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The 2022 Summit of Heads of State and Government of the Alliance was held in Madrid in June 28-30. The Summit took place in the context of a conventional threat to the security of the Euro – Atlantic area as well as in a time of war on the European soil. NATO leaders discussed strategically important issues facing the Alliance, endorsed the New Concept of the Alliance, and made a series of key decisions that will have a direct impact on the future of the Alliance. Namely, at the Summit, the leaders agreed on fundamental shifts regarding the deterrence and defense doctrine, on the challenges and threats from the South related to the fight against terrorism and the 360-degree approach to deterrence and defense. They agreed to invest more in NATO with the intention to increase common funding for the Alliance’s adaptation to growing challenges such as climate change, and invited Sweden and Finland to join the Alliance. The Leaders agreed on long-term support measures for Ukraine by strengthening the Comprehensive Assistance Package and reaffirmed common interests and shared values. The Summit has set NATO’s new strategic direction for the future, ensuring that the Alliance will continue to adapt in a changing world in order, at any moment to be ready to provide protection to over one billion people living within its borders.

Abstract Dysregulated epigenetic states are a hallmark of cancer and often arise from genetic alterations in epigenetic regulators. This includes missense mutations in histones, which, together with associated DNA, form nucleosome core particles. However, the oncogenic mechanisms of most histone mutations are unknown. Here, we demonstrate that cancer-associated histone mutations at arginines in the histone H3 N-terminal tail disrupt repressive chromatin domains, alter gene regulation, and dysregulate differentiation. We find that histone H3R2C and R26C mutants reduce transcriptionally repressive H3K27me3. While H3K27me3 depletion in cells expressing these mutants is exclusively observed on the minor fraction of histone tails harboring the mutations, the same mutants recurrently disrupt broad H3K27me3 domains in the chromatin context, including near developmentally regulated promoters. H3K27me3 loss leads to de-repression of differentiation pathways, with concordant effects between H3R2 and H3R26 mutants despite different proximity to the PRC2 substrate, H3K27. Functionally, H3R26C-expressing mesenchymal progenitor cells and murine embryonic stem cell-derived teratomas demonstrate impaired differentiation. Collectively, these data show that cancer-associated H3 N-terminal arginine mutations reduce PRC2 activity and disrupt chromatin-dependent developmental functions, a cancer-relevant phenotype.

BACKGROUND: Perinatal mood and anxiety disorders are common, serious complications of pregnancy. Disparities exist by race and income in the prevalence and treatment of these conditions, and overall treatment rates remain low. Outside of pregnancy, a small body of literature suggests that rural residency may contribute to higher rates of depression for those who identify as women. However, among more diverse populations, evidence suggests urban residency may be associated with higher rates of depression among women of color. It is not known whether these trends hold for mood and anxiety disorders during pregnancy and postpartum. OBJECTIVE: We examined differences in the detection and treatment of perinatal mood and anxiety disorders by rural and urban residents and assessed if the observed differences varied by maternal race or ethnicity. STUDY DESIGN: We conducted a cross-sectional study using linked Medicaid claims and birth certificate records from Oregon and South Carolina from 2016 to 2020. We identified perinatal mood and anxiety disorder diagnoses during the perinatal period (pregnancy and within 60 days postpartum) using International Classification of Disease 10th edition codes and enumerated receipt of pharmacotherapy and psychotherapy treatment using Medicaid claims. We used logistic regression models controlling for relevant clinical and sociodemographic characteristics to estimate associations between rural residence and mood disorder detection and treatment. RESULTS: Among the 185,809 births in our sample, 27% of births (n=50,820) were to people who lived in rural areas and 73% (n=134,989) to those in urban areas. The prevalence of any perinatal mood and anxiety disorders diagnosis was higher for urban residents (19.5%) than for rural residents (18.0%; P

Objective Despite growing consensus about the clinical value of preconception care (PCC), gaps and disparities remain in its delivery. This study aimed to examine the factors influencing behavior of health care providers around PCC in outpatient clinical settings in the United States. Methods Twenty health care providers who serve people of reproductive age were interviewed using semi-structured interviews. Data was coded based on a modified Theoretical Domains Framework and analyzed using deductive content analysis. Results We interviewed eight family medicine physicians, four obstetricians/gynecologists, seven nurse practitioners, and one nurse midwife. Overall, we found a wide variety in practices and attitudes towards PCC. Barriers and challenges to delivering PCC were shared across sites. We identified six themes that influenced provider behavior around PCC: (1) lack of knowledge of PCC guidelines, (2) perception of lack of preconception patient contact, (3) pessimism around patient 'compliance,' (4) opinion about scope of practice, (5) clinical site structure, and (6) reliance on the patient/provider relationship. Conclusions for Practice Overall, our findings call for improved provider understanding of PCC and creative incorporation into current health care culture and practice. Given that PCC-specific visits are perceived by some as outside the norm of clinical offerings, providers may need to incorporate PCC into other encounters, as many in this study reported doing. We amplify the call for providers to understand how structural inequities may influence patient behavior and the value of standardized screening, within and beyond PCC, as well as examination of implicit and explicit provider bias., Author(s): Erin C. Nacev [sup.1] [sup.2] , Madelyne Z. Greene [sup.3] , Mireya P. Taboada [sup.1] [sup.4] , Deborah B. Ehrenthal [sup.5] [sup.6] Author Affiliations: (1) grid.14003.36, 0000 0001 2167 [...]

The states face complementary with both conventional and non-conventional threats to global security and peace. If yesterday someone thought that conventional conflict in Europe is not possible, today it has to think differently. Contemporary threats are in symbiosis with global security trends that significantly affect resilience and direct the security of countries. Terrorism, hybrid warfare, cyber threats, climate changes, icecaps melt and new transport corridors open, such as the Northern Sea Route in the High North, outer space, Emerging and Disruptive Technologies (EDTs), scarcity of energy the security, threats posed by Russia, a competitive challenge of China as well as EU energy and economic challenges, upgraded by the EU geo-strategic partnership, the current threat of more frequent periodic pandemic presence, are some part of the trends, challenges and threats which countries in the Euro-Atlantic area are faced. The fast changing and rapidly evolving nature is a common feature of modern security trends, challenges and threats. Dealing with indicated security trends and threats requires fundamental changes in the mind set of perception of security by redefining the concepts of security and reorganizing the global security architecture in EuroAtlantic Area. States often face an invisible adversary who is both their ally and their common enemy. Hybrid warfare and cyber threats are specifics warfare in alternative space, where “the battles” being fought in cyberspace, through disinformation, disintegration and the abuse of Internet through malicious operations on social networks. These clashes are more like battles of narratives in cyberspace than real - time battles on the battlefield. The multitude of information, i.e. disinformation that is placed, confused the public, and no one knows where it is and what the truth is. The challenge of such warfare affects the security of states expressed through the implications of their defence, multiplying the instability that leads to new vulnerabilities and crises. Artificial intelligence, EDTs presents at the same time are both, a new opportunities and risk, and together they are a key element for maintaining the military and technological edge of the states. The control of outer space is becoming increasingly important for the security as well as for the economy, energy and prosperity of states with far-reaching consequences that can have a destructive impact similar as conventional warfare. Consequently, each international organization and institution builds its own concept and strategy to dealing with such security trends, challenges and threats. The report of the reflection group “NATO 2030: United for a New Era” is a NATO’s vision for dealing with such global security trends, challenges and threats in the next decade and beyond. This document provides guidance on how the Alliance will adapt to new global security trends, challenges and threats. The practical operationalization of the mechanisms for dealing with them is expected to be formalized with the New Strategic Concept of the Alliance, announced by the NATO Secretary General Stoltenberg to be adopted in mid-2022. The EU, for its part, has developed a Strategic Compass. Only the UN seems to be resistant on the change. However, the efficiency of new concepts and strategies for dealing with contemporary challenges remains to be tested in practice.

BackgroundPatient experience surveys are widely used to capture the patient-reported quality of care and are increasingly being used for formal reporting purposes. There is evidence that certain patient subgroups are less likely to respond to traditional CAHPS surveys. As patient-facing technologies become more common, it is important to examine whether tablet-based patient experience surveys have the potential to promote responses from more diverse populations.ObjectivesTo develop, gain perspectives about, and pilot an English and Spanish low-literacy adaptation of the Consumer Assessment of Healthcare Providers & Systems Clinician & Group Survey (CG-CAHPS) administered on a tablet device at the point of care.Research designCognitive testing and evaluation of a quality improvement pilot comparing a tablet-based adaptation and traditional paper-based versions of the CG-CAHPS survey.SubjectsEnglish-speaking and Spanish-speaking patients receiving primary care in an urban community clinic.MeasuresTo compare the acceptability of low-literacy tablet-based and traditional paper-based patient experience surveys, we examined the concordance of responses between survey modes and preferences for modality, as well as perspectives on usability and reporting care experiences. We examined demographic differences in responses to tablet-based versus mailed surveys from a quality improvement pilot.ResultsThe majority of cognitive interview participants preferred a low-literacy, tablet-based survey over a paper-based survey with traditional wording. In a quality improvement pilot comparing tablet-based administration at the point of care versus mailed surveys, respondents to the tablet-based survey were more likely to be younger and Latino.ConclusionsIf designed with patient input, tablet-based surveys have the potential to improve the collection of patient experience data among diverse populations.

Sarcomas are rare tumours with many different subtypes and clinical outcomes; a broader knowledge of their genetic features is required. Here, the authors analyse 2138 soft tissue and bone sarcomas across 45 subtypes using MSK-IMPACT targeted sequencing and find genomic groups that are distinct from histological subgroups.

The activity of PD-1 blockade in patients with sarcoma has been modest so far. Here, the authors report the results of a pilot clinical trial to assess the efficacy and safety of bempegaldesleukin, a CD122-preferential interleukin-2 (IL-2) pathway agonist, in combination with the PD1 blockade (nivolumab) in patients with locally advanced or metastatic high-grade sarcoma.

For the need of engagement of the Armed Forces in support of civilian authorities and citizens is a topic on which there is a comprehensive consensus both at the national level and within the NATO member states. Controversy over the mechanisms of engagement, the precise definition of tasks, and the duration of the engagement of the Armed Forces. The Army of the Republic of North Macedonia supports the civilian component of the defense system in conditions when the other state institutions (including local self-government) will not be able to cope with the crisis, when there are threats to critical infrastructure and when the security and borders of the country are endangered. Whenever support is sought from the Army, it should be borne in mind that Armed Forces units should not be the first responder. The Armed Forces has to be engaged only in a situation where the crisis or state of emergency exceeds the capacities and capabilities of other state institutions and local authorities. The situation caused by the COVID 19 outbreak put to the test the civil readiness and resilience of the society in dealing with such situations and brought to the surface the necessity of engaging the capacities and capabilities of the Armеd Forces in different circumstances. Also, there was a need for normative and legal regulation of engagement of the Armed Forces units in support of civilian authorities and citizens in peacetime, in natural disasters, in crisis and state of emergency, as well as to prevent its possible abuse. The need for building resilience and response mechanisms in case of natural disasters and emergencies are an active component both at the national level of each country and in the context of integral and solidarity engagement of the Alliance. NATO’s approach to building resilience is based on the concepts of the Whole of Government Approach and the Whole of Society Approach.

Mutations in epigenetic pathways are common oncogenic drivers. Histones, the fundamental substrates for chromatin-modifying and remodelling enzymes, are mutated in tumours including gliomas, sarcomas, head and neck cancers, and carcinosarcomas. Classical 'oncohistone' mutations occur in the N-terminal tail of histone H3 and affect the function of polycomb repressor complexes 1 and 2 (PRC1 and PRC2). However, the prevalence and function of histone mutations in other tumour contexts is unknown. Here we show that somatic histone mutations occur in approximately 4% (at a conservative estimate) of diverse tumour types and in crucial regions of histone proteins. Mutations occur in all four core histones, in both the N-terminal tails and globular histone fold domains, and at or near residues that contain important post-translational modifications. Many globular domain mutations are homologous to yeast mutants that abrogate the need for SWI/SNF function, occur in the key regulatory 'acidic patch' of histones H2A and H2B, or are predicted to disrupt the H2B-H4 interface. The histone mutation dataset and the hypotheses presented here on the effect of the mutations on important chromatin functions should serve as a resource and starting point for the chromatin and cancer biology fields in exploring an expanding role of histone mutations in cancer. The characterization of missense histone mutations that occur across several cancer types provides insight into the potential role of these mutations in altering chromatin structure and potentially contributing to tumour development., Author(s): Benjamin A. Nacev [sup.1] [sup.2] , Lijuan Feng [sup.2] , John D. Bagert [sup.3] , Agata E. Lemiesz [sup.2] , JianJiong Gao [sup.1] , Alexey A. Soshnev [sup.2] , [...]

Traumatic ventricular septal defect (VSD) is a widely-recognized complication of both penetrating and blunt trauma. Most cases are repaired operatively without the long-term complications of pulmonary hypertension and heart failure that are associated with unrepaired congenital VSD in the pediatric population. To our knowledge, this is the first case report of a patient with a traumatic VSD who declined surgical repair at the time of injury and subsequently developed long-term complications of pulmonary hypertension and heart failure. With nearly 20 years of follow-up, this case demonstrates that the absence of surgical treatment in asymptomatic adult patients at the time of injury can lead to long-term complications associated with VSD. This case also shows that aggressive surgical treatment in patients with severe pulmonary vascular disease and heart failure secondary to traumatic VSD can be performed safely and should be considered in cases refractory to efficacious medical interventions.

The standard of care for managing a patient with an implant is to identify the item and to assess the relative safety of scanning the patient. Because the 1.5 T MR system is the most prevalent scanner in the world and 3 T is the highest field strength in widespread use, implants typically have "MR Conditional" (i.e., an item with demonstrated safety in the MR environment within defined conditions) labeling at 1.5 and/or 3 T only. This presents challenges for a facility that has a scanner operating at a field strength below 1.5 T when encountering a patient with an implant, because scanning the patient is considered "off‐label." In this case, the supervising physician is responsible for deciding whether to scan the patient based on the risks associated with the implant and the benefit of magnetic resonance imaging (MRI). For a passive implant, the MRI safety‐related concerns are static magnetic field interactions (i.e., force and torque) and radiofrequency (RF) field‐induced heating. The worldwide utilization of scanners operating below 1.5 T combined with the increasing incidence of patients with implants that need MRI creates circumstances that include patients potentially being subjected to unsafe imaging conditions or being denied access to MRI because physicians often lack the knowledge to perform an assessment of risk vs. benefit. Thus, physicians must have a complete understanding of the MRI‐related safety issues that impact passive implants when managing patients with these products on scanners operating below 1.5 T. This monograph provides an overview of the various clinical MR systems operating below 1.5 T and discusses the MRI‐related factors that influence safety for passive implants. Suggestions are provided for the management of patients with passive implants labeled MR Conditional at 1.5 and/or 3 T, referred to scanners operating below 1.5 T. The purpose of this information is to empower supervising physicians with the essential knowledge to perform MRI exams confidently and safely in patients with passive implants. Level of Evidence: 1 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]