bluuebunny/crossref_metadata_2025 huggingface dataset:
Trajectories of delinquency among young adult prisoners
Authors: Taefi Anabel , Hosser Daniela
Published: October 2019

Using latent class growth analysis, this prospective longitudinal study aimed to identify different trajectories of delinquency among prisoners ( N = 2352) of youth correctional facilities. Criminal behaviour was monitored with crime register data on individuals from ages 14 to 25. Analyses revealed four developmental pathways: early- and late-starting desisters (31.8 percent and 5.2 percent, respectively) and early- and late-starting persisters (21.2 percent and 41.8 percent, respectively). The effects of potential risk and protective factors from multiple domains (individual, family, peer and social factors) were analysed with analyses of variance and χ² tests for each of the distinct trajectory groups. The quantity of risk factors was higher throughout the observation period in the persisting groups. Cumulative disadvantages could often be found in the persistent trajectories when low social bonds and low commitment to social norms persisted until (early) adulthood. Similarly, higher social capital and social competencies were more prevalent among offenders who desisted from crime, regardless of the severity of their offences committed as adolescents.
Uncovering the Disconnect Between Nursing Workforce Policy Intentions, Implementation, and Outcomes: Lessons Learned From the Addition of a Nursing Assistant Role
Authors: Duffield Christine , Twigg Di , Roche Michael , Williams Anne , Wise Sarah
Published: October 2019

The use of nursing assistants has increased across health systems in the past 20 years, to alleviate licensed nurses' workload and to meet rising health care demands at lower costs. Evidence suggests that, when used as a substitute for licensed nurses, assistants are associated with poorer patient and nurse outcomes. Our multimethods study evaluated the impact of a policy to add nursing assistants to existing nurse staffing in Western Australia's public hospitals, on a range of outcomes. In this article, we draw the metainferences from previously published quantitative data and unpublished qualitative interview data. A longitudinal analysis of patient records found significantly higher rates adverse patient outcomes on wards that introduced nursing assistants compared with wards that did not. These findings are explained with ward-level data that show nursing assistants were added to wards with preexisting workload and staffing problems and that those problems persisted despite the additional resources. There were also problems integrating assistants into the nursing team, due to ad hoc role assignments and variability in assistants' knowledge and skills. The disconnect between policy intention and outcomes reflects a top-down approach to role implementation where assistants were presented as a solution to nurses' workload problems, without an understanding of the causes of those problems. We conclude that policy makers and managers must better understand individual care environments to ensure any new roles are properly tailored to patient and staff needs. Further, standardized training and accreditation for nursing assistant roles would reduce the supervisory burden on licensed nurses.
Seismic design and analysis of reinforced concrete buckling-restrained braced frame buildings with multi-performance criteria
Authors: Yue Yanchao , Chen Tangbing , Bai Yongtao , Lu Xiaoming , Wang Yan , Musanyufu Josephine
Published: October 2019

Buckling-restrained braces play a critical role as the first-defendant line in dissipating seismic energy and are often used in concrete frame structures to ensure that the main beam–column members are “undamaged” or significantly elastic during medium earthquakes. The design of the reinforced concrete frame structures with buckling-restrained brace is generally based on the assumption of shear deformation of the structure. The conventional seismic design considers the “second-defendant line design” based on the geometric relationship between the axial deformation and strength of buckling-restrained braces and stratified deformation. This article proposes iterative optimization of the buckling-restrained brace design method and layout scheme based on the nonlinear structural response of the calibrated numerical model, and then approximates the nonlinear structure scheme using a linear method. Time history analyses are performed to prove that the linear design method is highly conservative for estimating seismic intensity, and the proposed design method provides more efficient damage distributions in frame components. The results of the nonlinear performance evaluation and energy analysis indicate that the method proposed in this article can meet the performance design requirements achieving multi-performance criteria.
Analysis of thin film flow of generalized Maxwell fluid confronting withdrawal and drainage on non-isothermal cylindrical surfaces
Authors: Ullah Saif , Akhtar Kareem , Khan Nadeem Alam , Ullah Arshad
Published: October 2019

This investigation is concerned with the study of thin film flow of a generalized Maxwell fluid along with slip conditions, confronting withdrawal and drainage on non-isothermal cylindrical surfaces. The governing equations have been formulated from the continuity equation, momentum equation, and energy equation. Analytical solutions for the velocity field, volume flow rate, average film velocity, tangential stress, and temperature are obtained in series form through the Binomial expansion technique in both withdrawal and drainage cases. The well-known solutions for a Newtonian fluid are regained as a particular case of our acquired general solutions in all flow cases. In addition, solutions for the power-law fluid model, executing alike motion, can be recovered as a limiting case of our acquired general solutions. The influence of different dimensionless parameters on all physical quantities (i.e. velocity, volume flow rate, average film velocity, tangential stress, and temperature profile) is examined and discussed graphically for both generalized Maxwell and Newtonian fluids.
Risk factors and clinical outcomes in chronic coronary and peripheral artery disease: An analysis of the randomized, double-blind COMPASS trial
Authors: Vanassche Thomas , Verhamme Peter , Anand Sonia S , Shestakovska Olga , Fox Keith AA , Bhatt Deepak L , Avezum Alvaro , Alings Marco , Aboyans Victor , Maggioni Aldo P , Widimsky Petr , Berkowitz Scott D , Yusuf Salim , Connolly Stuart J , Eikelboom John W , Bosch Jackie
Published: October 2019

Aims

Secondary prevention in patients with coronary artery disease and peripheral artery disease involves antithrombotic therapy and optimal control of cardiovascular risk factors. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) study, adding low-dose rivaroxaban on top of aspirin lowered cardiovascular events, but there is limited data about risk factor control in secondary prevention. We studied the association between risk factor status and outcomes, and the impact of risk factor status on the treatment effect of rivaroxaban, in a large contemporary population of patients with coronary artery disease or peripheral artery disease.

Methods and results

We reported ischemic events (cardiovascular death, stroke, or myocardial infarction) in participants from the randomized, double-blind COMPASS study by individual risk factor (blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity), and by number of risk factors. We compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone within each risk factor category and tested for interaction between risk factor status and antithrombotic regimen. Complete baseline risk factor status was available in 27,117 (99%) patients. Status and number of risk factors were both associated with increased risk of ischemic events. Rates of ischemic events (hazard ratio 2.2; 95% confidence interval 1.8–2.6) and cardiovascular death (hazard ratio 2.0; 1.5–2.7) were more than twofold higher in patients with 4–6 compared with 0–1 risk factors ( p < 0.0001 for both). Rivaroxaban reduced event rates independently of the number of risk factors ( p interaction 0.93), with the largest absolute benefit in patients with the highest number of risk factors.

Conclusion

More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events.
Aging in the Context of HIV/AIDS: Spaces for Renegotiation and Recomposition of Mutual Solidarity in Burkina Faso
Authors: Ouedraogo Ramatou , Attané Anne , Gyasi Razak M
Published: October 2019

Purpose:

The HIV-infected older people in sub-Saharan Africa are inevitably vulnerable to chronic health-related conditions, yet the needed social support for these people is mostly inadequate. Drawing on the anthropology of disease and health paradigms, this study explores the recomposition of multidimensional and multidirectional nature of mutual familial support for older people living with or affected by HIV/AIDS in Burkina Faso.

Methods:

We conducted multiple in-depth interviews among 147 individuals recruited from nonprofit organizations in Ouagadougou, Bobo-Dioulasso, Ouahigouya, and Yako through 2 projects funded by the National Agency for AIDS Research. Thematic and narrative analytical frameworks were used to analyze the data.

Results:

We found that older people suffered serious socioeconomic and psychological challenges associated with HIV/AIDS. Older people were particularly vulnerable to the double burden of HIV/AIDS and caregiving responsibility for family members infected with the disease. However, the infected older people who received adequate treatment and familial support regained sociocultural positions as agents for cultural transition and material/emotional resources.

Conclusions:

Although HIV/AIDS potentially renegotiated the nature, intensity, and direction of familial support for vulnerable older people, the extrafamily solidarity seems an integral part of the great cycle of reciprocity and intrafamily mutual support. Health and policy interventions targeted at strengthening the interpersonal relationships and support for HIV/AIDS-infected and HIV/AIDS-affected older people are needed to improve their independence and well-being.
Emerging Christianity in Cambodia: People Movement to Christ or Playground for Global Christianity?
Authors: Brandner Tobias
Published: October 2019

Present-day Christianity in Cambodia is less than thirty years old; virtually all traces of its earlier history were eradicated by the Khmer Rouge. The article offers a portrait of this young church and introduces mission patterns, growth factors, and challenges for this emerging church. It critically discusses the entanglement of global and local factors, as well as the diversity of mission agents engaged in Cambodia. The article concludes that churches successfully present themselves as a training ground for emerging global citizens, attracting young people to a faith movement that connects them with a global network.
The transcriptome of CMML monocytes is highly inflammatory and reflects leukemia-specific and age-related alterations
Authors: Franzini Anca , Pomicter Anthony D. , Yan Dongqing , Khorashad Jamshid S. , Tantravahi Srinivas K. , Than Hein , Ahmann Jonathan M. , O’Hare Thomas , Deininger Michael W.
Published: October 2019

Key Points

CMML monocytes exhibit a proinflammatory transcriptional signature, contributing to malignant expansion and increased cardiovascular risk.
Prestroke statins use reduces oxidized low density lipoprotein levels and improves clinical outcomes in patients with atrial fibrillation related acute ischemic stroke
Authors: He Lanying , Xu Ronghua , Wang Jian , Zhang Lili , Zhang Lijuan , Zhao Wang , Dong Weiwei
Published: October 2019

Background

Atrial fibrillation (AF) is a common cause of cerebral infarction, which could lead to endothelial dysfunction, increased reactive oxygen species (ROS) and oxidized low density lipoprotein (Ox-LDL).AF is associated with higher mortality and more severe neurologic disability. Statins may exert neuroprotective effects that are independent of LDL-C lowering. The purpose of our study was to investigate whether prestroke statins use could reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS).

Methods

This was a multicenter prospective study that involved four medical centers, 242 AIS patients with AF were identified, who underwent a comprehensive clinical investigation and a 72 h-Holter electrocardiogram monitoring. All patients were divided into two groups: prestroke statins use and no prestroke statins use groups, who were followed up for 3 months. Plasma Ox-LDL levels were measured using enzyme-linked immunosorbent assay (ELISA) on admission and at 3 months. The outcome was death, major disability (modified Rankin Scale score ≥ 3), and composite outcome (death/major disability) at 3 months after AIS.

Results

One hundred thirty-six patients were in no prestroke statins use group, and 106 in prestroke statins use group. Plasma Ox-LDL levels were significantly lower in prestroke statins use than in no prestroke statins use on admission and at 3 months (P < 0.001). Plasma Ox-LDL levels on admission were associated with 3-month mortality [adjusted odds ratio (OR), 1.05; 95% confidence interval (CI), 0.99–1.12; P = 0.047]. In fully adjusted models, prestroke statins use was associated with reduced 3-month mortality [adjusted OR, 0.38; 95% CI, 0.16–0.91; P = 0.031)], major disability (adjusted OR, 0.38; 95% CI, 0.15–0.99; P = 0.047), and composite outcome (adjusted OR, 0.31; 95% CI, 0.17–0.74; P = 0.009).

Conclusions

Prestroke statins use can reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related AIS.
Effectiveness of a brief psychological mindfulness-based intervention for the treatment of depression in primary care: study protocol for a randomized controlled clinical trial
Authors: Lopez-Montoyo Alba , Quero Soledad , Montero-Marin Jesus , Barcelo-Soler Alberto , Beltran Maria , Campos Daniel , Garcia-Campayo Javier
Published: October 2019

Background

Depressive symptoms are quite prevalent in Primary Care (PC) settings. The treatment as usual (TAU) in PC is pharmacotherapy, despite the high relapse rates it produces. Many patients would prefer psychotherapy, but specialized services are overloaded. Studies that apply Mindfulness-Based Interventions (MBIs) for the treatment of depression have obtained significant improvements. Brief low-intensity approaches delivered from PC could be a promising approach. This study aims to compare a low-intensity mindfulness intervention for the treatment of depression in PC using different intervention formats – a face-to-face MBI delivered in a group and the same MBI individually applied on the Internet – to a control group that will receive PC medical treatment as usual.

Methods

A randomized controlled clinical trial will be conducted in PC, with about 120 depressed patients allocated (1:1:1) to three groups: “face-to-face MBI + TAU”, “Internet-delivered MBI + TAU”, and “TAU alone”. The MBI programs will be composed of four modules. The primary outcome will be depressive symptoms, measured through the Beck Depression Inventory, assessed at pre- and post-treatment and 6- and 12-month follow-ups. Other outcomes will be mindfulness, happiness, affectivity, quality of life, and the use of healthcare services. Intention-to-treat analysis using linear mixed models adjusted for baseline scores and routine sociodemographic analysis that could show baseline differences will be conducted. Per-protocol secondary outcome analyses will also be performed.

Discussion

This is the first Spanish RCT to apply a low-intensity face-to-face MBI (plus TAU) to treat depression in PC settings compared to TAU (alone). Moreover, this study will also make it possible to evaluate the same MBI program (plus TAU), but Internet-delivered, considering their cost-effectiveness. Positive results from this RCT might have an important impact on mental health settings, helping to decrease the overload of the system and offering treatment alternatives beyond antidepressant medication through high-quality, flexible PC interventions.

Trial registration

Clinical Trials.gov NCT03034343. Trial Registration date 24 January 2017, retrospectively registered.
Identifying tuberculous pleural effusion using artificial intelligence machine learning algorithms
Authors: Ren Zenghua , Hu Yudan , Xu Ling
Published: October 2019

Background

The differential diagnosis of tuberculous pleural effusion (TPE) is challenging. In recent years, artificial intelligence (AI) machine learning algorithms have started being used to an increasing extent in disease diagnosis due to the high level of efficiency, objectivity, and accuracy that they offer.

Methods

Data samples on 192 patients with TPE, 54 patients with parapneumonic pleural effusion (PPE), and 197 patients with malignant pleural effusion (MPE) were retrospectively collected. Based on 28 different features obtained via statistical analysis, TPE diagnostic models using four machine learning algorithms (MLAs), namely logistic regression, k-nearest neighbors (KNN), support vector machine (SVM) and random forest (RF) were established and their respective diagnostic performances were calculated. The respective diagnostic performances of each of the four algorithmic models were compared with that of pleural fluid adenosine deaminase (pfADA). Based on 12 features with the most significant impacts on the accuracy of the RF model, a new RF model was designed for clinical application. To demonstrate its external validity, a prospective study was conducted and the diagnostic performance of the RF model was calculated.

Results

The respective sensitivity and specificity of each of the four TPE diagnostic models were as follows: logistic regression – 80.5 and 84.8%; KNN– 78.6 and 86.6%; SVM – 83.2 and 85.9%; and RF – 89.1 and 93.6%. The sensitivity and specificity of pfADA were 85.4 and 84.1%, respectively, at the best cut-off value of 17.5 U/L. RF was the superior method among the four MLAs, and was also superior to pfADA. The newly designed RF model (based on 12 out of 28 features) exhibited an acceptable performance rate for the diagnosis of TPE with a sensitivity and specificity of 90.6 and 92.3%, respectively. In the prospective study, its sensitivity and specificity were 100.0 and 90.0%, respectively.

Conclusions

Establishing a model for the diagnosis of TPE using RF resulted in a more effective, economical, and faster diagnostic method. This method could enable clinicians to diagnose and treat TPE more effectively.
Infrared thermography in children: a reliable tool for differential diagnosis of peripheral microvascular dysfunction and Raynaud’s phenomenon?
Authors: Martini Giorgia , Cappella Michela , Culpo Roberta , Vittadello Fabio , Sprocati Monica , Zulian Francesco
Published: October 2019

Background

Infrared Thermography (IRT) has been used for over 30 years in the assessment of Raynaud Phenomenon (RP) and other peripheral microvascular dysfunctions in adults but, to date, very little experience is available on its use in children for this purpose. The first aim of the study was to assess reproducibility of thermographic examination after cold exposure by comparing inter-observer agreement in thermal imaging interpretation. The secondary aim was to evaluate whether IRT is reliable to diagnose and differentiate peripheral circulation disturbances in children.

Methods

Children with clinical diagnosis of primary Raynaud’s phenomenon (PRP), secondary RP (SRP), acrocyanosis (AC) and age-matched controls underwent sequential measurements of skin temperature at distal interphalangeal (DIP) and metacarpophalangeal (MCP) joints with IRT at baseline and for 10 min after cold challenge test. Intraclass correlation coefficient (ICC) was calculated for inter-rater reliability in IRT interpretation, then temperature variations at MCP and DIP joints and the distal-dorsal difference (DDD) were analysed.

Results

Fourteen PRP, 16 SRP, 14 AC and 15 controls entered the study. ICC showed excellent agreement (> 0.93) for DIPs and MCPs in 192 measures for each subject. Patients with PRP, SRP and acrocyanosis showed significantly slower recovery at MCPs (p < 0.05) and at DIPs (p < 0.001) than controls. At baseline, higher temperature at DIPs and lower at MCPs was observed in PRP compared with SRP with significantly lower DDD (p < 0.001). Differently from AC, both PRP and SRP showed gain of temperature at DIPs and less at MCPs after cold challenge. PRP but not SRP patients returned to DIPs basal temperature by the end of re-warming time. Analysis of DDD confirmed that controls and PRP, SRP and AC patients significantly differed in fingers recovery pattern (p < 0.05).

Conclusion

IRT appears reliable and reproducible in identifying children with peripheral microvascular disturbances. Our results show that IRT examination pointed out that PRP, SRP and AC patients present significant differences in basal extremities temperature and in re-warming pattern after cold challenge therefore IRT can be suggested as an objective tool for diagnosis and monitoring of disease.
Of microbes and mange: consistent changes in the skin microbiome of three canid species infected with Sarcoptes scabiei mites
Authors: DeCandia Alexandra L. , Leverett Kennedy N. , vonHoldt Bridgett M.
Published: October 2019

Background

Sarcoptic mange is a highly contagious skin disease caused by the ectoparasitic miteSarcoptes scabiei. Although it afflicts over 100 mammal species worldwide, sarcoptic mange remains a disease obscured by variability at the individual, population and species levels. Amid this variability, it is critical to identify consistent drivers of morbidity, particularly at the skin barrier.

Methods

Using culture-independent next generation sequencing, we characterized the skin microbiome of three species of North American canids: coyotes (Canis latrans), red foxes (Vulpes vulpes) and gray foxes (Urocyon cinereoargenteus). We compared alpha and beta diversity between mange-infected and uninfected canids using the Kruskal–Wallis test and multivariate analysis of variance with permutation. We used analysis of composition of microbes and gneiss balances to perform differential abundance testing between infection groups.

Results

We found remarkably consistent signatures of microbial dysbiosis associated with mange infection. Across genera, mange-infected canids exhibited reduced microbial diversity, altered community composition and increased abundance of opportunistic pathogens. The primary bacteria comprising secondary infections wereStaphylococcus pseudintermedius, previously associated with canid ear and skin infections, andCorynebacteriumspp., previously found among the gut flora ofS. scabieimites and hematophagous arthropods.

Conclusions

This evidence suggests that sarcoptic mange infection consistently alters the canid skin microbiome and facilitates secondary bacterial infection, as seen in humans and other mammals infected withS. scabieimites. These results provide valuable insights into the pathogenesis of mange at the skin barrier of North American canids and can inspire novel treatment strategies. By adopting a “One Health” framework that considers mites, microbes and the potential for interspecies transmission, we can better elucidate the patterns and processes underlying this ubiquitous and enigmatic disease.
Upgrading a high performance computing environment for massive data processing
Authors: Ponce Lucas M. , Santos Walter dos , Meira Wagner , Guedes Dorgival , Lezzi Daniele , Badia Rosa M.
Published: October 2019

High-performance computing (HPC) and massive data processing (Big Data) are two trends that are beginning to converge. In that process, aspects of hardware architectures, systems support and programming paradigms are being revisited from both perspectives. This paper presents our experience on this path of convergence with the proposal of a framework that addresses some of the programming issues derived from such integration. Our contribution is the development of an integrated environment that integretes (i) COMPSs, a programming framework for the development and execution of parallel applications for distributed infrastructures; (ii) Lemonade, a data mining and analysis tool; and (iii) HDFS, the most widely used distributed file system for Big Data systems. To validate our framework, we used Lemonade to create COMPSs applications that access data through HDFS, and compared them with equivalent applications built with Spark, a popular Big Data framework. The results show that the HDFS integration benefits COMPSs by simplifying data access and by rearranging data transfer, reducing execution time. The integration with Lemonade facilitates COMPSs’s use and may help its popularization in the Data Science community, by providing efficient algorithm implementations for experts from the data domain that want to develop applications with a higher level abstraction.
Macrophage activation syndrome, a rare complication of primary Sjögren’s syndrome: a case report
Authors: Kane B. S. , Niasse M. , Faye A. , Diack N. D. , Djiba B. , Dieng M. , Sow M. , Ndao A. C. , Diagne N. , Ndongo S. , Pouye A.
Published: October 2019

Background

The association of macrophage activation syndrome and primary Sjögren’s syndrome has been rarely reported in the literature. We report the first observation of this association in Africa, south of the Sahara, and we discuss the diagnosis and therapeutic challenge.

Case presentation

A 26-year-old Mauritanian and Berber woman was followed for primary Sjögren’s syndrome. After a voluntary cessation of her usual background treatment, she was admitted to our department for an outbreak of her illness. A clinical examination revealed anemic syndrome, peripheral polyarthritis, coughing rales at both pulmonary bases, and fever at 39.5 °C. On biologic examination, there was bicytopenia with anemia at 5.70 g/dl, lymphopenia at 796/mm3, a biological inflammatory syndrome with a sedimentation rate at 137 mm in the first hour, C-reactive protein at 97 mg/l, hyperferritinemia at 1778 mg/l (9 normal value), and hypergammaglobulinemia at 20.7 g/l of polyclonal appearance. The triglycerides were 1.95 g/l (1.4 normal value) and the lactate dehydrogenase level was 491 IU/l (1.5 normal value). Cytological examination of a medullary puncture revealed an image of hemophagocytosis. An infectious screening was negative. Thoracic computed tomography showed non-specific interstitial lung disease. A diagnosis of macrophage activation syndrome complicating primary Sjögren’s syndrome was selected with a probability of 97.2%, according to H-Score. The evolution was favorable under a treatment including etoposide (VP-16).

Conclusion

Macrophage activation syndrome is a rare entity, rarely reported during primary Sjögren’s syndrome. Its spontaneous evolution is invariably fatal. There is no consensus on therapeutic treatment. Etoposide is a therapeutic option especially in forms refractory to corticosteroid therapy.
Rapid one-step enzyme immunoassay and lateral flow immunochromatographic assay for colistin in animal feed and food
Authors: Wang Jiayi , Zhou Jinyu , Chen Yiqiang , Zhang Xinpei , Jin Yongpeng , Cui Xiaojing , He Dongting , Lai Wenqing , He Lidong
Published: October 2019

Background

Colistin (polymyxin E) is a kind of peptide antibiotic which has been approved in animal production for the purposes of disease prevention, treatment, and growth promotion. However, the wide use of colistin in animal feed may accelerate the spread of colistin-resistance gene MCR-1 from animal production to human beings, and its residue in animal-origin food may also pose serious health hazards to humans. Thus, it is necessary to develop corresponding analytical methods to monitor the addition of colistin in animal feed and the colistin residue in animal-origin food.

Results

A one-step enzyme-linked immunosorbent assay (ELISA) and a lateral flow immunochromatographic assay (LFIA) for colistin were developed based on a newly developed monoclonal antibody. The ELISA showed a 50% inhibition value (IC50) of 9.7 ng/mL with assay time less than 60 min, while the LFIA had a strip reader-based detection limit of 0.87 ng/mL in phosphate buffer with assay time less than 15 min. For reducing the non-specific adsorption of colistin onto sample vial, the components of sample extraction solution were optimized and proved to greatly improve the assay accuracy. The spiked recovery experiment showed that the recoveries of colistin from feed, milk and meat samples were in the range of 77.83% to 113.38% with coefficient of variations less than 13% by ELISA analysis and less than 18% by LFIA analysis, respectively. Furthermore, actual sample analysis indicated that the two immunoassays can produce results consistent with instrumental analysis.

Conclusions

The developed assays can be used for rapid qualitative or quantitative detection of colistin in animal feed and food.
In vivo and in vitro toxicity evaluation of liposome-encapsulated sirolimus
Authors: Abud Murilo Batista , Louzada Ricardo Noguera , Isaac David Leonardo Cruvinel , Souza Leonardo Gomes , dos Reis Ricardo Gomes , Lima Eliana Martins , de Ávila Marcos Pereira
Published: October 2019

Background

To evaluate the in vivo and in vitro toxicity of a new formulation of liposome-encapsulated sirolimus (LES).

Methods

In vitro experiments were done using ARPE-19 and HRP cells. An MTT assay was used to determine cell metabolic activity and a TUNEL assay for detecting DNA fragmentation. In vivo experiments were conducted on New Zealand albino rabbits that received intravitreal injections of empty liposomes (EL) or different concentrations of LES. Histopathological and immunohistochemical analyses were performed on the rabbit’s eyes following injection.

Results

Eighteen eyes of nine rabbits were used. MTT assay cell viability was 95.04% in group 1 (12.5 µL/mL LES). 92.95% in group 2 (25 µL/mL LES), 91.59% in group 3 (50 µL/mL LES), 98.09% in group 4 (12.5 µL/mL EL), 95.20% on group 5 (50 µL/mL EL), 98.53% in group 6 (50 µL/mL EL), and 2.84% on group 8 (50 µL/mL DMSO). There was no statistically significant difference among groups 1 to 7 in cell viability (p = 1.0), but the comparison of all groups with group 8 was significant (p < 0.0001). The TUNEL assay comparing two groups was not statistically significant from groups 1 to 7 (p = 1.0). The difference between groups 1 to 7 and group 8 (p < 0.0001) was significant. Histopathological changes were not found in any group. No activation of Müller cells was detected.

Conclusion

A novel formulation of LES delivered intravitreally did not cause in vitro toxicity, as evaluated by MTT and TUNEL assays, nor in vivo toxicity as evaluated by histopathology and immunohistochemistry in rabbit eyes.
The trans-DATA study: aims and design of a translational breast cancer prognostic marker identification study
Authors: de Ruijter Tim C. , Smits Kim M. , Aarts Maureen J. , van Hellemond Irene E. G. , Van Neste Leander , de Vries Bart , Peer Petronella G. M. , Veeck Jürgen , van Engeland Manon , Tjan-Heijnen Vivianne C. G.
Published: October 2019

Background

The effect of extended adjuvant aromatase inhibition in hormone-positive breast cancer after sequential tamoxifen, aromatase inhibitor treatment of 5 years was recently investigated by the DATA study. This study found no statistically significant effect of prolonged aromatase therapy. However, subgroup analysis showed post hoc statistically significant benefits in certain sub-populations. The trans-DATA study is a translational sub-study aiming to identify DNA methylation markers prognostic of patient outcome.

Methods

Patients from the DATA study are included in the trans-DATA study. Primary breast tumour tissue will be collected, subtyped and used for DNA isolation. A genome-wide DNA methylation discovery assay will be performed on 60 patients that had a distant recurrence and 60 patients that did not have a distant recurrence using the Infinium Methylation EPIC Bead Chip platform. Differentially methylated regions of interest will be selected based on Akaike’s Information Criterion, Gene Ontology Analysis and correlation between methylation and expression levels. Selected candidate genes will subsequently be validated in the remaining patients using qMSP.

Discussion

The trans-DATA study uses a cohort derived from a clinical randomised trial. This study was designed to avoid common pitfalls in marker discovery studies such as selection bias, confounding and lack of reproducibility. In addition to the usual clinical risk factors, the results of this study may identify predictors of high recurrence risk in hormone receptor-positive breast cancer patients treated with sequential tamoxifen and aromatase inhibitor therapy.
Patient and in vitro fertilization (IVF) cycle characteristics associated with variable blastulation rates: a retrospective study from the Duke Fertility Center (2013–2017)
Authors: Jones Carrie A. , Acharya Kelly S. , Acharya Chaitanya R. , Raburn Douglas , Muasher Suheil J.
Published: October 2019

Background

To evaluate the association of patient and IVF cycle characteristics with blastulation rate and formation of high-quality blastocysts

Results

We analyzed autologous blastocyst cycles from 2013 to 2017. Cycles were subdivided into low (< 33%), intermediate (33–66%), and high (> 66%) blastulation rates. Embryo quality was assigned by embryologists using Gardner Criteria. R statistical package was used, and the blastulation groups were compared using analysis of variance (ANOVA) for continuous variables and chi-squared tests for categorical variables. The Bonferroni correction was used to adjust for multiple comparisons. One hundred seventeen IVF cycles met our inclusion criteria. Of these, 20 (17.1%) had low, 74 (63.2%) had intermediate, and 23 (19.7%) had high blastulation rates. Low blastulation rate was associated with a lower number of blastocysts, including fewer high-quality blastocysts. The mean number of oocytes retrieved was highest (18.1) in the group with the lowest blastulation rate, and lowest (13.4) in those with the highest blastulation rate, although this did not reach statistical significance. There were no significant differences between blastulation rates and age, gravidity, prior live birth, anti-mullerian hormone, estradiol and progesterone levels on the day of ovulation trigger, follicle-stimulating hormone dose, or fertility diagnosis.

Conclusions

High blastulation rate is associated with a greater number of blastocysts, including a greater number of high-quality blastocysts. Higher oocyte yield, however, is not associated with improved blastulation rates. Blastulation rates, blastocyst number, and quality remain difficult to predict based on cycle characteristics alone, and oocyte yield may not be an accurate predictor of either outcome.
Deep-learning electromagnetic monitoring coupled to fluid flow simulators
Authors: Colombo Daniele , Li Weichang , Sandoval-Curiel Ernesto , McNeice Gary W.
Published: October 2019

Reservoir characterization and monitoring represent some of the most ambitious goals for geophysical methods. Several challenges are involved, including sensitivity to the parameter changes and resolution of the obtained results. Electromagnetic (EM) methods are attractive for reservoir applications due to the high sensitivity of the resistivity parameter to oil/water saturations. Crosswell EM and surface-to-borehole EM provide opportunities for reservoir monitoring. The EM inverse problem, however, is highly nonconvex and ill-posed so as to necessitate significant preconditioning in the form of a priori information and regularization that impact resolution. We explore the use of machine-learning (ML) techniques in the form of deep-learning neural networks for implementing EM-based reservoir monitoring coupled with a dynamic fluid flow simulator. A crosswell acquisition setup is modeled in the framework of a realistic water-alternating-gas reservoir simulation scenario for enhanced oil recovery. Several reservoir saturation instances are generated and converted into resistivity, and corresponding crosswell EM data are generated using an electric source and a multicomponent (electric-magnetic) receiver assemblage. The U-Net deep-learning network is modified for the purpose of training and validation in which saturation models and the corresponding EM data are used. We also test the sensitivity of the deep-learning inversion to multiple EM components, noise in the data, generalization problems, and 3D reconstruction ability in which we use 3D convolutional neural network layers. In all cases, ML inversion proves to be robust with good resilience to increased noise levels. Prediction results indicate excellent reconstruction capabilities with resolution comparable to the reservoir models used by the simulator. Our results suggest that ML inversion through deep learning can become an efficient approach to data-driven and physics-constrained reservoir monitoring in which the sensitivity of EM-based techniques to fluid saturations can be fully exploited without compromising the resolution and accuracy of the results.
Open-Sourced CIViC Annotation Pipeline to Identify and Annotate Clinically Relevant Variants Using Single-Molecule Molecular Inversion Probes
Authors: Barnell Erica K. , Waalkes Adam , Mosior Matt C. , Penewit Kelsi , Cotto Kelsy C. , Danos Arpad M. , Sheta Lana M. , Campbell Katie M. , Krysiak Kilannin , Rieke Damian , Spies Nicholas C. , Skidmore Zachary L. , Pritchard Colin C. , Fehniger Todd A. , Uppaluri Ravindra , Govindan Ramaswamy , Griffith Malachi , Salipante Stephen J. , Griffith Obi L.
Published: October 2019

PURPOSE

Clinical targeted sequencing panels are important for identifying actionable variants for patients with cancer; however, existing approaches do not provide transparent and rationally designed clinical panels to accommodate the rapidly growing knowledge within oncology.

MATERIALS AND METHODS

We used the Clinical Interpretations of Variants in Cancer (CIViC) database to develop an Open-Sourced CIViC Annotation Pipeline (OpenCAP). OpenCAP provides methods to identify variants within the CIViC database, build probes for variant capture, use probes on prospective samples, and link somatic variants to CIViC clinical relevance statements. OpenCAP was tested using a single-molecule molecular inversion probe (smMIP) capture design on 27 cancer samples from 5 tumor types. In total, 2,027 smMIPs were designed to target 111 eligible CIViC variants (61.5 kb of genomic space).

RESULTS

When compared with orthogonal sequencing, CIViC smMIP sequencing demonstrated a 95% sensitivity for variant detection (n = 61 of 64 variants). Variant allele frequencies for variants identified on both sequencing platforms were highly concordant (Pearson’s r = 0.885; n = 61 variants). Moreover, for individuals with paired tumor and normal samples (n = 12), 182 clinically relevant variants missed by orthogonal sequencing were discovered by CIViC smMIP sequencing.

CONCLUSION

The OpenCAP design paradigm demonstrates the utility of an open-source and open-access database built on attendant community contributions with peer-reviewed interpretations. Use of a public repository for variant identification, probe development, and variant interpretation provides a transparent approach to build dynamic next-generation sequencing–based oncology panels.
Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer
Authors: Argiris Athanassios , Li Shuli , Savvides Panayiotis , Ohr James P. , Gilbert Jill , Levine Marshall A. , Chakravarti Arnab , Haigentz Jr Missak , Saba Nabil F. , Ikpeazu Chukwuemeka V. , Schneider Charles J. , Pinto Harlan A. , Forastiere Arlene A. , Burtness Barbara
Published: October 2019

PURPOSE

We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

PATIENTS AND METHODS

Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved.

RESULTS

The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95% CI, 0.70 to 1.09; P = .22). At 2, 3, and 4 years, the OS rates were 25.2% v 18.1%, 16.4% v 10.0%, and 11.8% v 6.4% for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95% CI, 0.65 to 1.04; P = .10), with a median OS of 14.2 months on BC v 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months v 4.3 months with chemotherapy ( P = .0014). Overall response rates were 35.5% with BC and 24.5% with chemotherapy ( P = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7% v 0.5%; P < .001) and treatment-related deaths (9.3% v 3.5%; P = .022) with BC versus chemotherapy.

CONCLUSION

The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.
Clinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer
Authors: Sjöström Martin , Chang S. Laura , Fishbane Nick , Davicioni Elai , Zhao Shuang G. , Hartman Linda , Holmberg Erik , Feng Felix Y. , Speers Corey W. , Pierce Lori J. , Malmström Per , Fernö Mårten , Karlsson Per
Published: October 2019

PURPOSE

Most patients with early-stage breast cancer are treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) to prevent locoregional recurrence (LRR). However, no genomic tools are used currently to select the optimal RT strategy.

METHODS

We profiled the transcriptome of primary tumors on a clinical grade assay from the SweBCG91-RT trial, in which patients with node-negative breast cancer were randomly assigned to either whole-breast RT after BCS or no RT. We derived a new classifier, Adjuvant Radiotherapy Intensification Classifier (ARTIC), comprising 27 genes and patient age, in three publicly available cohorts, then independently validated ARTIC for LRR in 748 patients in SweBCG91-RT. We also compared previously published genomic signatures for ability to predict benefit from RT in SweBCG91-RT.

RESULTS

ARTIC was highly prognostic for LRR in patients treated with RT (hazard ratio [HR], 3.4; 95% CI, 2.0 to 5.9; P < .001) and predictive of RT benefit ( Pinteraction = .005). Patients with low ARTIC scores had a large benefit from RT (HR, 0.33 [95% CI, 0.21 to 0.52], P < .001; 10-year cumulative incidence of LRR, 6% v 21%), whereas those with high ARTIC scores benefited less from RT (HR, 0.73 [95% CI, 0.44 to 1.2], P = .23; 10-year cumulative incidence of LRR, 25% v 32%). In contrast, none of the eight previously published signatures were predictive of benefit from RT in SweBCG91-RT.

CONCLUSION

ARTIC identified women with a substantial benefit from RT as well as women with a particularly elevated LRR risk in whom whole-breast RT was not sufficiently effective and, thus, in whom intensified treatment strategies such as tumor-bed boost, and possibly regional nodal RT, should be considered. To our knowledge, ARTIC is the first classifier validated as predictive of benefit from RT in a phase III clinical trial with patients randomly assigned to receive or not receive RT.
Implementation and efficacy of a large-scale radiation oncology case-based peer-review quality program across a multinational cancer network.
Authors: Ludmir Ethan B. , Hoffman Karen E. , Jhingran Anuja , Ip Mee-Chung Puscilla , Frey Seth D. , Ning Matthew S. , Minsky Bruce D. , McAleer Mary Frances , Chronowski Gregory , Arzu Isidora , Reed Valerie Klairisa , Garg Amit K. , Roberts Terence , Ashish Patel , Olson Michael R. , Selek Ugur , Gabel Molly , Koong Albert , Herman Joseph M. , Kuban Deborah A.
Published: October 2019

1

Background: With rapid community expansion of academic cancer centers, ensuring high-quality delivery of care across all affiliated network sites is critical. Here we report the results of a radiation oncology peer-review system implemented across a large multinational cancer network. Methods: Weekly radiation oncology peer-review conferences were held between network centers and the main campus of a major cancer system; results of standardized peer-review for each case were recorded. Peer-review resulted in each case being scored as concordant or nonconcordant on initial review; nonconcordance was based on institutional guidelines, national standards, and/or expert opinion. Results: Between 2014 and 2018, 28,730 patient radiation treatment plans underwent peer-review at 10 network centers. The peer-review case volume increased over this study period, from 1,420 cases in 2014 to 9,112 in 2018, concomitant with network expansion. Examining cases reviewed in 2018 (N = 9,112), the most-commonly reviewed cases by disease site were breast (28.9%), head and neck (HN; 13.9%), and lung (12.6%). Of all cases in 2018, 452 (5.0%) were deemed nonconcordant. Higher nonconcordance rates were noted for HN cases (14.0%), and lower rates for lung cases (2.3%; p < 0.001). Of nonconcordant HN cases, the majority (69.5%) were deemed nonconcordant based on target volume delineation. Of nonconcordant breast cases, most (67.1%) were nonconcordant based on radiation field design. For centers added to the network during the study period, we observed a significant decrease in the nonconcordance rate over time after joining the network (average annual decrease of 5.4% in nonconcordant cases; p < 0.001). Conclusions: These data demonstrate the feasibility and efficacy of a large-scale multinational cancer network radiation oncology weekly peer-review program. Nonconcordance rates were highest for HN cases, primarily due to target volume delineation. With improved nonconcordance rates for newly-added network centers, these results offer the promise of improving the quality of radiotherapy delivery across an extensive cancer network with a major academic center as the nucleus.