First metals discovery and development the sacral component phenomenon

This article is accentuated on the civilizational significance of the first industrial metals discovery, it reveals the prerequisites for the development of ores and the main stages of metals mastering connected with centuries-old experience of the previous mining activities of mankind. The authors suggest the hypothesis that the metallurgy was born in the depths of sustainable communities of archaic miners, which were motivated by not only utilitarian but also sacral factors. A new hypothesis is examined in comparison to the established versions of accidental discovery of metals

Shielded development of bottom gas hydrates

Purpose. The research aims to show the system features of the existing development methods, which create significant risks of investment in the production of methane gas hydrates, as well as to disclose a new way and conceptual approach to the shielded development of methanohydrates. Methods. Comparative technical and economic analysis of mining methods, constructive and technological justifications. Findings. Reduction of risks and a significant reduction in the means of extraction can be achieved by replacing local impacts on the productive seam by forming a vast zone of simultaneous dissociation of the gas hydrate deposit and controlled withdrawal of the produced gas into the water space shielded by gas gathering shells. Originality. The research provides for realization of the idea suggesting simultaneous dissociation of large areas of the gas hydrate deposit, management of the targeted process of methane gas hydrates penetration into the water space and its accumulation under the extensive gas gathering shield, wherefrom it is removed by the bottom pipe transport. Practical implications. The proposed concept and a new method for shielded development of bottom gas hydrates substantiate technological stages and constructive elements of its implementation.Мета. Показати системні особливості існуючих способів розробки, які створюють значні ризики інвестицій у видобуток метану газогідратів. Розкрити новий спосіб і концептуальний підхід до екранованої розробки метаногідратів. Методика. Порівняльний техніко-економічний аналіз способів видобутку, конструктивні й технологічні обґрунтування. Результати. Зменшення ризиків і значне скорочення коштів видобутку може бути досягнете заміною локальних впливів на продуктивний пласт формуванням розлогої зони одночасної дисоціації газогідратного покладу й керованим виведенням отриманого газу у водний простір, екранований газозбірними оболонками. Наукова новизна. Реалізується концепція одночасної дисоціації великих площ газогідратного покладу, управління цілеспрямованим процесом потрапляння вивільненого метану газогідратів у водний простір і накопичення його під розлогим газозбірним екраном, з якого він відводиться донним трубним транспортом. Практична значимість. Запропонована концепція й новий спосіб екранованої розробки донних газогідратів, обґрунтовані технологічні етапи й конструктивні елементи його здійснення.Цель. Показать системные особенности существующих способов разработки, которые создают значительные риски инвестиций в добычу метана газогидратов. Раскрыть новый способ и концептуальный подход к экранированной разработки метаногидратов. Методика. Сравнительный технико-экономический анализ способов добычи, конструктивные и технологические обоснования. Результаты. Уменьшение рисков и значительное сокращение средств добычи может быть достигнуто заменой локальных воздействий на продуктивный пласт формированием обширной зоны одновременной диссоциации газогидратной залежи и управляемым выводом полученного газа в водное пространство, экранированный газосборными оболочками. Научная новизна. Реализуется концепция одновременной диссоциации больших площадей газогидратной залежи, управления целенаправленным процессом попадания освобожденного метана газогидратов в водное пространство и накопления его под раскидистым газосборным экраном, с которого он отводится донным трубным транспортом. Практическая значимость. Предложенная концепция и новый способ экранированной разработки донных газогидратов, обоснованные технологические этапы и конструктивные элементы его осуществления.Автори вдячні авторам колективної монографії “Газогідрати. Гідратоутворення та основи розробки газових гідратів” (зокрема В.І. Бондаренку, О.Ю. Витязю, М.Л. Зоценку, К.С. Сай, Е.О. Максимовій), яка надихнула їх на пошуки нових шляхів освоєння газогідратних родовищ

Feasibility of undertaking off-site infant eye-tracking assessments of neuro-cognitive functioning in early-intervention centres

Recent work suggests that differences in functional brain development are already identifiable in 6- to 9-month-old infants from low socio-economic status (SES) backgrounds. Investigation of early SES-related differences in neuro-cognitive functioning requires the recruitment of large and diverse samples of infants, yet it is often difficult to persuade low-SES parents to come to a university setting. One solution is to recruit infants through early intervention children’s centres (CCs). These are often located in areas of high relative deprivation to support young children. Given the increasing portability of eye-tracking equipment, assessment of large clusters of infants could be undertaken in centres by suitably trained early intervention staff. Here we report on a study involving 174 infants and their parents, carried out in partnership with CCs, exploring the feasibility of this approach, We report the processes of setting up the project and participant recruitment. We report the diversity of sample obtained on the engagement of CC staff in training and the process of assessment itself. We report the quality of the data obtained, and the levels of engagement of parents, and infants. We conclude that this approach has great potential for recruiting large and diverse samples worldwide, provides sufficiently reliable data, and is engaging to staff, parents and infants

Morphological model for underground crossings of water objects

The construction of morphological model is considered for undesirable events regarding urban objects, as well as the consequences of such events, including interruption of operation, feasibility and time of restoration, material damage and casualties, ecological risks. Using this model, two-stage modified morphological analysis was conducted for two types of objects: pipe and tunnel depressed sewers. The results of comparison for depressed sewer crossings using the developed model are demonstrated both for the whole multitude of potential undesirable events and for the specific scenarios of sabotage, landslide, operational damage. The advantage of a tunneled depressed sewer over a pipe one is justified from the standpoint of minimization of technogenic and ecological risks of sewage draining

Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla

<p>Abstract</p> <p>Background</p> <p>Omptins are a family of outer membrane proteases that have spread by horizontal gene transfer in Gram-negative bacteria that infect vertebrates or plants. Despite structural similarity, the molecular functions of omptins differ in a manner that reflects the life style of their host bacteria. To simulate the molecular adaptation of omptins, we applied site-specific mutagenesis to make Epo of the plant pathogenic <it>Erwinia pyrifoliae </it>exhibit virulence-associated functions of its close homolog, the plasminogen activator Pla of <it>Yersinia pestis</it>. We addressed three virulence-associated functions exhibited by Pla, i.e., proteolytic activation of plasminogen, proteolytic degradation of serine protease inhibitors, and invasion into human cells.</p> <p>Results</p> <p>Pla and Epo expressed in <it>Escherichia coli </it>are both functional endopeptidases and cleave human serine protease inhibitors, but Epo failed to activate plasminogen and to mediate invasion into a human endothelial-like cell line. Swapping of ten amino acid residues at two surface loops of Pla and Epo introduced plasminogen activation capacity in Epo and inactivated the function in Pla. We also compared the structure of Pla and the modeled structure of Epo to analyze the structural variations that could rationalize the different proteolytic activities. Epo-expressing bacteria managed to invade human cells only after all extramembranous residues that differ between Pla and Epo and the first transmembrane β-strand had been changed.</p> <p>Conclusions</p> <p>We describe molecular adaptation of a protease from an environmental setting towards a virulence factor detrimental for humans. Our results stress the evolvability of bacterial β-barrel surface structures and the environment as a source of progenitor virulence molecules of human pathogens.</p

Cyber Security: China and Russia\u27s Erosion of 21st Century United States\u27 Hegemony

With Russia and China emerging as challengers to U.S. hegemony, the use of cyber warfare could tilt the current balance of power in either of their favors. Using various methods, hackers can acquire sensitive information and destroy online infrastructures. In the development of cyber warfare, China has become a seasoned veteran with computer virus operations dating back to 199714. Russia has emerged as a cyber aggressor, as seen in Russia’s cyber attacks on several countries in the last decade. This paper argues that, with the growth of foreign cyber technology, the probability of cyberspace being used as a military front by state or non-state actors against the United States increases

Effects of an 18-week exercise programme started early during breast cancer treatment: a randomised controlled trial

Background: Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue. Methods: This multi-centre controlled trial randomly assigned 204 breast cancer patients to usual care (n = 102) or supervised aerobic and resistance exercise (n = 102). By design, all patients received chemotherapy between baseline and 18 weeks. Fatigue (i.e., primary outcome at 18 weeks), quality of life, anxiety, depression, and physical fitness were measured at 18 and 36 weeks. Results: Intention-to-treat mixed linear model analyses showed that physical fatigue increased significantly less during cancer treatment in the intervention group compared to control (mean between-group differences at 18 weeks: -1.3; 95 % CI -2.5 to -0.1; effect size -0.30). Results for general fatigue were comparable but did not reach statistical significance (-1.0, 95% CI -2.1; 0.1; effect size -0.23). At 18 weeks, submaximal cardiorespiratory fitness and several muscle strength tests (leg extension and flexion) were significantly higher in the intervention group compared to control, whereas peak oxygen uptake did not differ between groups. At 36 weeks these differences were no longer statistically significant. Quality of life outcomes favoured the exercise group but were not significantly different between groups. Conclusions: A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength. Exercise early during treatment of breast cancer can be recommended. At 36 weeks, these effects were no longer statistically significant. This might have been caused by the control participants' high physical activity levels during follow-up

Effectiveness of an e-health tennis-specific injury prevention programme : randomised controlled trial in adult recreational tennis players

BACKGROUND : Despite reported injury rates of up to 3 per 1000 hours exposure, there are no evidence-based prevention programmes in tennis. PURPOSE : To evaluate the effectiveness of an e-health prevention programme for reducing tennis injury prevalence. STUDY DESIGN : Two-arm, researcher-blinded randomised controlled trial. METHODS : Adult tennis players of all playing levels were randomised in an unsupervised programme lasting 12 weeks (TennisReady group or control group). The primary outcome was the overall injury prevalence over a 16-week period, measured at 2 weekly intervals with the Oslo Sports and Trauma Research Centre questionnaire. Estimates for the primary outcome and associated 95% CIs were obtained using generalised estimating equation models. Secondary outcome scores included prevalence of substantial injuries, overall incidence, adherence and time-loss injuries. RESULTS : A total of 579 (83%) (TennisReady n=286, control n=293) participants were included in the primary analysis. The mean injury prevalence was 37% (95% CI 33% to 42%) in the TennisReady vs 38% (95% CI 34% to 42%) in the control group (adjusted p-value 0.93). The prevalence of substantial injuries was 11% (95% CI 9% to 14%) in the TennisReady vs 12% (95% CI 9% to 15%) in the control group (p value of 0.79). Analysis of the secondary outcome scores showed no difference between groups. The mean prevalence rates between high (8%) and low (92%) adherent groups were 32% (95% CI 23% to 44%) and 37% (95% CI 33% to 42%), respectively (p value 0.36). CONCLUSION : Providing an unsupervised e-health tennis-specific exercise programme did not reduce the injury rates and should not be implemented. TRIAL REGISTRATION NUMBER : NTR6443.http://bjsm.bmj.comhj2023Sports Medicin

The PRO-RCC study:a long-term PROspective Renal Cell Carcinoma cohort in the Netherlands, providing an infrastructure for ‘Trial within Cohorts’ study designs

BACKGROUND: Ongoing research in the field of both localized, locally advanced and metastatic renal cell carcinoma has resulted in the availability of multiple treatment options. Hence, many questions are still unanswered and await further research. A nationwide collaborative registry allows to collect corresponding data. For this purpose, the Dutch PROspective Renal Cell Carcinoma cohort (PRO-RCC) has been founded, for the prospective collection of long-term clinical data, patient reported outcome measures (PROMs) and patient reported experience measures (PREMs).METHODS: PRO-RCC is designed as a multicenter cohort for all Dutch patients with renal cell carcinoma (RCC). Recruitment will start in the Netherlands in 2023. Importantly, participants may also consent to participation in a 'Trial within cohorts' studies (TwiCs). The TwiCs design provides a method to perform (randomized) interventional studies within the registry. The clinical data collection is embedded in the Netherlands Cancer Registry (NCR). Next to the standardly available data on RCC, additional clinical data will be collected. PROMS entail Health-Related Quality of Life (HRQoL), symptom monitoring with optional ecological momentary assessment (EMA) of pain and fatigue, and optional return to work- and/or nutrition questionnaires. PREMS entail satisfaction with care. Both PROMS and PREMS are collected through the PROFILES registry and are accessible for the patient and the treating physician.TRIAL REGISTRATION: Ethical board approval has been obtained (2021_218) and the study has been registered at ClinicalTrials.gov (NCT05326620).DISCUSSION: PRO-RCC is a nationwide long-term cohort for the collection of real-world clinical data, PROMS and PREMS. By facilitating an infrastructure for the collection of prospective data on RCC, PRO-RCC will contribute to observational research in a real-world study population and prove effectiveness in daily clinical practice. The infrastructure of this cohort also enables that interventional studies can be conducted with the TwiCs design, without the disadvantages of classic RCTs such as slow patient accrual and risk of dropping out after randomization.</p

Differences in Trial and Real-world Populations in the Dutch Castration-resistant Prostate Cancer Registry

__Background:__ Trials in castration-resistant prostate cancer (CRPC) treatment have shown improved outcomes, including survival. However, as trial populations are selected, results may not be representative for the real-world population. The aim of this study was to assess the differences between patients treated in a clinical trial versus standard care during the course of CRPC in a real-world CRPC population. __Design, setting, and participants:__ Castration-resistant Prostate Cancer Registry is a population-based, observational, retrospective registry. CRPC patients from 20 hospitals in the Netherlands have been included from 2010 to 2013. __Outcome measurements and statistical analysis:__ Baseline characteristics, systemic treatment, and overall survival were the main outcomes. Descriptive statistics, multivariate Cox regression, and multiple imputations with the Monte Carlo Markov Chain method were used. __Results and limitations:__ In total, 1524 patients were enrolled of which 203 patients had participated in trials at any time. The median follow-up period was 23 mo. Patients in the trial group were significantly younger and had less comorbidities. Docetaxel treatment was more freque