bluuebunny/crossref_metadata_2025 huggingface dataset:
The Determinants of the Technical Efficiency of Acute Inpatient Care in Canada
Authors: Wang Li , Grignon Michel , Perry Sheril , Chen Xi‐Kuan , Ytsma Alison , Allin Sara , Gapanenko Katerina
Published: April 2018

Objective

To evaluate the technical efficiency of acute inpatient care at the pan‐Canadian level and to explore the factors associated with inefficiency—why hospitals are not on their production frontier.

Data Sources/Study Setting

Canadian Management Information System (MIS) database (CMDB) and Discharge Abstract Database (DAD) for the fiscal year of 2012–2013.

Study Design

We use a nonparametric approach (data envelopment analysis) applied to three peer groups (teaching, large, and medium hospitals, focusing on their acute inpatient care only). The double bootstrap procedure (Simar and Wilson 2007) is adopted in the regression.

Data Collection/Extraction Methods

Information on inpatient episodes of care (number and quality of outcomes) was extracted from the DAD. The cost of the inpatient care was extracted from the CMDB.

Principal Findings

On average, acute hospitals in Canada are operating at about 75 percent efficiency, and this could thus potentially increase their level of outcomes (quantity and quality) by addressing inefficiencies. In some cases, such as for teaching hospitals, the factors significantly correlated with efficiency scores were not related to management but to the social composition of the caseload. In contrast, for large and medium nonteaching hospitals, efficiency related more to the ability to discharge patients to postacute care facilities. The efficiency of medium hospitals is also positively related to treating more clinically noncomplex patients.

Conclusions

The main drivers of efficiency of acute inpatient care vary by hospital peer groups. Thus, the results provide different policy and managerial implications for teaching, large, and medium hospitals to achieve efficiency gains.
Review article: A scoping review of physiotherapists in the adult emergency department
Authors: Ferreira Giovanni E , Traeger Adrian C , Maher Chris G
Published: April 2018

To provide an overview of the literature that considers physiotherapists working in the ED in relation to their roles, training levels, patient profile, safety, effectiveness, efficiency, cost‐effectiveness and the provision of low‐value care. We performed a scoping review of the literature. Four databases (PubMed, EMBASE, CINAHL and Cochrane CENTRAL) were searched from their inception to December 2016 and we updated searches on PubMed in September 2017. Two reviewers independently screened studies for eligibility. We performed a narrative synthesis of quantitative data. We included 27 studies: five randomised controlled trials (n = 1434), 12 prospective observational studies (n = 153 767), six retrospective studies (n = 9968), two survey studies (n = 61), one case report (n = 3) and one qualitative study (n = 11). Physiotherapists primarily managed patients with low urgency musculoskeletal conditions. Physiotherapists appeared to have similar clinical effectiveness and costs compared to other health providers (four randomised controlled trials). Physiotherapists were associated with increased efficiency (eight observational studies) and reduced low‐value care (one observational study). Three observational studies reported very low adverse event rates. However, none of the studies followed participants to measure adverse events that became apparent after the ED visit, nor did they consider unsafe discharge decisions or suboptimal follow‐up care. The available evidence suggests that physiotherapists may be as effective as other health providers in managing low urgency musculoskeletal conditions in the ED. There is uncertainty about appropriate training and a lack of robust studies investigating the efficiency, safety and cost‐effectiveness of this model of care.
Ruminal metagenomic libraries as a source of relevant hemicellulolytic enzymes for biofuel production
Authors: Duque Estrella , Daddaoua Abdelali , Cordero Baldo F. , Udaondo Zulema , Molina‐Santiago Carlos , Roca Amalia , Solano Jennifer , Molina‐Alcaide Eduarda , Segura Ana , Ramos Juan‐Luis
Published: April 2018

The success of second‐generation (2G) ethanol technology relies on the efficient transformation of hemicellulose into monosaccharides and, particularly, on the full conversion of xylans into xylose for over 18% of fermentable sugars. We sought new hemicellulases using ruminal liquid, after enrichment of microbes with industrial lignocellulosic substrates and preparation of metagenomic libraries. Among 150 000 fosmid clones tested, we identified 22 clones with endoxylanase activity and 125 with β‐xylosidase activity. These positive clones were sequenced en masse, and the analysis revealed open reading frames with a low degree of similarity with known glycosyl hydrolases families. Among them, we searched for enzymes that were thermostable (activity at > 50°C) and that operate at high rate at pH around 5. Upon a wide series of assays, the clones exhibiting the highest endoxylanase and β‐xylosidase activities were identified. The fosmids were sequenced, and the corresponding genes cloned, expressed and proteins purified. We found that the activity of the most active β‐xylosidase was at least 10‐fold higher than that in commercial enzymatic fungal cocktails. Endoxylanase activity was in the range of fungal enzymes. Fungal enzymatic cocktails supplemented with the bacterial hemicellulases exhibited enhanced release of sugars from pretreated sugar cane straw, a relevant agricultural residue.
Calcified cerebral emboli: Incidence and implications
Authors: Bardon Miguel , Hanson Julian , O'Brien Bill , Naeem Adil
Published: April 2018

Introduction

Calcified cerebral emboli are an increasingly recognized cause of ischaemic stroke, although recognition amongst general radiologists and clinicians can be limited. Recent literature suggests that calcified cerebral emboli are likely more common than originally thought. This study aims to define the prevalence of calcified cerebral emboli as the most likely aetiology within a cohort of confirmed cases of acute stroke, as well as compare and contrast these cases with cases of ‘incidental’ intracranial calcification.

Methods

Cases of confirmed stroke between May 2014 and May 2017 were reviewed by two readers to assess for the most likely aetiology. Cases of presumed calcified cerebral embolus were categorized in to ‘possible’ or ‘definite’. The morphology, distribution and density were analysed by two independent readers, then subsequently discussed to reach a consensus. Cases were further studied in terms of likely proximal embolic source, therapeutic interventions and clinical outcomes. A further random selection of 220 non‐contrast CT head examinations were reviewed over the same time period to assess for the presence of calcification which was favoured to be ‘intravascular’ using the same criteria.

Results

A total of 220 cases of confirmed stroke were reviewed. Thirteen of these cases were thought to be most likely secondary to calcified cerebral emboli (5.9%). Of the 13 cases, eight were considered ‘definite’ as previous premorbid imaging without calcification was available. Twelve patients had emboli within the anterior circulation and only one patient had an embolus in the posterior circulation. Moderate calcified atherosclerotic disease was noted within the aorta and carotid arteries of all patients. Of the 220 patients within the control group, three cases were thought to have intracranial calcification most likely to be intravascular without clinical sequelae or other supportive imaging findings of infarct.

Conclusion

Previously thought to be a rare complication of intra‐arterial instrumentation, calcified cerebral emboli have been shown to more commonly be associated with spontaneous cerebral infarction. Whilst literature in this area remains scant, recognition and differentiation of this entity has important clinical applications regarding immediate diagnosis of stroke on non‐contrast imaging, modified treatment in the acute setting as well as in regards to recurrent event prognosis and secondary prevention.
Differential clinical presentation of Adamantiades–Behçet's disease in non‐endemic and endemic areas: retrospective data from a Middle‐European cohort study
Authors: Moosmann Thomas , Veraar Cécilia , Brunner Jürgen , Fraedrich Gustav , Frech Andreas , Horninger Wolfgang , Ratzinger Gudrun , Streif Werner , Teuchner Barbara , Willeit Johann , Zlamy Manuela , De Zordo Tobias , Schirmer Michael
Published: April 2018

Objectives

To assess demographical and clinical data in a Middle‐European cohort of patients with Adamantiades–Behçet's disease (ABD), together with the use of medication in adherence to international guidelines.

Methods

In a retrospective cohort study, in‐ and outpatients of an Austrian secondary and tertiary university hospital center were analyzed independent from the medical discipline involved. After ethics approval, screening for ABD‐patients in the clinical information system resulted in 1821 documents from 1997 to 2016. Patients fulfilling the International Criteria for Behçet's Disease were included, and ABD symptoms and signs together with medical interventions for immunosuppression, anticoagulation and pain management were identified by individual chart reviews and evaluated for conformity with international recommendations.

Results

A total of 76 ABD patients were identified with 39.1% Austrian and 37.0% Turkish origin. Genital aphthae and skin manifestations were more frequent, neurological, gastrointestinal and vascular manifestations less frequent in ABD patients of Turkish origin living in Austria compared to those living in Turkey (each P < 0.05). The male‐to‐female ratio averaged 0.86 (0.39 in patients with Austrian and 1.43 with Turkish backgrounds), and was 3.3 in patients with venous manifestations. Out of 174 medical interventions, 55.2% fully matched the European League Against Rheumatism recommendations of 2008, and 93.7% were considered at least as equal to the recommendations. Indications for tumor necrosis factor inhibition were in line with the 2007 Sfikakis recommendations.

Conclusions

In this Middle‐European ABD cohort clinical presentations between patients of Austrian and Turkish origin do not strongly vary, whereas Turkish patients from the non‐endemic Innsbruck cohort present differently compared to patients living in Turkey. The role of such cohort analyses will increase, from the epidemiological as well as the management perspective.
Perioperative hyperoxia and post‐operative cardiac complications in adults undergoing non‐cardiac surgery: Systematic review protocol
Authors: Petersen C. , Wetterslev J. , Meyhoff C. S.
Published: April 2018

Background

Oxygen therapy is used liberally for all patients undergoing anaesthesia. Recent studies have raised concerns that it may not be without complications when arterial oxygen concentrations reach supranormal concentrations (hyperoxia). Studies of oxygen therapy have raised concerns that the risk of myocardial injury and infarction is elevated in patients with hyperoxia due to vasoconstriction and formation of reactive oxygen species. Due to lack of symptoms or silent ischaemia, post‐operative myocardial injury may be missed clinically. In some studies, perioperative hyperoxia has been linked to increased long‐term mortality, but cardiac complications are sparsely evaluated. The aim of this review is to summarize current evidence to assess the risk and benefits of perioperative hyperoxia on post‐operative cardiac complications.

Methods

This systematic review will include meta‐analyses and Trial Sequential Analyses. We will include randomized clinical trials with patients undergoing non‐cardiac surgery if the allocation separates patients into a target of either higher (above 0.60) or lower (below 0.40) inspired oxygen fraction. To minimize the risk of systematic error, we will assess the risk of bias of the included trials using the Cochrane Risk of Bias Tool. The overall quality of evidence for each outcome will be assessed with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE).

Discussion

This systematic review will provide data on a severe, albeit rare, potential risk of oxygen therapy. We will do a trial sequential analysis to assess the robustness of results as well as help estimate the required patient size for future clinical trials.
Spindle cell rhabdomyosarcoma of the anterior mandible manifesting as a periapical lesion of pulpal origin: Case report
Authors: Sadhasivam Vanitha , Sherwood I. Anand , Gutmann James L. , Gururaj N. , Mahalakshmi V. , Doss Daffney M.
Published: April 2018

A 25‐year‐old male patient presented with swelling and pain in the mandibular anterior region for the previous 6 months. He had a history of repeated traumatic episodes associated with his lower incisors. A periapical radiograph revealed a radiolucent lesion involving the apices of the lower incisors, whereas cone beam computed tomography revealed a large osteolytic lesion involving all mandibular incisors and loss of labial and lingual cortical plates. Histological, immunohistochemical and bone scan examination of the curetted tissue established a differential diagnosis of spindle cell rhabdomyosarcoma of the anterior mandible. Such rare but life‐threatening oral cancers can be correctly diagnosed and treated only through systematic analysis of clinical findings and examining the diseased tissue with histological and other diagnostic procedures.
Safety of sofosbuvir‐based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study
Authors: Anty R. , Favre G. , Coilly A. , Rossignol E. , Houssel‐Debry P. , Duvoux C. , De Ledinghen V. , Di Martino V. , Leroy V. , Radenne S. , Kamar N. , Canva V. , D'Alteroche L. , Durand F. , Dumortier J. , Lebray P. , Besch C. , Tran A. , Canivet C. M. , Botta‐Fridlund D. , Montialoux H. , Moreno C. , Conti F. , Silvain C. , Perré P. , Habersetzer F. , Abergel A. , Debette‐Gratien M. , Dharancy S. , Esnault V. L. M. , Fougerou‐Leurent C. , Cagnot C. , Diallo A. , Veislinger A. , Danjou H. , Samuel D. , Pageaux G.‐P. , Duclos‐Vallée J.‐C. ,   the ANRS CO23 CUPILT Study Group
Published: April 2018

Background

In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir‐based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable.

Aim

To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time.

Methods

In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease–Epidemiology Collaboration (CKD‐EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre‐treatment, on‐treatment and post‐treatment periods were 9 months, 3‐9 months and 4.5 months. Interactions between eGFR slopes and the pre‐treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On‐treatment eGFR slopes were separated in tertiles. Pre‐ and post‐treatment eGFR slopes were compared globally and according to tertiles.

Results

The post‐treatment eGFR slope was significantly better than pre‐treatment eGFR slope (+0.18 (IQR −0.76 to +1.32) vs −0.11 (IQR −1.01 to +0.73) mL/min/1.73 m2/month, P = 0.03) independently of the pre‐treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child‐Pugh B and C vs lower stages, P = 0.38). Tertiles of on‐treatment eGFR slopes were −1.71 (IQR −2.54 to −1.48), −0.78 (IQR −1.03 to −0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2/month. Pre‐ and post‐treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73).

Conclusion

The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir‐based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.
High body mass index is associated with increased risk of treatment failure and surgery in biologic‐treated patients with ulcerative colitis
Authors: Kurnool S. , Nguyen N. H. , Proudfoot J. , Dulai P. S. , Boland B. S. , Vande Casteele N. , Evans E. , Grunvald E. L. , Zarrinpar A. , Sandborn W. J. , Singh S.
Published: April 2018

Background

Though pharmacokinetic studies suggest accelerated biologic drug clearance with increasing body weight, evidence of obesity's impact on clinical outcomes in biologic‐treated patients with ulcerative colitis (UC) is inconsistent.

Aim

To evaluate the impact of obesity on real world response to biological therapy in patients with UC.

Methods

In a single‐centre retrospective cohort study between 2011‐2016 of biologic‐treated patients with UC, we evaluated treatment response by baseline body mass index (BMI). Primary outcome was treatment failure (composite outcome of IBD‐related surgery/hospitalisation or treatment modification including dose escalation, treatment discontinuation or addition of corticosteroids); secondary outcomes were risk of IBD‐related surgery/hospitalisation and endoscopic remission. We conducted multivariate Cox proportional hazard analyses to evaluate the independent impact of BMI on clinical outcomes. Stratified analysis by weight‐based regimens (infliximab) or fixed‐dose regimens (adalimumab, golimumab, vedolizumab, certolizumab pegol) was performed.

Results

We included 160 biologic‐treated UC patients (50% males, 55% on infliximab) with median (IQR) age 36 y (26‐52) and BMI 24.3 kg/m2 (21.4‐28.7). On multivariate analysis, each 1 kg/m2 increase in BMI was associated with 4% increase in the risk of treatment failure (adjusted hazard ratio [aHR], 1.04 [95% CI, 1.00‐1.08]) and 8% increase in the risk of surgery/hospitalisation (aHR, 1.08 [1.02‐1.14]). The effect on treatment failure was seen in patients on weight‐based dosing regimens or fixed‐dose therapies.

Conclusion

BMI is independently associated with increased risk of treatment failure in biologic‐treated patients with UC, independent of dosing regimen.
Use of Non‐Vitamin K Antagonist Oral Anticoagulants 2008–2016: A Danish Nationwide Cohort Study
Authors: Haastrup Simone Bonde , Hellfritzsch Maja , Rasmussen Lotte , Pottegård Anton , Grove Erik Lerkevang
Published: April 2018

We aimed to provide detailed utilization data on the total use of non‐vitamin K antagonist oral anticoagulants (NOACs) since their introduction in 2008. Using the nationwide Danish National Prescription Registry, we identified all individuals filling prescriptions for NOACs 2008–2016. We reported the development in incident and prevalent users and explored baseline characteristics and treatment persistence according to treatment indication. A total of 126,691 NOAC users were identified within the Danish population of 5.7 million inhabitants. The annual incidence and prevalence increased rapidly reaching 10 and 17 per 1000 individuals in 2016. Patients received NOACs due to atrial fibrillation (AF) (43%), venous thromboembolism (VTE) prophylaxis after arthroplastic surgery (17%), VTE (12%) and no registered indication (28%). The most frequently used NOAC was rivaroxaban (n = 52,431), followed by dabigatran (n = 47,067), apixaban (n = 27,116) and edoxaban (n = 77). The proportion of AF and VTE patients initiating low‐dose NOACs were between 23% and 50%. Patients treated with NOAC for VTE primarily received rivaroxaban. We observed a trend towards increased use of apixaban and rivaroxaban at the expense of dabigatran. Treatment persistence was highly dependent on treatment indication. Persistence to NOAC after 3 years was only 62% in AF compared to 28% for VTE. We documented an accelerating increase in the use of all four NOACs in the first 8 years after introduction. We have identified areas requiring further attention, including reasons for missing indications, potential inappropriate dosing and low long‐term persistence with NOACs in patients with AF.
MILFM: Multiple Index Latent Factor Model Based on High-Dimensional Features
Authors: Yang Hojin , Zhu Hongtu , Ibrahim Joseph G.
Published: April 2018

The aim of this article is to develop a multiple-index latent factor modeling (MILFM) framework to build an accurate prediction model for clinical outcomes based on a massive number of features. We develop a three-stage estimation procedure to build the prediction model. MILFM uses an independent screening method to select a set of informative features, which may have a complex nonlinear relationship with the outcome variables. Moreover, we develop a latent factor model to project all informative predictors onto a small number of local subspaces, which lead to a few key features that capture reliable and informative covariate information. Finally, we fit the regularized empirical estimate to those key features in order to accurately predict clinical outcomes. We systematically investigate the theoretical properties of MILFM, such as risk bounds and selection consistency. Our simulation results and real data analysis show that MILFM outperforms many state-of-the-art methods in terms of prediction accuracy.
Pseudo and Conditional Score Approach to Joint Analysis of Current Count and Current Status Data
Authors: Wen Chi-Chung , Chen Yi-Hau
Published: April 2018

We develop a joint analysis approach for recurrent and nonrecurrent event processes subject to case I interval censorship, which are also known in literature as current count and current status data, respectively. We use a shared frailty to link the recurrent and nonrecurrent event processes, while leaving the distribution of the frailty fully unspecified. Conditional on the frailty, the recurrent event is assumed to follow a nonhomogeneous Poisson process, and the mean function of the recurrent event and the survival function of the nonrecurrent event are assumed to follow some general form of semiparametric transformation models. Estimation of the models is based on the pseudo-likelihood and the conditional score techniques. The resulting estimators for the regression parameters and the unspecified baseline functions are shown to be consistent with rates of square and cubic roots of the sample size, respectively. Asymptotic normality with closed-form asymptotic variance is derived for the estimator of the regression parameters. We apply the proposed method to a fracture-osteoporosis survey data to identify risk factors jointly for fracture and osteoporosis in elders, while accounting for association between the two events within a subject.
On the Analysis of Discrete Time Competing Risks Data
Authors: Lee Minjung , Feuer Eric J. , Fine Jason P.
Published: April 2018

Regression methodology has been well developed for competing risks data with continuous event times, both for the cause-specific hazard and cumulative incidence functions. However, in many applications, including those from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute, the event times may be observed discretely. Naive application of continuous time regression methods to such data is not appropriate. We propose maximum likelihood inferences for estimation of model parameters for the discrete time cause-specific hazard functions, develop predictions for the associated cumulative incidence functions, and derive consistent variance estimators for the predicted cumulative incidence functions. The methods are readily implemented using standard software for generalized estimating equations, where models for different causes may be fitted separately. For the SEER data, it may be desirable to model different event types on different time scales and the methods are generalized to accommodate such scenarios, extending earlier work on continuous time data. Simulation studies demonstrate that the methods perform well in realistic set-ups. The methodology is illustrated with stage III colon cancer data from SEER.
The Flushtration Count Illusion: Attribute substitution tricks our interpretation of a simple visual event sequence
Authors: Thomas Cyril , Didierjean André , Kuhn Gustav
Published: April 2018

When faced with a difficult question, people sometimes work out an answer to a related, easier question without realizing that a substitution has taken place (e.g., Kahneman, 2011, Thinking, fast and slow. New York, Farrar, Strauss, Giroux). In two experiments, we investigated whether this attribute substitution effect can also affect the interpretation of a simple visual event sequence. We used a magic trick called the ‘Flushtration Count Illusion’, which involves a technique used by magicians to give the illusion of having seen multiple cards with identical backs, when in fact only the back of one card (the bottom card) is repeatedly shown. In Experiment 1, we demonstrated that most participants are susceptible to the illusion, even if they have the visual and analytical reasoning capacity to correctly process the sequence. In Experiment 2, we demonstrated that participants construct a biased and simplified representation of the Flushtration Count by substituting some attributes of the event sequence. We discussed of the psychological processes underlying this attribute substitution effect.
Perceived peer and school norm effects on youth antisocial and prosocial behaviours through intergroup contact in Northern Ireland
Authors: McKeown Shelley , Taylor Laura K.
Published: April 2018

In adolescence, youth spend a high proportion of their time with their peers and in school; it is hardly surprising therefore that perceptions of peer and school norms have a strong influence on their attitudes and behaviours. These norms, however, do not always influence youth in the same way. Building on past research, the present study examines the role of peer norms and school norms in influencing the quantity and quality of intergroup contact, as well as the impact of such contact on positive and negative intergroup behaviours. Youth (aged 14–16) living in Northern Ireland (N = 466, evenly split by religion and gender) were recruited through their school as part of a two‐wave study and completed a series of survey measures including intergroup contact (quality and quantity), norms (peer and school), and participation in sectarian antisocial behaviour and outgroup prosocial behaviour. Mediation analysis was conducted in Mplus. Controlling for wave 1 responses on contact and behavioural outcomes, findings demonstrate that more positive peer norms are associated with less participation in antisocial behaviour and more participation in prosocial outgroup behaviours through increased and better quality intergroup contact. Positive school norms were also associated with increased prosocial behaviour, but only though better quality contact. Findings demonstrate the relative importance of peer norms compared to school norms for this age group. The results have implications for school‐based interventions that aim to improve intergroup relations and highlight the importance of peer networks to promote more positive outgroup behaviours in divided societies such as Northern Ireland.
A high‐resolution sea‐level proxy dated using quartz OSL from the Holocene Skagen Odde spit system, Denmark
Authors: Clemmensen Lars B. , Hougaard Iben W. , Murray Andrew S. , Pedersen Simone S.
Published: April 2018

The contact between wave‐influenced foreshore and aeolian‐influenced backshore sediments (BA boundary) in raised spit deposits (Skagen Odde) is here used as a proxy for palaeo‐sea level over the past 7600 years. The elevation of the BA boundary was measured at 57 sample sites along the northwestern coast of the spit, and the age of these sites determined by optically stimulated luminescence (OSL) dating of quartz grains. The elevation of the BA boundary with age gives past variation in relative sea level; relative sea level rose between c. 7600 and c. 6250 years ago, when it reached a peak value around 12.5 m above present mean sea level (apmsl), followed by a slow sea‐level fall until c. 4600 years ago before it dropped rapidly to reach 2 m apmsl c. 2000 years ago. From the new data it is tentatively deduced that the land uplift rate declined from about 3 mm a−1 6000 years ago to about 1.5 mm a−1 2000 years ago (low estimate), or alternatively from 5 mm a−1 5000 years ago to 1.5 mm a−1 2000 years ago (extreme estimate). These data indicate that the long‐term average rate of vertical land movement during the past 5000 years was around 1.8 mm a−1 (low estimate) or around 2.5 mm a−1 (extreme estimate). These values seem reasonable compared with a modern value of about 1.6 to 1.7 mm a−1. The lack of an independent data set illustrating the isostatic uplift history with time, however, precludes the construction of a well‐constrained eustatic sea‐level curve.
From humans to hydra: patterns of cancer across the tree of life
Authors: Albuquerque Thales A. F. , Drummond do Val Luisa , Doherty Aoife , de Magalhães João Pedro
Published: April 2018

Cancer is a disease of multicellularity; it originates when cells become dysregulated due to mutations and grow out of control, invading other tissues and provoking discomfort, disability, and eventually death. Human life expectancy has greatly increased in the last two centuries, and consequently so has the incidence of cancer. However, how cancer patterns in humans compare to those of other species remains largely unknown. In this review, we search for clues about cancer and its evolutionary underpinnings across the tree of life. We discuss data from a wide range of species, drawing comparisons with humans when adequate, and interpret our findings from an evolutionary perspective. We conclude that certain cancers are uniquely common in humans, such as lung, prostate, and testicular cancer; while others are common across many species. Lymphomas appear in almost every animal analysed, including in young animals, which may be related to pathogens imposing selection on the immune system. Cancers unique to humans may be due to our modern environment or may be evolutionary accidents: random events in the evolution of our species. Finally, we find that cancer‐resistant animals such as whales and mole‐rats have evolved cellular mechanisms that help them avoid neoplasia, and we argue that there are multiple natural routes to cancer resistance.
Are in‐migrant proprietors driving or enhancing cultural heritage tourism in transitioning resource‐dependent communities? The case of Trinity, Newfoundland and Labrador
Authors: Mitchell Clare J. A. , Shannon Meghan
Published: April 2018

Key Messages

In‐migrants’ externally accumulated capital may influence path creation.

Newcomer and returnee proprietors in Trinity use recombination, layering, and conversion to augment an existing branching innovating tourism trajectory.

Civic‐minded in‐migrants helped create the path; their presence may be a precursor to private investment.
Pigment epithelium‐derived factor/vascular endothelial growth factor ratio plays a crucial role in the spontaneous regression of infant hemangioma and in the therapeutic effect of propranolol
Authors: Zhu Liuqing , Xie Jinye , Liu Zhenyin , Huang Zhijian , Huang Mao , Yin Haofan , Qi Weiwei , Yang Zhonghan , Zhou Ti , Gao Guoquan , Zhang Jing , Yang Xia
Published: April 2018

Infantile hemangioma (IH) is a benign tumor that is formed by aberrant angiogenesis and that undergoes spontaneous regression over time. Propranolol, the first‐line therapy forIH, inhibits angiogenesis by downregulating activation of the vascular endothelial growth factor (VEGF) pathway, which is hyperactivated inIH. However, this treatment is reportedly ineffective for 10% of tumors, and 19% of patients relapse after propranolol treatment. Both pro‐angiogenic and anti‐angiogenic factors regulate angiogenesis, and pigment epithelium‐derived factor (PEDF) is the most effective endogenous anti‐angiogenic factor.PEDF/VEGFratio controls many angiogenic processes, but its role inIHand the relationship between this ratio and propranolol remain unknown. Results of the present study showed that thePEDF/VEGFratio increased during the involuting phase ofIHcompared with the proliferating phase. Similarly, in hemangioma‐derived endothelial cells (HemEC), which were isolated with magnetic beads, increasing thePEDF/VEGFratio inhibited proliferation, migration, and tube formation and promoted apoptosis. Mechanistically, theVEGFreceptors (VEGFR1 andVEGFR2) andPEDFreceptor (laminin receptor,LR) were highly expressed in bothIHtissues and HemEC, andPEDFinhibited HemECfunction by binding toLR. Interestingly, we found that propranolol increased thePEDF/VEGFratio but did so by loweringVEGFexpression rather than by upregulatingPEDFas expected. Furthermore, the combination ofPEDFand propranolol had a more suppressive effect on HemEC. Consequently, our results suggested that thePEDF/VEGFratio played a pivotal role in the spontaneous regression ofIHand that the combination ofPEDFand propranolol might be a promising treatment strategy for propranolol‐resistantIH.
Modeling Prosocial Behavior Increases Helping in 16‐Month‐Olds
Authors: Schuhmacher Nils , Köster Moritz , Kärtner Joscha
Published: April 2018

In two experiments, the imitation of helping behavior in 16‐month‐olds was investigated. In Study 1 (N = 31), infants either observed an adult model helping or not helping another individual before they had the opportunity to assist an unfamiliar experimenter. In one of two tasks, more children helped in the prosocial model condition than in the no model control condition. In Study 2 (N = 60), a second control condition was included to test whether infants imitated the prosocial intention (no neediness control). Children in the prosocial model condition helped more readily than children in the no model condition, with the second control condition falling in between. These findings propose that modeling provides a critical learning mechanism in early prosocial development.
Distribution and progression of add power among people in need of near correction
Authors: Han Xiaotong , Lee Pei Ying , Liu Chi , He Mingguang
Published: April 2018

Importance

This study helps to better understand the need and trend in presbyopic add power in the aging society.

Background

Distribution and progression of presbyopic add power in East Asian population is largely unknown.

Design

Prospective cohort study.

Participants

About 303 participants from a population‐based study of residents aged 35 years and older in Guangzhou, China.

Methods

Visual acuity (VA) test and non‐cycloplegic automated refraction were performed at baseline in 2008 and the 6‐year follow‐up per standardized protocol. Participants with presenting near VA ≤ 20/40 underwent distance subjective refraction and add power measurement by increasing plus lens at a standard distance of 40 cm at each visit.

Main outcome measures

Add power at baseline and follow‐ups.

Results

Mean (standard deviation) age of the study participants was 57.6 (11.1) years and 50.2% were female. The mean add power at baseline was 1.43, 1.73, 2.03 and 2.20 diopters (D) for individuals in the age groups of 35–44, 45–54, 55–64 and 65+ years, respectively. Participants with older age and lower educational level had significantly higher add power requirements (P < 0.001). The overall 6‐year increase in add power was 0.15D (95% CI: 0.06 to 0.25), and was smaller in myopic subjects (P = 0.03). Baseline age and add power, but not changes in biometric factors, were associated with longitudinal change in add power (P < 0.001).

Conclusions and Relevance

Distribution and progression of add power in Chinese was different from that previously suggested by Caucasian studies. More studies are needed to establish up‐to‐date age‐related add power prescription norms for population of different ethnicities.
Endoscopic ultrasound diagnosis of Merkel cell carcinoma metastasising to pancreas
Authors: Pinho J. , Montezuma D. , Monteiro P. , Dinis‐Ribeiro M. , Bastos P.
Published: April 2018

Merkel cell carcinoma (MCC) is a rare primary neuroendocrine tumor of the skin. Distant metastasis of MCC to the pancreas are rarely seen. The authors describe the case of a MCC metastatic to the pancreas diagnosed by EUS‐FNA, with special emphasis on cytological features and immunocytochemistry.
The Redevelopmental State: Governing Surplus Life and Land in the ‘Urban Age’
Authors: Doshi Sapana
Published: April 2018

This article theorizes changing configurations of development governance emerging as states attempt to reconcile two contradictory pressures of global urbanization: dispossessing capitalist accumulation and demands for inclusive welfare. It introduces the ‘redevelopmental state’ as a dynamic spatio‐political framework for understanding how hegemonic rule is tenuously forged amid potentially volatile urban land struggles. Whereas Northern urban redevelopment theories are less attentive to post‐colonial urbanization processes and most developmental state scholarship has not focused on cities, the redevelopmental state offers an alternative conceptualization. It centres on how emerging regimes of territorial rule, development and political participation contour access to land and social benefits in Southern cities. Forged at key conjunctures of social pressure, these redevelopmental state spaces work through and beyond formal policies and institutions, and articulate with nationalist cultural politics of belonging and aspiration that foster consent for redevelopment while also legitimating exclusions, violence and dispossession. A case study of Mumbai illustrates redevelopmental state spaces that suture ethno‐religious nationalism, urbanized accumulation and populist welfare to unevenly distribute life capacities, garnering both cooperation and contestation. The article concludes by suggesting ways this spatially attuned framing can provide insights into the recent rise of ethno‐nationalism and authoritarian populism around the world.
Gesture helps learners learn, but not merely by guiding their visual attention
Authors: Wakefield Elizabeth , Novack Miriam A. , Congdon Eliza L. , Franconeri Steven , Goldin‐Meadow Susan
Published: April 2018

Teaching a new concept through gestures—hand movements that accompany speech—facilitates learning above‐and‐beyond instruction through speech alone (e.g., Singer & Goldin‐Meadow, ). However, the mechanisms underlying this phenomenon are still under investigation. Here, we use eye tracking to explore one often proposed mechanism—gesture's ability to direct visual attention. Behaviorally, we replicate previous findings: Children perform significantly better on a posttest after learning through Speech+Gesture instruction than through Speech Alone instruction. Using eye tracking measures, we show that children who watch a math lesson with gesture do allocate their visual attention differently from children who watch a math lesson without gesture—they look more to the problem being explained, less to the instructor, and are more likely to synchronize their visual attention with information presented in the instructor's speech (i.e., follow along with speech) than children who watch the no‐gesture lesson. The striking finding is that, even though these looking patterns positively predict learning outcomes, the patterns do not mediate the effects of training condition (Speech Alone vs. Speech+Gesture) on posttest success. We find instead a complex relation between gesture and visual attention in which gesture moderates the impact of visual looking patterns on learning—following along with speech predicts learning for children in the Speech+Gesture condition, but not for children in the Speech Alone condition. Gesture's beneficial effects on learning thus come not merely from its ability to guide visual attention, but also from its ability to synchronize with speech and affect what learners glean from that speech.
Effectiveness and safety of rivaroxaban vs warfarin in people with non‐valvular atrial fibrillation and diabetes: an administrative claims database analysis
Authors: Coleman C. I. , Bunz T. J. , Eriksson D. , Meinecke A.‐K. , Sood N. A.
Published: April 2018

Aim

To assess the effectiveness and safety of rivaroxaban vs warfarin in people with non‐valvular atrial fibrillation and diabetes treated in routine practice.

Methods

Using US MarketScan claims data for the period November 2011 to December 2016, we identified oral anticoagulation‐naïve people with non‐valvular atrial fibrillation and diabetes (Type 1 or Type 2) and ≥12 months of continuous insurance coverage prior to the qualifying oral anticoagulation dispensing time. Rivaroxaban users were 1:1 propensity score‐matched to warfarin users. Participants were followed until an event, oral anticoagulation switch/discontinuation, insurance disenrolment or end of follow‐up. Rates (events/100 person‐years) of the composite of stroke or systemic embolism and major bleeding were compared using Cox regression and reported as hazard ratios and 95% CIs.

Results

We assessed 5517 rivaroxaban users (20% received the reduced dose) and 5517 warfarin users with non‐valvular atrial fibrillation and diabetes (~97% with Type 2 diabetes) with a median (interquartile range) available follow‐up of 1.5 (0.7, 2.7) years. Rivaroxaban was associated with nonsignificant reductions in stroke or systemic embolism (0.87 vs 1.35/100 person‐years; hazard ratio 0.68, 95% CI 0.44–1.05) and ischaemic stroke (0.69 vs 0.93/100 person‐years; hazard ratio 0.78, 95% CI 0.48–1.30) compared with warfarin. No differences in major bleeding (2.7 vs 3.0/100 person‐years; hazard ratio 0.96, 95% CI 0.74–1.25) were observed. Similar results were seen when analysis was limited to standard‐dose rivaroxaban. Reduced‐dose rivaroxaban was associated with a significantly decreased hazard of stroke or systemic embolism and ischaemic stroke, without an increase in major bleeding risk.

Conclusions

Rivaroxaban has effectiveness and safety at least as good as those of warfarin in people with diabetes and non‐valvular atrial fibrillation treated in routine clinical practice.
New classification of geometric ventricular patterns in severe aortic stenosis: Could it be clinically useful?
Authors: Di Nora Concetta , Cervesato Eugenio , Cosei Iulian , Ravasel Andreea , Popescu Bogdan A. , Zito Concetta , Carerj Scipione , Antonini‐Canterin Francesco , Popescu Andreea C.
Published: April 2018

Background

In severe aortic stenosis, different left ventricle (LV) remodeling patterns as a response to pressure overload have distinct hemodynamic profiles, cardiac function, and outcomes. The most common classification considers LV relative wall thickness and LV mass index to create 4 different groups. A new classification including also end‐diastolic volume index has been recently proposed.

Aim

To describe the prevalence of the newly identified remodeling patterns in patients with severe aortic stenosis and to evaluate their clinical relevance according to symptoms.

Methods

We analyzed 286 consecutive patients with isolated severe aortic stenosis. Current guidelines were used for echocardiographic evaluation. Symptoms were defined as the presence of angina, syncope, or NYHA class III–IV.

Results

The mean age was 75 ± 9 years, 156 patients (54%) were men, while 158 (55%) were symptomatic. According to the new classification, the most frequent remodeling pattern was concentric hypertrophy (57.3%), followed by mixed (18.9%) and dilated hypertrophy (8.4%). There were no patients with eccentric remodeling; only 4 patients had a normalLV geometry. Symptomatic patients showed significantly more mixed hypertrophy (P < .05), while the difference regarding the prevalence of the other patterns was not statistically significant. When we analyzed the distribution of the classic 4 patterns stratified by the presence of symptoms, however, we did not find a significant difference (P = .157).

Conclusions

The new classification had refined the description of different cardiac geometric phenotypes that develop as a response to pressure overload. It might be superior to the classic 4 patterns in terms of association with symptoms.
Global and regional left ventricular circumferential strain during incremental cycling and isometric knee extension exercise
Authors: Beaumont Alexander , Sculthorpe Nicholas , Hough John , Unnithan Viswanath , Richards Joanna
Published: April 2018

Background

The objective of this study was to investigate left ventricular (LV) circumferential strain responses to incremental cycling and isometric knee extension exercises.

Methods

Twenty‐six healthy male participants (age = 30 ± 6 years) were used to study LV global (GCS) and regional circumferential strain at the apex (ACS) and base (BCS) during incremental cycling at 30% and 60% work rate maximum (Wmax) and short‐duration (15 seconds contractions) isometric knee extensions at 40% and 75% maximum voluntary contraction (MVC) using two‐dimensional speckle tracking echocardiography.

Results

During cycling (n = 22), GCS increased progressively from rest to 60% Wmax (−22.85 ± 3.26% to −29.87 ± 2.59%, P < .01). ACS increased from rest to 30% Wmax (−26.29 ± 4.84% to −36.84 ± 6.94%, P < .01) and then remained unchanged to 60% Wmax (−40.72 ± 4.06%, P = .068). BCS decreased from rest to 30% Wmax (−19.41 ± 2.79 to −17.51 ± 4.66%, P = .05) and then remained unchanged to 60% Wmax. During isometric knee extension (n = 23), GCS decreased from rest to 40% MVC (−22.63 ± 3.46 to −20.10 ± 2.78%, P < .05) and then remained unchanged to 75% MVC. Similarly, BCS decreased from rest to 40% MVC (−19.21 ± 2.58% to −13.55 ± 3.45%, P < .01) and then remained unchanged, whereas ACS did not change with exercise intensity (rest, −26.05 ± 5.34%; 40% MVC, −26.64 ± 4.53% and 75% MVC −27.22 ± 5.34%, all P > .05).

Conclusion

Global circumferential strain increased stepwise during incremental cycling, mediated by the apex with trivial changes at the base. In contrast, GCS decreased during the isometric knee extension to 40% MVC and then plateaued, due to decreased BCS as ACS was maintained. A novel finding is that the GCS response appears to be exercise modality dependant and is the consequence of region‐specific changes.
An analysis of clinical transition stresses experienced by dental students: A qualitative methods approach
Authors: Botelho M. , Gao X. , Bhuyan S. Y.
Published: April 2018

Introduction

Stress in dental students is well established with potential psychological distress, emotional exhaustion and burnout‐related symptoms. Little attention has been given to the problems encountered by dental students during the transition from theoretical or paraclinical training to the clinical environment. The aim of this study was to adopt a qualitative research methods approach to understand the perceived stressors during students’ clinical transition and provide insights for curriculum planners to enhance learning.

Methods

This study analysed four groups of 2nd‐ and 3rd‐year BDS students’ experiences in focus group interviews relating to their pre‐clinical and clinical transitions. The interviews were recorded and transcribed verbatim, and a thematic analysis was performed using an inductive qualitative approach.

Results

Key overlapping domains identified were the transition gap and stresses. The transition gap was subclassified into knowledge and skill (hard and soft), and stresses was subcategorised into internal and external stresses. On first coming to clinics, students experienced knowledge gaps of unfamiliar clinical treatments with mismatches between knowledge acquisition and clinical exposure. Students felt incompetent owing to the stresses attributable to curriculum design, staff and the patient. This negatively affected their confidence and clinical performance.

Conclusion

A range of challenges have been identified that will allow curriculum designer's to plan a more supportive learning experience to help students during their transition to clinical practice giving them timely knowledge, confidence and clinical performance to better prepare them for entering clinics.