bluuebunny/crossref_metadata_2025 huggingface dataset:
How to make a 350-m-thick lowstand systems tract in 17,000 years: The Late Pleistocene Po River (Italy) lowstand wedge
Authors: Pellegrini Claudio , Maselli Vittorio , Gamberi Fabiano , Asioli Alessandra , Bohacs Kevin M. , Drexler Tina M. , Trincardi Fabio
Published: February 2017

The 350-m-thick succession of the Po River lowstand wedge (Italy) associated with the Last Glacial Maximum (deposited over ∼17 k.y) contains stratal architecture at a physical scale commonly attributed to much longer time scales, with complex, systematically varying internal clinothem characteristics. This study investigated clinothem stacking patterns and controls through the integration of seismic reflection data with sediment attributes, micropaleontology, regional climate, eustacy, and high-resolution age control possible only in Quaternary sequences. Three clinothem types are differentiated based on topset geometry, shelf-edge and onlap-point trajectory, internal seismic facies, and interpreted bottomset deposits: type A has moderate topset aggradation, ascending shelf-edge trajectory, and mass-transport bottomset deposits; type B has eroded topset, descending shelf-edge trajectory, and bottomset distributary channel-lobe complexes; and type C has maximal topset aggradation, ascending shelf-edge trajectory, and concordant bottomsets. Type A and C clinothems exhibit reduced sediment bypass and delivery to the basin, whereas type B clinothems are associated with short intervals of increased sediment export from the shelf to deeper water. Clinothems individually span a range of 0.4–4.7 k.y., contemporaneous with significant eustatic and climate changes, but their stacking patterns resemble those found in ancient successions and ascribed to significantly longer durations, indicating that (1) the response time of ancient continental margin–scale systems to high-frequency variations in accommodation and sediment supply could be as short as centuries, (2) even millennial- to centennial-scale stratal units can record substantial influence of allogenic controls, and (3) sandy deposits can be compartmentalized even in a short-duration lowstand systems tract.
Approaching confidentiality at a familial level in genomic medicine: a focus group study with healthcare professionals
Authors: Dheensa Sandi , Fenwick Angela , Lucassen Anneke
Published: February 2017

Objectives

Clinical genetics guidelines from 2011 conceptualise genetic information as confidential to families, not individuals. The normative consequence of this is that the family's interest is the primary consideration and genetic information is shared unless there are good reasons not to do so. We investigated healthcare professionals' (HCPs') views about, and reasoning around, individual and familial approaches to confidentiality and how such views influenced their practice.

Method

16 focus groups with 80 HCPs working in/with clinical genetics services were analysed, drawing on grounded theory.

Results

Participants raised seven problems with, and arguments against, going beyond the individual approach to confidentiality. These problems fell into two overlapping categories: ‘relationships’ and ‘structures’. Most participants had never considered ways to—or thought it was impossible to—treat familial genetic information and personal information differently. They worried that putting the familial approach into practice could disrupt family dynamics and erode patient trust in the health service. They also thought they had insufficient resources to share information and feared that sharing might change the standard of care and make them more vulnerable to liability.

Conclusions

A familial approach to confidentiality has not been accepted or adopted as a standard, but wider research suggests that some of the problems HCPs perceived are surmountable and sharing in the interest of the family can be achieved. However, further research is needed to explore how personal and familial genetic information can be separated in practice. Our findings are relevant to HCPs across health services who are starting to use genome tests as part of their routine investigations.
Effects of pulmonary rehabilitation in lung transplant candidates: a systematic review
Authors: Hoffman Mariana , Chaves Gabriela , Ribeiro-Samora Giane Amorim , Britto Raquel Rodrigues , Parreira Verônica Franco
Published: February 2017

Objectives

The aim of this systematic review of randomised controlled trials (RCTs), and quasi-experimental and retrospective studies is to investigate the effects of pulmonary rehabilitation (PR) in patients with advanced chronic disease on the waiting list for lung transplantation.

Setting

PR performed for inpatient or outpatient lung transplant candidates.

Intervention

PR programme including aerobic exercise training and/or resistance exercise training.

Primary and secondary outcomes

Quality of life and exercise capacity (primary outcomes). Survival rate after transplant surgery; pulmonary function; respiratory muscle strength; psychological aspects; upper and lower extremity muscle strength and adverse effects (secondary outcomes). Two review authors independently selected the studies, assessed study quality and extracted data. Studies in any language were included.

Results

This was a systematic review and studies were searched on the Cochrane Library, MEDLINE, EMBASE, CINAHL and PEDro. Experimental and retrospective studies evaluating the effects of PR in candidates for lung transplantation (>18 years old) with any lung diseases were included. 2 RCTs, and two quasi-experimental and two retrospectives studies, involving 1305 participants were included in the review. 5 studies included an enhancement reported in quality of life using the Short Form 36 questionnaire and showed improvements in some domains. All studies included exercise capacity evaluated through 6 min walk test and in five of them, there were improvements in this outcome after PR. Owing to the different characteristics of the studies, it was not possible to perform a meta-analysis.

Conclusions

Studies included in this review showed that PR is an effective treatment option for patients on the waiting list for lung transplantation and can improve quality of life and exercise capacity in those patients. Although individual studies reported positive effects of PR, this review shows that there is a need for more studies of a high methodological quality addressing PR effects in lung transplant candidates.

Trial registration number

PROSPERO CDR42015025110.
Ranitidine: forgotten drug of delayed gastric emptying
Authors: Veevers Abbie E , Oxberry Stephen G
Published: February 2017

Delayed gastric emptying in the presence or absence of mechanical bowel obstruction can cause distressing symptoms in palliative care patients. We present two patients, both with vomiting due to delayed gastric emptying and gastric outlet obstruction secondary to pancreatic cancer, treated with subcutaneous ranitidine resulting in a symptomatic response. We hypothesise that ranitidine is a useful adjunct to standard treatment with prokinetic agents or octreotide in such patients and potentially those with proximal mechanical bowel obstruction from other malignancies with associated delayed gastric emptying.
The edges of the wedges: a systematic approach to trap definition and risking for stratigraphic, combination and sub-unconformity traps
Authors: Stirling Eleanor J. , Fugelli Edith M. G. , Thompson Mark
Published: February 2017

In recent years, stratigraphic and combination traps such as Buzzard (UK North Sea) and Jubilee (Ghana) have attracted much industry attention. Such trap types are generally considered higher risk than structural traps, and understanding them represents a challenge for explorers, as numerous less successful (often amplitude-driven) attempts have demonstrated. Owing to their perceived high risk, stratigraphic traps are often drilled late in a basin's exploration history; however, we assert that consideration of stratigraphic traps should be part of any frontier exploration programme because they occur in all basin types and depositional settings, and allow new plays to be opened up. Additionally, stratigraphic, combination and sub-unconformity traps offer the chance to rejuvenate exploration in mature basins, as recent discoveries like the Edvard Grieg Field (Norwegian North Sea) have shown.

Focusing on clastic systems, and using a combination of seismic examples and models, we present two aspects of stratigraphic trap exploration: (1) the regional and local factors that favour the development of stratigraphic trap edges; and (2) a systematic method for defining and risking the trap edges, avoiding the common problem of over-risking. These two methods, used together and applied consistently, allow explorers to focus on the right area of a basin and to risk stratigraphic traps appropriately, for a fair comparison with structural traps.
Temozolomide in the Era of Precision Medicine
Authors: Thomas Anish , Tanaka Mamoru , Trepel Jane , Reinhold William C. , Rajapakse Vinodh N. , Pommier Yves
Published: February 2017

In the January 1, 2017, issue of Cancer Research, Nagel and colleagues demonstrate the value of assays that determine the DNA repair capacity of cancers in predicting response to temozolomide. Using a fluorescence-based multiplex flow cytometric host cell reactivation assay that provides simultaneous readout of DNA repair capacity across multiple pathways, they show that the multivariate drug response models derived from cell line data were applicable to patient-derived xenograft models of glioblastoma. In this commentary, we first outline the mechanism of activity and current clinical application of temozolomide, which, until now, has been largely limited to glioblastoma. Given the challenges of clinical application of functional assays, we argue that functional readouts be approximated by genomic signatures. In this context, a combination of MGMT activity and mismatch repair (MMR) status of the tumor are important parameters that determine sensitivity to temozolomide. More reliable methods are needed to determine MGMT activity as DNA methylation, the current standard, does not accurately reflect the expression of MGMT. Also, genomics for MMR are warranted. Furthermore, based on patterns of MGMT expression across different solid tumors, we make a case for revisiting temozolomide use in a broader spectrum of cancers based on our current understanding of its molecular basis of activity. Cancer Res; 77(4); 823–6. ©2017 AACR.
Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study
Authors: Ramanathan Ramesh K. , Korn Ronald L. , Raghunand Natarajan , Sachdev Jasgit C. , Newbold Ronald G. , Jameson Gayle , Fetterly Gerald J. , Prey Joshua , Klinz Stephan G. , Kim Jaeyeon , Cain Jason , Hendriks Bart S. , Drummond Daryl C. , Bayever Eliel , Fitzgerald Jonathan B.
Published: February 2017

Purpose: To determine whether deposition characteristics of ferumoxytol (FMX) iron nanoparticles in tumors, identified by quantitative MRI, may predict tumor lesion response to nanoliposomal irinotecan (nal-IRI).

Experimental Design: Eligible patients with previously treated solid tumors had FMX-MRI scans before and following (1, 24, and 72 hours) FMX injection. After MRI acquisition, R2* signal was used to calculate FMX levels in plasma, reference tissue, and tumor lesions by comparison with a phantom-based standard curve. Patients then received nal-IRI (70 mg/m2 free base strength) biweekly until progression. Two percutaneous core biopsies were collected from selected tumor lesions 72 hours after FMX or nal-IRI.

Results: Iron particle levels were quantified by FMX-MRI in plasma, reference tissues, and tumor lesions in 13 of 15 eligible patients. On the basis of a mechanistic pharmacokinetic model, tissue permeability to FMX correlated with early FMX-MRI signals at 1 and 24 hours, while FMX tissue binding contributed at 72 hours. Higher FMX levels (ranked relative to median value of multiple evaluable lesions from 9 patients) were significantly associated with reduction in lesion size by RECIST v1.1 at early time points (P < 0.001 at 1 hour and P < 0.003 at 24 hours FMX-MRI, one-way ANOVA). No association was observed with post-FMX levels at 72 hours. Irinotecan drug levels in lesions correlated with patient's time on treatment (Spearman ρ = 0.7824; P = 0.0016).

Conclusions: Correlation between FMX levels in tumor lesions and nal-IRI activity suggests that lesion permeability to FMX and subsequent tumor uptake may be a useful noninvasive and predictive biomarker for nal-IRI response in patients with solid tumors. Clin Cancer Res; 23(14); 3638–48. ©2017 AACR.
Bevacizumab May Differentially Improve Ovarian Cancer Outcome in Patients with Proliferative and Mesenchymal Molecular Subtypes
Authors: Kommoss Stefan , Winterhoff Boris , Oberg Ann L. , Konecny Gottfried E. , Wang Chen , Riska Shaun M. , Fan Jian-Bing , Maurer Matthew J. , April Craig , Shridhar Viji , Kommoss Friedrich , du Bois Andreas , Hilpert Felix , Mahner Sven , Baumann Klaus , Schroeder Willibald , Burges Alexander , Canzler Ulrich , Chien Jeremy , Embleton Andrew C. , Parmar Mahesh , Kaplan Richard , Perren Timothy , Hartmann Lynn C. , Goode Ellen L. , Dowdy Sean C. , Pfisterer Jacobus
Published: February 2017

Purpose: Recent progress in understanding the molecular biology of epithelial ovarian cancer has not yet translated into individualized treatment for these women or improvements in their disease outcome. Gene expression has been utilized to identify distinct molecular subtypes, but there have been no reports investigating whether or not molecular subtyping is predictive of response to bevacizumab in ovarian cancer.

Experimental Design: DASL gene expression arrays were performed on FFPE tissue from patients enrolled on the ICON7 trial. Patients were stratified into four TCGA molecular subtypes. Associations between molecular subtype and the efficacy of randomly assigned therapy with bevacizumab were assessed.

Results: Molecular subtypes were assigned as follows: 122 immunoreactive (34%), 96 proliferative (27%), 73 differentiated (20%), and 68 mesenchymal (19%). In univariate analysis patients with tumors of proliferative subtype obtained the greatest benefit from bevacizumab with a median PFS improvement of 10.1 months [HR, 0.55 (95% CI, 0.34–0.90), P = 0.016]. For the mesenchymal subtype, bevacizumab conferred a nonsignificant improvement in PFS of 8.2 months [HR 0.78 (95% CI, 0.44–1.40), P = 0.41]. Bevacizumab conferred modest improvements in PFS for patients with immunoreactive subtype (3.8 months; P = 0.08) or differentiated subtype (3.7 months; P = 0.61). Multivariate analysis demonstrated significant PFS improvement in proliferative subtype patients only [HR, 0.45 (95% CI, 0.27–0.74), P = 0.0015].

Conclusions: Ovarian carcinoma molecular subtypes with the poorest survival (proliferative and mesenchymal) derive a comparably greater benefit from treatment that includes bevacizumab. Validation of our findings in an independent cohort could enable the use of bevacizumab for those patients most likely to benefit, thereby reducing side effects and healthcare cost. Clin Cancer Res; 23(14); 3794–801. ©2017 AACR.
Healthcare Resource Availability, Quality of Care, and Acute Ischemic Stroke Outcomes
Authors: O'Brien Emily C. , Wu Jingjing , Zhao Xin , Schulte Phillip J. , Fonarow Gregg C. , Hernandez Adrian F. , Schwamm Lee H. , Peterson Eric D. , Bhatt Deepak L. , Smith Eric E.
Published: February 2017

Background

Healthcare resources vary geographically, but associations between hospital‐based resources and acute stroke quality and outcomes remain unclear.

Methods and Results

Using Get With The Guidelines‐Stroke and Dartmouth Atlas of Health Care data, we examined associations between healthcare resource availability, stroke care, and outcomes. We categorized hospital referral regions with high‐, medium‐, or low‐resource levels based on the 2006 national per‐capita availability median of 6 relevant acute stroke care resources. Using multivariable logistic regression, we examined healthcare resource level and in‐hospital quality and outcomes. Of 1 480 308 admitted ischemic stroke patients (2006–2013), 28.8% were hospitalized in low‐, 44.4% in medium‐, and 26.9% in high‐resource hospital referral regions. Quality‐of‐care/timeliness metrics, adjusted length of stay, and in‐hospital mortality were similar across all resource levels.

Conclusions

Significant variation exists in regional availability of healthcare resources for acute ischemic stroke treatment, yet among Get With the Guidelines‐Stroke hospitals, quality of care and in‐hospital outcomes did not differ by regional resource availability.
Novel Thrombolytic Drug Based on Thrombin Cleavable Microplasminogen Coupled to a Single‐Chain Antibody Specific for Activated GPIIb/IIIa
Authors: Bonnard Thomas , Tennant Zachary , Niego Be'Eri , Kanojia Ruchi , Alt Karen , Jagdale Shweta , Law Lok Soon , Rigby Sheena , Medcalf Robert Lindsay , Peter Karlheinz , Hagemeyer Christoph Eugen
Published: February 2017

Background

Thrombolytic therapy for acute thrombosis is limited by life‐threatening side effects such as major bleeding and neurotoxicity. New treatment options with enhanced fibrinolytic potential are therefore required. Here, we report the development of a new thrombolytic molecule that exploits key features of thrombosis. We designed a recombinant microplasminogen modified to be activated by the prothrombotic serine‐protease thrombin (HtPlg), fused to an activation‐specific anti–glycoprotein IIb/
III
a single‐chain antibody (
SCE
5), thereby hijacking the coagulation system to initiate thrombolysis.

Methods and Results

The resulting fusion protein named
SCE
5‐HtPlg shows in vitro targeting towards the highly abundant activated form of the fibrinogen receptor glycoprotein IIb/
III
a expressed on activated human platelets. Following thrombin formation,
SCE
5‐HtPlg is activated to contain active microplasmin. We evaluate the effectiveness of our targeted thrombolytic construct in two models of thromboembolic disease. Administration of
SCE
5‐HtPlg (4 μg/g body weight) resulted in effective thrombolysis 20 minutes after injection in a ferric chloride–induced model of mesenteric thrombosis (48±3% versus 92±5% for saline control,
P
<0.01) and also reduced emboli formation in a model of pulmonary embolism (
P
<0.01 versus saline). Furthermore, at these effective therapeutic doses, the
SCE
5‐HtPlg did not prolong bleeding time compared with saline (
P
=0.99).

Conclusions

Our novel fusion molecule is a potent and effective treatment for thrombosis that enables in vivo thrombolysis without bleeding time prolongation. The activation of this construct by thrombin generated within the clot itself rather than by a plasminogen activator, which needs to be delivered systemically, provides a novel targeted approach to improve thrombolysis.
Randomized Trial of Compression Duration After Transradial Cardiac Catheterization and Intervention
Authors: Lavi Shahar , Cheema Asim , Yadegari Andrew , Israeli Zeev , Levi Yaniv , Wall Sabrina , Alemayehu Mistre , Parviz Yasir , Murariu Bogdan‐Dorian , McPherson Terry , Syed Jaffer , Bagur Rodrigo
Published: February 2017

Background

Radial artery occlusion is a known complication following transradial cardiac catheterization. A shorter duration of postprocedural radial clamp time may reduce radial artery occlusion (
RAO
) but might be associated with incomplete hemostasis.

Methods and Results

In total, 568 patients undergoing transradial diagnostic cardiac catheterization were randomly assigned to either 20 minutes (ultrashort) or 60 minutes (short) hemostatic compression time using patent hemostasis. Subsequently, clamp pressure was reduced gradually over 20 minutes. Access site hemostasis and
RAO
were assessed after clamp removal. Repeated assessment of
RAO
was determined at 1 week in 210 (37%) patients. Mean age was 64±11 years, and 30% were female. Percutaneous coronary intervention was performed in 161 patients.
RAO
immediately after clamp removal was documented in 14 (4.9%) and 8 (2.8%) patients in the 20‐ and 60‐minute clamp application groups, respectively (
P
=0.19). The incidence of grade 1 hematoma was higher in the 20‐minute group (6.7% versus 2.5%,
P
=0.015).
RAO
at 1 week after the procedure was 2.9% and 0.9% in the 20‐ and 60‐minute groups, respectively (
P
=0.36). Requirement for clamp retightening (36% versus 16%,
P
=0.01) was higher among patients who had
RAO
. Need for clamp retightening was the only independent predictor of
RAO
(
P
=0.04).

Conclusions

Ultrashort radial clamp application of 20 minutes is not preferable to a short duration of 60 minutes. The 60‐minute clamp duration is safe and provides good access site hemostasis with low
RAO
rates.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02269722.
‘The skies the limit!’
Authors: Fox Sarah Jane , Ismail Rosida
Published: February 2017

Although legal practitioners recognise the terminology ‘open skies’ there is no one accepted definition. The principle aim maybe the same, namely ‘to democratise aviation’ but interpretation and practice translates through into variances and divisions as to how liberal nations are willing to be. This paper explores the concept and development of ‘open-skies’ with the intention of questioning whether this hypothesis is a realistic and an accomplishable objective.

This paper commences with a relevant-contextualised, historical exploration of open-skies agreements. The development of the us and eu are analysed before the research discusses the on-going developments in terms of the ‘potential’ of, and ‘difficulties’ in, realising asean-eu and asean-us open skies agreement.

The findings show the challenges and successes within the global aviation sector as viewed from this triangulated approach, and the conclusion drawn is that there remains impediments which will be difficult to overcome.
Socially Inclusive Teaching
Authors: Gale Trevor , Mills Carmen , Cross Russell
Published: February 2017

Like other western nations such as the United States and the United Kingdom, Australia’s record of education outcomes for marginalized groups is troubling, whether the comparisons are made within the nation or with other OECD nations. Although recent Australian Governments have sought to overhaul funding for schools and universities, on their own, more resources for educational institutions are not enough to redress problems of disadvantage and to achieve social justice. Also required is a focus on the pedagogic work (PW) of teachers and, by implication, their teacher educators. Central to this article is the argument that pedagogy is the most strategic place to begin this work because of its location as a central message system in education. In this article we conceive of PW as comprising of belief, design, and action. From these are derived three principles on which to build a socially inclusive pedagogy that creates opportunities for all students, whatever their circumstances, to participate more fully in education. Our focus on advancing a conceptual understanding of socially inclusive pedagogy is informed by a theory and politics of transformation, which seek to engage with the deep structures that generate injustice within schools and teacher education.
Adapting to sensing and actuation variations in multi-robot coverage
Authors: Pierson Alyssa , Figueiredo Lucas C , Pimenta Luciano CA , Schwager Mac
Published: February 2017

This article considers the problem of multi-robot coverage control, where a group of robots has to spread out over an environment to provide coverage. We propose a new approach for a group of robots carrying out this collaborative task that will adapt online to performance variations among the robots. Two types of performance variations are considered: variations in sensing performance (e.g. differences in sensor types, calibration, or noise), and variations in actuation (e.g. differences in terrain, vehicle types, or lossy motors). The robots have no prior knowledge of the relative strengths of their performance compared to the others in the team. We present an algorithm that learns the relative performance variations among the robots online, in a distributed fashion, and automatically compensates by assigning the weak robots a smaller portion of the environment and the strong robots a larger portion. Using a Lyapunov-type proof, we show that the robots converge to a locally optimal coverage configuration. The algorithm is also demonstrated in both MATLAB simulations and experiments with Pololu m3pi ground robots.
The fiscal politics of welfare state expansion: The case of social insurance in Israel
Authors: Koreh Michal
Published: February 2017

Through a new perspective that draws on the theoretical insights of Fiscal Sociology, the article explores the role of fiscal imperatives for periods of welfare state expansion. By tracing the process of social insurance (SI) financing decisions in the early 1970s, a critical juncture in the development of the Israeli welfare state, the article challenges the implicit assumption in the literature that SI financing is solely aimed at covering the costs of its programmes. The findings show that SI contributions can be driven by ‘nonsocial’ motives related to the state’s broader fiscal concerns. Furthermore, and in contrast to the tendency to associate fiscal imperatives with retrenchment policies and austerity, the article shows that fiscal relations between the state and its SI system can have also positive effects on the welfare state, leading to new entitlements and increased expenditures.
Facing forwards, looking backwards: Coming to terms with continuing uneven development in Europe
Authors: Hudson Ray
Published: February 2017

At a time of major changes in the geography of the global economy, and following the major financial and economic crises of 2007/2008, the European Union (EU) is marked by deepening uneven economic development, between and within the territories of its 28 (for now) member states. This is one expression of neo-liberalisation as the dominant political force in the EU, combined with deep austerity policies in response to the crises of 2007/2008. Within the Eurozone, a common currency without a common fiscal policy further intensified inequalities, especially between the economies of the north and south of the EU. These developments had profound political ramifications as the promise of increasing economic growth and material well-being has been rudely shattered for many people and unemployment, poverty and ill-being have burgeoned in many parts of the EU. The political response to this – in ways reminiscent of the 1930s – has been a resurgence of regressive virulent right-wing nationalisms, sometimes with fascistic tendencies, as people have come to see the EU, and neoliberal globalisation, as inimical to their interests. This tendency has been further intensified by inflows of migrants and refugees, many in response to neo-imperialist ventures in the Middle East. This is most starkly (so far) the case in the UK, leading to the British Exit from the European Community (BREXIT) vote to leave the EU. There are counter-tendencies, locally based political movements that espouse a more humane social democratic model of the EU, but there seems little chance of these cohering politically to challenge the dominant view.
Social capital and cannabis supply
Authors: Scott John G , Grigg Jodie , Barratt Monica , Lenton Simon
Published: February 2017

The distribution of cannabis in Australia is examined with reference to motivations for supplying drugs. We argue that the distribution of cannabis in Australia is best understood with reference to the concept of social supply, where a supplier, not considered to be a ‘drug dealer proper’, brokers, facilitates or sells drugs, for little or no financial gain to friends and acquaintances. The article draws on data from surveys and interviews with 200 young Australian cannabis users, almost all of whom had also supplied cannabis at some point in their lifetime. We further theorise the concept of social supply with reference to social capital. We argue that a sociological understanding of drug distribution should focus on drug communities, as opposed to markets, describing the features of social organisation that exist between people within social networks and related implications that such features might have in terms of social harm and well-being.
First names and social distinction: Middle-class naming practices in Australia
Authors: Lindsay Jo , Dempsey Deborah
Published: February 2017

Naming practices provide a novel way to explore contemporary gender and class processes in Australia. Names are important everyday symbols of social location and signify family history, gender, class, ethnicity and religion. In an individualised society a name is the ultimate personal ‘brand’ and is used to locate children in social space. In this article we draw on qualitative interviews with 41 parents to focus on class and gender distinctions in naming practices. Naming a child was considered to be an important responsibility and names were viewed as central to identity and social classification. Through our exploration of naming preferences and judgements by middle-class parents, contemporary processes of social distinction come to light. Discussion of name choices illustrated parental aspirations and fears and the drawing of symbolic class-, gender- and sexuality-based cultural boundaries in Australia.
Myeloproliferative neoplasm stem cells
Authors: Mead Adam J. , Mullally Ann
Published: February 2017

Myeloproliferative neoplasms (MPNs) arise in the hematopoietic stem cell (HSC) compartment as a result of the acquisition of somatic mutations in a single HSC that provides a selective advantage to mutant HSC over normal HSC and promotes myeloid differentiation to engender a myeloproliferative phenotype. This population of somatically mutated HSC, which initiates and sustains MPNs, is termed MPN stem cells. In >95% of cases, mutations that drive the development of an MPN phenotype occur in a mutually exclusive manner in 1 of 3 genes: JAK2, CALR, or MPL. The thrombopoietin receptor, MPL, is the key cytokine receptor in MPN development, and these mutations all activate MPL-JAK-STAT signaling in MPN stem cells. Despite common biological features, MPNs display diverse disease phenotypes as a result of both constitutional and acquired factors that influence MPN stem cells, and likely also as a result of heterogeneity in the HSC in which MPN-initiating mutations arise. As the MPN clone expands, it exerts cell-extrinsic effects on components of the bone marrow niche that can favor the survival and expansion of MPN stem cells over normal HSC, further sustaining and driving malignant hematopoiesis. Although developed as targeted therapies for MPNs, current JAK2 inhibitors do not preferentially target MPN stem cells, and as a result, rarely induce molecular remissions in MPN patients. As the understanding of the molecular mechanisms underlying the clonal dominance of MPN stem cells advances, this will help facilitate the development of therapies that preferentially target MPN stem cells over normal HSC.
Renal safety of lithium in HIV-infected patients established on tenofovir disoproxil fumarate containing antiretroviral therapy: analysis from a randomized placebo-controlled trial
Authors: Decloedt Eric H. , Lesosky Maia , Maartens Gary , Joska John A.
Published: February 2017

Background

The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination.

Objective

We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment.

Methods

We included HIV-infected adults with cognitive impairment established on ART for at least 6 months with a suppressed viral load attending public sector ART clinics in Cape Town, South Africa. We excluded participants with an eGFR <60 mL/min and treated with medications predisposing to lithium toxicity. We reviewed participants weekly for the first month for adverse events followed by 4 weekly visits for renal function assessment, adverse event monitoring and adherence. Lithium dose was titrated to achieve the maintenance target plasma concentration of between 0.6 and 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo.

Results

We included 23 participants allocated to the lithium arm and 30 participants allocated to the placebo arm. Baseline characteristics were not statistically different with a mean age of 37.7 and 40.8 years, a median time on ART of 33 and 40 months and an eGFR of 139.3 and 131.0 mL/min in the lithium and placebo arms respectively. There was no statistical significant difference in the reduction in eGFR or increase in potassium between the two arms during the 24 weeks.

Conclusions

We found that 24-week treatment of HIV-infected patients with lithium and TDF did not result in increased nephrotoxicity.

Trial registration The study was registered on the Pan African Clinical Trials Registry (PACTR) with the identifier number PACTR201310000635418. Registered 11 October 2013 before the first participant was enrolled
Plug‐in‐Gait calculation of the knee adduction moment in people with knee osteoarthritis during shod walking: comparison of two different foot marker models
Authors: Paterson Kade L. , Hinman Rana S. , Metcalf Ben R. , Bennell Kim L. , Wrigley Tim V.
Published: February 2017

Background

Understanding how kinematic multi‐segment foot modelling influences the utility of Plug‐in‐Gait calculations of the knee adduction moment (KAM) during shod walking is relevant to knee osteoarthritis (OA). Multi‐segment foot markers placed on the skin through windows cut in to the shoe provide a more accurate representation of foot mechanics than the traditional marker set used by Plug‐in‐Gait, which uses fewer markers, placed on the shoe itself. We aimed to investigate whether Plug‐in‐Gait calculation of the KAM differed when using a kinematic multi‐segment foot model compared to the traditional Plug‐in‐Gait marker set.

Methods

Twenty people with medial knee OA underwent gait analysis in two test conditions: i) Plug‐in‐Gait model with its two standard foot markers placed on the shoes and; ii) Plug‐in‐Gait with the heel marker virtualised from a modified‐Oxford Foot Model where 8 ft markers were placed on the skin through windows cut in shoe uppers. Outcomes were the peak KAM, KAM impulse and other knee kinetic and kinematic variables.

Results

There were no differences (P > 0.05) in any gait variables between conditions. Excellent agreement was found for all outcome variables, with high correlations (r > 0.88‐0.99, P < 0.001), narrow limits of agreement and no proportional bias (R2 = 0.03–0.14, P > 0.05). The mean difference and 95% confidence intervals for peak KAM were also within the minimal detectable change range demonstrating equivalence.

Conclusions

Plug‐in‐Gait calculations of the KAM are not altered when using a kinematic multi‐segment foot marker model with skin markers placed through windows cut in to the shoe, instead of the traditional marker set placed on top of shoes. Researchers may be confident that applying either foot model does not change the calculation of the KAM using Plug‐in‐Gait.
Lariat capping as a tool to manipulate the 5′ end of individual yeast mRNA species in vivo
Authors: Krogh Nicolai , Pietschmann Max , Schmid Manfred , Jensen Torben Heick , Nielsen Henrik
Published: February 2017

The 5′ cap structure of eukaryotic mRNA is critical for its processing, transport, translation, and stability. The many functions of the cap and the fact that most, if not all, mRNA carries the same type of cap makes it difficult to analyze cap function in vivo at individual steps of gene expression. We have used the lariat capping ribozyme (LCrz) from the myxomycete Didymium to replace the mRNA m7G cap of a single reporter mRNA species with a tiny lariat in which the first and the third nucleotide are joined by a 2′, 5′ phosphodiester bond. We show that the ribozyme functions in vivo in the budding yeast Saccharomyces cerevisiae presumably without cofactors and that lariat capping occurs cotranscriptionally. The lariat-capped reporter mRNA is efficiently exported to the cytoplasm where it is found to be oligoadenylated and evenly distributed. Both the oligoadenylated form and a lariat-capped mRNA with a templated poly(A) tail translates poorly, underlining the critical importance of the m7G cap in translation. Finally, the lariat-capped RNA exhibits a threefold longer half-life compared to its m7G-capped counterpart, consistent with a key role for the m7G cap in mRNA turnover. Our study emphasizes important activities of the m7G cap and suggests new utilities of lariat capping as a molecular tool in vivo.
Acute Kidney Injury in Patients Treated with Vancomycin and Piperacillin‐Tazobactam: A Retrospective Cohort Analysis
Authors: Rutter W. Cliff , Burgess Donna R. , Talbert Jeffery C. , Burgess David S.
Published: February 2017

BACKGROUND

Empiric antimicrobial therapy often consists of the combination of gram‐positive coverage with vancomycin (VAN) and gram‐negative coverage, specifically an antipseudomonal beta‐lactam such as piperacillin‐tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports show higher nephrotoxicity rates among patients treated with the combination of VAN and PTZ.

OBJECTIVE

This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI) compared to VAN and PTZ monotherapies.

DESIGN, SETTING, AND PATIENTS

This is a retrospective cohort analysis of adult patients without renal disease receiving VAN, PTZ, or the combination from September 1, 2010 through August 31, 2014 at an academic medical center.

MEASUREMENTS

The primary outcome was AKI incidence as defined by the Risk, Injury, Failure, Loss, End‐stage (RIFLE) criteria.

METHODS

Continuous and categorical variables were assessed with appropriate tests. Univariate and multivariate logistic regressions were performed to assess for associations between variables and AKI incidence. Subanalyses based on severity of illness were performed.

RESULTS

Overall, 11,650 patients were analyzed, with 1647 (14.1%) developing AKI. AKI was significantly more frequent in the VAN/PTZ group (21%) compared to either monotherapy group (VAN 8.3%, PTZ 7.8%, P < 0.001 for both). Combination therapy was independently associated with higher AKI odds compared to monotherapy with either agent (adjusted odds ratio [aOR], 2.03; 95% confidence interval [CI], 1.74‐2.39; aOR, 2.31; 95% CI, 1.97‐2.71, for VAN and PTZ, respectively). Receipt of concomitant nephrotoxic drugs was independently associated with increased AKI rates, as were increased duration of therapy, hospital length of stay, increasing severity of illness, and increasing baseline renal function.

CONCLUSIONS

In this study of more than 10,000 patients, VAN combined with PTZ was associated with twice the odds of AKI development compared to either agent as monotherapy. This demonstrates the need for judicious use of combination empiric therapy.
Screening for Depression in Hospitalized Medical Patients
Authors: IsHak Waguih William , Collison Katherine , Danovitch Itai , Shek Lili , Kharazi Payam , Kim Tae , Jaffer Karim Y. , Naghdechi Lancer , Lopez Enrique , Nuckols Teryl
Published: February 2017

Depression among hospitalized patients is often unrecognized, undiagnosed, and therefore untreated. Little is known about the feasibility of screening for depression during hospitalization, or whether depression is associated with poorer outcomes, longer hospital stays, and higher readmission rates. We searched PubMed and PsycINFO for published, peer‐reviewed articles in English (1990‐2016) using search terms designed to capture studies that tested the performance of depression screening tools in inpatient settings and studies that examined associations between depression detected during hospitalization and clinical or utilization outcomes. Two investigators reviewed each full‐text article and extracted data. The prevalence of depression ranged from 5% to 60%, with a median of 33%, among hospitalized patients. Several screening tools identified showed high sensitivity and specificity, even when self‐administered by patients or when abbreviated versions were administered by individuals without formal training. With regard to outcomes, studies from several individual hospitals found depression to be associated with poorer functional outcomes, worse physical health, and returns to the hospital after discharge. These findings suggest that depression screening may be feasible in the inpatient setting, and that more research is warranted to determine whether screening for and treating depression during hospitalization can improve patient outcomes.
Exploring senior nurses' understanding of compassionate leadership in the community
Authors: Ali Sulekha , Terry Louise
Published: February 2017

Developing compassionate leadership is a priority since high profile failings in older people care have come to light. Little is known regarding how compassionate leadership is perceived in community health care organisations. The aim was to understand how leaders and senior staff within a Community NHS Trust perceive compassionate leadership and its importance. This qualitative study employed semi-structured, audio-recorded interviews analysed using interpretative phenomenological analysis. Purposive sampling was used to recruit nursing leaders (n=11) within one Community NHS Trust. Leading and caring with compassion are particularly important in the community. Compassionate leadership involves role modelling, person-centred care and compassion towards staff not just patients. A concept of ‘gritty compassion’ was identified which could lead to a loss of compassion. Community organisations need compassionate leaders who lead with their heads and their hearts and ensure that patients, clients and families feel cared for not merely treated.
Protective effect of cinnamon against cadmium-induced hepatorenal oxidative damage in rats
Authors: Abdeen Ahmed , Ghonim Ahmed , El-Shawarby Ragab , Abdel-Aleem Nabila , El-Shewy Elham , Abdo Mohamed , Abdelhiee Ehab
Published: February 2017

Background: Cadmium (Cd) is a well-known hazardous environmental contaminant. It exerts its toxicity through induction of lipid peroxidation and reduction of cellular antioxidant. Therefore, in this study, we investigated whether cinnamon could protect against Cd toxicity in liver and kidney.Materials and methods: Forty male Wister rats (130-135 gm) were divided randomly into 4 groups/ 10 rats each. Control, cinnamon, cadmium, and Cinn+Cd groups received distilled water, cinnamon extract (200 mg/kg b.wt. orally), cadmium chloride (5 mg/kg b.wt. orally), and Cd plus cinnamon, respectively. Blood, liver, and kidney samples were collected after 8 weeks of treatment. Erythrogram, leukogram, liver and kidney functions, and oxidative status (MDA, CAT, and TAC) were determined.Results and discussion: Cd-treated animals showed significant increases in serum ALT, AST, creatinine, and urea indicating hepatic and renal damage. Cd-induced oxidative stress was observed by marked decease TAC accompanied by increase in MDA which contributed in liver and kidney dysfunction. Co-treatment of Cd with cinnamon has improved the oxidation profile by increasing the TAC and decreasing the lipid peroxidation. Cinnamon ameliorated the toxic effect of Cd, which observed by improvement of liver and kidney functions.Conclusion:Â  High antioxidants content of cinnamon could protect the liver and kidney from Cd toxicity.Â
Hypercontractivity, supercontractivity, ultraboundedness and stability in semilinear problems
Authors: Addona Davide , Angiuli Luciana , Lorenzi Luca
Published: February 2017

We study the Cauchy problem associated to a family of nonautonomous semilinear equations in the space of bounded and continuous functions over

ℝ
d

{\mathbb{R}^{d}}

and in

L
p

{L^{p}}

-spaces with respect to tight evolution systems of measures. Here, the linear part of the equation is a nonautonomous second-order elliptic operator with unbounded coefficients defined in

I
×

ℝ
d

{I\times\mathbb{R}^{d}}

, (I being a right-halfline).
To the above Cauchy problem we associate a nonlinear evolution operator, which we study in detail, proving some summability improving properties. We also study the stability
of the null solution to the Cauchy problem.
Accuracy of cerebrospinal fluid Aβ1-42 measurements: evaluation of pre-analytical factors using a novel Elecsys immunosassay
Authors: Rozga Malgorzata , Bittner Tobias , Höglund Kina , Blennow Kaj
Published: February 2017

Background:

A decreased level of Aβ1-42 in cerebrospinal fluid (CSF) is characteristic of Alzheimer disease and often used to support clinical diagnosis. The measured concentration of CSF Aβ1-42, however, depends strongly on several pre-analytical and analytical “confounding” factors such as sample collection, material of testing tube, CSF handling and storage procedures (e.g. transfer to new tubes after centrifugation, freeze-thaw effects). As a consequence, substantial variations in the measured levels of this biomarker are observed even for the same sample. This study investigates whether the accuracy of quantitative analysis of CSF Aβ1-42 can be improved by pre-analytical treatment of CSF with agents that could potentially reduce a freeze-thaw and adhesion-related depletion of Aβ1-42 from CSF, including modulators of Aβ aggregation and cryoprotecting or anti-adhesion agents.

Methods:

The concentration of CSF Aβ1-42 was assessed with a novel Elecsys immunoassay developed for quantification of Aβ1-42 in human CSF.

Results:

Low-molecular weight Aβ oligomerization inhibitors, β-sheet breaker peptides, or the mid domain 4G8 antibody do not improve the stability of CSF Aβ1-42 during a repeated freeze-thaw treatment. Cryoprotecting agents reduce a freeze-thaw dependent loss of Aβ1-42 only when spiked to CSF to final concentration of 300 mM or higher. Adhesion of Aβ1-42 can be prevented by pre-treating CSF with Tween or by using tubes with a siliconized surface.

Conclusions:

Between-center variability in measured level of CSF Aβ1-42 can be reduced only by standardized CSF collection into one specific tube that, without centrifugation, transfer or other types of pre-analytical processing, is directly analyzed after sample collection.