bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between metformin therapy and incidence, recurrence and mortality of prostate cancer: evidence from a meta‐analysis
Authors: Deng Dan , Yang Yuan , Tang Xiaojun , Skrip Laura , Qiu Jingfu , Wang Yang , Zhang Fan
Published: February 2015

Objective

Previous studies suggested that metformin is associated with decreased risk of cancer; however, results specifically addressing the potential association with prostate cancer were limited and contradictory. This study considers the association between metformin and the incidence, mortality and recurrence of prostate cancer by performing a meta‐analysis of observational studies.

Methods

Literatures published before January 2014 were searched by using databases of PubMed and Embase. Pooled relative risks (RRs) were determined using a random effects model to evaluate the strength of association between metformin therapy and risk of prostate cancer.

Results

Thirteen studies involving a total of 334 532 participants were included in this meta‐analysis. Compared with the control group, metformin therapy was associated with significantly decreased incidence of prostate cancer [RR = 0.88, 95% confidence interval (CI) [0.78, 0.99], p = 0.03, I2 = 74.7%]. However, metformin therapy was not associated with decreased all‐cause mortality (RR = 1.07, 95% CI [0.86, 1.32], p = 0.55, I2 = 58.2%) or decreased recurrence of prostate cancer (RR = 0.90, 95% CI [0.75, 1.09], p = 0.27, I2 = 0.0%). No publication bias was detected (pBegg = 0.55, pEgger = 0.46).

Conclusions

The present study suggested that metformin therapy may decrease the incidence of prostate cancer but that there was no association between the treatment and all‐cause mortality or recurrence. It is recommended that this finding should be considered carefully and confirmed with further studies. Copyright © 2015 John Wiley & Sons, Ltd.
Multiple cis elements and GATA factors regulate a cuticle collagen gene in Caenorhabditis elegans
Authors: Yin Jianghua , Madaan Uday , Park Amy , Aftab Neelum , Savage‐Dunn Cathy
Published: February 2015

The cuticle of the nematode Caenorhabditis elegans is a specialized extracellular matrix whose major component is collagen. Cuticle collagens are encoded by a large multigene family consisting of more than 150 members. Cuticle collagen genes are expressed in epidermis (hypodermis) and may be stage‐specific or cyclically expressed. We identified cuticle collagen genes as transcriptional targets of the DBL‐1 TGF‐β‐related signaling pathway. These studies prompted us to investigate the cis‐regulatory sequences required for transcription of one of the target genes, col‐41. We generated reporter constructs that reproduce stage‐ and tissue‐specific expression of fluorescent markers. We identify four conserved sequence elements that are required for transcription of reporters. Finally, we provide evidence that col‐41 expression is controlled by a sequence element containing two GATA sites and by the epidermal GATA transcription factors ELT‐1 and ELT‐3. genesis 53:278–284, 2015. © 2015 Wiley Periodicals, Inc.
Types and Mechanisms of Science‐Driven Institutional Change: The case of desertification control in northern China
Authors: Yang Lihua , Li Chen
Published: February 2015

Science plays an important role in institutional change, but the types and mechanisms of science‐driven institutional change have received little attention in the mainstream discourse concerning institutions, institutional change and social governance. Comparing 25 cases using data from surveys, interviews, observations and a meta‐analysis of archives regarding desertification control in northern China, this study found that, although science influenced the results of desertification control through influencing institutional change, its influence was also constrained by the types and working principles of science‐driven institutional change. When analyzing the application of different methods of desertification control, the type of biological control that dominates the interaction (biological‐control‐dominant interaction) may be that of science‐driven intuitional change variables with the highest desertification control performance, whereas for the participants in desertification control the type of high participation and multiple interactions may be the variable with the greatest influence. This study also proposes nine principles for effective science‐driven institutional change that address collaborative, effective and sustainable applications and extensions of advanced scientific methods, effective collaboration among various social actors and organizations, and localized, collaborative and nested laws, regulations and rules regarding desertification control. Stronger rules result in more effective science‐driven institutional changes. These findings provide an outline for reforming the models of science‐driven institutional change and implementing future science and technology policies for desertification control and other types of ecological and environmental governance. This study also provides a theoretical and empirical foundation for further research concerning science‐driven institutional change. Copyright © 2015 John Wiley & Sons, Ltd and ERP Environment
Blockade of PD‐1 or p38 MAP kinase signaling enhances senescent human CD8+ T‐cell proliferation by distinct pathways
Authors: Henson Sian M. , Macaulay Richard , Riddell Natalie E. , Nunn Craig J. , Akbar Arne N.
Published: February 2015

Immune enhancement is desirable in situations where decreased immunity results in increased morbidity. We investigated whether blocking the surface inhibitory receptor PD‐1 and/or p38 MAP kinase could enhance the proliferation of the effector memory CD8+ T‐cell subset that re‐expresses CD45RA (EMRA) and exhibits characteristics of senescence, which include decreased proliferation and telomerase activity but increased expression of the DNA damage response related protein γH2AX. Blocking of both PD‐1 and p38 MAPK signaling in these cells enhanced proliferation and the increase was additive when both pathways were inhibited simultaneously in both young and old human subjects. In contrast, telomerase activity in EMRA CD8+ T cells was only enhanced by blocking the p38 but not the PD‐1 signaling pathway, further indicating that nonoverlapping signaling pathways were involved. Although blocking p38 MAPK inhibits TNF‐α secretion in the EMRA population, this decrease was counteracted by the simultaneous inhibition of PD‐1 signaling in these cells. Therefore, end‐stage characteristics of EMRA CD8+ T cells are stringently controlled by distinct and reversible cell signaling events. In addition, the inhibition of PD‐1 and p38 signaling pathways together may enable the enhancement of proliferation of EMRA CD8+ T cells without compromising their capacity for cytokine secretion.
Efficacy and cost‐effectiveness: A study of different treatment approaches in a tertiary pain centre
Authors: Vanhaudenhuyse A. , Gillet A. , Malaise N. , Salamun I. , Barsics C. , Grosdent S. , Maquet D. , Nyssen A‐S. , Faymonville M‐E.
Published: February 2015

Background

Chronic pain is considered to be a complex phenomenon, involving an interrelation of biological, psychosocial and sociocultural factors. Currently, no single treatment or therapy can address all aspects of this pathology. In our expert tertiary pain centre, we decide to assess the effectiveness of four treatments for chronic pain classically proposed in our daily clinical work: physiotherapy; psycho‐education; physiotherapy combined with psycho‐education; and self‐hypnosis/self‐care learning.

Methods

This study included 527 chronic pain patients, with a mean duration of pain of 10 years. Patients were allocated either to one of the four pre‐cited treatment groups or to the control group. Pain intensity, quality of life, pain interference, anxiety and depression were assessed before and after treatment.

Results

This study revealed a significant positive effect on pain interference and anxiety in patients included in the physiotherapy combined with psycho‐education group, after 20 sessions spread over 9 months of treatment. The most prominent results were obtained for patients allocated to the self‐hypnosis/self‐care group, although they received only six sessions over a 9‐month period. These patients showed significant benefits in the areas of pain intensity, pain interference, anxiety, depression and quality of life.

Conclusions

This clinical report demonstrates the relevance of biopsychosocial approaches in the improvement of pain and psychological factors in chronic pain patients. The study further reveals the larger impact of self‐hypnosis/self‐care learning treatment, in addition to a cost‐effectiveness benefit of this treatment comparative to other interventions.
Structural health monitoring of progressive damage
Authors: Mollineaux M. , Rajagopal R.
Published: February 2015

Structural health monitoring requires tracking the progression of damage in a structure over time. In this paper, we propose a model for progressive damage that utilizes a hidden Markov model where multiple states represent the severity and type of damage. Sensor observations are generated according to a process conditional on each state. An efficient algorithm for sequential inference of damage from collected data is proposed and tested using experimental data from a structural frame. Copyright © 2015 John Wiley & Sons, Ltd.
Dimensionless fragility curves for rocking response to near‐fault excitations
Authors: Dimitrakopoulos Elias G. , Paraskeva Themelina S.
Published: February 2015

This paper assesses the seismic fragility of single degree of freedom rocking structures within a probabilistic framework. The focus is on slender rigid structures that exhibit negative stiffness during rocking. The analysis considers ground motions with near‐fault characteristics, either solely coherent pulses or synthetic ground motions that include, in addition, a stochastic high‐frequency component. The study offers normalized fragility curves that estimate the overturning tendency, as well as the peak response rotation of a rocking structure. It shows that the use of bivariate intensity measures (IMs) can lead to superior fragility curves compared with conventional univariate IMs. Regardless, the study advocates the use of dimensionless–orientationless IMs that offer an approximately ‘universal’ description of rocking behavior/fragility, a normalized description almost indifferent to the amplitude and the predominant frequency of the excitation or the size and the slenderness of the rocking structure. Importantly, the analysis unveils hidden order in rocking response. There exists a critical peak ground acceleration, below and above which, peak rocking response scales differently. In particular, when the structure does not overturn, the peak rotation follows approximately a biplanar pattern with respect to the intensity and the predominant frequency of the excitation. Finally, the analysis verifies that rocking overturning depends primarily on the velocity characteristics of the ground motion. Copyright © 2015 John Wiley & Sons, Ltd.
Defining an exposure–response relationship for suspended kaolin clay particulates and aquatic organisms: Work toward defining a water quality guideline for suspended solids
Authors: Gordon Andrew K. , Palmer Carolyn G.
Published: February 2015

Water quality guidelines for suspended solids generally rely on the percentage departure from reference condition, an approach that has been criticized. Attempts to develop a biological effects-base guideline have, however, been confounded by low data availability. Furthermore, the high biological response variability to suspended solids exposure suggests that organisms are responding not only to exposure concentration and duration but also to other mechanisms of effect associated with suspended particles (e.g., size, shape, and geochemical composition). An alternative option is to develop more situation and site specific guidelines by generating biological effects data to suspended particles of a particular geochemistry and restricted size range. With this in mind, aquatic organism responses to kaolin clay particle exposure were collated from the literature and incorporated into 2 exposure–response relationship approaches. The species sensitivity distribution approach produced a hazardous concentration affecting 5% of species estimate of 58 mg/L for mortality responses, and 36 mg/L for sublethal data. The severity-of-ill-effect approach produced similar estimates for lethal and sublethal data. These results suggest that aquatic organisms are slightly more tolerant of kaolin clay particles than particles from barite or bentonite clays, based on results from previous studies on these clay types. This type of information can enable better estimates of the risk faced by aquatic organisms exposed to suspended solids. For example, when the sediments of a particular water body are dominated by a particular type of clay particle, then the most appropriate exposure–response relationship can be applied. Environ Toxicol Chem 2015;34:907–912. © 2015 SETAC
Network activity underlying the illusory self‐attribution of a dummy arm
Authors: Limanowski Jakub , Blankenburg Felix
Published: February 2015

Neuroimaging has demonstrated that the illusory self‐attribution of body parts engages frontal and intraparietal brain areas, and recent evidence further suggests an involvement of visual body‐selective regions in the occipitotemporal cortex. However, little is known about the principles of information exchange within this network. Here, using automated congruent versus incongruent visuotactile stimulation of distinct anatomical locations on the participant's right arm and a realistic dummy counterpart in an fMRI scanner, we induced an illusory self‐attribution of the dummy arm. The illusion consistently activated a left‐hemispheric network comprising ventral premotor cortex (PMv), intraparietal sulcus (IPS), and body‐selective regions of the lateral occipitotemporal cortex (LOC). Importantly, during the illusion, the functional coupling of the PMv and the IPS with the LOC increased substantially, and dynamic causal modeling revealed a significant enhancement of connections from the LOC and the secondary somatosensory cortex to the IPS. These results comply with the idea that the brain's inference mechanisms rely on the hierarchical propagation of prediction error. During illusory self‐attribution, unpredicted ambiguous sensory input about one's body configuration may result in the generation of such prediction errors in visual and somatosensory areas, which may be conveyed to parietal integrative areas. Hum Brain Mapp 36:2284–2304, 2015. © 2015 Wiley Periodicals, Inc.
Striatal and midbrain connectivity with the hippocampus selectively boosts memory for contextual novelty
Authors: Kafkas Alexandros , Montaldi Daniela
Published: February 2015

The role of contextual expectation in processing familiar and novel stimuli was investigated in a series of experiments combining eye tracking, functional magnetic resonance imaging, and behavioral methods. An experimental paradigm emphasizing either familiarity or novelty detection at retrieval was used. The detection of unexpected familiar and novel stimuli, which were characterized by lower probability, engaged activity in midbrain and striatal structures. Specifically, detecting unexpected novel stimuli, relative to expected novel stimuli, produced greater activity in the substantia nigra/ventral tegmental area (SN/VTA), whereas the detection of unexpected familiar, relative to expected, familiar stimuli, elicited activity in the striatum/globus pallidus (GP). An effective connectivity analysis showed greater functional coupling between these two seed areas (GP and SN/VTA) and the hippocampus, for unexpected than for expected stimuli. Within this network of midbrain/striatal–hippocampal interactions two pathways are apparent; the direct SN–hippocampal pathway sensitive to unexpected novelty and the perirhinal–GP–hippocampal pathway sensitive to unexpected familiarity. In addition, increased eye fixations and pupil dilations also accompanied the detection of unexpected relative to expected familiar and novel stimuli, reflecting autonomic activity triggered by the functioning of these two pathways. Finally, subsequent memory for unexpected, relative to expected, familiar, and novel stimuli was characterized by enhanced recollection, but not familiarity, accuracy. Taken together, these findings suggest that a hippocampal–midbrain network, characterized by two distinct pathways, mediates encoding facilitation and most critically, that this facilitation is driven by contextual novelty, rather than by the absolute novelty of a stimulus. This contextually sensitive neural mechanism appears to elicit increased exploratory behavior, leading subsequently to greater recollection of the unexpected stimulus. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc.
Estimation of soil hydraulic properties and their uncertainty through the Beerkan infiltration experiment
Authors: Ghavidelfar Saeed , Shamseldin Asaad Y. , Melville Bruce W.
Published: February 2015

The Beerkan method based on in situ single‐ring water infiltration experiments along with the relevant specific Beerkan estimation of soil transfer parameters (BEST) algorithm is attractive for simple soil hydraulic characterization. However, the BEST algorithm may lead to erroneous or null values for the saturated hydraulic conductivity and sorptivity especially when there are only few infiltration data points under the transient flow state, either for sandy soil or soils in wet conditions. This study developed an alternative algorithm for analysis of the Beerkan infiltration experiment referred to as BEST‐generalized likelihood uncertainty estimation (GLUE). The proposed method estimates the scale parameters of van Genuchten water retention and Brooks–Corey hydraulic conductivity functions through the GLUE methodology. The GLUE method is a Bayesian Monte Carlo parameter estimation technique that makes use of a likelihood function to measure the goodness‐of‐fit between modelled and observed data. The results showed that using a combination of three different likelihood measurements based on observed transient flow, steady‐state flow and experimental steady‐state infiltration rate made the BEST‐GLUE procedure capable of performing an efficient inverse analysis of Beerkan infiltration experiments. Therefore, it is more applicable for a wider range of soils with contrasting texture, structure, and initial and saturated water content. Copyright © 2015 John Wiley & Sons, Ltd.
Osteotomy Healing in Children With Osteogenesis Imperfecta Receiving Bisphosphonate Treatment
Authors: Anam Emad A , Rauch Frank , Glorieux Francis H , Fassier François , Hamdy Reggie
Published: February 2015

A decade ago our group had reported that osteotomy healing was commonly delayed in children with moderate to severe osteogenesis imperfecta (OI) who were treated with intravenous pamidronate infusions. We subsequently maintained a bisphosphonate infusion–free interval of 4 months after osteotomy and changed the surgical approach (use of an osteotome instead of a power saw). In addition, zoledronic acid has become the standard intravenous bisphosphonate for treatment of OI at our institution. In the present study, we compared osteotomy healing before and after these changes were instituted. We evaluated bone healing post-osteotomy on standard radiographs after 261 intramedullary rodding procedures involving osteotomies (139 femur, 112 tibia) in 110 patients (age at surgery 1.2 to 20.4 years). Delayed healing was diagnosed when the osteotomy line was visible 12 months after the event. We observed delayed bone healing after 48 of the 114 osteotomies (42%) performed with the new approach, and in 106 of the 147 osteotomies (72%) using the previous approach (p = 0.001). The odds for delayed osteotomy healing were significantly lower with the new approach even after adjustment for age, sex, height Z-score, weight Z-score, OI type, and bone involved (odds ratio = 0.17; 95% confidence interval 0.16–0.47). Thus, delayed osteotomy healing occurred less frequently in the past 10 years than in the decade before that. It is likely that this improved result is attributable to the implemented changes in both medical and surgical management. © 2015 American Society for Bone and Mineral Research.
Associations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D With Bone Mineral Density, Bone Mineral Density Change, and Incident Nonvertebral Fracture
Authors: Swanson Christine M , Srikanth Priya , Lee Christine G , Cummings Steven R , Jans Ivo , Cauley Jane A , Bouillon Roger , Vanderschueren Dirk , Orwoll Eric S , Nielson Carrie M ,   for the Osteoporotic Fractures in Men MrOS Study Research Group
Published: February 2015

Relationships between 1,25-dihydroxyvitamin D (1,25(OH)2D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)2D with bone mineral density (BMD), BMD change, and incident non-vertebral fractures in a cohort of older men and compared them with those of 25-hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual-energy X-ray absorptiometry (DXA) data (4.5 years of follow-up). A case-cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)2D were tested for each outcome. Over an average follow-up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)2D had lower baseline BMD. 1,25(OH)2D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)2D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)2D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)2D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)2D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)2D. These results do not support the hypothesis that measures of 1,25(OH)2D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research.
The Effect of Discontinuing Treatment With Blosozumab: Follow-up Results of a Phase 2 Randomized Clinical Trial in Postmenopausal Women With Low Bone Mineral Density
Authors: Recknor Christopher P , Recker Robert R , Benson Charles T , Robins Deborah A , Chiang Alan Y , Alam Jahangir , Hu Leijun , Matsumoto Toshio , Sowa Hideaki , Sloan John H , Konrad Robert J , Mitlak Bruce H , Sipos Adrien A
Published: February 2015

Administration of blosozumab, a humanized monoclonal antibody that binds sclerostin, increases bone formation and bone mineral density (BMD) in postmenopausal women with low BMD. To evaluate the effect of discontinuing blosozumab, we studied women enrolled in a 1-year randomized, placebo-controlled phase 2 trial for an additional year after they completed treatment. Of the 120 women initially enrolled in the study, 106 women completed treatment and continued into follow-up; 88 women completed 1 year of follow-up. At the beginning of follow-up, groups remained balanced for age, race, and body mass index, but lumbar spine and total hip BMD were increased in prior blosozumab groups, reflecting an anabolic treatment effect. At the end of follow-up, 1 year after discontinuing treatment, lumbar spine BMD remained significantly greater than placebo in women initially treated with blosozumab 270 mg every 2 weeks (Q2W) and blosozumab 180 mg Q2W (6.9% and 3.6% above baseline, respectively). Total hip BMD also declined after discontinuation of treatment but at 1 year after treatment remained significantly greater than placebo in women initially treated with blosozumab 270 mg Q2W and blosozumab 180 mg Q2W (3.9% and 2.6% above baseline, respectively). During follow-up, median serum P1NP was not consistently different between the prior blosozumab groups and placebo. A similar pattern was apparent for median serum C-terminal telopeptide of type 1 collagen (CTx) levels, with more variability. Mean serum total sclerostin concentration increased with blosozumab, indicating target engagement, and declined to baseline after discontinuation. There were no adverse events considered related to prior treatment with blosozumab. Anti-drug antibodies generally declined in patients who had detectable levels during prior treatment. These findings support the continued study of blosozumab as an anabolic therapy for treatment of osteoporosis. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
Smad1/5 and Smad4 Expression Are Important for Osteoclast Differentiation
Authors: Tasca Amy , Stemig Melissa , Broege Aaron , Huang Brandon , Davydova Julia , Zwijsen An , Umans Lieve , Jensen Eric D. , Gopalakrishnan Raj , Mansky Kim C.
Published: February 2015

To investigate the necessity of the canonical BMP pathway during osteoclast differentiation, we created osteoclasts with a conditional gene deletion for Smad1 and Smad5 (SMAD1/5), or Smad4 using adenovirus expressing CRE recombinase (Ad‐CRE). Reduction of either Smad4 or Smad1/5 expression resulted in fewer and smaller multinuclear cells compared to control cells. We also detected changes in osteoclast enriched genes, demonstrated by decreased Dc‐stamp and cathepsin K expression in both Smad4 and Smad1/5 Ad–CRE osteoclasts, and changes in c‐fos and Nfatc1 expression in only Smad4 Ad–CRE cells. Lastly we also detected a significant decrease in resorption pits and area resorbed in both the Smad4 and Smad1/5 Ad‐CRE osteoclasts. Because we inhibited osteoclast differentiation with loss of either Smad4 or Smad1/5 expression, we assessed whether BMPs affected osteoclast activity in addition to BMP's effects on differentiation. Therefore, we treated mature osteoclasts with BMP2 or with dorsomorphin, a chemical inhibitor that selectively suppresses canonical BMP signaling. We demonstrated that BMP2 stimulated resorption in mature osteoclasts whereas treatment with dorsomorphin blocks osteoclast resorption. These results indicate that the BMP canonical signaling pathway is important for osteoclast differentiation and activity. J. Cell. Biochem. 116: 1350–1360, 2015. © 2015 Wiley Periodicals, Inc.
An Uncontrolled Trial of a Present‐Focused Cognitive‐Behavioral Conjoint Therapy for Posttraumatic Stress Disorder
Authors: Pukay‐Martin Nicole D. , Torbit Lindsey , Landy Meredith S. H. , Wanklyn Sonya G. , Shnaider Philippe , Lane Jeanine E. M. , Monson Candice M.
Published: February 2015

Objective

The efficacy of a present‐focused version of cognitive‐behavioral conjoint therapy for posttraumatic stress disorder (CBCT for PTSD) was examined in a community sample.

Method

Seven couples completed pretreatment assessments, including measures of clinician‐, self‐ and partner‐rated PTSD symptoms and relationship satisfaction. Six couples completed present‐focused CBCT for PTSD and all posttreatment assessments. A seventh couple terminated their relationship prior to completing treatment; therefore, they completed posttreatment symptom measures, but not ratings of relationship satisfaction.

Results

Results revealed significant decreases in PTSD symptoms that were associated with medium‐to‐large effect sizes. Medium effect sizes for changes in relationship satisfaction were found, though were only significant for partners.

Conclusion

Results from this pilot study suggest that present‐focused CBCT for PTSD may be a promising alternative for individuals who are unwilling to engage in a trauma‐focused treatment.
Contrasting models of parity‐mode evolution in squamate reptiles
Authors: Pyron R. Alexander , Burbrink Frank T.
Published: February 2015

Recent analyses using large‐scale phylogenies suggest a radically different history for the evolution of live birth and egg laying in squamate reptiles (lizards and snakes) than traditionally understood. What is the ancestral condition for lizards and snakes? How frequently does live bearing evolve in egg‐laying lineages? Can the eggshell ever re‐evolve in live‐bearing lineages? Answering these fundamental questions about the evolution of key physiological processes will require additional data from genomic, developmental, and fossil data. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 467–472, 2015. © 2014 Wiley Periodicals, Inc.
Reduction of inappropriate exit prescriptions for proton pump inhibitors: A before‐after study using education paired with a web‐based quality‐improvement tool
Authors: McDonald Emily G. , Jones Janelle , Green Laurence , Jayaraman Dev , Lee Todd C.
Published: February 2015

BACKGROUND

Proton pump inhibitors (PPIs) are overprescribed despite concerns regarding associated adverse drug events.

OBJECTIVE

To reduce inappropriate PPI prescriptions using hospitalization as the point of contact to effect meaningful change.

DESIGN

Before‐after study design.

SETTING

Forty‐six–bed medical clinical teaching unit in a 417‐bed university teaching hospital in Montreal, Canada.

PATIENTS

Four hundred sixty‐four consecutively admitted patients in the preintervention control group, and 640 consecutively admitted patients in the intervention group.

INTERVENTION

A monthly educational intervention paired with a Web‐based quality improvement tool.

MEASUREMENTS

We determined the proportion of patients admitted on PPIs, their indications, and appropriateness of use. We then compared the proportion of patients whose PPIs were discontinued at discharge before and after our intervention.

RESULTS

Forty‐four percent of patients were already using a PPI prior to their hospitalization. In evaluated patients, only 54% of these patients had an evidence‐based indication for ongoing use. The proportion of PPIs discontinued at hospital discharge increased from 7.7% per month in the 6 months prior to intervention, to 18.5% per month postintervention (P = 0.03).

CONCLUSIONS

Strategies to combat PPI overuse are needed to improve the overall quality of patient care. We significantly reduced discharge prescriptions for PPIs through the implementation of an educational initiative paired with a Web‐based quality improvement tool. An active interventional strategy is likely required considering the increasingly recognized and preventable adverse events associated with PPI misuse. Journal of Hospital Medicine 2015;10:281–286. © 2015 Society of Hospital Medicine
Drug–drug plasma protein binding interactions of ivacaftor
Authors: Schneider Elena K. , Huang Johnny X. , Carbone Vincenzo , Baker Mark , Azad Mohammad A. K. , Cooper Matthew A. , Li Jian , Velkov Tony
Published: February 2015

Ivacaftor is a novel cystic fibrosis (CF) transmembrane conductance regulator (CFTR) potentiator that improves the pulmonary function for patients with CF bearing a G551D CFTR‐protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co‐administered CF drugs may compete for the same plasma protein binding sites and impact the free drug concentration. This, in turn, could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This biochemical study compares the binding affinity of ivacaftor and co‐administered CF drugs for human serum albumin (HSA) and α1‐acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site‐selective probes. Because of their ability to strongly compete for the ivacaftor binding sites on HSA and AGP, drug–drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole, and loratadine. The significance of these plasma protein drug–drug interactions is also interpreted in terms of molecular docking simulations. This in vitro study provides valuable insights into the plasma protein drug–drug interactions of ivacaftor with co‐administered CF drugs. The data may prove useful in future clinical trials for a staggered treatment that aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor. Copyright © 2015 John Wiley & Sons, Ltd.
Fast imaging strategies for mouse kidney perfusion measurement with pseudocontinuous arterial spin labeling (pCASL) at ultra high magnetic field (11.75 tesla)
Authors: Prevost Valentin H. , Girard Olivier M. , Callot Virginie , Cozzone Patrick J. , Duhamel Guillaume
Published: February 2015

Background

To derive an adapted protocol at ultra high magnetic field for mouse kidney perfusion measurements using pCASL in combination with three widely available fast imaging readouts: segmented SE EPI (sSE EPI), RARE, and TrueFISP.

Methods

pCASL sSE EPI, pCASL RARE, and pCASL TrueFISP were used for the acquisition of mouse kidney perfusion images in the axial and coronal planes at 11.75T. Results were compared in terms of perfusion sensitivity, signal‐to‐noise ratio (SNR), blood flow values, intrasession and intersession repeatability, and image quality (subjectively classified into three grades: good, satisfactory, and unacceptable).

Results

Renal cortex perfusion measurements were performed within 2 min with pCASL RARE/pCASL TrueFISP and 4 min with pCASL sSE EPI. In an axial direction, SNR values of 6.6/5.6/2.8, perfusion sensitivity values of 16.1 ± 3.7/13.6 ± 2.4/13.4 ± 1.0 %, blood flow values of 679 ± 149/466 ± 111/572 ± 46 mL/100 g/min and in‐ROI variations values of 192/161/181 mL/100 g/min were obtained with pCASL sSE EPI/pCASL RARE/pCASL TrueFISP. Highest SNR per unit of time (1.8) and highest intra/intersession reliability (92.9% and 95.1%) were obtained with pCASL RARE, which additionally presented highly reproducible satisfactory image quality. In coronal plane, significantly lower SNR, perfusion sensitivity and perfusion values were obtained for all techniques compared with that in the axial plane (P < 0.05) due to magnetization saturation effects.

Conclusion

pCASL RARE demonstrated more advantages for longitudinal preclinical kidney perfusion studies at ultra high magnetic field. J. Magn. Reson. Imaging 2015;42:999–1008.
Occurrence of trans monounsaturated and polyunsaturated fatty acids in Colwellia psychrerythraea strain 34H
Authors: Hashimoto Mikako , Orikasa Yoshitake , Hayashi Hidenori , Watanabe Kentaro , Yoshida Kiyohito , Okuyama Hidetoshi
Published: February 2015

Colwellia psychrerythraea strain 34H is an obligately psychrophilic bacterium that has been used as a model cold‐adapted microorganism because of its psychrophilic growth profile, significant production of cold‐active enzymes, and cryoprotectant extracellular polysaccharide substances. However, its fatty acid components, particularly trans unsaturated fatty acids and long‐chain polyunsaturated fatty acids (LC‐PUFAs), have not been fully investigated. In this study, we biochemically identified Δ9‐trans hexadecenoic acid [16:1(9t)] and LC‐PUFAs such as docosahexaenoic acid. These results are comparable with the fact that the strain 34H genome sequence includes pfa and cti genes that are responsible for the biosynthesis of LC‐PUFAs and trans unsaturated fatty acids, respectively. Strain 34H cells grown under static conditions at 5 °C had higher levels of 16:1(9t) than those grown under shaken conditions, and this change was accompanied by an antiparallel decrease in the levels of Δ9‐cis hexadecenoic acid [16:1(9c)], suggesting that the cis‐to‐trans isomerization reaction of 16:1(9c) is activated under static (microanaerobic) culture conditions, that is, the enzyme could be activated by the decreased dissolved oxygen concentration of cultures. On the other hand, the levels of LC‐PUFAs were too low (less than 3% of the total), even for cells grown at 5 °C, to evaluate their cold‐adaptive function in this bacterium.
Longshore wind, waves and currents: climate and climate projections at Ninety Mile Beach, southeastern Australia
Authors: O'Grady Julian G. , McInnes Kathleen L. , Colberg Frank , Hemer Mark A. , Babanin Alexander V.
Published: February 2015

It is shown that Lakes Entrance, a township located at the northern end of Ninety Mile Beach in southeastern Australia, is situated in a region that may experience noticeable changes in longshore wind, wave and ocean currents compared to present day climate variability as a consequence of the southward shifting subtropical ridge (STR) predicted in global climate change models. These changes could modify sediment transport in the littoral zone and impact the coastline position. Thirty‐year hindcasts of winds, coastal currents and waves are shown to agree well with available observations and provide a long‐term dataset of the climate variability. Hindcasts of coastal ocean currents and waves indicate that while the annual net mean wave and current transport are in opposing directions, their seasonal adjusted monthly anomalies are positively correlated. Furthermore they are also correlated with the position of the STR location index. On seasonal to annual time scales a weak connection between the transport variables and Southern Oscillation Index (SOI) is found. It appears that during multiple years of positive (negative) SOI conditions the STR is located north (south) of its mean monthly position, resulting in anomalous eastward (westward) transport. The four climate models used in this study indicate a southward shift in the STR for most months under a high emission future. In summer months the shift in the STR results in both increased summer westward wind‐driven currents and westward wave forcing. Changes in winter months are less related to the STR location and it is discussed that the contraction and increased intensity of the westerly storm belt linked to Southern Annular Mode could possibly influence the transport. The analysis is presented at the coastal scale to provide insights into how these changes may affect net transport across the littoral zone in more detailed numerical nearshore sediment transport modelling.
Recent changes in summer precipitation in Northeast China and the background circulation
Authors: Han Tingting , Chen Huopo , Wang Huijun
Published: February 2015

This study documents recent changes in the characteristics of summer (July–August–September) precipitation in Northeast China (NEC). A significant shift to less precipitation occurred in 1999–2012 as compared with that in 1984–1998. The reduced precipitation in the later period is closely associated with the large‐scale anomalous high pressure over East Asia and anomalous descending motion over NEC. Furthermore, the significant reductions in the total cloud cover and moisture content also contribute to the reduced precipitation over NEC. To investigate the possible mechanism for the decadal shift of summer precipitation, a northeast Asian summer monsoon (NEASM) index is defined to describe the monsoon circulation over NEC. The results indicate that the NEASM has weakened since 1999 and is concurrent with the shift of the Pacific Decadal Oscillation (PDO) to the negative phase. Warming sea surface temperature (SST) in the North Pacific can zonally reduce the land‐sea thermal contrast and lead to a weak NEASM. Further investigation indicates that the negative phase of the PDO has significant impacts on the atmospheric circulation associated with the NEASM. Additionally, changes in synchronous Arctic sea ice cover (SIC) also likely induce an anomalous sinking movement and weaken water vapour transport; thus, the summer precipitation over NEC decreases.
A hybrid procedure for classifying synoptic weather types for Louisiana, USA
Authors: Lewis Amanda B. , Keim Barry D.
Published: February 2015

A hybrid synoptic classification procedure for classifying Louisiana weather types based on the manual Muller system is presented. This procedure produces a synoptic classification system for Louisiana that harnesses the strengths of both manual and automated classifications, while eliminating the weaknesses. The Muller weather types archive from 1981 to 2001 is used in conjunction with the National Center for Atmospheric Research (NCAR)/National Centers for Environmental Prediction (NCEP) Reanalysis dataset to develop sea level pressure composites for each Muller weather type. The composites are used as seeds in an automated correlation‐based algorithm to generate weather types from 1981 to 2001. Results of the automated procedure are compared to the Muller weather type catalog. Despite systematic differences between the two classifications, including the inability of the hybrid procedure to identify frontal placement, the hybrid classification correctly matched the Muller weather type for 52% of the seed days. In addition, the automated catalog captured the seasonal distribution and interannual variability of the Muller types remarkably well. The hybrid synoptic weather classification system applied to weather properties at Shreveport and New Orleans showed significant differences between weather types. The automated procedure does not replicate the Muller weather type classification exactly; however, it is homogenous within itself and has value for describing the variability of surface weather in Louisiana. In fact, it is arguably advantageous for some applications, owing to its objectivity, speed, and reproducibility.
The effect of nitrification inhibitors on the nitrous oxide (N2O) release from agricultural soils—a review
Authors: Ruser Reiner , Schulz Rudolf
Published: February 2015

The use of nitrification inhibitors (NI) is a technique which is able to improve N fertilizer use efficiency, to reduce nitrate leaching and to decrease the emission of the climate‐relevant gas N2O simultaneously, particularly in moderately fertilized agricultural systems adapted to plant N demand. The ammonia monooxygenase (AMO) is the first enzyme which is involved in the oxidation of NH$ _4^+ $ to NO$ _3^ - $ in soils. The inhibition of the AMO by NIs directly decreases the nitrification rate and it reduces the NO$ _3^- $ concentration which serves as substrate for denitrification. Hence, the two main pathways of N2O production in soils are blocked or their source strength is at least decreased. Although it has been shown that archaea are also able to oxidize NH3, results from literature suggest that the enzymatic activity of NH3 oxidizing bacteria is the most important target for NIs because it was much stronger affected. The application of NIs to reduce N2O emissions is most effective under conditions in which the NI remains close to the N ‐ fertilizer. This is the case when the NI was sprayed on mineral ‐ N fertilizer granules or thoroughly mixed with liquid fertilizers. Most serious problems of spatial separation of NI and substrate emerge on pasture soils, where N2O hotspots occur under urine and to a lesser extent under manure patches. From the few studies on the effect of different NI quantities it seems that the amount of NI necessary to reduce N2O emissions is below the recommendations for NI amounts in practice.

NIs can improve the fertilizer value of liquid manure. For instance, the addition of NIs to slurry can increase N uptake and yield of crops when NO$ _3^ - $ ‐ N leaching losses are reduced. It has clearly been demonstrated that NIs added to cattle slurry are very effective in reducing N2O as well as NO emissions after surface application and injection of slurry into grassland soils. In flooded rice systems NIs can reduce CH4 emission significantly, whereas the effect on CO2 emission is varying. On the other hand, as an effect of the delay of nitrification by NIs, NH3 emission might increase when N fertilizers are not incorporated into the soil. As compared to other measures NIs have a high potential to reduce N2O emissions from agricultural soils. Further, no other measure has so consistently been proofed according its efficiency to reduce N2O emissions. From the published data [Akiyama et al. (2010) and more recent data from the years 2010–2013; 140 data sets in total] a reduction potential of approx. 35% seems realistic; however, further measurements in different management systems, particularly in regions with intense frost/thaw cycles seem necessary to confirm this reduction potential. These measurements generally should cover a whole annual cycle.
“The Constant State of Becoming”: Power, Identity, and Discomfort on the Anti‐Oppressive Learning Journey
Authors: Hart Andrew , Montague Jane
Published: February 2015

The development of a clear personal and professional identity—“knowing oneself”—is frequently cited as a key factor in supporting anti‐oppressive practice. In the field of health and social care, work placements are a major vehicle for equipping students to become anti‐oppressive practitioners committed to making effective diversity interventions in a range of organizational settings. This article highlights some of the tensions inherent in the formation of such an identity and pays particular attention to issues such as discomfort, power inequalities, the discursive production of the self, and ways in which educational and workplace organizational settings can simultaneously promote and inhibit such identity development. The article concludes that the discomfort experienced by students as part of this learning process is not only inevitable but necessary to becoming an anti‐oppressive practitioner and that the narrative process offers ways of empowering both students and service users to challenge oppression.
Career Progression of Equality and Diversity Professionals in U.K. National Health Service Organizations: A Knowledge Review
Authors: Archibong Uduak , Harvey Brendon , Baxter Carol , Jogi Mohamed
Published: February 2015

This paper presents a knowledge review on the career progression of Equality and Diversity professionals within the British National Health Service. Adopting a multidimensional methodological approach, the review involved examining literature of published and unpublished literature including scientific journals, statistics, and national and international reports to highlight research gaps, consultation with experts, and documentary analysis of job advertisements. Thematic analysis was utilized to examine and report patterns within data generated from the multiple data collection methods. The review identified the concept of career undergoing a fundamental shift in strategy and consequent overhaul of traditional organizational structures in all sectors. New boundaryless organizations have presented the possibility of boundaryless careers, resulting in the renegotiation of the psychological contract between employee and employer. The knowledge review has identified that more needs to be addressed, from both employee and employer perspectives, to ensure that conditions are in place for such competences to flourish.