bluuebunny/crossref_metadata_2025 huggingface dataset:
Population pharmacokinetic/pharmacodynamic modelling of the effects of axomadol and its O‐demethyl metabolite on pupil diameter and nociception in healthy subjects
Authors: Mangas‐Sanjuan Víctor , Pastor José Martín , Rengelshausen Jens , Bursi Roberta , Troconiz Iñaki F.
Published: February 2016

Aim

The aim of the present study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) properties of the active components of axomadol and to quantify their contribution to observed the pupillometric and analgesic (measured through the cold pressor test) effects linking the PD engagement biomarker with clinical response.

Methods

Healthy subjects (n = 74) received either placebo or axomadol orally at doses ranging from 66 mg to 225 mg following multiple dosing regimens in two separate clinical trials. Plasma concentrations of the two enantiomers of axomadol and their metabolites, and PD responses were measured at specific times. The population analysis was performed using NONMEM 7.2.

Results

The kinetics of the parent drug and its metabolite could be described simultaneously using an extra compartment mimicking the liver, where the metabolite is formed. The SS parent compound elicited a plasma concentration‐dependent increase in pupil diameter, with estimates (percentage relative standard errors) of maximal effect (Emax) and plasma concentration exerting a half‐maximal effect (C50) of 0.79 (17.4) mm, and 90.7 (27) ng ml−1, respectively. The predicted effect site concentrations of the RR O‐demethyl metabolite decreased the pupil diameter linearly, with an estimate of the slope of 0.00967 (18.7) mm·ml ng−1. An additive model, integrating the net effect on pupil diameter, described adequately the reduction in pain with a linear function. The PK/PD model revealed that each 0.5 mm change in pupil diameter is associated with a 10% decrease in cold pressor area under the concentration–time curve effects.

Conclusions

The PK/PD analysis performed enabled the individual contributions of the active compounds to the observed effects to be identified and quantified. These effects were in accordance with the known mechanisms of action – namely, opioid agonism and noradrenaline reuptake inhibition.
E‐learning in order to improve drug prescription for hospitalized older patients: a cluster‐randomized controlled study
Authors: Franchi Carlotta , Tettamanti Mauro , Djade Codjo Dgnefa , Pasina Luca , Mannucci Pier Mannuccio , Onder Graziano , Gussoni Gualberto , Manfellotto Dario , Bonassi Stefano , Salerno Francesco , Nobili Alessandro ,   on behalf of ELICADHE Investigators
Published: February 2016

Aims

The aim of the study was to evaluate the effect of an e‐learning educational program meant to foster the quality of drug prescription in hospitalized elderly patients.

Methods

Twenty geriatric and internal medicine wards were randomized to intervention (e‐learning educational program) or control (basic geriatric pharmacology notions). Logistic regression analysis was used in order to assess the effect of the intervention on the use of potentially inappropriate medication (PIM, primary outcome) at hospital discharge. Secondary outcomes were a reduced prevalence of at least one potential drug–drug interaction (DDI) and potentially severe DDI at discharge. Mortality rate and incidence of re‐hospitalizations were other secondary outcomes assessed at the 12‐month follow‐up.

Results

A total of 697 patients (347 in the intervention and 350 in the control arms) were enrolled. No difference in the prevalence of PIM at discharge was found between arms (OR 1.29 95%CI 0.87–1.91). We also found no decrease in the prevalence of DDI (OR 0.67 95%CI 0.34–1.28) and potentially severe DDI (OR 0.86 95%CI 0.63–1.15) at discharge, nor in mortality rates and incidence of re‐hospitalization at 12‐month follow‐up.

Conclusions

This e‐learning educational program had no clear effect on the quality of drug prescription and clinical outcomes in hospitalized elderly patients. Given the high prevalence of PIMs and potential DDIs recorded in the frame of this study, other approaches should be developed in order to improve the quality of drug prescription in this population.
The pharmacodynamics, safety and pharmacokinetics of single doses of the motilin agonist, camicinal, in type 1 diabetes mellitus with slow gastric emptying
Authors: Hellström Per M , Tack Jan , Johnson Lakshmi Vasist , Hacquoil Kimberley , Barton Matthew E , Richards Duncan B , Alpers David H , Sanger Gareth J , Dukes George E
Published: February 2016

Background and Purpose

Here we have investigated the pharmacokinetics, pharmacodynamics and safety of single doses of camicinal in type 1 diabetes mellitus (T1DM) patients with a history of slow gastric emptying with symptoms consistent with gastroparesis.

Experimental Approach

In a randomized, double‐blind, placebo‐controlled, incomplete block, three‐period, two‐centre crossover study, patients received oral administration of placebo and two of the three possible doses of camicinal (25, 50 or 125 mg). Gastric emptying (13C‐octanoic acid breath test), pharmacokinetics and safety were primary outcomes.

Key Results

Nine of the 10 patients enrolled completed the study. Gastric half‐emptying time decreased by −95 min (95% CI: −156.8, −34.2) after a single dose of camicinal 125 mg compared with placebo (52 vs. 147 min, P < 0.05), representing a 65% improvement. A decrease of the gastric half‐emptying time compared with placebo (approximately 39 min) was observed with camicinal 25 and 50 mg, representing a 27% reduction for both doses (not statistically significant). A positive exposure–response relationship was demonstrated across all doses. The effects of camicinal on gastric half‐emptying time were not influenced by fasting glucose levels. Single doses up to 125 mg were well tolerated. Camicinal was well absorbed, exhibiting linear and approximately dose‐proportional pharmacokinetic characteristics and a clear exposure–response relationship with gastric emptying.

Conclusions and Implications

Camicinal significantly accelerated gastric emptying of solids in T1DM patients following administration of a single oral dose. Camicinal was well tolerated and exhibited similar pharmacokinetic characteristics in diabetic patients to those previously reported in healthy volunteers.
Xenotransplantation elicits salient tumorigenicity of adult T‐cell leukemia‐derived cells via aberrant AKT activation
Authors: Yamaguchi Kazunori , Takanashi Tomoka , Nasu Kentaro , Tamai Keiichi , Mochizuki Mai , Satoh Ikuro , Ine Shoji , Sasaki Osamu , Satoh Kennichi , Tanaka Nobuyuki , Harigae Hideo , Sugamura Kazuo
Published: February 2016

The transplantation of human cancer cells into immunodeficient NOD/SCID/IL‐2Rγcnull (NOG) mice often causes highly malignant cell populations like cancer stem cells to emerge. Here, by serial transplantation in NOG mice, we established two highly tumorigenic adult T‐cell leukemia‐derived cell lines, ST1‐N6 and TL‐Om1‐N8. When transplanted s.c., these cells formed tumors significantly earlier and from fewer initial cells than their parental lines ST1 and TL‐Om1. We found that protein kinase B (AKT) signaling was upregulated in ST1‐N6 and TL‐Om1‐N8 cells, and that this upregulation was due to the decreased expression of a negative regulator, INPP5D. Furthermore, the introduction of a constitutively active AKT mutant expression vector into ST1 cells augmented the tumorigenicity of the cells, whereas treatment with the AKT inhibitor MK‐2206 attenuated the progression of tumors induced by ST1‐N6 cells. Collectively, our results reveal that the AKT signaling pathway plays a critical role in the malignancy of adult T‐cell leukemia‐derived cells.
Development of Children's Estimation Skills: The Ambiguous Role of Their Familiarity With Numerals
Authors: Ebersbach Mirjam
Published: February 2016

Estimating magnitudes is central to life, as well as to mathematics. Symbolic estimates involve assigning symbolic numerals to nonsymbolic magnitudes (or vice versa), whereas nonsymbolic estimates refer to mapping between two nonsymbolic magnitudes. In general, estimates on both types of tasks become more accurate with age and among adults, are more accurate for smaller than larger magnitudes. However, children and adults show task‐specific biases in their estimates. Moreover, young children systematically over‐ or underestimate, especially concerning smaller magnitudes. In this article, I discuss potential explanations for children's estimation biases, considering children's familiarity with numerals, which enhances their ability to discriminate between numerals but seems to temporarily make their estimates in their familiar number range less accurate. I also consider developmental asynchronies in the production and comprehension of number words.
Increase in the length of superficial temporal artery biopsy over 14 years
Authors: Au Cheryl P , Sharma Neil S , McCluskey Peter , Ghabrial Raf
Published: February 2016

Background

Giant cell arteritis is a systemic inflammatory vasculitis of large‐sized and medium‐sized arteries. Superficial temporal artery biopsy of at least 20 mm has traditionally been the standard length for histopathology to accurately diagnose giant cell arteritis. Recent studies suggest than a post‐fixation superficial temporal artery biopsy length of 7 to 10 mm is adequate for diagnosing giant cell arteritis.

Design

This is a retrospective observational study.

Participants or samples

The participants were all patients who underwent superficial temporal artery biopsy at Royal Prince Alfred Hospital, a large tertiary teaching hospital in Sydney, Australia, from 2008 to 2014.

Methods

Patients were identified using computerized hospital databases. Superficial temporal artery biopsy lengths were obtained from the histopathology reports.

Main outcome measures

We aimed to compare the superficial temporal artery biopsy lengths performed at a large tertiary hospital over the past 7 years, to those performed from 2000 to 2005, and to determine the frequency of diagnosis of giant cell arteritis over the two time periods.

Results

There was a total of 96 superficial temporal artery biopsies performed from 2008 to 2014. The superficial temporal artery biopsy mean (standard deviation) length was 16.0(7.3) mm. This represented a significant (P = 0.015) increase in mean superficial temporal artery biopsy length when compared with a previous audit performed from 2000 to 2005 where the mean (standard deviation) superficial temporal artery biopsy was 11.7(6.2) mm. Of the 96 TABs, 20 (20.8%) were positive for giant cell arteritis, compared with a giant cell arteritis positivity rate of 20.4% for the previous audit period from 2000 to 2005.

Conclusion

There has been a significant improvement in the length of superficial temporal artery biopsy performed at a tertiary hospital. Despite the increase in superficial temporal artery biopsy lengths, the giant cell arteritis positivity rate has remained stable.
Correlation of obstructive sleep apnoea and laryngopharyngeal reflux: phmetry study
Authors: Elhennawi D.M. , Ahmed M.R. , Abou‐halawa A.S.
Published: February 2016

Objective

To study the correlation of obstructive sleep apnoea (OSA) and laryngopharyngeal reflux (LPR).

Design

A descriptive study.

Setting

Suez Canal University Hospital, Ismailia, Egypt.

Patients

62 patients with polysomnography confirmed OSA.

Intervention

Patients were evaluated with ambulatory 24‐h double channel pH monitoring.

Results

Mean reflux symptom index in the study group was 9 ± 5.5, and it was > 13 in all patients with severe OSA. Signs of LPR reflux were present in 34 (55%) patients. Abnormal reflux was detected in the distal oesophagus in 41 patients (66%) and in the proximal oesophagus in 21 patients (34%). Patients with severe OSA had significantly higher nocturnal LPR reflux episodes compared to patients with mild disease (P < .05). Number of reflux episodes and total duration of reflux during sleep are significantly correlated to degree of OSA (P < .05). No difference was found in relation to age or sex. Daytime reflux was not related to the degree of obstructive sleep apnoea (P > .05).

Conclusion

LPR is common in patients with OSA. Patients with severe OSA have significantly higher nocturnal LPR. This should be considered when treating this group of patients.
Feasibility study from a randomized controlled trial of standard closure of a stoma site vs biological mesh reinforcement
Authors:   the Reinforcement of Closure of Stoma Site (ROCSS) Collaborative and the West Midlands Research Collaborative
Published: February 2016

Aim

Hernia formation occurs at closed stoma sites in up to 30% of patients. The Reinforcement of Closure of Stoma Site (ROCSS) randomized controlled trial is evaluating whether placement of biological mesh during stoma closure safely reduces hernia rates compared with closure without mesh, without increasing surgical or wound complications. This paper aims to report recruitment, deliverability and safety from the internal feasibility study.

Method

A multicentre, patient and assessor blinded, randomized controlled trial, delivered through surgical trainee research networks. A 90‐patient internal feasibility study assessed recruitment, randomization, deliverability and early (30 day) safety of the novel surgical technique (ClinicalTrials.gov registration number NCT02238964).

Results

The feasibility study recruited 90 patients from the 104 considered for entry (45 to mesh, 45 to no mesh). Seven of eight participating centres randomized patients within 30 days of opening. Overall, 41% of stomas were created for malignant disease and 73% were ileostomies. No mesh‐specific complications occurred. Thirty‐one postoperative adverse events were experienced by 31 patients, including surgical site infection (9%) and postoperative ileus (6%). One mesh was removed for re‐access to the abdominal cavity, for reasons unrelated to the mesh. Independent review by the Data Monitoring and Ethics Committee of adverse event data by treatment allocation found no safety concerns.

Conclusion

Multicentre randomization to this trial of biological mesh is feasible, with no early safety concerns. Progression to the full Phase III trial has continued. ROCSS shows that trainee research networks can efficiently develop and deliver complex interventional surgical trials.
An analysis of the accuracy of computed tomography colonography when defining anatomy for novel full‐thickness colonic excision techniques in early colonic neoplasia
Authors: Currie A. C. , Burling D. , Mainta E. , Ilangovan R. , Moorghen M. , Lung P. , Faiz O , Kennedy R. H.
Published: February 2016

Aim

Full‐thickness laparo‐endoscopic excision (FLEX) is a new technique developed for the full‐thickness excision of colonic adenomas and, potentially, early cancer, avoiding the need for colectomy. FLEX requires accurate preoperative characterization of three key morphological features of the tumour, including its relation to the mesenteric border, its diameter and the circumferential extent of involvement of the bowel wall. This study evaluated the accuracy of CT colonography (CTC) for the assessment of these features in early colonic tumours.

Method

Consecutive patients undergoing CTC prior to colonic resection for complex benign polyps or UICC Stage 1 cancer were retrospectively analysed by two specialist gastrointestinal radiologists blinded to the subsequent histopathological findings. The location of the tumour in relation to the mesenteric border, its maximum diameter and the circumferential extent of involvement of the colonic wall were correlated with the histopathological examination of the surgical resection specimen. Pearson's correlation coefficient (r) and Kappa agreement (κ) were used to compare the maximum diameter and the circumferential extent of involvement of the colonic wall.

Results

Twenty‐eight patients with early colonic neoplasia were included. All had had a surgical segmental resection. Four had a benign adenoma and 24 had a TNM Stage 1 cancer. Histopathological assessment of the resected surgical specimen showed that 21 of the 28 lesions were located on the mesenteric border. The median diameter was 35 (interquartile range 28–42) mm; 13 lesions involved less than one‐third of the circumference, 11 between one and two‐thirds and four more than two‐thirds. CTC correctly identified the location of the lesion in relation to the mesenteric border in all 28 cases. Correlation between CTC and histopathology was good for the assessment of the maximum diameter of the lesion (r = 0.81) and the circumferential extent of involvement of the colonic wall (κ = 0.76).

Conclusion

CTC can accurately assess the key morphological features for the selection of patients with early colonic neoplasia for full‐thickness laparo‐endoscopic excision.
Language Reflects “Core” Cognition: A New Theory About the Origin of Cross‐Linguistic Regularities
Authors: Strickland Brent
Published: February 2016

The underlying structures that are common to the world's languages bear an intriguing connection with early emerging forms of “core knowledge” (Spelke & Kinzler, 2007), which are frequently studied by infant researchers. In particular, grammatical systems often incorporate distinctions (e.g., the mass/count distinction) that reflect those made in core knowledge (e.g., the non‐verbal distinction between an object and a substance). Here, I argue that this connection occurs because non‐verbal core knowledge systematically biases processes of language evolution. This account potentially explains a wide range of cross‐linguistic grammatical phenomena that currently lack an adequate explanation. Second, I suggest that developmental researchers and cognitive scientists interested in (non‐verbal) knowledge representation can exploit this connection to language by using observations about cross‐linguistic grammatical tendencies to inspire hypotheses about core knowledge.
Pilot study of a novel, large‐bore, fully covered self‐expandable metallic stent for unresectable distal biliary malignancies
Authors: Mukai Tsuyoshi , Yasuda Ichiro , Isayama Hiroyuki , Iwashita Takuji , Itoi Takao , Kawakami Hiroshi , Kogure Hirofumi , Nakai Yousuke
Published: February 2016

Background and Aim

In patients with unresectable malignant distal biliary obstruction, covered self‐expandable metallic stents (CSEMS) may remain patent longer than uncovered self‐expandable metallic stents as a result of tumor ingrowth prevention. One main cause of recurrent biliary obstruction (RBO) in CSEMS is sludge formation, which can be prevented using a large‐bore stent. Therefore, we developed a novel, 12‐mm diameter fully covered SEMS (FCSEMS) and investigated its clinical safety, efficacy, and rate of adverse events.

Methods

This prospective, multicenter pilot study, which ran between June 2011 and November 2012, included 38 consecutive patients with unresectable malignant distal biliary obstruction. All patients underwent endoscopic insertion of our novel stent. Primary endpoint was non‐RBO rate 6 months after placement.

Results

Technical and functional success rates of the procedures were 100%. Six‐month non‐RBO rate was 50%, and median time to RBO was 184 days. Median survival time was 241 days. Twelve patients died within 6 months after stent placement without RBO. RBO was observed in 10 patients (26%), with seven experiencing stent occlusion and three experiencing stent migration. Adverse events other than RBO (at <30 days) developed in six patients (16%; cholecystitis, one; pancreatitis, one; hyperamylasemia, one; pancreatic ductitis, one; abdominal pain, two). Stent removal for reintervention was successfully completed in eight patients.

Conclusion

Our novel FCSEMS may be safe and effective for managing malignant distal obstruction with an acceptable incidence of adverse events.
Relation of Pulmonary Artery Pressure and Renal Impairment in ST Segment Elevation Myocardial Infarction Patients
Authors: Shacham Yacov , Gal‐Oz Amir , Topilsky Yan , Keren Gad , Arbel Yaron
Published: February 2016

Background

Recent reports have demonstrated the adverse effects of venous congestion on renal function in patients having heart failure. None of the above trials, however, included patients with acute ischemia.

Hypothesis

Echocardiographic correlates of increased right ventricular afterload would be associated with an increased risk of acute kidney injury (AKI) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI).

Methods

We conducted a retrospective study of consecutive 930 STEMI patients who underwent primary PCI and had a full echocardiography study performed within 72 hours of hospital admission between June 2011 and December 2014.

Results

Echocardiography demonstrated that patients with AKI had significantly lower left ventricular (LV) ejection fraction, higher systolic pulmonary artery pressure (SPAP), and right atrial pressures (P < 0.001 for all). Following the performance of logistic multivariate analysis model, SPAP (HR 1.07, 95% CI 1.04–1.11; P < 0.001) and LV ejection fraction (HR 0.95, 95% CI 0.92–0.99; P = 0.03) emerged as independent predictors of AKI. On receiver operating characteristic (ROC) curve analysis, the optimal cutoff value of SPAP to predict AKI was measured as more than 32 mmHg, with 71% sensitivity and 62% specificity (AUC 0.739, 95% CI 0.671–0.806, P < 0.001).

Conclusions

Among STEMI patients undergoing primary PCI, worse LV function and elevated SPAP were associated with increased risk of AKI.
Dorsolateral neostriatum contribution to incentive salience: opioid or dopamine stimulation makes one reward cue more motivationally attractive than another
Authors: DiFeliceantonio Alexandra G. , Berridge Kent C.
Published: February 2016

Pavlovian cues for rewards can become attractive incentives: approached and ‘wanted’ as the rewards themselves. The motivational attractiveness of a previously learned cue is not fixed, but can be dynamically amplified during re‐encounter by simultaneous activation of brain limbic circuitry. Here it was reported that opioid or dopamine microinjections in the dorsolateral quadrant of the neostriatum (DLS) of rats selectively amplify attraction toward a previously learned Pavlovian cue in an individualized fashion, at the expense of a competing cue. In an autoshaping (sign‐tracking vs. goal‐tracking) paradigm, microinjection of the mu opioid receptor agonist (DAMGO) or dopamine indirect agonist (amphetamine) in the DLS of sign‐tracker individuals selectively enhanced their sign‐tracking attraction toward the reward‐predictive lever cue. By contrast, DAMGO or amphetamine in the DLS of goal‐trackers selectively enhanced prepotent attraction toward the reward‐proximal cue of sucrose dish. Amphetamine also enhanced goal‐tracking in some sign‐tracker individuals (if they ever defected to the dish even once). That DLS enhancement of cue attraction was due to stronger motivation, not stronger habits, was suggested by: (i) sign‐trackers flexibly followed their cue to a new location when the lever was suddenly moved after DLS DAMGO microinjection; and (ii) DAMGO in the DLS also made sign‐trackers work harder on a new instrumental nose‐poke response required to earn presentations of their Pavlovian lever cue (instrumental conditioned reinforcement). Altogether, the current results suggest that DLS circuitry can enhance the incentive salience of a Pavlovian reward cue, selectively making that cue a stronger motivational magnet.
Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats
Authors: Drion Cato M. , Borm Lars E. , Kooijman Lieneke , Aronica Eleonora , Wadman Wytse J. , Hartog Aloysius F. , van Vliet Erwin A. , Gorter Jan A.
Published: February 2016

Objective

Inhibition of the mammalian target of rapamycin (mTOR) pathway has been suggested as a possible antiepileptogenic strategy in temporal lobe epilepsy (TLE). Here we aim to elucidate whether mTOR inhibition has antiepileptogenic and/or antiseizure effects using different treatment strategies in the electrogenic post–status epilepticus (SE) rat model.

Methods

Effects of mTOR inhibitor rapamycin were tested using the following three treatment protocols: (1) “stop‐treatment”—post‐SE treatment (6 mg/kg/day) was discontinued after 3 weeks; rats were monitored for 5 more weeks thereafter, (2) “pretreatment”—rapamycin (3 mg/kg/day) was applied during 3 days preceding SE; and (3) “chronic phase‐treatment”—5 days rapamycin treatment (3 mg/kg/day) in the chronic phase. We also tested curcumin, an alternative mTOR inhibitor with antiinflammatory and antioxidant effects, using chronic phase treatment. Seizures were continuously monitored using video–electroencephalography (EEG) recordings; mossy fiber sprouting, cell death, and inflammation were studied using immunohistochemistry. Blood was withdrawn regularly to assess rapamycin and curcumin levels with high performance liquid chromatography (HPLC).

Results

Stop‐treatment led to a strong reduction of seizures during the 3‐week treatment and a gradual reappearance of seizures during the following 5 weeks. Three days pretreatment did not prevent seizure development, whereas 5‐day rapamycin treatment in the chronic phase reduced seizure frequency. Washout of rapamycin was slow and associated with a gradual reappearance of seizures. Rapamycin treatment (both 3 and 6 mg/kg) led to body growth reduction. Curcumin treatment did not reduce seizure frequency or lead to a decrease in body weight.

Significance

The present study indicates that rapamycin cannot prevent epilepsy in the electrical stimulation post‐SE rat model but has seizure‐suppressing properties as long as rapamycin blood levels are sufficiently high. Oral curcumin treatment had no effect on chronic seizures, possibly because it did not reach the brain at adequate levels.
Market and design solutions to the short‐term economic impacts of marine reserves
Authors: Ovando Daniel , Dougherty Dawn , Wilson Jono R
Published: February 2016

Well‐managed fisheries support healthy ocean ecosystems, coastal livelihoods and food security for millions of people. However, many communities lack the resources to implement effective fisheries management. No‐take marine reserves are a ubiquitous management intervention that provide conservation benefits and under certain circumstances can provide long‐term fishery benefits as a result of larval and adult emigration from reserve boundaries. But, support for marine reserves by fishery participants is often limited due to short‐term economic impacts resulting from foregone yields. In this study, we examine the timing and magnitude of economic impacts of marine reserves by utilizing a novel metric that discounts future economic benefits of enhanced productivity resulting from reserve protection. We ask under what circumstances long‐term benefits outweigh short‐term impacts of marine reserve implementation. We simulate fisheries for six species commonly caught in coastal environments and show that while conservation benefits accrue rapidly, more than a decade is often required to provide net fisheries benefits, even under circumstances favourable for reserves. We explore a suite of strategies for mitigating these short‐term economic losses, including flexible reserve designs, loans and enhanced ex‐vessel revenues. Results indicate that market‐based incentives show promise to offset short‐term economic losses. Our findings highlight the importance of understanding and communicating likely outcomes from marine reserve implementation and the need to engage supply chain actors to incentivize marine conservation that minimizes impacts to fishermen.
The influence of the biological pump on ocean chemistry: implications for long‐term trends in marine redox chemistry, the global carbon cycle, and marine animal ecosystems
Authors: Meyer K. M. , Ridgwell A. , Payne J. L.
Published: February 2016

The net export of organic matter from the surface ocean and its respiration at depth create vertical gradients in nutrient and oxygen availability that play a primary role in structuring marine ecosystems. Changes in the properties of this ‘biological pump’ have been hypothesized to account for important shifts in marine ecosystem structure, including the Cambrian explosion. However, the influence of variation in the behavior of the biological pump on ocean biogeochemistry remains poorly quantified, preventing any detailed exploration of how changes in the biological pump over geological time may have shaped long‐term shifts in ocean chemistry, biogeochemical cycling, and ecosystem structure. Here, we use a 3‐dimensional Earth system model of intermediate complexity to quantitatively explore the effects of the biological pump on marine chemistry. We find that when respiration of sinking organic matter is efficient, due to slower sinking or higher respiration rates, anoxia tends to be more prevalent and to occur in shallower waters. Consequently, the Phanerozoic trend toward less bottom‐water anoxia in continental shelf settings can potentially be explained by a change in the spatial dynamics of nutrient cycling rather than by any change in the ocean phosphate inventory. The model results further suggest that the Phanerozoic decline in the prevalence ocean anoxia is, in part, a consequence of the evolution of larger phytoplankton, many of which produce mineralized tests. We hypothesize that the Phanerozoic trend toward greater animal abundance and metabolic demand was driven more by increased oxygen concentrations in shelf environments than by greater food (nutrient) availability. In fact, a lower‐than‐modern ocean phosphate inventory in our closed system model is unable to account for the Paleozoic prevalence of bottom‐water anoxia. Overall, these model simulations suggest that the changing spatial distribution of photosynthesis and respiration in the oceans has exerted a first‐order control on Earth system evolution across Phanerozoic time.
Field and laboratory studies reveal interacting effects of stream oxygenation and warming on aquatic ectotherms
Authors: Verberk Wilco C.E.P. , Durance Isabelle , Vaughan Ian P. , Ormerod Steve J.
Published: February 2016

Aquatic ecological responses to climatic warming are complicated by interactions between thermal effects and other environmental stressors such as organic pollution and hypoxia. Laboratory experiments have demonstrated how oxygen limitation can set heat tolerance for some aquatic ectotherms, but only at unrealistic lethal temperatures and without field data to assess whether oxygen shortages might also underlie sublethal warming effects. Here, we test whether oxygen availability affects both lethal and nonlethal impacts of warming on two widespread Eurasian mayflies, Ephemera danica, Müller 1764 and Serratella ignita (Poda 1761). Mayfly nymphs are often a dominant component of the invertebrate assemblage in streams, and play a vital role in aquatic and riparian food webs. In the laboratory, lethal impacts of warming were assessed under three oxygen conditions. In the field, effects of oxygen availability on nonlethal impacts of warming were assessed from mayfly occurrence in 42 293 UK stream samples where water temperature and biochemical oxygen demand were measured. Oxygen limitation affected both lethal and sublethal impacts of warming in each species. Hypoxia lowered lethal limits by 5.5 °C (±2.13) and 8.2 °C (±0.62) for E. danica and S. ignita respectively. Field data confirmed the importance of oxygen limitation in warmer waters; poor oxygenation drastically reduced site occupancy, and reductions were especially pronounced under warm water conditions. Consequently, poor oxygenation lowered optimal stream temperatures for both species. The broad concordance shown here between laboratory results and extensive field data suggests that oxygen limitation not only impairs survival at thermal extremes but also restricts species abundance in the field at temperatures well below upper lethal limits. Stream oxygenation could thus control the vulnerability of aquatic ectotherms to global warming. Improving water oxygenation and reducing pollution can provide key facets of climate change adaptation for running waters.
What Have We Learned From Brain Functional Connectivity Studies in Migraine Headache?
Authors: Maleki Nasim , Gollub Randy L.
Published: February 2016

Over the past 20 years, headache syndromes, especially migraine, have benefited significantly from the knowledge gained through neuroimaging studies. This article is focused on the neuroimaging studies of the functional organization and connectivity of the migraine brain. First, data sources and the study design elements in functional neuroimaging studies of the brain connectivity in migraine headaches are discussed. Then, the article reviews the findings to date and discusses how functional connectivity studies have contributed to a better understanding of the mechanisms of the migraine disease by extending the focus from a single region or structure to a network of regions and structures and the interactions among them. Finally, the potential scenarios for the translation of connectivity knowledge to the benefit for patients are discussed.
Listening to the consumer voice: developing multilingual cancer information resources for people affected by liver cancer
Authors: Robotin Monica C. , Porwal Mamta , Hopwood Max , Nguyen Debbie , Sze Minglo , Treloar Carla , George Jacob
Published: February 2016

Background

In Australia, liver cancer incidence is rising, particularly among people born in hepatitis B‐endemic countries. We sought to build an understanding of the information needs of people affected by liver cancer, to inform the design of in‐language consumer information resources.

Methods

We searched the World Wide Web for available in‐language consumer information and conducted a literature search on consumers’ information needs and their preferred means of accessing it. Qualitative data collection involved bilingual researchers conducting focus group discussions (26 participants) and in‐depth interviews (22 participants) with people affected by liver cancer in English, Vietnamese, Cantonese and Mandarin. Sessions were audio‐recorded, transcribed, translated and thematically analysed. The key themes and salient findings informed the development of in‐language multimedia information resources.

Results

Many consumer resources did not cater for people with low literacy levels. The participants wanted more information on cancer diagnostic and treatment options, nutrition and Chinese Medicine and experienced communication challenges speaking to health professionals. While Vietnamese speakers relied entirely on information provided by their doctors, other participants actively searched for additional treatment information and commonly used the Internet to source it. We developed multilingual, multimedia consumer information resources addressing identified consumer information needs through an iterative process, in collaboration with our multilingual consumer panel. These resources are available in four languages, as separate modules accessible online and in DVD format.

Conclusion

This process enabled the development of user‐friendly patient resources, which complement health‐care provider information and supports informed patient decision making.
Antioxidant and antitumour activities of exopolysaccharide from liquid‐cultured Grifola frondosa by chemical modification
Authors: Zhang Wenna , Lu Yongming , Zhang Yaping , Ding Qiuying , Hussain Sajid , Wu Qingxi , Pan Wenjuan , Chen Yan
Published: February 2016

Grifola frondosa is a popular edible mushroom for its tasty flavour and can be used as a dietary supplement for its functional substances. In this study, an exopolysaccharide (EPS), purified from the submerged culture of G. frondosa, was chemically modified to obtain its carboxymethylated (CM‐EPS) and selenising derivatives (Se‐EPS). The chemical characteristics of these polysaccharides were determined based on high‐performance liquid chromatography (HPLC) and infrared analysis (IR). The antioxidant and antitumour activities of EPS and its derivatives were further investigated, respectively. The results showed that the antioxidant capacity of CM‐EPS and Se‐EPS were much better than that of EPS. Moreover, the Se‐EPS could significantly inhibit the proliferation of Hela cells compared with EPS. This study demonstrated that the carboxymethylation and selenylation played a great influence on enhancing the antioxidant and antitumour activities of exopolysaccharides from G. frondosa.
Effects of aqueous ozone treatments on microbial load reduction and shelf life extension of fresh‐cut apple
Authors: Liu Chenghui , Ma Tao , Hu Wenzhong , Tian Mixia , Sun Lu
Published: February 2016

Aqueous ozone was first used to take the place of chlorine as fresh‐cut apples sanitiser. Aqueous ozone (1.4 mg L−1) treatments were evaluated for their effectiveness on microbial growth, quality attributes and shelf life of fresh‐cut apples. The results indicated that aqueous ozone treatments for 5 and 10 min achieved accepted microbial quality and, respectively, reduced total bacteria counts by 1.83 and 2.13 log10CFU g−1 compared with the control samples on the 12th day. The ethylene production, polyphenol oxidase and peroxidase activities, and total phenol and malondialdehyde contents were reduced by aqueous ozone treatments. In addition, this sanitiser also delayed the quality deterioration of fresh‐cut apples and enhanced their antioxidant capacity. Therefore, it was recommended to sanitise fresh‐cut apples with aqueous ozone (1.4 mg L−1) for 5 min, which applied to industrial production requirement for both efficiency and costs and could extend the shelf life up to 10 days.
Mouse and human CD8+ CD28low regulatory T lymphocytes differentiate in the thymus
Authors: Vuddamalay Yirajen , Attia Mehdi , Vicente Rita , Pomié Céline , Enault Geneviève , Leobon Bertrand , Joffre Olivier , Romagnoli Paola , van Meerwijk Joost P.M.
Published: February 2016

Regulatory T (Treg) lymphocytes play a central role in the control of immune responses and so maintain immune tolerance and homeostasis. In mice, expression of the CD8 co‐receptor and low levels of the co‐stimulatory molecule CD28 characterizes a Treg cell population that exerts potent suppressive function in vitro and efficiently controls experimental immunopathology in vivo. It has remained unclear if CD8+ CD28low Treg cells develop in the thymus or represent a population of chronically activated conventional T cells differentiating into Treg cells in the periphery, as suggested by their CD28low phenotype. We demonstrate that functional CD8+ CD28low Treg cells are present in the thymus and that these cells develop locally and are not recirculating from the periphery. Differentiation of CD8+ CD28low Treg cells requires MHC class I expression on radioresistant but not on haematopoietic thymic stromal cells. In contrast to other Treg cells, CD8+ CD28low Treg cells develop simultaneously with CD8+ CD28high conventional T cells. We also identified a novel homologous naive CD8+ CD28low T‐cell population with immunosuppressive properties in human blood and thymus. Combined, our data demonstrate that CD8+ CD28low cells can develop in the thymus of mice and suggest that the same is true in humans.
The ICN Leadership For Change™ Programme – 20 years of growing influence
Authors: Ferguson Stephanie L. , Al Rifai Fatima , Maay'a Maisa , Nguyen Luu Bich , Qureshi Kristine , Tse Alice M. , Casken John , Parsons Teresa , Shannon Maureen , Napa Maria Diana , Samson‐Langidrik Malia , Jeadrik Glorine
Published: February 2016

Aim

The aim of this article was to present experiences from the field in the context of the International Council of Nurses' Leadership for Change™ programme, which celebrates 20 years of excellence in 2016 for developing the leadership and management capacity of nurses worldwide.

Background

The programme was launched in 1996 in order to boost nurse participation in the healthcare policy‐making process, globally, and to foster within the nursing profession the requisite skills for nurses to lobby for and assume a greater responsibility in the leadership and management of health care services.

Introduction

Over the course of two decades, the programme has been implemented in cooperation between ICN, national nurses associations, the World Health Organization, Ministries of Health and a variety of donor organizations such as the W.K. Kellogg Foundation and development agencies such as USAID and AUSAID. The programme has been implemented in more than 60 nations throughout Africa, Asia, Europe, the Middle East, Latin America and the Pacific Islands, to name a few regions.

Methods

This article offers an overview of the impact that certified ICN LFC nurse trainers and their colleagues have had in the United Arab Emirates, Vietnam and the United States of America and is affiliated islands and the North Pacific Islands.

Results

Twenty years of growth and empowerment are now the ongoing legacy of the ICN LFC Program, which has graduated and deployed nurse trainers around the world and achieved significant advances in the professional development of nurse leaders on an international scale.

Implications for nursing and health policy

Nurse leaders can improve the health and well‐being of their nations in collaboration with consumers and other key stakeholders. Nurse leaders are critical in improving health systems, their work places and broader societal challenges through sound nursing practice, education, research and evidence‐based health and social policy change.
Capricious, or tied to history's apron strings? Floristic regions in north‐west European brambles (RubussubgenusRubus, Rosaceae)
Authors: Haveman Rense , Bijlsma Rienk‐Jan , de Ronde Iris , Schaminée Joop H. J.
Published: February 2016

Aim

To classify and describe distributional patterns in apomicticRubussubgenusRubusin north‐west Europe and to characterize the major regions by statistically derived character species.

Location

North‐western Europe, in particular Ireland, the United Kingdom, the Netherlands, Denmark and Germany.

Methods

We usedtwinspananalysis to distinguish hierarchically ordered phytogeographical regions using grid‐based distributional patterns of bramble species, Dufrêne–Legendre indicator species analysis to define character species for the regions, and descriptive statistical analysis of broad‐scale abiotic factors derived from theLANMAPlandscape classification for each region.

Results

Grid cells were classified into 114 initial groups and 12 regions (florulas), forming three major bramble territories. Up to 15 indicator species could be assigned to each florula. The florulas in the British Isles are geographically isolated, unlike those on the continent. The florulas differ in minimum temperature in January, mean precipitation in August, and elevation. Although a clear view of the relationship between the bramble flora in the British Isles and the continental flora is obscured by the lack of data from Belgium and France, the major biogeographical patterns coincide with the genetic structure of the genus as published by Sochoret al. (). Other factors forming the basis for the observed patterns are isolation (especially in the British Isles), and arguably also landscape history and landscape patterns.

Main conclusions

Phytogeographical patterns inRubussubg.Rubusare strongly influenced by historical factors and can be traced back to the hybridization of sexualRubus ulmifolius,Rubus canescensandRubusser.Glandulosiespecially. Geographical and ecological factors also play a role in the realization of large‐scale patterns, but these factors seem to be closely tied to the history and genetic structure of the genus through inherited ecology from the ancestral species.
Autonomy and Monitoring
Authors: Barrenechea‐méndez Marco a. , Ortín‐Ángel Pedro , Rodes Eduardo C.
Published: February 2016

This paper provides a theoretical and empirical analysis of an under‐explored consequence of granting autonomy to workers: monitoring. In the principal‐agent model that we develop, granting autonomy allows workers to carry out innovative tasks in the workplace. Given that innovative tasks are more difficult to monitor, the model predicts a positive relationship between autonomy and monitoring. Relying on information about blue‐collar workers coming from a dataset of Spanish industrial plants, we provide strong support for this prediction.
Do Business Groups Change With Market Development?
Authors: Larrain Borja , Urzúa I. Francisco
Published: February 2016

Khanna and Yafeh hypothesize that business groups should be more common in economies with less developed markets and institutions. We test the time‐series version of this hypothesis by looking at changes in Chilean groups over 20 years (1990–2009). In this period, Chile experienced a deep economic transformation as measured by common proxies of market development (e.g., per capita income doubled). Despite this dramatic transformation, groups remained mostly unchanged in terms of relative size, industrial diversification, vertical integration, control structures, internal capital markets, and reliance on external funds (minority equity plus debt). Only leverage increased. Also, groups' initial conditions were uncorrelated with market development at the time of formation. This evidence casts doubts on the institutional‐voids hypothesis, although more subtle institutional voids, not captured by the type of macro proxies we use, might explain the existence and resilience of business groups.
Hylobius abietis L. feeding on the novel host Pinus brutia Ten. increases emission of volatile organic compounds
Authors: Semiz G. , Erbilgin N. , Holopainen J. K.
Published: February 2016

Plants respond to feeding by herbivorous insects by producing volatile organic chemicals, which mediate interactions between herbivores and plants. Yet, few studies investigated whether such plant responses to herbivory differ between historical host and novel plants. Here, we investigated whether herbivory by the pine weevil Hylobius abietis causes a release of volatile organic chemicals from a novel tree Pinus brutia and compared the relative amounts of volatiles released from herbivore's historical hosts and P. brutia. We collected volatiles emitted from P. brutia seedlings that were either subjected to feeding by H. abietis or no feeding. Our results indicated that feeding increased emission of volatile compounds, composed of monoterpenes and sesquiterpenes, and that the emission was several fold higher in the damaged seedlings than in undamaged seedlings. In particular, emission of monoterpenes and sesquiterpenes increased by 4.4‐and 10‐fold in the damaged plants, respectively. Strikingly, individual monoterpenes and sesquiterpenes showed much greater dissimilarity between damaged and undamaged seedlings. Furthermore, several minor monoterpenes showed negative relationships with the weevil gnawed area. We discussed these results with the results of previous studies focused on historical host plants of H. abietis and hypothesized the ecological relevance and importance of our results pertaining relevance to the plant–herbivory interactions.
Reproductive biology of the southern thorny skate Amblyraja doellojuradoi (Chondrichthyes, Rajidae)
Authors: Delpiani G.
Published: February 2016

The total lengths (LT) of 193 males (209–556 mm) and 130 females (275–515 mm) of Amblyraja doellojuradoi, a commercial by‐catch species on the Argentinean continental shelf, which are increasingly retained, were analysed. No sexual dimorphism was observed in the LT at which 50% of individuals were sexually mature; males matured at 448 mm and females at 411 mm, c. 80 and 82% of maximum LT. The hepato‐somatic index was similar among sexes, but significantly different between maturity stages, being lower in mature than immature specimens. Males had no seasonal difference in the hepato‐somatic index and females had the lowest index in autumn. The gonado‐somatic index was lower in males than in females and significantly higher in mature than immature specimens of both sexes. Males had the highest index in autumn and females had no seasonal difference. Collectively, these results would indicate that A. doellojuradoi breeds in autumn.