bluuebunny/crossref_metadata_2025 huggingface dataset:
Joint model robustness compared with the time-varying covariate Cox model to evaluate the association between a longitudinal marker and a time-to-event endpoint
Authors: Arisido Maeregu W. , Antolini Laura , Bernasconi Davide P. , Valsecchi Maria G. , Rebora Paola
Published: December 2019

Background

The recent progress in medical research generates an increasing interest in the use of longitudinal biomarkers for characterizing the occurrence of an outcome. The present work is motivated by a study, where the objective was to explore the potential of the long pentraxin 3 (PTX3) as a prognostic marker of Acute Graft-versus-Host Disease (GvHD) after haematopoietic stem cell transplantation. Time-varying covariate Cox model was commonly used, despite its limiting assumptions that marker values are constant in time and measured without error. A joint model has been developed as a viable alternative; however, the approach is computationally intensive and requires additional strong assumptions, in which the impacts of their misspecification were not sufficiently studied.

Methods

We conduct an extensive simulation to clarify relevant assumptions for the understanding of joint models and assessment of its robustness under key model misspecifications. Further, we characterize the extent of bias introduced by the limiting assumptions of the time-varying covariate Cox model and compare its performance with a joint model in various contexts. We then present results of the two approaches to evaluate the potential of PTX3 as a prognostic marker of GvHD after haematopoietic stem cell transplantation.

Results

Overall, we illustrate that a joint model provides an unbiased estimate of the association between a longitudinal marker and the hazard of an event in the presence of measurement error, showing improvement over the time-varying Cox model. However, a joint model is severely biased when the baseline hazard or the shape of the longitudinal trajectories are misspecified. Both the Cox model and the joint model correctly specified indicated PTX3 as a potential prognostic marker of GvHD, with the joint model providing a higher hazard ratio estimate.

Conclusions

Joint models are beneficial to investigate the capability of the longitudinal marker to characterize time-to-event endpoint. However, the benefits are strictly linked to the correct specification of the longitudinal marker trajectory and the baseline hazard function, indicating a careful consideration of assumptions to avoid biased estimates.
Development of the DAGIS intervention study: a preschool-based family-involving study promoting preschoolers’ energy balance-related behaviours and self-regulation skills
Authors: Ray Carola , Kaukonen Riikka , Lehto Elviira , Vepsäläinen Henna , Sajaniemi Nina , Erkkola Maijaliisa , Roos Eva
Published: December 2019

Background

Preschoolers’ energy balance-related behaviours (EBRBs) and self-regulation skills are important for their later health. Few preschool-based interventions aiming to promote preschoolers’ EBRBs and self-regulation skills, simultaneously reducing differences in EBRBs, due to children’s socio-economic status (SES) background, have been conducted. This study will present the Increased Health and Wellbeing in Preschools (DAGIS) intervention development process applying the Intervention Mapping (IM) framework.

Methods

The development of the DAGIS intervention study, a preschool level clustered randomized controlled trial (RCT), was based on the IM framework. The protocol in IM guides the development process of an intervention through six steps: needs assessment and logic model of the problem, programme outcomes and objectives, design of the programme, production, implementation plan, and evaluation plan.

Results

The needs assessment, part of the step 1 in IM, yielded the base for the DAGIS logic model of change. The model includes objectives related to changes in children’s EBRBs, self-regulation skills, and in psychosocial and physical environment that is determined by parents and early educators. A 22-week programme was developed, and materials for preschools and families were produced. A feasibility study of the recruitment processes, acceptability of the materials and methods, and implementation was conducted. The DAGIS intervention study was conducted September 2017–May 2018 as a clustered RCT including a comprehensive effectiveness and process evaluation. The process evaluation was run throughout the intervention targeting preschools and families.

Conclusion

A preschool-based family-involving programme was developed in the DAGIS intervention study by applying the IM protocol. It was a time- and resource-consuming process. However, the systematic planning, development, and running of the programme have reinforced a comprehensive evaluation, which is a strength in the intervention. The results from the evaluation will enhance the knowledge of how to promote EBRBs and self-regulation skills among preschoolers, and diminish SES differences in them.

Trial registration

ISRCTN57165350(Prospectively registered January the 8th, 2015).
Influence of psychiatric or social backgrounds on clinical decision making: a randomized, controlled multi-centre study
Authors: Yamauchi Yosuke , Shiga Takashi , Shikino Kiyoshi , Uechi Takahiro , Koyama Yasuaki , Shimozawa Nobuhiko , Hiraoka Eiji , Funakoshi Hiraku , Mizobe Michiko , Imaizumi Takahiro , Ikusaka Masatomi
Published: December 2019

Background

Frequent and repeated visits from patients with mental illness or free medical care recipients may elicit physicians’ negative emotions and influence their clinical decision making. This study investigated the impact of the psychiatric or social background of such patients on physicians’ decision making about whether to offer recommendations for further examinations and whether they expressed an appropriate disposition toward the patient.

Methods

A randomized, controlled multi-centre study of residents in transitional, internal medicine, or emergency medicine was conducted in five hospitals. Upon randomization, participants were stratified by gender and postgraduate year, and they were allocated to scenario set 1 or 2. They answered questions pertaining to decision-making based on eight clinical vignettes. Half of the eight vignettes presented to scenario set 1 included additional patient information, such as that the patient had a past medical history of schizophrenia or that the patient was a recipient of free care who made frequent visits to the doctor (biased vignettes). The other half included no additional information (neutral vignettes). For scenario set 2, the four biased vignettes presented to scenario set 1 were neutralized, and the four neutral vignettes were rendered biased by providing additional information. After reading, participants answered decision-making questions regarding diagnostic examination, interventions, or patient disposition. The primary analysis was a repeated-measures ANOVA on the mean management accuracy score, with patient background information as a within-subject factor (no bias, free care recipients, or history of schizophrenia).

Results

A total of 207 questionnaires were collected. Repeated-measures ANOVA showed that additional background information had influence on mean accuracy score (F(7, 206) = 13.84, p <  0.001 partial η2 = 0.063). Post hoc pairwise multiple comparison test, Sidak test, showed a significant difference between schizophrenia and no bias condition (p <  0.05). The ratings for patient likability were lower in the biased vignettes compared to the neutral vignettes, which was associated with the lower utilization of medical resources by the physicians.

Conclusions

Additional background information on past medical history of schizophrenia increased physicians’ mistakes in decision making. Patients’ psychiatric backgrounds should not bias physicians’ decision-making. Based on these findings, physicians are recommended to avoid being influenced by medically unrelated information.
Towards the automation of early-stage human embryo development detection
Authors: Raudonis Vidas , Paulauskaite-Taraseviciene Agne , Sutiene Kristina , Jonaitis Domas
Published: December 2019

Background

Infertility and subfertility affect a significant proportion of humanity. Assisted reproductive technology has been proven capable of alleviating infertility issues. In vitro fertilisation is one such option whose success is highly dependent on the selection of a high-quality embryo for transfer. This is typically done manually by analysing embryos under a microscope. However, evidence has shown that the success rate of manual selection remains low. The use of new incubators with integrated time-lapse imaging system is providing new possibilities for embryo assessment. As such, we address this problem by proposing an approach based on deep learning for automated embryo quality evaluation through the analysis of time-lapse images. Automatic embryo detection is complicated by the topological changes of a tracked object. Moreover, the algorithm should process a large number of image files of different qualities in a reasonable amount of time.

Methods

We propose an automated approach to detect human embryo development stages during incubation and to highlight embryos with abnormal behaviour by focusing on five different stages. This method encompasses two major steps. First, the location of an embryo in the image is detected by employing a Haar feature-based cascade classifier and leveraging the radiating lines. Then, a multi-class prediction model is developed to identify a total cell number in the embryo using the technique of deep learning.

Results

The experimental results demonstrate that the proposed method achieves an accuracy of at least 90% in the detection of embryo location. The implemented deep learning approach to identify the early stages of embryo development resulted in an overall accuracy of over 92% using the selected architectures of convolutional neural networks. The most problematic stage was the 3-cell stage, presumably due to its short duration during development.

Conclusion

This research contributes to the field by proposing a model to automate the monitoring of early-stage human embryo development. Unlike in other imaging fields, only a few published attempts have involved leveraging deep learning in this field. Therefore, the approach presented in this study could be used in the creation of novel algorithms integrated into the assisted reproductive technology used by embryologists.
New considerations on pathways involved in acute traumatic coagulopathy: the thrombin generation paradox
Authors: Gangloff Cedric , Mingant Fanny , Theron Michael , Galinat Hubert , Grimault Ollivier , Ozier Yves , Pichavant-Rafini Karine
Published: December 2019

Background

An acute traumatic coagulopathy (ATC) is observed in about one third of severely traumatized patients. This early, specific, and endogenous disorder is triggered by the association of trauma and hemorrhage. The early phase of this condition is characterized by the expression of a bleeding phenotype leading to hemorrhagic shock and the late phase by a prothrombotic profile leading to multiple organ failure. The physiopathology of this phenomenon is still poorly understood. Hypotheses of disseminated intravascular coagulation, activated protein C-mediated fibrinolysis, fibrinogen consumption, and platelet functional impairment were developed by previous authors and continue to be debated. The objective of this study was to observe general hemostasis disorders in case of ATC to confront these hypotheses.

Method

Four groups of 15 rats were compared: C, control; T, trauma; H, hemorrhage; and TH, trauma and hemorrhage. Blood samples were drawn at baseline and 90 min. Thrombin generation tests, platelet aggregometry, and standard hemostasis tests were performed.

Results

Significant differences were observed between the baseline and TH groups for aPTT (17.9 ± 0.8 s vs 24.3 ± 1.4 s,p< 0.001, mean ± SEM), MAP (79.7 ± 1.3 mmHg vs 43.8 ± 1.3 mmHg,p< 0.001, mean ± SEM), and hemoglobin (16.5 ± 0.1 g/dL vs 14.1 ± 0.3 g/dL,p< 0.001, mean ± SEM), indicating the presence of an hemorrhagic shock due to ATC. Compared to all other groups, coagulation factor activities were decreased in the TH group, but endogenous thrombin potential was (paradoxically) higher than in group C (312 ± 17 nM/min vs. 228 ± 23 nM/min;p= 0.016; mean ± SEM). We also observed a subtle decrease in platelet count and function in case of ATC and retrieved an inversed linear relationship between fibrinogen concentration and aPTT (intercept, 26.53 ± 3.16; coefficient, − 3.40 ± 1.26; adjustedR2: 0.1878;p= 0.0123).

Conclusions

The clinical-biological profile that we observed, combining normal thrombin generation, fibrinogen depletion, and a hemorrhagic phenotype, reinforced the hypothesis of activated protein C mediated-fibrinolysis. The key role of fibrinogen, but not of the platelets, was confirmed in this study. The paradoxical preservation of thrombin generation suggests a protective mechanism mediated by rhabdomyolysis in case of major trauma. Based on these results, we propose a new conception concerning the pathophysiology of ATC.
N-myc downstream-regulated gene 1 inhibits the proliferation of colorectal cancer through emulative antagonizing NEDD4-mediated ubiquitylation of p21
Authors: Zhang Sen , Yu Chaoran , Yang Xiao , Hong Hiju , Lu Jiaoyang , Hu Wenjun , Hao Xiaohui , Li Shuchun , Aikemu Batuer , Yang Guang , He Zirui , Zhang Luyang , Xue Pei , Cai Zhenghao , Ma Junjun , Zang Lu , Feng Bo , Yuan Fei , Sun Jing , Zheng Minhua
Published: December 2019

Background

N-myc downstream-regulated gene 1 (NDRG1) has been shown to play a key role in tumor metastasis. Recent studies demonstrate that NDRG1 can suppress tumor growth and is related to tumor proliferation; however, the mechanisms underlying these effects remain obscure.

Methods

Immunohistochemistry (IHC) was used to detect NDRG1 and p21 protein expression in colorectal cancer tissue, and clinical significance of NDRG1 was also analyzed. CCK-8 assay, colony formation assay, flow cytometry, and xenograft model were used to assess the effect of NDRG1 on tumor proliferation in vivo and in vitro. The mechanisms underlying the effect of NDRG1 were investigated using western blotting, immunofluorescence, immunoprecipitation, and ubiquitylation assay.

Results

NDRG1 was down-regulated in CRC tissues and correlated with tumor size and patient survival. NDRG1 inhibited tumor proliferation through increasing p21 expression via suppressing p21 ubiquitylation. NDRG1 and p21 had a positive correlation both in vivo and in vitro. Mechanistically, E3 ligase NEDD4 could directly interact with and target p21 for degradation. Moreover, NDRG1 could emulatively antagonize NEDD4-mediated ubiquitylation of p21, increasing p21 expression and inhibit tumor proliferation.

Conclusion

Our study could fulfill potential mechanisms of the NDRG1 during tumorigenesis and metastasis, which may serve as a tumor suppressor and potential target for new therapies in human colorectal cancer.
Protocol for a partially nested randomized controlled trial to evaluate the effectiveness of the Scleroderma Patient-centered Intervention Network Support Group Leader EDucation (SPIN-SSLED) Program
Authors:   SPIN-SSLED Support Group Advisory Team, Thombs Brett D. , Aguila Kylene , Dyas Laura , Carrier Marie-Eve , Fedoruk Claire , Horwood Linda , Cañedo-Ayala Mara , Sauvé Maureen , Kwakkenbos Linda , Malcarne Vanessa L. , El-Baalbaki Ghassan , Peláez Sandra , Connolly Kerri , Hudson Marie , Platt Robert W.
Published: December 2019

Background

Some people with rare diseases rely on peer-led support groups for disease-specific education and emotional and practical support. Systemic sclerosis (SSc), or scleroderma, is a rare autoimmune connective tissue disease. Many people with SSc cannot access support groups, and, when support groups exist, they may not be sustained due to challenges that could be addressed via leader training. The Scleroderma Patient-centered Intervention Network (SPIN), along with SSc patient organization partners, developed a training program for SSc patient support group leaders, the Scleroderma Support group Leader EDucation (SPIN-SSLED) Program. We recently completed a feasibility trial in which we successfully delivered the program to two groups of support group leaders who reported a high level of satisfaction with the program and its delivery. The primary objective of the full-scale SPIN-SSLED trial is to evaluate the effect of the program on support group leaders’ self-efficacy for carrying out their leadership role. Secondary objectives include evaluating effects on leader burnout, leader satisfaction (participation efficacy), and emotional distress.

Methods/design

The SPIN-SSLED trial is a pragmatic randomized controlled trial (RCT) in which 180 support group leaders will be randomly allocated to training groups of 6 participants each or to a waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups, but not in the waitlist control. Participants allocated to the training program will receive the 13-module SPIN-SSLED Program, delivered via webinar over the course of 3 months in weekly 60–90-min sessions. The primary outcome is leader self-efficacy, measured by the Scleroderma Support Group Leader Self-efficacy Scale post-intervention. Secondary outcomes are leader self-efficacy at 3 months post-intervention, and leader burnout, volunteer job satisfaction (participation efficacy), and emotional distress post-intervention and at 3 months post-intervention.

Discussion

The SPIN-SSLED trial will test whether a training program for SSc patient support group leaders increases the self-efficacy of group leaders to carry out leadership tasks. The program has the potential to significantly improve the effectiveness and sustainability of existing SSc support groups, to increase the number of available support groups, and to be adapted for other chronic diseases.

Trial registration

ClinicalTrials.gov, NCT03965780. Registered on 29 May 2019.
Pulmonary Metastasectomy versus Continued Active Monitoring in Colorectal Cancer (PulMiCC): a multicentre randomised clinical trial
Authors:   PulMiCC Trial Group, Treasure Tom , Farewell Vern , Macbeth Fergus , Monson Kathryn , Williams Norman R , Brew-Graves Chris , Lees Belinda , Grigg Olivia , Fallowfield Lesley
Published: December 2019

Background

Lung metastasectomy in the treatment of advanced colorectal cancer has been widely adopted without good evidence of survival or palliative benefit. We aimed to test its effectiveness in a randomised controlled trial (RCT).

Methods

Multidisciplinary teams in 13 hospitals recruited participants with potentially resectable lung metastases to a multicentre, two-arm RCT comparing active monitoring with or without metastasectomy. Other local or systemic treatments were decided by the local team. Randomisation was remote and stratified by site with minimisation for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, the number of metastases, and carcinoembryonic antigen level. The central Trial Management Group were blind to patient allocation until completion of the analysis. Analysis was on intention to treat with a margin for non-inferiority of 10%.

Results

Between December 2010 and December 2016, 65 participants were randomised. Characteristics were well-matched in the two arms and similar to those in reported studies: age 35 to 86 years (interquartile range (IQR) 60 to 74); primary resection IQR 16 to 35 months previously; stage at resection T1, 2 or 3 in 3, 8 and 46; N1 or N2 in 31 and 26; unknown in 8. Lung metastases 1 to 5 (median 2); 16/65 had previous liver metastases; carcinoembryonic antigen normal in 55/65. There were no other interventions in the first 6 months, no crossovers from control to treatment, and no treatment-related deaths or major adverse events. The Hazard ratio for death within 5 years, comparing metastasectomy with control, was 0.82 (95%CI 0.43, 1.56).

Conclusions

Because of poor and worsening recruitment, the study was stopped. The small number of participants in the trial (N = 65) precludes a conclusive answer to the research question given the large overlap in the confidence intervals in the proportions still alive at all time points. A widely held belief is that the 5-year absolute survival benefit with metastasectomy is about 35%: 40% after metastasectomy compared to < 5% in controls. The estimated survival in this study was 38% (23–62%) for metastasectomy patients and 29% (16–52%) in the well-matched controls. That is the new and important finding of this RCT.

Trial registration

ClinicalTrials.gov, ID:NCT01106261. Registered on 19 April 2010
LTR_FINDER_parallel: parallelization of LTR_FINDER enabling rapid identification of long terminal repeat retrotransposons
Authors: Ou Shujun , Jiang Ning
Published: December 2019

Annotation of plant genomes is still a challenging task due to the abundance of repetitive sequences, especially long terminal repeat (LTR) retrotransposons. LTR_FINDER is a widely used program for the identification of LTR retrotransposons but its application on large genomes is hindered by its single-threaded processes. Here we report an accessory program that allows parallel operation of LTR_FINDER, resulting in up to 8500X faster identification of LTR elements. It takes only 72 min to process the 14.5 Gb bread wheat (Triticum aestivum) genome in comparison to 1.16 years required by the original sequential version. LTR_FINDER_parallel is freely available at https://github.com/oushujun/LTR_FINDER_parallel.
Evaluation of MDR1 and MRPA genes expression in different types of dry cutaneous leishmaniasis
Authors: Fekrisoofiabadi Maryam , Fekri Meisam , Moradabadi Alireza , Vahidi Reza , Khaleghi Morteza , Ram Maryam , Dabiri Shahriar
Published: December 2019

Objective

The resistance to antimony-containing glucantime is a major obstacle to successful treatment, especially in endemic areas. Looking the molecular mechanisms involved in this drug resistance will help in choosing the best treatment. The aim of this study was to evaluate the expression of multidrug-resistance 1 (MDR1) and multidrug-resistance protein A (MRPA) genes in acute, chronic non-lupoid, and chronic lupoid forms of dry type cutaneous leishmaniasis (DTCL).

Results

MDR1 gene was over-expressed as 14.4- and 1.56-folds in the chronic lupoid and acute forms compared with the chronic non-lupoid form, respectively. Results comparison showed P < 0.05 between the chronic non-lupoid and acute groups, P < 0.01 between acute and chronic lupoid groups, and P < 0.001 between the chronic non-lupoid and chronic lupoid groups. MRPA gene was over-expressed as 266 and 17.7-fold in the chronic lupoid and chronic non-lupoid forms compared with the acute form, respectively. Statistical analysis showed P < 0.01 between the chronic non-lupoid and chronic lupoid groups, P < 0.05 between acute and chronic non-lupoid groups, and P < 0.001 between the acute and chronic lupoid groups.
Lsr operon is associated with AI-2 transfer and pathogenicity in avian pathogenic Escherichia coli
Authors: Zuo Jiakun , Yin Huifang , Hu Jiangang , Miao Jinfeng , Chen Zhaoguo , Qi Kezong , Wang Zhihao , Gong Jiansen , Phouthapane Vanhnaseng , Jiang Wei , Mi Rongsheng , huang Yan , Wang Chen , Han Xiangan
Published: December 2019

The function of Autoinducer-2 (AI-2) which acts as the signal molecule of LuxS-mediated quorum sensing, is regulated through the lsr operon (which includes eight genes: lsrK, lsrR, lsrA, lsrC, lsrD, lsrB, lsrF, and lsrG). However, the functions of the lsr operon remain unclear in avian pathogenic Escherichia coli (APEC), which causes severe respiratory and systemic diseases in poultry. In this study, the presence of the lsr operon in 60 APEC clinical strains (serotypes O1, O2, and O78) was investigated and found to be correlated with serotype and has the highest detection rate in O78. The AI-2 binding capacity of recombinant protein LsrB of APEC (APEC-LsrB) was verified and was found to bind to AI-2 in vitro. In addition, the lsr operon was mutated in an APEC strain (APEC94Δlsr(Cm)) and the mutant was found to be defective in motility and AI-2 uptake. Furthermore, deletion of the lsr operon attenuated the virulence of APEC, with the LD50 of APEC94Δlsr(Cm) decreasing 294-fold compared with wild-type strain APEC94. The bacterial load in the blood, liver, spleen, and kidneys of ducks infected with APEC94Δlsr(Cm) decreased significantly (p < 0.0001). The results of transcriptional analysis showed that 62 genes were up-regulated and 415 genes were down-regulated in APEC94Δlsr(Cm) compared with the wild-type strain and some of the down-regulated genes were associated with the virulence of APEC. In conclusion, our study suggests that lsr operon plays a role in the pathogenesis of APEC.
Sustainable intensification of beef production in Colombia—Chances for product differentiation and price premiums
Authors: Charry Andrés , Narjes Manuel , Enciso Karen , Peters Michael , Burkart Stefan
Published: December 2019

To promote the adoption of more sustainable cattle production systems in Colombia (mainly silvopastoral systems with improved forages), some sector stakeholders have proposed the development of differentiated, higher value beef products. However, there have been no rigorous estimations of local market potential and consumer preferences for these hypothetical products yet. On the other hand, while there are clear efforts concerning the environmental impacts of cattle production, its animal welfare implications have taken a secondary place. This research attempts to evaluate the consumer’s response to both the environmental and animal welfare aspects of more sustainable food systems by (i) determining the characteristics of a consumer segment for sustainably produced beef using contingent valuation methods and (ii) estimating the marginal willingness to pay (MWTP) for animal welfare compliance and the environmental benefits derived from sustainable intensification within the identified consumer segment, employing a Discrete Choice Experiment (DCE). In addition, the study estimates the effect of information on consumer’s MWTP for environmentally friendlier beef. Results show that consumers within the identified segment are willing to pay on average 40.2% more for beef certified with both animal welfare and eco-friendly standards, with an increase of nearly 10% after being provided with information of the sector’s environmental impacts. These findings support some of the current climate change mitigation strategies in the national cattle industry while highlighting relevant opportunities and trade-offs in the context of a developing country.
Applying indirect open-circuit calorimetry to study energy expenditure in gnotobiotic mice harboring different human gut microbial communities
Authors: Halatchev Ilia G. , O’Donnell David , Hibberd Matthew C. , Gordon Jeffrey I.
Published: December 2019

Given the increasing use of gnotobiotic mouse models for deciphering the effects of human microbial communities on host biology, there is a need to develop new methods for characterizing these animals while maintaining their isolation from environmental microbes. We describe a method for performing open-circuit indirect calorimetry on gnotobiotic mice colonized with gut microbial consortia obtained from different human donors. In this illustrative case, cultured collections of gut bacterial strains were obtained from obese and lean co-twins. The approach allows microbial contributions to host energy homeostasis to be characterized.
Advancing the implementation and sustainment of medication assisted treatment for opioid use disorders in prisons and jails
Authors: Ferguson Warren J. , Johnston Joan , Clarke Jennifer G. , Koutoujian Peter J. , Maurer Kathleen , Gallagher Colleen , White Julie , Nickl Dyana , Taxman Faye S.
Published: December 2019

Background

Opioid use disorder (OUD) is among the most prevalent medical condition experienced by incarcerated persons, yet medication assisted therapy (MAT) is uncommon. Four jail and prison systems partnered with researchers to document their adoption of MAT for incarcerated individuals with opioid use disorders (OUD) using their established treatment protocols. Employing the EPIS (Exploration, Planning, Implementation, and Sustainment) framework, programs report on systematic efforts to expand screening, treatment and provide linkage to community-based care upon release.

Results

All four systems were engaged with implementation of MAT at the outset of the study. Thus, findings focus more on uptake and penetration as part of implementation and sustainment of medication treatment. The prevalence of OUD during any given month ranged from 28 to 65% of the population in the participating facilities. All programs developed consistent approaches to screen individuals at intake and provided care coordination with community treatment providers at the time of release. The proportion of individuals with OUD who received MAT ranged considerably from 9 to 61%. Despite efforts at all four sites to increase utilization of MAT, only one site achieved sustained growth in the proportion of individuals treated over the course of the project. Government leadership, dedicated funding and collaboration with community treatment providers were deemed essential to adoption of MAT during implementation phases. Facilitators for MAT included increases in staffing and staff training; group education on medication assisted therapies; use of data to drive change processes; coordination with other elements of the criminal justice system to expand care; and ongoing contact with individuals post-release to encourage continued treatment. Barriers included lack of funding and space and institutional design; challenges in changing the cultural perception of all approved treatments; excluding or discontinuing treatment based on patient factors, movement or transfer of individuals; and inability to sustain care coordination at the time of release.

Conclusions

Adoption of evidence-based medication assisted therapies for OUD in prisons and jails can be accomplished but requires persistent effort to identify and overcome challenges and dedicated funding to sustain programs.
Comparison of scandium-44 g with other PET radionuclides in pre-clinical PET phantom imaging
Authors: Ferguson Simon , Jans Hans-Sonke , Wuest Melinda , Riauka Terence , Wuest Frank
Published: December 2019

Purpose

The decay characteristics of radionuclides in PET studies can impact image reconstruction. 44gSc has been the topic of recent research due to potential theranostic applications and is a promising radiometal for PET imaging. In this study, the reconstructed images from phantom measurements with scandium in a small-animal PET scanner are compared with 18F and two prominent radiometals: 64Cu and 68Ga

Methods

Three phantoms filled with 18F, 64C, 68Ga, and 44gSc were imaged in the Siemens Inveon PET scanner. The NEMA image quality phantom was used to determine the recovery coefficients (RCs), spill-over ratios (SORs), and noise (%SD) under typical pre-clinical imaging conditions. Image contrast was determined using a Derenzo phantom, while the coincidence characteristics were investigated using an NEC phantom. Three reconstruction algorithms were used, namely filtered back projection (FBP), ordered subset expectation maximization (OSEM), and maximum a-posteriori (MAP).

Results

Image quality parameters were measured for 18F, 64Cu, 68Ga, and 44gSc respectively; using FBP, the %SD are 5.65, 5.88, 7.28, and 7.70; the RCs for the 5-mm rod are 0.849, 1.01, 0.615, and 0.825; the SORs in water are 0.0473, 0.0595, 0.141, 0.0923; and the SORs in air are 0.0589, 0.0484, 0.0525, and 0.0509. The contrast measured in the 2.5-mm rods are 0.674, 0.637, 0.196, and 0.347. The NEC rate with 44gSc increased at a slower rate than 18F and 68Ga as a function of activity in the field of view.

Conclusion

44gSc demonstrates intermediate behavior relative to 18F and 68Ga with regard to RC and contrast measurements. It is a promising radionuclide for preclinical imaging.
Nonlinear pre and post-buckled analysis of curved beams using differential quadrature element method
Authors: Zare M. , Asnafi A.
Published: December 2019

This paper studied the in-plane elastic stability including pre and post-buckling analysis of curved beams considering the effects of shear deformations, rotary inertia, and the geometric nonlinearity due to large deformations. Firstly, the governing nonlinear equations of motion were derived. The problem was solved performing both the static and dynamic analysis using the numerical method of differential quadrature element method (DQEM) which is a new and efficient numerical method for rapidly solving linear and nonlinear differential equations. Firstly, the method was applied to the equilibrium equations, leading to a nonlinear algebraic system of equations that would be solved utilizing an arc length strategy. Secondly, the results of the static part were employed to linearize the dynamic differential equations of motion and their corresponding boundary and continuity conditions. Without any loss of generality, a clamped-clamped curved beam under a concentrated load was considered to obtain the buckling loads, natural frequencies, and mode shapes of the beam throughout the method. To validate the proposed method, the beam was modeled using a finite element simulation. A great agreement between the results was seen that showed the accuracy of the proposed method in predicting the pre and post-buckling behavior of the beam. The investigation also included an examination of the curvature parameter influencing the dynamic behavior of the problem. It was shown that the values of buckling loads were completely influenced by the curvature of the beam; also, due to the sharp change of longitudinal stiffness after bucking, the symmetric mode shapes changed more than it was expected.
Does the manual insertion torque of smartpegs affect the outcome of implant stability quotients (ISQ) during resonance frequency analysis (RFA)?
Authors: Kästel Ingrid , de Quincey Giles , Neugebauer Jörg , Sader Robert , Gehrke Peter
Published: December 2019

Background

There is disagreement about the optimal torque for tightening smartpegs for resonance frequency analysis (RFA). Subjective finger pressure during hand tightening could affect the reliability of the resulting values. The aim of the current study was therefore to assess whether or not the insertion torque of a smartpeg magnetic device influences the implant stability quotient (ISQ) value during RFA.

Methods

Thirty self-tapping screw implants (XiVE S, Dentsply Sirona Implants, Bensheim, Germany) with a diameter of 3.8 mm and a length of 11 mm were inserted in three cow ribs with a bone quality of D1. The RFA value of each implant was measured (Ostell, FA W&H Dentalwerk, Bürmoos, Austria) in two orthogonal directions (mesial and buccal) after tightening the corresponding smartpeg type 45 with a mechanically defined value of 5 Ncm (Meg Torq device, Megagen, Daegu, South Korea) (test). Additionally, 4 different examiners measured the RFA after hand tightening the smartpegs, and the results were compared (control). Insertion torque values were determined by measuring the unscrew torque of hand seated smartpegs (Tohnichi Manufacturing Co. Ltd, Tokyo, Japan).

Results

The ISQ values varied from 2 to 11 Ncm by hand tightening and from 2 to 6 Ncm by machine tightening. The comparison of hand and machine tightening of smartpegs displayed only minor differences in the mean ISQ values with low standard deviations (mesial 79.76 ± 2,11, buccal 77.98 ± 2,) and no statistical difference (mesialp= 0,343 and buccalp= 0,890).

Conclusions

Manual tightening of smartpeg transducers allows for an objective and reliable determination of ISQ values during RFA.
Cerebral infarction detected after laparoscopic partial hepatectomy: case report
Authors: Kobayashi Atsushi , Shirozu Kazuhiro , Karashima Yuji , Matsushita Katsuyuki , Yamaura Ken
Published: December 2019

Background

Bleeding and carbon dioxide (CO2) gas embolism have been reported as serious complications associated with laparoscopic surgery. We present a case of cerebral infarction presumably caused by CO2 gas embolism during laparoscopic hepatectomy.

Case presentation

During liver resection, the end-tidal CO2 suddenly dropped from 40 to 21 mmHg. Simultaneously, ST elevation in lead II and ST depression in lead V5 of the electrocardiogram were observed. After improvement of these electrocardiographic changes, surgery was continued. Postoperatively, incomplete paralysis was present in the right arm and leg. Magnetic resonance imaging revealed cerebral infarction in the broad area of the left cerebral cortex. These complications might have been caused by paradoxical embolism.

Conclusion

We should always keep in mind the risk of cerebral infarction with neurological deficits in the case of laparoscopic surgery. Careful monitoring and appropriate treatment for gas embolism are necessary during laparoscopic surgery.
Constipation in chronic kidney disease: it is time to reconsider
Authors: Ikee Ryota , Yano Kazuhiro , Tsuru Tomomi
Published: December 2019

Constipation is highly prevalent in patients with chronic kidney disease (CKD) and is primarily characterized by decreased intestinal motility. This chronic disorder affects the quality of life of patients. However, nephrologist and dialysis clinicians have long had a disproportionately limited understanding of constipation. Accumulating evidence has revealed a relationship between constipation and cardiovascular disease and CKD. The pathogenesis of constipation in CKD patients is multifactorial: decreased physical activity, comorbidities affecting bowel movement, such as diabetes mellitus, cerebrovascular disease, and hyperparathyroidism, a restricted dietary intake of plant-based fiber-rich foods, and multiple medications, including phosphate binders and potassium-binding resins, have all been implicated. CKD is associated with alterations in the composition and function of the gut microbiota, so-called gut dysbiosis. Recent studies showed that CKD-related gut dysbiosis decreased intestinal motility via intestinal inflammation or the increased generation of gut-derived uremic toxins, such as indoxyl sulfate and p-cresyl sulfate. Furthermore, the gastrointestinal secretion of mucin was found to be decreased in CKD animal models, which may delay colonic transit by diminished lubrication in the alimentary tract. Thus, CKD-related gut dysbiosis may play a role in constipation, but limited information is currently available. Since constipation is often intractable, particularly in CKD patients, every available means needs to be employed in its treatment. The effects of probiotics, prebiotics, and synbiotics on the composition of the gut microbiota and gut-derived uremic toxins have been increasingly reported. However, their effects on stool consistency or frequency in CKD patients remain unclear. Some laxatives may be beneficial for improving not only bowel habits but also gut dysbiosis. Further studies are required to elucidate the CKD-specific pathogenesis of constipation and develop novel effective treatment options.
Optimization of energy exchange in microgrid networks: a coalition formation approach
Authors: Essayeh Chaimaa , Fenni Mohammed Raiss El , Dahmouni Hamza
Published: December 2019

In this paper, we elaborate a new strategy based on cooperative game theory models to encourage and manage the interactions in a MicroGrid network. The proposed strategy optimizes the cooperation and the energy exchange in a distributed μGrid network. The strategy consists of a two stage algorithm: Coalition formation algorithm which was specifically created to approximate the optimal set of coalitions that return considerable savings. And the Matching game to manage the energy exchange inside each coalition. The performance of our strategy was verified through simulations. These latter show that the losses can be considerably decreased by the use of the proposed strategy: the rate of the loss reduction can reach up to 20% if the two stages are applied on the network. Moreover, the strategy proved to have a fast convergence which makes it operational for real implemented networks.
Diagnosis of an intestinal mucormycosis ‘fungus ball’ located with PET/CT with [18F] FDG-PET/CT
Authors: Gallo Franklin , Vija Lavinia , Le Grand Sophie , Moukarbel Nada , Mortele Koen , Gabiache Erwan , Courbon Frédéric , Tavitian Suzanne , Dierickx Lawrence O.
Published: December 2019

Mucormycosis is a life-threatening infection with most commonly rhino-orbital-cerebral and pulmonary syndromes that mostly occurs in immunocompromised patients. FDG-PET/CT emerged as a sensitive non-invasive tool to identify systemic mucormycosis. We present a 59-year-old woman for whom a PET/CT with 18F-FDG was performed in search of a primary location of mucormycosis with non-contributive conventional workup. A large left abdominal mass was seen, compatible with a fungus ball, with intense parietal uptake and without any central uptake. The localization of the infection provided a target for surgery and permitted to adapt the therapeutic strategy. After resection, the final diagnosis was consistent with mucormycosis. To our knowledge, this is the first report of a PET/CT image with FDG showing an intestinal fungus ball. PET/CT with 18F-FDG may contribute to the management of patients with fungal infections of unknown origin.
Metagenomic discovery and co-infection of diverse wobbly possum disease viruses and a novel hepacivirus in Australian brushtail possums
Authors: Chang Wei-Shan , Eden John-Sebastian , Hartley William J. , Shi Mang , Rose Karrie , Holmes Edward C.
Published: December 2019

Background

Australian brushtail possums (Trichosurus vulpecula) are an introduced pest species in New Zealand, but native to Australia where they are protected for biodiversity conservation. Wobbly possum disease (WPD) is a fatal neurological disease of Australian brushtail possums described in New Zealand populations that has been associated with infection by the arterivirus (Arteriviridae) wobbly possum disease virus (WPDV-NZ). Clinically, WPD-infected possums present with chronic meningoencephalitis, choroiditis and multifocal neurological symptoms including ataxia, incoordination, and abnormal gait.

Methods

We conducted a retrospective investigation to characterise WPD in native Australian brushtail possums, and used a bulk meta-transcriptomic approach (i.e. total RNA-sequencing) to investigate its potential viral aetiology. PCR assays were developed for case diagnosis and full genome recovery in the face of extensive genetic variation.

Results

We identified genetically distinct lineages of arteriviruses from archival tissues of WPD-infected possums in Australia, termed wobbly possum disease virus AU1 and AU2. Phylogenetically, WPDV-AU1 and WPDV-AU2 shared only ~ 70% nucleotide similarity to each other and the WPDV-NZ strain, suggestive of a relatively ancient divergence. Notably, we also identified a novel and divergent hepacivirus (Flaviviridae) - the first in a marsupial - in both WPD-infected and uninfected possums, indicative of virus co-infection.

Conclusions

We have identified marsupial-specific lineages of arteriviruses in mainland Australia that are genetically distinct from that in New Zealand, in some cases co-infecting animals with a novel hepacivirus. Our study provides new insight into the hidden genetic diversity of arteriviruses, the capacity for virus co-infection, and highlights the utility of meta-transcriptomics for disease investigation in a One Health context.
Molecular Biomarkers in Localized Prostate Cancer: ASCO Guideline
Authors: Eggener Scott E. , Rumble R. Bryan , Armstrong Andrew J. , Morgan Todd M. , Crispino Tony , Cornford Philip , van der Kwast Theodorus , Grignon David J. , Rai Alex J. , Agarwal Neeraj , Klein Eric A. , Den Robert B. , Beltran Himisha
Published: December 2019

PURPOSE

This guideline provides recommendations for available tissue-based prostate cancer biomarkers geared toward patient selection for active surveillance, identification of clinically significant disease, choice of postprostatectomy adjuvant versus salvage radiotherapy, and to address emerging questions such as the relative value of tissue biomarkers compared with magnetic resonance imaging.

METHODS

An ASCO multidisciplinary Expert Panel, with representatives from the European Association of Urology, American Urological Association, and the College of American Pathologists, conducted a systematic literature review of localized prostate cancer biomarker studies between January 2013 and January 2019. Numerous tissue-based molecular biomarkers were evaluated for their prognostic capabilities and potential for improving management decisions. Here, the Panel makes recommendations regarding the clinical use and indications of these biomarkers.

RESULTS

Of 555 studies identified, 77 were selected for inclusion plus 32 additional references selected by the Expert Panel. Few biomarkers had rigorous testing involving multiple cohorts and only 5 of these tests are commercially available currently: Onco type Dx Prostate, Prolaris, Decipher, Decipher PORTOS, and ProMark. With various degrees of value and validation, multiple biomarkers have been shown to refine risk stratification and can be considered for select men to improve management decisions. There is a paucity of prospective studies assessing short- and long-term outcomes of patients when these markers are integrated into clinical decision making.

RECOMMENDATIONS

Tissue-based molecular biomarkers (evaluating the sample with the highest volume of the highest Gleason pattern) may improve risk stratification when added to standard clinical parameters, but the Expert Panel endorses their use only in situations in which the assay results, when considered as a whole with routine clinical factors, are likely to affect a clinical decision. These assays are not recommended for routine use as they have not been prospectively tested or shown to improve long-term outcomes—for example, quality of life, need for treatment, or survival. Additional information is available at www.asco.org/genitourinary-cancer-guidelines .