bluuebunny/crossref_metadata_2025 huggingface dataset:
An assessment of advance relatives approach for brain death organ donation
Authors: Michaut Carine , Baumann Antoine , Gregoire Hélène , Laviale Corinne , Audibert Gérard , Ducrocq Xavier
Published: June 2017

Background:

Advance announcement of forthcoming brain death has developed to enable intensivists and organ procurement organisation coordinators to more appropriately, and separately from each other, explain to relatives brain death and the subsequent post-mortem organ donation opportunity.

Research aim:

The aim was to assess how potentially involved healthcare professionals perceived ethical issues surrounding the strategy of advance approach.

Research design:

A multi-centre opinion survey using an anonymous self-administered questionnaire was conducted in the six-member hospitals of the publicly funded East of France regional organ and tissue procurement network called ‘Prélor’.

Participants:

The study population comprised 460 physicians and nurses in the Neurosurgical, Surgical and Medical Intensive Care Units, the Stroke Units and the Emergency Departments.

Ethical considerations:

The project was approved by the board of the Lorraine University Diploma in Medical Ethics and the Prélor Network administrators.

Main findings:

A slight majority of 53.5% of respondents had previously participated in an advance relatives approach: 83% of the physicians and 42% of the nurses. A majority of healthcare professionals (68%) think that the main justification for advance relatives approach is the comprehensive care of the dying patient and the research of his or her most likely opinion (74%). The misunderstanding of the related issues by relatives is an obstacle for 47% of healthcare professionals and 51% think that the answer given by the relatives regarding the most likely opinion of the person regarding post-mortem organ donation really corresponds to the person opinion in only 50% of the cases or less.

Conclusion:

Time given by advance approach should be employed to help and enable relatives to authentically bear the values and interests of the potential donor in the post-mortem organ donation discussion. Nurses’ attendance of advance relatives approach seems necessary to enable them to optimally support the families facing death and post-mortem organ donation issues.
A Multicenter Analysis of Factors Associated With Apixaban-Related Bleeding in Hospitalized Patients With End-Stage Renal Disease on Hemodialysis
Authors: Steuber Taylor D. , Shiltz Dane L. , Cairns Alex C. , Ding Qian , Binger Katie J. , Courtney Julia R.
Published: June 2017

Background: In 2014, the United States Food and Drug Administration approved a labeling change for apixaban to include recommendations for patients with severe renal impairment and patients with end-stage renal disease (ESRD) on hemodialysis (HD), though these recommendations are largely based on pharmacokinetic and pharmacodynamic data. Objective: Identify variables associated with bleeding events in hospitalized patients with ESRD on HD receiving apixaban. Methods: This retrospective, multicenter cohort study evaluated hospitalized patients with ESRD on HD receiving apixaban from January 1, 2013, through March 31, 2016. Correlational analysis and logistic regression were completed to identify factors associated with bleeding. Results: A total of 114 adults were included in the analysis. The median length of stay (LOS) was 6.2 (interquartile range = 3.8-11.9) days and bleeding events occurred in a total of 17 patients (15%). A weak correlation was identified for higher cumulative apixaban exposure, increased number of HD sessions while receiving apixaban, and increased hospital LOS ( P < 0.05; correlation coefficient < 0.40). When controlling for confounders, logistic regression revealed that composite bleeding events were independently increased by continuation of outpatient apixaban (odds ratio = 13.07; 95% CI = 1.54-110.54; P = 0.018), increased total daily dose of apixaban (odds ratio = 1.72; 95% CI = 1.20 to 2.48; P = 0.003), and total HD sessions while receiving apixaban (odds ratio = 2.04; 95% CI = 1.06-3.92; P = 0.033). Conclusion: The association between these factors and increased bleeding should prompt concern for long-term anticoagulation with apixaban in patients with ESRD receiving chronic HD.
New insights into the burden and costs of multiple sclerosis in Europe: Results for Austria
Authors: Berger Thomas , Kobelt Gisela , Berg Jenny , Capsa Daniela , Gannedahl Mia ,   The European Multiple Sclerosis Platform
Published: June 2017

Introduction:

In order to estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated.

Objectives and Methods:

This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in EUR 2015.

Results:

A total of 516 patients (mean age, 53 years) participated in Austria; 72% were below retirement age, and of these, 46% were employed. Employment was related to disability, and MS affected productivity at work for 77% of those working. Overall, 94% and 67% of patients experienced fatigue and cognition as a problem. Mean utility and total annual costs were 0.778 and 25,100€ at Expanded Disability Status Scale (EDSS) 0–3, 0.579 and 44,100€ at EDSS 4–6.5, and 0.244 and 73,800€ at EDSS 7–9. The mean cost of a relapse was estimated at 2563€.

Conclusion:

This study illustrates the burden of MS on Austrian patients and provides current data on MS that are important for development of health policies.
New insights into the burden and costs of multiple sclerosis in Europe: Results for the Netherlands
Authors: Uitdehaag Bernard , Kobelt Gisela , Berg Jenny , Capsa Daniela , Dalén Johan ,   The European Multiple Sclerosis Platform
Published: June 2017

Introduction:

To estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated.

Objectives and Methods:

This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, from the societal perspective, in EUR 2015.

Results:

A total of 382 patients (mean age: 54 years) participated in the Netherlands; 81% were below retirement age and of these, 31% were employed. Employment was inversely related to disease severity, and MS affected productivity at work for 82% of patients. Overall, 96% and 73% of patients experienced fatigue and cognitive difficulties, respectively, as a problem. Mean utility and annual costs were 0.744 and €23,100 at Expanded Disability Status Scale (EDSS) 0–3, 0.595 and €32,300 at EDSS 4–6.5, and 0.297 and €50,500 at EDSS 7–9. The mean cost of a relapse was estimated at €3000.

Conclusion:

This study provides current data on MS in the Netherlands that are important for the development of health policies and to estimate the value of current and future treatments.
New insights into the burden and costs of multiple sclerosis in Europe: Results for Sweden
Authors: Brundin Lou , Kobelt Gisela , Berg Jenny , Capsa Daniela , Eriksson Jennifer ,   The European Multiple Sclerosis Platform
Published: June 2017

Background:

To assess the value of management strategies in multiple sclerosis (MS), outcome data have to be combined with cost data. This requires that cost data be regularly updated.

Objective and methods:

This study is part of a cross-sectional retrospective study in 16 countries collecting current data on resource consumption, work capacity and health-related quality of life (HRQoL). Descriptive analyses are presented by level of severity; costs are estimated in the societal perspective, in 2015 SEK.

Results:

A total of 1864 patients (mean age 56 years) participated in Sweden; 74% were below retirement age, and of these, 55% were employed. MS was reported to affect productivity at work in 78% of patients. Overall, 94% and 72% of patients felt that fatigue and cognition were a problem, respectively. The mean utility and costs were 0.757 and 244,000SEK at Expanded Disability Status Scale (EDSS) 0–3, 0.563 and 384,000SEK at EDSS 4–6.5 and 0.202 and 888,000SEK at EDSS 7–9, respectively. The average cost of a relapse was 36,900SEK.

Conclusion:

This study illustrates the burden of MS on Swedish patients and provides current data that are important for the development of health policies.
In the event of a variable text
Authors: Carpenter JR
Published: June 2017

Walter J Ong argues: ‘The spoken word is always an event, a movement in time, completely lacking in the thing-like repose of the written or printed word’. Digital writing has given rise to a new regime of enunciation in which written words refuse repose. This essay argues that although spoken, written and printed words operate within radically different temporal planes, spoken words also have thing-like properties and written and printed words also move through time. Digital writing has given rise to a new regime of signification unforeseen by Ong in which written words refuse repose. Jay David Bolter argues that digital writing ‘challenges the logocentric notion that writing should be merely the servant of spoken language…The writer and reader can create and examine structures on the computer screen that have no easy equivalent in speech’. N Katherine Hayles argues that, in digital media, the text ‘becomes a process, an event brought into existence when the program runs…The [text] is “eventilized,” made more an event and less a discrete, self-contained object with clear boundaries in space and time’. Jean-Jacques Lecercle argues that language is a constructed system, constantly subject to change…‘We therefore need to conceive of language not as a stable, arrested system, but as a system of variations’. This essay draws upon a diverse corpus of literary, media and performance theory and practice to establish a critical framework for examining the performance of variable texts throughout the entire apparatus of hardware, software, networks, bodies and spaces within and through which they operate and propagate. This framework is applied to a number of examples of digital writing which incorporates variability, instability, transformation and change into the process of composition, resulting in texts which are both physical and digital, confusing and confound boundaries between speaking, writing and reading.
Revenge is sour, but is forgiveness sweet? Psychological health and cortisol reactivity among women with experiences of abuse
Authors: Ysseldyk Renate , Matheson Kimberly , Anisman Hymie
Published: June 2017

This study examined the relations among women’s experiences of abuse, forgiveness, revenge, psychological health, and physiological stress reactivity. Both dispositional (Study 1; N = 103) and state (Study 2; N = 258) forgiveness and vengeance were associated with psychological symptoms. However, the relation between revenge and greater depression was magnified among psychologically abused women, whereas—unexpectedly—the positive link between forgiveness and psychological health was strengthened among physically abused women. Moreover, while revenge coincided with increased cortisol reactivity following any relationship conflict, this was only evident for forgiveness following physical abuse. The complex interactions among these variables are discussed within a stress and coping framework.
Living within our means: The UK news construction of the austerity frame over time
Authors: Basu Laura
Published: June 2017

In 2008, the financial crisis exploded onto the global scene, causing a world-wide recession and damage to public finances. Governments quickly switched from fiscal stimulus to retrenchment. Despite economic stagnation, falling living standards and rising not falling government debt, rulers have stuck to their austerity guns since then. Arguably, the mainstream media have played a central role in communicating austerity to publics. This article analyses the framing of austerity by the UK media over time, from the financial meltdown of 2008 until late 2015. It charts the emergence of a fledgeling austerity narrative from before the term was in common use, the establishment of a dominant austerity frame in 2009, the building of the frame before and after the 2010 elections and the fluctuations within the frame after 2010. It finds that, although there are considerable differences among the five outlets studied and changes over time, the central message overall has been that some degree of austerity is painful but necessary, and the general population is constructed as obliged to pay for the crisis.
Main Plant Extracts’ Active Properties Effective on Scopolamine-Induced Memory Loss
Authors: Balmus Ioana-Miruna , Ciobica Alin
Published: June 2017

Alzheimer’s disease leads to progressive cognitive function loss, which may impair both intellectual capacities and psychosocial aspects. Although the current knowledge points to a multifactorial character of Alzheimer’s disease, the most issued pathological hypothesis remains the cholinergic theory. The main animal model used in cholinergic theory research is the scopolamine-induced memory loss model. Although, in some cases, a temporary symptomatic relief can be obtained through targeting the cholinergic or glutamatergic neurotransmitter systems, no current treatment is able to stop or slow cognitive impairment. Many potentially successful therapies are often blocked by the blood–brain barrier since it exhibits permeability only for several classes of active molecules. However, the plant extracts’ active molecules are extremely diverse and heterogeneous regarding the biochemical structure. In this way, many active compounds constituting the recently tested plant extracts may exhibit the same general effect on acetylcholine pathway, but on different molecular ground, which can be successfully used in Alzheimer’s disease adjuvant therapy.
A Novel All-Inside Arthroscopic Technique for Radial-Sided Triangular Fibrocartilage Complex Tears: A Case Report and Review of Literature
Authors: Edgerton Michael T. , Kollmorgen Robert C.
Published: June 2017

Background: Triangular fibrocartilage complex (TFCC) injuries are a known cause of ulnar-sided wrist pain. Wrist arthroscopy is the gold standard for diagnosis of these lesions and is becoming a more frequent method of treatment. Isolated radial-sided tears are uncommon and treatment of these lesions is controversial. There are few reports on repair techniques. Here we report on a novel arthroscopic, all-inside technique for traumatic radial-sided TFCC tears that resulted in full range of motion, significant improvement in pain, and ultimately return to sport. Methods: This is a single case report describing an all-inside, arthroscopic repair of a radial-sided TFCC tear. The techniques and postoperative protocol are discussed. Clinical outcomes were reported at final follow-up of 3.5 months. Results: At final follow-up, our patient had full wrist range of motion, 95% strength, occasional 1/10 pain, and returned to sport at her previous level of play. There were no complications. Conclusion: Although just a single case report, our patient had an excellent result based on modified Mayo wrist score. When comparing our result and the previous literature, this technique seems to be a valid method for addressing radial-sided TFCC tears.
The impact of data errors on the outcome of randomized clinical trials
Authors: Buyse Marc , Squifflet Pierre , Coart Elisabeth , Quinaux Emmanuel , Punt Cornelis JA , Saad Everardo D
Published: June 2017

Background/aims

Considerable human and financial resources are typically spent to ensure that data collected for clinical trials are free from errors. We investigated the impact of random and systematic errors on the outcome of randomized clinical trials.

Methods

We used individual patient data relating to response endpoints of interest in two published randomized clinical trials, one in ophthalmology and one in oncology. These randomized clinical trials enrolled 1186 patients with age-related macular degeneration and 736 patients with metastatic colorectal cancer. The ophthalmology trial tested the benefit of pegaptanib for the treatment of age-related macular degeneration and identified a statistically significant treatment benefit, whereas the oncology trial assessed the benefit of adding cetuximab to a regimen of capecitabine, oxaliplatin, and bevacizumab for the treatment of metastatic colorectal cancer and failed to identify a statistically significant treatment difference. We simulated trial results by adding errors that were independent of the treatment group (random errors) and errors that favored one of the treatment groups (systematic errors). We added such errors to the data for the response endpoint of interest for increasing proportions of randomly selected patients.

Results

Random errors added to up to 50% of the cases produced only slightly inflated variance in the estimated treatment effect of both trials, with no qualitative change in the p-value. In contrast, systematic errors produced bias even for very small proportions of patients with added errors.

Conclusion

A substantial amount of random errors is required before appreciable effects on the outcome of randomized clinical trials are noted. In contrast, even a small amount of systematic errors can severely bias the estimated treatment effects. Therefore, resources devoted to randomized clinical trials should be spent primarily on minimizing sources of systematic errors which can bias the analyses, rather than on random errors which result only in a small loss in power.
Detailed magnetic resonance imaging features of a case series of primary gliosarcoma
Authors: Sampaio Luísa , Linhares Paulo , Fonseca José
Published: June 2017

Objective

We aimed to characterise the magnetic resonance imaging (MRI) features of a case series of primary gliosarcoma, with the inclusion of diffusion-weighted imaging and perfusion imaging with dynamic susceptibility contrast MRI.

Materials and methods

We conducted a retrospective study of cases of primary gliosarcoma from the Pathology Department database from January 2006 to December 2014. Clinical and demographic data were obtained. Two neuroradiologists, blinded to diagnosis, assessed tumour location, signal intensity in T1 and T2-weighted images, pattern of enhancement, diffusion-weighted imaging and dynamic susceptibility contrast MRI studies on preoperative MRI.

Results

Seventeen patients with primary gliosarcomas had preoperative MRI study: seven men and 10 women, with a mean age of 59 years (range 27–74). All lesions were well demarcated, supratentorial and solitary (frontal n = 5, temporal n = 4, parietal n = 3); 13 tumours abutted the dural surface (8/13 with dural enhancement); T1 and T2-weighted imaging patterns were heterogeneous and the majority of lesions (12/17) showed a rim-like enhancement pattern with focal nodularities/irregular thickness. Restricted diffusion (mean apparent diffusion coefficient values 0.64 × 10–3 mm2/s) in the more solid/thick components was present in eight out of 11 patients with diffusion-weighted imaging study. Dynamic susceptibility contrast MRI study ( n = 8) consistently showed hyperperfusion in non-necrotic/cystic components on relative cerebral volume maps.

Conclusions

The main distinguishing features of primary gliosarcoma are supratentorial and peripheral location, well-defined boundaries and a rim-like pattern of enhancement with an irregular thick wall. Diffusion-weighted imaging and relative cerebral volume map analysis paralleled primary gliosarcoma with high-grade gliomas, thus proving helpful in differential diagnosis.
Publication Rate of Podium Presentations From the North American Spine Society Annual Meetings
Authors: Raudenbush Brandon , Frost Chelsea , Okafor Richard , Chen Chongshu , Qui Xing , Mesfin Addisu
Published: June 2017

Study Design:

Observational study.

Objectives:

To determine the publication rate of podium presentations from the North American Spine Society (NASS) annual meetings from the years 2009 to 2011.

Methods:

In April 2015, a PubMed search was conducted using titles from the paper presentations as well as the authors. Of the search results that were found, the specific scientific journal in which the article was published was recorded. We analyzed further the top 4 destination journals and trends in publications in these journals over the study period. No study funding was obtained for this research, and there are no potential conflicts of interest or associated biases.

Results:

Over the study period, 671 paper presentations were available and 342 were published (51% publication rate). The highest publication rate was from the 2011 annual meeting, with 55.3%, and the lowest year was 2010, with a rate of 46.43%. Spine (32.75%), The Spine Journal (19.01%), Journal of Neurosurgery Spine (7.31%), and European Spine Journal (6.73%) were the top 4 destination journals. Over the study period, we found a significant decrease in publication rate in Spine ( P = .001) and a significant increase in publication rate in The Spine Journal ( P = .003). There were no significant difference in publication rate over the study period in Journal of Neurosurgery Spine ( P = .15) or European Spine Journal ( P = .23).

Conclusions:

This is the first study to our knowledge evaluating the publication rate of podium presentations from recent North American Spine Society annual meetings. We found an overall publication rate of 51%.
Black Women’s Recommendations for Developing Effective Type 2 Diabetes Programming
Authors: Hurt Tera R. , Seawell Asani H. , Cutrona Carolyn , O’Connor Margaret C. , Camp Randie D. , Duran Roxanne , Elderts Reid , Green Chrishelda , Hara Vanessa , Pattee Jenna
Published: June 2017

The purpose of this study was to learn from 29 Black women how to develop effective Type 2 diabetes programming. Three focus groups were held in Des Moines, Iowa, during fall 2012. Results highlighted themes related to diabetes knowledge, diabetes management and prevention, physical activity, diet, and diabetes management programming. Opinions were shared as to whether family members should be included in programs for supporting those diagnosed with diabetes. These results provided guidance and ideas to scholars and health care professionals aiming to improve effectiveness of diabetes programs for Black women and families.
Beyond Endemic Burkitt Lymphoma: Navigating Challenges of Differentiating Childhood Lymphoma Diagnoses Amid Limitations in Pathology Resources in Lilongwe, Malawi
Authors: El-Mallawany Nader Kim , Mutai Mercy , Mtete Idah , Gopal Satish , Stanley Christopher C. , Wasswa Peter , Mtunda Mary , Chasela Mary , Kamiyango William , Villiera Jimmy , Fedoriw Yuri , Montgomery Nathan D. , Liomba George N. , Kampani Coxcilly , Krysiak Robert , Westmoreland Katherine D. , Kim Maria H. , Slone Jeremy S. , Scheurer Michael E. , Allen Carl E. , Mehta Parth S. , Kazembe Peter N.
Published: June 2017

Background. Although Burkitt lymphoma (BL) is the most common childhood lymphoma in sub-Saharan Africa, Hodgkin lymphoma (HL) and other non-Hodgkin lymphomas occur. Diagnosing non-jaw mass presentations is challenging with limited pathology resources. Procedure. We retrospectively analyzed 114 pediatric lymphomas in Lilongwe, Malawi, from December 2011 to June 2013 and compared clinical versus pathology-based diagnoses over two time periods. Access to pathology resources became more consistent in 2013 compared with 2011-2012; pathology interpretations were based on morphology only. Results. Median age was 8.4 years (2.1-16.3). The most common anatomical sites of presentation were palpable abdominal mass 51%, peripheral lymphadenopathy 35%, and jaw mass 34%. There were 51% jaw masses among clinical diagnoses versus 11% in the pathology-based group ( P < .01), whereas 62% of pathology diagnoses involved peripheral lymphadenopathy versus 16% in the clinical group ( P < .01). The breakdown of clinical diagnoses included BL 85%, lymphoblastic lymphoma (LBL) 9%, HL 4%, and diffuse large B-cell lymphoma (DLBCL) 1%, whereas pathology-based diagnoses included HL 38%, BL 36%, LBL 15%, and DLBCL 11% ( P < .01). Lymphoma diagnosis was pathology confirmed in 19/66 patients (29%) in 2011-2012 and 28/48 (60%) in 2013 ( P < .01). The percentage of non-BL diagnoses was consistent across time periods (35%); however, 14/23 (61%) non-BL diagnoses were pathology confirmed in 2011-2012 versus 16/17 (94%) in 2013. Conclusions. Lymphomas other than Burkitt accounted for 35% of childhood lymphoma diagnoses. Over-reliance on clinical diagnosis for BL was a limitation, but confidence in non-BL diagnoses improved with time as pathology confirmation became standard. Increased awareness of non-BL lymphomas in equatorial Africa is warranted.
Safety evaluation of galacto-oligosaccharides
Authors: Zhou Yuting , Kruger Claire , Ravi GS , Kumar DP Santhosh , Vijayasarathi SK , Lavingia Mayuri , Chen Xiaoyan , Ambriz Pamela
Published: June 2017

Galacto-oligosaccharides (GOS) have been added to infant formulas and conventional foods as prebiotics all over the world. The present study was conducted to assess the subchronic toxicity of a GOS syrup (VITAGOS™) when administered orally by gavage daily at 0, 1020, 2041, and 4082 mg GOS syrup/kg/day to male and female Sprague-Dawley rats to deliver doses of 0, 500, 1000, and 2000 mg GOS/kg/day for 90 days. Throughout the entire treatment period, no abnormal clinical signs or mortalities were observed. Similarly, no test article-related toxicologically adverse findings were seen in body weight, feed consumption, ophthalmological findings, hematology, coagulation, clinical chemistry, urinalysis, organ weights, and gross pathology or histopathology. Significant increases in the cecum weight of males and females treated with 2000 mg GOS/kg/day were associated with mucosal hypertrophy/hyperplasia; no changes in the cecum were noted at lower doses. The organ weight and histopathological changes noted in the cecum are consistent with findings in rats administered other poorly digestible and fermentable substances; thus, this is considered to be an adaptive rather than toxic response. The No-Observed-Adverse-Effect-Levels for VITAGOS™ is 4082 mg GOS syrup/kg body weight/day or 2000 mg GOS/kg body weight/day.
Comment on “The experimental determination of hydromagnesite precipitation rates at 22.5– 75°C” by Berninger, U.-N., Jordan, G., Schott, J. and Oelkers, E.H.
Authors: Xiong Yongliang , Cetiner Ziya
Published: June 2017

In this work, we tested the equilibrium constant of hydromagnesite [Mg5(CO3)4(OH)2·4H2O] at 22.5°C proposed by Berninger et al. (2014) against field observations. By field observations we mean that analytical resultsoriginate from samples in the natural environment. In our test, we calculated saturation states of hydromagnesite, using the equilibrium constant of hydromagnesite at 22.5°C from Berninger et al., for the carbonate lakes in Qinghai-Xizang Plateau in China and for Salda Lake in Turkey,based on the hydrochemical data from literature. The predictions based on this equilibrium constant indicate that all of these lakes are strongly under-saturated with respect to hydromagnesite. However, hydromagnesite has been shown to form in all of these lakes. Therefore, this equilibrium constant is clearly in direct contradiction with field observations, leading to the conclusion that the equilibrium constant of hydromagnesite of Berninger et al. (2014) is not suitable for geochemical modelling.
Ethnicity, sex, and age are determinants of red blood cell storage and stress hemolysis: results of the REDS-III RBC-Omics study
Authors: Kanias Tamir , Lanteri Marion C. , Page Grier P. , Guo Yuelong , Endres Stacy M. , Stone Mars , Keating Sheila , Mast Alan E. , Cable Ritchard G. , Triulzi Darrell J. , Kiss Joseph E. , Murphy Edward L. , Kleinman Steve , Busch Michael P. , Gladwin Mark T.
Published: June 2017

Key Points

Genetic and biological variability in blood donors may impact RBC predisposition to hemolysis during cold storage and after transfusion. Male sex, Asian or African American racial background, and older age (>45 years) are significant modifiers of hemolysis.
Urban green and grey space in relation to respiratory health in children
Authors: Tischer Christina , Gascon Mireia , Fernández-Somoano Ana , Tardón Adonina , Lertxundi Materola Aitana , Ibarluzea Jesus , Ferrero Amparo , Estarlich Marisa , Cirach Marta , Vrijheid Martine , Fuertes Elaine , Dalmau-Bueno Albert , Nieuwenhuijsen Mark J. , Antó Josep M. , Sunyer Jordi , Dadvand Payam
Published: June 2017

We assessed the effect of three different indices of urban built environment on allergic and respiratory conditions.

This study involved 2472 children participating in the ongoing INMA birth cohort located in two bio-geographic regions (Euro-Siberian and Mediterranean) in Spain. Residential surrounding built environment was characterised as 1) residential surrounding greenness based on satellite-derived normalised difference vegetation index (NDVI), 2) residential proximity to green spaces and 3) residential surrounding greyness based on urban land use patterns. Information on wheezing, bronchitis, asthma and allergic rhinitis up to age 4 years was obtained from parent-completed questionnaires. Logistic regression and generalised estimating equation modelling were performed.

Among children from the Euro-Siberian region, higher residential surrounding greenness and higher proximity to green spaces were negatively associated with wheezing. In the Mediterranean region, higher residential proximity to green spaces was associated with a reduced risk for bronchitis. A higher amount of residential surrounding greyness was found to increase the risk for bronchitis in this region.

Associations between indices of urban residential greenness and greyness with respiratory diseases differ by region. The pathways underlying these associations require further exploration.
Predicting risk of undiagnosed COPD: development and validation of the TargetCOPD score
Authors: Haroon Shamil , Adab Peymane , Riley Richard D. , Fitzmaurice David , Jordan Rachel E.
Published: June 2017

Chronic obstructive pulmonary disease (COPD) is greatly underdiagnosed worldwide and more efficient methods of case-finding are required. We developed and externally validated a risk score to identify undiagnosed COPD using primary care records.

We conducted a retrospective cohort analysis of a pragmatic cluster randomised controlled case-finding trial in the West Midlands, UK. Participants aged 40–79 years with no prior diagnosis of COPD received a postal or opportunistic screening questionnaire. Those reporting chronic respiratory symptoms were assessed with spirometry. COPD was defined as presence of relevant symptoms with a post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal. A risk score was developed using logistic regression with variables available from electronic health records for 2398 participants who returned a postal questionnaire. This was externally validated among 1097 participants who returned an opportunistic questionnaire to derive the c-statistic, and the sensitivity and specificity of cut-points.

A risk score containing age, smoking status, dyspnoea, prescriptions of salbutamol and prescriptions of antibiotics discriminated between patients with and without undiagnosed COPD (c-statistic 0.74, 95% CI 0.68–0.80). A cut-point of ≥7.5% predicted risk had a sensitivity of 68.8% (95% CI 57.3–78.9%) and a specificity of 68.8% (95% CI 65.8.1–71.6%).

A novel risk score using routine data from primary care electronic health records can identify patients at high risk for undiagnosed symptomatic COPD. This score could be integrated with clinical information systems to help primary care clinicians target patients for case-finding.
Long-term volume-targeted pressure-controlled ventilation: sense or nonsense?
Authors: Arellano-Maric Maria Paola , Gregoretti Cesare , Duiverman Marieke , Windisch Wolfram
Published: June 2017

The technology underlying the development of novel ventilatory modes for long-term noninvasive ventilation of patients with chronic hypercapnia is continuously evolving. Volume-targeted pressure-controlled ventilation is a hybrid ventilation mode designed to combine the advantages of conventional ventilation modes, while avoiding their drawbacks. However, manufacturers have created different names and have patented algorithms and set-up variables, which can result in confusion for physicians and respiratory therapists. In addition, clear evidence for the superiority of this novel mode has not yet been established. These factors have most likely hindered more widespread use of this mode in clinical practice. The current review presents the rationale, working principles, characteristics and set-up recommendations associated with volume-targeted modes. In addition, it summarises the clinical and laboratory studies that have challenged this mode.
Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin–lysoPA axis in COPD
Authors: Naz Shama , Kolmert Johan , Yang Mingxing , Reinke Stacey N. , Kamleh Muhammad Anas , Snowden Stuart , Heyder Tina , Levänen Bettina , Erle David J. , Sköld C. Magnus , Wheelock Åsa M. , Wheelock Craig E.
Published: June 2017

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.

Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform.

Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung.

These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence.
PTH monitoring after total parathyroidectomy with forearm auto-transplantation: Potential for spuriously high levels from grafted forearm
Authors: Khalil Diana , Kerr Paul D.
Published: June 2017

Background

We have identified a cause of falsely elevated parathyroid hormone (PTH) levels after total parathyroidectomy with forearm auto-transplantation (TPT-ATx). Our cases highlight the need to draw PTH samples remotely, away from forearm graft sites, to ensure accurate levels.

Case presentations

We report on four patients who were referred to our surgical team at an academic tertiary care center for what was perceived to be recurrent hyperparathyroidism 2–5 years following total parathyroidectomy with auto-transplantation. Further evaluation revealed highly discrepant results in these patients depending on where the blood was drawn, with spuriously high levels in blood drawn from the grafted arm (Range 337–3885 ng/l), and much lower levels when blood was drawn remotely away from the graft site (Range 9–242 ng/l). The difference in PTH level between the grafted forearm and remote site for these patients ranged between 328 and 3643 ng/l. Over the period these cases were accrued (2008–2012), 89 patients underwent TPT-ATx in our institution. Therefore, our case report series suggests that this phenomenon will be evident to a clinically important extent in at least 4% of patients.

Conclusions

One can acquire spuriously high PTH levels from grafted forearms, leading to the false diagnosis of recurrent hyperparathyroidism. We recommend PTH levels be drawn remotely from graft sites to ensure accurate systemic levels are reflected.
Adipose tissue macrophages develop from bone marrow–independent progenitors in Xenopus laevis and mouse
Authors: Hassnain Waqas Syed F , Noble Anna , Hoang Anh C , Ampem Grace , Popp Manuela , Strauß Sarah , Guille Matthew , Röszer Tamás
Published: June 2017

ATMs have a metabolic impact in mammals as they contribute to metabolically harmful AT inflammation. The control of the ATM number may have therapeutic potential; however, information on ATM ontogeny is scarce. Whereas it is thought that ATMs develop from circulating monocytes, various tissue-resident Mϕs are capable of self-renewal and develop from BM-independent progenitors without a monocyte intermediate. Here, we show that amphibian AT contains self-renewing ATMs that populate the AT before the establishment of BM hematopoiesis. Xenopus ATMs develop from progenitors of aVBI. In the mouse, a significant amount of ATM develops from the yolk sac, the mammalian equivalent of aVBI. In summary, this study provides evidence for a prenatal origin of ATMs and shows that the study of amphibian ATMs can enhance the understanding of the role of the prenatal environment in ATM development.
Seismic imaging and statistical analysis of fault facies models
Authors: Kolyukhin Dmitriy R. , Lisitsa Vadim V. , Protasov Maxim I. , Qu Dongfang , Reshetova Galina V. , Tveranger Jan , Tcheverda Vladimir A. , Vishnevsky Dmitry M.
Published: June 2017

Interpretation of seismic responses from subsurface fault zones is hampered by the fact that the geologic structure and property distributions of fault zones can generally not be directly observed. This shortcoming curtails the use of seismic data for characterizing internal structure and properties of fault zones, and it has instead promoted the use of interpretation techniques that tend to simplify actual structural complexity by rendering faults as lines and planes rather than volumes of deformed rock. Facilitating the correlation of rock properties and seismic images of fault zones would enable active use of these images for interpreting fault zones, which in turn would improve our ability to assess the impact of fault zones on subsurface fluid flow. We use a combination of 3D fault zone models, based on empirical data and 2D forward seismic modeling to investigate the link between fault zone properties and seismic response. A comparison of spatial statistics from the geologic models and the seismic images was carried out to study how well seismic images render the modeled geologic features. Our results indicate the feasibility of extracting information about fault zone structure from seismic data by the methods used.
Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals
Authors: Rivera Margarita , Locke Adam E. , Corre Tanguy , Czamara Darina , Wolf Christiane , Ching-Lopez Ana , Milaneschi Yuri , Kloiber Stefan , Cohen-Woods Sara , Rucker James , Aitchison Katherine J. , Bergmann Sven , Boomsma Dorret I. , Craddock Nick , Gill Michael , Holsboer Florian , Hottenga Jouke-Jan , Korszun Ania , Kutalik Zoltan , Lucae Susanne , Maier Wolfgang , Mors Ole , Müller-Myhsok Bertram , Owen Michael J. , Penninx Brenda W. J. H. , Preisig Martin , Rice John , Rietschel Marcella , Tozzi Federica , Uher Rudolf , Vollenweider Peter , Waeber Gerard , Willemsen Gonneke , Craig Ian W. , Farmer Anne E. , Lewis Cathryn M. , Breen Gerome , McGuffin Peter
Published: June 2017

Background

Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.

Aims

To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.

Method

The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.

Results

In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.

Conclusions

This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
CD33 Splicing Polymorphism Determines Gemtuzumab Ozogamicin Response in De Novo Acute Myeloid Leukemia: Report From Randomized Phase III Children’s Oncology Group Trial AAML0531
Authors: Lamba Jatinder K. , Chauhan Lata , Shin Miyoung , Loken Michael R. , Pollard Jessica A. , Wang Yi-Cheng , Ries Rhonda E. , Aplenc Richard , Hirsch Betsy A. , Raimondi Susana C. , Walter Roland B. , Bernstein Irwin D. , Gamis Alan S. , Alonzo Todd A. , Meshinchi Soheil
Published: June 2017

Purpose

Gemtuzumab ozogamicin (GO), a CD33-targeted immunoconjugate, is a re-emerging therapy for acute myeloid leukemia (AML). CD33 single nucleotide polymorphism rs12459419 C>T in the splice enhancer region regulates the expression of an alternatively spliced CD33 isoform lacking exon2 (D2-CD33), thus eliminating the CD33 IgV domain, which is the antibody-binding site for GO, as well as diagnostic immunophenotypic panels. We aimed to determine the impact of the genotype of this splicing polymorphism in patients with AML treated with GO-containing chemotherapy.

Patients and Methods

CD33 splicing single nucleotide polymorphism was evaluated in newly diagnosed patients with AML randomly assigned to receive standard five-course chemotherapy alone (No-GO arm, n = 408) or chemotherapy with the addition of two doses of GO once during induction and once during intensification (GO arm, n = 408) as per the Children’s Oncology Group AAML0531 trial.

Results

The rs12459419 genotype was CC in 415 patients (51%), CT in 316 patients (39%), and TT in 85 patients (10%), with a minor allele frequency of 30%. The T allele was significantly associated with higher levels of D2-CD33 transcript ( P < 1.0E−6) and with lower diagnostic leukemic cell surface CD33 intensity ( P < 1.0E−6). Patients with the CC genotype had significantly lower relapse risk in the GO arm than in the No-GO arm (26% v 49%; P < .001). However, in patients with the CT or TT genotype, exposure to GO did not influence relapse risk (39% v 40%; P = .85). Disease-free survival was higher in patients with the CC genotype in the GO arm than in the No-GO arm (65% v 46%, respectively; P = .004), but this benefit of GO addition was not seen in patients with the CT or TT genotype.

Conclusion

Our results suggest that patients with the CC genotype for rs12459419 have a substantial response to GO, making this a potential biomarker for the selection of patients with a likelihood of significant response to GO.
Biomarker-Based Phase II Trial of Savolitinib in Patients With Advanced Papillary Renal Cell Cancer
Authors: Choueiri Toni K. , Plimack Elizabeth , Arkenau Hendrik-Tobias , Jonasch Eric , Heng Daniel Y.C. , Powles Thomas , Frigault Melanie M. , Clark Edwin A. , Handzel Amir A. , Gardner Humphrey , Morgan Shethah , Albiges Laurence , Pal Sumanta Kumar
Published: June 2017

Purpose

Patients with advanced papillary renal cell carcinoma (PRCC) have limited therapeutic options. PRCC may involve activation of the MET pathway, for example, through gene amplification or mutations. Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective MET tyrosine kinase inhibitor. We report results of a single-arm, multicenter, phase II study evaluating the safety and efficacy of savolitinib in patients with PRCC according to MET status.

Patients and Methods

Patients with histologically confirmed locally advanced or metastatic PRCC were enrolled and received savolitinib 600 mg orally once daily. MET-driven PRCC was defined as any of the following: chromosome 7 copy gain, focal MET or HGF gene amplification, or MET kinase domain mutations. Efficacy was assessed according to MET status. Safety, toxicity, and patient-reported health-related quality-of-life outcomes were assessed in all patients.

Results

Of 109 patients treated, PRCC was MET driven in 44 (40%) and MET independent in 46 (42%); MET status was unknown in 19 (17%). MET-driven PRCC was strongly associated with response; there were eight confirmed partial responders with MET-driven disease (18%), but none with MET-independent disease ( P = .002). Median progression-free survival for patients with MET-driven and MET-independent PRCC was 6.2 months (95% CI, 4.1 to 7.0 months) and 1.4 months (95% CI, 1.4 to 2.7 months), respectively (hazard ratio, 0.33; 95% CI, 0.20 to 0.52; log-rank P < .001). The most frequent adverse events associated with savolitinib were nausea, fatigue, vomiting, and peripheral edema.

Conclusion

These data show activity and tolerability of savolitinib in the subgroup of patients with MET-driven PRCC. Furthermore, molecular characterization of MET status was more predictive of response to savolitinib than a classification based on pathology. These findings justify investigating savolitinib in MET-driven PRCC.