Current National Research Articles

ОЦЕНКА СОРТООБРАЗЦОВ ЯРОВОЙ МЯГКОЙ ПШЕНИЦЫ ПО ПОКАЗАТЕЛЯМ КАЧЕСТВА ЗЕРНА В ИЗМЕНЯЮЩИХСЯ УСЛОВИЯХ СРЕДНЕВОЛЖСКОГО РЕГИОНА

The research was conducted in 2019-2021 in the forest-steppe zone of Samara region. The purpose of the research is to screen samples of the world collection of spring soft wheat according to grain quality indicators in the conditions of the Middle Volga region to identify sources valuable for breeding. The soil of the site is typical low-humus medium-sized light clay chernozem. Meteorological conditions differed by years and from the long-term norm, but were generally characterized as arid. The hydrothermal humidification coefficient was 0.48 in 2019, 0.52 in 2020, 0.39 in 2021, and 0.73 for many years. The object of research is 130 samples of different ecological and geographical origin, single repetition, standard - zoned variety Tulaykovskaya Nadezhda. Grain quality indicators were evaluated according to the methodology of the State Commission for Variety Testing and the current National standards of the Russian Federation. According to the results of the research, varieties of spring soft wheat with high values of quality indicators were identified. According to physical properties – grain nature (831...864 g/l) and vitreousness (80...89 %), the following varieties were distinguished: Kinelskaya Niva, Kinelskaya Yubileynaya, Kinelskaya 2020 (Kinel), Tulaykovskaya 116, Ekada 113 (Bezenchuk), Burlak, Ulyanovskaya 105 (Ulyanovsk), Saratovskaya 73, Saratovskaya 74, Liniya 666, Albidum 28 (Saratov), Orenburgskaya 23 (Orenburg), Stepnaya Volna (Altai region). The samples exceeded the standard by 1...34 g/l and 1...10%, respectively. According to technological properties, high protein content (17.40...20.56%) and gluten (40.13...49.26 %) were noted varietals: Kinelskaya 59, Erythrospermum 5289 (Kinel), Sibirskiy Alyans, Stepnaya Niva (Altai region), Novosibirskaya 15, Novosibirskaya 31, Novosibirskaya 41, Polyushko (Novosibirsk), Omskaya 37, Omskaya 38, OmGAU 100, Sigma (Omsk), Balkysh (Tatarstan), Nikon (Ulyanovsk), Gunner (Canada), Long Fu 13 (China), Digana (Switzerland). The excess over the standard was 1.88...5.04% and 4.13...13.26%, respectively. The selected cultivars are recommended to be used in the breeding process as parent forms to create varieties with high grain quality indicators.

Real-world evaluation of early remdesivir in high-risk COVID-19 outpatients during Omicron including BQ.1/BQ.1.1/XBB.1.5

BackgroundA trial performed among unvaccinated, high-risk outpatients with COVID-19 during the delta period showed remdesivir reduced hospitalization. We used our real-world data platform to determine the effectiveness of remdesivir on reducing 28-day hospitalization among outpatients with mild-moderate COVID-19 during an Omicron period including BQ.1/BQ.1.1/XBB.1.5.MethodsWe did a propensity-matched, retrospective cohort study of non-hospitalized adults with SARS-CoV-2 infection between April 7, 2022, and February 7, 2023. Electronic healthcare record data from a large health system in Colorado were linked to statewide vaccination and mortality data. We included patients with a positive SARS-CoV-2 test or outpatient remdesivir administration. Exclusion criteria were other SARS-CoV-2 treatments or positive SARS-CoV-2 test more than seven days before remdesivir. The primary outcome was all-cause hospitalization up to day 28. Secondary outcomes included 28-day COVID-related hospitalization and 28-day all-cause mortality.ResultsAmong 29,270 patients with SARS-CoV-2 infection, 1,252 remdesivir-treated patients were matched to 2,499 untreated patients. Remdesivir was associated with lower 28-day all-cause hospitalization (1.3% vs. 3.3%, adjusted hazard ratio (aHR) 0.39 [95% CI 0.23–0.67], p < 0.001) than no treatment. All-cause mortality at 28 days was numerically lower among remdesivir-treated patients (0.1% vs. 0.4%; aOR 0.32 [95% CI 0.03–1.40]). Similar benefit of RDV treatment on 28-day all-cause hospitalization was observed across Omicron periods, aOR (95% CI): BA.2/BA2.12.1 (0.77[0.19–2.41]), BA.4/5 (0.50[95% CI 0.50–1.01]), BQ.1/BQ.1.1/XBB.1.5 (0.21[95% CI 0.08–0.57].ConclusionAmong outpatients with SARS-CoV-2 during recent Omicron surges, remdesivir was associated with lower hospitalization than no treatment, supporting current National Institutes of Health Guidelines.

Forgotten responsibilities? Nordic truth commissions, Sámi history, and the difficulty of transnational perspectives on historical responsibility

The article studies the Norwegian, Finnish and Swedish truth commissions dealing with state-Sámi (an indigenous population living in northern Scandinavia, Finland and north-western Russia) relations through the concept of transnational historical justice. The fact that three separate commissions are studying the history of the Sámi has been criticized by earlier researchers, but never from the perspective of intergenerational, and more specifically historical justice. Our study of the mandate documents and the report of the Norwegian commission (the only one published in the time of writing of this article) points to constructive ways forward that could acknowledge and better embrace the transnational character of Sámi history, especially in terms of historical justice. We also study in what way the Norwegian commission worked within and stretched the framework set by the mandate document. Our conclusion is that the lack of transnationalism in the mandate and work of the commissions leads to historical Sámi individuals and groups being forgotten. These are historical groups and individuals whose existence does not fit in neatly in the presentist perspective of the commissions, projecting the current nation state borders back in time. For this reason, historical justice toward these groups is also a forgotten issue in the mandate and work of the commissions.

Profiles of sulfonylurea use in Diabetes Mellitus type 2: an analysis of clinical practice over the last 10 years

AimsDescribing the evolution over time in the use of sulfonylureas (SUs) and the characteristics of patients at first prescription and at interruption of treatment with SUs. MethodsRetrospective evaluation of data from the Italian Association of Diabetologists (AMD) Annals registry (2010–2020), about T2D patients who started treatment with SUs. The longitudinal probability of remaining on SUs was estimated by Kaplan Meier survival curves. ResultsSU prescription decreased from 30.7 % (2010) to 12.9 % (2020). Patients started on SU were 68.2 ± 11.2 years old, mostly males (55.5 %), with diabetes duration = 10.1 ± 8.3 years, BMI = 29.7 ± 5.5 kg/m2, and HbA1c = 8.3 ± 1.7 % [67 mmol/mol]. After one year, the probability of staying on SU was 85.4 %, 75.9 % after two years, 68.2 % after 3 years, 56.6 % after 5 years. Patients who discontinued SUs had higher BMI and HbA1c, were younger, more often males and treated with insulin. Over time, the percentage of subjects switched to metformin, DPP4i, SGLT2i, and GLP1RA increased, whereas use of glinides, glitazones, acarbose and insulin declined. ConclusionsThese data suggest a consensus, slowly, but increasingly aligning with the current National indications of dismissing SUs for the treatment of T2D. The new drugs for diabetes should represent a preferable choice in all patients who do not have specific contraindications.

Paving a Way for “TB Mukt Bharat”: A Snapshot of India's TB Elimination Program

AbstractTuberculosis (TB) remains a significant global health challenge, particularly in countries like India, where it is a leading cause of mortality. This article provides an overview of India's efforts to combat TB through its national TB programs, tracing their evolution from the National TB Program in 1962 to the current National TB Elimination Program (NTEP) launched in 2020. The NTEP aims to eliminate TB by ensuring universal access to high-quality diagnosis and treatment services. The program emphasizes prevention, detection, treatment, and capacity building, aligning with global initiatives like the World Health Organization's End TB Strategy. Key components of the NTEP include free diagnostic services, treatment regimens for drug-sensitive and drug-resistant TB, and TB preventive therapy. The program also includes robust patient support systems, such as incentive schemes and transport support, to improve treatment outcomes. Through these comprehensive strategies, India seeks to achieve its goal of a TB-free nation by 2025, aligning with global Sustainable Development Goals.

Decarbonisation at least cost: an analysis of the optimal portfolio of instruments

Purpose This paper aims to propose a methodology for assessing an optimal portfolio of investment instruments that minimise the social costs of decarbonising economic activity while improving the environmental objectives proposed in EU legislation. Design/methodology/approach The methodology defines the net social cost of decarbonisation related to a portfolio of four instruments: installation of solar PV and wind generation, thermal insulation of households and deployment of heat pumps. The social cost is minimised by restricting it to the minimum level of the targets proposed in the Spanish National Energy and Climate Plan to reduce greenhouse gas emissions, increase generation from renewable sources and reduce energy consumption. The empirical approach also includes differences between regions according to the expected effect for instruments. Findings The application of this methodology to the environmental objectives defined in the current Spanish National Energy and Climate Plan for 2030 concludes that it is clearly possible to reduce the social cost of decarbonisation while improving environmental performance through a reorientation of investment instruments. In this case, such a reorientation would be based on a minimisation of efforts in thermal insulation of households and a maximisation of measures aimed at the installation of heat pumps. Originality/value The paper proposes a novel methodology for a social cost assessment that improves the allocation of a portfolio of environmental instruments. This portfolio could be extended in further work to include instruments related to transport or support for industrial decarbonisation, such as the deployment of renewable hydrogen, among others.

The Role of Immunotherapy in the Management of Esophageal Cancer in Patients Treated with Neoadjuvant Chemoradiation: An Analysis of the National Cancer Database.

The current National Comprehensive Cancer Network advises neoadjuvant chemoradiotherapy followed by surgery for locally advanced cases of esophageal cancer. The role of immunotherapy in this context is under heavy investigation. Patients with esophageal adenocarcinoma were identified in the National Cancer Database (NCDB) from 2004 to 2019. Three groups were generated as follows: (a) no immunotherapy, (b) neoadjuvant immunotherapy, and (c) adjuvant immunotherapy. Overall survival was evaluated using the Kaplan-Meier method and Cox proportional hazard analysis, adjusting for previously described risk factors for mortality. Of the total 14,244 patients diagnosed with esophageal adenocarcinoma who received neoadjuvant chemoradiation, 14,065 patients did not receive immunotherapy, 110 received neoadjuvant immunotherapy, and 69 received adjuvant immunotherapy. When adjusting for established risk factors, adjuvant immunotherapy was associated with significantly improved survival compared to no immunotherapy and neoadjuvant immunotherapy during a median follow-up period of 35.2 months. No difference was noted among patients who received no immunotherapy vs. neoadjuvant immunotherapy in the same model. In this retrospective analysis of the NCDB, receiving adjuvant immunotherapy offered a significant survival advantage compared to no immunotherapy and neoadjuvant immunotherapy in the treatment of esophageal adenocarcinoma. The addition of neoadjuvant immunotherapy to patients treated with neoadjuvant chemoradiation did not improve survival in this cohort. Further studies are warranted to investigate the long-term outcomes of immunotherapy in esophageal cancer.

Efficacy, effectiveness and immunogenicity of reduced HPV vaccination schedules: A review of available evidence.

Current National Advisory Committee on Immunization (NACI) guidance recommends human papillomavirus (HPV) vaccines be administered as a two or three-dose schedule. Recently, several large clinical trials have reported the clinical benefit of a single HPV vaccine dose. As a result, the World Health Organization released updated guidance on HPV vaccines in 2022, recommending a two-dose schedule for individuals aged 9-20 years, and acknowledging the use of an alternative off-label single dose schedule. The objective of this overview is to provide a detailed account of the available evidence comparing HPV vaccination schedules, which was considered by NACI when updating recommendations on HPV vaccines. To identify relevant evidence, existing systematic reviews were leveraged where possible. Individual studies were critically appraised, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence. Available evidence suggests that a one, two, or three-dose HPV vaccine schedule may provide similar protection from HPV infection. While antibody levels against HPV vaccine types were statistically significantly lower with a single dose schedule compared to two or three doses, titres were sustained for up to 16 years. The clinical significance of lower antibody titres is unknown, as there is no established immunologic correlate of protection. While the available evidence on single-dose HPV vaccination schedules shows a one-dose schedule is highly effective, continued follow-up of single-dose cohorts will be critical to understanding the relative duration of protection for reduced dose schedules and informing future NACI guidance on HPV vaccines.

BSACI guidance for the implementation of Palforzia® peanut oral immunotherapy in the United Kingdom: A Delphi consensus study

AbstractBackgroundPalforzia® enables the safe and effective desensitisation of children with peanut allergy. The treatment pathway requires multiple visits for dose escalation, up‐dosing, monitoring of patients taking maintenance therapy and conversion onto daily real‐world peanut consumption. The demand for peanut immunotherapy outstrips current National Health Service (NHS) capacity and requires services to develop a national consensus on how best to offer Palforzia® in a safe and equitable manner. We undertook a Delphi consensus exercise to determine guidance statements for the implementation of Palforzia®‐based immunotherapy in the NHS.MethodsWe undertook focus groups with children and young people who had received peanut immunotherapy to assess what was important for them and their carers. Common themes from patients formed the basis of creating draft statements. A panel of 18 multi‐disciplinary professionals engaged in two rounds of anonymised voting to adapt the statements and score their importance. A final consensus workshop consolidated any variation in comments and scores to develop the final guidance statements.ResultsThe panel achieved consensus on 91% (29/32) of guidance statements, demonstrating strong consensus around pragmatic principles for assuring the integrity of consent, safety and conversion from Palforzia® to real‐world peanut products. The greatest amount of feedback was generated from three broad issues; (i) whether eligibility assessment should include compulsory peanut challenges and whether these should be designed to assess the threshold at which patients react to peanut, (ii) the governance processes to best ensure that patients' interests are prioritised and (iii) how to safely transition young people to other services, or discharge them, while they are taking daily peanut.ConclusionsThis consensus highlights the urgent need for the NHS to increase capacity for undertaking diagnostic food challenges as well as developing Palforzia® immunotherapy pathways. The voting panel agreed that families of peanut allergic children should be made aware of immunotherapy, that eligibility assessment should include how co‐morbid conditions are managed and that services should monitor for adverse effects. The finalised statements are now published online for clinical practice in the UK. These guidance statements will be adapted in the coming years as more evidence is published and as the international experience of peanut immunotherapy evolves.

A second hereditary cancer predisposition syndrome in a patient with lynch syndrome and three primary cancers

Current National Comprehensive Cancer Network ® (NCCN ®) guidelines for Colorectal Genetic/Familial High-Risk Assessment provide limited guidance for genetic testing for individuals with already diagnosed hereditary cancer conditions. We are presenting the case of a 36-year-old woman who was diagnosed with Lynch Syndrome at age 23 after genetic testing for a familial variant (c.283del) in the MLH1 gene. The patient had a previous history of Hodgkin Lymphoma at the time of familial variant testing, and she would later develop stage IIIa cecal adenocarcinoma at age 33 and metastatic papillary thyroid carcinoma at age 35. The patient’s family history included a first-degree relative who was diagnosed with colorectal cancer at age 39, multiple second-degree relatives with colorectal, endometrial, and stomach cancer, and third and fourth-degree relatives with breast cancer. In light of her personal and family history, a comprehensive cancer panel was recommended. This panel found a second hereditary cancer predisposition syndrome: a likely pathogenic variant (c. 349 A > G) in the CHEK2 gene. This specific CHEK2 variant was recently reported to confer a moderately increased risk for breast cancer. The discovery of this second cancer predisposition syndrome had important implications for the patient’s screening and risk management. While uncommon, the possibility of an individual having multiple cancer predisposition syndromes is important to consider when evaluating patients and families for hereditary cancer, even when a familial variant has been identified.

Realisation of the triple-point of Argon: comparison between two devices

A new cryostat for the realization of the triple-point of the argon (83.8058 K), a defining fixed point of the International Temperature Scale of 1990 (ITS-90), was acquired at Italian National Metrological Institute (INRiM). The new system, manufactured by Fluke, is intended to substitute the current National reference, a model developed at BNM-INM in the 1975. The main difference between the two system is in the way to control the temperature. In the BNM-INM device the temperature is controlled adjusting the pressure of liquid nitrogen bath, in the Fluke system instead, an electrical heater wrapped around the argon cell is used, following cryogenic practice. This paper describes the result of the direct comparison and shows typical phase transitions obtained with the two argon systems. Then, a complete uncertainty budget is evaluated for the new Fluke system and compared with the National standard.

Nationalism - News or Heritage

The text is based on several empirical studies dealing with the question – whether the current nationalism in Bulgaria (compared to other Balkan countries) is inherited from previous periods, i.e. – whether it is "immanently inherent" to the Bulgarian nation, or whether it is the result of specific conjunctures and is activated on specific occasions. The question is also examined – whether the motivation for nationalist mobilization is always due to "innate" or "inherited" nationalism, or whether it can be different – social, economic, political, seen as "purely" nationalist.

Impact of American Society of Breast Surgeons (ASBS) guidelines on genetic testing (GT) rates among patients with breast cancer (BC).

e22537 Background: Identifying patients with pathogenic germline genetic variants can inform clinical decision-making and risk assessment. Previous studies have suggested low rates of GT in BC patients overall and disproportionately lower rates of GT among black patients. This may be explained in part by clinicians failing to understand the current National Comprehensive Cancer Network (NCCN) GT guidelines, which are complex. In February 2019, the ASBS released updated guidelines recommending GT for all patients with a personal history of BC. The objective of this study was to evaluate the impact of the ASBS guideline change on GT utilization for all BC patients, and for black BC patients in particular. Methods: This retrospective cohort study included 4386 BC patients who were diagnosed and/or treated at the Siteman Cancer Center (SCC) in St. Louis, MO from January 1, 2017 to December 31, 2020. The pre-guideline period included those patients diagnosed between January 1, 2017 and July 25th, 2019 and the post-guideline period included those diagnosed between July 26, 2019 and December 31, 2020. Within the study period, Myriad Genetics was used almost exclusively for GT by breast oncologists and surgeons at SCC. Myriad data was queried to identify all BC patients at SCC with GT. Data including self-reported race/ethnicity, BC subtype (triple negative breast cancer (TNBC) vs other), insurance type (public vs private), and family history of BC (yes vs no) was collected from the electronic medical record (EMR) independently by authors. Multivariate logistic regression analyses and difference in difference (DiD) analyses were performed to compare GT rates pre- and post-guideline change. Results: There was no significant difference in the rate of GT among BC patients pre- vs post-guideline change (17% vs 14.8%, p = 0.05). Similarly, there was no significant difference in GT rates pre- vs post-guideline change for non-Hispanic black (NHB) (14.6% vs 13.1%) and non-Hispanic white (NHW) subgroups (17.8% vs 15.2%) using DiD analysis (p = 0.96). Patients with a family history of BC (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.17-1.69, p &lt; 0.01) and TNBC (OR 1.47, 95% CI 1.15-1.86, p &lt; 0.01) were more likely to receive GT. Patients aged greater than 50 years (OR 0.44, 95% CI 0.37-0.54, p &lt; 0.001) and those with public insurance were less likely to receive GT (OR 0.82, 95% CI 0.67-1.02, p = 0.07). DiD analyses identified no significant differences pre- and post-guideline change for these subgroups. Conclusions: Despite the recent broadening of GT guidelines by ASBS, GT rates remain low among patients with BC. We found no significant impact of the guideline change on the uptake of GT among our population of BC patients overall or by race/ethnicity, family history, BC subtype, age, or insurance status. Multidisciplinary efforts are needed to improve guideline implementation and uptake of GT in BC patients.

Marine predators segregate interspecifically by space and time in a sheltered coastal bay.

Marine predators are vital to the healthy functioning of coastal ecosystems, but to understand their roles, it is necessary to elucidate their movement ecology, particularly in relation to one another. A decade's worth of acoustic telemetry data (2011-2020) from Algoa Bay, South Africa, was investigated to determine how two mesopredatory species (teleosts: dusky kob Argyrosomus japonicus, n = 11, and leervis Lichia amia, n = 16) and two top predatory species (sharks: ragged-tooth sharks Carcharias taurus, n = 45, and white sharks Carcharodon carcharias, n = 31) used and shared this bay ecosystem. Multi-annual seasonal fidelity to the bay was exhibited by all species, but differences in residency were observed among species. Similarly, species used space in the bay differently-the teleosts moved less and had movements restricted to the central and western inshore regions of the bay. Conversely, the sharks roamed more, but detections were concentrated in the western part of the bay for C. taurus and in the eastern part of the bay for C. carcharias. Social network analysis showed that species segregated in space and time on a fine scale. However, there was some interaction observed between C. taurus, L. amia, and A. japonicus, but to varying degrees. This is likely because of strong habitat preferences exhibited by each species and predator-prey relationships between these predatory guilds. Results highlight that the sheltered marine Algoa Bay is a resource-rich environment, supporting multiple predators with different hunting strategies albeit similar prey preferences. Finally, these species are likely afforded some protection by the current Greater Addo Elephant National Park Marine Protected Area in the bay but are vulnerable to fishing pressure when they leave this ecosystem.

An exploration into the nature and extent of diversity within history classrooms in Kent

AbstractEver since the 1970s, politicised debates have raged over the teaching of history, dubbed the ‘history wars’. These debates continue to impact primary and secondary teachers' choices of history curriculum foci to this day. This research aimed to discover history teachers' understanding of how to develop diversity within their history curricula and to discuss the possible pitfalls of their decision making. We set out to answer the following questions: (1) How do history teachers and subject leads understand the concept of diversification within the history curriculum? (2) How are schools approaching the diversification of their history curriculum? We carried out this project collaboratively with 10 history teachers and subject leads from four primary and three secondary schools in Kent, South‐East England. As a result, we have developed a model of ‘school diversification’ and make several recommendations to support the development and teaching of increasingly diverse history lessons, within the confines of the current National Curriculum. This project adds to the literature by privileging the voice of teachers within classrooms and including collaboration between teachers of all phases within history education in English schools to support the development of diversity within their practice.

Open energy system modelling for low-emission hydrogen roadmap planning: The case of Colombia

Climate change is driving the need for new approaches to energy production and utilization globally, contributing to the mitigation of greenhouse gas (GHG) emissions. Low-emission hydrogen is recognized as a key energy vector for decarbonization, and numerous countries are currently evaluating strategies and roadmaps for its integration. Colombia, with its abundant renewable resources, is poised as a potential player in hydrogen production. This study presents a techno-economic assessment of hydrogen pathways and their cross-sectoral interactions within the Colombian energy system. By employing an open energy system optimization framework (OSeMOSYS), we modelled a detailed supply-demand hydrogen chain and analysed a series of scenarios from 2021 to 2050, including a sensitivity analysis. Our results show that hydrogen pathways will require 2–6.4 Mt/year in hydrogen production, 8–27 GW in new installed capacity, and US$50–80 billion in investments, with favourable impacts in GHG mitigation, energy imports, and socioeconomic benefits. We use these findings to suggest an update to the targets of the current National Hydrogen Roadmap focused on a higher ambition to deploy a full hydrogen economy. Our open methodology provides a valuable tool for conducting further assessments in developing countries interested in defining low-emission hydrogen roadmaps.

Co-occurring EGFR p.E709X Mutation Mediates Primary Resistance to the Third-Generation EGFR-TKIs in EGFR p.G719X-Mutant Patients with Advanced NSCLC.

The current National Comprehensive Cancer Network (NCCN) guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in the absence of head-to-head trials comparing afatinib with osimertinib in EGFR p.G719X-mutant patients, it is unclear which regimen is the preferred treatment option. A large cohort of 4,228 treatment-naïve patients with lung cancer who underwent targeted next-generation sequencing (NGS) testing was screened for EGFR p.G719X mutation. A multicenter cohort involving 68 EGFR p.G719X-mutant patients with advanced NSCLC and NGS profiling was retrospectively enrolled to evaluate clinical responses to afatinib (n = 37) and the third-generation EGFR-TKIs (n = 31). Ba/F3 cells stably expressing the EGFR p.G719A mutation were created to investigate the response to EGFR-TKIs in vitro. Concurrent EGFR p.E709X mutations, being the most frequent co-occurring EGFR mutation in EGFR p.G719X-mutant NSCLC (∼30%), exerted a detrimental effect on outcomes in patients treated with third-generation EGFR-TKI [G719X/E709X vs. G719X; objective response rate (ORR): 0.00% vs. 47.62%, P < 0.001; mPFS: 7.18 vs. 14.2 months, P = 0.04, respectively]. Conversely, no significant difference was found in the treatment efficacy of afatinib between EGFR p.G719X/E709X and EGFR p.G719X patients (G719X/E709X vs. G719X; ORR: 71.43% vs. 56.67%, P = 0.99; mPFS: 14.7 vs. 15.8 months, P = 0.69, respectively). In vitro experiments elucidated a resistant drug sensitivity and poor inhibition of EGFR phosphorylation in Ba/F3 cells expressing EGFR p.G719A/E709K mutation upon the third-generation EGFR-TKI treatment. Co-occurring EGFR p.E709X mutation mediated primary resistance to the third-generation EGFR-TKIs in EGFR p.G719X-mutant patients but remained sensitive to afatinib. A personalized treatment strategy should be undertaken based on the coexisting EGFR p.E709X mutation status.

The Concept of Total Defense Options of the Republic of Serbia

With the current National Security Strategy, the Republic of Serbia has adopted the total defense concept to respond to the proclaimed military neutrality. The decision in question, among other things, affects the direction of the overall defense capability of the state and society as a whole. There are several fundamentally important issues in which a choice must be made. One of the essential questions is which tasks are best performed under the auspices of the Armed Forces and which should be assigned to civilian actors. In other words, a clear division of responsibilities between the civilian and Armed Forces involved in total defense is necessary. On the other hand, the Republic of Serbia has a negative legacy that dates back to the conflict on the territory of the former state, as well as certain decisions that contradict the decision to develop a total defense and confident decisions that have a direct impact on the adopted concept of national defense. The paper presents the possible content of the total defense of the Republic of Serbia through the analysis of the concept on the examples of individual countries. In this connection, it should be noted that the Defense Strategy of the Republic of Serbia had to expand the content of the total defense concept. This is necessary not only for a more complete understanding but also for the fact that the provisions of the Strategy are further operationalized through documents of lower generality.

Safer and more efficient vital signs monitoring protocols to identify the deteriorating patients in the general hospital ward: an observational study.

The frequency at which patients should have their vital signs (e.g. blood pressure, pulse, oxygen saturation) measured on hospital wards is currently unknown. Current National Health Service monitoring protocols are based on expert opinion but supported by little empirical evidence. The challenge is finding the balance between insufficient monitoring (risking missing early signs of deterioration and delays in treatment) and over-observation of stable patients (wasting resources needed in other aspects of care). Provide an evidence-based approach to creating monitoring protocols based on a patient's risk of deterioration and link these to nursing workload and economic impact. Our study consisted of two parts: (1) an observational study of nursing staff to ascertain the time to perform vital sign observations; and (2) a retrospective study of historic data on patient admissions exploring the relationships between National Early Warning Score and risk of outcome over time. These were underpinned by opinions and experiences from stakeholders. Observational study: observed nursing staff on 16 randomly selected adult general wards at four acute National Health Service hospitals. Retrospective study: extracted, linked and analysed routinely collected data from two large National Health Service acute trusts; data from over 400,000 patient admissions and 9,000,000 vital sign observations. Observational study found a variety of practices, with two hospitals having registered nurses take the majority of vital sign observations and two favouring healthcare assistants or student nurses. However, whoever took the observations spent roughly the same length of time. The average was 5:01 minutes per observation over a 'round', including time to locate and prepare the equipment and travel to the patient area. Retrospective study created survival models predicting the risk of outcomes over time since the patient was last observed. For low-risk patients, there was little difference in risk between 4 hours and 24 hours post observation. We explored several different scenarios with our stakeholders (clinicians and patients), based on how 'risk' could be managed in different ways. Vital sign observations are often done more frequently than necessary from a bald assessment of the patient's risk, and we show that a maximum threshold of risk could theoretically be achieved with less resource. Existing resources could therefore be redeployed within a changed protocol to achieve better outcomes for some patients without compromising the safety of the rest. Our work supports the approach of the current monitoring protocol, whereby patients' National Early Warning Score 2 guides observation frequency. Existing practice is to observe higher-risk patients more frequently and our findings have shown that this is objectively justified. It is worth noting that important nurse-patient interactions take place during vital sign monitoring and should not be eliminated under new monitoring processes. Our study contributes to the existing evidence on how vital sign observations should be scheduled. However, ultimately, it is for the relevant professionals to decide how our work should be used. This study is registered as ISRCTN10863045. This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/05/03) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 6. See the NIHR Funding and Awards website for further award information.

Exploring the GMO narrative through labeling: strategies, products, and politics

ABSTRACT Labels are influential signals in the marketplace intended to inform and to eliminate buyer confusion. Despite this, food labels continue to be the subject of debate. None more so than non-GMO (genetically modified organisms) labels. This manuscript provides a timeline of the evolution of GMO labels beginning with the early history of the anti-GMO movement to the current National Bioengineered Food Disclosure Standard in the United States. Using media and market intelligence data collected through Buzzsumo™ and Mintel™, public discourse of GMOs is analyzed in relation to sociopolitical events and the number of new food products with anti-GMO labels, respectively. Policy document and publication data is collected with Overton™ to illustrate the policy landscape for the GMO topic and how it has changed over time. Analysis of the collective data illustrates that while social media and policy engagement around the topic of GMOs has diminished over time, the number of new products with a GMO-free designation continues to grow. While discourse peaked at one point, and has since declined, our results suggest that the legacy of an anti-GMO narrative remains firmly embedded in the social psyche, evidenced by the continuing rise of products with GMO-free designation. Campaigns for GMO food labels to satisfy consumers’ right to know were successful and the perceived need for this information now appears to be self-sustaining.