bluuebunny/crossref_metadata_2025 huggingface dataset:
Echocardiographic predictors of worsening renal function in acute heart failure: observations from the RASHF registry
Authors: Soltani Mohammad Hossein , Jamshir Mohsen , Taghavi Sepideh , Golpira Reza , Nasiri Mohsen , Amin Ahmad , Abbaszade Marzbali Nargeuss , Naderi Nasim
Published: October 2018

Aims

Echocardiography is known as the most useful diagnostic test in the assessment of patients with heart failure (HF), and the prognostic significance of echocardiographic findings in HF is well known. In this report, we aim to present the prognostic significance of a limited set of echocardiographic parameters obtained within 24 h of admission of patients enrolled in the Rajaie Acute Systolic Heart Failure registry.

Methods and results

A total of 230 patients with the diagnosis of acute systolic HF (left ventricular ejection fraction ≤ 35%) were enrolled into the study. Transthoracic echocardiography was performed for all study population within 24 h of admission. The primary endpoint of the study was the occurrence of worsening renal function (WRF) during the hospitalization course.Acquiring data of transthoracic echocardiography within 24 h of admission was feasible in all study participants. The median (inter‐quartile range) of left ventricular ejection fraction was 20% (15–23%). Severe right ventricular dysfunction was observed in 21.5% of patients. The grade of inferior vena cava collapse and right ventricular systolic dysfunction were associated with WRF. In multivariable analysis, right ventricular systolic dysfunction was among the independent predictors of WRF [β = 0.8, P = 0.01, odds ratio (OR) = 2.4 (1.2–4.9)] and in‐hospital mortality [β = 0.6, P = 0.04, OR = 1.5 (0.5–4.6)].

Conclusions

Echocardiographic parameters are useful for baseline assessment and provide additional information besides other clinical variables for prognostication. Right ventricular dysfunction is the most important risk factor in developing WRF and in‐hospital mortality in patients with acute HF.
Application of High Intensity Ultrasound to Accelerate Crystallization of Anhydrous Milk Fat and Rapeseed Oil Blends
Authors: Gregersen Sandra Beyer , Frydenberg Rikke Ploug , Hammershøj Marianne , Dalsgaard Trine Kastrup , Andersen Ulf , Wiking Lars
Published: October 2018

In this study, the impact of high intensity ultrasound (HIU) treatment on anhydrous milk fat and milk fat/rapeseed oil blends with 10–30 w/w% rapeseed oil is examined. Effects of HIU treatment on crystallization kinetics, thermal behavior, microstructure, texture, and oxidation are evaluated. HIU treatment results in an acceleration of the crystallization process, especially for blends with a high rapeseed oil content. HIU treatment reduces the crystal size, however, HIU treatment does not have any significant effects on the melting behavior or hardness. No significant effects of HIU treatment on secondary oxidation products are observed, indicating that lipid oxidation is not facilitated by the HIU treatment.

Practical Application: A great potential exists for the use of use of high intensity ultrasound in the food industry to obtain a shorter and more controllable fat crystallization process. Results from this demonstrate how the impact of ultrasound treatment is affected by diluting a hard fat with liquid oil. Such effects are of great importance in, for instance, the dairy industry, where high intensity ultrasound potentially provides an additional processing tool in the production of spreadable blends based on milk fat and rapeseed oil. Ultrasound treatment is introduced in a circulating flow system, a more realistic representation of an industrial setting compared with commonly used probe based bath systems.

High intensity ultrasound accelerates the crystallization kinetics of anhydrous milk fat and rapeseed oil blends, resulting in the formation of smaller crystals but no differences in melting properties or hardness. This is obtained in a circulating flow cell, without detection of increased levels of secondary oxidation products.
PdII‐Mediated Oxidative Amination for Access to a 9‐Azabicyclo[4.2.1]nonane Compound Library and Anatoxin‐a
Authors: Dawood Rafid S. , Chidipudi Suresh R. , O'Connor Daniel C. , Lewis William , Hamza Daniel , Pearce Christopher A. , Jones Geraint , Wilkie Ross P. , Georgiou Irene , Storr Thomas E. , Moore Jonathan C. , Stockman Robert A.
Published: October 2018

Intramolecular oxidative amination of readily accessible aminocyclooct‐4‐enes provides rapid and regioselective access to the 9‐azabicyclo[4.2.1]nonane framework characteristic of the natural product anatoxin‐a (1). This has enabled the synthesis of sp3‐rich chemical scaffolds suitable for diversification. A library of 881 lead‐like compounds is reported alongside a formal synthesis of anatoxin‐a (1).
Boost your department's success by cracking the communication code
Authors: McCarthy Claudine
Published: October 2018

WASHINGTON, D.C. — Some people communicate from the heart, while others communicate from the head, and this causes a disconnect in their communication and relationships at work and beyond, according to Kevin DeShazo, a partner with Culture Wins, a division of GiANT Worldwide.
Guide students to on‐time graduation with cross‐enrollment opportunities
Authors: Sutton Halley
Published: October 2018

Damon Stevens came to California State University‐San Marcos for the first time as a transfer student from a local community college. By that time, he'd already served a full career in the Navy. With his military background, Stevens was asked to serve as student‐veteran peer mentor and tasked with assisting fellow student‐veterans with the transition from active duty to higher education. Stevens was then hired as a quality service representative in enrollment management services, providing support to current students under the university registrar and support to prospective students under the director of admissions.
Preliminary validation of the Yale Food Addiction Scale for Children 2.0: A dimensional approach to scoring
Authors: Schiestl Emma T. , Gearhardt Ashley N.
Published: October 2018

Objective

Assessment approaches for food addiction in younger samples have not been updated to reflect recently revised diagnostic approaches for addictive disorders. The aim of the current study is to develop a new dimensional approach to assess food addiction in adolescents that is psychometrically sound, developmentally appropriate, and reflective of the updated diagnostic criteria.

Methods

The dimensional Yale Food Addiction Scale for Children 2.0 (dYFAS‐C 2.0) and related measures were administered to 127 adolescents from the community in the United States. Endorsement rates for each question were reviewed, and the psychometric properties were evaluated.

Results

Problem‐focused symptoms had low endorsement rates and were excluded from the final version of the scale. The dYFAS‐C 2.0 demonstrated partial evidence for a one‐factor structure, had good internal consistency reliability, and was positively associated with emotional eating, external eating, and body mass index (BMI). The dYFAS‐C 2.0 also accounted for unique variance in BMI. Unexpectedly, the dYFAS‐C 2.0 was positively associated with restrained eating.

Conclusions

The dYFAS‐C 2.0 appears to have adequate psychometric properties for assessing food addiction in community samples of adolescents. Future research should evaluate the measure in clinical samples and investigate the association between food addiction and restrained eating over the lifespan.
The generalized predictive control of bacteria concentration in marine lysozyme fermentation process
Authors: Zhu Xianglin , Zhu Ziyan
Published: October 2018

Due to the high degree of strong coupling and nonlinearity of marine lysozyme fermentation process, it is difficult to accurately model the mechanism. In order to achieve real‐time online measurement and effective control of bacterial concentration during fermentation, a generalized predictive control method based on least squares support vector machines is proposed. The particle swarm optimization least squares support vector machine (PSO‐LS‐SVM) model of lysozyme concentration is established by optimizing the regularization parameters and the kernel parameters of the least squares support vector machine by particle swarm optimization. To avoid the nonlinear problems in predictive control, the model is linearized at each sampling point and the generalized predictive algorithm is used to predict the bacteria concentration of lysozyme. The experimental simulation shows that the least squares support vector machine model with particle swarm optimization can achieve good prediction effect. The linearized model performs generalized predictive control, which makes the total activity of the enzyme increased from 60% to 80% and the yield improved by 30%.
Short‐term and long‐term effects of pathogen reduction interventions on salmonellosis from whole chickens
Authors: Oscar Thomas P.
Published: October 2018

The current study was undertaken to evaluate short‐term and long‐term effects of pathogen reduction interventions on food safety. This was accomplished using a model that predicts risk of salmonellosis from whole chickens produced by different scenarios. Interventions investigated were a 50% pathogen reduction before retail (PR), a 50% pathogen reduction at serving by consumer education (CE), and a 75% pathogen reduction by PR + CE. Long‐term effects were simulated by reducing consumer resistance by an amount equal to reductions in pathogen exposure caused by interventions in the short‐term. In the short‐term, risk of salmonellosis was reduced (p < 0.05) from 0.42 to 0.21, 0.23, and 0.13 cases per 100,000 consumers by PR, CE, and PR + CE, respectively. However, in the long‐term, risk of salmonellosis was increased (p < 0.05) from 0.42 to 1.03, 1.08, and 2.20 cases per 100,000 consumers by PR, CE, and PR + CE, respectively. These results indicated that food safety benefits of pathogen reduction interventions reversed with time because of a decrease in consumer resistance to salmonellosis.
Does the environmental Kuznets curve exist between globalization and energy consumption? Global evidence from the cross‐correlation method
Authors: Shahbaz Muhammad , Mahalik Mantu Kumar , Shahzad Syed Jawad Hussain , Hammoudeh Shawkat
Published: October 2018

We explore the nexus between globalization and energy demand for 86 high‐, middle‐, and low‐income countries over the period 1970–2015. We use a simple approach based on the cross‐correlation to understand how globalization and energy consumption are related in terms of time lags and leads. Our findings show that for 64 out of the 86 countries (approximately 74%), there is clear evidence in support of the environmental Kuznets curve (EKC) hypothesis. The globalized environment (e.g., globalization) has been conducive for the majority of the countries in reducing their long‐term energy consumption. From a policy perspective, our findings suggest that the role of “globalization” in the EKC function should not be underestimated by policymakers and governments of these countries while designing a policy framework for the reduction of energy demand in the long run.
Performance Assessment of Water Delivery and Distribution in Som Kamla Amba Irrigation Scheme
Authors: Sharma Upma , Kothari Mahesh , Dashora Yogita
Published: October 2018

The objective of this study was to assess the water delivery performance of the Som Kamla Amba irrigation scheme located in the Dungarpur district of Rajasthan using adequacy, equity and dependability indicators. Three minors each at the head, mid and tail sections of main canals (Right and Left Main Canal) and branch canals (Aspur Branch Canal and Baroda Branch Canal) were selected. The ratio of water delivered (obtained from discharge measured at outlets) and water required (calculated from CROPWAT software) was determined for major rabi crops (wheat, barley, gram and mustard) grown in the command area in 2011–2012. Results had shown good (1.00 to 0.93), fair (0.84 to 0.80) and poor (0.42 to 0.18) adequacy at the head, mid and tail sections of each canal respectively. Also there is poor equity in water delivery as its value varied from 0.35 to 0.92. Dependability was found to be good at head, fair at mid and poor at tail sections. © 2018 John Wiley & Sons, Ltd.
MiR‐148a regulates bone marrow mesenchymal stem cells‐mediated fracture healing by targeting insulin‐like growth factor 1
Authors: Liu Hongzhi , Su Hao , Wang Xin , Hao Wei
Published: October 2018

The purpose of this study was to investigate the underlying molecular mechanisms of fracture healing mediated by bone marrow mesenchymal stem cells. Differentially expressed microRNAs in acutely injured subjects and healthy volunteers were screened by microarray analysis. The dual luciferase reporter system was used to verify whether insulin‐like growth factor 1 (IGF1) was the direct target gene regulated by miR‐148a. The expression level of miR‐148a and IGF1 after osteogenic differentiation was detected by quantitative real‐time polymerase chain reaction. Western blot was used to determine the protein expression of bone markers, including IGF1, runt‐related transcription factor 2 (Runx2), osteocalcin, and osteopontin in rat bone marrow–derived mesenchymal stem cells. Alkaline phosphatase and alizarin red staining was used to detect alkaline phosphatase activity and calcium deposition. An animal fracture model was used for in vivo experiments. MiR‐148a was highly expressed in acutely injured subjects compared with healthy volunteers, and IGF1 was a target of miR‐148a. Moreover, compared with the negative control group, IGF1 messenger RNA expression was significantly increased in the miR‐148a antagomir group. During osteogenic differentiation, the expression of IGF1, Runx2, osteocalcin, and osteopontin was higher in the miR‐148a antagomir group than other groups. In vivo experiments further confirmed that upregulation of IGF1 enhanced fracture healing efficiently by decreasing callus width and area and improving bone mineral density, maximum load, stiffness, and energy absorption. It was proved that IGF1 was the direct target gene of miR‐148a, and the use of rat bone marrow–derived mesenchymal stem cells with low expression of miR‐148a could improve fracture healing by upregulating IGF1.
MicroRNA‐212 suppresses nonsmall lung cancer invasion and migration by regulating ubiquitin‐specific protease‐9
Authors: Chen Wei , Huang Yuye , Zhang Shufen , Zheng Xiaoxiao , Xie Shangzhi , Mao Jiayan , Cai Ying , Lu Xuemei , Hu Liqiang , Shen Jian , Dong Ying , Chai Kequn
Published: October 2018

MicroRNAs (miRNAs) play crucial roles in various biological processes, including migration, proliferation, differentiation, cell cycling, and apoptosis. Epithelial‐mesenchymal transition (EMT) has been shown to be related to the capability of migration and invasion in many tumor cells. In this study, we used wound‐healing assay and transwell invasion to analysis the capability of migration and invasion in non–small‐cell lung carcinoma (NSCLC), respectively. The expression of ubiquitin‐specific protease‐9‐X‐linked (USP9X) and miR‐212 messenger RNA (mRNA) was determined by quantitative real‐time polymerase chain reaction and Western blot analysis was used to determine the E‐cadherin and vimentin expression. Our results showed that miR‐212 mimic inhibited cell migration and invasion, while miR‐212 inhibitor increased cell migration and invasion. There was no significant difference between WP1130 and miR‐212 mimic combined with WP1130 groups. Moreover, WP1130 inhibited the capability of the migration and invasion of NSCLC cells. Western blot analysis displayed that miR‐212 mimic upregulated E‐cadherin expression and downregulated vimentin expression, while miR‐212 inhibitor downregulated E‐cadherin and upregulated vimentin expression. These data showed that miR‐212 regulated NSCLC cell invasion and migration by regulating USP9X expression. Taken together, these findings indicated that miR‐212 regulated NSCLC cells migration and invasion through targeting USP9X involved in EMT.
An alternative total synthesis of Patulolide A
Authors: Konidena Lakshmi Narayana Sharma , Chettu Suresh Kumar , Mukkavilli Praveena , Valluru Krishna Reddy , N.S. Kameswara Rao , Nowduri Annapurna , Korupolu Raghu Babu
Published: October 2018

A new total synthesis of [R]‐Patulolide A from readily available (R)‐propylene epoxide obtained using the asymmetric synthetic approach is reported. The key reactions involved are ozonolysis and Yamaguchi macrolactonization, resulting in the ring system.
Adapting psychotherapy to patient reactance level: A meta‐analytic review
Authors: Beutler Larry E. , Edwards Christopher , Someah Kathleen
Published: October 2018

Resistance and its extreme variation, reactance, are uniformly observed across varieties of psychotherapy. Social psychologists note that reactant individuals prove to be less so when offered a receptive and nondirective environment. We provide definitions of reactance, review its frequent measures, and offer a clinical example. A meta‐analysis of 13 controlled studies (1,208 patients) examined the degree to which treatment outcomes are enhanced when therapists offer less directive treatments to high‐reactance patients. The results revealed a large effect size (d = .79), confirming that highly reactant individuals did better in psychotherapy when the therapist assumed a reflective and nondirective stance than a directive and authoritative one. To a lesser degree, the opposite was also true. Limitations of the research and diversity considerations are noted. Practice recommendations are provided to minimize a patient’s reactant behavior.
Stages of change and psychotherapy outcomes: A review and meta‐analysis
Authors: Krebs Paul , Norcross John C. , Nicholson Joseph M. , Prochaska James O.
Published: October 2018

The transtheoretical model and the stages of change are often used to adapt treatment to the individual client. The aims of this study were to review the stages of change and popular measures of change readiness in psychotherapy and to conduct a meta‐analysis of the relation between readiness measures and psychotherapy outcomes. We report data from 76 studies, encompassing 25,917 patients. Moderate‐sized effects (d = 0.41) were found for the association among multiple disorders, including substance and alcohol use, eating disorders, and mood disorders. Outcomes were a function of the pretreatment stage of change; that is, the farther a patient along the stages, the better the treatment outcomes. This review added 37 studies to the data reported in 2010, further strengthening the link between readiness and therapy outcomes. The article concludes with limitations of the research, diversity considerations, and therapeutic practices for stage matching in psychotherapy specifically and behavioral health more generally.
Feasibility of early multimodal interventions for elderly patients with advanced pancreatic and non‐small‐cell lung cancer
Authors: Naito Tateaki , Mitsunaga Shuichi , Miura Satoru , Tatematsu Noriatsu , Inano Toshimi , Mouri Takako , Tsuji Tetsuya , Higashiguchi Takashi , Inui Akio , Okayama Taro , Yamaguchi Teiko , Morikawa Ayumu , Mori Naoharu , Takahashi Toshiaki , Strasser Florian , Omae Katsuhiro , Mori Keita , Takayama Koichi
Published: October 2018

Background

Combinations of exercise and nutritional interventions might improve the functional prognosis for cachectic cancer patients. However, high attrition and poor compliance with interventions limit their efficacy. We aimed to test the feasibility of the early induction of new multimodal interventions specific for elderly patients with advanced cancer Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) programme.

Methods

This was a multicentre prospective single‐arm study. We recruited 30 of 46 screened patients aged ≥70 years scheduled to receive first‐line chemotherapy for newly diagnosed, advanced pancreatic, or non‐small‐cell lung cancer. Physical activity was measured using pedometers/accelerometer (Lifecorder®, Suzuken Co., Ltd., Japan). An 8 week educational intervention comprised three exercise and three nutritional sessions. The exercise interventions combined home‐based low‐intensity resistance training and counselling to promote physical activity. Nutritional interventions included standard nutritional counselling and instruction on how to manage symptoms that interfere with patient's appetite and oral intake. Supplements rich in branched‐chain amino acids (Inner Power®, Otsuka Pharmaceutical Co., Ltd., Japan) were provided. The primary endpoint of the study was feasibility, which was defined as the proportion of patients attending ≥4 of six sessions. Secondary endpoints included compliance and safety.

Results

The median patient age was 75 years (range, 70–84). Twelve patients (40%) were cachectic at baseline. Twenty‐nine patients attended ≥4 of the six planned sessions (96.7%, 95% confidence interval, 83.3 to 99.4). One patient dropped out due to deteriorating health status. The median proportion of days of compliance with supplement consumption and exercise performance were 99% and 91%, respectively. Adverse events possibly related to the NEXTAC programme were observed in five patients and included muscle pain (Grade 1 in two patients), arthralgia (Grade 1 in one patient), dyspnoea on exertion (Grade 1 in one patient), and plantar aponeurositis (Grade 1 in one patient).

Conclusions

The early induction of multimodal interventions showed excellent compliance and safety in elderly patients with newly diagnosed pancreatic and non‐small‐cell lung cancer receiving concurrent chemotherapy. We are now conducting a randomized phase II study to measure the impact of these interventions on functional prognosis.
Power to participants: a call for person‐centred HIV prevention services and research
Authors: Pantelic Marija , Stegling Christine , Shackleton Sally , Restoy Enrique
Published: October 2018

Introduction

While biomedical HIV prevention offers promise for preventing new HIV infections, access to and uptake of these technologies remain unacceptably low in some settings. New models for delivery of HIV prevention are clearly needed. This commentary highlights the potential of person‐centred programming and research for increasing the cultural relevance, applicability and use of efficacious HIV prevention strategies. It calls for a shift in perspective within HIV prevention programmes and research, whereby people are recognized for their agency rather than assumed to be passive beneficiaries or research participants.

Discussion

Person‐centred HIV prevention reorientates power dynamics so that individuals (rather than interventions) are at the centre of the response. Respecting personal choice and agency – and understanding how these are shaped by the context in which people exercise these choices – are critical dimensions of the person‐centred approach. Community‐based participatory research should be employed to inform and evaluate person‐centred HIV prevention. We argue that community‐based participatory research is an orientation rather than a method, meaning that it can be integrated within a range of research methods including randomized controlled trials. But embracing community‐based participatory approaches in HIV prevention research requires a systemic shift in how this type of research is reported in high impact journals and in how research impact is conceived. Community‐based organizations have a critical role to play in both person‐centred HIV prevention and research.

Conclusions

HIV prevention is situated at the intersection of unprecedented opportunity and crisis. Person‐centred approaches to HIV prevention and research shift power dynamics, and have the potential to ensure a more sustainable response with each individual actively participating in their own care and meaningfully contributing to the production of knowledge on HIV prevention. This approach taps into the resourcefulness, resilience and knowledge of the person and their communities, to strengthen research and programmes, making them more relevant, appropriate and effective.
Strengthening stakeholder engagement through ethics review in biomedicalHIVprevention trials: opportunities and complexities
Authors: Slack Catherine , Wilkinson Abigail , Salzwedel Jessica , Ndebele Paul
Published: October 2018

Introduction

Clinical trials of biomedicalHIVprevention modalities require the cooperation of multiple stakeholders. Key stakeholders, such as community members, may have stark vulnerabilities. Consequently, calls forHIVprevention researchers to implement “stakeholder engagement” are increasingly common. Such engagement is held to benefit inter‐stakeholder relations, stakeholders themselves and the research itself. The ethics review process presents a unique opportunity to strengthen stakeholder engagement practices inHIVprevention trials. However, this is not necessarily straightforward. In this article, we consider several complexities. First, is stakeholder engagement a legitimate component of what Research Ethics Committees (RECs) should review forHIVprevention trials? Second, what are the core features of engagement that should be under ethics review? Third, what are the key practices that should be highlighted in ethics review?

Methods

To address these questions, we examined the international ethics guidelines specialized for such trials (UNAIDS2012,UNAIDS‐AVAC GPP2011) and directly applicable to such trials (CIOMS2016;WHO2011). Thematic analysis was used to code and analyse these guidelines.

Results and discussion

Ethics guidelines supportRECreview of engagement. Guidance recommends that engagement be broad and inclusive; early and sustained; and dynamic and responsive. Broad engagement practices include evaluating the context, planning in writing, and resourcing.RECs should assess engagement as part of a comprehensive review, and recommend revisions where necessary. Researchers should profile key elements of engagement valued in ethics guidance, when they draft ethics submissions. Importantly, the ethics review process should not undermine the ‘dynamic responsiveness’ required for excellent engagement in this field.

Conclusions

As evidence‐informed engagement strategies emerge, these should inform the ethics submission and review process. Both parties in the review process should strive to avoid a superficial, check‐list type approach that caricatures what should be a thorough, nuanced ethics review of a rich, responsive engagement process.
Stakeholder engagement to informHIVclinical trials: a systematic review of the evidence
Authors: Day Suzanne , Blumberg Meredith , Vu Thi , Zhao Yang , Rennie Stuart , Tucker Joseph D.
Published: October 2018

Introduction

Stakeholder engagement is an essential component ofHIVclinical trials. We define stakeholder engagement as an input by individuals or groups with an interest inHIVclinical trials to inform the design or conduct of said trials. Despite its value, stakeholder engagement to informHIVclinical trials has not been rigorously examined. The purpose of our systematic review is to examine stakeholder engagement forHIVclinical trials and compare it to the recommendations of theUNAIDS/AVACGood Participatory Practice (GPP) guidelines.

Methods

We used thePRISMAchecklist and identified English language studies describing stakeholder engagement to informHIVclinical trials. Four databases (PubMed, Ovid,CINAHLand Web of Science) and six journals were searched, with additional studies identified using handsearching and expert input. Two independent reviewers examined citations, abstracts and full texts. Data were extracted on country, engagement methods, stakeholder types and purpose of stakeholder engagement. Based on theGPPguidelines, we examined how frequently stakeholder engagement was conducted to inform clinical trial research question development, protocol development, recruitment, enrolment, follow‐up, results and dissemination.

Results and discussion

Of the 917 citations identified, 108 studies were included in the analysis. Forty‐eight studies (44.4%) described stakeholder engagement in high‐income countries, thirty (27.8%) in middle‐income countries and nine (8.3%) in low‐income countries. Fourteen methods for stakeholder engagement were identified, including individual (e.g. interviews) and group (e.g. community advisory boards) strategies. Thirty‐five types of stakeholders were engaged, with approximately half of the studies (60; 55.6%) engagingHIV‐affected community stakeholders (e.g. people living withHIV, at‐risk or related populations of interest). We observed greater frequency of stakeholder engagement to inform protocol development (49 studies; 45.4%) and trial recruitment (47 studies; 43.5%). Fewer studies described stakeholder engagement to inform post‐trial processes related to trial results (3; 2.8%) and dissemination (11; 10.2%).

Conclusions

Our findings identify important directions for future stakeholder engagement research and suggestions for policy. Most notably, we found that stakeholder engagement was more frequently conducted to inform early stages ofHIVclinical trials compared to later stages. In order to meet recommendations established in theGPPguidelines, greater stakeholder engagement across all clinical trial stages is needed.
Collateral benefits: how the practical application of Good Participatory Practice can strengthen HIV research in sub‐Saharan Africa
Authors: Baron Deborah , Essien Thandekile , Pato Sinazo , Magongo Miliswa , Mbandazayo Nomthandazo , Scorgie Fiona , Rees Helen , Delany‐Moretlwe Sinead
Published: October 2018

Introduction

The Good Participatory Practice (GPP): Guidelines for Biomedical HIV Prevention Trials, second edition (2011) were developed to provide clinical trial sponsors and implementers with a formal stakeholder engagement framework. As one of the largest African research institutes, Wits Reproductive Health and HIV Institute (Wits RHI) became an early adopter of GPP by implementing its principles within large‐scale national and regional clinical trials. This article examines Wits RHI's lessons learned from implementing GPP, its ongoing efforts to institutionalize GPP, and the yet to be realized potential in creating fully sustainable structures for meaningful stakeholder engagement in HIV prevention research, implementation science and beyond.

Discussion

For the past seven years, Wits RHI has undertaken both centralized leadership roles in implementing GPP across multi‐party regional research consortia as well as overseeing GPP for smaller investigator‐driven trials. Through this iterative roll‐out of GPP, key lessons have emerged. Obtaining upfront funding to support GPP activities throughout and between the research life cycle, and a trained multi‐disciplinary team of GPP practitioners have helped facilitate an enabling environment for GPP implementation. We further recommend formally integrating stakeholder engagement into study documents, including monitoring and evaluation plans with indicators and performance metrics, to assist teams to track and refine their GPP strategies. Finally, institutionalizing resources and supporting organization‐wide GPP along with ongoing support can help build efficiencies and maximize economies of scale toward a pragmatic and innovative application of the GPP Guidelines.

Conclusions

Thanks to a growing global network of GPP practitioners and a burgeoning GPP Community of Practice, there has been substantive progress in making GPP an integral component of clinical HIV prevention research. The Wits RHI experience highlights the possibilities and the challenges to translating the GPP principles into concrete practices within specific clinical trials and across a research institute. Realizing the full potential of GPP, including direct and indirect – ‘collateral benefits’ will require the collective buy‐in and support from sponsors, implementers and community stakeholders across the research field. As the HIV prevention research field expands, however, a more conscious and systematic implementation of GPP is timely.
Preoperative Oral Branched‐Chain Amino Acid Supplementation Suppresses Intraoperative and Postoperative Blood Lactate Levels in Patients Undergoing Major Hepatectomy
Authors: Nanno Yoshihide , Toyama Hirochika , Terai Sachio , Mizumoto Takuya , Tanaka Motofumi , Kido Masahiro , Ajiki Tetsuo , Fukumoto Takumi
Published: October 2018

Background: Lactate production is exacerbated by surgical stress. We sought to determine whether branched‐chain amino acid (BCAA) supplementation could decrease blood lactate levels in patients undergoing hepatectomy. Methods: A total of 275 consecutive patients who underwent hepatectomy of ≥2 segments were retrospectively reviewed. Blood lactate levels in patients treated with BCAA supplementation before hepatectomy (December 2011 to December 2016) were compared with levels in patients who were not pretreated (January 2008 to November 2011). Results: Postoperative lactate levels were significantly lower in patients who received preoperative BCAA supplementation than in those who did not (2.6 vs 3.4 mmol/L; P < .001). Intraoperative blood lactate levels, which were evaluated after induction of general anesthesia, were also lower in those who received BCAA supplementation than in those who did not (1.1 vs 1.5 mmol/L, respectively; P < .001). A multiple regression analysis revealed that preoperative BCAA supplementation was independently associated with decreased postoperative and intraoperative lactate levels (P = .030 and P < .001, respectively). Conclusion: Preoperative BCAA supplementation decreased intraoperative and postoperative blood lactate levels in patients undergoing major hepatectomy.
Close Relationship Between Immunological/Inflammatory Markers and Myopenia and Myosteatosis in Patients With Colorectal Cancer: A Propensity Score Matching Analysis
Authors: Okugawa Yoshinaga , Toiyama Yuji , Yamamoto Akira , Shigemori Tsunehiko , Kitamura Ayame , Ichikawa Takashi , Ide Shozo , Kitajima Takahito , Fujikawa Hiroyuki , Yasuda Hiromi , Okita Yoshiki , Hiro Junichiro , Araki Toshimitsu , McMillan Donald C. , Miki Chikao , Kusunoki Masato
Published: October 2018

Background

The systemic inflammatory response (SIR) via host‐tumor interactions has been termed the seventh hallmark of cancer, and several studies demonstrated that SIR might be a pivotal mediator for progression of cancer cachexia. The objective of this study was to clarify the correlation between sarcopenia and SIR in patients with colorectal cancer (CRC).

Methods

A total of 308 patients with CRC were enrolled in this study. Preoperative psoas muscle mass index and intramuscular adipose tissue content were evaluated using preoperative computed tomographic images, and the correlation between body composition status and several SIR markers, including C‐reactive protein (CRP), serum albumin level, neutrophil‐lymphocyte ratio, platelet‐lymphocyte ratio, and systemic immune‐inflammation index (SII) was assessed using statistical methods.

Results

Whereas preoperative myosteatosis was not correlated with clinicopathological factors except for aging and the presence of lymphovascular invasion, preoperative myopenia was significantly associated with well‐established clinicopathological factors. Furthermore, the presence of myopenia was significantly correlated with elevated CRP, SII, and neutrophil‐platelet score, and decreased lymphocyte‐monocyte ratio, prognostic nutrition index, and serum albumin level. Logistic regression analysis revealed that an elevated CRP concentration was an independent risk factor for the presence of preoperative myopenia (odds ratio [OR] 2.49, 95% CI: 1.31–4.72; P = .005). Furthermore, these findings were validated using propensity score matching analysis (OR 2.35, 95% CI: 1.17–4.75; P = .017).

Conclusion

Quantification of preoperative CRP could identify patients at high risk for development of myopenia who will likely require individualized treatment plans, including postoperative nutrition intervention, rehabilitation, and oncological follow‐up in patients with CRC.
Conjugated Linoleic Acid Regulates Body Composition and Locomotor Activity in a Sex‐Dependent Manner in Drosophila melanogaster
Authors: Chen Phoebe B. , Kim Ju Hyeon , Kim Daeyoung , Clark John M. , Park Yeonhwa
Published: October 2018

Conjugated linoleic acid (CLA) has been reported to be a bioactive food component. However, there is limited knowledge on the sex‐dependent effects of CLA on energy metabolism. In the present study, Drosophila melanogaster was used to investigate the sex‐dependent effects of CLA with respect to body fat, muscle, locomotion, and a key metabolic regulator, AMP‐activated protein kinase α (AMPKα). Adult flies were fed a cornmeal‐based fly food with 0.5% of CLA oil (50:50 of cis‐9,trans‐11 and trans‐10,cis‐12 CLA isomers in triacylglycerol (TAG) form), 0.5% safflower oil (high in linoleic acid [LNA] as control), or 0.5% water (as blank) for 5 days. Accumulation of CLA in tissue was verified using gas chromatography–mass spectrometry. CLA‐fed flies had reduced TAG and increased locomotor activity when compared to LNA‐fed control flies. In addition, CLA increased the muscle content when compared to the blank. Moreover, following CLA supplementation, increased AMPKα activity was observed in females, but not in males. These sex‐dependent metabolic effects of CLA may be due to physiological differences in lipid metabolism and nutrient requirements. In conclusion, CLA promoted the body composition and locomotion behavior in D. melanogaster and regulated the sex‐specific metabolism in part via AMPKα. As key physiological processes are conserved between fly and human, information obtained from this research could provide valuable insights into sex‐dependent responses to CLA in humans.
OVERCOMING INCUMBENT CHALLENGES TO BUSINESS MODEL INNOVATION
Authors: Johnson Mark W.
Published: October 2018

Business model innovation is a hot topic these days, but Johnson has been working in and writing about it for years. Here he explains “white space pursuits,” which he describes as “venture[s] into markets that the company hasn't served before, with new and different products and services.” He illustrates how companies such as Sony and Kodak held on too long to what became outdated models. Leaders can inform relevant stakeholders and place potential innovations in context, “describing the threats and opportunities they are facing that are impelling them to move past their core and its adjacencies, and explaining why remaining too close to home is actually a greater risk than a well‐managed trip into the white space.”
A large list of small cardinal characteristics of Boolean algebras
Authors: Monk J. Donald
Published: October 2018

A large list of mostly known small cardinal characteristics of Boolean algebras is given and relationships between them (mostly known) are described. Many open problems are formulated.
Extension of the mutation spectrum of PAX6 from three Chinese congenital aniridia families and identification of male gonadal mosaicism
Authors: Bai Zhouxian , Kong Xiangdong
Published: October 2018

Background

Congenital aniridia is a severe autosomal dominant binocular developmental disorder, the primary feature of which is congenital absence or hypoplasia of the iris. PAX6 is the main disease‐causing gene of congenital aniridia; inheritance is autosomal dominant. But the current mutations do not fully explain this disorder.

Methods

We investigated the mutation profile of genes related in three Chinese families with congenital aniridia through targeted sequencing technology. And we validated the candidate variants by PCR‐based Sanger sequencing. Different degree impairments of islet function were observed in the patients with aniridia by carbohydrate tolerance butter and insulin release tests in our study.

Results

We identified four novel mutations of PAX6 from three Chinese families with congenital aniridia, which included heterozygous double mutation c.879_880delCA (p.S294Cfs*46) and c.1124C>G (p.P375R) in Family 1 with three patients, heterozygous frameshift mutation c.308delG (p.P103Qfs*21) in Family 2 with one patient, and c.1192delT (p.S398Pfs*126) in Family 3 with two patients. The three frameshift mutations of PAX6 are co‐segregated with the aniridia from controls in the families, but the novel missense mutation is not co‐segregated with the phenotype. The frameshift mutations in Family 1 and Family 2 have effects to truncate the protein, but the frameshift mutation in Family 3 will prolong it. We confirmed the phenomenon of male gonadal mosaicism of PAX6 by the sequencing of two linked novel mutations in Family 1. Most of the patients with isolated aniridia have different degrees of islet damage through related clinical tests.

Conclusion

It is therefore noteworthy that we found different types of pathogenic mutation, which have effects of truncating or prolonging protein leaded by frameshift mutation. Our results of this study extended the pathogenic mutation spectrum of PAX6 for congenital aniridia and demonstrated the male germline chimerism by molecular experiments.
Over‐discretized SENSE reconstruction and B0 correction for accelerated non‐lipid‐suppressed 1H FID MRSI of the human brain at 9.4 T
Authors: Nassirpour Sahar , Chang Paul , Kirchner Thomas , Henning Anke
Published: October 2018

The aim of this work was to use post‐processing methods to improve the data quality of metabolite maps acquired on the human brain at 9.4 T with accelerated acquisition schemes. This was accomplished by combining an improved sensitivity encoding (SENSE) reconstruction with a B0 correction of spatially over‐discretized magnetic resonance spectroscopic imaging (MRSI) data.

Since MRSI scans suffer from long scan duration, investigating different acceleration techniques has recently been the focus of several studies. Due to strong B0 inhomogeneity and strict specific absorption rate (SAR) limitations at ultra‐high fields, the use of a low‐SAR sequence combined with an acceleration technique that is compatible with dynamic B0 shim updating is preferable. Hence, in this study, a non‐lipid‐suppressed ultra‐short TE and TR 1H free induction decay MRSI sequence is combined with an in‐plane SENSE acceleration technique to obtain high‐resolution metabolite maps in a clinically feasible scan time. One of the major issues in applying parallel imaging techniques to non‐lipid‐suppressed MRSI is the presence of strong lipid aliasing artifacts, which if not thoroughly resolved will hinder the accurate quantification of the metabolites of interest. To achieve a more robust reconstruction, an over‐discretized SENSE reconstruction (with direct control over the shape of the spatial response function) was combined with an over‐discretized B0 correction. This method is compared with conventional SENSE reconstruction for seven acceleration schemes on four healthy volunteers.

The over‐discretized method consistently outperformed conventional SENSE, resulting in an average of 23 ± 1.2% higher signal‐to‐noise ratio and 8 ± 2.9% less error in the fitting of the N‐acetylaspartate signal over a whole brain slice. The highest achievable acceleration factor with the proposed technique was determined to be 4. Finally, using the over‐discretized method, high‐resolution (97 μL nominal voxel size) metabolite maps can be acquired in 3.75 min at 9.4 T. This enables the acquisition of high‐resolution metabolite maps with more spatial coverage at ultra‐high fields.
Ratiometric NOE(−1.6) contrast in brain tumors
Authors: Zu Zhongliang
Published: October 2018

Recently, a new nuclear Overhauser enhancement (NOE)‐mediated saturation transfer effect at around −1.6 ppm from water, termed NOE(−1.6), was reported to show hypointense signals in brain tumors. Similar to chemical exchange saturation transfer or magnetization transfer (MT) effects, which depend on the solute pool concentration, the exchange/coupling rate, the solute transverse relaxation rate, etc., the NOE(−1.6) effect should also depend on these factors. Since the exchange rate is relevant to tissue pH, and the coupling rate and the solute transverse relaxation rate are relevant to the motional property of the coupled molecules, further studies to quantify the contribution from only the exchange/coupling rate and the solute transverse relaxation rate are always interesting. The purpose of this paper is to apply a ratiometric approach to the NOE(−1.6) effect to obtain a metric that is more specific to the NOE coupling rate and the solute transverse relaxation rate than the NOE(−1.6) signal amplitude. Simulations indicate that the ratiometric approach allows us to rule out nearly all of the non‐specific factors including the solute pool concentration, solute and water longitudinal relaxation rates, direct water saturation, and semi‐solid MT effects, and provides a more specific NOE coupling rate‐ and solute transverse relaxation rate‐weighted signal. Animal studies show that the ratiometric NOE(−1.6) decreases dramatically in brain tumors, which suggests that the change in the NOE(−1.6) coupling rate and/or the solute transverse relaxation rate are major contributors to the previously observed hypointense NOE(−1.6) signal in tumors.
Hyperemesis Gravidarum
Authors: Austin Kerstin , Wilson Kelley , Saha Sumona
Published: October 2018

Nausea and vomiting of pregnancy affect the majority of pregnancies, while the most severe version, hyperemesis gravidarum (HG), affects a much smaller subset of women. Despite the prevalence of nausea and vomiting of pregnancy and the severe consequences of HG, the pathophysiology of these conditions is not fully understood. Currently, it is thought that a combination of hormonal factors accounts for their development. Multiple treatments have been described for nausea and vomiting of pregnancy and HG with varying levels of success. In this paper we describe the epidemiology of nausea and vomiting of pregnancy and HG, the recommended workup, their proposed etiologic factors, treatments, and their potential impact on mother and baby.
Asymmetric sensorineural hearing loss is a risk factor for late‐onset hearing loss in pediatric cancer survivors following cisplatin treatment
Authors: Robertson Margaret S. , Hayashi Susan S. , Camet Miranda L. , Trinkaus Kathryn , Henry Jennifer , Hayashi Robert J.
Published: October 2018

Background

Ototoxicity is a significant complication of cisplatin treatment. Hearing loss can be symmetric or asymmetric, and may decline after therapy. This study examined the risks of asymmetric and late‐onset hearing loss (LOHL) in cisplatin‐treated pediatric patients with cancer.

Methods

A retrospective review of 993 patients’ medical and audiological charts from August 1990 to March 2015 was conducted using stringent criteria to characterize patients with asymmetric hearing loss (AHL) or LOHL. Audiologic data were reviewed for 248 patients that received cisplatin to assess cisplatin‐induced sensorineural hearing loss and its associated risk factors.

Results

Of the patients evaluable for AHL, 26% exhibited this finding. Of those evaluable for LOHL, 42% of the patients’ hearing worsened more than 6 months after therapy completion. Radiation and type of cancer diagnosis were major risk factors for both AHL and LOHL. Furthermore, LOHL was linked to age of diagnosis, noncranial radiation, and longer audiologic follow‐up. AHL was strongly associated with LOHL—60% of patients with AHL also had LOHL. Logistic regression analysis revealed that patients with AHL (OR 6.3, 95% CI: 2.2‐17.8, P = 0.0005) or those receiving radiation (OR 3.2, 95% CI: 1.2‐8.6, P = 0.02) were at greatest risk for LOHL.

Conclusion

Children receiving cisplatin therapy are at risk for developing AHL and LOHL. Those that have received radiation and/or with AHL are at increased risk for further hearing decline. Long‐term monitoring of these patients is important for early intervention as hearing diminishes.