bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of transcriptomic biomarkers of endometrial receptivity in personalized embryo transfer for patients with repeated implantation failure
Authors: He Aihua , Zou Yangyun , Wan Cheng , Zhao Jing , Zhang Qiong , Yao Zhongyuan , Tian Fen , Wu Hong , Huang Xi , Fu Jing , Hu Chunxu , Sun Yue , Xiao Lan , Yang Tianli , Hou Zhaojuan , Dong Xin , Lu Sijia , Li Yanping
Published: April 2021

Background

Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF.

Methods

This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group.

Results

The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830;P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718;P = 0.111) when transferring blastocysts.

Conclusions

The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET.

Trial registrationChinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017,http://www.chictr.org.cn/index.aspx
The gut microbiota is associated with the small intestinal paracellular permeability and the development of the immune system in healthy children during the first two years of life
Authors: Kaczmarczyk Mariusz , Löber Ulrike , Adamek Karolina , Węgrzyn Dagmara , Skonieczna-Żydecka Karolina , Malinowski Damian , Łoniewski Igor , Markó Lajos , Ulas Thomas , Forslund Sofia K. , Łoniewska Beata
Published: April 2021

Background

The intestinal barrier plays an important role in the defense against infections, and nutritional, endocrine, and immune functions. The gut microbiota playing an important role in development of the gastrointestinal tract can impact intestinal permeability and immunity during early life, but data concerning this problem are scarce.

Methods

We analyzed the microbiota in fecal samples (101 samples in total) collected longitudinally over 24 months from 21 newborns to investigate whether the markers of small intestinal paracellular permeability (zonulin) and immune system development (calprotectin) are linked to the gut microbiota. The results were validated using data from an independent cohort that included the calprotectin and gut microbiota in children during the first year of life.

Results

Zonulin levels tended to increase for up to 6 months after childbirth and stabilize thereafter remaining at a high level while calprotectin concentration was high after childbirth and began to decline from 6 months of life. The gut microbiota composition and the related metabolic potentials changed during the first 2 years of life and were correlated with zonulin and calprotectin levels. Faecal calprotectin correlated inversely with alpha diversity (Shannon index, r = − 0.30, FDR P (Q) = 0.039). It also correlated with seven taxa; i.a. negatively with Ruminococcaceae (r = − 0.34, Q = 0.046), and Clostridiales (r = − 0.34, Q = 0.048) and positively withStaphylococcus(r = 0.38, Q = 0.023) and Staphylococcaceae (r = 0.35, Q = 0.04), whereas zonulin correlated with 19 taxa; i.a. with Bacillales (r = − 0.52, Q = 0.0004), Clostridiales (r = 0.48, Q = 0.001) and theRuminococcus(torquesgroup) (r = 0.40, Q = 0.026). When time intervals were considered only changes in abundance of theRuminococcus(torquesgroup) were associated with changes in calprotectin (β = 2.94, SE = 0.8, Q = 0.015). The dynamics of stool calprotectin was negatively associated with changes in two MetaCyc pathways: pyruvate fermentation to butanoate (β = − 4.54, SE = 1.08, Q = 0.028) andClostridium acetobutylicumfermentation (β = − 4.48, SE = 1.16, Q = 0.026).

Conclusions

The small intestinal paracellular permeability, immune system-related markers and gut microbiota change dynamically during the first 2 years of life. TheRuminococcus(torquesgroup) seems to be especially involved in controlling paracellular permeability.Staphylococcus,Staphylococcaceae, Ruminococcaceae, and Clostridiales, may be potential biomarkers of the immune system. Despite observed correlations their clear causation and health consequences were not proven. Mechanistic studies are required.

Graphic abstract
Effects of tree species diversity and stand structure on carbon stocks of homestead forests in Maheshkhali Island, Southern Bangladesh
Authors: Baul Tarit Kumar , Chakraborty Avinanda , Nandi Rajasree , Mohiuddin Mohammed , Kilpeläinen Antti , Sultana Taslima
Published: April 2021

Background

The homestead forests of Bangladesh occupy 0.27 million hectares (10% of the total forested area) and have potential to store carbon (C) and conserve biodiversity. Small scale forestry practices, however, are lacking reliable estimation of C stocks and tree species diversity. This may hinder successful implementation of REDD + and similar mechanisms as they concentrate on large-scale forests. This study aimed to estimate the above- and below-ground carbon stocks in homestead forests of Maheshkhali Island in Bangladesh and how tree species diversity and stand structural variation affect these C stocks. We randomly surveyed a total of 239 homestead forests in the hillside, beachside, and inland in 2019.

Results

Tree biomass C stocks were 48–67% greater in the inland and hillside forests than in the beachside due to significantly greater stand density, basal area, tree diameter. In total we found 52 tree species, but most abundant species in the inland and hillside forests,Mangifera indica,Samanea saman, andArtocarpus heterophyllusstored the most C in tree biomass. Greater tree species richness and diversity index in the inland and hillside forests indicated greater above- and below-ground tree biomass C stocks. An increase in tree species richness and diversity index by one unit was found to increase the tree biomass C stock by 22 and 30 Mg C ha−1, respectively. The total soil C stock was also affected by tree species diversity, stand density, and their interaction with soil properties. Total soil C stocks were greatest (51 Mg ha−1) in the inland forests, having also the greatest stand density and tree species richness. C stock in soil surface was greatest in the hillside forests due to the greatest litterfall, but the average share of litterfall from the total biomass C was only 0.1%.

Conclusions

Homestead forest ecosystems could store 96 Mg C ha−1in total, which can contribute to climate change mitigation by generating C credits for small-scale homestead forests owners. Above- and below-ground tree biomass C stocks were found to correlate with tree species diversity, which may also contribute to biodiversity conservation in the REDD + in Bangladesh and countries alike.
Simultaneous development of COVID-19 pneumonia and pulmonary metastasis in a known case of chondrosarcoma: a case report
Authors: Rakhsha Afshin , Mahboubi-Fooladi Zahra , Jafari Anya
Published: April 2021

Background

The outbreak of coronavirus disease 2019 (COVID-19) started in December 2020, and is a global problem now. There are several sets of established data regarding computed tomography (CT) findings in COVID-19 pneumonia with many differential diagnoses. During the early days of the pandemic, there was little data regarding lung CT features of COVID-19 in a cancer patient. In this paper, we described a rare case of simultaneous presentation of COVID-19 with pulmonary metastasis.

Case presentation

A Persian patient with a history of chondrosarcoma presented to our clinic during the COVID-19 pandemic with a new-onset cough. He had experienced no recurrence during previous follow-up visits. Chest CT scan revealed numerous bilateral small peripheral and perilymphatic pulmonary nodules, unilateral ground-glass patch, and nodular interlobular septal thickening. Biopsy of the pulmonary nodules established pulmonary metastasis of chondrosarcoma origin, and pharyngeal reverse transcription polymerase chain reaction (RT-PCR) was positive for COVID-19.

Conclusion

Pulmonary metastasis should be considered as a differential diagnosis of COVID-19 features in cancer patients in the pandemic era.
Trajectory planning in UAV emergency networks with potential underlaying D2D communication based on K-means
Authors: Zhang Shuo , Shi Shuo , Feng Tianming , Gu Xuemai
Published: April 2021

At present, unmanned aerial vehicles (UAVs) have been widely used in communication systems, and the fifth-generation wireless system (5G) has further promoted the vigorous development of them. The trajectory planning of UAV is an important factor that affects the timeliness and completion of missions, especially in scenarios such as emergency communications and post-disaster rescue. In this paper, we consider an emergency communication network where a UAV aims to achieve complete coverage of potential underlaying device-to-device (D2D) users. Trajectory planning issues are grouped into clustering and supplementary phases for optimization. Aiming at trajectory length and sum throughput, two trajectory planning algorithms based on K-means are proposed, respectively. In addition, in order to balance sum throughput with trajectory length, we present a joint evaluation index. Then relying on this index, a third trajectory optimization algorithm is further proposed. Simulation results show the validity of the proposed algorithms which have advantages over the well-known benchmark scheme in terms of trajectory length and sum throughput.
Chronic disease multimorbidity among the Canadian population: prevalence and associated lifestyle factors
Authors: Geda Nigatu Regassa , Janzen Bonnie , Pahwa Punam
Published: April 2021

Background

Chronic diseases is increasingly becoming one of the most pressing public health concerns in most part of the world, including the Canadian population. The purpose of this study was to estimate the prevalence of multimorbidity in the general population based on 14 major chronic diseases and examine associations with lifestyle/behavioral factors.

Methods

The data source was the 2015–2016 Canadian Community Health Survey (CCHS). The CCHS is a cross sectional, complex multi-stage survey based on information collected from 109,659 participants aged 12+, covering all provinces and territories. Multimorbidity was defined as the co-occurrence of two or more chronic diseases within a person. Multiple logistic regression was used to examine the key determinants of multimorbidity.

Results

The prevalence of multimorbidity was 33 %. Adjusting for sociodemographic variables, there was an increased odd of multimorbidity for those having a sedentary lifestyle (AOR = 1.06; CI:1.01–1.11) and being obese (AOR = 1.37; CI:1.32–1.43) or overweight (AOR = 2.65; CI: 2.54–2.76). There were two statistically significant interactions, between sex and smoking, and between immigration status and alcohol intake. Smoking was more strongly associated with multimorbidity in females than males. The association between alcohol intake and multimorbidity was also dependent upon immigration status.

Conclusions

Given the high prevalence of multimorbidity among the general Canadian population, policy makers and service providers should give more attention to the behavioral/lifestyle factors which significantly predicted multimorbidity. Policy and program efforts that promote a healthy lifestyle should be a priority.
Correction to: Adapting inpatient addiction medicine consult services during the COVID‑19 pandemic
Authors: Harris Miriam T. H. , Peterkin Alyssa , Bach Paxton , Englander Honora , Lapidus Emily , Rolley Theresa , Weimer Melissa B. , Weinstein Zoe M.
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
EU FP7 research funding for an orphan drug (Orfadin®) and vaccine (Hep C) development: a success and a failure?
Authors: Schmidt L. , Sehic O. , Wild C.
Published: April 2021

Background

We considered the extent of the contribution of publicly funded research to the late-stage clinical development of pharmaceuticals and medicinal products, based on the European Commission (EC) FP7 research funding programme. Using two EC FP7-HEALTH case study examples—representing two types of outcomes—we then estimated wider public and charitable research funding contributions.

Methods

Using the publicly available database of FP7-HEALTH funded projects, we identified awards relating to late-stage clinical development according to the systematic application of inclusion and exclusion criteria, classified them according to product type and clinical indication, and calculated total EC funding amounts. We then identified two case studies representing extreme outcomes: failure to proceed with the product (hepatitis C vaccine) and successful market authorisation (Orfadin® for alkaptonuria). Total public and philanthropic research funding contributions to these products were then estimated using publicly available information on funding.

Results

12.3% (120/977) of all EC FP7-HEALTH awards related to the funding of late-stage clinical research, totalling € 686,871,399. Pharmaceutical products and vaccines together accounted for 84% of these late-stage clinical development research awards and 70% of its funding. The hepatitis C vaccine received total European Community (FP7 and its predecessor, EC Framework VI) funding of €13,183,813; total public and charitable research funding for this product development was estimated at € 77,060,102. The industry sponsor does not consider further development of this product viable; this now represents public risk investment. FP7 funding for the late-stage development of Orfadin® for alkaptonuria was so important that the trials it funded formed the basis for market authorisation, but it is not clear whether the price of the treatment (over €20,000 per patient per year) adequately reflects the substantial public funding contribution.

Conclusions

Public and charitable research funding plays an essential role, not just in early stage basic research, but also in the late-stage clinical development of products prior to market authorisation. In addition, it provides risk capital for failed products. Within this context, we consider further discussions about a public return on investment and its reflection in pricing policies and decisions justified.
Potential risk analysis and experience summarization of unstable factors of cranial fixation devices in neurosurgical operations: three-case reports and systematic review
Authors: Cheng Gaopeng , Hao Shuyu , Ye Zhifen , Wang Bao , Huangpu Bin , Zhang Pengfei , Wang Hao , Hao Qiang
Published: April 2021

Background

The use of cranial fixation devices in neurosurgery is very common, which is considered to be an important auxiliary method for many craniotomies. However, previous studies have reported complications of using cranial fixation devices, including brain tissue, nerve and blood vessel damage, scalp laceration, subcutaneous hematoma, etc. Some of the complications are serious and even potentially fatal, and the causes of which may be related to the incorrect use of cranial fixation devices. Although there are no serious complications in our review, the cause of that needs to be further summarized and analyzed, as so to minimize the serious consequences caused by the cranial fixation device slippage and ensure the safety of the patients’ surgical procedure.

Case presentation

In our recent work, we have continuously found three cases of unstable cranial fixation devices, which make us to analyze the possible factors and summarize experience combined with the review of other senior neurosurgeons (more than 3 years of working experience) from different departments of neurosurgery.

Conclusions

Based on our recent incidents of unstable cranial fixation and the experience of investigating and analyzing senior doctors from different neurosurgery centers, we summarized experience to minimize the risk of unstable cranial fixation. We tried a variety of options, including a safe anatomical location for cranial fixation, teamwork, and communication with anesthesiologists and itinerant nurses, to ensure the stability of the patient’s cranial fixation devices. The data obtained in this survey has great limitations, including the doctor’s personal prejudice and dependence on anecdotal memories. Therefore, the data should be interpreted with caution. However, there are still some modes that can help to better understand the use of safe cranial fixation. Based on the above research and analysis, we have made recommendations that may help neurosurgeons to avoid preventable complications
Artificial Intelligence–Assisted Prediction of Late-Onset Cardiomyopathy Among Childhood Cancer Survivors
Authors: Güntürkün Fatma , Akbilgic Oguz , Davis Robert L. , Armstrong Gregory T. , Howell Rebecca M. , Jefferies John L. , Ness Kirsten K. , Karabayir Ibrahim , Lucas John T. , Srivastava Deo Kumar , Hudson Melissa M. , Robison Leslie L. , Soliman Elsayed Z. , Mulrooney Daniel A.
Published: April 2021

PURPOSE

Early identification of childhood cancer survivors at high risk for treatment-related cardiomyopathy may improve outcomes by enabling intervention before development of heart failure. We implemented artificial intelligence (AI) methods using the Children's Oncology Group guideline–recommended baseline ECG to predict cardiomyopathy.

MATERIAL AND METHODS

Seven AI and signal processing methods were applied to 10-second 12-lead ECGs obtained on 1,217 adult survivors of childhood cancer prospectively followed in the St Jude Lifetime Cohort (SJLIFE) study. Clinical and echocardiographic assessment of cardiac function was performed at initial and follow-up SJLIFE visits. Cardiomyopathy was defined as an ejection fraction < 50% or an absolute drop from baseline ≥ 10%. Genetic algorithm was used for feature selection, and extreme gradient boosting was applied to predict cardiomyopathy during the follow-up period. Model performance was evaluated by five-fold stratified cross-validation.

RESULTS

The median age at baseline SJLIFE evaluation was 31.7 years (range 18.4-66.4), and the time between baseline and follow-up evaluations was 5.2 years (0.5-9.5). Two thirds (67.1%) of patients were exposed to chest radiation, and 76.6% to anthracycline chemotherapy. One hundred seventeen (9.6%) patients developed cardiomyopathy during follow-up. In the model based solely on ECG features, the cross-validation area under the curve (AUC) was 0.87 (95% CI, 0.83 to 0.90), whereas the model based on clinical features had an AUC of 0.69 (95% CI, 0.64 to 0.74). In the model based on ECG and clinical features, the cross-validation AUC was 0.89 (95% CI, 0.86 to 0.91), with a sensitivity of 78% and a specificity of 81%.

CONCLUSION

AI using ECG data may assist in the identification of childhood cancer survivors at increased risk for developing future cardiomyopathy.
Short Diagnosis-to-Treatment Interval Is Associated With Higher Circulating Tumor DNA Levels in Diffuse Large B-Cell Lymphoma
Authors: Alig Stefan , Macaulay Charles W. , Kurtz David M. , Dührsen Ulrich , Hüttmann Andreas , Schmitz Christine , Jin Michael C. , Sworder Brian J. , Garofalo Andrea , Shahrokh Esfahani Mohammad , Nabet Barzin Y. , Soo Joanne , Scherer Florian , Craig Alexander F. M. , Casasnovas Olivier , Westin Jason R. , Gaidano Gianluca , Rossi Davide , Roschewski Mark , Wilson Wyndham H. , Meignan Michel , Diehn Maximilian , Alizadeh Ash A.
Published: April 2021

PURPOSE

Patients with Diffuse Large B-cell Lymphoma (DLBCL) in need of immediate therapy are largely under-represented in clinical trials. The diagnosis-to-treatment interval (DTI) has recently been described as a metric to quantify such patient selection bias, with short DTI being associated with adverse risk factors and inferior outcomes. Here, we characterized the relationships between DTI, circulating tumor DNA (ctDNA), conventional risk factors, and clinical outcomes, with the goal of defining objective disease metrics contributing to selection bias.

PATIENTS AND METHODS

We evaluated pretreatment ctDNA levels in 267 patients with DLBCL treated across multiple centers in Europe and the United States using Cancer Personalized Profiling by Deep Sequencing. Pretreatment ctDNA levels were correlated with DTI, total metabolic tumor volumes (TMTVs), the International Prognostic Index (IPI), and outcome.

RESULTS

Short DTI was associated with advanced-stage disease ( P < .001) and higher IPI ( P < .001). We also found an inverse correlation between DTI and TMTV ( RS = −0.37; P < .001). Similarly, pretreatment ctDNA levels were significantly associated with stage, IPI, and TMTV (all P < .001), demonstrating that both DTI and ctDNA reflect disease burden. Notably, patients with shorter DTI had higher pretreatment ctDNA levels ( P < .001). Pretreatment ctDNA levels predicted short DTI independent of the IPI ( P < .001). Although each risk factor was significantly associated with event-free survival in univariable analysis, ctDNA level was prognostic of event-free survival independent of DTI and IPI in multivariable Cox regression (ctDNA: hazard ratio, 1.5; 95% CI [1.2 to 2.0]; IPI: 1.1 [0.9 to 1.3]; −DTI: 1.1 [1.0 to 1.2]).

CONCLUSION

Short DTI largely reflects baseline tumor burden, which can be objectively measured using pretreatment ctDNA levels. Pretreatment ctDNA levels therefore have utility for quantifying and guarding against selection biases in prospective DLBCL clinical trials.
Brentuximab Vedotin Combined With Chemotherapy in Patients With Newly Diagnosed Early-Stage, Unfavorable-Risk Hodgkin Lymphoma
Authors: Kumar Anita , Casulo Carla , Advani Ranjana H. , Budde Elizabeth , Barr Paul M. , Batlevi Connie L. , Caron Philip , Constine Louis S. , Dandapani Savita V. , Drill Esther , Drullinsky Pamela , Friedberg Jonathan W. , Grieve Clare , Hamilton Audrey , Hamlin Paul A. , Hoppe Richard T. , Horwitz Steven M. , Joseph Ashlee , Khan Niloufer , Laraque Leana , Matasar Matthew J. , Moskowitz Alison J. , Noy Ariela , Palomba Maria Lia , Schöder Heiko , Straus David J. , Vemuri Shreya , Yang Joanna , Younes Anas , Zelenetz Andrew D. , Yahalom Joachim , Moskowitz Craig H.
Published: April 2021

PURPOSE

To improve curability and limit long-term adverse effects for newly diagnosed early-stage (ES), unfavorable-risk Hodgkin lymphoma.

METHODS

In this multicenter study with four sequential cohorts, patients received four cycles of brentuximab vedotin (BV) and doxorubicin, vinblastine, and dacarbazine (AVD). If positron emission tomography (PET)-4–negative, patients received 30-Gy involved-site radiotherapy in cohort 1, 20-Gy involved-site radiotherapy in cohort 2, 30-Gy consolidation-volume radiotherapy in cohort 3, and no radiotherapy in cohort 4. Eligible patients had ES, unfavorable-risk disease. Bulk disease defined by Memorial Sloan Kettering criteria (> 7 cm in maximal transverse or coronal diameter on computed tomography) was not required for cohorts 1 and 2 but was for cohorts 3 and 4. The primary end point was to evaluate safety for cohort 1 and to evaluate complete response rate by PET for cohorts 2-4.

RESULTS

Of the 117 patients enrolled, 116 completed chemotherapy, with the median age of 32 years: 50% men, 98% stage II, 86% Memorial Sloan Kettering–defined disease bulk, 27% traditional bulk (> 10 cm), 52% elevated erythrocyte sedimentation rate, 21% extranodal involvement, and 56% > 2 involved lymph node sites. The complete response rate in cohorts 1-4 was 93%, 100%, 93%, and 97%, respectively. With median follow-up of 3.8 years (5.9, 4.5, 2.5, and 2.2 years for cohorts 1-4), the overall 2-year progression-free and overall survival were 94% and 99%, respectively. In cohorts 1-4, the 2-year progression-free survival was 93%, 97%, 90%, and 97%, respectively. Adverse events included neutropenia (44%), febrile neutropenia (8%), and peripheral neuropathy (54%), which was largely reversible.

CONCLUSION

BV + AVD × four cycles is a highly active and well-tolerated treatment program for ES, unfavorable-risk Hodgkin lymphoma, including bulky disease. The efficacy of BV + AVD supports the safe reduction or elimination of consolidative radiation among PET-4–negative patients.
Organelle tethering, pore formation and SNARE compensation in the late endocytic pathway
Authors: Davis Luther J. , Bright Nicholas A. , Edgar James R. , Parkinson Michael D. J. , Wartosch Lena , Mantell Judith , Peden Andrew A. , Luzio J. Paul
Published: April 2021

To provide insights into the kiss-and-run and full fusion events resulting in endocytic delivery to lysosomes, we investigated conditions causing increased tethering and pore formation between late endocytic organelles in HeLa cells. Knockout of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) VAMP7 and VAMP8 showed, by electron microscopy, the accumulation of tethered lysosome-associated membrane protein (LAMP)-carrier vesicles around multivesicular bodies, as well as the appearance of ‘hourglass’ profiles of late endocytic organelles attached by filamentous tethers, but did not prevent endocytic delivery to lysosomal hydrolases. Subsequent depletion of the SNARE YKT6 reduced this delivery, consistent with it compensating for the absence of VAMP7 and VAMP8. We also investigated filamentous tethering between multivesicular bodies and enlarged endolysosomes following depletion of charged multi-vesicular body protein 6 (CHMP6), and provide the first evidence that pore formation commences at the edge of tether arrays, with pore expansion required for full membrane fusion.
Cardiopulmonary Exercise Testing in the Coronavirus Disease — 2019 Era: Safety and Protocol Considerations
Authors: Duscha Brian D. , Johnson Johanna L. , Bennett William C. , Ball Kelsey N. , Mae Fos Liezl B. , Reaves Megan A. , Kraus William E.
Published: April 2021

Cardiopulmonary exercise testing (CPX) is a valuable tool in both clinical practice and research settings. Therefore, it is advantageous for human performance laboratories to continue operating during the coronavirus disease 2019 (COVID-19) pandemic. All institutions should adhere to general COVID-19 guidelines provided by the Centers for Disease Control. Because of the testing environment, CPX laboratories must consider additional precautionary safety measures. This article provides recommendations for modifying the CPX protocol to ensure safety for all stakeholders during the pandemic. These modifications are universal across all populations, types of institutions and testing modalities. Preliminary measures include careful review of federal, local, and institutional mandates. The description outlines how to evaluate a testing environment and alter workflow. Guidelines are provided on what specific personal protective equipment should be acquired; as well as necessary actions before, during, and after the CPX test. These precautions will limit the possibility of both clients and staff from contracting or spreading the disease while maintaining testing volume in the laboratory.
A Few Bad Apples? Racial Bias in Policing
Authors: Goncalves Felipe , Mello Steven
Published: April 2021

We estimate the degree to which individual police officers practice racial discrimination. Using a bunching estimation design and data from the Florida Highway Patrol, we show that minorities are less likely to receive a discount on their speeding tickets than White drivers. Disaggregating this difference to the individual police officer, we estimate that 42 percent of officers practice discrimination. We then apply our officer- level discrimination measures to various policy-relevant questions in the literature. In particular, reassigning officers across locations based on their lenience can effectively reduce the aggregate disparity in treatment (JEL H76, J15, K42)
Cross-Region Transfer Multipliers in a Monetary Union: Evidence from Social Security and Stimulus Payments
Authors: Pennings Steven
Published: April 2021

US federal transfers to individuals are large, countercyclical, vary geographically, and are often credited with helping to stabilize regional economies. This paper estimates the short-run effects of these transfers using plausibly exogenous regional variation in temporary stimulus payments and permanent Social Security benefit increases. States that received larger transfers tended to grow faster contemporaneously, with a multiplier of around 1.5 for permanent transfers and 1/3 for temporary transfers. Results are broadly consistent with an open-economy New Keynesian model. At business cycle frequencies, cross-region transfer multipliers are not large, suggesting only modest gains in regional stabilization from US federal automatic stabilizers. (JEL E12, E32, E62, H23, H55, R12)
An Experiment in Candidate Selection
Authors: Casey Katherine , Kamara Abou Bakarr , Meriggi Niccoló F.
Published: April 2021

Are ordinary citizens or political party leaders better positioned to select candidates? While the American primary system lets citizens choose, most democracies rely instead on party officials to appoint or nominate candidates. The consequences of these distinct design choices are unclear: while officials are often better informed about candidate qualifications, they may value traits, like party loyalty or willingness to pay for the nomination, at odds with identifying the best performer. We partnered with both major political parties in Sierra Leone to experimentally vary how much say voters have in selecting Parliamentary candidates. Estimates suggest that more democratic procedures increase the likelihood that parties select voters’ most preferred candidates and favor candidates with stronger records of public goods provision. (JEL D72, H41, O17)
Teaching mathematics as a way of thinking – not calculating
Authors: Devlin Keith
Published: April 2021

Matemaatilise mõtlemise tähendusrikkad aspektid on uurimine, kahtlemine, süsteemne töö, visualiseerimine, hüpoteeside püstitamine, oma seisukohtade selgitamine, üldistamine, põhjendamine ja tõestamine, aga mitte rangete protseduuride teostamine, mida teevad kas masinad või mida peetakse "madalama taseme" mehaaniliseks tegevuseks. Vt näiteks Stacey (2006);  Devlini (2012a, b, c); Singhi jt (2018); NRICH-i (2020) töid.Siinses essees keskendutakse matemaatilisele mõtlemisele. Kuid enne alustamist tuleks mainida, et oma kirjutises lähtun vaatenurgast, mis on omandatud karjääri jooksul, millesse mahtusid nii akadeemilised  teadusuuringud puhtas matemaatikas kui ka rakendusmatemaatikaga seotud maailm, kus tegelesin paljude reaalsete probleemidega nii eraettevõtluse kui ka valitsuse heaks. 

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Prognostic analysis of mortality in the cohort of the Chernobyl cleanup workers
Authors: Gorski A. , Maksyutov M. , Tumanov K. , Kochergina E. , Zelenskaya N. , Ivanov V
Published: April 2021

Purpose: Analysis and prognosis of mortality rate, specific causes of death and mortality structure in the male cohort of the Chernobyl cleanup workers monitored from 1992 over 2017.

Materials and methods: Analysis and prognosis of mortality among the Chernobyl cleanup workers for the follow up period 1992-2017 were based on personal death records stored at the National Radiation Epidemiological Registry (NRER). The workers entered the exclusion zone in 1986 and in 1987, who had documented dose records were included in the monitoring cohort. In 1992 the cohort size was 72432 persons , average radiation dose was 130.8 mGy. For the period of the cohort monitoring 27051 cleanup workers died with the following causes of death: malignant neoplasms – 4621 cases, circulatory diseases – 11410 cases, traumas and poisoning – 5110 cases, other –5910. To prognose mortality and mortality structure data on age-specific intensity of partial mortality and total mortality during the monitoring period were used.

Results: The predicted size of the cohort will be 22,000 persons in 2030. Mortality structure in 2017: malignant neoplasms – 17%; circulatory diseases – 42%; traumas and poisoning – 19%, other – 22%. The mortality structure in 2030 will be: malignant neoplasms – 24%; circulatory diseases – 49%; traumas and poisoning – 11%, other – 16%. Cleanup workers’ the average time left to live estimated in 2017 was 11.1 years (their average age in 2017 was 62.4 years), it means that their average life expectancy will be 73.5 years. Average life expectancy of Russian males is 70.4 years. Increased life span of the cleanup workers can be due to their good health, social support including regular special medical examination, the effect of the natural selection cannot be excluded as well.

Conclusion: Results of the study can serve as example of organization of high effective specialized medical examination of the Chernobyl cleanup workers. The research outcomes will be useful for analysis of mortality among members of a closed population following exposure to hazardous technogeneous factors.
Results of Preclinical Safety Tests of Radiopharmaceutical with 90Y for Intra-arterial Radioembolization of Liver Cancer
Authors: Klement'eva O. , Vlasova O , Stepchenkov D , Luneva K , Ternovskaya K , Petriev V , Stepchenkova E , Kuznetsov Aleksey , Artamonov S , Murashin K , Shegai P , Ivanov S , Kaprin A.
Published: April 2021

Purpose: Performing a safety study of a radiopharmaceutical drug with yttrium-90 for intra-arterial radioembolization of inoperable patients with primary and metastatic liver cancer. Material and methods: The developed radiopharmaceutical is a microspheres of human blood albumin with a diameter of 25-40 microns, modified with diethylenetriaminpentaacetic acid and labeled with 90Y radionuclide. The safety of the radiopharmaceutical was studied by the following indicators: acute toxicity of lyophilized reagents, subchronic toxicity of the radiopharmaceutical on two types of animals, local irritant effect of the radiopharmaceutical therapeutic activity in equivalent terms on laboratory animals, specific toxicity (allergizing effect) of lyophilized reagents for the preparation of a radiopharmaceutical drug. Female and male BALB/C mice, Wistar rats, chinchilla rabbits, and albino Guinea pigs were taken as experimental animals. All animals were obtained from certified laboratory animal nurseries. Results: During acute toxicity studies, the maximum safe dose of an inactive drug was determined. In terms of per person, it exceeds the intended dose for clinical use by almost 20 times. The study of the subchronic toxicity of the radiopharmaceutical did not reveal any symptoms of intoxication. The survival rate of the animals during the entire observation period was absolute. Standard behavior and appearance were observed in animals. The dynamics of body weight was positive, and the body temperature of rats and rabbits did not exceed the limits allowed. Samples of the finished dosage form of the drug did not have a local irritant effect. The solution of inactive components of lyophilized reagents for the preparation of a radiopharmaceutical drug did not have an allergenic effect in quantities ten times higher than the doses administered to a person. Conclusion: According to the results of preclinical studies, the radiopharmaceutical should be considered safe for use. The results of preclinical studies allow us to recommend the drug for clinical research.
METHOD FOR ESTIMATING THE MEASURED EXPOSURE RATE OVER THE THYROID CORRESPONDING TO CERTAIN LEVELS OF THE ABSORBED DOSE IN THE THYROID FOR THE PUBLIC IN THE EARLY PERIOD AFTER A LARGE RADIATION ACCIDENT
Authors: Shinkarev S. , Kvacheva Yu , Grachev M. , Androsova A , Yatsenko V. , Budyka A , Kuten' Cemen , Khrutchinsky A
Published: April 2021

In case of a large radiation accident at the nuclear power station the most important radiation hazard for the public is internal exposure to the thyroid from radioiodine. The IAEA standard published in 2013 and accounting the experience of the Chernobyl and Fukushima accidents, recommends that, in the first 1-6 days after an inhalation intake of radioiodine the exposure rate over the thyroid be measured for the public and be guided by the following operational criteria: (a) 0.5 μSv · h-1 for children under the age of 7 years, and (b) 2 μSv ·h-1 for children over 7 years and adults. These operational criteria are indicative estimates corresponding to the dose range 100–200 mGy in the thyroid for all age groups. However, a wider range of thyroid doses and a more detailed breakdown of children into five age groups according to the recommendations of the ICRP are of interest. The purpose of this paper is to develop a method for estimating the values of the measured exposure rate over the thyroid corresponding to certain levels of the absorbed dose in the thyroid for members of the public of different ages for various conditions of inhalation of radioiodine intake and times of measurement in the early period after a radiation accident. According to the method developed in the paper for the committed absorbed dose 100-200 mGy in the thyroid the exposure rates over the thyroid were calculated depending upon the time of inhalation intake after the accident and the time span between the moment of intake and the moment of measurement, which were equal to: 0.6– 4 μSv ·h-1 - for children of 1 year and 4–27 μSv · h-1 – for adults. These values are significantly higher than those recommended by the IAEA Standard 0.5 μSv · h-1 and 2 μSv · h-1, respectively. It is important to stress that the IAEA recommendations provide conservative estimates of the measured exposure rate over the thyroid in order to maximize the coverage of critical group of the public for further dosimetric and medical examination. For example, for some options of the time of radioiodine inhalation intake and the time of measurement, the IAEA recommended the values of the exposure rate over the thyroid that can lead to an overestimation of the absorbed dose in the thyroid gland by a factor of up to 10.
Concerning the Tritium Dose at the Cellular Level
Authors: Timofeev L , Maksimov A , Kochetkov O. , Klochkov V.
Published: April 2021

Purpose: To adapt traditional method of soft beta emitters’ dose calculation to the individual biological cells, to estimate the value of absorbed dose-rate factors for different tritium compounds on a cellular level. Material and methods: Approximation for point-source function obtained by L.V. Timofeev, G.B. Radzievsky et al. was used to adapt macroscopic beta-particle dosimetry methods to the area of subcellular structures. Results: Using the introduced concept of irradiated cell model base states the analytical expressions for absorbed dose in subcellular structures were suggested for non-uniform activity distributions of soft beta emitters in human tissue. The values of absorbed dose-rate factors for the case of organically bounded tritium confined to the nucleus (1.8 mGy/decay for 3H-thymidine) and for the case of tritiated water uniformly distributed throughout tissue (3.510-3 mGy/decay) were obtained. Conclusion: It can be assumed that traditional method of soft beta emitters’ dose calculation is adapted to the individual biological cells. The proposed methodology is supposed to be used in the future when constructing, based on experimental data, a biokinetic model of the intake of tritium organic compounds in the human body.
PENGARUH JOKOWI EFFECT TERHADAP REAKSI SAHAM PERUSAHAAN YANG TERDAFTAR PADA JAKARTA ISLAMIC INDEX
Authors: Abdullah Lalu Muhamad , Fitriani Dyah
Published: April 2021

This study examined, abnormalreturn differences, and differences in the volume traded on the stock companies listed on the Jakarta index Islamic Index before and after the announcement of the nomination of events Joko Widodo as President. Population in this research that companies listed on the index JII. Objects in this study is 30 companies. The sampling technique means that all members of the saturated sample or population used as a sample in the study. Data collection techniques with methods of documentation obtained from yahoo finance, IDX. Analysis tools used in this research that Paired samples t-test and One Sample T-test with SPSS 20 software. The test results on the effect of Jokowi effect on the reaction of the company’s shares are listed on the index can be concluded there is abnormalreturn JII daily before and after the announcement. However, there were no differences in abnormalreturn and volume of sales before and after the announcement.
ANALISIS FAKTOR-FAKTOR YANG MEMPENGARUHI PENYALURAN KREDIT PERBANKAN PADA BANK UMUM DI BURSA EFEK INDONESIA
Authors: Pratiwi Septiana Icha , Sulistiyani Tina
Published: April 2021

This research is aimed to obtain empirical evidence on the factors affecting the distribution of bank credit. There are many factors affecting the distribution of bank credit. However, this research was only limited by dominant factors affecting the distribution of bank credit obtained from bank credit theories and the results from previous research studies. Therefore, factors which were the selected independent variables in this research were Third Party Funds (DPK), Capital Adequacy Ratio (CAR), Non Performing Loan (NPL), Return On Assets (ROA), and Loan to Deposit Ratio (LDR). While the dependent variables were the distribution of bank credit which was proxied by Loan to Asset Ratio (LAR) variable. The results of the research indicates that simultaneously, the variables of DPK, CAR, NPL, ROA, dan LDR significantly affect  the distribution of bank credit in the period 2010-2012. While partially, a result was obtained that DPK, NPL, and LDR variables significantly affect the distribution of bank credit. Meanwhile CAR and ROA variables do no significantly affect the distribution of bank credit in the period 2010-2012
PENGARUH KEPUTUSAN INVESTASI, KEPUTUSAN PENDANAAN DAN KEBIJAKAN DIVIDEN TERHADAP NILAI PERUSAHAAN PADA PERUSAHAAN LQ45 YANG TERDAFTAR DI BURSA EFEK INDONESIA
Authors: Widyawati Nur Aini , Fitriani Dyah
Published: April 2021

This study aimed to examine the effect of investment decisions, financing decisions and dividend policy on firm value in the LQ-45 firm listed on the Indonesia Stock Exchange. Population as well as the sample in this study is the LQ-45 firm listed on the Indonesia Stock Exchange 2007-2011 period which has complete financial statements are expressed in dollars and pay dividends continuously over the study period, which amounted  to 9 companies. The dependent variable used is the value of the company (PBV) while the independent variable is investment (PER), funding (DER) and dividend policy (DPR). In this study using a multiple linier regression and classical assumption. Assessment of the effect of independent variables on the dependent variable was partially or simulataneously, and analysis tools in this study using eviews. Partial results of the study showed that investment decisions have a significant effect on firm value, funding decisions have no significant effect on firm value and dividend policy has no significant effect on firm value.
PENGARUH MOTIVASI, KOMPENSASI, DAN LINGKUNGAN KERJA KARYAWAN TERHADAP KINERJA KARYAWAN DI KANTOR DINAS SOSIAL TENAGA KERJA DAN TRANSMIGRASI KOTA YOGYAKARTA
Authors: Badriyah Badriyah , Muttaqiyathun Ani
Published: April 2021

This  research  aims  to  understand  how  the  influence  of  motivation, compensation  and workplace on the performance of employees at department office social  man power  and  transmigration the city of Yogyakarta bot  a partial as well as simultaneous or together. The population on this research is Employees who worked at social department office of  manpower and transmigration city of Yogyakarta. The sample collection  technique  in  this  research  use  of  sampling  methods  purposive. The total sample taken in this research as many  81 respondents. The source of data from the study  used  data  primary  obtained  from  the  results  of  questionnaires  compiled  using likert scale. This study using data analysis techniques is the quantitative analysis (linear regression analysis double, t test and test f). Test results t show that the significance of the variables ( x1 ) 0,007 value <  α = 0.05, then motivation influential significantly to employee performance, then motivation influential significantly to employee performance, variable compensation ( x2 ) 0,038 < value  α  =  0.05  then compensation significant of the performance of  employees and variable workplace (x3) 0,048  <  value α = 0.05 and a significant effect on the employees in social department office of manpower and transmigration the city of Yogyakarta.