bluuebunny/crossref_metadata_2025 huggingface dataset:
Excitability, synaptic balance, and addiction: The homeostatic dynamics of ionotropic glutamatergic receptors in VTA after cocaine exposure
Authors: Moulin Thiago C. , Schiöth Helgi B.
Published: June 2020

Glutamatergic AMPA and NMDA receptors in the ventral tegmental area (VTA) are central for cocaine first exposure and posterior craving maintenance. However, the exact rules that coordinate the synaptic dynamics of these receptors in dopaminergic VTA neurons and behavioral outcomes are poorly understood. Additionally, synaptic homeostatic plasticity is present in response to chronic excitability changes in neuronal circuits, adjusting the strength of synapses to stabilize the firing rate. Despite having correspondent mechanisms, little is known about the relationship between continuous cocaine exposure and homeostatic synaptic changes in the VTA neurons. Here, we assess the role of homeostatic mechanisms in the neurobiology of cocaine addiction by providing a brief overview of the parallels between cocaine-induced synaptic potentiation and long-term synaptic adaptations, focusing on the regulation of GluA1- and GluN1- containing receptors.
Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass
Authors: Naase Hatam , Harling Leanne , Kidher Emaddin , Sepehripour Amir , Nguyen Bao , Kapelouzou Alkistis , Cokkinos Dennis , Stavridis George , Angelini Gianni , Evans Paul C. , Athanasiou Thanos
Published: June 2020

Objectives

Cardiac surgery can lead to post-operative end-organ complications secondary to activation of systemic inflammatory response. We hypothesize that surgical trauma or cardiopulmonary bypass (CPB) may initiate systemic inflammatory response via release of mitochondrial DNA (mtDNA) signaling Toll-like receptor 9 (TLR9) and interleukin-6 production (IL-6).

Materials and methods

The role of TLR9 in systemic inflammatory response in cardiac surgery was studied using a murine model of sternotomy and a porcine model of sternotomy and CPB. mtDNA and IL-6 were measured with and without TLR9-antagonist treatment. To study ischemia-reperfusion injury, we utilized an ex-vivo porcine kidney model.

Results

In the rodent model (n = 15), circulating mtDNA increased 19-fold (19.29 ± 3.31, p < 0.001) and plasma IL-6 levels increased 59-fold (59.06 ± 14.98) at 1-min post-sternotomy compared to pre-sternotomy. In the murine model (n = 11), administration of TLR-9 antagonists lowered IL-6 expression post-sternotomy when compared to controls (59.06 ± 14.98 vs. 5.25 ± 1.08) indicating that TLR-9 is a positive regulator of IL-6 after sternotomy. Using porcine models (n = 10), a significant increase in circulating mtDNA was observed after CPB (Fold change 29.9 ± 4.8, p = 0.005) and along with IL-6 following renal ischaemia-reperfusion. Addition of the antioxidant sulforaphane reduced circulating mtDNA when compared to controls (FC 7.36 ± 0.61 vs. 32.0 ± 4.17 at 60 min post-CPB).

Conclusion

CPB, surgical trauma and ischemic perfusion injury trigger the release of circulating mtDNA that activates TLR-9, in turn stimulating a release of IL-6. Therefore, TLR-9 antagonists may attenuate this response and may provide a future therapeutic target whereby the systemic inflammatory response to cardiac surgery may be manipulated to improve clinical outcomes.
DDIEM: drug database for inborn errors of metabolism
Authors: Abdelhakim Marwa , McMurray Eunice , Syed Ali Raza , Kafkas Senay , Kamau Allan Anthony , Schofield Paul N , Hoehndorf Robert
Published: June 2020

Background

Inborn errors of metabolism (IEM) represent a subclass of rare inherited diseases caused by a wide range of defects in metabolic enzymes or their regulation. Of over a thousand characterized IEMs, only about half are understood at the molecular level, and overall the development of treatment and management strategies has proved challenging. An overview of the changing landscape of therapeutic approaches is helpful in assessing strategic patterns in the approach to therapy, but the information is scattered throughout the literature and public data resources.

Results

We gathered data on therapeutic strategies for 300 diseases into the Drug Database for Inborn Errors of Metabolism (DDIEM). Therapeutic approaches, including both successful and ineffective treatments, were manually classified by their mechanisms of action using a new ontology.

Conclusions

We present a manually curated, ontologically formalized knowledgebase of drugs, therapeutic procedures, and mitigated phenotypes. DDIEM is freely available through a web interface and for download at http://ddiem.phenomebrowser.net.
A moonshot approach toward the management of cancer patients in the COVID-19 time: what have we learned and what could the Italian network of cancer centers (Alliance Against Cancer, ACC) do after the pandemic wave?
Authors: Silvestris Nicola , Apolone Giovanni , Botti Gerardo , Ciliberto Gennaro , Costantini Massimo , De Paoli Paolo , Franceschi Silvia , Opocher Giuseppe , Paradiso Angelo , Pronzato Paolo , Sgambato Alessandro , De Maria Ruggero
Published: June 2020

If we focus our attention on seven main features of COVID-19 infection (heterogeneity, fragility, lack of effective treatments and vaccines, “miraculous cures”, psychological suffering, deprivation, and globalization), we may establish parallelism with the challenges faced in the steep road to the understanding and treatment of neoplastic diseases. How the similarities between these two conditions can help us cope with the emergency effort represented by the management of cancer patients in the COVID-19 era, today and in the future? In a manner similar to the Cancer Moonshot initiative in the United States, we can hypothesize a multinational moonshot project towards the management of cancer patients during COVID-19 pandemic. In particular, we believe that the main road to elaborate meaningful scientific evidence is represented by the collection of all the data on COVID-19 and cancer comorbidity that are and will become available in cancer centers, coupled with the design of large clinical studies. To address this goal, it is essential to identify the entity that can produce this scientific evidences and the potentially most successful research strategy to undertake. The largest Italian organization for cancer research, Alliance Against Cancer (Alleanza Contro il Cancro, ACC), is called to play a scientific leadership in addressing these challenges, which requires the coordination of oncology teams at regional, national, and international levels. To fulfill this commitment, ACC will create a liaison with health government agencies in order to develop “dynamic” indications able to fight such an unpredictable pandemic.
Effectiveness of inspiratory muscle training associated with a cardiac rehabilitation program on sympathetic activity and functional capacity in patients with heart failure: a study protocol for a randomized controlled trial
Authors: Leite Jéssica Costa , Brandão Daniella Cunha , Brandão Simone Cristina Soares , Fuzari Helen Kerlen Bastos , Vidal Tainá Maria , Frutuoso Jasiel , Remígio Maria Inês , de Araújo Bruna Thays Santana , Campos Shirley Lima , Dornelas de Andrade Armele
Published: June 2020

Background

Individuals affected by heart failure (HF) may present fatigue, dyspnea, respiratory muscle weakness, and sympathetic activity hyperstimulation of the myocardium, among other symptoms. Conducting cardiac rehabilitation (CR) programs can be associated with inspiratory muscle training. The aim of this study was to evaluate the efficacy of inspiratory muscular training (IMT) associated with a CR program on modulating myocardial sympathetic activity and maximal functional capacity, submaximal functional capacity, thickness, and mobility of the diaphragm muscle in patients with HF.

Methods

We will conduct a clinical, controlled, randomized, double-blind trial that will include sedentary men and women who are 21–60 years old and who have diagnosed systolic HF and a left ventricular ejection fraction of less than 45%. Participants will be randomly assigned to one of two groups: experimental and control. The control group will follow the conventional CR protocol, and the experimental group will follow the conventional CR protocol associated with IMT 7 days a week. The two proposed exercise protocols will have a frequency of three times a week for a period of 12 weeks. The sympathetic innervation of the cardiac muscle, the maximum and submaximal functional capacity, diaphragm mobility and thickness, and the quality of life of the participants will be evaluated before and after the intervention protocol.

Discussion

This clinical trial will be the first study to investigate the additional effects of IMT on CR in sympathetic hyperstimulation in the myocardium. The results of this study will contribute to developing therapeutic strategies collaborating to elucidate whether the association of IMT with CR can induce clinical benefits for patients with HF.

Trial registration

ClinicalTrials.gov identifier: NCT02600000. Registered November 9, 2015. Retrospectively registered.
Achieving blood pressure control targets in hypertensive patients of rural China – a pilot randomized trial
Authors: Huang Xiao , Liu Lishun , Song Yun , Gao Lan , Zhao Min , Bao Huihui , Qin Xianhui , Wu Yanqing , Wu Qinghua , Bi Chonglei , Yue Aiping , Fang Chongqian , Ma Hai , Cui Yimin , Tang Genfu , Li Ping , Zhang Yan , Li Jianping , Wang Binyan , Xu Xiping , Wang Hong , Parati Gianfranco , Spence J. David , Wang Xiaobin , Huo Yong , Chen Guangliang , Cheng Xiaoshu ,   for the investigators of intensive BP control in China
Published: June 2020

Background

This study aimed to test the feasibility and titration methods used to achieve specific blood pressure (BP) control targets in hypertensive patients of rural China.

Methods

A randomized, controlled, open-label trial was conducted in Rongcheng, China. We enrolled 105 hypertensive participants aged over 60 years, and who had no history of stroke or cardiovascular disease. The patients were randomly assigned to one of three systolic-BP target groups: standard: 140 to < 150 mmHg; moderately intensive: 130 to < 140 mmHg; and intensive: < 130 mmHg. The patients were followed for 6 months.

Discussion

The optimal target for systolic blood pressure (SBP) lowering is still uncertain worldwide and such information is critically needed, especially in China. However, in China the rates of awareness, treatment and control are only 46.9%, 40.7%, and 15.3%, respectively. It is challenging to achieve BP control in the real world and it is very important to develop population-specific BP-control protocols that fully consider the population’s characteristics, such as age, sex, socio-economic status, compliance with medication, education level, and lifestyle. This randomized trial showed the feasibility and safety of the titration protocol to achieve desirable SBP targets (< 150, < 140, and < 130 mmHg) in a sample of rural, Chinese hypertensive patients. The three BP target groups had similar baseline characteristics. After 6 months of treatment, the mean SBP measured at an office visit was 137.2 mmHg, 131.1 mmHg, and 124.2 mmHg, respectively, in the three groups. Home BP and central aortic BP measurements were also obtained. At 6 months, home BP measurements (2 h after drug administration) showed a mean SBP of 130.9 mmHg in the standard group, 124.9 mmHg in the moderately intensive group, and 119.7 mmHg in the intensive group. No serious adverse events were recorded over the 6-month study period. Rates of adverse events, including dry cough, palpitations, and arthralgia, were low and showed no significant differences between the three groups. This trial provided real-world experience and laid the foundation for a future, large-scale, BP target study.

Trial registration

Feasibility Study of the Intensive Systolic Blood Pressure Control; ClinicalTrials.gov, ID: NCT02817503. Registered retrospectively on 29 June 2016.
Determination of efficacy and toxicity of diclofenac microemulsion formulation for musculoskeletal pain: an observational study
Authors: Banh Hoan Linh , Cave Andrew
Published: June 2020

Objective

Musculoskeletal pain is often caused by injury to the bones, muscles, tendons, ligaments or nerves. Symptoms can be localized or generalized. Mild-moderate symptoms are treated with topical/oral over the counter drugs. Microemulsion delivery formulations are thermodynamically stable, have superior bioavailability and better penetration of lipophilic and hydrophilic drug into the dermis. A prospective observational study in patients: 18 years or older, with mild-moderate musculoskeletal pain; with severe pain without adequate pain control; with severe pain and could not tolerate oral agents; with renal impairment were invited to try diclofenac 2% in microemulsion foam. They were followed up at 2 and 4 weeks. A 50% reduction on a visual analog pain scale was considered success. Adverse events were defined as irritation, gastrointestinal upset/bleed, rectal bleed, and hematemesis. The objective was to determine the efficacy and toxicity of diclofenac 2% in microemulsion foam.

Results

Thirteen consecutive patients with musculoskeletal pain consented to participate. Two patients were lost to follow up. Two of the 11 patients reported minimal improvement, while nine patients reported minimum 50% reduction. No adverse effects were reported. Diclofenac 2% in microemulsion foam is effective in the treatment of mild to moderate musculoskeletal pain and well tolerated.
Voxel-based comparison of [68Ga]Ga-RM2-PET/CT and [68Ga]Ga-PSMA-11-PET/CT with histopathology for diagnosis of primary prostate cancer
Authors: Fassbender Thomas Franz , Schiller Florian , Zamboglou Constantinos , Drendel Vanessa , Kiefer Selina , Jilg Cordula A. , Grosu Anca-Ligia , Mix Michael
Published: June 2020

Background

Focal therapies or focally escalated therapies of primary prostate cancer are becoming more and more important. This increases the need to identify the exact extension of the intraprostatic tumor and possible dominant intraprostatic lesions by imaging techniques. While the prostate-specific membrane antigen (PSMA) is already a well-established target for imaging of prostate cancer cells, the gastrin-releasing peptide receptor (GRPR) seems to provide interesting additional information. Histopathology was used to examine the extent to which the single and combined image information of PET scans targeting GRPR and PSMA might lead to better tumor delineation.

Methods

Eight patients with histologically proven primary prostate cancer underwent two positron emission tomography with computer tomography scans, [68Ga]Ga-RM2-PET/CT (RM2-PET) and [68Ga]Ga-PSMA-11-PET/CT (PSMA-PET), prior to radical prostatectomy. RM2-PET data were correlated voxel-wise to a voxel-based model of the histopathologic tumor volume information. The results were compared to, correlated to, and combined with the correlation of PSMA-PET data analyzed analogously.

Results

In 4/8 patients, RM2-PET showed a higher signal in histologically proven tumor regions compared to PSMA. There were also tumor regions where PSMA-PET showed a higher signal than GRPR in 4/8 patients. A voxel-wise correlation of RM2-PET against histopathology yielded similar results compared to the correlation of PSMA-PET against histopathology, while PSMA-PET is the slightly better performing imaging technique. The combined information of both tracers yielded the best overall result, although this effect was not statistically significant compared to RM2-PET alone.

Conclusions

Qualitative and quantitative findings in this preliminary study with 8 patients indicate that RM2-PET and PSMA-PET partially show not only the same, but also distinct regions of prostate cancer. Patients with pPCa might profit from information given by tracers targeting GRPR and PSMA simultaneously, in terms of a better delineation of the gross tumor volume.
Healthcare consumption after a change in health insurance coverage: a French quasi-natural experiment
Authors: Sevilla-Dedieu Christine , Billaudeau Nathalie , Paraponaris Alain
Published: June 2020

Background

Compared with the number of studies performed in the United States, few studies have been conducted on the link between health insurance and healthcare consumption in Europe, likely because most European countries have compulsory national health insurance (NHI) or a national health service (NHS). Recently, a major French private insurer, offering voluntary complementary coverage in addition to the compulsory NHI, replaced its single standard package with a range of offers from basic coverage (BC) to extended coverage (EC), providing a quasi-natural experiment to test theoretical assumptions about consumption patterns.

Methods

Reimbursement claim data from 85,541 insurees were analysed from 2009 to 2018. Insurees who opted for EC were matched to those still covered by BC with similar characteristics. Difference-in-differences (DiD) models were used to compare both the monetary value and physical quantities of healthcare consumption before and after the change in coverage.

Results

As expected, the DiD models revealed a strongly significant, though transitory (mainly during the first year), increase after the change in coverage for EC insurees, particularly for costly care such as dental prostheses and spectacles. Surprisingly, consumption seemed to precede the change in coverage, suggesting that one possible determinant of opting for more coverage may be previous unplanned expenses.

Conclusion

Both catching-up behaviour and moral hazard are likely to play a role in the observed increase in healthcare consumption.
Effects of endotoxin adsorber hemoperfusion on sublingual microcirculation in patients with septic shock: a randomized controlled trial
Authors: Chen Shih-Hong , Chan Wing-Sum , Liu Chih-Min , Chiu Ching-Tang , Chao Anne , Wu Vin-Cent , Sheng Wang-Huei , Lai Chien-Heng , Wang Ming-Jiuh , Yeh Yu-Chang
Published: June 2020

Background

Endotoxins can induce an excessive inflammatory response and result in microcirculatory dysfunction. Polymyxin-B hemoperfusion (PMX-HP) has been recognized to effectively remove endotoxins in patients with sepsis and septic shock, and a rat sepsis model revealed that PMX-HP treatment can maintain a better microcirculation. The primary aim of this study was to investigate the effect of PMX-HP on microcirculation in patients with septic shock.

Methods

Patients with septic shock were enrolled and randomized to control and PMX-HP groups. In the PMX-HP group, patients received the first session of PMX-HP in addition to conventional septic shock management within 24 h after the onset of septic shock; the second session of PMX-HP was provided after another 24 h as needed.

Results

Overall, 28 patients finished the trial and were analyzed. The mean arterial pressure and norepinephrine infusion dose did not differ significantly between the control and PMX-HP groups after PMX-HP treatment. At 48 h after enrollment, total vessel density (TVD) and perfused vessel density (PVD) were higher in the PMX-HP group than in the control group [TVD 24.2 (22.1–24.9) vs. 21.1 (19.9–22.9) mm/mm2; p = 0.007; PVD 22.9 (20.9–24.9) vs. 20.0 (18.9–21.6) mm/mm2, p = 0.008].

Conclusions

This preliminary study observed that PMX-HP treatment improved microcirculation but not clinical outcomes in patients with septic shock at a low risk of mortality. Nevertheless, larger multicenter trials are needed to confirm the effect of PMX-HP treatment on microcirculation in patients with septic shock at intermediate- and high-risk of mortality.

Trial registration ClinicalTrials.gov protocol registration ID: NCT01756755. Date of registration: December 27, 2012. First enrollment: October 6, 2013. https://clinicaltrials.gov/ct2/show/NCT01756755
Assessment of interprofessional competence in undergraduate health professions education: protocol for a systematic review of self-report instruments
Authors: Allvin Renée , Thompson Carl , Edelbring Samuel
Published: June 2020

Background

Health practitioners from different professions, and with differing competencies, need to collaborate to provide quality care. Competencies in interprofessional working need developing in undergraduate educational preparation. This paper reports the protocol for a systematic review of self-report instruments to assess interprofessional learning in undergraduate health professionals’ education.

Methods

We will search PubMed, Web of Science, CINAHL and ERIC from January 2010 onwards. A combination of search terms for interprofessional learning, health professions, psychometric properties, assessment of learning and assessment tools will be used. Two reviewers will independently screen all titles, abstracts and full-texts. Potential conflicts will be resolved through discussion. Quantitative and mixed-methods studies evaluating interprofessional learning in undergraduate health professions education (e.g. medicine, nursing, occupational and physical therapy, pharmacy and psychology) will be included. Methodological quality of each reported instrument, underpinning theoretical frameworks, and the effects of reported interventions will be assessed. The overall outcome will be the effectiveness of instruments used to assess interprofessional competence. Primary outcomes will be the psychometric properties (e.g. reliability, discriminant and internal validity) of instruments used. Secondary outcomes will include time from intervention to assessment, how items relate to specific performance/competencies (or general abstract constructs) and how scores are used (e.g. to grade students, to improve courses or research purposes). Quantitative summaries in tabular format and a narrative synthesis will allow recommendations to be made on the use of self-report instruments in practice.

Discussion

Many studies use self-report questionnaires as tools for developing meaningful interprofessional education activities and assessing students’ interprofessional competence. This systematic review will evaluate both the benefits and limitations of reported instruments and help educators and researchers (i) choose the most appropriate existing self-report instruments to assess interprofessional competence and (ii) inform the design and conduct of interprofessional competency assessment using self-report instruments.

Systematic review registration

Open Science Framework [https://osf.io/vrfjn].
Some approximation properties of new Kantorovich type q-analogue of Balázs–Szabados operators
Authors: Hamal Hayatem , Sabancigil Pembe
Published: June 2020

In this paper, we define a new Kantorovich type q-analogue of the Balázs–Szabados operators, we give some local approximation properties of these operators and prove a Voronovskaja type theorem.
Development of human prostate cancer stem cells involves epigenomic alteration and PI3K/AKT pathway activation
Authors: Wu Jingjing , Cang Shundong , Liu Christina , Ochiai Whitman , Chiao Jen Wei
Published: June 2020

Background

Human prostate cancer spheres endowed with stem cell properties have been obtained from androgen-dependent cell line LNCaP after exposure to an epigenomic modulator phenethyl isothiocynate (PEITC). Sphere cells can self-renew and grow with androgen, and also without androgen. Little is known about the signaling pathway and mechanism in the development of the stem cells in the spheres.

Methods

Expression of phosphoinositol-3 kinase (PI3K) pathway members and histone acetylation were quantified in the tumor spheres and LNCaP cells by western immunoblotting.

Results

The level of phosphorylated AKT was significantly increased in the sphere stem cells than the LNCaP cells at an average of 7.4 folds (range 5.8–10.7 folds), whereas the P27 level was elevated 5.4 folds (range 4.8–6.3 folds) (P < 0.05). The acetylation level on histone H3 lysine 9 was decreased.

Conclusions

PEITC appears to regulate the epigenome through histone acetylation and activate the PI3K/AKT pathway in the LNCaP cells. This mechanism may be responsible in part for the development of the prostate cancer stem cells.
SICE: an improved missing data imputation technique
Authors: Khan Shahidul Islam , Hoque Abu Sayed Md Latiful
Published: June 2020

In data analytics, missing data is a factor that degrades performance. Incorrect imputation of missing values could lead to a wrong prediction. In this era of big data, when a massive volume of data is generated in every second, and utilization of these data is a major concern to the stakeholders, efficiently handling missing values becomes more important. In this paper, we have proposed a new technique for missing data imputation, which is a hybrid approach of single and multiple imputation techniques. We have proposed an extension of popular Multivariate Imputation by Chained Equation (MICE) algorithm in two variations to impute categorical and numeric data. We have also implemented twelve existing algorithms to impute binary, ordinal, and numeric missing values. We have collected sixty-five thousand real health records from different hospitals and diagnostic centers of Bangladesh, maintaining the privacy of data. We have also collected three public datasets from the UCI Machine Learning Repository, ETH Zurich, and Kaggle. We have compared the performance of our proposed algorithms with existing algorithms using these datasets. Experimental results show that our proposed algorithm achieves 20% higher F-measure for binary data imputation and 11% less error for numeric data imputations than its competitors with similar execution time.
Hybrid medical simulation – a systematic literature review
Authors: Brown Wayne J. , Tortorella Richard A. W.
Published: June 2020

Health-care education based upon technology enabled mannequins (high-fidelity simulators) is a costly investment for colleges and universities. However, a hybrid model using wearable technology integrated with human actors (standardized patients) may present a cost-effective alternative to high fidelity simulation training scenarios. A systematic literature review of papers published from 1960 to 2019 illustrates that hybrid simulation can be as effective as high fidelity simulators in certain training scenarios while at the same time providing a superior training context to enhance learners patient to care-giver interactions and to better immerse the trainee in the feelings and emotion of the scenario.
Recreational off-highway vehicle crashes resulting in victims being treated at a regional trauma center: mechanisms and contributing factors
Authors: Jennissen Charles A. , Reaney Meaghan T. , Denning Gerene M.
Published: June 2020

Background

Recreational off-highway vehicles (ROVs) have become increasingly popular in recent years; however, crash epidemiology is not well described. ROVs travel at least 30 mph, and unlike all-terrain vehicles, have a rollover protective structure (ROPS) and seat belts or a harness system for occupants. This study’s objective was to evaluate the demographics, mechanisms, injuries, and associated risk factors of ROV crashes.

Methods

A retrospective chart review was performed for patients of all ages with ROV-related injuries presenting to a Level 1 trauma center from 2004 to 2017. Cases were identified by ICD-9/10 codes and narrative searches. Person- and crash-related variables were examined in relation to injury outcomes including body area injured, injury severity score, and disposition (e.g. hospitalization, intensive care unit admission). Descriptive, bivariate (chi-square, Fishers exact test), and linear regression analyses were performed.

Results

Seventy-two patients with ROV-related injuries were identified. The number of injured patients increased over the study period (p < 0.01). Patients were 49% youth < 16 years old, 63% males, and 99% Caucasian. Half of the injured (51%) were passengers, with a higher proportion of youth being passengers (70%) as compared to adults (35%) (p < 0.01). Nearly one-third (30%) of crash victims < 16 years old were ROV drivers. Twenty-nine percent of all crashes occurred on roadways. Almost 40% of injured adults crashed at night, while all youth were injured during the day (p < 0.01). The primary crash mechanism was a rollover (67%). Only one patient was documented as being helmeted, and approximately one-fourth (24%) sustained head injuries and/or loss of consciousness. Other documented injuries included those to the face (20%), chest (22%), abdomen (11%), extremities (58%), and skin (51%). Over 90% of narratives were consistent with victims being unrestrained. Nearly three-fourths (74%) of victims were hospitalized and 26% required ICU care, one-half (53%) of these being children.

Conclusions

Although ROVs have ROPs, lack of helmet and safety belt use are reducing their benefit. Youth are a large proportion of those injured in ROV crashes, often while driving despite vehicle operation recommended only for those ≥16 years old. Increased public education is needed regarding proper safety measures while operating and riding ROVs.
5-year efficacy of all surface laser ablation with cross-linking (ASLA-XTRA) for the treatment of myopia
Authors: Aslanides Ioannis M. , Hafezi Farhad , Chen Shihao , Mukherjee Hatch , Selimis Vasileios , Maragkos Ilias , Lu Nanji , Kymionis George
Published: June 2020

Background

The purpose of our study is to examine the long (5-year) efficacy of the all surface laser ablation (ASLA) combined with accelerated cross-linking (CXL) for the treatment of myopia without the use of mitomycin-C (MMC).

Methods

This retrospective study consisted of 202 eyes of 118 myopic (SD: 2.41, range: − 1.50 to − 12.75 D) patients (44 males, 74 females). Mean age was 28.50 years (SD: 6.45, range: 18 to 51 years) that underwent ASLA with accelerated CXL for the treatment of their myopia.

Results

The patients underwent routine postoperative assessment on the 1st, 3rd, 7th day and in the 1st, 3rd, 6th and 12th month, 30th month (±6 months), 4th and 5th year. The mean spherical equivalent (SEq) refractive error changed from − 6.41 ± 2.41 D preoperatively to − 0.02 ± 0.53 D at 5 years postoperatively. The haze score was 0.18, 0.25 and 0.28 at 1, 3 and 6 months postoperatively. At 12 months after the treatment, no eyes had significant corneal haze and in all the following postoperative time intervals the haze traces were gone.

Conclusion

ASLA combined with accelerated CXL (ASLA-XTRA) appears to be safe, efficacious and offering very good refractive results. The potential additional benefits of this modality are the stabilizing effect of the refraction and its sterilization effect on the treated cornea without the potential side effects of MMC.
Shipping and the Paris climate agreement: a focus on committed emissions
Authors: Bullock Simon , Mason James , Broderick John , Larkin Alice
Published: June 2020

The concept of “committed emissions” allows us to understand what proportion of the Paris-constrained and rapidly diminishing global carbon dioxide (CO2) budget is potentially taken up by existing infrastructure. Here, this concept is applied to international shipping, where long-lived assets increase the likelihood for high levels of committed emissions. To date, committed emissions studies have focussed predominantly on the power sector, or on global analyses in which shipping is a small element, with assumptions of asset lifetimes extrapolated from other transport modes. This study analyses new CO2, ship age and scrappage datasets covering the 11,000 ships included in the European Union’s new emissions monitoring scheme (EU MRV), to deliver original insights on the speed at which new and existing shipping infrastructure must be decarbonised. These results, using ship-specific assumptions on asset lifetimes, show higher committed emissions for shipping than previous estimates based on asset lifetimes similar to the road transport sector. The estimated baseline committed emissions value is equivalent to 85–212% of the carbon budget for 1.5 °C that is available for these EU MRV ships, with the central case exceeding the available carbon budget. The sector does, however, have significant potential to reduce this committed emissions figure without premature scrappage through a combination of slow speeds, operational and technical efficiency measures, and the timely retrofitting of ships to use zero-carbon fuels. Here, it is shown that if mitigation measures are applied comprehensively through strong and rapid policy implementation in the 2020s, and if zero-carbon ships are deployed rapidly from 2030, it is still possible for the ships in the EU MRV system to stay within 1.5 °C carbon budgets. Alongside this, as there are wide variations between and within ship types, this new analysis sheds light on opportunities for decision-makers to tailor policy interventions to deliver more effective CO2 mitigation. Delays to appropriately stringent policy implementation would mean additional measures, such as premature scrappage or curbing the growth in shipping tonne-km, become necessary to meet the Paris climate goals.
Mapping water-abundant zones using transient electromagnetic and seismic methods when tunneling through fractured granite in the Qinling Mountains, China
Authors: Liu Bin , Fan Kerui , Nie Lichao , Li Xiu , Liu Fusheng , Li Limin , Wang Jiansen , Sun Huaifeng , Chen Lei
Published: June 2020

Severe water inrush currently halts the excavation of the Qinling Water Transportation Tunnel and has even stopped tunneling. Based on the geologic conditions of the construction area, the source of water inrush is abundant groundwater in fractured granite. To accurately predict water inrush, we must know the location, geometry, and boundary information of water-abundant zones before excavation. We have developed a field study of integrated seismic and transient electromagnetic (TEM) applications to map the water-abundant zones ahead of the tunnel face. Before the in-tunnel survey, numerical experiments based on excavation and drilling records verified the feasibility of our scheme. To reveal the fractured zones that may be filled with groundwater, an equitraveltime plane algorithm was used in the seismic data processing. Then, the TEM apparent resistivity was calculated to investigate the water-bearing condition of the fractured zones. To detect the water-abundant zone boundaries, we conducted migration imaging of the TEM pseudowavefield that was extracted from the measured TEM signals. A correlation stacking process to extract the TEM pseudowavefield was used to mitigate the ill-posed effect in the inverse wavefield transformation and obtain boundary information of the water-abundant zones. As expected, the results revealed the depth and geometry of the front and rear boundaries of two water-abundant zones 30 m ahead of the tunnel face, which is consistent with drilling and excavation records after the survey. The results of our case study indicate that the integration of seismic imaging, apparent resistivity imaging, and TEM pseudowavefield migration is an efficient and cost-effective method to provide the location, geometry, and boundary information of water-abundant zones.
Creating probabilistic 3D models of lithofluid facies using machine-learning algorithms
Authors: Keynejad Saba , Sbar Marc L. , Johnson Roy A.
Published: June 2020

Mapping facies variations is a fundamental element in the study of reservoir characteristics. From identifying a pay zone to estimating the reservoir capacity, a hydrocarbon field’s development plan depends to a great extent on a reliable model of lithofacies and fluid content variations throughout the reservoir. The starting point usually is creating 1D facies models based on core samples and drilling reports at each well location. Sparse well locations and the inherent heterogeneity in the reservoir properties make it essential to incorporate the resultant 1D models into a 3D model of facies distribution that includes information about the probability of their occurrence. New techniques using machine learning (ML) to build 3D lithofluid facies (LFF) models can incorporate the prediction of different lithofacies regarding their potential hydrocarbon content, along with the uncertainties of the prediction. We have applied a fuzzy inference system, as an expert-oriented approach, and two separate ML algorithms, to different seismic and elastic attributes to model the LFF classes within the Heidrun oil and gas field. The results, compared with the test wells, show that ML methods could successfully predict the distribution of gas and oil sands within the field, in very good agreement with the known fluid contact intervals. Moreover, the predictions of shale and brine sands vary depending on the method but also are consistent with our knowledge of this field. Comparison between the results confirms the higher reliability of ML methods. Importantly, ML methods provide a better way of investigating and quantifying the uncertainty of the predictions. Implementing ML algorithms in reservoir characterization reduces the risk of drilling unnecessary wells due to false discoveries and can lead to more economical development of hydrocarbon resources.
Unveiling the 3D undercover structure of a Precambrian intrusive complex by integrating airborne magnetic and gravity gradient data into 3D quasi-geology model building
Authors: Sun Jiajia , Melo Aline Tavares , Kim Jae Deok , Wei Xiaolong
Published: June 2020

Mineral exploration under a thick sedimentary cover naturally relies on geophysical methods. We have used high-resolution airborne magnetic and gravity gradient data over northeast Iowa to characterize the geology of the concealed Precambrian rocks and evaluate the prospectivity of mineral deposits. Previous researchers have interpreted the magnetic and gravity gradient data in the form of a 2D geologic map of the Precambrian basement rocks, which provides important geophysical constraints on the geologic history and mineral potentials over the Decorah area located in the northeast of Iowa. However, their interpretations are based on 2D data maps and are limited to the two horizontal dimensions. To fully tap into the rich information contained in the high-resolution airborne geophysical data, and to further our understanding of the undercover geology, we have performed separate and joint inversions of magnetic and gravity gradient data to obtain 3D density contrast models and 3D susceptibility models, based on which we carried out geology differentiation. Based on separately inverted physical property values, we have identified 10 geologic units and their spatial distributions in 3D which are all summarized in a 3D quasi-geology model. The extension of 2D geologic interpretation to 3D allows for the discovery of four previously unidentified geologic units, a more detailed classification of the Yavapai country rock, and the identification of the highly anomalous core of the mafic intrusions. Joint inversion allows for the classification of a few geologic units further into several subclasses. We have demonstrated the added value of the construction of a 3D quasi-geology model based on 3D separate and joint inversions.
Serum Profile of microRNAs Linked to Bone Metabolism During Sequential Treatment for Postmenopausal Osteoporosis
Authors: Yavropoulou Maria P , Anastasilakis Athanasios D , Makras Polyzois , Papatheodorou Athanasios , Rauner Martina , Hofbauer Lorenz C , Tsourdi Elena
Published: June 2020

Context

Serum expression of microRNAs (miRs) related to bone metabolism is affected by antiosteoporotic treatment.

Objective

To investigate the effect of sequential treatments on miR expression in postmenopausal women with osteoporosis.

Design

Observational, open label, nonrandomized clinical trial.

Setting

A single-center outpatient clinic.

Patients and Interventions

Denosumab (Dmab) was administered for 12 months in 37 women who were treatment-naïve (naïve group) (n = 11) or previously treated with teriparatide (TPTD group) (n = 20) or zoledronate (ZOL group) (n = 6).

Main Outcome Measures

Relative serum expression of miRs linked to bone metabolism at 3 and 6 months of Dmab treatment.

Results

Baseline relative expression of miR-21a-5p, miR-23a-3p, miR-29a-3p, and miR-338-3p was higher in the TPTD group, while the relative expression of miR-21a-5p was lower in the ZOL group compared to the naïve group. Dmab decreased the relative expression of miR-21a-5p at 3 months (fold change [FC] 0.43, P < 0.001) and 6 months (FC 0.34, P < 0.001), and miR-338-3p and miR-2861 at 6 months (FC 0.31, P = 0.041; FC 0.52, P = 0.016, respectively) in the whole cohort. In subgroup analyses, Dmab decreased the relative expression of miR-21a-5p, miR-29a-3p, miR-338-3p, and miR-2861 at 3 months (FC 0.13, P < 0.001; FC 0.68, P = 0.044; FC 0.46, P = 0.012; and FC 0.16, P < 0.001, respectively) and 6 months (FC 0.1, P < 0.001; FC 0.52, P < 0.001; FC 0.04, P = 0.006; and FC 0.2, P < 0.001, respectively) only within the TPTD group.

Conclusions

TPTD treatment potentially affects the expression of the pro-osteoclastogenic miR-21a-5p and miRs related to the expression of osteoblastic genes RUNX2 (miR23a-3p), COL1 (miR-29a-3p), and HDAC5 (miR-2861), while sequential treatment with Dmab acts in the opposite direction.
Representing the Planet: Affect, Scale, and Utopia
Authors: Sergeant David
Published: June 2020

The discourses of planetarity and globalization are both governed by the relationship between the maximal scale of the world and the subsidiary scalar levels that constitute it. However, if in globalization those subsidiary levels are envisioned as converging on a homogenous whole, in planetarity the aim is to maintain them in a dialogic relationality. On the face of it, such a recalibration seems relatively straightforward. However, the three novels discussed in this essay suggest that the retention of the maximal scale as a constituting frame for representation risks forestalling any attempt to move beyond the paradigms of globalization. In both Doris Lessing's The Four-Gated City (1969) and Ben Lerner's 10:04 (2015), the relationship between parts and whole takes shape via the medium of affect, as the defining characteristic of the part becomes a desire for the whole that is seemingly destined to extinguish it. Consequently, both novels turn to a formal modeling in which individual and collective can supposedly blend without either suffering reduction—a maneuver also characteristic of many theoretical discussions of planetarity. Kim Stanley Robinson's Aurora (2015), in contrast, self-consciously repudiates the possibility of representing the maximal scale, instead prioritizing narrative over the kinds of formal modeling seen in the other texts. This point of difference allows the periodization entailed by the planetary turn to engage with the work of that preeminent theorist of periodization, Fredric Jameson: in particular, with his account of the relationship between spatiality, temporality, and the utopian impulse.
Ralph Ellison's Contemporaneity
Authors: Persson Torleif
Published: June 2020

This article begins by noting that recent debates about the relevance of Ralph Ellison's Invisible Man to contemporary American culture enact an opposition between historicism (the idea that the novel is a Jim Crow artifact) and universalism (the idea that it transcends the circumstances of its production). The author then argues that Ellison's novel models a contemporaneity that cannot be equated to either the assertion or disavowal of contemporaneousness. At the heart of this account stands the narrator's sense that he “must emerge,” which follows from his perception that he has failed to communicate the nature of his invisibility to his reader, and that his act of writing has therefore disarmed him. The article shows that the narrator's emergence—an event that is necessitated by the narrative but which the narrative, by the very logic of that necessity, cannot itself contain—constitutes the hinge between the textual temporality of his underground existence and the social temporality that abuts it. As such, it offers the possibility that these two temporalities—which may be thought of as referring to the temporality of writing and the temporality of reading, respectively—may be linked, and that this linkage could lead to forms of recognition that appear only at the limit of narrative form.
Transcriptional repression of Myc underlies the tumour suppressor function of AGO1 in Drosophila
Authors: Zaytseva Olga , Mitchell Naomi C. , Guo Linna , Marshall Owen J. , Parsons Linda M. , Hannan Ross D. , Levens David L. , Quinn Leonie M.
Published: June 2020

Here, we report novel tumour suppressor activity for the Drosophila Argonaute family RNA-binding protein AGO1, a component of the miRNA-dependent RNA-induced silencing complex (RISC). The mechanism for growth inhibition does not, however, involve canonical roles as part of the RISC; rather, AGO1 controls cell and tissue growth by functioning as a direct transcriptional repressor of the master regulator of growth, Myc. AGO1 depletion in wing imaginal discs drives a significant increase in ribosome biogenesis, nucleolar expansion and cell growth in a manner dependent on Myc abundance. Moreover, increased Myc promoter activity and elevated Myc mRNA in AGO1-depleted animals requires RNA polymerase II transcription. Further support for transcriptional AGO1 functions is provided by physical interaction with the RNA polymerase II transcriptional machinery (chromatin remodelling factors and Mediator Complex), punctate nuclear localisation in euchromatic regions and overlap with Polycomb Group transcriptional silencing loci. Moreover, significant AGO1 enrichment is observed on the Myc promoter and AGO1 interacts with the Myc transcriptional activator Psi. Together, our data show that Drosophila AGO1 functions outside of the RISC to repress Myc transcription and inhibit developmental cell and tissue growth.

This article has an associated ‘The people behind the papers’ interview.
How do hoverflies use their righting reflex?
Authors: Verbe Anna , Varennes Léandre P. , Vercher Jean-Louis , Viollet Stéphane
Published: June 2020

When taking off from a sloping surface, flies have to reorient themselves dorsoventrally and stabilize their body by actively controlling their flapping wings. We have observed that the righting is achieved solely by performing a rolling manoeuvre. How flies manage to do this has not yet been elucidated. It was observed here for the first time that hoverflies’ reorientation is entirely achieved within 6 wingbeats (48.8ms) at angular roll velocities of up to 10×103 °/s and that the onset of their head rotation consistently follows that of their body rotation after a time-lag of 16ms. The insects’ body roll was found to be triggered by the asymmetric wing stroke amplitude, as expected. The righting process starts immediately with the first wingbeat and seems unlikely to depend on visual feedback. A dynamic model for the fly's righting reflex is presented, which accounts for the head/body movements and the time-lag recorded in these experiments. This model consists of a closed-loop control of the body roll, combined with a feedforward control of the head/body angle. During the righting manoeuvre, a strong coupling seems to exist between the activation of the halteres (which measure the body's angular speed) and the gaze stabilization reflex. These findings again confirm the fundamental role played by the halteres in both body and head stabilisation processes.