bluuebunny/crossref_metadata_2025 huggingface dataset:
The Coalition and the Decline of Majoritarianism in the UK
Authors: Gay Oonagh , Schleiter Petra , Belu Valerie
Published: April 2015

The United Kingdom has traditionally featured many aspects of the majoritarian model of democracy: its first‐past‐the‐post electoral system tends towards producing single‐party majorities, while its legislative decision rules concentrate policy‐making power in the hands of the resulting single‐party governments. However, in an unprecedented break with the UK's postwar conventions, the Conservatives and Liberal Democrats formed a coalition following the general election of 2010. In this article, we examine some of the Coalition's impacts on governing and constitutional conventions, placing them in a comparative European context. We conclude that the Coalition reflects a shift towards the less majoritarian forms of politics prevalent in continental Europe, and that some of these changes are likely to persist even after the end of the current government.
Secondary Behavioural Incentives: Bonus Points and Rugby Professionals
Authors: Lenten Liam J. A. , Winchester Niven
Published: April 2015

We examine the impact of secondary incentives by evaluating agent behaviour in a professional sport that rewards multiple outcomes. Our analysis focuses on the Super Rugby competition, which awards four points for a win and bonus points for scoring four or more tries and/or losing by seven or fewer points. Using binary response models, we find that significantly more tries are scored by teams late in matches when they can earn the try bonus point with one more try, but only when the match result itself is already likely decided. This result offers important evidence on multitasking by professionals.
Near‐infrared spectroscopy (NIRS) predicts non‐structural carbohydrate concentrations in different tissue types of a broad range of tree species
Authors: Ramirez Jorge A. , Posada Juan M. , Handa I. Tanya , Hoch Günter , Vohland Michael , Messier Christian , Reu Björn
Published: April 2015

The allocation of non‐structural carbohydrates (NSCs) to reserves constitutes an important physiological mechanism associated with tree growth and survival. However, procedures for measuring NSC in plant tissue are expensive and time‐consuming. Near‐infrared spectroscopy (NIRS) is a high‐throughput technology that has the potential to infer the concentration of organic constituents for a large number of samples in a rapid and inexpensive way based on empirical calibrations with chemical analysis.

The main objectives of this study were (i) to develop a general NSC concentration calibration that integrates various forms of variation such as tree species and tissue types and (ii) to identify characteristic spectral regions associated with NSC molecules. In total, 180 samples from different tree organs (root, stem, branch, leaf) belonging to 73 tree species from tropical and temperate biomes were analysed. Statistical relationships between NSC concentration and NIRS spectra were assessed using partial least squares regression (PLSR) and a variable selection procedure (competitive adaptive reweighted sampling, CARS), in order to identify key wavelengths.

Parsimonious and accurate calibration models were obtained for total NSC (r2 of 0·91, RMSE of 1·34% in external validation), followed by starch (r2 = 0·85 and RMSE = 1·20%) and sugars (r2 = 0·82 and RMSE = 1·10%). Key wavelengths coincided among these models and were mainly located in the 1740–1800, 2100–2300 and 2410–2490 nm spectral regions.

This study demonstrates the ability of general calibration model to infer NSC concentrations across species and tissue types in a rapid and cost‐effective way. The estimation of NSC in plants using NIRS therefore serves as a tool for functional biodiversity research, in particular for the study of the growth–survival trade‐off and its implications in response to changing environmental conditions, including growth limitation and mortality.
Positive end‐expiratory pressure titration at bedside using electrical impedance tomography in post‐operative cardiac surgery patients
Authors: Karsten J. , Grusnick C. , Paarmann H. , Heringlake M. , Heinze H.
Published: April 2015

Background

Post‐operative positive end‐expiratory pressure (PEEP) setting to minimize the risk of ventilator‐associated lung injury is still controversial. Assessment of regional ventilation distribution by electrical impedance tomography (EIT) might be superior as compared with global parameters. The aim of this prospective observational study was to compare global dynamic compliance (CRS) with different EIT indices during a short clinical applicable descending PEEP trial.

Methods

Twenty mechanically ventilated patients after elective cardiac surgery received a standard recruitment manoeuvre (RM) following descending PEEP trial in steps of 2 cmH2O from PEEP 14 cmH2O to 6 cmH2O. During baseline and all PEEP steps, CRS was assessed and regional ventilation distribution was measured by means of EIT. The individual ‘best’ PEEP values for the derived EIT indices and CRS were calculated and compared.

Results

The descending PEEP trial lasted less than 10 min. CRS increased after the RM and showed a maximum value at PEEP 8 cmH2O. Ventilation distribution shifted more to dependent lung regions after RM and back to more non‐dependent regions during the PEEP trial. Individual ‘best’ PEEP by CRS showed significantly lower values than ‘best’ PEEP by ventilation distribution measured with EIT indices.

Conclusion

During a short descending PEEP trial at bedside, EIT is capable of following the status of regional ventilation distribution in ventilated patients. The ‘best’ PEEP value identified by individual maximum CRS was lower than optimal PEEP levels as determined by means of EIT indices. EIT could help setting PEEP in post‐operative ventilated patients.
Translation and validation of the Danish version of the postoperative quality of recovery score QoR‐15
Authors: Kleif J. , Edwards H. M. , Sort R. , Vilandt J. , Gögenur I.
Published: April 2015

Background

Patient perceived quality of recovery is an important outcome after surgery and should be measured in clinical trials. Quality of recovery after surgery and general anaesthesia can be measured by the QoR‐15. A high score indicates a good recovery and the score ranges from 0 to 150. The aim of this study was to translate the QoR‐15 questionnaire into Danish and do a full psychometric evaluation of the Danish version.

Methods

A translation and cultural adaption of the original version of the QoR‐15 into a Danish version, the QoR‐15D, was performed. After obtaining consent, patients undergoing elective abdominal, orthopaedic or gynaecological surgery under general anaesthesia were included. Patients completed the QoR‐15D before surgery and on the first postoperative day. The validity, reliability, responsiveness and clinical feasibility of the QoR‐15D were evaluated.

Results

One hundred and forty patients returned their pre‐ and postoperative questionnaire successfully giving a completion rate of 56%. The postoperative QoR‐15 score was negatively correlated with duration of surgery (ρ = −0.21, 95% CI: −0.04 to −0.36, P < 0.02) and postoperative stay (ρ = −0.28, 95% CI: −0.12 to −0.43, P < 0.01). Postoperative QoR‐15D scores were inversely related to the extent of surgery: minor, intermediate or major (127 ± 22, 106 ± 29 and 96 ± 24, respectively, P < 0.01). Cronbach's alpha and split‐half reliability was 0.90 and 0.88. Test–retest reliability was 0.99 (95% CI: 0.94–1.00). Cohen's effect size was 1.13 and the standardized response mean was 0.82.

Conclusion

The QoR‐15D has preserved the validity, excellent reliability, high degree of responsiveness and the clinical feasibility of the original English version.
The rapidly escalating cost of treating colorectal cancer in Australia
Authors: Ananda Sumitra , Kosmider Suzanne , Tran Ben , Field Kathryn , Jones Ian , Skinner Iain , Guerrieri Mario , Chapman Michael , Gibbs Peter
Published: April 2015

Aims

Considerable progress in cancer treatment is leading to better outcomes, but the cost of therapy is placing increasing pressure on the health system. Understanding the real‐world cost of therapies for each stage will become increasingly important in informing treatment selection and health policy.

Methods

To explore the cost of treating colorectal cancer in the modern era, data were entered onto a prospective database at four hospitals. We estimated the impact of bevacizumab by using data from July 2009, and projected the likely impact of the recent listing of cetuximab. The utility of these data for estimating the cost‐effectiveness of treatment was explored.

Results

Cancer stage and age at diagnosis were major determinants of treatment received and the associated cost. The cost of early stage disease has not substantially changed whereas therapies such as oxaliplatin and irinotecan were significant contributors to substantial increases in stage IV disease, now $71 156 per patient. Bevacizumab has added at least $10 247 per patient and we estimate that cetuximab will add a further $12 022. An exploratory analysis of the cost‐effectiveness of oxaliplatin for adjuvant therapy of stage III colon cancer suggests that this is well within the accepted range.

Conclusion

These data suggest that recent progress in the treatment of later stages of colorectal cancer is being achieved at significant financial cost. The increased costs of managing later stages of disease make an investment in prevention and early detection ever more attractive.
Cost of cancer care for patients undergoing chemotherapy: The Elements of Cancer Care study
Authors: Ward Robyn L , Laaksonen Maarit A , van Gool Kees , Pearson Sallie‐Anne , Daniels Ben , Bastick Patricia , Norman Richard , Hou Changhao , Haywood Philip , Haas Marion
Published: April 2015

Aim

To determine the monthly treatment costs for each element of cancer care in patients receiving chemotherapy and to apportion the burden of cost by financing agent (Commonwealth, State government, private health insurer, patient).

Methods

A cohort of 478 patients (54% breast, 33% colorectal and 13% non‐small‐cell lung cancer) were recruited from 12 centers representing metropolitan and regional settings in public and private sectors. Primary data were linked to secondary data held in New South Wales state (Admitted Patients and Emergency Department Data) and Commonwealth (Medicare and Pharmaceutical Benefits) databases. The monthly treatment costs of each element of care and the funding agent were calculated from secondary health data.

Results

Across all tumor types, the mean monthly treatment cost was $4162 (10%–90% quantiles $1018–$8098; range $2853 [adjuvant colorectal] to $5622 [metastatic lung]), with 54% of this cost borne by Commonwealth government, 26% by private health insurers, 14% by State government and 6% by patients. The mean monthly costs of treating metastatic disease were $1415 greater than those for adjuvant therapy. The mean monthly costs were contributed to by inpatient care ($1657, 40%), chemotherapy prescriptions ($1502, 36%), outpatient care ($452, 11%) and administration of chemotherapy ($364, 9%).

Conclusion

All four funders have a shared incentive to reduce absolute monthly treatment costs since their proportional contribution is relatively constant for most tumor types and stages. There are opportunities to reduce cancer care costs by minimizing the risk of inpatient hospital admissions that arise from chemotherapy administration and by recognizing incentives for cost‐shifting.
Amelioration of allergic airway inflammation in mice by regulatory IL‐35 through dampening inflammatory dendritic cells
Authors: Dong J. , Wong C. K. , Cai Z. , Jiao D. , Chu M. , Lam C. W. K.
Published: April 2015

Background

IL‐35, a new member of the IL‐12 family, is an inhibitory cytokine produced by regulatory T and B lymphocytes that play a suppressive role in the inflammatory diseases.

This study focuses on the cellular mechanism regulating the anti‐inflammatory activity of IL‐35 in asthmatic mice.

Methods

Ovalbumin‐induced asthmatic and humanized asthmatic mice were adopted to evaluate the in vivo anti‐inflammatory activities of IL‐35. For monitoring the airway, Penh value (% baseline) was measured using a whole‐body plethysmograph.

Results

In this study using ovalbumin‐induced asthmatic mice, we observed that intraperitoneal injection of IL‐35 during the allergen sensitization stage was more efficient than administration in the challenge stage for the amelioration of airway hyper‐responsiveness. This was reflected by the significantly reduced concentration of asthma‐related Th2 cytokines IL‐5 and IL‐13, as well as eosinophil counts in bronchoalveolar lavage fluid (all P < 0.05). IL‐35 also significantly attenuated the accumulation of migratory CD11b+CD103− dendritic cells (DC) in the mediastinal lymph node (mLN) and lung of mice (all P < 0.05). IL‐35 markedly inhibited the ovalbumin‐induced conversion of recruited monocytes into inflammatory DC, which were then substantially reduced in mLN to cause less T‐cell proliferation (all P < 0.05). Further study using the humanized asthmatic murine model also indicated human IL‐35 exhibited a regulatory impact on allergic asthma.

Conclusion

Our findings suggest that IL‐35 can act as a crucial regulatory cytokine to inhibit the development of allergic airway inflammation via suppressing the formation of inflammatory DC at the inflammatory site and their accumulation in the draining lymph nodes.
Hysterectomies in Finland in 1990–2012: comparison of outcomes between trainees and specialists
Authors: Jokinen Ewa , Brummer Tea , Jalkanen Jyrki , Fraser Jaana , Heikkinen Anna‐Mari , Mäkinen Juha , Sjöberg Jari , Tomàs Eija , Mikkola Tomi S. , Härkki Päivi
Published: April 2015

Objective

To assess trends for hysterectomy methods in the Nordic countries and to compare outcomes of hysterectomies in Finland done by trainees with those done by specialists.

Design

Register‐based study.

Setting

NOMESCO database for the Nordic countries and the Finnish Hospital Discharge Register.

Population

National prospective cohort of 5279 hysterectomies in Finland.

Methods

Numbers of hysterectomies in the Nordic countries were collected in 1995–2011 and in Finland in 1990–2012. The Finhyst study to collect data on hysterectomies for benign indications was carried out in Finland in 2006. Information concerning patients, surgeons, and hysterectomy outcome was analysed.

Main outcome measures

Hysterectomy numbers and methods. Operating time, blood loss, and complications in hysterectomies done by trainees and specialists.

Results

In Finland, the rate of hysterectomies has been reduced by approximately 50% since the 1990s and is now similar to that in the other Nordic countries. The laparoscopic method is twice as common in Finland as in other Nordic countries, constituting 35–40% of all hysterectomies. The operating time for all hysterectomy methods was 16–25% longer among trainees than specialists. For the abdominal or laparoscopic methods there were no significant differences in the complication rates between the groups. In the vaginal approach, blood loss of ≥1000 mL was slightly more common in operations done by trainees (1.3% vs. 2.6%, p = 0.037).

Conclusions

Laparoscopic hysterectomy is more common in Finland than in the other Nordic countries. Although trainees need more time to operate, there were no differences between the trainees and the specialists with regard to major complication rates.
Identification of human papillomavirus in pterygium
Authors: Hamed‐Azzam Shirin , Edison Natalia , Briscoe Daniel , Mukari Abed , Elmalah Irit
Published: April 2015

Purpose

The purpose of this study was to evaluate the involvement of human papillomavirus in the pathogenesis of primary and recurrent pterygium in northern Israel.

Methods

A retrospective study examined 100 randomly chosen pterygium specimens with solar elastosis, from 100 patients who underwent pterygium surgery during 2012–2013 at the Emek Medical Center. All the specimens were analysed for evidence of human papillomavirus infection by immunohistochemistry.

Results

Human papillomavirus was not detected in any of the 100 pterygia samples by immunohistochemistry. These used samples were taken from 100 patients with mean age of 51.5 years and a primary: recurrent ratio of 8.09:1.

Conclusion

We conclude from our study that human papillomavirus infection does not appear to be an important pathogenic factor of pterygium in Israel.
Healthy term and moderately preterm infants have similar cerebral oxygen saturation and cerebral blood flow volumes during early post‐natal transition
Authors: Demel A , Feilke K , Schöning M , Wolf M , Poets CF , Franz AR
Published: April 2015

Aim

This pilot study evaluated changes in regional cerebral oxygen saturation and cerebral blood flow volume during the transitional period in healthy term and moderately preterm infants.

Methods

The cohort comprised 16 preterm infants and seven full‐term infants with mean gestational ages of 34 and 39 weeks, respectively. Longitudinal measurements were conducted during the first three days after birth. Regional cerebral oxygen saturation was determined bilaterally by frequency domain near‐infrared spectroscopy. Flow volumes were determined in internal carotid and vertebral arteries by multiplying the time‐averaged velocity by the cross‐sectional area: cerebral blood flow volume was calculated as the sum of flow volumes and adjusted for brain weight.

Results

Brain weight‐adjusted cerebral blood flow volumes and regional cerebral oxygen saturation were similar in preterm and term infants. Regional cerebral oxygen saturation did not correlate with brain weight‐adjusted cerebral blood flow volume. Right and left brain weight‐adjusted internal carotid flow volumes did not correlate with right and left regional cerebral oxygen saturation.

Conclusion

Our findings suggest that during the first three days after birth there was adequate cardiorespiratory adaptation, cerebral perfusion and adequate compensation through the arterial circle of Willis in both healthy term and moderately preterm infants.
Systematic review with network meta‐analysis: comparative efficacy and safety of budesonide and mesalazine (mesalamine) for Crohn's disease
Authors: Moja L. , Danese S. , Fiorino G. , Del Giovane C. , Bonovas S.
Published: April 2015

Background

Budesonide and mesalazine (mesalamine) are commonly used in the medical management of patients with mild to moderate Crohn's disease.

Aim

To assess their comparative efficacy and harm using the methodology of network meta‐analysis.

Methods

A comprehensive search of Medline, Embase, the Cochrane Library and ClinicalTrials.gov, through October 2014, was performed to identify randomised controlled trials (RCTs) that recruited adult patients with active or quiescent Crohn's disease, and compared budesonide or mesalazine with placebo, or against each other, or different dosing strategies of one drug.

Results

Twenty‐five RCTs were combined using Bayesian network meta‐analysis. Budesonide 9 mg/day, or at higher doses (15 or 18 mg/day), was shown superior to placebo for induction of remission [odds ratio (OR), 2.93; 95% credible interval (CrI), 1.52–5.39, and OR, 3.28; CrI, 1.46–7.55 respectively] and ranks at the top of the hierarchy of the competing treatments. For maintenance of remission, budesonide 6 mg/day demonstrated superiority over placebo (OR, 1.69; CrI, 1.05–2.75), being also at the best ranking position among all compared treatment strategies. No other comparisons (i.e. different doses of mesalazine vs. placebo or budesonide, for induction or maintenance of remission) reached significance. The occurrence of withdrawals due to adverse events was not shown different between budesonide, mesalazine and placebo, in both the induction and maintenance phases.

Conclusions

Budesonide, at the doses of 9 mg/day, or higher, for induction of remission in active mild or moderate Crohn's disease, and at 6 mg/day for maintenance of remission, appears to be the best treatment choice.
Diabetes and the risk of infections with immunomodulator therapy in inflammatory bowel diseases
Authors: Ananthakrishnan A. N. , Cagan A. , Cai T. , Gainer V. S. , Shaw S. Y. , Churchill S. , Karlson E. W. , Murphy S. N. , Kohane I. , Liao K. P.
Published: April 2015

Background

Infections are an important concern in patients using immunosuppressive therapy for their inflammatory bowel disease (IBD). Diabetes affects nearly 10% of Americans. Whether it confers an additional risk with immunosuppression in IBD has not been examined previously.

Aim

To examine the association between diabetes and infections with immunomodulator use in IBD

Methods

Using a validated, multi‐institutional IBD cohort, we identified all patients who received at least one prescription for immunomodulators (thiopurines, methotrexate). Our primary outcome was infection within 1 year of the prescription of the immunomodulator. Multivariable logistic regression adjusting for relevant confounders was used to estimate the independent association with diabetes.

Results

Our study included 2766 patients receiving at least one prescription for immunomodulators among whom 210 (8%) developed an infection within 1 year. Patients who developed an infection were likely to be older, have more comorbidities, more likely to have received a prescription for steroids but similar in initiation of anti‐TNF therapy within that year. Only 8% of those without an infection had diabetes compared to 19% of those who developed an infection within 1 year [odds ratio (OR) 2.74, 95% confidence interval (CI) 1.88–3.98, P < 0.001]. On multivariate analysis, diabetes was independently associated with a nearly two‐fold increase in risk of infections (OR: 1.80, 95% CI: 1.20–2.68). There was no increase in risk of infections with addition of anti‐TNF therapy (OR: 1.14, 95% CI: 0.80–1.63).

Conclusion

Diabetes is an independent risk factor for infection in IBD patients using immunomodulator therapy.
Systematic review with meta‐analysis: post‐infectious irritable bowel syndrome after travellers' diarrhoea
Authors: Schwille‐Kiuntke J. , Mazurak N. , Enck P.
Published: April 2015

Background

Gastrointestinal infection is known as a risk factor for the development of the irritable bowel syndrome (post‐infectious irritable bowel syndrome, PI‐IBS). The incidence of PI‐IBS ranges between 3% and over 30% of people after infectious gastroenteritis.

Aim

To perform a meta‐analysis pools and report data concerning the relative risk (RR) of PI‐IBS after TD.

Methods

Database search using Medline through PubMed, Scopus, EBM Reviews (Cochrane Database of Systematic Reviews) and PsycINFO was performed to identify relevant studies. Those that met the inclusion criteria were pooled. A random effects model (Mantel‐Haenszel) was performed.

Results

Six eligible studies were found. In three of six studies, the authors reported a statistically significant association of TD and PI‐IBS. The pooled RR was 3.35 (95% CI: 2.22–5.05) with a significant overall effect (P < 0.00001). Overall PI‐IBS incidence was 5.4% in TD subjects and 1.4% in healthy subjects. There was no significant heterogeneity within the pooled studies (I2 = 5%). Self‐reported TD alone resulted in an over 1.5‐fold RR for PI‐IBS compared to laboratory‐confirmed TD [RR 3.90 (95% CI: 2.35–6.49) vs. RR 2.42 (95% CI: 1.22–4.78)].

Conclusions

There is a strong association between travellers' diarrhoea and post‐infectious irritable bowel syndrome. Self‐reports of exposure seem to result in a higher post‐infectious irritable bowel syndrome occurrence than laboratory‐confirmed cases of travellers' diarrhoea, but further studies are needed to confirm this finding. Finally, potential influences of the selection of an appropriate study population on post‐infectious irritable bowel syndrome epidemiology are discussed.
Quantifying the influence of sill intrusion on the thermal evolution of organic‐rich sedimentary rocks in nonvolcanic passive margins: an example from ODP 210‐1276, offshore Newfoundland, Canada
Authors: Peace Alexander , McCaffrey Ken , Imber Jonathan , Hobbs Richard , van Hunen Jeroen , Gerdes Keith
Published: April 2015

Intrusive magmatism is an integral and understudied component in both volcanic and nonvolcanic passive margins. Here, we investigate the thermal effects of widespread (ca. 20 000 km2) intrusive magmatism on the thermal evolution of organic‐rich sedimentary rocks on the nonvolcanic Newfoundland passive margin. ODP 210‐1276 (45.41°N, 44.79°W) intersects two sills: an older, upper sill and a younger, lower sill that are believed to correspond to the high amplitude ‘U‐reflector’ observed across the Newfoundland Basin. A compilation of previous work collectively provides; (1) emplacement depth constraints, (2) vitrinite reflectance data and (3) 40Ar/39Ar dates. Collectively, these data sets provide a unique opportunity to model the conductive cooling of the sills and how they affect thermal maturity of the sedimentary sequence. A finite differences method was used to model the cooling of the sills, with the model outputs then being entered into the EASY%Ro vitrinite reflectance model. The modelled maturation profile for ODP 210‐1276 shows a significant but localized effect on sediment maturity as a result of the intrusions. Our results suggest that even on nonvolcanic margins, intrusive magmatism can significantly influence the thermal evolution in the vicinity of igneous intrusions. In addition, the presence of widespread sills on nonvolcanic passive margins such as offshore Newfoundland may be indicative of regional‐scale thermal perturbations that should be considered in source rock maturation studies.
Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS‐PC Study
Authors: Yamaue Hiroki , Tsunoda Takuya , Tani Masaji , Miyazawa Motoki , Yamao Kenji , Mizuno Nobumasa , Okusaka Takuji , Ueno Hideki , Boku Narikazu , Fukutomi Akira , Ishii Hiroshi , Ohkawa Shinichi , Furukawa Masayuki , Maguchi Hiroyuki , Ikeda Masafumi , Togashi Yosuke , Nishio Kazuto , Ohashi Yasuo
Published: April 2015

Gemcitabine is a key drug for the treatment of pancreatic cancer; however, with its limitation in clinical benefits, the development of another potent therapeutic is necessary. Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis, and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide (elpamotide). Based on the promising results of this phase I trial, a multicenter, randomized, placebo‐controlled, double‐blind phase II/III clinical trial has been carried out for pancreatic cancer. The eligibility criteria included locally advanced or metastatic pancreatic cancer. Patients were assigned to either the Active group (elpamotide + gemcitabine) or Placebo group (placebo + gemcitabine) in a 2:1 ratio by the dynamic allocation method. The primary endpoint was overall survival. The Harrington–Fleming test was applied to the statistical analysis in this study to evaluate the time‐lagged effect of immunotherapy appropriately. A total of 153 patients (Active group, n = 100; Placebo group, n = 53) were included in the analysis. No statistically significant differences were found between the two groups in the prolongation of overall survival (Harrington–Fleming P‐value, 0.918; log–rank P‐value, 0.897; hazard ratio, 0.87, 95% confidence interval [CI], 0.486–1.557). Median survival time was 8.36 months (95% CI, 7.46–10.18) for the Active group and 8.54 months (95% CI, 7.33–10.84) for the Placebo group. The toxicity observed in both groups was manageable. Combination therapy of elpamotide with gemcitabine was well tolerated. Despite the lack of benefit in overall survival, subgroup analysis suggested that the patients who experienced severe injection site reaction, such as ulceration and erosion, might have better survival.
Preferences for return of incidental findings from genome sequencing among women diagnosed with breast cancer at a young age
Authors: Kaphingst K.A. , Ivanovich J. , Biesecker B.B. , Dresser R. , Seo J. , Dressler L.G. , Goodfellow P.J. , Goodman M.S.
Published: April 2015

While experts have made recommendations, information is needed regarding what genome sequencing results patients would want returned. We investigated what results women diagnosed with breast cancer at a young age would want returned and why. We conducted 60 semi‐structured, in‐person individual interviews with women diagnosed with breast cancer at age 40 or younger. We examined interest in six types of incidental findings and reasons for interest or disinterest in each type. Two coders independently coded interview transcripts; analysis was conducted using NVivo 10. Most participants were at least somewhat interested in all six result types, but strongest interest was in actionable results (i.e. variants affecting risk of a preventable or treatable disease and treatment response). Reasons for interest varied between different result types. Some participants were not interested or ambivalent about results not seen as currently actionable. Participants wanted to be able to choose what results are returned. Participants distinguished between types of individual genome sequencing results, with different reasons for wanting different types of information. The findings suggest that a focus on actionable results can be a common ground for all stakeholders in developing a policy for returning individual genome sequencing results.
Ex Ante Welfare Analysis of Technological Change: The Case of Nitrogen Efficient Maize for African Soils
Authors: Kostandini Genti , La Rovere Roberto , Guo Zhe
Published: April 2015

This study evaluates the potential impacts of the Improved Maize for African Soils (IMAS) project in two countries of Africa: Kenya and South Africa. The IMAS varieties offer significant yield advantages for regions where low or no fertilizer is used. The analysis uses spatial production data and household data to account for the level of fertilizer use in different agroecological zones of the country as well as different types of maize producing households. Results suggest that IMAS will deliver a total of US$586 million in gross benefits with US$136 million and US$100 million of benefits to producers in Kenya and South Africa, respectively, and an additional US$112 million to consumers in Kenya and US$238 million to consumers in South Africa. These benefits could help more than 1 million people escape poverty in the two countries by 2025. Household level results suggest that small households in areas with relatively low levels of fertilizer use stand to gain significant benefits.
A systematic review on the correlation between skeletal and jawbone mineral density in osteoporotic subjects
Authors: Calciolari Elena , Donos Nikolaos , Park Jung‐Chul , Petrie Aviva , Mardas Nikos
Published: April 2015

Objectives

The aim of this systematic review was to assess whether the systemic skeletal reduction of bone mineral density (BMD) that characterizes osteoporotic subjects is also associated with a reduction of BMD in the jawbones.

Material and methods

Two reviewers searched independently and in duplicate three databases up to May 2014 and assessed the risk of bias using a tailored version of the Newcastle–Ottawa scale (NOS). Only papers reporting either Pearson's correlation coefficient or Spearman's rank correlation coefficient between skeletal and jawbone mineral density in more than five osteoporotic subjects were selected.

Results

From 1763 citations, 64 full‐text papers were screened and five papers that met the inclusion criteria were included in the final analysis. None of the included studies complied with all NOS criteria, and as only two studies were eligible for meta‐analysis, this was not performed.

Conclusions

Only limited conclusions can be drawn from this systematic review, due to the small number of studies included, their heterogeneity, and their high risk of bias. Future studies that take into consideration both upper and lower jaws, that use the same technique to measure skeletal and jaw BMD (ideally dual‐energy X‐ray absorptiometry, DXA), and that account for confounding variables (such as medications/diseases affecting bone metabolism and demographics) are needed to provide more robust conclusions.
Patient‐centered outcomes comparing digital and conventional implant impression procedures: a randomized crossover trial
Authors: Joda Tim , Brägger Urs
Published: April 2015

Objectives

The aim of this randomized controlled trial was to compare patient‐centered outcomes during digital and conventional implant impressions.

Material and methods

In a crossover study design, intraoral scanning (IOS) [test] as well as classical polyether impressions [control] were both performed on 20 patients for single‐tooth replacement with implant‐supported crowns. The sequential distribution of either starting with the test or the control procedure was randomly selected. Patients' perception and satisfaction on the level of convenience‐related factors were assessed with visual analogue scale (VAS) questionnaires. In addition, clinical work time was separately recorded for test and control procedures. Statistical analyses were performed with Wilcoxon signed‐rank tests and corrected for multiple testing by the method of Holm.

Results

On VAS ranging from 0 to 100, patients scored a mean convenience level of 78.6 (SD ± 14.0) in favor of IOS compared to conventional impressions with 53.6 (SD ± 15.4) [P = 0.0001]. All included patients would prefer the digital workflow if in the future they could choose between the two techniques. Secondary, IOS was significantly faster with 14.8 min (SD ± 2.2) compared to the conventional approach with 17.9 min (SD ± 1.1) [P = 0.0001].

Conclusion

Based on the findings of this investigation, both impression protocols worked successfully for all study participants capturing the 3D implant positions. However, the digital technique emerges as the most preferred one according to patient‐centered outcomes and was more time‐effective compared to conventional impressions.
Age‐Related Changes in Resting‐State Networks of A Large Sample Size of Healthy Elderly
Authors: Huang Chun‐Chao , Hsieh Wen‐Jin , Lee Pei‐Lin , Peng Li‐Ning , Liu Li‐Kuo , Lee Wei‐Ju , Huang Jon‐Kway , Chen Liang‐Kung , Lin Ching‐Po
Published: April 2015

Aims

Population aging is burdening the society globally, and the evaluation of functional networks is the key toward understanding cognitive changes in normal aging. However, the effect of age on default mode subnetworks has not been documented well, and age‐related changes in many resting‐state networks remain debatable. The purpose of this study was to propose more precise results for these issues using a large sample size.

Methods

We used group‐level meta‐ICA analysis and dual regression approach for identifying resting‐state networks from functional magnetic resonance imaging data of 430 healthy elderly participants. Partial correlation was used to observe age‐related correlations within and between resting‐state networks.

Results

In the default mode network, only the ventral subnetwork negatively correlated with age. Age‐related decrease in functional connectivity was also noted in the auditory, right frontoparietal, sensorimotor, and visual medial networks. Further, some age‐related increases and decreases were observed for between‐network correlations.

Conclusion

The results of this study suggest that only the ventral default mode subnetwork had age‐related decline in functional connectivity and several reverse patterns of resting‐state networks for network development. Understanding age‐related network changes may provide solutions for the impact of population aging and diagnosis of neurodegenerative diseases.
Cross‐Situational Learning of Minimal Word Pairs
Authors: Escudero Paola , Mulak Karen E. , Vlach Haley A.
Published: April 2015

Cross‐situational statistical learning of words involves tracking co‐occurrences of auditory words and objects across time to infer word‐referent mappings. Previous research has demonstrated that learners can infer referents across sets of very phonologically distinct words (e.g., WUG, DAX), but it remains unknown whether learners can encode fine phonological differences during cross‐situational statistical learning. This study examined learners’ cross‐situational statistical learning of minimal pairs that differed on one consonant segment (e.g., BON–TON), minimal pairs that differed on one vowel segment (e.g., DEET–DIT), and non‐minimal pairs that differed on two or three segments (e.g., BON–DEET). Learners performed above chance for all pairs, but performed worse on vowel minimal pairs than on consonant minimal pairs or non‐minimal pairs. These findings demonstrate that learners can encode fine phonetic detail while tracking word‐referent co‐occurrence probabilities, but they suggest that phonological encoding may be weaker for vowels than for consonants.
TGF‐β signalling prevents pancreatic beta cell death after proliferation
Authors: Lei Chen , Zhou Xiaoling , Pang Yi , Mao Yuanyuan , Lu Xixuan , Li Meijuan , Zhang Jie
Published: April 2015

Objectives

Maintenance of functional beta cell mass is critical for prevention of diabetes. The transforming growth factor‐beta (TGF‐β) receptor signalling pathway plays an essential role in pancreatic development. However, its involvement in control of post‐natal beta cell growth has only been recently reported.

Materials and methods

Here, we studied the role of TGF‐β receptor signalling in beta cell proliferation after 50% partial pancreatectomy (PPx), using beta cell‐specific TGF‐β receptor II (TBR2)‐mutated mice.

Results

Consistent with previous reports, we found that inhibition of TGF‐β receptor signalling in beta cells resulted in slightly higher beta cell mass 1 week after PPx, due to greater beta cell proliferation. However, beta cell mass in these beta cell‐specific TBR2‐mutated mice significantly decreased by 12 weeks after PPx, resulting from increase in beta cell apoptosis.

Conclusions

Our data thus suggest that TGF‐β receptor signalling may be required for prevention of beta cell death after proliferation, and highlight this pathway as an essential regulator during post‐natal beta cell homoeostasis.
Icariin induces osteogenic differentiation of bone mesenchymal stem cells in a MAPK‐dependent manner
Authors: Wu Yuqiong , Xia Lunguo , Zhou Yuning , Xu Yuanjin , Jiang Xinquan
Published: April 2015

Objectives

Icariin, a flavonoid isolated from Epimedium pubescens, has previously been identified to exert beneficial effects on preventing bone loss and promoting bone regeneration. However, molecular mechanisms for its anabolic action have, up to now, remained largely unknown.

Materials and methods

Effects of icariin on cell proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) were systematically evaluated. To characterize underlying mechanisms, its effects on mitogen‐activated protein kinase (MAPK) signalling pathways were determined.

Results

Results showed that icariin might not have enhanced effects on cell proliferation. However, it seemed to significantly enhance osteogenic differentiation of BMSCs, demonstrated by increasing alkaline phosphatase (ALP) activity and gene expression of collagen type I (Col I), osteocalcin (OCN) and osteopotin (OPN). It was demonstrated that icariin rapidly phosphorylated extracellular signal‐regulated kinase (ERK), p38 kinase and c‐Jun N terminal kinase (JNK). Furthermore, icariin‐stimulated osteogenic effects on BMSCs were dramatically attenuated by treatment with either specific ERK inhibitor of PD98059, p38 inhibitor of SB202190 or JNK inhibitor SP600125.

Conclusions

These results provide a potential mechanism of anabolic activity of icariin on BMSCs involving ERK, p38 and JNK MAPK pathways.
Perceived barriers to utilise methadone maintenance therapy among male injection drug users in rural areas of southern Thailand
Authors: Khampang Roongnapa , Assanangkornchai Sawitri , Teerawattananon Yot
Published: April 2015

Introduction and Aims

Methadone maintenance therapy (MMT) has been proven to be effective and cost‐effective in treating dependence on opioids. However, concerns remain that geographical, financial and other hidden barriers may hinder access to MMT, especially in rural areas where health services are limited. The objective of this study was to determine factors associated with utilisation of MMT by injection drug users (IDUs) living in Songkhla province.

Design and Methods

A cross‐sectional study among 159 IDUs in Songkhla province of southern Thailand was conducted. Participants were recruited using a snowball technique. Data were collected from July 2013 to January 2014 via face‐to‐face interviews.

Results

Around one‐forth (24.5%) of participants had difficulties travelling to MMT clinics because of the long distance, long travelling time and lack of a private vehicle. Twenty‐four percent faced difficulties with the clinic's opening hours and 28% faced difficulties paying for the cost of travel. IDUs who utilised the MMT perceived risks of injection drug use differently compared with those who did not. Younger or Muslim IDUs were less likely to attend MMT. IDUs who perceived that MMT was effective were more likely to utilise MMT.

Discussion and Conclusions

Physical accessibility, affordability and acceptability play an essential role in MMT utilisation. Developing alternatives that reduce the travelling time, costs for IDUs and more convenient operation hours to suit their lifestyles may increase the utilisation of MMT. Intensive consultation before starting MMT is highly recommended. [Khampang R, Assanangkornchai S, Teerawattananon Y. Perceived barriers to utilise methadone maintenance therapy among male injection drug users in rural areas of southern Thailand. Drug Alcohol Rev 2015;34:645–53]
Roles of Hippo signaling pathway in size control of organ regeneration
Authors: Hayashi Shinichi , Yokoyama Hitoshi , Tamura Koji
Published: April 2015

Animals have an intrinsic regeneration ability for injured tissues and organs. Species that have high regeneration ability such as newts can regenerate an organ with exactly the same size and shape as those of the original one. It has been unclear how a regenerating organ grows and ceases growth at an appropriate size. Organ size control in regeneration is seen in various organs of various species that have high regeneration ability. In animal species that do not have sufficient regeneration ability, a wound heals (the injury is closed, but lost parts are not regenerated), but an organ cannot be restored to its original size. On the other hand, perturbation of regeneration sometimes results in oversized or extra structures. In this sense, organ size control plays essential roles in proper regeneration. In this article, we introduce the concept of size control in organ regeneration regulated by the Hippo signaling pathway. We focused on the transcriptional regulator Yap, which shuttles between the nuclei and cytoplasm to exert a regulatory function in a context‐dependent manner. The Yap‐mediated Hippo pathway is thought to sense cell density, extracellular matrix (ECM) contact and cell position and to regulate gene expression for control of organ size. This mechanism can reasonably explain size control of organ regeneration.
Toxicity profile and treatment delays in NOPHO ALL2008—comparing adults and children with Philadelphia chromosome‐negative acute lymphoblastic leukemia
Authors: Toft Nina , Birgens Henrik , Abrahamsson Jonas , Griškevičius Laimonas , Hallböök Helene , Heyman Mats , Klausen Tobias Wirenfeldt , Jónsson Ólafur Gísli , Palk Katrin , Pruunsild Kaie , Quist‐Paulsen Petter , Vaitkeviciene Goda , Vettenranta Kim , Asberg Ann , Helt Louise Rold , Frandsen Thomas , Schmiegelow Kjeld
Published: April 2015

Objectives

Cure rates improve when adolescents and young adults with acute lymphoblastic leukemia (ALL) are treated according to pediatric protocols. Assumed risks of toxicities and associated delays in treatment have played a role in setting upper age limits. The aim of this study was to examine the toxicity profile and treatment delays in NOPHO ALL2008 comparing children and adults.

Methods

We collected information on 19 treatment‐related toxicities, systematically captured at 3‐month intervals throughout therapy, and time intervals between 12 consecutive treatment phases for 1076 patients aged 1–45 yrs treated according to the Nordic/Baltic ALL2008 protocol.

Results

No adults died during induction. The duration of induction therapy and postinduction treatment phases did not differ between children and adults, except for patients 18–45 yrs being significantly delayed during two of nine high‐risk blocks (median number of days for patients 1–9, 10–17, and 18–45 yrs; the glucocorticosteroid/antimetabolite‐based block B1: 24, 26, and 29 d, respectively, P = 0.001, and Block 5 (in most cases also a B block): 29, 29, and 37 d, respectively, P = 0.02). A higher incidence of thrombosis with increasing age was found; highest odds ratio 5.4 (95% CI: (2.6;11.0)) for patients 15–17 yrs compared with children 1–9 yrs (P < 0.0001). Risk of avascular osteonecrosis was related to age with the highest OR for patients 10–14 yrs (OR = 10.4 (95% CI: (4.4;24.9)), P < 0.0001).

Conclusion

Adults followed and tolerated the NOPHO ALL2008 protocol virtually as well as children, although thrombosis and avascular osteonecrosis was most common among adolescents.
Mean reticulocyte volume: a specific parameter to screen for hereditary spherocytosis
Authors: Xu Yuchan , Yang Wang , Liao Lin , Deng Zengfu , Qiu Yuling , Chen Wenqiang , Lin Faquan
Published: April 2015

This study assessed the value of mean reticulocyte volume (MRV) for differential diagnosis of hereditary spherocytosis (HS) so as to develop conventional and new specific screen indexes. Subjects in this study were divided into three groups: 53 cases in HS group, 217 cases in hemolytic anemia control group (109 cases of thalassemia (THAL), 56 cases of glucose‐6‐phosphate dehydrogenase G6PD deficiency anemia, and 52 cases of autoimmune hemolytic anemia (AIHA)), and 100 cases in healthy control group. We analyzed erythrocyte and reticulocyte parameters including MRV, mean sphered corpuscular volume, mean corpuscular hemoglobin concentration, and immature reticulocyte fraction. Results demonstrated that MRV was significantly lower in the HS group but significantly higher in the AIHA and G6PD deficiency anemia groups than that in the healthy control group (P = 0.000). MRV was not significantly different between the AIHA and G6PD deficiency anemia groups (P = 0.977) and between the healthy control and THAL groups (P = 0.168). The area under the ROC curve of MRV for diagnosis of HS was 0.942, with a standard error of 0.019, 95% confidence interval of 0.905–0.979, and optimal critical diagnosis point of 95.77 fL. When the MRV was ≤95.77 fL, the sensitivity and specificity for diagnosis of HS were 86.80% and 91.20%, respectively. Therefore, MRV is a general and specific new index for screening HS and important for differential diagnosis of different types of hemolytic anemia.