bluuebunny/crossref_metadata_2025 huggingface dataset:
Cholesterol trials and mortality
Authors: Warren John B. , Dimmitt Simon B. , Stampfer Hans G.
Published: April 2016

An overview of clinical trials can reveal a class effect on mortality that is not apparent from individual trials. Most large trials of lipid pharmacotherapy are not powered to detect differences in mortality and instead assess efficacy with composite cardiovascular endpoints. We illustrate the importance of all‐cause mortality data by comparing survival in three different sets of the larger controlled lipid trials that underpin meta‐analyses. These trials are for fibrates and statins. Fibrate treatment in five of the six main trials was associated with a decrease in survival, one fibrate trial showed a non‐significant reduction in mortality that can be explained by a different target population. In secondary prevention, statin treatment increased survival in all five of the main trials, absolute mean increase ranged from 0.43% to 3.33%, the median change was 1.75%, which occurred in the largest trial. In primary prevention, statin treatment increased survival in six of the seven main trials, absolute mean change in survival ranged from −0.09% to 0.89%, median 0.49%. Composite safety endpoints are rare in these trials. The failure to address composite safety endpoints in most lipid trials precludes a balanced summary of risk–benefit when a composite has been used for efficacy. Class effects on survival provide informative summaries of the risk–benefit of lipid pharmacotherapy. We consider that the presentation of key mortality/survival data adds to existing meta‐analyses to aid personal treatment decisions.
A phase 1, open‐label, dose‐escalation study of pralatrexate in combination with bortezomib in patients with relapsed/refractory multiple myeloma
Authors: Dunn Tamara J. , Dinner Shira , Price Elizabeth , Coutré Steven E. , Gotlib Jason , Hao Ying , Berube Caroline , Medeiros Bruno C. , Liedtke Michaela
Published: April 2016

Pralatrexate inhibits folic acid metabolism, and preclinical studies have shown that it is cytotoxic to multiple myeloma cells. This phase 1 study investigated the safety and efficacy of pralatrexate in combination with bortezomib in adults with relapsed or refractory multiple myeloma. A standard 3 + 3 design was used. Patients received intravenous pralatrexate at doses ranging from 10 to 30 mg/m2 and intravenous bortezomib at a dose of 1·3 mg/m2 on days 1, 8 and 15 of each 4‐week cycle. Eleven patients were enrolled and completed a median of two cycles. The maximum tolerated dose was 20 mg/m2. Two patients experienced dose‐limiting toxicity of mucositis. The most frequent non‐haematological toxicities were fatigue (55%) and mucositis (45%). There were three serious adverse events in three patients: rash, sepsis and hypotension. One patient (9%) had a very good partial response, 1 (9%) had a partial response, 1 (9%) had minimal response and two (18%) had progressive disease. The median duration of response was 4 months, the median time to next treatment was 3·4 months and the median time to progression was 4 months. Pralatrexate, in combination with bortezomib, was generally safe and demonstrated modest activity in relapsed or refractory multiple myeloma. Clinicaltrials.gov identifier: NCT01114282.
Refining the phenotypical and mutational spectrum of Taybi‐Linder syndrome
Authors: Putoux A. , Alqahtani A. , Pinson L. , Paulussen A.D.C. , Michel J. , Besson A. , Mazoyer S. , Borg I. , Nampoothiri S. , Vasiljevic A. , Uwineza A. , Boggio D. , Champion F. , de Die‐Smulders C.E. , Gardeitchik T. , van Putten W.K. , Perez M.J. , Musizzano Y. , Razavi F. , Drunat S. , Verloes A. , Hennekam R. , Guibaud L. , Alix E. , Sanlaville D. , Lesca G. , Edery P.
Published: April 2016

Taybi‐Linder syndrome (TALS, OMIM 210710) is a rare autosomal recessive disorder belonging to the group of microcephalic osteodysplastic primordial dwarfisms (MOPD). This syndrome is characterized by short stature, skeletal anomalies, severe microcephaly with brain malformations and facial dysmorphism, and is caused by mutations in RNU4ATAC. RNU4ATAC is transcribed into a non‐coding small nuclear RNA which is a critical component of the minor spliceosome. We report here four foetuses and four unrelated patients with RNU4ATAC mutations. We provide antenatal descriptions of this rare syndrome including unusual features found in two twin foetuses with compound heterozygosity for two rare mutations who presented with mild intrauterine growth retardation and atypical dysmorphic facial features. We also carried out a literature review of the patients described up to now with RNU4ATAC mutations, affected either with TALS or Roifman syndrome, a recently described allelic disorder.
Protein phosphatase 4 plays dual roles during cell proliferation
Authors: Huang Xiuqing , Liu Jin , Shen Tao , Meng Xiangyu , Dou Lin , Lin Yajun , Li Jian
Published: April 2016

Objectives

Protein phosphatase 4 (PP4) has been reported to be indispensable for cell proliferation and survival. Deletion of PP4 has been shown to induce abnormal and even lethal events in growth and development both in lower eukaryotes and in mammals. However, until now, effects of PP4 up‐regulation have remained unclear.

Materials and methods

To test effects of PP4 on cell proliferation, cell cycle and morphology in HepG2 cells, it was down‐regulated using PP4 siRNA or its activity was inhibited using PP4RL (a PP4 phosphatase‐dead mutant) adenoviruses. Alternatively, PP4 was up‐regulated using PP4 adenoviruses. Next, we used a functional proteomic approach to identify proteins that may interact with PP4. Furthermore, we performed rescue experiments to verify the possible mechanisms.

Results

To our surprise, we found that both up‐regulation and inhibition of PP4 inhibited cell proliferation. Unlike PP4 inhibition, PP4 up‐regulation induced prominent arrest at the prometaphase/metaphase transition by causing defects in chromosome alignment and spindle assembly. Moreover, we identified scaffold attachment factor A (SAF‐A) (an important protein required for kinetochore‐microtubule attachment that participates in the prometaphase/metaphase transition), to be a novel protein that interacts with PP4, using a proteomic approach. Thus, mutual regulatory mechanisms exist between PP4 and SAF‐A. Interactions between PP4 and SAF‐A played a role in prometaphase/metaphase transition.

Conclusions

Our data demonstrate a novel regulatory mechanism involving PP4 in cell proliferation.
Speech discrimination in 11‐month‐old bilingual and monolingual infants: a magnetoencephalography study
Authors: Ferjan Ramírez Naja , Ramírez Rey R. , Clarke Maggie , Taulu Samu , Kuhl Patricia K.
Published: April 2016

Language experience shapes infants' abilities to process speech sounds, with universal phonetic discrimination abilities narrowing in the second half of the first year. Brain measures reveal a corresponding change in neural discrimination as the infant brain becomes selectively sensitive to its native language(s). Whether and how bilingual experience alters the transition to native language specific phonetic discrimination is important both theoretically and from a practical standpoint. Using whole head magnetoencephalography (MEG), we examined brain responses to Spanish and English syllables in Spanish‐English bilingual and English monolingual 11‐month‐old infants. Monolingual infants showed sensitivity to English, while bilingual infants were sensitive to both languages. Neural responses indicate that the dual sensitivity of the bilingual brain is achieved by a slower transition from acoustic to phonetic sound analysis, an adaptive and advantageous response to increased variability in language input. Bilingual neural responses extend into the prefrontal and orbitofrontal cortex, which may be related to their previously described bilingual advantage in executive function skills. A video abstract of this article can be viewed at:https://youtu.be/TAYhj‐gekqw
Modelling the cost‐effectiveness of adopting risk‐stratified approaches to extended screening intervals in the national diabetic retinopathy screening programme in Scotland
Authors: Scotland G. , McKeigue P. , Philip S. , Leese G. P. , Olson J. A. , Looker H. C. , Colhoun H. M. , Javanbakht M.
Published: April 2016

Aims

To assess the cost‐effectiveness of adopting risk‐stratified approaches to extended screening intervals in the national diabetic retinopathy screening programme in Scotland.

Methods

A continuous‐time hidden Markov model was fitted to national longitudinal screening data to derive transition probabilities between observed non‐referable and referable retinopathy states. These were incorporated in a decision model simulating progression, costs and visual acuity outcomes for a synthetic cohort with a covariate distribution matching that of the Scottish diabetic screening population. The cost‐effectiveness of adopting extended (2–year) screening for groups with no observed retinopathy was then assessed over a 30–year time horizon.

Results

Individuals with a current grade of no retinopathy on two consecutive screening episodes face the lowest risk of progressing to referable disease. For the cohort as a whole, the incremental cost per quality‐adjusted life year gained for annual vs. biennial screening ranged from approximately £74 000 (for those with no retinopathy and a prior observed grade of mild or observable background retinopathy) to approximately £232 000 per quality‐adjusted life year gained (for those with no retinopathy on two consecutive screening episodes). The corresponding incremental cost‐effectiveness ratios in the subgroup with Type 1 diabetes were substantially lower; approximately £22 000 to £85 000 per quality‐adjusted life year gained, respectively.

Conclusions

Biennial screening for individuals with diabetes who have no retinopathy is likely to deliver significant savings for a very small increase in the risk of adverse visual acuity and quality of life outcomes. There is greater uncertainty regarding the long‐term cost‐effectiveness of adopting biennial screening in younger people with Type 1 diabetes.
Survey of student attitudes towards digital simulation technologies at a dental school in China
Authors: Ren Q. , Wang Y. , Zheng Q. , Ye L. , Zhou X. D. , Zhang L. L.
Published: April 2016

Introduction

Digital simulation technologies have become widespread in healthcare education, especially in dentistry; these technologies include digital X‐ray images, digital microscopes, virtual pathology slides and other types of simulation. This study aimed to assess students’ attitudes towards digital simulation technologies at a large, top‐ranked dental school in China, as well as find out how students compare the digital technologies with traditional training methods.

Methods

In April 2015, a custom‐designed questionnaire was distributed to a total of 389 students who had received digital technology and simulation‐based training in West China Dental School during 2012–2014.

Results

Results of a cross‐sectional survey show that most students accept digital simulation technology; they report that the technology is stimulating and facilitates self‐directed and self‐paced learning.

Conclusion

These findings, together with the objective advantages of digital technology, suggest that digital simulation training offers significant potential for dental education, highlighting the need for further research and more widespread implementation.
Integration of ultrasound imaging into pre‐clinical dental education
Authors: Kondrashova T. , De Wan D. , Briones M. U. , Kondrashov P.
Published: April 2016

Introduction

Patients have complex healthcare needs and typically require more than one healthcare discipline to address issues regarding their health. Interprofessional teams of healthcare professionals may be able to address these complex needs and improve patient outcomes by combining resources. To evaluate the feasibility of integrating ultrasound into a dental school curriculum to teach anatomy as part of an interprofessional education experience, the current study surveyed first‐year dental students to determine their perceptions of the integration of ultrasound techniques into the curriculum.

Materials and Methods

Ultrasound laboratory exercises were developed for first‐year dental students as part of their anatomy course. The exercises were focused on head, neck and abdominal anatomy. To assess student perception of the integration of ultrasound into the dental curriculum, a survey was created specifically for the current study.

Results

Between 2013 and 2015, two classes of first‐year dental students participated in the ultrasound laboratory exercise and completed the survey (n = 83). Student survey responses suggested ultrasound was a valuable teaching tool because it allowed them to visualise anatomical structures using live imaging. They also agreed that the ultrasound laboratory exercises were an efficient learning tool, but the majority did not believe that they would use ultrasound regularly in their future practice.

Conclusions

Results of the current study suggested first‐year dental students were satisfied with the integration of ultrasound techniques into the dental curriculum. Survey results indicated that the students enjoyed the ultrasound laboratory exercise and felt ultrasound was an effective learning tool.
Do tropical rain forest soils have greater nematode diversity than High Arctic tundra? A metagenetic comparison of Malaysia and Svalbard
Authors: Kerfahi Dorsaf , Tripathi Binu M. , Porazinska Dorota L. , Park Jungok , Go Rusea , Adams Jonathan M.
Published: April 2016

Aim

Latitudinal differences in diversity have long fascinated ecologists. It is unclear whether small soil animals such as nematodes show latitudinal differences in diversity. Based on hypotheses concerning the basis for greater tropical diversity, and by analogy with other groups, we predicted (1) greater alpha diversity in the equatorial tropics than the High Arctic, (2) greater beta and gamma diversity in the tropics. We also predicted (3) no species overlap between the tropics and the High Arctic, and (4) lower abundance of root feeding and insect parasitic nematodes in the high Arctic.

Location

We sampled at three sites in equatorial rain forest in Malaysia at 2° N and three sites in High Arctic tundra in Svalbard at 79° N.

Methods

In Malaysia and Svalbard, three sets of 1‐m2 samples were taken, in interrupted grids. Nematodes were extracted using a Baermann funnel. Bulk DNA was amplified by polymerase chain reaction for the 18S rRNA gene, followed by 454‐pyrosequencing.

Results

Comparing operational taxonomic unit (OTU)‐based nematode communities (99% sequence similarity), averaged alpha diversity per 1‐m2 quadrat showed no difference between Malaysia and Svalbard. However, the classic beta diversity and gamma diversity of nematodes was higher for Malaysia.

Main conclusions

There was, surprisingly, no difference in the alpha diversity of nematodes between Malaysia and Svalbard. However, for beta and gamma diversity, diversity was higher in Malaysia. There was also considerable OTU overlap between the two regions, suggesting that very broad climatic niches are common in nematode ecology. Plant root feeders and insect parasites were relatively more common in Svalbard. Overall, we found a mixed and complex picture in terms of agreement with what would be predicted on the basis of ecological theory and observations on other groups. While further confirmatory studies would be beneficial, there is a need to incorporate these new findings in the formulation of hypotheses and tests for the underlying causes of latitudinal trends.
Effects of silymarin on biochemical and oxidative stress markers in end‐stage renal disease patients undergoing peritoneal dialysis
Authors: Firuzi Omidreza , Khajehrezaei Soraya , Ezzatzadegan Shahrokh , Nejati Maryam , Jahanshahi Keramat‐Allah , Roozbeh Jamshid
Published: April 2016

IntroductionEnd‐stage renal disease (ESRD) patients especially those undergoing dialysis are vulnerable to several complications, in particular those related to oxidative stress. Silymarin is an herbal medicine commonly used as an antioxidant in different pathologies.

MethodsTo evaluate the effect of silymarin on biochemical and oxidative stress markers, 50 ESRD patients undergoing peritoneal dialysis were randomly divided into two groups of silymarin (n = 28) and control (n = 22) and received silymarin (140 mg every 8 hours) or placebo for 2 months, respectively. Ferric reducing antioxidant power and total 8‐iso‐prostaglandin F2αwere measured in plasma, while catalase enzyme activity was measured in erythrocytes of both groups before and after treatment.

FindingsFerric reducing antioxidant power values after treatment were significantly decreased in silymarin group compared to before treatment values (17.2 ± 2.9 and 15.9 ± 3.1 µM equivalent of quercetin/dL, respectively, P < 0.05). Conversely, catalase levels were increased 17.3% after silymarin consumption, while it was decreased 9.1% in control group. Further, hemoglobin (from 10.94 ± 2.17 to 11.54 ± 2.03 g/dL, P < 0.05) and albumin levels (from 3.48 ± 0.67 to 3.61 ± 0.53 g/dL, P < 0.05) were significantly increased after silymarin administration.

DiscussionIt is concluded that silymarin could be regarded as a supplementary therapy for ESRD patients undergoing peritoneal dialysis in order to reduce complications.
Meal replacements as a strategy for weight loss in obese hemodialysis patients
Authors: Lassemillante Annie‐Claude M. , Oliver Veronica , Hickman Ingrid , Murray Eryn , Campbell Katrina L.
Published: April 2016

Introduction There is currently limited evidence on the use or safety of meal replacements as part of a low– or very–low‐calorie diet in patients with renal insufficiency; however, these are occasionally used under dietetic supervision in clinical practice to achieve the desired weight loss for kidney transplant. This case series reports on the safety and efficacy of a weight loss practice utilizing meal replacements among hemodialysis patients, who needed to lose weight for kidney transplant.

Methods Five hemodialysis patients were prescribed a modified low‐calorie diet (950 kcal and 100 g protein per day) comprising three meal replacements (Optifast®), one main meal, and two low‐potassium fruits per day. Dietary requirements and restrictions were met for all participants. Dialysis prescriptions, weight (predialysis and postdialysis), interdialytic weight gain, biochemistry, and medications were monitored during the study period for up to 12 months.

Findings Participants were aged between 46 and 61 years, and the median time on the low‐calorie diet was 364 days. Phosphate binders were temporarily ceased for one participant for reasons unrelated to this program and no other safety concerns were recorded. The low‐calorie diet resulted in energy deficits ranging from 1170 kcal to 2160 kcal, and all participants lost weight (median 7% [range 5.2%–11.4%]). The most dramatic weight change appeared to occur by week 12, and declining adherence led to erratic weight change thereafter.

Discussion This modified low‐calorie diet was safe and effective to use in this population. Meal replacements are a useful weight loss strategy in hemodialysis patients, therefore, offering an alternative to usual weight loss protocols.
The Childhood and Adolescent Migraine Prevention (CHAMP) Study: A Report on Baseline Characteristics of Participants
Authors: Powers Scott W. , Hershey Andrew D. , Coffey Christopher S. , Chamberlin Leigh A. , Ecklund Dixie J.D. , Sullivan Stephanie M. , Klingner Elizabeth A. , Yankey Jon W. , Kashikar‐Zuck Susmita , Korbee Leslie L. , Costigan Michele L. , Riss Holly H. , Porter Linda L.
Published: April 2016

Objective

To describe baseline headache characteristics of children and adolescents participating in a multicenter, randomized, double‐blinded, placebo‐controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo for the prevention of migraine (CHAMP Study).

Methods

Children and adolescents (age 8–17 years old, inclusive) diagnosed with migraine with or without aura, having headaches at least four times per month were enrolled from 2012 through 2014. The trial involved a baseline period (minimum of 28 days) during which prospective diaries were completed and demographics and headache features obtained.

Results

A total of 488 children and adolescents (mean age 14.0 ± 2.4 years) agreed to participate in the trial, with 361 randomized and 127 not randomized. Randomized subjects had a 5.5 ± 3.1 year history of headaches, with 15.1 ± 7.1 headache days per month (based upon retrospective report at screening visit). Prospective diaries reported 11.5 ± 6.1 headache days per 28 day baseline. Across this 28 day period, reported headache days per week were stable (about 3 headache days per week). Recording of individual headache features by diary (n = 4136 headache days) showed characteristics consistent with migraine (mean duration 10.5 ± 8.1 hours, mean severity 6.0 ± 2.1, 60% throbbing, 55% with activity worsening headaches, 55% with photophobia, and 47% with phonophobia).

Conclusions

Baseline data from the CHAMP Study suggested that the randomized sample was representative of the real world population of children and adolescents that present for treatment of migraine. Headaches in children and adolescents recorded during a 28 day prospective baseline period in this multi‐site comparative effectiveness study did not change over the course of the baseline period, even though a clear diagnosis, recommendation for effective acute treatment, and standardized education about healthy habits occurred prior to the diary collection period.
Headache Education in Adult Neurology Residency: A Survey of Program Directors and Chief Residents
Authors: Ahmed Zubair A. , Faulkner Larry R.
Published: April 2016

Objective

This cross‐sectional study reassesses the status of headache didactics and clinical training in adult neurology residency programs in the United States to determine if program directors and chief residents feel that current training in headache is adequate.

Background

Headache is among the most common new complaints to both the neurology and primary care clinic and represents a significant economic burden. However, headache remains both under‐diagnosed and under‐treated. Of those who seek treatment only 28% report they are very satisfied with their management. One possible cause for dissatisfaction is inadequate education of treating physicians. Two studies in 2002 and 2005 that collectively surveyed all 125 adult neurology residency programs concluded that more evidence was needed to evaluate the adequacy of headache education in these programs. A survey of neurology residency department chairs and program directors in 2005 also evaluated the status of headache education in adult neurology training programs and concluded the same.

Methods

We surveyed 133 neurology residency program directors and 213 chief residents. Program directors and chief residents were asked about the amount of headache didactics, amount of clinical exposure to headache, perceived adequacy of current training and if plans existed to increase headache education through didactics or clinical exposure.

Results

Seventy‐two program directors (54%) and 117 chief residents (55%) responded. Twenty‐six percent of programs reported a mandatory headache clinic. Of these, 35% of programs reported <2 weeks of clinic, 54% of programs reported 2‐4 weeks, and 12% of programs reported > 4 weeks of clinic. Fifty‐one percent of program directors felt more than 4 weeks of clinical exposure to headache was needed to adequately prepare neurology residents. Ninety‐six percent of program directors surveyed believed their residents were adequately prepared to diagnose and treat headache disorders. Twenty‐one percent had plans to increase didactic time and 26% planned to incorporate more clinical exposure.

Conclusions

Despite a modest increase in headache didactics in neurology residency programs over the last decade, many program directors and chief residents report that their programs do not include what they believe to be adequate educational experiences in headache. Although the overwhelming majority of neurology residency programs reported that residents were adequately prepared to diagnose and treat headache disorders, about a fourth of programs still felt the need to increase the amount of didactic and clinical exposure dedicated toward the management of headache disorders.
The Evidence for Prescription Information for Possible Use of a Repeated Dose of Oral Triptans: A Comment
Authors: Tfelt‐Hansen Peer , Jespersen Stine F.
Published: April 2016

A repeated dose of an oral triptan has been shown in randomized controlled trials (RCTs) to be ineffective as a treatment for no or partial response 2 hours after initial dosing but effective as treatment for headache recurrence. In the official prescription information in the United States, the United Kingdom, and Denmark repeated dosing of all seven oral triptans are recommended for headache recurrence but some triptans are also recommended for no or partial response, a use of a triptan deemed to be not beneficial in European and Canadian migraine guidelines. In summary, not all recommendations are based on evidence from RCTs. In addition, some recommendations are ambiguous and patients need clearer instructions. An example of such a clear British instruction in a patient leaflet instruction is presented at the end of the paper.
Microwave‐assisted extraction in goji berries: effect on composition and bioactivity, evaluated through conventional and nonconventional methodologies
Authors: Carvalho Ana P. , Mendes Marta , Moreira Manuela M. , Cruz Diana , Magalhães Júlia M. C. S. , Barroso M. Fátima , Ramalhosa M. J. , Duarte Abel , Guido Luís , Gomes Ana M. , Matos Cristina Delerue
Published: April 2016

This study aimed to evaluate the effect of microwave‐assisted extraction (MAE) parameters on the composition and bioactivity of goji (Lycium barbarum) extracts. Extracts were obtained under a central composite design combination of experimental conditions, and characterised through HPLC‐DAD; their bioactive capacity was ascertained for antimicrobial and antioxidant capacity, the later by spectrophotometric [2,2‐azinobis (3‐ ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt‐radical scavenging activity assay – 413–748 mg ascorbic acid equivalents/100 g DW and oxygen radical absorbance capacity – 1901–2292 mg trolox equivalents/100 g DW] and electrochemical (DNA‐based sensor – 3571–6602 mg ascorbic acid/100 g DW) methods. The quantitative profile of phenolic compounds was strongly dependent on MAE conditions. Significant correlations were found between the presence of several flavonoids and solvent composition, as well as between phenolic acids with methoxy group and the response to DNA‐based sensor. Results may improve targeted extractions for specific compounds, leading to the achievement of extracts richer in antioxidant capacity, as well as in the tailoring of the biosensor response sensitivity to the composition of the extracts under analysis.
The Challenge of Integration: A Review of the M&A Integration Literature
Authors: Steigenberger Norbert
Published: April 2016

The integration of acquired or merging firms is a key driver of the success or failure of mergers and acquisitions (M&As). Over the last 30 years, a substantial body of research has addressed M&A integration, offering rich but widely dispersed insights into this phenomenon. This paper takes stock of the current knowledge, based on a review of articles published in scholarly journals. The review advances the conceptual understanding of the phenomenon by inductively developing an overarching framework for the M&A integration literature, where integration success is a function of context, structural and communication‐based interventions, which interact with collective sensemaking processes and negotiations among integration stakeholders. Based on this framework, a research agenda is suggested. I proposes that, in particular, the interaction between structural interventions and leadership warrants further study. Also, little is known about integration project management and integration team composition or the interaction between integration context and collective sensemaking processes. Finally, there is a shortage of research on temporal dynamics within integration projects. The review demonstrates that M&A scholars made substantial progress regarding our understanding of the M&A integration process, yet much remains to be done.
Quality of warfarin control in atrial fibrillation patients in South East Queensland, Australia
Authors: Bernaitis N. , Badrick T. , Davey A. K. , Anoopkumar‐Dukie S.
Published: April 2016

Background

Warfarin is widely prescribed to decrease the risk of stroke in atrial fibrillation (AF) patients. Due to patient variability in response, regular monitoring is required, and time in therapeutic range (TTR) used to indicate quality of warfarin control with a TTR>60% is recommended. Recently, an Australian Government review of anticoagulants identified the need to establish current warfarin control and determine the potential place of the newer oral anticoagulants.

Aim

To determine warfarin control by a pathology practice in Queensland, Australia and identify factors influencing TTR.

Methods

Retrospective data were collected from Sullivan Nicolaides Pathology, a major pathology practice offering a warfarin care programme in Australia. Patients enrolled in their programme as of September 2014 were included in the study. TTR was calculated using INR test results, and test dates using the Rosendaal method with mean patient TTR were used for analysis and comparison. Exclusions were target therapeutic range outside 2.0–3.0, less than two INR tests and programme treatment time of less than 30 days.

Results

The eligible 3692 AF patients had 73.6% of INR tests within the therapeutic range. The mean TTR was 81%, with 97% of patients above a TTR of 60%. TTR was not significantly influenced by age, gender or socioeconomic factors.

Conclusions

The observed mean TTR of over 80% is superior to the minimum recommended threshold of 60%. The TTR achieved by the Queensland pathology practice demonstrates that dedicated warfarin programmes can produce high‐quality warfarin care, ensuring the full benefit of warfarin for Australian patients.
Adoption of direct oral anticoagulants for stroke prevention in atrial fibrillation
Authors: Baker D. , Wilsmore B. , Narasimhan S.
Published: April 2016

Background

Direct oral anticoagulants (DOAC) are being increasingly utilised for stroke prevention in atrial fibrillation (AF) and atrial flutter.

Aims

To analyse the adoption and application of these drugs in a regional hospital inpatient cohort and compare with national prescribing data.

Methods

Digital medical records identified prescribed anticoagulants for patients admitted with AF and atrial flutter during 2013–2014. Analysis of patient demographics and stroke risk identified trends in prescribing DOAC versus warfarin. For broader comparison, data from the Pharmaceuticals Benefits Scheme were sourced to determine the nation‐wide adoption of DOAC.

Result

Of the 615 patients identified, 505 (255 in 2013, 250 in 2014) had sufficient records to include in the study. From 2013 to 2014, DOAC prescriptions increased from 9 to 28% (P < 0.001), warfarin and aspirin remained comparatively stable (38–34%, 22–20%), and those prescribed no medication declined (17–8%, P < 0.001). DOAC were prescribed to patients with lower CHA2DS2VASc scores than warfarin (3.6 vs 4.4; P = 0.005), lower HAS‐BLED scores (1.7 vs 2.3; P < 0.01), higher glomerular filtration rates; 70 vs 63 ml/min; P = 0.002) and younger age (74 vs 77 years; P = 0.006). Nationally, warfarin prescriptions are higher in total numbers but increasing at a slower rate than DOAC, which increased 10‐fold (101 158 in 2013, 1 095 985 in 2014).

Conclusion

DOAC prescribing grew rapidly from 2013 to 2014, regionally and nationally. Warfarin prescriptions have remained stable, indicating that more patients are being appropriately anticoagulated for AF who previously were not. DOAC were found to be prescribed to patients with lower CHA2DS2VASc and HAS‐BLED scores, younger age and higher glomerular filtration rates. Aspirin therapy remains over utilised in AF.
A Comparative Analysis of Real and Accrual Earnings Management around Initial Public Offerings under Different Regulatory Environments
Authors: Alhadab M. , Clacher I. , Keasey K.
Published: April 2016

While earnings management around IPOs has been researched in a number of settings, there has been a relative absence of work that analyses the impact of the regulatory environment on such activities. We find that the regulatory environment does impact the real and accrual earnings management activities of IPO firms. Our results show that IPO firms listing on the lightly regulated UK Alternative Investment Market (AIM) have higher (lower) levels of accrual‐based and sales‐based (discretionary expenses‐based) earnings management around the IPO than firms listing on the more heavily regulated Main market in the UK.
CFD Simulation of Airflow and Heat Transfer During Forced‐Air Precooling of Apples
Authors: Han Jia‐wei , BadÍa‐melis R. , Yang Xin‐ting , Ruiz‐garcia L. , Qian Jian‐ping , Zhao Chun‐jiang
Published: April 2016

In this work, we study how different air‐inflow velocities affect the apple‐temperature distribution during forced‐convection cooling of individual apples by simultaneously modeling airflow and heat transfer. In general, an increase in airflow velocity increases the cooling rate and heat transfer fluxes across the apple surface and decreases cooling time. The results show that a reasonable increase in cooling rate is obtained with an increase in airflow velocity to 2.5 m/s; any further increase in airflow velocity simply wastes energy because it leads to a relatively low increase in cooling and heat transfer fluxes across the apple surface. By comparing the temperature simulated with and without accounting for respiratory heat, the maximum temperature difference is ∼0.033 K during cooling. Therefore, respiratory heat has a negligible effect on the temperature variations of fruit. The model was verified by comparing its results with those of experiments. The predicted results are consistent with the measured results.

Practical Applications

To ensure the quality and safety of horticultural products and extend their storage and shelf life across the entire cold chain, a critical step in the postharvest cold chain is the rapid precooling after harvest to remove field heat. In this work, we investigate how to improve the cooling rate and minimize the cooling time during forced‐convection cooling of apples. In addition, the effect of respiratory heat on temperature variations of fruit is also studied. This research provides not only a more detailed understanding of flow distribution and temperature variations of fruit during cooling, but also a reliable theoretical basis for minimizing unnecessary energy consumption during forced‐convection cooling of produce.
Connecting global‐ and local‐scale flood risk assessment: a case study of the Rhine River basin flood hazard
Authors: Gusyev M. , Gädeke A. , Cullmann J. , Magome J. , Sugiura A. , Sawano H. , Takeuchi K.
Published: April 2016

This flood hazard study is the first step towards linking global and local scales of flood risk assessment under the International Flood Initiative (IFI) Flagship Project. To simulate river discharges, we utilised a 600‐arcsec grid block‐wise TOP (BTOP) model to represent the global scale and constructed a local scale 15‐arcsec grid BTOP model for the Rhine River basin. Both BTOP models showed similar statistical performances with observed daily river flows, especially for the 1993 and 1995 floods. For both scales, we calculated flood peak discharges using the Gumbel distribution with L‐moments in R from the simulated BTOP daily discharges. The obtained flood peak discharges of both scales were comparable with available gauging station records. For the flood inundation simulation, the 600‐arcsec flood peaks were disaggregated to the 15‐arcsec scale as input to the Flood Inundation Model (FID), and the resulting 15‐arcsec FID maps of 10‐, 100‐ and 200‐year return periods had similar extents with the existing official flood hazard maps of high, medium and low probability floods, respectively. These preliminary results demonstrate the possibility of obtaining an acceptable flood hazard assessment on a global scale and serve as a starting point for connecting global and local scales of flood risk assessment.
Microbial Quality and Histamine Producing Microflora Analysis of the Ice Used for Fish Preservation
Authors: Economou Vangelis , Gousia Panagiota , Kemenetzi Despoina , Sakkas Hercules , Papadopoulou Chrissanthy
Published: April 2016

The aim of the present study was the estimation of the microbiological quality of ice used for fish preservation. Samples of flake ice, produced either from potable or seawater were collected monthly during a 12 month period and were examined for total heterotrophic count (THC) at 37°C and 5°C, total and fecal coliforms, enterococci, Pseudomonas spp., staphylococci, fungi, Vibrio spp., and histamine producing bacteria (HPB). THC at 37°C was higher than the IPIA limit in 15% of the samples (9/60). In 91.67% of the samples (55/60) at least one fecal coliform colony was counted, with three of them (5%) exhibiting counts larger than 100 CFU/100g. All samples tested positive for enterococci, with 6 samples (10%) exhibiting counts greater than 100 CFU/100g. From the 282 isolates characterized as HPB, 24.10% were Pseudomonas spp. (n = 67), 20.86% belonged to Enterobacteriaceae (n = 58) and 19.42% were Staphylococcus spp. (n = 54). Therefore, the ice used for fish preservation can be a potential source of microbial contamination, particularly of HPB; ice production from safe potable water should be practiced in order to safeguard public health.

Practical Applications

Ice is used extensively for fish preservation, providing an easy and cost effective way to control temperature of stored fish. Ice is a possible vehicle of pathogens contaminating the fish. The present research provides insight in the potential microbial contamination of fish by ice. Factors such as the nature of the water (potable water, seawater) used for ice production and the ice production process (small scale production at the retail store, production in an ice facility) were examined. Also, the involvement of ice as source of histamine producing bacteria was assessed based on the isolation, identification and enumeration of histamine producing bacteria in the examined ice samples. Therefore the results of this study provide useful data that can be applied to minimize the microbial burden of fish due to contaminated ice, to lengthen fish storage life and to avoid pathogen transmission to the consumers.
Development and Application of the Quality Index Method (QIM) for Farmed Tambaqui (Colossoma macropomum) Stored Under Refrigeration
Authors: Araújo Wanessa Shuelen Costa , De Lima Consuelo Lúcia Sousa , Peixoto Joele Maria Regina S. , Lourenço Lúcia De Fátima Henriques
Published: April 2016

This research aimed to assess the freshness of farmed tambaqui (Colossoma macropomum) eviscerated and stored in ice for 30 days. The changes observed in the fish over storage were monitored through sensory evaluation Quality Index Method (QIM), pH, total volatile basic nitrogen (TVB‐N), thiobarbituric acid reactive substances (TBARS), and microbiological analyses (coagulase‐positive staphylococcus, Salmonella spp., coliforms at 45C, and mesophilic and psychrotrophic bacteria counts). The Quality Index (QI) showed a linear increase, ranging from 0 (maximum freshness) to 34 (total loss of freshness), with a strong correlation (R2 = 0.988) with storage time. The microbiological analyses showed that the psychrotrophic bacteria count went over the recommended limit after the 26th day. TVB‐N ranged from 4.01 to 15.92 mg/100 g; pH, from 6.01 to 6.57; and TBARS, from 0.01 to 0.14 mg MDA/kg between the 1st and 30th days of storage. The sensory, physicochemical, and microbiological analyses established that eviscerated tambaqui stored in ice is appropriate for consumption up until the 22nd day.

Practical Applications

The QIM takes into account the diversity among species and defines the sensory quality parameters for fish freshness. Sensory analysis has been shown to be an important tool to assess sensory quality of fresh fish and is largely used by sanitary inspection agencies. The QIM established that eviscerated tambaqui (C. macropomum) stored in ice at 0C remained proper for consumption until the 22nd day. The results of the application of QIM to marketed fish species can establish the product's shelf life which is a very important for the industry and for consumers. QIM: Development and Application of a Sensory Protocol for Farmed Tambaqui (C. macropomum).
Statin use and the risk of colorectal adenoma: A meta‐analysis
Authors: Jung Yoon Suk , Park Chan Hyuk , Eun Chang Soo , Park Dong Il , Han Dong Soo
Published: April 2016

Background

Although statin use has been reported to reduce the risk of colorectal cancer beyond its cholesterol‐lowering effects, the benefit of statins against colorectal adenoma has not been fully clarified. We aimed to investigate the association between statin use and the risk of colorectal adenoma.

Methods

We conducted a systematic literature search on MEDLINE, EMBASE, and the Cochrane Library using the primary keywords “adenoma,” “polyp,” “colorectal,” “colon,” “rectal,” “rectum,” “neoplasia,” “neoplasm,” “statin,” “3‐hydroxy‐3‐methylglutaryl‐coenzyme A,” and “HMG‐CoA.” Studies were included if they evaluated the association between statin use and adenoma and reported relative risks (RRs) or odds ratios or provided data for estimation. Pooled estimates were calculated using the random‐effects model.

Results

Six studies including 13 239 patients were analyzed. The median proportion of patients with any adenoma was 29.7% (range, 20.9–38.4%) in patients taking statins and 31.2% (range, 19.6–63.4%) in patients not taking statins across included studies. The median proportion of patients with advanced adenoma in those taking statins was 7.7% (range, 3.1–27.2%), whereas that in patients not taking statins was 11.3% (range, 3.5–32.4%). On meta‐analysis, statin use did not significantly affect the risk of any adenoma (pooled RR = 0.901; 95% confidence interval [CI], 0.735–1.104); however, it was associated with a lower risk of advanced adenoma (pooled RR = 0.833; 95% CI, 0.750–0.925).

Conclusions

Statin use seems to be associated with a reduced risk of advanced adenoma, but not any adenoma. Statins may prevent neoplastic progression of adenomas rather than the development of adenomas.
Asian consensus statements on endoscopic management of walled‐off necrosis. Part 2: Endoscopic management
Authors: Isayama Hiroyuki , Nakai Yousuke , Rerknimitr Rungsun , Khor Christopher , Lau James , Wang Hsiu‐Po , Seo Dong Wan , Ratanachu‐ek Thawee , Lakhtakia Sundeep , Ang Tiing Leong , Ryozawa Shomei , Hayashi Tsuyoshi , Kawakami Hiroshi , Yamamoto Natusyo , Iwashita Takuji , Itokawa Fumihide , Kuwatani Masaki , Kitano Masayuki , Hanada Keiji , Kogure Hirofumi , Hamada Tsuyoshi , Ponnudurai Ryan , Moon Jong Ho , Itoi Takao , Yasuda Ichiro , Irisawa Atsushi , Maetani Iruru
Published: April 2016

Walled‐off necrosis (WON) is a new term for encapsulated necrotic tissue after severe acute pancreatitis. Various terminologies such as pseudocyst, necroma, pancreatic abscess, and infected necrosis were previously used in the literature, resulting in confusion. The current and past terminologies must be reconciled to meaningfully interpret past data. Recently, endoscopic necrosectomy was introduced as a treatment option and is now preferred over surgical necrosectomy when the expertise is available. However, high‐quality evidence is still lacking, and there is no standard management strategy for WON. The consensus meeting aimed to clarify the diagnostic criteria for WON and the role of endoscopic interventions in its management. In the Consensus Conference, 27 experts from eight Asian countries took an active role and examined key clinical aspects of WON diagnosis and endoscopic management. Statements were crafted based on literature review and expert opinion, employing the modified Delphi method. All statements were substantiated by the level of evidence and the strength of the recommendation. We created 27 consensus statements for WON diagnosis and management, including details of endoscopic procedures. When there was not enough solid evidence to support the statements, this was clearly acknowledged to facilitate future research. Proposed management strategies were formulated and are illustrated using flow charts. These recommendations, which are based on the best current scientific evidence and expert opinion, will be useful for guiding endoscopic management of WON. Part 2 of this statement focused on the endoscopic management of WON.
Tracking Water Footprints at the Micro and Meso Scale: An Application to Spanish Tourism by Regions and Municipalities
Authors: Cazcarro Ignacio , Duarte Rosa , Sánchez Chóliz Julio
Published: April 2016

Making the link between the different economic scales—local, regional, and global—and the impacts associated with more global behavior is a natural extension of traditional environmentally extended input‐output (I‐O) modeling. In this article, we highlight the capabilities of combining the meso level (i.e., regional) I‐O models with geographical information systems (GIS) and micro data to lower the spatial scale. This methodology lets us provide information to municipalities (what we call the micro scale) on their water footprints (WFs) at a lower spatial level than that of Spanish regions (what we call meso scale), at which economic I‐O data are available. Based on a multiregional I‐O model for the Spanish regions, we analyze the local water impacts of tourism activity in Spain. We focus on the explicit spatial identification of areas of strong final demand (normally the most populated) tracking back the associated footprints to the original hotspots or vulnerable areas (micro scale), where most water withdrawal had taken place. The spatial divergence between the production and the consumption responsibilities arise because consumers and producers usually have very different characteristics, particularly with respect to tourism. We find highest geographic dispersion of WFs of consumption arising from domestic tourism, followed by domestic household consumption, and finally foreign tourism WF. Foreign tourism WF is more concentrated in time and space. Foreign tourism in Andalusia requires directly and indirectly (WF) 617 cubic hectometers (hm3) and in Madrid 440 hm3, indicating that such tourism in both regions accounts for some of the highest water intensities per euro (€) spent by a foreign tourist, around 0.1 cubic meters/€.