bluuebunny/crossref_metadata_2025 huggingface dataset:
Library orientation in blackboard: supporting online and distance learners
Authors: Schrecker Diane L.
Published: July 2017

Purpose

This paper presents a comprehensive review of the poster session “Library orientation in blackboard: supporting online and distance learners” presented at the Association of College and Research Libraries (ACRL) 2017 conference in Baltimore, Maryland.

Design/methodology/approach

Development of AU Library Student Orientation in Blackboard is discussed from the initial course proposal up to its completion of first year use. Orientation modules are reviewed and include purpose, organization and technology resources utilized to deliver content.

Findings

Complete library orientation information including project timeline, marketing, learning management systems (LMS) usage data, survey and assessment outcomes, video viewing statistics and plans for moving forward are provided.

Practical implications

This paper details steps taken and resources used to develop an online library orientation suitable for any LMS. Project design, orientation module structure and select orientation resources are provided.

Originality/value

This paper addresses the need for academic library orientation to support online and distant learners by delivering a practical library introduction in Blackboard.
Assembly of microbial communities in replicate nutrient‐cycling model ecosystems follows divergent trajectories, leading to alternate stable states
Authors: Pagaling Eulyn , Vassileva Kristin , Mills Catherine G. , Bush Timothy , Blythe Richard A. , Schwarz‐Linek Jana , Strathdee Fiona , Allen Rosalind J. , Free Andrew
Published: July 2017

We studied in detail the reproducibility of community development in replicate nutrient‐cycling microbial microcosms that were set up identically and allowed to develop under the same environmental conditions. Multiple replicate closed microcosms were constructed using pond sediment and water, enriched with cellulose and sulphate, and allowed to develop over several months under constant environmental conditions, after which their microbial communities were characterized using 16S rRNA gene sequencing. Our results show that initially similar microbial communities can follow alternative – yet stable – trajectories, diverging in time in a system size‐dependent manner. The divergence between replicate communities increased in time and decreased with larger system size. In particular, notable differences emerged in the heterotrophic degrader communities in our microcosms; one group of steady state communities was enriched with Firmicutes, while the other was enriched with Bacteroidetes. The communities dominated by these two phyla also contained distinct populations of sulphate‐reducing bacteria. This biomodality in community composition appeared to arise during recovery from a low‐diversity state that followed initial cellulose degradation and sulphate reduction.
Quality and yield of Ricotta cheese as affected by milk fat content and coagulant type
Authors: Ortiz Araque Leidy C , Darré Magali , Ortiz Cristian M , Massolo Juan F , Vicente Ariel R
Published: July 2017

Milk processing conditions can exert a large influence on the quality of acid‐coagulated cheeses. Herein, we evaluated the influence of milk fat content and coagulant type on Ricotta yield and physical, chemical and sensory properties. Fat‐free Ricotta was hard and whiter than reduced‐fat or full‐fat Ricotta. Ricotta produced from low‐fat and whole milk showed no differences in acceptability, indicating that fat content could be substantially reduced without impairing quality. Milk coagulation by citric acid decreased Ricotta moisture, firmness and yield, whereas calcium chloride produced a white Ricotta with desired firmness and high consumer acceptability.
Hygiene: microbial strategies to reduce pathogens and drug resistance in clinical settings
Authors: Caselli Elisabetta
Published: July 2017

Healthcare‐associated infections (HAIs) are a global concern, affecting all western hospitals, and profoundly impairing the clinical outcome of up to 15% of all hospitalized patients. Persistent microbial contamination of hospital surfaces has been suggested to contribute to HAIs onset, representing a reservoir for hospital pathogens. On the other hand, conventional chemicals‐based sanitation do not prevent recontamination and can select drug‐resistant strains, resulting in over 50% of surfaces persistently contaminated. There is therefore an urgent need for alternative sustainable and effective ways to control pathogens contamination and transmission. Toward this goal, we recently reported that a probiotic‐based sanitation can stably decrease surface pathogens up to 90% more than conventional disinfectants, without selecting resistant species. This paper summarizes some of our most significant results.
Integrated structural biology and molecular ecology of N‐cycling enzymes from ammonia‐oxidizing archaea
Authors: Tolar Bradley B. , Herrmann Jonathan , Bargar John R. , van den Bedem Henry , Wakatsuki Soichi , Francis Christopher A.
Published: July 2017

Knowledge of the molecular ecology and environmental determinants of ammonia‐oxidizing organisms is critical to understanding and predicting the global nitrogen (N) and carbon cycles, but an incomplete biochemical picture hinders in vitro studies of N‐cycling enzymes. Although an integrative structural and dynamic characterization at the atomic scale would advance our understanding of function tremendously, structural knowledge of key N‐cycling enzymes from ecologically relevant ammonia oxidizers is unfortunately extremely limited. Here, we discuss the challenges and opportunities for examining the ecology of ammonia‐oxidizing organisms, particularly uncultivated Thaumarchaeota, through (meta)genome‐driven structural biology of the enzymes ammonia monooxygenase (AMO) and nitrite reductase (NirK).
Caloric restriction impacts plasma microRNAs in rhesus monkeys
Authors: Schneider Augusto , Dhahbi Joseph M. , Atamna Hani , Clark Josef P. , Colman Ricki J. , Anderson Rozalyn M.
Published: July 2017

Caloric restriction (CR) is one of the most robust interventions shown to delay aging in diverse species, including rhesus monkeys (Macaca mulatta). Identification of factors involved in CR brings a promise of translatability to human health and aging. Here, we show that CR induced a profound change in abundance of circulating microRNAs (miRNAs) linked to growth and insulin signaling pathway, suggesting that miRNAs are involved in CR's mechanisms of action in primates. Deep sequencing of plasma RNA extracts enriched for short species revealed a total of 243 unique species of miRNAs including 47 novel species. Approximately 70% of the plasma miRNAs detected were conserved between rhesus monkeys and humans. CR induced or repressed 24 known and 10 novel miRNA species. Regression analysis revealed correlations between bodyweight, adiposity, and insulin sensitivity for 10 of the CR‐regulated known miRNAs. Sequence alignment and target identification for these 10 miRNAs identify a role in signaling downstream of the insulin receptor. The highly abundant miR‐125a‐5p correlated positively with adiposity and negatively with insulin sensitivity and was negatively regulated by CR. Putative target pathways of CR‐associated miRNAs were highly enriched for growth and insulin signaling that have previously been implicated in delayed aging. Clustering analysis further pointed to CR‐induced miRNA regulation of ribosomal, mitochondrial, and spliceosomal pathways. These data are consistent with a model where CR recruits miRNA‐based homeostatic mechanisms to coordinate a program of delayed aging.
The Study of Depressive Disorders Using the PSE‐ID‐CATEGO System
Authors: Bebbington P. , Sturt E. , Kumakura N.
Published: July 2017

The PSE‐CATEGO‐ID system and its approach to the sub‐classification of depression is described. The principle of sub‐classification partly corresponds to the empirical relationships between symptoms on affective disorder. Comparison of CATEGO and DSM III demonstrates that major differences of classification can arise because of differences of the classificatory algorithm even though similar lists of symptoms are used. Empirical studies of the PSE‐CATEGORO‐ID system are described and their importance in providing evidence for a rational choice between classificatory system is emphasised.
Depressive Syndromes and Scales in the AMDP‐system
Authors: Pietzcker A. , Gebhardt R.
Published: July 2017

The Association for Methodology and Documentation in Psychiatry was founded in 1965 by a group of psychiatrists from Germany, Switzerland and Austria. It developed a uniform and comprehensive system for the documentation of psychopathological, somatic, and anamnestic findings, the AMP‐System. In 1979 a revised system was introduced, the AMDP‐System.

In the AMP‐System there are 5 suggestions as to syndrome scale construction based on analyses of data of psychiatric clinics in Munich (2 samples), in Zurich (1 sample), and in Berlin (2 samples). The corresponding syndromes of the different solutions are highly intercorrelated. In the AMDP‐System final syndrome scales were constructed on the basis of combined samples of the psychiatric clinics of the universities in Munich and in Berlin. The AMDP syndrome scales show a high similarity with the AMP syndrome scales, whereby a good comparability is ensured between older studies using the AMP‐ and present studies using the AMDP‐System.

All syndrome scale solutions include, besides 6 or 7 other syndromes, like a paranoid‐hallucinatory and a manic syndrome, two syndromes especially pertinent to the assessment of depressive states: the depressive and the apathy syndromes. The syndromes are described and it is shown how they and other syndromes discriminate different depressive diseases (defined by ICD‐diagnoses).

There is a considerable overlap in psychology between the diagnostic groups — in spite of a remarkable good discrimination of these groups by psychopathological syndromes — therefore the patients were classified de novo by cluster analysis in more homogenous groups regarding psychopathology. The results are illustrated by some “depressive” clusters in comparison to depressive diagnostic groups.
Building an Efficient Financial System in China: A Need for Stronger Market Discipline
Authors: Huang Yiping , Wang Xu
Published: July 2017

China has built a very comprehensive financial system, but has not let the market mechanism work freely. This unique pattern, rooted in China's dual‐track reform strategy between state and non‐state sectors, did not prevent a strong economic performance in the past, but is now a main cause of economic inefficiency and financial risks. The rapid development of digital finance is a back‐door way of financial liberalization, responding to both old repressive policies and new technologies. To accomplish the mission of building an efficient financial system, the government needs to take at least three further steps in financial reform: creating a level‐playing field; freeing up the market mechanism; and improving regulation. The key test lies in the effective enforcement of market discipline for corporate and financial institutions.
Local Government Debt and Firm Leverage: Evidence from China
Authors: Liang Yousha , Shi Kang , Wang Lisheng , Xu Juanyi
Published: July 2017

China's local government debt financing has been expanded aggressively to support infrastructure investment, especially since the enactment of four‐trillion‐yuan stimulus plan to stimulate the economy post global financial crisis. At the same time, the rapid increase of firm‐level leverage ratio of state‐owned enterprises (SOEs) and the decline of leverage ratio of non‐SOEs jointly deteriorated China's credit misallocation problem. In this study, we empirically test the effect of local government debton firm leverage in China. We find that an expansion of local government debt significantly crowded out the leverage of non‐SOEs, while crowded in that of SOEs. Moreover, the effect differed across industries and sectors.
China's New Role in the International Financial Architecture
Authors: Drysdale Peter , Triggs Adam , Wang Jiao
Published: July 2017

The rise of China is challenging the international financial architecture in a number of ways. This paper highlights three that are of critical importance: the challenge of absorbing massive Chinese savings; the incorporation of China into a cohesive global financial safety net; and the organisation of China's participation in funding the demand for international investment projects. The global financial architecture needs to be reformed. But what role should China play? The paper defines the options open to China and the opportunities and barriers it will face. We argue that China can work with the established economic powers in reforming the existing architecture. At the same time, China seeks cooperation in building new institutions and organisations that fill gaps in the existing arrangements. But no matter how international financial diplomacy plays out in the near term, deep financial and economic reform at home will alone deliver China a central role in the international financial architecture. Domestic reform could also attend to some of the challenges that currently plague China's impact on the system. The success or failure of these domestic reforms will be at the crux of the strength or fragility of the international financial architecture in the years ahead.
Genome‐wide association analysis identifies the genetic basis of fat deposition in the tails of sheep (Ovis aries)
Authors: Xu S.‐S. , Ren X. , Yang G.‐L. , Xie X.‐L. , Zhao Y.‐X. , Zhang M. , Shen Z.‐Q. , Ren Y.‐L. , Gao L. , Shen M. , Kantanen J. , Li M.‐H.
Published: July 2017

Fat‐tailed sheep (Ovis aries) can survive in harsh environments and satisfy human's intake of dietary fat. However, the animals require more feed, which increases the cost of farming. Thus, most farmers currently prefer thin‐tailed, short‐tailed or docked sheep. To date, the molecular mechanism of the formation of fat tails in sheep has not been completely elucidated. Here, we conducted a genome‐wide association study using phenotypes and genotypes (the Ovine Infinium HD SNP BeadChip genotype data) of two breeds of contrasting tail types (78 Small‐tailed and 78 Large‐tailed Han sheep breeds) to identify functional genes and variants associated with fat deposition. We identified four significantly (rs416433540, rs409848439, rs408118325 and rs402128848) and three approximately associated autosomal SNPs (rs401248376, rs402445895 and rs416201901). Gene annotation indicated that the surrounding genes (CREB1, STEAP4, CTBP1 and RIP140, also known as NRIP1) function in lipid storage or fat cell regulation. Furthermore, through an X‐chromosome‐wide association analysis, we detected significantly associated SNPs in the OARX: 88–89 Mb region, which could be a strong candidate genomic region for fat deposition in tails of sheep. Our results represent a new genomic resource for sheep genetics and breeding. In addition, the findings provide novel insights into genetic mechanisms of fat deposition in the tail of sheep and other mammals.
Fibre Dissection and Sectional Study of the Major Porcine Cerebral White Matter Tracts
Authors: Pascalau R. , Szabo B.
Published: July 2017

White matter anatomy is the basis for numerous applications in neurology, neurosurgery and fundamental neuroscience. Although the porcine brain is frequently used as experimental model in these fields of research, the description of its white matter is not as thorough as in the human brain or other species. Thus, the aim of this study is to describe the porcine white matter tracts in a complex manner. Two stepwise dissection protocols adapted from human anatomy were performed on six adult pig brain hemispheres prepared according to the Klingler method. Other four hemispheres were sectioned along section planes that were chosen similar to the Talairach coordinate system. As a result, three commissural tracts, seven association tracts and one projection tract were identified: corpus callosum, fornix, commissura rostralis, the short‐association tracts, fasciculus longitudinalis superior, fasciculus uncinatus, fasciculus longitudinalis inferior, fasciculus occipitofrontalis inferior, cingulum, tractus mamillothalamicus and capsula interna. They were described and illustrated from multiple points of view, focusing on their trajectory, position, dimensions and anatomical relations. All in all, we achieved a three‐dimensional understanding of the major tracts. The results are ready to be applied in future imagistic or experimental studies.
Anterior Femoral Bow and Possible Effect on the Stifle Joint: A Comparison between Humans and Dogs
Authors: Ocal M. K. , Sabanci S. S. , Cobanoglu M. , Enercan M.
Published: July 2017

The aim of the study was to compare the anterior bow of the femur between dogs and humans in terms of the possible impact on the stifle joint. The femoral radiographs obtained retrospectively were used to determine the angles and positions of the anterior bow in both dogs (n = 135) and humans (n = 57). Descriptive statistics and Pearson's correlation analysis were used for the statistical analyses of the variables. The mean anterior bow angle (ABA) was 18.3 ± 2.02° and 4.88 ± 1.24° in dogs and humans, respectively. The bow position was at the distal shaft in dogs (64.9 ± 2.04%) and almost at the mid‐shaft of the bone (46.5 ± 5.52%) in humans. The ABA was related to the bow position in both humans and dogs. Additionally, the angle correlated with age in humans, while it was correlated with weight and breed in dogs. In conclusion, it is suggested that the anterior bow should be used as a landmark on the femoral axis for the biomechanical research of stifle joint, and dog stifle could be used as a suitable model for human knee in experimental studies for clinicians, while making sure that ethical principles are fully respected.
Prevalence and predictors of substance use disorders among homeless women seeking primary care: An 11 site survey
Authors: Upshur Carole Christofk , Jenkins Darlene , Weinreb Linda , Gelberg Lillian , Orvek Elizabeth Aaker
Published: July 2017

Background and Objectives

Homeless women have shown high rates of substance use disorders (SUD), but many studies are more than a decade old, limited in geographic location, or focus only on women living outdoors or in shelters. The purpose of this study was to obtain a more current and representative sample of homeless women and the prevalence and predictors of substance use disorders among women seeking primary care at Health Care for the Homeless clinics across the US.

Methods

Eleven Health Care for the Homeless (HCH) clinics in nine states contributed proportionally to a sample of n = 780 female patients who completed a self‐administered survey including demographics, housing history, health, mental health, and drug and alcohol use.

Results

Compared to the general population of women, rates were four times higher for an alcohol use disorder, and 12 times higher for a drug use disorder.

Discussion and Conclusions

The findings indicate a significant need for SUD services, with an equally high need for mental health services. In addition, high rates of victimization and use of tobacco, and overall poor health status, indicate overall health disparities.

Scientific Significance

Addressing barriers to full integration of substance use and mental health services, such as improving screening, reimbursement, clinician training, and addressing biases about motivation of this population to engage in treatment, are necessary to improve the health of women seeking care in HCH settings. (Am J Addict 2017;26:680–688)
The impact after 50 years of a new medical education programme with a regional workforce mission
Authors: Hays Richard , Bowles Sarah , Brown Terry , Lawler Anthony , Vickers James
Published: July 2017

Background

Tasmania established its medical programme in 1965 to produce graduates to address medical workforce recruitment challenges. Many Tasmanian graduates work in Tasmania, but workforce problems continue. This paper reports the workforce outcomes of the first 42 graduating cohorts.

Methods

A database for all University of Tasmania medical graduates from the years 1970 to 2011 was developed by combining information from university, registration and local workforce survey databases.

Results

A total of 2012 doctors graduated from 1971 to 2011 and 1707 (85%) were registered, most commonly in general practice (45.8%), medicine (13%), anaesthetics (7.9%), surgery (7.5%), psychiatry (4.3%), emergency medicine (35, 3.5%), paediatrics (3.4%) and pathology (3.3%). While 41.9% worked in Tasmania, they comprised 35.6% of the local workforce and were clustered around the two larger cities. The proportion entering general practice has fallen since 1980s.

Discussion

The contribution of the Tasmanian medical programme is substantial but appears less than other regional medical schools. Relatively few work in smaller communities, particularly in specialties other than general practice. Lifestyle choices and the availability of training opportunities and career positions might be contributing factors. The medical school has established clinical schools in rural communities, promoted admission of rural applicants and increased rural clinical placement opportunities, with some early signs of success.

Conclusion

The Tasmanian medical programme is important in this regional, island economy, but the rural and remote communities have not benefited as much as the two larger cities. Sustaining a regional workforce mission over time might require frequent adjustments to admissions and curriculum processes.
Vascular and metabolic comorbidities in open‐angle glaucoma with low‐ and high‐teen intraocular pressure: a cross‐sectional study from South Korea
Authors: Lee Si Hyung , Kim Gyu Ah , Lee Wonseok , Bae Hyoung Won , Seong Gong Je , Kim Chan Yun
Published: July 2017

Purpose

To assess the associations between vascular and metabolic comorbidities and the prevalence of open‐angle glaucoma (OAG) with low‐teen and high‐teen intraocular pressure (IOP) in Korea.

Methods

Cross‐sectional data from the Korean National Health and Nutrition Examination Survey from 2008 to 2012 were analysed. Participants diagnosed with OAG with normal IOP were further classified into low‐teen IOP (IOP ≤ 15 mmHg) and high‐teen IOP (15 mmHg < IOP ≤ 21 mmHg) groups. Using multiple logistic regression analyses, the associations between vascular and metabolic comorbidities and the prevalence of glaucoma were investigated for the low‐ and high‐teen IOP groups.

Results

The prevalences of hypertension, hyperlipidemia, ischaemic heart disease, stroke and metabolic syndrome were significantly higher among subjects with low‐teen OAG compared with normal subjects, while only the prevalences of hypertension and stroke were higher among subjects with high‐teen OAG compared with normal subjects. In multivariate logistic regression models adjusted for confounding factors, low‐teen OAG was significantly associated with hypertension (OR, 1.68; 95% CI, 1.30–2.18), hyperlipidemia (OR, 1.49; 95% CI, 1.07–2.08), ischaemic heart disease (OR, 1.83; 95% CI, 1.07–3.11), stroke (OR, 1.91; 95% CI, 1.12–3.25) and metabolic syndrome (OR, 1.46; 95% CI, 1.12–1.90). High‐teen OAG was only associated with stroke (OR, 2.58; 95% CI, 1.20–5.53).

Conclusion

Various vascular and metabolic comorbidities were significantly associated with low‐teen OAG, but not with high‐teen OAG. These data support the hypothesis that vascular factors play a more significant role in the pathogenesis of OAG with low‐teen baseline IOP.
Psychometric properties of the Malay Schizotypal Personality Questionnaire: Measurement invariance and latent mean comparisons in Malaysian adults
Authors: Barron David , Morgan Kevin D. , Towell Tony , Jaafar Jas L. , Swami Viren
Published: July 2017

Introduction

The Schizotypal Personality Questionnaire (SPQ) is a widely used self‐report measurement instrument for the assessment of schizotypal personality traits. However, the factor structure of the SPQ has been a matter of some debate. As a contribution to this debate, we examined the factor structure of the SPQ in Malaysian adults.

Method

A total of 382 Malaysian adults completed a Malay translation of the SPQ. Confirmatory factory analysis was used to examine the fit of 3‐ and 4‐factor solutions for the higher‐order dimensionality of the SPQ. Ethnic invariance for the best‐fitting model was tested at the configural, metric, and scalar levels, and a multivariate analysis of variance was used to examine sex and ethnicity differences in domain scores.

Results

The 4‐factor model provided a better fit to the data than did the 3‐factor model. The 4‐factor model also demonstrated partial measurement invariance across ethnic groups. Latent mean comparisons for sex and ethnicity revealed a number of significant differences for both factors, but effect sizes were small.

Discussion

The 4‐factor structure of the SPQ received confirmatory support and can be used in Malay‐speaking populations.
Letter: functional dyspepsia is associated with duodenal eosinophilia in an Australian paediatric cohort—methodological issues to avoid misinterpretation
Authors: Safiri S. , Ayubi E.
Published: July 2017

Linked Content

This article is linked to Wauters et al papers. To view these articles visit https://doi.org/10.1111/apt.14045 and https://doi.org/10.1111/apt.14178.
Laparoscopic total gastrectomy for advanced gastric cancer in a patient with situs inversus totalis
Authors: Shibata Kengo , Kawamura Hideki , Ichikawa Nobuki , Shibuya Kazuaki , Yoshida Tadashi , Ohno Yosuke , Homma Shigenori , Taketomi Akinobu
Published: July 2017

Situs inversus totalis (SIT) is a rare congenital anomaly. Generally, laparoscopic surgery is difficult to perform in patients with SIT because of both the potential challenges associated with unexpected vascular anomalies and the lack of standardized strategy for handling such cases. This is the first report of laparoscopic total gastrectomy with lymph node dissection for advanced gastric cancer in a patient with SIT. A 79‐year‐old man with SIT was diagnosed with advanced gastric cancer. We performed laparoscopic total gastrectomy with modified D2 lymph node dissection (D2 without splenectomy) and esophagojejunal anastomosis using an overlap method involving retrocolic Roux‐en‐Y reconstruction. The total operating time was 232 min, and blood loss was 110 mL. There were no postoperative complications. In summary, laparoscopic total gastrectomy for gastric cancer can be performed safely, even in a patient with SIT.
Expression level of the cytochrome P450c21 (CYP21) protein correlating to drip loss in pigs
Authors: Kaewkot Aungsuma , Boonkaewwan Chaiwat , Noosud Jatuporn , Kayan Autchara
Published: July 2017

Drip loss is an important meat quality trait of fresh meat affecting economic losses. The cytochrome P450c21 (CYP21) protein has a role on cortisol production and depends on stress. This might affect meat quality. The present study aimed to investigate the expression of CYP21 protein in correlation with drip loss. The samples were taken from the Longissimus dorsi muscle to evaluate drip loss (n = 300). Five muscles per group (low and high drip loss) were selected to evaluate CYP21 protein expression levels. Statistical analysis revealed that CYP21 protein expression levels were significantly difference between the drip loss groups. The high drip loss group had higher CYP21 protein expression levels than the low drip loss group (P < 0.05). Moreover, the high drip loss group had higher optical density values of the CYP21 protein band than the low drip loss group (P < 0.05). In conclusion, the expression of CYP21 protein will provide the basis for information and better understanding of the mechanisms related to drip loss in pork. Further study is warranted to validate these results in other populations.
Elotuzumab plus lenalidomide/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT‐2 follow‐up and post‐hoc analyses on progression‐free survival and tumour growth
Authors: Dimopoulos Meletios A. , Lonial Sagar , White Darrell , Moreau Philippe , Palumbo Antonio , San‐Miguel Jesus , Shpilberg Ofer , Anderson Kenneth , Grosicki Sebastian , Spicka Ivan , Walter‐Croneck Adam , Magen Hila , Mateos Maria‐Victoria , Belch Andrew , Reece Donna , Beksac Meral , Bleickardt Eric , Poulart Valerie , Sheng Jennifer , Sy Oumar , Katz Jessica , Singhal Anil , Richardson Paul
Published: July 2017

The randomized phase III ELOQUENT‐2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab + lenalidomide/dexamethasone (ELd) versus lenalidomide/dexamethasone (Ld) in relapsed/refractory multiple myeloma. ELd reduced the risk of disease progression/death by 30% versus Ld (hazard ratio [HR] 0·70). Median time from diagnosis was 3·5 years. We present extended 3‐year follow‐up data. Endpoints included progression‐free survival (PFS), overall response rate (ORR) and interim overall survival (OS). Exploratory post‐hoc analyses included impact of time from diagnosis and prior lines of therapy on PFS, and serum M‐protein dynamic modelling. ORR was 79% (ELd) and 66% (Ld) (P = 0·0002). ELd reduced the risk of disease progression/death by 27% versus Ld (HR 0·73; P = 0·0014). Interim OS demonstrated a trend in favour of ELd (P = 0·0257); 1‐, 2‐ and 3‐year rates with ELd versus Ld were: 91% versus 83%, 73% versus 69% and 60% versus 53%. In patients with ≥ median time from diagnosis and one prior therapy, ELd resulted in a 53% reduction in the risk of progression/death versus Ld (HR 0·47). Serum M‐protein dynamic modelling showed slower tumour regrowth with ELd. Adverse events were comparable between arms. ELd provided a durable and clinically relevant improvement in efficacy, with minimal incremental toxicity.
Guidelines for the use of imaging in the management of patients with myeloma
Authors: Chantry Andrew , Kazmi Majid , Barrington Sally , Goh Vicky , Mulholland Nicola , Streetly Matthew , Lai Maggie , Pratt Guy ,   the British Society for Haematology Guidelines
Published: July 2017

The role of imaging in myeloma has gained increasing importance over the past few years. The recently revised definition of myeloma from the International Myeloma Working Group (IMWG) includes cross sectional imaging as a method to define bone disease and also incorporates its use in the disease definition for patients with suspected smouldering myeloma. The National Institute for Health and Care Excellence myeloma guidelines also recommend cross sectional imaging for patients with suspected myeloma. There is also increasing use of imaging in disease assessments and the International Myeloma Working Group has recently incorporated imaging in defining new response categories of minimal residual disease negativity, with or without imaging‐based evidence of disease. Plain X‐rays have previously been the standard imaging modality included in a myeloma work up at presentation but evidence is mounting for use of cross‐sectional modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and 18fluoro‐deoxyglucose (18F‐FDG) positron emission tomography (PET)/CT. Funding and therefore availability of newer imaging techniques remains a barrier. Here, we propose an evidence‐based approach to the use and technical application of the latest imaging modalities at diagnosis and in the follow‐up of patients with myeloma and plasmacytoma.
Bone marrow biopsies do not impact response assessment for follicular lymphoma patients treated on clinical trials
Authors: Rutherford Sarah C. , Li Valery , Ghione Paola , Chen Zhengming , Martin Peter , Leonard John P.
Published: July 2017

Clinical trials enrolling follicular lymphoma (FL) patients typically require bone marrow biopsies (BMBs) at baseline and at a subsequent point if complete response is achieved. These procedures are painful, take time and add cost. We hypothesized that BMBs do not provide information significant for response assessment in most follicular lymphoma patients on clinical trials. We identified 99 patients treated on clinical trials for follicular lymphoma between 2000 and 2016. BMBs resulted in a possible response assessment change in 1·0% of patients (95% confidence interval: 0·0–5·5%). We conclude that mandatory BMBs at baseline and for response assessment are unnecessary in clinical trials for follicular lymphoma.
Collective Bargaining and Technological Investment: The Case of Nurses’ Unions and the Transition from Paper‐Based to Electronic Health Records
Authors: Litwin Adam Seth
Published: July 2017

Does the presence of a unionized nursing workforce retard US hospitals’ transition from paper‐based to electronic health records (EHRs)? After tying archival data on hospitals’ structural features and health information technology (IT) investment patterns to self‐gathered data on unionism, I find that hospitals that bargain collectively with their registered nurses (RNs) appear to delay or forego the transition away from paper, consistent with existing theory and research in industrial relations and institutional economics. However, this relationship is fully mediated by a hospital's payer mix: those serving a larger share of less lucrative, elderly, disabled and indigent patients are more likely to adopt EHRs if they are unionized than if they are not, a result that holds even at the median payer mix. Indeed, this accords with research on the interplay of labour and technology as the aforementioned dynamics are driven entirely by RN‐exclusive bargaining units for whom the new IT serves as a complement rather than as a substitute in production. Given the outsized role that unions play in the US healthcare sector, the overall sluggish performance of the sector, and the expectations that policymakers have for EHRs, evidence that these unions are welfare‐enhancing should be welcome news.
Intersection of retinoblastoma tumor suppressor function, stem cells, metabolism, and inflammation
Authors: Kitajima Shunsuke , Takahashi Chiaki
Published: July 2017

The Retinoblastoma (RB) tumor suppressor regulates G1/S transition during cell cycle progression by modulating the activity of E2F transcription factors. The RB pathway plays a central role in the suppression of most cancers, and RB mutation was initially discovered by virtue of its role in tumor initiation. However, as cancer genome sequencing has evolved to profile more advanced and treatment‐resistant cancers, it has become increasingly clear that, in the majority of cancers, somatic RB inactivation occurs during tumor progression. Furthermore, despite the presence of deregulation of cell cycle control due to an INK4A deletion, additional CCND amplification and/or other mutations in the RB pathway, mutation or deletion of the RB gene is often observed during cancer progression. Of note, RB inactivation during cancer progression not only facilitates G1/S transition but also enhances some characteristics of malignancy, including altered drug sensitivity and a return to the undifferentiated state. Recently, we reported that RB inactivation enhances pro‐inflammatory signaling through stimulation of the interleukin‐6/STAT3 pathway, which directly promotes various malignant features of cancer cells. In this review, we highlight the consequences of RB inactivation during cancer progression, and discuss the biological and pathological significance of the interaction between RB and pro‐inflammatory signaling.
Inactivating mutations and hypermethylation of the NKX2‐1/TTF‐1 gene in non‐terminal respiratory unit‐type lung adenocarcinomas
Authors: Matsubara Daisuke , Soda Manabu , Yoshimoto Taichiro , Amano Yusuke , Sakuma Yuji , Yamato Azusa , Ueno Toshihide , Kojima Shinya , Shibano Tomoki , Hosono Yasuyuki , Kawazu Masahito , Yamashita Yoshihiro , Endo Shunsuke , Hagiwara Koichi , Fukayama Masashi , Takahashi Takashi , Mano Hiroyuki , Niki Toshiro
Published: July 2017

The major driver mutations of lung cancer, EGFR mutations and EML4‐ALK fusion, are mainly detected in terminal respiratory unit (TRU)‐type lung adenocarcinomas, which typically show lepidic and/or papillary patterns, but are rarely associated with a solid or invasive mucinous morphology. In order to elucidate the key genetic events in non‐TRU‐type lung cancer, we carried out whole‐exome sequencing on 43 non‐TRU‐type lung adenocarcinomas based on morphology (17 acinar, nine solid, and two enteric adenocarcinomas, and 15 adenocarcinomas with a mucinous morphology). Our analysis identified mutations in TP53 (16/43, 37.2%), KRAS (13/43, 30.2%), and NKX2‐1/TTF‐1 (7/43; 16.3%) as the top three significantly mutated genes, while the EGFR mutation was rare (1/43, 2.3%) in this cohort. Eight NKX2‐1/TTF‐1 mutations (five frameshift, two nonsense, and one missense) were identified, with one case harboring two distinct NKX2‐1/TTF‐1 mutations (one missense and one frameshift). Functional assays with the NK2 homeobox 1 (NKX2‐1)/thyroid transcription factor 1 (TTF‐1) mutants revealed that none of them retain the activity as a transcriptional factor. Histologically, invasive mucinous adenocarcinomas accounted for most of the NKX2‐1/TTF‐1 mutations (five cases), as well as one enteric and one acinar adenocarcinoma. Immunohistochemistry showed that the cohort was largely divided into TTF‐1‐postive/hepatocyte nuclear factor 4‐α (HNF4‐α)‐negative and TTF‐1‐negative/HNF4‐α‐positive groups. NKX2‐1/TTF‐1 mutations were exclusively found in the latter, in which the gastrointestinal markers, mucin 5AC and cytokeratin 20, were frequently expressed. Bisulfite sequencing revealed that the NKX2‐1/TTF‐1 gene body was highly methylated in NKX2‐1/TTF‐1‐negative cases, including those without the NKX2‐1/TTF‐1 mutations. The genetic or epigenetic inactivation of NKX2‐1/TTF‐1 may play an essential role in the development and aberrant differentiation of non‐TRU‐type lung adenocarcinomas.
Modeling the Early Language Trajectory of Language Development When the Measures Change and Its Relation to Poor Reading Comprehension
Authors: Petscher Yaacov , Justice Laura M. , Hogan Tiffany
Published: July 2017

This study examined change in early language comprehension from 15 to 54 months for fifth‐grade typical readers (n = 35), poor decoders (n = 11), or poor comprehenders (n = 16) from a nationally representative study of early child‐care experiences. Changing measures of language comprehension were captured across early childhood for the 62 children. Multiple‐group quasi‐simplex and latent growth models were used on rank‐transformed outcomes to examine children's relative rank change. Results showed that future poor comprehenders significantly declined in language comprehension over time relative to others who gradually improved. Efforts to improve language skills as a means to improve reading comprehension hinge upon the perspective that language weaknesses are a causal contributor to reading difficulties.
Nerve growth factor regulation and production by macrophages in osteoarthritic synovium
Authors: Takano S , Uchida K , Inoue G , Miyagi M , Aikawa J , Iwase D , Iwabuchi K , Matsumoto T , Satoh M , Mukai M , Minatani A , Takaso M
Published: July 2017

Nerve growth factor (NGF) functions to modulate osteoarthritis (OA)-associated pain. Although recent studies suggest that tumour necrosis factor (TNF)-α and interleukin (IL)-1β mediate NGF activity in human synovial fibroblasts, the regulation of NGF expression in human synovial macrophages remains unclear. Here, we examined the role of macrophages in the production and regulation of synovial (SYN) NGF in osteoarthritic knee joints by examining the mRNA expression of TNF-α and IL-1β in freshly isolated CD14-positive (macrophage-rich fraction) and CD14-negative cells (fibroblast-rich fraction) in synovial tissue from OA patients by quantitative polymerase chain reaction. We also examined the effects of IL-1β and TNF-α on NGF mRNA expression in cultured CD14-positive (macrophage-rich fraction) and CD14-negative cells (fibroblast-rich fraction). In addition, to examine the contribution of macrophages to NGF, TNF-α and IL-1β expression, we injected clodronate liposomes systemically into STR/Ort mice, an osteoarthritis animal model, to deplete macrophages. TNF-α and IL-1β mRNA levels in CD14-positive cells from the SYN of OA patients was significantly higher than that in CD14-negative cells, while NGF expression did not differ markedly between the two cell fractions. In addition, treatment of human cultured CD14-positive and -negative cells with IL-1β and TNF-α enhanced NGF mRNA and protein levels. Expression of NGF, IL-1β and TNF-α was also reduced significantly in STR/Ort mice upon macrophage depletion. These findings suggest that IL-1β and TNF-α regulate NGF expression and production in synovial macrophages and fibroblasts in osteoarthritic joints.
Significant augmentation of regulatory T cell numbers occurs during the early neonatal period
Authors: Hayakawa S , Ohno N , Okada S , Kobayashi M
Published: July 2017

Regulatory T cells (Tregs) control immune responses by suppressing various inflammatory cells. Tregs in newborn babies may play an important role in preventing excessive immune responses during their environmental change. We examined the number and phenotype of Tregs during the neonatal period in 49 newborn babies. Tregs were characterized by flow cytometry using cord blood (CB) and peripheral blood (PB) from the early (7–8 days after birth) and late (2–4 weeks after birth) neonatal periods. CD4+forkhead box protein 3 (FoxP3+) T cells were classified into resting Tregs (CD45RA+FoxP3low), activated Tregs (CD45RA– FoxP3high) and newly activated T cells (CD45RA– FoxP3low). Compared with CB and PB during the late neonatal period, the percentage of Tregs and all Treg subpopulations in the CD4+ lymphocyte population were increased significantly during the early neonatal period. Furthermore, the proportion and absolute number of activated Tregs were increased markedly compared with other Treg subpopulations, such as resting Tregs and newly activated T cells (non-Tregs), in the early neonatal period. Increased Tregs concomitantly expressed the suppressive molecule cytotoxic T lymphocyte antigen-4 (CTLA-4). The up-regulated expression of chemokine receptor 4 (CCR4) and down-regulated expression of CCR7 were also observed in expanded Tregs. When cord blood cells were cultured in vitro with CD3 monoclonal antibodies (mAb) for 5 days, CD4+CD45RA–FoxP3high cells were increased significantly during the culture. Thus, the presence of increased activated Tregs in early neonates may play an important role in immunological regulation by suppressing excessive T cell activation caused by the immediate exposure to ubiquitous antigens after birth.
Evaluating the impact of optical coherence tomography in diabetic retinopathy screening for an Aboriginal population
Authors: O'Halloran Richard A , Turner Angus W
Published: July 2017

Importance

Optical coherence tomography is used routinely in management of diabetic eye disease but has not been evaluated in Australian outreach settings for screening programmes.

Background

The study aims to evaluate the use of optical coherence tomography combined with a fundus camera compared with a fundus camera only in a telehealth diabetic retinopathy screening programme for Aboriginal Australians.

Design

Retrospective comparative study was used.

Participants

The study included patients with diabetes at two Aboriginal Health Services.

Methods

An intervention group was studied in 2015 using a Topcon 3D optical coherence tomography‐1 Maestro combined with optical coherence tomography/fundus camera. A control group was studied in 2014 using a DRS non‐mydriatic fundus camera. Fundus photographs were emailed to trained retinal graders for review. Optical coherence tomography scans were graded by ophthalmologists via remote TeamViewer access.

Main Outcome Measure

Referral rates to an eye health professional and the rate of inadequate photographs.

Results

Two hundred and twenty‐two patients were included, with 80 in the control group and 142 in the intervention group. There was a significantly higher rate of inadequate fundus photographs in the intervention group (31.0% vs. 13.8%). Although there was a higher rate of referral to an eye health professional in the intervention group (39.6% vs. 30.0%), this was not significant. Diabetic retinopathy and maculopathy was evident in 32.3% and 12.0% of adequate fundus photographs, respectively. Diabetic macular oedema was present in 3.6% of optical coherence tomography scans.

Conclusions and Relevance

The combined optical coherence tomography fundus camera provided no advantage for diabetic retinopathy screening compared with fundus photography in an Australian programme. The rate of referral to an eye health professional was not reduced with a higher rate of inadequate fundus photographs.
Attribute‐preserving gamut mapping of measured BRDFs
Authors: Sun Tiancheng , Serrano Ana , Gutierrez Diego , Masia Belen
Published: July 2017

Reproducing the appearance of real‐world materials using current printing technology is problematic. The reduced number of inks available define the printer's limited gamut, creating distortions in the printed appearance that are hard to control. Gamut mapping refers to the process of bringing an out‐of‐gamut material appearance into the printer's gamut, while minimizing such distortions as much as possible. We present a novel two‐step gamut mapping algorithm that allows users to specify which perceptual attribute of the original material they want to preserve (such as brightness, or roughness). In the first step, we work in the low‐dimensional intuitive appearance space recently proposed by Serrano et al. [SGM*16], and adjust achromatic reflectance via an objective function that strives to preserve certain attributes. From such intermediate representation, we then perform an image‐based optimization including color information, to bring the BRDF into gamut. We show, both objectively and through a user study, how our method yields superior results compared to the state of the art, with the additional advantage that the user can specify which visual attributes need to be preserved. Moreover, we show how this approach can also be used for attribute‐preserving material editing.
Line Integration for Rendering Heterogeneous Emissive Volumes
Authors: Simon Florian , Hanika Johannes , Zirr Tobias , Dachsbacher Carsten
Published: July 2017

Emissive media are often challenging to render: in thin regions where only few scattering events occur the emission is poorly sampled, while sampling events for emission can be disadvantageous due to absorption in dense regions. We extend the standard path space measurement contribution to also collect emission along path segments, not only at vertices. We apply this extension to two estimators: extending paths via scattering and distance sampling, and next event estimation. In order to do so, we unify the two approaches and derive the corresponding Monte Carlo estimators to interpret next event estimation as a solid angle sampling technique. We avoid connecting paths to vertices hidden behind dense absorbing layers of smoke by also including transmittance sampling into next event estimation. We demonstrate the advantages of our line integration approach which generates estimators with lower variance since entire segments are accounted for. Also, our novel forward next event estimation technique yields faster run times compared to previous next event estimation as it penetrates less deeply into dense volumes.