bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Utilization, Utility, and Reimbursement for Expanded Genomic Panel Testing in Adult Oncology
Authors: Hsiao Susan J. , Sireci Anthony N. , Pendrick Danielle , Freeman Christopher , Fernandes Helen , Schwartz Gary K. , Henick Brian S. , Mansukhani Mahesh M. , Roth Kevin A. , Carvajal Richard D. , Oberg Jennifer A.
Published: September 2020

PURPOSE

The routine use of large next-generation sequencing (NGS) pan-cancer panels is required to identify the increasing number of, but often uncommon, actionable alterations to guide therapy. Inconsistent coverage and variable payment is hindering NGS adoption into clinical practice. A review of test utilization, clinical utility, coverage, and reimbursement was conducted in a cohort of patients diagnosed with high-risk cancer who received pan-cancer panel testing as part of their clinical care.

MATERIALS AND METHODS

The Columbia Combined Cancer Panel (CCCP), a 467-gene panel designed to detect DNA variations in solid and liquid tumors, was performed in the Laboratory of Personalized Genomic Medicine at Columbia University Irving Medical Center. Utilization was characterized at test order. Results were reviewed by a molecular pathologist, followed by a multidisciplinary molecular tumor board where clinical utility was classified by consensus. Reimbursement was reviewed after payers provided final coverage decisions.

RESULTS

NGS was performed on 359 high-risk tumors from 349 patients. Reimbursement data were available for 246 cases. The most common reason providers ordered CCCP testing was for patients diagnosed with a treatment-resistant or recurrent tumor (n = 214; 61%). Findings were clinically impactful for 229 cases (64%). Molecular alterations that may inform future therapy in the event of progression or relapse were found in 42% of cases, and a targeted therapy was initiated in 23 cases (6.6%). The majority of tests were denied coverage by payers (n = 190; 77%). On average, insurers reimbursed 10.75% of the total NGS service charge.

CONCLUSION

CCCP testing identified clinically impactful alterations in 64% of cases. Limited coverage and low reimbursement remain barriers, and broader reimbursement policies are needed to adopt pan-cancer NGS testing that benefits patients into clinical practice.
IRX3/5 regulate mitotic chromatid segregation and limb bud shape
Authors: Tao Hirotaka , Lambert Jean-Philippe , Yung Theodora M. , Zhu Min , Hahn Noah A. , Li Danyi , Lau Kimberly , Sturgeon Kendra , Puviindran Vijitha , Zhang Xiaoyun , Gong Wuming , Chen Xiao Xiao , Anderson Gregory , Garry Daniel J. , Henkelman R. Mark , Sun Yu , Iulianella Angelo , Kawakami Yasuhiko , Gingras Anne-Claude , Hui Chi-chung , Hopyan Sevan
Published: September 2020

Pattern formation is influenced by transcriptional regulation as well as by morphogenetic mechanisms that shape organ primordia, although factors that link these processes remain under-appreciated. Here we show that, apart from their established transcriptional roles in pattern formation, IRX3/5 help to shape the limb bud primordium by promoting the separation and intercalation of dividing mesodermal cells. Surprisingly, IRX3/5 are required for appropriate cell cycle progression and chromatid segregation during mitosis, possibly in a nontranscriptional manner. IRX3/5 associate with, promote the abundance of, and share overlapping functions with coregulators of cell division such as the cohesin subunits SMC1, SMC3, NIPBL and CUX1. The findings imply that IRX3/5 coordinate early limb bud morphogenesis with skeletal pattern formation.
Juvenile hormone acts through FoxO to promote Cdc2 and Orc5 transcription for polyploidy-dependent vitellogenesis
Authors: Wu Zhongxia , He Qiongjie , Zeng Baojuan , Zhou Haodan , Zhou Shutang
Published: September 2020

Vitellogenin (Vg) is prerequisite to egg production and embryonic development after oviposition in oviparous animals. In many insects, juvenile hormone (JH) promotes fat body cell polyploidization for massive Vg synthesis required for maturation of multiple oocytes, but the underlying mechanisms remain poorly understood. Using the migratory locust Locusta migratoria as a model system, we report here that JH induces the dephosphorylation of Forkhead box O transcription factor (FoxO) through a signaling cascade including leucine carboxyl methyltransferase 1 (LCMT1) and protein phosphatase 2A (PP2A). JH promotes PP2A activity via LCMT1-mediated methylation, consequently triggering FoxO dephosphorylation. Dephosphorylated FoxO binds to the upstream of two endocycle-related genes, cell-division-cycle 2 (Cdc2) and origin-recognition-complex subunit 5 (Orc5) and activates their transcription. Depletion of FoxO, Cdc2 or Orc5 results in blocked polyploidization of fat body cells, accompanied by markedly reduced Vg expression, impaired oocyte maturation and arrested ovarian development. The results suggest that JH acts via LCMT1-PP2A-FoxO to regulate Cdc2 and Orc5 expression and enhance ploidy of fat body cells in preparation for large-scale Vg synthesis required for synchronous maturation of multiple eggs.
Cargo-Mediated Recruitment of the Endocytic Adaptor Protein Sla1
Authors: Tolsma Thomas O. , Febvre Hallie P. , Olson Deanna M. , Di Pietro Santiago M.
Published: September 2020

Endocytosis of plasma membrane proteins is mediated by their interaction with adaptor proteins. Conversely, emerging evidence suggests adaptor protein recruitment to the plasma membrane may depend on binding to endocytic cargo. To test this idea we analyzed the yeast adaptor protein Sla1, which binds membrane proteins harboring the endocytic signal NPFxD via the Sla1 SHD1 domain. Consistently, SHD1 point mutations that disrupt NPFxD binding caused a proportional reduction of Sla1-GFP recruitment to endocytic sites. Furthermore, simultaneous SHD1 point mutation and deletion of the SR region linking Sla1 to coat proteins Pan1 and End3 resulted in total loss of Sla1-GFP recruitment to the plasma membrane. The data suggests multiple interactions are needed for recruitment to the membrane. Interestingly, a Sla1 fragment containing just the third SH3 domain – which binds ubiquitin – and SHD1, displayed broad surface localization suggesting plasma membrane recruitment is mediated by interaction with both NPFxD-containing and ubiquitinated plasma membrane proteins. Our results also imply that a Sla1 NPF motif adjacent to the SR region may regulate the Sla1-cargo interaction, mechanistically linking Sla1 cargo binding to endocytic site recruitment.
Regenerative Injectable Therapies: Current Evidence
Authors: West William H. , Beutler Anthony I. , Gordon Christopher R.
Published: September 2020

Regenerative medicine is a growing field of musculoskeletal treatments that focuses on amplifying the body's natural healing properties to improve function and pain after injury. Regenerative treatments are applied locally at the site of injury and work though different mechanisms, some of which are unexplained at this time. Current evidence demonstrates benefit for certain regenerative treatments, but further standardization of treatments and additional studies are required to provide additional data to support specific regenerative treatments. This review seeks to explore the evidence and discuss appropriate use of the most common regenerative treatments including platelet-rich plasma, prolotherapy, autologous mesenchymal stem cells, human-derived allograft products, and saline.
Concussions in Ice Hockey — Moving Toward Objective Diagnoses and Point-of-care Treatment: A Review
Authors: Pender Sara C. , Smith Aynsley M. , Finnoff Jonathan T. , Huston John , Stuart Michael J.
Published: September 2020

The incidence of sport-related concussion coupled with a doubling of the participation rate in youth hockey over the past two decades provides impetus for the review of the most promising concussion treatment options. This narrative review summarizes the future treatment options for sport-related concussions in ice hockey, while acknowledging their generalizability to concussion in all sports. Symptom assessment, sign observation, as well as cognitive and balance testing, have historically been used to diagnose a concussion. These methods continue to improve, but the need for effective treatments is clear. Pharmacologic, transcranial light, and nutritional supplement treatment options for concussion warranting further investigation have been identified. Dimethyl fumarate is an immunomodulatory compound thought to trigger antioxidant gene expression. Memantine reduces apoptosis and astrogliosis by inhibiting the calcium influx into cells normally caused by glutamate's activation ofN-methyl-d-aspartate receptors. Thioredoxin-mimetic peptides and transcranial photobiomodulation temper the effects of the energy crisis by acting as free radical scavengers. In addition, seven neuroprotective nutritional supplements have been identified: berberine, creatine, curcumin, melatonin, omega-3 fatty acids, resveratrol, and vitamins. An estimated US $1.1 billion has been spent on unsuccessful traumatic brain injury clinical trials. As our ability to accurately diagnose concussion improves, dimethyl fumarate, memantine, thioredoxin-mimetic peptides, transcranial photobiomodulation, and nutritional supplements (berberine, creatine, curcumin, melatonin, omega-3 fatty acids, resveratrol, and vitamins) warrant further preclinical and clinical examination in advancing the treatment of sport-related concussions.
Inflammation Mediates Exercise Effects on Fatigue in Patients with Breast Cancer
Authors: HIENSCH ANOUK E. , MIJWEL SARA , BARGIELA DAVID , WENGSTRÖM YVONNE , MAY ANNE M. , RUNDQVIST HELENE
Published: September 2020

Purpose

The randomized controlled OptiTrain trial showed beneficial effects on fatigue after a 16-wk exercise intervention in patients with breast cancer undergoing adjuvant chemotherapy. We hypothesize that exercise alters systemic inflammation and that this partially mediates the beneficial effects of exercise on fatigue.

Methods

Two hundred and forty women scheduled for chemotherapy were randomized to 16 wk of resistance and high-intensity interval training (RT-HIIT), moderate-intensity aerobic and high-intensity interval training (AT-HIIT), or usual care (UC). In the current mechanistic analyses, we included all participants with >60% attendance and a random selection of controls (RT-HIIT = 30, AT-HIIT = 27, UC = 29). Fatigue (Piper Fatigue Scale) and 92 markers (e.g., interleukin-6 [IL-6] and tumor necrosis factor α [TNF-α]) were assessed at baseline and postintervention. Mediation analyses were conducted to explore whether changes in inflammation markers mediated the effect of exercise on fatigue.

Results

Overall, chemotherapy led to an increase in inflammation. The increases in IL-6 (pleiotropic cytokine) and CD8a (T-cell surface glycoprotein) were however significantly less pronounced after RT-HIIT compared with UC (−0.47, 95% confidence interval = −0.87 to −0.07, and −0.28, 95% confidence interval = −0.57 to 0.004, respectively). Changes in IL-6 and CD8a significantly mediated the exercise effects on both general and physical fatigue by 32.0% and 27.7%, and 31.2% and 26.4%, respectively. No significant between-group differences in inflammatory markers at 16 wk were found between AT-HIIT and UC.

Conclusions

This study is the first showing that supervised RT-HIIT partially counteracted the increase in inflammation during chemotherapy, i.e., IL-6 and soluble CD8a, which resulted in lower fatigue levels postintervention. Exercise, including both resistance and high-intensity aerobic training, might be put forward as an effective treatment to reduce chemotherapy-induced inflammation and subsequent fatigue.
Attenuated Rapid-Onset Vasodilation to Forearm Muscle Contraction in Black Men
Authors: KAUR JASDEEP , BARBOSA THALES C. , NANDADEVA DAMSARA , YOUNG BENJAMIN E. , STEPHENS BRANDI Y. , BROTHERS R. MATTHEW , FADEL PAUL J.
Published: September 2020

Purpose

Non-Hispanic Black individuals have a blunted ability to vasodilate at rest compared with other racial groups. Limited studies have investigated blood flow responses to exercise in Black individuals. Recently, our laboratory demonstrated that Black men exhibit attenuated increases in forearm vascular conductance (FVC) during steady-state rhythmic handgrip. The mechanisms for this remain unknown. Herein, we used single muscle contractions, a modality that allows for assessment of rapid-onset vasodilation (ROV) independent of major elevations in shear stress, tissue metabolism, and systemic hemodynamics.

Methods

Ten young, healthy Black and White men performed single forearm contractions at 20%, 40%, and 60% maximal voluntary contraction (MVC). In addition, cuff inflations were performed on the forearm to examine the contribution of mechanical compression to ROV. Forearm blood flow (FBF; duplex Doppler ultrasound), heart rate (ECG), and mean arterial pressure (Finometer) were continuously measured. FVC was calculated as FBF/mean arterial pressure.

Results

Baseline FVC (White men vs Black men, 0.75 ± 0.11 vs 0.80 ± 0.09 mL·min−1·mm Hg−1; P = 0.73), FBF, and MVCs (White men vs Black men, 54 ± 2 vs 54 ± 2 kg; P = 0.95) were similar between the groups. After single contractions, both groups exhibited intensity-dependent FVC and FBF increases during ROV; however, these responses were attenuated in the Black group at all intensities (e.g., 60%MVC FVC: White men vs Black men, +371% ± 37% vs +220% ± 23% baseline; P = 0.001). FVC and FBF responses to cuff inflation alone were also attenuated in Black individuals (P < 0.001).

Conclusions

Collectively, these data indicate that Black men have an overall blunted ability to rapidly vasodilate compared with young White men.
Detection and segmentation of erythrocytes in multispectral label-free blood smear images for automatic cell counting
Authors: Doumun Solange , Dabo Sophie , Zoueu Jérémie
Published: September 2020

In this work we propose an efficient approach to image segmentation for multispectral images of unstained blood films and automatic counting of erythrocytes. Our method takes advantage of Beer–Lambert’s law by using, first, a statistical standardisation equation applied to transmittance images, followed by the local adaptive threshold to detect the blood cells and hysteresis contour closing to obtain the complete blood cell boundaries, and finally the watershed algorithm is used. With this method, image pre-processing is not required, which leads to time savings. We obtained the following results that show that our technique is effective, efficient and fast: Precision of 98.47 % and Recall of 98.23 %, a degree of precision (F-Measurement) of 98.34 % and an Accuracy of 96.75 %.
Model Averaging and Its Use in Economics
Authors: Steel Mark F. J.
Published: September 2020

The method of model averaging has become an important tool to deal with model uncertainty, for example in situations where a large amount of different theories exist, as are common in economics. Model averaging is a natural and formal response to model uncertainty in a Bayesian framework, and most of the paper deals with Bayesian model averaging. The important role of the prior assumptions in these Bayesian procedures is highlighted. In addition, frequentist model averaging methods are also discussed. Numerical techniques to implement these methods are explained, and I point the reader to some freely available computational resources. The main focus is on uncertainty regarding the choice of covariates in normal linear regression models, but the paper also covers other, more challenging, settings, with particular emphasis on sampling models commonly used in economics. Applications of model averaging in economics are reviewed and discussed in a wide range of areas including growth economics, production modeling, finance and forecasting macroeconomic quantities. (JEL C11, C15, C20, C52, O47).
Commanding Nature by Obeying Her: A Review Essay on Joel Mokyr’s A Culture of Growth
Authors: Spolaore Enrico
Published: September 2020

Why is modern society capable of cumulative innovation? In A Culture of Growth: The Origins of the Modern Economy, Joel Mokyr persuasively argues that sustained technological progress stemmed from a change in cultural beliefs. The change occurred gradually during the seventeenth and eighteenth centuries and was fostered by an intellectual elite that formed a transnational community and adopted new attitudes toward the creation and diffusion of knowledge, setting the foundation for the ethos of modern science. The book is a significant contribution to the growing literature that links culture and economics. This review discusses Mokyr’s historical analysis in relation to the following questions: What is culture and how should we use it in economics? How can culture explain modern economic growth? Will the culture of growth that caused modern prosperity persist in the future? (JEL N00, N13, N33, O30, O52, Z10)
Improving the image quality of DWI in breast cancer: comparison of multi-shot DWI using multiplexed sensitivity encoding to conventional single-shot echo-planar imaging DWI
Authors: Baxter Gabrielle C , Patterson Andrew J , Woitek Ramona , Allajbeu Iris , Graves Martin J , Gilbert Fiona
Published: September 2020

Objective:

To compare diffusion-weighted images (DWI) acquired using single-shot echo-planar imaging (ss-EPI) and multiplexed sensitivity encoding (MUSE) in breast cancer.

Methods

20 females with pathologically confirmed breast cancer (age 51 ± 12 years) were imaged with ss-EPI-DWI and MUSE-DWI. ADC, normalised ADC (nADC), blur and distortion metrics and qualitative image quality scores were compared. The Crété-Roffet and Mattes mutual information metrics were used to evaluate blurring and distortion, respectively. In a breast phantom, six permutations of MUSE-DWI with varying parallel acceleration factor and number of shots were compared. Differences in ADC and nADC were compared using the coefficient of variation in the phantom and a paired t-test in patients. Differences in blur, distortion and qualitative metrics were analysed using a Wilcoxon signed-rank test.

Results:

There was a low coefficient of variation (<2%) in ADC between ss-EPI-DWI and all MUSE-DWI permutations acquired using the phantom. 22 malignant and three benign lesions were identified in 20 patients. ADC values measured using MUSE were significantly lower compared to ss-EPI for malignant but not benign lesions (p < 0.001, p = 0.21). nADC values were not significantly different (p = 0.62, p = 0.28). Blurring and distortion improved with number of shots and acceleration factor, and significantly improved with MUSE in patients (p < 0.001, p = 0.002). Qualitatively, image quality improved using MUSE.

Conclusion:

MUSE improves the image quality of breast DWI compared to ss-EPI.

Advances in knowledge:

MUSE-DWI has superior image quality and reduced blurring and distortion compared to ss-EPI-DWI in breast cancer.
Νεολαία, αριστερή ψήφος και ριζοσπαστισμός τη δεύτερη δεκαετία του 2000
Authors: Παντελίδου-Μαλούτα Μάρω , Ζηργάνου-Καζολέα Λίνα
Published: September 2020

Το άρθρο αυτό έχει ως στόχο να απαντήσει στο ερώτημα αν η σύγχρονη νεολαία στην Ελλάδα, μετά την ή/και λόγω της κρίσης, μπορεί να χαρακτηριστεί ως ριζοσπαστική, βάσει του είδους της πολιτικής κοσμοαντίληψης και συμπεριφοράς που εκδηλώθηκαν από σημαντικό κομμάτι της. Κι εάν, συνεπώς, θα μπορούσε να προσληφθεί ως δυνητική κινητήρια δύναμη κοινωνικών κατά το πρότυπο της νεολαίας της Μεταπολίτευσης. Από μια άποψη αποτελεί συνέχεια προηγούμενου άρθρου (Παντελίδου Μαλούτα, 2015), όπου έγινε προσπάθεια να καταδειχθεί τάση «επιστροφής» της νεολαίας στην πολιτική ήδη από το 2008, τάση η οποία εντάθηκε και διευρύνθηκε στην κρίση. Επεκτείνοντας την προβληματική εκείνη, και θεωρώντας ως δεδομένα τα στοιχεία που καταδεικνύουν τη στροφή των νέων προς την Αριστερά, και την «επιστροφή» τους στην πολιτική αρχικά μέσω δυναμικών μορφών συμμετοχής, θα επιδιωχθεί εδώ να προσεγγιστεί με τη βοήθεια δεδομένων ποιοτικής έρευνας, το αρχικό ερώτημα: Αποτελεί o ριζοσπαστισμός σήμερα καθοριστικό ιδεολογικό και συμπεριφορικό χαρακτηριστικό της νεολαίας; Λέξεις κλειδιά: Νεολαία, πολιτική δράση, ριζοσπαστισμός, Aριστερά, ψήφος των νέων  AbstractThis article aims at answering whether today’s youth in Greece could be defined as radical, based on the kind of political behavior and worldview manifested by a significant part of young people. And, hence, whether it could be perceived as a potential driving force of social change, according to the example of the youth of “Metapolitefsi”. In a way, this article draws from and further continues a previous article (Παντελίδου-Μαλούτα, 2015), which sought to illustrate Greek youth’s tendency to “return” to politics; a development already evident since 2008 that intensified during the crisis. Delving deeper into this rationale and taking into account data which attest to the youth’s turn towards the Left and return to politics, initially through dynamic modes of participation, here, we will employ qualitative research data in an attempt to approach the original question: Does radicalism constitute a defining ideological and behavioral characteristic of today’s youth? Key wordsYouth politics, voting behavior, radicalism, political attitudes, the Left
Obesity and Bone
Authors: Proietto Joseph
Published: September 2020

Obesity and osteoporosis are both common conditions with high rates of morbidity and mortality. There is a relationship between obesity and bone. There are multiple factors that influence the risk of fracture, including the quality of bone, the risk of falls, and the padding around the bone. These multiple factors partly explain the finding that obesity protects against fractures in some sites while increasing the risk in other parts of the body. While it is well known that increased weight builds bone, there are several mechanisms related to the obese state that make the bone more fragile. These include the increased production of bone marrow fat cells at the expense of bone-forming osteoblasts, an increase in inflammatory cytokines leading to the activation of bone-resorbing osteoclasts, mutations in theFTOgene, and obesity-induced increased osteoblast senescence. Surprisingly, the relationship between bone and obesity is not unidirectional; there is now evidence that osteocytes are able to regulate body weight by acting as weighing machines.
GFF Utilities: GffRead and GffCompare
Authors: Pertea Geo , Pertea Mihaela
Published: September 2020

Summary: GTF (Gene Transfer Format) and GFF (General Feature Format) are popular file formats used by bioinformatics programs to represent and exchange information about various genomic features, such as gene and transcript locations and structure. GffRead and GffCompare are open source programs that provide extensive and efficient solutions to manipulate files in a GTF or GFF format. While GffRead can convert, sort, filter, transform, or cluster genomic features, GffCompare can be used to compare and merge different gene annotations.

Availability and implementation: GFF utilities are implemented in C++ for Linux and OS X and released as open source under an MIT license  (https://github.com/gpertea/gffread, https://github.com/gpertea/gffcompare).
Iron overload parameters and early detection of cardiac disease among Egyptian children and young adults with β-thalassaemia major and sickle cell disease: a cross-sectional study
Authors: Salama Khaled , Abdelsalam Amina , Eldin Hadeel Seif , Youness Eman , Selim Yasmeen , Salama Christine , Hassanein Gehad , Samir Mohamed , Zekri Hanan
Published: September 2020

Background: Cardiac, hepatic and pancreatic T2* measured by magnetic resonance imaging (MRI) has been proven to be an accurate and non-invasive method for measuring iron overload in iron overload conditions. There is accumulating evidence that pancreatic iron can predict cardiac iron in young children because the pancreas loads earlier than the heart. The aim of our study was to investigate cardiac function and cardiac iron and their relation to pancreatic iron among patients with β-thalassaemia major (βTM) and sickle cell disease (SCD).

Methods: 40 βTM and 20 transfusion-dependant SCD patients were included along with 60 healthy age-matched controls. Echocardiography and Tissue Doppler Imaging were performed for all subjects as well as the control group.  Hepatic, cardiac and pancreatic iron overload in cases were assessed by MRI T2*.

Results: The study group consisted of 40 βTM and 20 transfusion dependant SCD patients with mean age 13.7 years and mean frequency of transfusion/year 12. Mean cardiac T2* was 32.9 ms and mean myocardial iron concentration was 0.7 mg/g; One patient had cardiac iron overload of moderate severity. Mean pancreatic T2* was 22.3 ms with 20 patients having mild pancreatic iron overload.

Pancreatic T2* correlated positively with main pulmonary artery diameter (p=0.046), peak late diastolic velocity at septal mitral annulus (p=0.038), peak early diastolic velocity at tricuspid annulus (p=0.001) and mitral annular plane systolic excursion (p=0.01); and negatively with end systolic pulmonary artery pressure (p=0.007). We couldn’t test the predictability of pancreatic T2* in relation to cardiac T2* as only one patient had cardiac T2*<20 ms.

Conclusion: Assessment of pancreatic T2* in multi-transfused patients with βTM and SCD can predict myocardial dysfunction. No direct relation between pancreatic iron and cardiac siderosis was detected.
Adaptive platform trials using multi-arm, multi-stage protocols: getting fast answers in pandemic settings
Authors: Noor Nurulamin M. , Pett Sarah L. , Esmail Hanif , Crook Angela M. , Vale Claire L. , Sydes Matthew R. , Parmar Mahesh K.B.
Published: September 2020

Global health pandemics, such as coronavirus disease 2019 (COVID-19), require efficient and well-conducted trials to determine effective interventions, such as treatments and vaccinations. Early work focused on rapid sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequent in-vitro and in-silico work, along with greater understanding of the different clinical phases of the infection, have helped identify a catalogue of potential therapeutic agents requiring assessment.

In a pandemic, there is a need to quickly identify efficacious treatments, and reject those that are non-beneficial or even harmful, using randomised clinical trials. Whilst each potential treatment could be investigated across multiple, separate, competing two-arm trials, this is a very inefficient process. Despite the very large numbers of interventional trials for COVID-19, the vast majority have not used efficient trial designs.

Well conducted, adaptive platform trials utilising a multi-arm multi-stage (MAMS) approach provide a solution to overcome limitations of traditional designs. The multi-arm element allows multiple different treatments to be investigated simultaneously against a shared, standard-of-care control arm. The multi-stage element uses interim analyses to assess accumulating data from the trial and ensure that only treatments showing promise continue to recruitment during the next stage of the trial.

The ability to test many treatments at once and drop insufficiently active interventions significantly speeds up the rate at which answers can be achieved. This article provides an overview of the benefits of MAMS designs and successes of trials, which have used this approach to COVID-19. We also discuss international collaboration between trial teams, including prospective agreement to synthesise trial results, and identify the most effective interventions. We believe that international collaboration will help provide faster answers for patients, clinicians, and health care systems around the world, including for future waves of COVID-19, and enable preparedness for future global health pandemics.
Impact of COVID-19 on utilization of maternal, newborn and child health services in Nigeria: protocol for a country-level mixed-methods study
Authors: Akaba Godwin , Dirisu Osasuyi , Okunade Kehinde , Adams Eseoghene , Ohioghame Jane , Obikeze Obioma , Izuka Emmanuel , Sulieman Maryam , Edeh Michael
Published: September 2020

Background: Battling with COVID-19 and providing essential services along the continuum of care could be challenging. This study will evaluate the impact of COVID-19 on utilization of maternal, newborn and child health (MNCH) services in Nigeria and explore the barriers being experienced by women and their families in getting access to MNCH services, as well as other contextual factors that may have shaped the utilization of MNCH services during the COVID-19 pandemic.

Methods and analysis: The study will adopt an observational mixed-methods study design involving 18 health care facilities delivering MNCH services in six selected states across six geopolitical zones of Nigeria. We will retrieve longitudinal data on MNCH services from all selected hospitals three months before and after the first recorded case of COVID-19 in Nigeria. Qualitative data will be collected using in-depth interviews conducted via mobile phones or ZOOM meeting platforms among stakeholder participants (users of MNCH services, health workers and policymakers) to ascertain their perceptions on how COVID-19 has shaped the utilization of MNCH services. We will triangulate quantitative and qualitative data to better understand the impact of COVID-19 on the utilization of MNCH services in Nigeria.

Ethics and dissemination: Ethics approvals have been obtained from the Health Research Ethics Committee of the tertiary hospitals involved in the study. Our findings will provide the first evidence from an African setting on the impact of COVID-19 on the utilization of MNCH services using a mixed-methods study design for policy formulation towards sustained MNCH service delivery.
Estados de Conservação
Authors: Tavares Claudia Barbosa Vieira
Published: September 2020

Estados de Conservação é uma série de dípticos fotográficos. Durante a travessia de uma única estrada, no estado de Minas Gerais em 2016, o cenário vai se modificando e descortinando um panorama de assombro. Montanhas são fatiadas pela mineração, há longas extensões de plantação de eucalipto, morros estão desmatados pela atividade pecuarista. Estado, aqui, aponta para um estar em mudança, no qual, a cada momento, pode haver uma variação de condição. Conservar remete a ideia de reter memória, conter no tempo, de estabelecer um limiar entre vida e morte, continuidade e fim.
“No intenso agora” e o presente na História
Authors: Madalen Rafael Garcia , Lemos Anna Paula Soares , De Oliveira Joaquim Humberto Coelho
Published: September 2020

Neste artigo, o documentário No intenso agora (2017), de João Moreira Salles, se corresponde com o conceito de presença, de Hans Ulrich Gumbrecht. A motivação para o encontro entre o documentarista e o crítico literário deve-se ao modo como em No intenso agora a abordagem da concepção de tempo se faz num momento de transição.
A ESPIRITUALIDADE SUMÉRIA COMO AGENTE DO PLURALISMO RELIGIOSO MESOPOTÂMICO
Authors: Toledo Túlio , Telles Luana
Published: September 2020

O presente artigo busca apresentar e esclarecer questões relacionadas ao contexto religioso da Suméria. A diversidade de povos no território mesopotâmico e suas distintas representações aparecem como importantes modelos de estruturação civilizacional e religiosa do Oriente Próximo. Para entender tal cenário, foi necessário, primeiramente, um estudo do contexto histórico-religioso-político da região do Sul da Mesopotâmia. Ao analisar esse contexto presente na idade antiga, reconhece-se a presença de um intenso pluralismo religioso e suas variadas manifestações no cotidiano dessas culturas, além de um intenso sincretismo, em que, a base desse sistema religioso ancorava-se nos ideais sumérios. A importância da simbologia dos templos e das divindades padroeiras sustentava o imaginário tanto dos indivíduos, como do funcionamento daquelas cidades.
A DINÂMICA DE AUTORIDADE NA VILLA: O VILICUS E A ADMINISTRAÇÃO DA PROPRIEDADE AGRÍCOLA
Authors: Nascimento Fabiana Martins
Published: September 2020

O presente artigo tem por objetivo analisar de que forma se estruturava a dinâmica de autoridade entre os sujeitos envolvidos no processo produtivo da villa. A presente análise se concentrará nas relações que o vilicus, o escravo administrador, mantinha tanto com seu superior, o proprietário (e também seu senhor) quanto com seus subordinados, a vilica, os demais escravos.
Blended learning: the future for nursing?
Authors: Foster Sam
Published: September 2020

Sam Foster, Chief Nurse, Oxford University Hospitals, considers how greater use of digital technology during the pandemic has introduced the profession to different ways of providing nurse education
Correlation between self-efficacy and self-esteem in patients with an intestinal stoma
Authors: Nasiriziba Fariba , Saati Maryam , Haghani Hamid
Published: September 2020

Background:

Patients with an intestinal stoma experience psychological difficulties, including disturbances in self-efficacy and self-esteem. There is evidence that they are interdependent.

Aim:

This study aimed to determine the correlation between self-efficacy and self-esteem in patients with an intestinal stoma.

Methods:

A descriptive-correlational study was conducted with 155 patients with an intestinal stoma. Participants were selected using convenience sampling. Data were collected using demographic questions, the stoma self-efficacy scale and the Rosenberg self-esteem scale, and analysed using descriptive and analytical statistics.

Findings:

Seventy-nine men and 76 women took part; the 50–70 years age group had the highest proportion of participants. Regarding diagnosis, 52.26% had cancer and 45.81% had inflammatory bowel disease or related conditions. Pearson's correlation coefficient indicated a positive, significant correlation between total self-efficacy and its dimensions with self-esteem (P<0.001; r=0.54).

Conclusion:

Self-efficacy is positively correlated with self-esteem in patients with an intestinal stoma. It is recommended that educational interventions are planned and implemented to boost self-esteem and self-efficacy in these patients.
Opioid drugs: a high risk prescribing area?
Authors: Robertson Deborah
Published: September 2020

Deborah Robertson provides an overview of recently published articles that may be of interest to non-medical prescribers. Should you wish to look at any of the papers in more detail, a full reference is provided
A Meta-Analysis of the Effects of Arduino-Based Education in Korean Primary and Secondary Schools in Engineering Education
Authors: Lee Eunsang
Published: September 2020

The Arduino microcontroller enables ordinary people to perform professional tasks that only traditional engineering professionals could perform. Recently, several educational cases have been applied to primary and secondary schools, which is a desirable attempt to popularize engineering education. This study meta-analyzed the effects of Arduino-based education in primary and secondary schools in Korea from the perspective of engineering education. Accordingly, 16 academic journals and dissertations were selected that verified educational effects by Arduino-based education to primary and secondary students in Korea, and 31 effect sizes were confirmed. According to the results of this study, the overall average effect size was 0.656, which confirmed that Arduino-based education had a positive educational effect. Furthermore, this study calculated the effect size as measured by categorical and continuous variables such as school level, the inclusion of curriculum, giftedness, publication status, the programming language used, publication year, number of sessions, and number of students. Implications were suggested from the perspective of engineering education. This study is meaningful because it suggests the application of Arduino to primary and secondary schools in engineering education by confirming the positive educational effect of Arduino-based education.
Evaluation of a Decision Support System for Variable-Rate Irrigation in a Humid Region
Authors: Sui Ruixiu , O’Shaughnessy Susan A. , Evett Steven R. , Andrade-Rodriguez Alejandro , Baggard Jonnie
Published: September 2020

Highlights

An Irrigation Scheduling Supervisory Control and Data Acquisition (ISSCADA) system was tested against a soil electrical conductivity (EC) based method for variable-rate irrigation (VRI).

Soil EC was used to create irrigation prescription in EC-based VRI.

ISSCADA generated VRI prescriptions using canopy temperature, soil water content, and weather data.

ISSCADA-based VRI reduced irrigation water use and increased irrigation water productivity.

Abstract. Use of variable-rate irrigation (VRI) technology has the potential to improve irrigation water use efficiency (IWUE). VRI hardware is commercially available and can be implemented in any center pivot or lateral move irrigation system. However, practical methods and algorithms for creating VRI prescriptions have become the bottleneck in accelerating the adoption of VRI. An Irrigation Scheduling Supervisory Control and Data Acquisition (ISSCADA) system for VRI was evaluated for two years in a humid region in the Mississippi Delta. The ISSCADA system was used to manage irrigation of soybeans for two seasons. In field practice, the ISSCADA system scanned the field for canopy temperature and collected soil water data from time domain reflectometers and weather data from a nearby weather station. The ISSCADA system automatically generated VRI prescription maps. The maps were modified to include plots managed using soil electrical conductivity (EC) based VRI prescriptions. Test results indicated that there was no difference in crop yield between EC-based VRI and ISSCADA-based VRI management. However, ISSCADA-based VRI management reduced irrigation water use and increased irrigation water productivity in comparison with EC-based VRI. There is great potential for the use of ISSCADA for VRI in humid regions. Keywords: Canopy temperature, Soil electrical conductivity, Soil moisture sensor, Soil water sensor, Soybean, Variable rate irrigation.
On Voynich Alphabet Analysis With Relation to the Old Indian Dialects
Authors: Zelinka Ivan , Dao Tran Trong
Published: September 2020

This paper is discussing our new research direction in the Voynich manuscript research. While our previous papers have been dealing with the research that has been based on fractal property analyses or graph properties analyses, where the graph has been constructed from the Voynich manuscript word sequences (Fig. 1), this paper discusses another kind of research on Voynich manuscript. This research is focused on the compassion of the letters or alphabets from Voynich manuscript with another selected alphabets from a different dialect, in that case, dialect from the Indian language. The reason is to point out the possibility that we can identify the origin of the Voynich manuscript alphabets based on the graphical conversion between letters from different dialects. Because this research is a very wide and deep topic, we publish in this paper only basic ideas, simulations and discuss all problems which have been found during those experimentation as well as outlining of the future directions of the research in an outlined way.
LiFi grid: a machine learning approach to user-centric design
Authors: Pashazanoosi Mohamadreza , Alireza Nezamalhosseini S. , Salehi Jawad A.
Published: September 2020

A novel machine learning (ML) clustering algorithm, named
light-fidelity (LiFi) Grid, is proposed to design amorphous cells of
LiFi access points (APs) in order to maximize the minimum
signal-to-interference-plus-noise ratio (SINR) from the viewpoint of
user-centric (UC) network design. The algorithm consists of two
phases. Explicitly, the first phase consists of finding clusters of
user densities based on the mean-shift (MS) clustering algorithm. In
contrast to some other clustering algorithms, such as K-means, MS does
not need to know the number of clusters in advance. Furthermore, the
combined transmission scheme is assumed in each cell. In the second
phase, this paper proposes a novel clustering algorithm that addresses
the problem of grouping APs based on the positions of users—UC
design—in optical wireless networks (OWNs). Hence, it addresses the
dynamic resource allocation problem in OWNs if APs are considered as
network resources. Based on the maximization of minimum SINR metric,
LiFi Grid demonstrates the superior performance relative to
conventional fixed-shape cell-centric network designs. Additionally,
full compatibility of the LiFi Grid clustering algorithm with the
Institute of Electrical and Electronics Engineers standard 802.15.7 is
also shown.
Predicting the refractive index of amorphous materials using the Bruggeman effective medium approximation
Authors: Sela Maor , Haspel Carynelisa
Published: September 2020

Previous studies have shown that the Lorentz–Lorenz relationship, or molar refractivity/specific refractivity effective medium approximation, enables a reasonable prediction of the refractive index of amorphous water ice, given the refractive index of crystalline water ice. In the current study, we show that the Bruggeman effective medium approximation provides an even closer match to measurements of the refractive index of several amorphous materials, given the refractive index of their crystalline phase. We show that the Bruggeman effective medium approximation provides a good match to measurements of the refractive index of amorphous ice as well. Thus, assuming that the volume fraction of the scattering centers is a constant for a given amorphous material (with respect to a given range of wavelengths) seems to be a more robust assumption than assuming that the molar mass and molar refractivity or specific refractivity are preserved in going from the crystalline state to the amorphous state of the same material. Our results have implications for astrophysics applications, as well as for the optics of non-crystalline materials in general.
High-order DBR semiconductor lasers: effect of grating parameters on grating performance
Authors: E Siyu , Zhou Yinli , Zhang Xing , Zhang Jianwei , Huang Youwen , Zeng Yugang , Cui Jinjiang , Liu Yun , Ning Yongqiang , Wang Lijun
Published: September 2020

In this paper, a high-order distributed Bragg reflector (DBR)
semiconductor laser operating at 1064 nm is demonstrated based on
simulation analysis. To get optimal Bragg grating characteristics,
four parameters of the Bragg grating were analyzed in detail.
Forty-nine-order Bragg gratings were designed with a reflectivity of
6% and a FWHM of 3 nm, which can realize mode selection while lasing.
The Bragg gratings were designed to maximize the use of light.
Transmission of the rear laser facet is theoretically 0. This
simulation result provides a simple and efficient DBR semiconductor
laser scheme without cavity surface coating.
Quantum Well Laser Diode Frequency Comb in the 2 μm Region
Authors: Sterczewski Lukasz A. , Frez Clifford , Forouhar Siamak , Burghoff David , Bagheri Mahmood
Published: September 2020

We present the first semiconductor laser frequency comb in the 2 μm region. The source relies of an inherent gain nonlinearity in a quantum well laser diode, which promotes frequency-modulated operation with sub-THz spectral coverage.
Microstructured surfaces for colored and non-colored sky radiative cooling
Authors: Blandre Etienne , Yalçin Refet Ali , Joulain Karl , Drévillon Jérémie
Published: September 2020

We propose a simple structure for passive sky radiative cooling made of a surface-textured layer of silica on a silver substrate. Using electromagnetic simulations, we show that the optical properties of such structures are near-ideal, due to the large reflectivity of silver in the solar spectrum and the large emissivity of silica in the infrared. Surface texturation is key to obtain near-unity emissivity in the infrared. By using thin transparent layers sandwiched between silver layers at the bottom of the structures, resonant absorption can be obtained, leading to coloration while keeping acceptable radiative cooling power. Using multiple resonator increases the color palette that can be obtained.
Three-dimensional electrochemical etching by grid ditching for multi-wavelength visible-light emission on porous silicon
Authors: Lin Jia-Chuan , Huang Yu-Chen
Published: September 2020

A new approach of three-dimensional electro-chemical etchings both in vertical and lateral current directions on grid ditched Si pn-structures is originally proposed. Lateral etchings on the different ditched zones cause different porosities on porous Si, which emit visible lights of different wavelengths under ultraviolet light stimulation. Therefore, a single Si-based chip is capable of emitting visible light with tunable and multiple wavelengths simultaneously by this new approach. Moreover, the etching conditions on porous Si films and their related wavelengths can be fine-tuned by area sizes. Compared with the conventional method, the new approach provides a new option for multi-wavelength chip design with a precise patterning for porous Si without any mask and photoresist.
Elevating the density and intensity of hot spots by repeated annealing for high-efficiency SERS
Authors: Hou Liping , Shao Mingrui , Li Zhaoxiang , Zhao Xiaofei , Liu Aihua , Zhang Chao , Xiu XianWu , Yu Jing , Li Zhen
Published: September 2020

The simultaneous output of highly sensitive and reproducible signals for surface-enhanced Raman spectroscopy (SERS) technology remains difficult. Here, we propose a two-dimensional (2D) composite structure using the repeated annealing method with MoS2 film as the molecular adsorbent. This method provides enlarged Au nanoparticle (NP) density with much smaller gap spacing, and thus dramatically increases the density and intensity of hot spots. The MoS2 films distribute among the hot spots, which is beneficial for uniform molecular adsorption, and further increases the sensitivity of the SERS substrate. Three kinds of molecules were used to evaluate the SERS substrate. Ultra-sensitive, highly repetitive, and stable SERS signals were obtained, which would promote the application process of SERS technology in quantitative analysis and detection.
Upconversion-luminescent hydrogel optical probe for in situ dopamine monitoring
Authors: Zhou Bingqian , Guo Jingjing , Yang Changxi , Kong Lingjie
Published: September 2020

Dopamine (DA), as a neurotransmitter in human brain, plays a crucial role in reward motivation and motor control. An improper level of DA can be associated with neurological disorders such as schizophrenia and Parkinson’s disease. To quantify DA, optical DA sensors have emerged as an attractive platform due to their capability of high-precision and label-free measurement, and immunity to electromagnetic interference. However, the lack of selectivity, limited biocompatibility, and complex fabrication processes are challenges that hinder their clinical applications. Here, we report a soft and biocompatible luminescent hydrogel optical sensor capable of recognizing and quantifying DA with a simple and compact interrogation setup. The sensor is made of a hydrogel optical fiber (HOF) incorporated with upconversion nanoparticles (UCNPs). DA molecules are detected through the luminescence energy transfer (LET) between the UCNPs and the oxidation products of DA, while the light-guiding HOF enables both excitation and emission collection of the UCNPs. The hydrogel sensor provides an optical readout that shows a linear response up to 200 μmol/L with a detection limit as low as 83.6 nmol/L. Our results show that the UCNP-based hydrogel sensor holds great promise of serving as a soft and biocompatible probe for monitoring DA in situ.