level in both FL and SL treatments. Chewing time increased by increasing the FPL, while increasing the F:C enhanced the chewing time per kilogram DMI and reduced animal's abnormal behaviour.
Effects of two calculolytic diets on parameters of feline mineral metabolism
Authors: Pineda C. , Aguilera‐Tejero E. , Raya A. I. , Montes de Oca A. , Rodriguez M. , Lopez I.
Published: May 2015

OBJECTIVES

To evaluate the influence of two feline calculolytic diets on selected parameters of mineral metabolism.

MATERIALS AND METHODS

Two dry commercial diets designed for struvite urolith dissolution were evaluated in 14 cats. The study was designed as a two‐sequence, four‐period crossover protocol with a baseline period, two 60‐day “run‐in” periods in which calculolytic diets (Diet 1 and Diet 2) were fed and one 30‐day “wash‐out” period. Data are expressed as median (range).

RESULTS

Feeding the calculolytic diets for two months did not alter plasma concentrations of calcium, phosphorus, magnesium and parathyroid hormone. A significant (P < 0.05 in each case) decline in calcitriol was observed after administering both diets from 236.4 (122.4–429.6) to 170.4 (108.0–394.3) pmol/L (Diet 1) and from 278.4 (153.6–492.0) to 177.1 (87.6–392.4) pmol/L (Diet 2). Cats fed Diet 1 showed a significant increase in urine calcium concentration (from 0.3 (0.2–0.5) to 0.4 (0.3–0.7) mmol/L). Magnesium concentration in urine was significantly increased with both diets, from 1.4 (0.1–1.7) to 1.5 (1.3–2.4) mmol/L (Diet 1) and from 1.1 (0.4–1.9) to 2.0 (0.1–3.1) mmol/L (Diet 2).

CLINICAL SIGNIFICANCE

Both diets resulted in an increased urinary concentration of magnesium, through different mechanisms: urine acidification (Diet 1) and increased sodium load (Diet 2).
Esophagogastric junction morphology is associated with a positive impedance‐pH monitoring in patients with GERD
Authors: Tolone S. , de Cassan C. , de Bortoli N. , Roman S. , Galeazzi F. , Salvador R. , Marabotto E. , Furnari M. , Zentilin P. , Marchi S. , Bardini R. , Sturniolo G. C. , Savarino V. , Savarino E.
Published: May 2015

Background

High‐resolution manometry (HRM) provides information on esophagogastric junction (EGJ) morphology, distinguishing three different subtypes. Data on the correlation between EGJ subtypes and impedance‐pH detected reflux patterns are lacking. We aimed to correlate the EGJ subtypes with impedance‐pH findings in patients with reflux symptoms.

Methods

Consecutive patients with suspected gastroesophageal reflux disease (GERD) were enrolled. All patients underwent HRM and impedance‐pH testing off‐therapy. EGJ was classified as: Type I, no separation between the lower esophageal sphincter (LES) and crural diaphragm (CD); Type II, minimal separation (>1 and <2 cm); Type III, ≥2 cm separation. We measured esophageal acid exposure time (AET), number of total reflux episodes and symptom association analysis.

Key Results

We enrolled 130 consecutive patients and identified 46.2% Type I EGJ, 38.5% Type II, and 15.4% Type III patients. Type III subjects had a higher number of reflux episodes (61 vs 45, p < 0.03, vs 25, p < 0.001), a greater mean AET (12.4 vs 4.2, p < 0.02, vs 1.5, p < 0.001) and a greater positive symptom association (75% vs 72%, p = 0.732 vs 43.3%, p < 0.02) compared with Type II and I patients, respectively. Furthermore, Type II subjects showed statistically significant (overall p < 0.01) increased reflux when compared with Type I patients. Type III and II EGJ morphologies had a more frequent probability to show a positive multichannel intraluminal impedance pH monitoring than Type I (95% vs 84% vs 50%, p < 0.001).

Conclusions & Inferences

Increasing separation between LES and CD can cause a gradual and significant increase in reflux. EGJ morphology may be useful to estimate an abnormal impedance‐pH testing in GERD patients.
Bacterial‐induced calcium oscillations are common to nitrogen‐fixing associations of nodulating legumes and non‐legumes
Authors: Granqvist Emma , Sun Jongho , Op den Camp Rik , Pujic Petar , Hill Lionel , Normand Philippe , Morris Richard J. , Downie J. Allan , Geurts Rene , Oldroyd Giles E. D.
Published: May 2015

Plants that form root‐nodule symbioses are within a monophyletic ‘nitrogen‐fixing’ clade and associated signalling processes are shared with the arbuscular mycorrhizal symbiosis. Central to symbiotic signalling are nuclear‐associated oscillations in calcium ions (Ca2+), occurring in the root hairs of several legume species in response to the rhizobial Nod factor signal.

In this study we expanded the species analysed for activation of Ca2+ oscillations, including non‐leguminous species within the nitrogen‐fixing clade.

We showed that Ca2+ oscillations are a common feature of legumes in their association with rhizobia, while Cercis, a non‐nodulating legume, does not show Ca2+ oscillations in response to Nod factors from Sinorhizobium fredii NGR234. Parasponia andersonii, a non‐legume that can associate with rhizobia, showed Nod factor‐induced calcium oscillations to S. fredii NGR234 Nod factors, but its non‐nodulating sister species, Trema tomentosa, did not. Also within the nitrogen‐fixing clade are actinorhizal species that associate with Frankia bacteria and we showed that Alnus glutinosa induces Ca2+ oscillations in root hairs in response to exudates from Frankia alni, but not to S. fredii NGR234 Nod factors.

We conclude that the ability to mount Ca2+ oscillations in response to symbiotic bacteria is a common feature of nodulating species within the nitrogen‐fixing clade.
Perspectives on depression—past, present, futurea
Authors: Barchas Jack D. , Brody Benjamin D.
Published: May 2015

Depression presents a wide canvas for considering some approaches, issues, and problems in the study of major categories of mental illness in the context of current behavioral and molecular neurobiology. The study of depression encompasses multiple interactions among psychiatry, neurology, and neuroscience, as well as interactions with a host of other disciplines. This paper considers issues from an American perspective and discusses topics including historical aspects of the ways humanity has struggled with depression; the growth of approaches, and the “wars” in psychiatry in the middle of the 20th century between different ideologies; the development of psychiatry as a behavioral science inclusive of many disciplines; current diagnostic systems such as theDiagnostic and Statistical Manual of Mental Disorders(DSM‐5) of the American Psychiatric Association, and theICD‐10 Classification of Mental and Behavioral Disordersof the World Health Organization; the efforts to delineate subtypes of depression; the search for new neurobiological and behavioral targets in the context of the National Institute of Mental Health's Research Domain Criteria framework; and examples of potential future discoveries and disciplines that may ultimately improve treatment.
Welfare, Autonomy, and the Autonomy Fallacy
Authors: Dorsey Dale
Published: May 2015

In this article, I subject the claim that autonomous choice is an intrinsic welfare benefit to critical scrutiny. My argument begins by discussing perhaps the most influential argument in favor of the intrinsic value of autonomy: the argument from deference. In response, I hold that this argument displays what I call the ‘Autonomy Fallacy’: the argument from deference has no power to support the intrinsic value of autonomy in comparison to the important evaluative significance of bare self‐direction (autonomous or not) or what I call ‘self‐direction tout court’. I defend the claim that the Autonomy Fallacy really is a fallacy, and show that my examination of the argument from deference has wider reverberations. Once we clearly distinguish between autonomy and self‐direction tout court, it becomes much less plausible to say that autonomy of itself is an intrinsic welfare benefit.
Moss‐made pharmaceuticals: from bench to bedside
Authors: Reski Ralf , Parsons Juliana , Decker Eva L.
Published: May 2015

Over the past two decades, the moss Physcomitrella patens has been developed from scratch to a model species in basic research and in biotechnology. A fully sequenced genome, outstanding possibilities for precise genome‐engineering via homologous recombination (knockout moss), a certified GMP production in moss bioreactors, successful upscaling to 500 L wave reactors, excellent homogeneity of protein glycosylation, remarkable batch‐to‐batch stability and a safe cryopreservation for master cell banking are some of the key features of the moss system. Several human proteins are being produced in this system as potential biopharmaceuticals. Among the products are tumour‐directed monoclonal antibodies with enhanced antibody‐dependent cytotoxicity (ADCC), vascular endothelial growth factor (VEGF), complement factor H (FH), keratinocyte growth factor (FGF7/KGF), epidermal growth factor (EGF), hepatocyte growth factor (HGF), asialo‐erythropoietin (asialo‐EPO, AEPO), alpha‐galactosidase (aGal) and beta‐glucocerebrosidase (GBA). Further, an Env‐derived multi‐epitope HIV protein as a candidate vaccine was produced, and first steps for a metabolic engineering of P. patens have been made. Some of the recombinant biopharmaceuticals from moss bioreactors are not only similar to those produced in mammalian systems such as CHO cells, but are of superior quality (biobetters). The first moss‐made pharmaceutical, aGal to treat Morbus Fabry, is in clinical trials.
Fractional carbon dioxide laser‐assisted photodynamic therapy for patients with actinic keratosis
Authors: Song Hyo Sang , Jung Soo‐Eun , Jang Yong Hyun , Kang Hee Young , Lee Eun‐So , Kim You Chan
Published: May 2015

Background/purpose

A relatively long incubation time is needed for photosensitizer absorption in conventional photodynamic therapy (PDT) for actinic keratosis (AK). The use of ablative CO2 fractional lasers (AFXLs) to increase drug delivery could shorten the incubation time. Here, we aimed to compare the efficacy between AFXL‐assisted PDT with a short incubation time and conventional PDT for AK.

Methods

Patients with histopathologically confirmed facial AK were randomly divided into two groups. The lesions were histopathologically classified into grades I–III. In the AFXL‐assisted PDT group, an ablative fractional laser was used for pretreatment, prior to the application of methyl aminolevulinate, with an incubation time of 90 min. Irradiation was performed with a 630‐nm light‐emitting diode. In the conventional PDT group, the incubation time was 180 min. All the patients received two rounds of PDT at 2‐week intervals and underwent clinical or histological evaluation at 10 weeks after the first PDT course.

Results

Twenty‐two patients underwent conventional PDT and 24 patients underwent AFXL‐assisted PDT. Thirty‐four AKs were included in the conventional PDT group, and 35 AKs were included in the AFXL‐assisted PDT group. The clearance rate was 64.7% in the conventional PDT and 71.4% in the AFXL‐assisted PDT group; no significant differences in the clearance rate were noted between the groups (P = 0.55). The clearance rates for each grade also did not significantly differ between the two groups.

Conclusions

The use of AFXL before PDT reduced the incubation time, but yielded similar treatment efficacy as compared to conventional PDT.
Achilles' heels of governance: Critical capacity deficits and their role in governance failures
Authors: Howlett Michael , Ramesh M.
Published: May 2015

This article assesses the usefulness of conceptions of policy capacity for understanding policy and governance outcomes. In order to shed light on this issue, it revisits the concept of governance, derives a model of basic governance types and discusses their capacity pre‐requisites. A model of capacity is developed combining competences over three levels of activities with analysis of resource capabilities at each level. This analysis is then applied to the common modes of governance. While each mode requires all types of capacity if it is to match its theoretically optimal potential, most on‐the‐ground modes do not attain their highest potential. Moreover, each mode has a critical type of capacity which serves as its principle vulnerability; its “Achilles' heel.” Without high levels of the requisite capacity, the governance mode is unlikely to perform as expected. While some hybrid modes can serve to supplement or reinforce each other and bridge capacity gaps, other mixed forms may aggravate single mode issues. Switching between modes or adopting hybrid modes is, therefore, a non‐trivial issue in which considerations of capacity issues in general andAchilles' heel capacities in particular should be a central concern.
Uniformity of Node Level Conflict Measures in Bayesian Hierarchical Models Based on Directed Acyclic Graphs
Authors: GÅSEMYR JøRUND
Published: May 2015

Hierarchical models defined by means of directed, acyclic graphs are a powerful and widely used tool for Bayesian analysis of problems of varying degrees of complexity. A simulation‐based method for model criticism in such models has been suggested by O'Hagan in the form of a conflict measure based on contrasting separate local information sources about each node in the graph. This measure is however not well calibrated. In order to rectify this, alternative mutually similar tail probability‐based measures have been proposed independently and have been proved to be uniformly distributed under the assumed model in quite general normal models with known covariance matrices. In the present paper, we extend this result to a variety of models. An advantage of this is that computationally costly pre‐calibration schemes needed for some other suggested methods can be avoided. Another advantage is that non‐informative prior distributions can be used when performing model criticism.
Testing block‐diagonal covariance structure for high‐dimensional data
Authors: Hyodo Masashi , Shutoh Nobumichi , Nishiyama Takahiro , Pavlenko Tatjana
Published: May 2015

A test statistic is developed for making inference about a block‐diagonal structure of the covariance matrix when the dimensionality p exceeds n, where n = N − 1 and N denotes the sample size. The suggested procedure extends the complete independence results. Because the classical hypothesis testing methods based on the likelihood ratio degenerate when p > n, the main idea is to turn instead to a distance function between the null and alternative hypotheses. The test statistic is then constructed using a consistent estimator of this function, where consistency is considered in an asymptotic framework that allows p to grow together with n. The suggested statistic is also shown to have an asymptotic normality under the null hypothesis. Some auxiliary results on the moments of products of multivariate normal random vectors and higher‐order moments of the Wishart matrices, which are important for our evaluation of the test statistic, are derived. We perform empirical power analysis for a number of alternative covariance structures.
Collaborative study for the characterization of a chikungunya virus RNA reference reagent for use in nucleic acid testing
Authors: Añez G. , Jiang Z. , Heisey D. A. R. , Kerby S. , Rios M. ,   The Chikungunya virus Collaborative Study Group
Published: May 2015

Background and Objectives

Infections with the mosquito‐borne chikungunya virus (CHIKV) can cause febrile illness or be asymptomatic. Laboratory diagnosis of CHIKV is often made with laboratory‐developed nucleic acid amplification technology (NAT) assays because there are no U.S. Food and Drug Administration (FDA)‐approved diagnostic or blood screening assays. We aimed to produce a well‐characterized CHIKV RNA reference reagent (CHIKV‐RR) for use in NAT assays.

Materials and Methods

A CHIKV RNA‐RR consisting of cell culture‐grown, heat‐inactivated CHIKV diluted in human plasma was assessed by 8 laboratories in a collaborative study. The participants were asked to test the CHIKV‐RR using their NAT assay(s) by qualitative testing (determination of RNA end‐point by testing log and half‐log dilutions followed by calculation of estimated NAT‐detectable units/ml, after adjustment for the sample volume used for testing), and by quantitative testing, when available.

Results

Results from the testing showed that the CHIKV‐RR had an estimated overall mean of 7·56 log10 detectable units/ml, ranging from 6·2 log10 to 8·6 log10.

Conclusions

The Center for Biologics for Evaluation and Research/FDA CHIKV RNA‐RR for NAT was established with a concentration of 7·56 log10 detectable units/ml.
Towards a hydrodynamically enhanced design and operation of primary settling tanks – Results of a long term in situ measurement investigation program
Authors: Patziger Miklós , Kiss Katalin
Published: May 2015

In modern wastewater treatment the function of primary settling tanks (PSTs) has become more complex comprising the control of readily biodegradable carbon between denitrification and biogas production by an optimum performance. This requires detailed investigations in order to obtain exact knowledge of the processes within PSTs. The article shows the results of the investigation of a PST comprising in situ flow measurements and removal efficiency analysis. The measurements were carried out at different surface overflow rates, which ranged from low to even higher values than those recommended by design guidelines. This was done in order to investigate the relationship between hydrodynamic processes and removal efficiency at high hydraulic loads. Inflowing and outflowing suspended solids concentrations and loads were recorded on‐line during the measurements. The measurements provided detailed insight into the flow processes within the PST as a first step towards hydrodynamically driven design and operation control of PSTs.
The Effect of Working Capital Management on Corporate Profitability: Evidence from Nigerian Food Product Firms
Authors: Muhammad Sabo , Saminu Jibril Rabi’U , Wambai Usman Sani K. , Ibrahim Fatima Bello , Ahmad Tjjani Habibu
Published: May 2015

The paper examines the impact of working capital management on corporate profitability through the periods of 2008 to 2012. The total of seven firms listed on the floor of the Nigerian Stock Exchange was studied, using secondary data generated from annual reports and accounts of the sampled companies and the Nigerian Stock Exchange Fact book. The data were analyzed by means of descriptive statistics and GLS regression analysis using STATA 11. The study finds a positive relationship among Average Collection Period (ACP), Current Ratio (CR) and the size of the firm (LOGSIZE) with Profitability and a negative relationship with Inventory Turnover Period (ITP), Average Payment Period (APP). The paper therefore recommends that cash collected should be re-invested into short-term investment to generate profits and fund left idle in the cash or excessive liquidity is costly and do not lead to profitability.
Perfusion pressure and blood flow determine microvascular apparent viscosity
Authors: Yalcin Ozlem , Ortiz Daniel , Williams Alexander T. , Johnson Paul C. , Cabrales Pedro
Published: May 2015

New Findings

What is the central question of this study?

The aim was to evaluate the effect of perfusion pressure on blood flow in small arterioles. The hypothesis was that blood flow regulates the thickness of the red‐cell‐free layer and, therefore, blood flow determines blood apparent viscosity and local vascular resistance in vascular networks with limited myogenic or metabolic regulation of blood flow.

What is the main finding and its importance?

Reduced perfusion pressures lowered volumetric flow rates and increased local vascular resistance, due to increased blood apparent viscosity. Thus, the local vascular resistance of small arterioles with limited myogenic or metabolic regulation of blood flow, appeared to be determined by changes in blood rheology rather than blood vessel diameter.

The study of blood flow regulation is important to understand and resolve pathological conditions. As blood is a complex non‐Newtonian multiphase system, the foundations of blood rheological properties have been obtained mostly in viscometers. However, blood rheological behaviour in vivo depends on the concentration of red blood cells (RBCs), their mechanical properties and the RBC hydrodynamics, including RBC migration away from the vessel wall in shear flow. This migration promotes the formation of a RBC‐depleted zone, or cell‐free layer (CFL), which reduces the apparent viscosity of blood. We hypothesize that perfusion pressure determines blood apparent viscosity in microvessels, as shear rate affects axial migration of RBCs by influencing the CFL thickness. In this study, we analysed the effects of perfusion pressure on blood flow in individual arterioles within the rat cremaster muscle preparation. Perfusion pressures to this microvascular bed were controlled by occlusions of the iliac artery using a pressure cuff. Blood flow measurements were obtained from direct measurements of blood flow velocity profile, as well as determination of CFL thickness using intravital microscopy. Our results indicate that perfusion pressure determines shear rates and the CFL thickness and its variations. In addition, blood flow reduction increased local vascular resistance by augmenting blood apparent viscosity rather than vascular hindrance. In conclusion, blood rheology could act as an intrinsic mechanism to further limit blood flow to tissue with limited myogenic and metabolic responses at low perfusion pressures.
Effect of Carbohydrate and Caffeine Ingestion on Badminton Performance
Authors: Clarke Neil D. , Duncan Michael J.
Published: May 2015

Purpose:

To investigate the effect of ingesting carbohydrate and caffeine solutions on measures that are central to success in badminton.

Methods:

Twelve male badminton players performed a badminton serve-accuracy test, coincidence-anticipation timing (CAT), and a choice reaction-time sprint test 60 min before exercise. Participants then consumed 7 mL/kg body mass of either water (PLA), 6.4% carbohydrate solution (CHO), a solution containing a caffeine dose of 4 mg/kg, or 6.4% carbohydrate and 4 mg/kg caffeine (C+C). All solutions were flavored with orange-flavored concentrate. During the 33-min fatigue protocol, participants were provided with an additional 3 mL/kg body mass of solution, which was ingested before the end of the protocol. As soon as the 33-min fatigue protocol was completed, all measures were recorded again.

Results:

Short-serve accuracy was improved after the ingestion of CHO and C+C compared with PLA (P = .001, ηp2 = .50). Long-serve accuracy was improved after the ingestion of C+C compared with PLA (P < .001, ηp2 = .53). Absolute error in CAT demonstrated smaller deteriorations after the ingestion of C+C compared with PLA (P < .05; slow, ηp2 = .41; fast, ηp2 = .31). Choice reaction time improved in all trials with the exception of PLA, which demonstrated a reduction (P < .001, ηp2 = .85), although C+C was faster than all trials (P < .001, ηp2 = .76).

Conclusion:

These findings suggest that the ingestion of a caffeinated carbohydrate solution before and during a badminton match can maintain serve accuracy, anticipation timing, and sprinting actions around the court.
A new strategy to ERADicate HER2-positive breast tumors?
Authors: Arora Sanjeevani , Golemis Erica A.
Published: May 2015

Targeting a proteotoxic stress response pathway may improve therapeutic outcomes for HER2-positive breast cancer patients.
Science Signaling
Podcast: 26 May 2015
Authors: Zhao Min , Devreotes Peter N. , VanHook Annalisa M.
Published: May 2015

A genetic screen identifies signaling pathways important for electrotaxis in the slime mold
Dictyostelium discoideum
.
Limiting metastasis with tRNA fragments
Authors: Prabakaran Sudhakaran
Published: May 2015

Transfer RNA fragments induced by hypoxia inhibit metastasis.
Dengue Antibody-Dependent Enhancement: Knowns and Unknowns
Authors: Halstead Scott B.
Published: May 2015

Dengue provides the most abundant example in human medicine and the greatest human illness burden caused by the phenomenon of intrinsic antibody-dependent infection enhancement (iADE). In this immunopathological phenomenon infection of monocytes or macrophages using infectious immune complexes suppresses innate antiviral systems, permitting logarithmic intracellular growth of dengue virus. The four dengue viruses evolved from a common ancestor yet retain similar ecology and pathogenicity, but although infection with one virus provides short-term cross-protection against infection with a different type, millions of secondary dengue infections occur worldwide each year. When individuals are infected in the virtual absence of cross-protective dengue antibodies, the dengue vascular permeability syndrome (DVPS) may ensue. This occurs in around 2 to 4% of second heterotypic dengue infections. A complete understanding of the biologic mechanism of iADE, dengue biology, and the mechanism of host responses to dengue infection should lead to a comprehensive and complete understanding of the pathogenesis of DVPS. A crucial emphasis must be placed on understanding ADE. Clinical and epidemiological observations of DVPS define the research questions and provide research parameters. This article will review knowledge related to dengue ADE and point to areas where there has been little research progress. These observations relate to the two stages of dengue illnesses: afferent phenomena are those that promote the success of the microorganism to infect and survive; efferent phenomena are those mounted by the host to inhibit infection and replication and to eliminate the infectious agent and infected tissues. Data will be discussed as “knowns” and “unknowns.”
Phage and Yeast Display
Authors: Sheehan Jared , Marasco Wayne A.
Published: May 2015

Despite the availability of antimicrobial drugs, the continued development of microbial resistance—established through escape mutations and the emergence of resistant strains—limits their clinical utility. The discovery of novel, therapeutic, monoclonal antibodies (mAbs) offers viable clinical alternatives in the treatment and prophylaxis of infectious diseases. Human mAb-based therapies are typically nontoxic in patients and demonstrate high specificity for the intended microbial target. This specificity prevents negative impacts on the patient microbiome and avoids driving the resistance of nontarget species. The
in vitro
selection of human antibody fragment libraries displayed on phage or yeast surfaces represents a group of well-established technologies capable of generating human mAbs. The advantage of these forms of microbial display is the large repertoire of human antibody fragments present during a single selection campaign. Furthermore, the
in vitro
selection environments of microbial surface display allow for the rapid isolation of antibodies—and their encoding genes—against infectious pathogens and their toxins that are impractical within
in vivo
systems, such as murine hybridomas. This article focuses on the technologies of phage display and yeast display, as these strategies relate to the discovery of human mAbs for the treatment and vaccine development of infectious diseases.