bluuebunny/crossref_metadata_2025 huggingface dataset:
Preconception Periodontitis and Risk of Spontaneous Abortion in a Prospective Cohort Study
Authors: Bond Julia C , Wise Lauren A , Fox Matthew P , Garcia Raul I , Murray Eleanor J , White Katharine O , Rothman Kenneth J , Hatch Elizabeth E , Heaton Brenda
Published: June 2023

Few studies have evaluated the association between periodontitis and spontaneous abortion (SAB), and all had limitations. We used data from the Pregnancy Study Online (PRESTO), a prospective preconception cohort study of 3,444 pregnancy planners in the United States and Canada (2019–2022), to address this question. Participants provided self-reported data on periodontitis diagnosis, treatment, and symptoms of severity (i.e., loose teeth) via the enrollment questionnaire. SAB (pregnancy loss at <20 weeks’ gestation) was assessed via bimonthly follow-up questionnaires. Participants contributed person-time from the date of a positive pregnancy test to the gestational week of SAB, loss to follow-up, or 20 weeks’ gestation, whichever came first. We fitted Cox regression models with weeks of gestation as the time scale to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs), and we used inverse probability of treatment weighting to account for differential loss to follow-up. We used probabilistic quantitative bias analysis to estimate the magnitude and direction of the effect of exposure misclassification bias on results. In weighted multivariable models, we saw no appreciable association between preconception periodontitis diagnosis (HR = 0.97, 95% CI: 0.76, 1.23) or treatment (HR = 1.01, 95% CI: 0.79, 1.27) and SAB. A history of loose teeth was positively associated with SAB (HR = 1.38, 95% CI: 0.88, 2.14). Quantitative bias analysis indicated that our findings were biased towards the null but with considerable uncertainty in the bias-adjusted results.
Evaluating Model Specification When Using the Parametric G-Formula in the Presence of Censoring
Authors: Chiu Yu-Han , Wen Lan , McGrath Sean , Logan Roger , Dahabreh Issa J , Hernán Miguel A
Published: June 2023

The noniterative conditional expectation (NICE) parametric g-formula can be used to estimate the causal effect of sustained treatment strategies. In addition to identifiability conditions, the validity of the NICE parametric g-formula generally requires the correct specification of models for time-varying outcomes, treatments, and confounders at each follow-up time point. An informal approach for evaluating model specification is to compare the observed distributions of the outcome, treatments, and confounders with their parametric g-formula estimates under the “natural course.” In the presence of loss to follow-up, however, the observed and natural-course risks can differ even if the identifiability conditions of the parametric g-formula hold and there is no model misspecification. Here, we describe 2 approaches for evaluating model specification when using the parametric g-formula in the presence of censoring: 1) comparing factual risks estimated by the g-formula with nonparametric Kaplan-Meier estimates and 2) comparing natural-course risks estimated by inverse probability weighting with those estimated by the g-formula. We also describe how to correctly compute natural-course estimates of time-varying covariate means when using a computationally efficient g-formula algorithm. We evaluate the proposed methods via simulation and implement them to estimate the effects of dietary interventions in 2 cohort studies.
390 Efficacy and safety of roflumilast cream 0.15% in adults and children aged ≥6 years with mild to moderate atopic dermatitis in two phase 3 trials (INTEGUMENT-1 and INTEGUMENT-2)
Authors: Simpson Eric , Eichenfield Lawrence , Gooderham Melinda  , Gonzalez Mercedes E , Hebert Adelaide , Papp Kim , Prajapati Vimal , Krupa David , Burnett Patrick , Berk David , Higham Robert
Published: June 2023

Roflumilast is a selective, highly potent phosphodie­sterase 4 inhibitor under investigation as a nonsteroidal, once-daily cream for treatment of atopic dermatitis (AD). INTEGUMENT-1 (n = 654; NCT04773587) and INTEGUMENT-2 (n = 683; NCT04773600) were identical phase 3 randomized controlled trials conducted in patients with AD aged ≥6 years with baseline Eczema Area and Severity Index (EASI) score ≥5 and Validated Investigator Global Assessment-AD (vIGA-AD) score of mild or moderate. Patients were randomized 2 : 1 to apply once-daily roflumilast cream 0.15% or vehicle for 4 weeks. The primary efficacy endpoint was vIGA-AD Success [defined as score of 0 (clear) or 1 (almost clear) with 2-grade improvement from baseline] at Week 4. Secondary endpoints included 75% improvement in EASI (EASI-75). At Week 4, significantly more roflumilast-treated than vehicle-treated patients achieved vIGA-AD Success (INTEGUMENT-1: 32.2% vs. 15.2%; P < 0.0001; INTEGUMENT-2: 28.9% vs. 12.0%; P < 0.0001) and EASI-75 (INTEGUMENT-1: 43.2% vs. 22.0%; P < 0.0001; INTEGUMENT-2: 42.0% vs. 19.7%; P < 0.0001). Incidence of treatment-emergent adverse events (AEs) was low in both arms, with most assessed as mild to moderate in severity. No AE occurred in more than 3.5% of patients in either arm with low rates of application site pain in both the roflumilast- and vehicle-treated patients (INTEGUMENT-1: 2.1% vs. 0.5%; INTEGUMENT-2: 0.9% vs. 0.9%). Local tolerability was favorable with >90% of roflumilast-treated patients reporting no or mild sensation across arms in both trials at any timepoint. Once-daily roflumilast cream 0.15% improved AD across multiple efficacy endpoints while demonstrating favorable safety and tolerability in two phase 3 trials.
399 Pooled safety analysis of lebrikizumab in patients with uncontrolled asthma from three randomized clinical trials
Authors: Corren Jonathan , Szefler Stanley J , Armstrong April W   , Natalie Chitra R , Zitnik Ralph  , Zhao Fangyi , Siu Kimberly , Lio Peter A   , Mourey Robert J
Published: June 2023

LAVOLTA (L)I, LII and ACOUSTICS were randomized, placebo-controlled, double-blinded, Phase 3 trials of lebrikizumab, a monoclonal antibody targeting interleukin-13, in patients with uncontrolled asthma (LI, NCT01867125; LII, NCT01868061; ACOUSTICS, NCT01875003). These studies failed to provide consistently significant efficacy results in uncontrolled asthma. This study aims to report pooled safety analysis of lebrikizumab in patients during the 52-week placebo-controlled period from the three clinical trials. Adults in LI and LII, adolescents (12–17 years) in ACOUSTICS, with uncontrolled asthma, prebronchodilator forced expiratory volume in 1 s 40–90% predicted and stable background therapy were randomized 1 : 1 : 1 to lebrikizumab 125 or 37·5 mg or placebo (PBO) subcutaneously once every 4 weeks. Safety analyses were based on all patients who received at least one dose of study drug, with patients grouped by assigned treatment. Safety was assessed using summary of adverse events (AEs). The proportions of patients who experienced treatment-emergent AEs [combined lebrikizumab doses (LEB), 1281 (77%) of 1661 patients vs. PBO, 650 (78%) of 883 patients], serious AEs (7.6% vs. 8.5%) and AEs leading to study drug discontinuation (3.4% vs. 3.6%) were similar between LEB and PBO. One death occurred in the PBO group. Similar frequencies of key safety events, including conjunctivitis (LEB, 1.6%; PBO, 1.7%), infections and infestations (LEB, 51.6%; PBO, 50.7%), and eosinophil-related disorders (LEB, 0.2%; PBO, 0.2%) were noted; higher frequency of eosinophilia (>500 eosinophils/mm3) was reported (LEB, 1.1%; PBO, 0%). The safety profile was similar between lebrikizumab and placebo in adults and adolescents with uncontrolled asthma.
400 Efficacy of lebrikizumab in patients who did not achieve protocol-defined criteria for response after initial 16 weeks of therapy
Authors: Guttman-Yassky Emma , Rosmarin David , Thyssen Jacob P , Weidinger Stephan , Bieber Thomas  , Elmaraghy Hany , Atwater Amber Reck  , Pierce Evangeline , Xu Chenjia  , Gimeno Helena Agell , Simpson Eric , Mourey Robert J
Published: June 2023

Lebrikizumab demonstrated robust efficacy during the first 16 weeks of treatment in ADvocate1 and ADvocate2. This study aims to describe the 52-week results of lebrikizumab-treated patients who did not meet the protocol-defined criteria for response at 16 weeks of treatment. During the induction period, patients were randomized 2 : 1 to lebrikizumab 250 mg or placebo every 2 weeks (Q2W) for 16 weeks. Protocol-defined criteria for response were characterized as achieving a 75% Eczema Area and Severity Index (EASI75) or an Investigator’s Global Assessment of 0 or 1 (IGA 0,1) with a ≥2-point improvement and without rescue medication use. At Week 16, patients from the lebrikizumab treatment arm, who did not reach the criteria for response, were assigned to the Escape arm (n = 215). These patients continued to receive lebrikizumab 250 mg Q2W for an additional 36 weeks. Endpoints and measurements included at week 52 were EASI75, EASI90, IGA (0,1) and pruritus. Pruritus was assessed using an 11-point Pruritus Numeric Rating Scale (NRS). Data are presented as observed results with no imputation for missing data. Pooled results for patients who did not respond to lebrikizumab and entered the escape arm show 36.1% achieved IGA (0,1) with 2-point improvement at Week 52. In the same population, 75.5% achieved EASI75, 44.2% achieved EASI90 and 66.4% reported 4-point improvement in Pruritus NRS. These results suggest that patients, who do not achieve protocol-defined response at 16 weeks of treatment, can be slow responders and derive benefit from continuing long-term therapy with lebrikizumab.
401 Safety and efficacy of lebrikizumab in adolescent patients with moderate-to-severe atopic dermatitis: an open-label study
Authors: Paller Amy , Flohr Carsten , Eichenfield Lawrence F , Irvine Alan , Pinto-Correia Ana  , Natalie Chitra R , Pierce Evangeline  , Reifeis Sarah , Lima Renata Gontijo , Laquer Vivian , Weidinger Stephan  , Isho Nadine
Published: June 2023

Atopic dermatitis (AD) can greatly impact quality of life in adolescents, and improved management is needed. Lebrikizumab, a high-affinity monoclonal antibody targeting interleukin (IL)-13, demonstrated clinical benefit in Phase 3 trials: ADvocate1, ADvocate2 and ADhere. This study aims to report 52-week safety and efficacy outcomes from ADore (NCT04250350), a Phase 3, open label study of lebrikizumab in adolescent patients with moderate-to-severe AD. Eligible adolescents (n = 206) (≥12 to <18 years; weighing ≥40 kg) received 500-mg loading doses at baseline and Week 2, and 250-mg lebrikizumab subcutaneous injections every 2-weeks (Q2W) for 52-weeks. Safety was monitored using adverse events (AEs), AEs leading to treatment discontinuation, vital signs and laboratory testing. Efficacy analyses included Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI). A total of 172 patients completed the treatment period. Low frequencies of AEs leading to treatment discontinuation (2.4%) and SAEs (2.4%) were reported. Overall, 134 (65.0%) patients reported at least one treatment-emergent adverse event, most being mild or moderate in severity, including 14 (6.8%) conjunctivitis events. Efficacy was rapid, with 14.4% achieving IGA (0,1) at Week 4, increasing to 46.3% at Week 16 and 62.6% at Week 52. The EASI-75 was 28.6% at Week 4, 73.2% at Week 16, and 81.9% at Week 52. The mean percent improvement from baseline to Week 52 in EASI was 86.0%. Lebrikizumab open-label 250-mg Q2W had a safety profile in adolescents with moderate-to-severe AD, which was consistent with previous trials, with 2.4% treatment discontinuation due to AEs. Lebrikizumab demonstrated efficacy, with 81.9% of patients achieving EASI-75 and 62.6% achieving IGA (0,1) at Week 52.
409 Efficacy and safety of upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: subgroup analysis of the Measure Up 1, Measure Up 2 and AD Up phase 3 clinical trials at 52 weeks
Authors: Paller Amy S , Mendes-Bastos Pedro , Eichenfield Lawrence F   , Soong Weily , Lio Peter  , Prajapati Vimal H , Platt Andrew M , Raymundo Eliza  , Liu John , Ladizinski Barry , Thyssen Jacob P
Published: June 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous morphology and intense pruritus. Previous clinical trials have demonstrated that upadacitinib (UPA) was superior to placebo (PBO) in the treatment of moderate-to-severe AD. Here, we analyse the efficacy and safety of UPA across 52 weeks in adolescent and adult subgroups from three phase 3 studies. Patients were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30) or PBO orally once daily, either alone or with concomitant topical corticosteroids. After 16 weeks, patients in the PBO group were randomized to the UPA15 or UPA30 groups. For both adolescent and adult subgroups at 52 weeks, the proportion of responders in the UPA15 and UPA30 groups was: ≥70% and 83% for EASI75, ≥31% and 47% for vIGA-AD 0/1 and ≥37% and 61% for Worst Pruritus Numeric Rating Scale improvement ≥4. Children’s Dermatology Life Quality Index (CDLQI) 0/1 was achieved by ≥15% (UPA15) and ≥28% (UPA30) of adolescents aged 12 to <16 years; DLQI 0/1 was achieved by ≥18% (UPA15) and ≥38% (UPA30) of adolescents aged 16 to <18 years and ≥30% (UPA15) and ≥45% (UPA30) of adults. Hospital Anxiety and Depression Scale (HADS-A and HADS-D) <8 was achieved in ≥28% of adolescents and ≥45% of adults for both treatment groups. Rates of serious adverse events (AEs) and serious AEs leading to discontinuation at week 52 were similar for both adolescents and adults. UPA15 and UPA30 responses in moderate-to-severe AD across 52 weeks were similar between adolescents and adults, with acceptable safety outcomes in both populations.
Morphological traits explain the individual position within resource-consumer networks of a Neotropical marsupial
Authors: de Camargo Nícholas F , de Oliveira Hernani F M , Ribeiro Juliana F , de Camargo Amabílio J A , Vieira Emerson M
Published: June 2023

Knowledge regarding the influence of individual traits on interaction patterns in nature can help understand the topological role of individuals within a network of intrapopulation interactions. We tested hypotheses on the relationships between individuals’ positions within networks (specialization and centrality) of 4 populations of the mouse opossum Gracilinanus agilis and their traits (i.e., body length, body condition, tail length relative to body length, sex, reproductive condition, and botfly parasitism) and also seasonal effects in the Brazilian savanna. Individuals with lower body length, better body condition, and relatively shorter tail were more specialized (i.e., less connected within the network). Individuals were also more specialized and less connected during the warm-wet season. The relationship between individuals’ position in the network and body traits, however, was independent of season. We propose that specialization may arise not only as a result of preferred feeding strategies by more capable individuals (i.e., those with better body condition and potentially prone to defend and access high-quality food resources) but also because of morphological constraints. Smaller/younger individuals (consequently with less experience in foraging) and short-tailed individuals (less skilled to explore the vertical strata of the vegetation) would feed only on a subset of the available food resources and consequently become more specialized. Moreover, individuals are more specialized during the warm-wet season because of high competition (population-dense period) and higher ecological opportunities (resource-rich period). Therefore, our study reveals the relevance of individual traits in shaping interaction patterns and specialization in populations.
Subclinical atherosclerosis and accelerated epigenetic age mediated by inflammation: a multi-omics study
Authors: Sánchez-Cabo Fátima , Fuster Valentín , Silla-Castro Juan Carlos , González Gema , Lorenzo-Vivas Erika , Alvarez Rebeca , Callejas Sergio , Benguría Alberto , Gil Eduardo , Núñez Estefanía , Oliva Belén , Mendiguren José María , Cortes-Canteli Marta , Bueno Héctor , Andrés Vicente , Ordovás Jose María , Fernández-Friera Leticia , Quesada Antonio J , Garcia Jose Manuel , Rossello Xavier , Vázquez Jesús , Dopazo Ana , Fernández-Ortiz Antonio , Ibáñez Borja , Fuster Jose Javier , Lara-Pezzi Enrique
Published: June 2023

Aims

Epigenetic age is emerging as a personalized and accurate predictor of biological age. The aim of this article is to assess the association of subclinical atherosclerosis with accelerated epigenetic age and to investigate the underlying mechanisms mediating this association.

Methods and results

Whole blood methylomics, transcriptomics, and plasma proteomics were obtained for 391 participants of the Progression of Early Subclinical Atherosclerosis study. Epigenetic age was calculated from methylomics data for each participant. Its divergence from chronological age is termed epigenetic age acceleration. Subclinical atherosclerosis burden was estimated by multi-territory 2D/3D vascular ultrasound and by coronary artery calcification. In healthy individuals, the presence, extension, and progression of subclinical atherosclerosis were associated with a significant acceleration of the Grim epigenetic age, a predictor of health and lifespan, regardless of traditional cardiovascular risk factors. Individuals with an accelerated Grim epigenetic age were characterized by an increased systemic inflammation and associated with a score of low-grade, chronic inflammation. Mediation analysis using transcriptomics and proteomics data revealed key pro-inflammatory pathways (IL6, Inflammasome, and IL10) and genes (IL1B, OSM, TLR5, and CD14) mediating the association between subclinical atherosclerosis and epigenetic age acceleration.

Conclusion

The presence, extension, and progression of subclinical atherosclerosis in middle-aged asymptomatic individuals are associated with an acceleration in the Grim epigenetic age. Mediation analysis using transcriptomics and proteomics data suggests a key role of systemic inflammation in this association, reinforcing the relevance of interventions on inflammation to prevent cardiovascular disease.
A Time of Healing: Can Social Engagement After Bereavement Reduce Trajectories of Depression After the Death of a Child?
Authors: Cha Hyungmin , Thomas Patricia A
Published: June 2023

Objectives

We work from a stress and life-course perspective to examine the mental health of parents who experienced the death of their child. We examine whether mental health eventually returns to pre-bereavement levels and how social engagement after bereavement may shape the recovery process of depressive symptoms.

Methods

We analyze discontinuous growth curve models to assess the association between a child’s death and trajectories of parents’ depressive symptoms from the 1998–2016 Health and Retirement Study. The sample includes 16,182 parents aged 50 years and older.

Results

Those who transitioned to bereavement experienced an elevation in depressive symptoms and a relatively long recovery time (e.g., 7 years) to their pre-bereavement mental health in our findings. However, when engaging in volunteer work after their loss, depressive symptoms reduce more quickly to their pre-bereavement levels. Volunteering offsets up to 3 years of the negative consequences of child loss.

Discussion

The death of a child is a traumatic event with extensive health consequences, but research should more fully examine the dynamic nature and potential mitigation of these health consequences over time. Our findings expand the temporal lens to encompass healing processes after bereavement, incorporating the importance of social engagement.
The Better Care Plan: a blueprint for improving America's healthcare system
Authors: Shortell Stephen M , Toussaint John T , Halvorson George C , Kingsdale Jon M , Scheffler Richard M , Schwartz Allyson Y , Wadsworth Peter A , Wilensky Gail
Published: June 2023

The United States falls far short of its potential for delivering care that is effective, efficient, safe, timely, patient-centered, and equitable. We put forward the Better Care Plan, an overarching blueprint to address the flaws in our current system. The plan calls for continuously improving care, moving all payers to risk-adjusted prospective payment, and creating national entities for collecting, analyzing, and reporting patient safety and quality-of-care outcomes data. A number of recommendations are made to achieve these goals.
Parastomal hernia containing the stomach—a rare complication
Authors: Bodimeade Chris , Troller Rebekka
Published: June 2023

A lady in her 70s presented to hospital with sudden onset nausea and excessive vomiting. She had a constant and worsening abdominal pain that radiated to the back but was focused on her stoma in the left iliac fossa. The patient had bilateral hernias and colostomy following a Hartman’s procedure for perforated diverticulosis in 2018 and had presented twice before in the last 6 months with similar symptoms. CT abdomen pelvis showed a large portion of the stomach in the parastomal hernia leading to a narrowing of the stomach at the hernia neck but no ischaemic changes. She was diagnosed with bowel obstruction and successfully treated with fluid resuscitation, proton pump inhibitors, analgesia, antiemetics and decompression of the stomach using large bore nasogastric tube. A total of 2600 ml fluid was aspirated in 24 h and her stoma restarted normal output. After 10 days she was discharged home.
On the expected purity of photometric galaxy surveys targeting the Cosmic Dawn
Authors: Furlanetto Steven R , Mirocha Jordan
Published: June 2023

Over the last three decades, photometric galaxy selection using the Lyman-break technique has transformed our understanding of the high-z Universe, providing large samples of galaxies at $3 \lesssim z \lesssim 8$ with relatively small contamination. With the advent of the JWST, the Lyman-break technique has now been extended to z ∼ 17. However, the purity of the resulting samples has not been tested. Here, we use a simple model, built on the robust foundation of the dark matter halo mass function, to show that the expected level of contamination rises dramatically at $z \gtrsim 10$, especially for luminous galaxies, placing stringent requirements on the selection process. The most luminous sources at $z \gtrsim 12$ are likely at least 10 000 times rarer than potential contaminants, so extensive spectroscopic follow-up campaigns may be required to identify a small number of target sources.
The Last Books of the Dead
Authors: Albert Florence
Published: June 2023

The Book of the Dead was used from the New Kingdom to the Roman Period. Even if its content and typological evolution of the corpus begin to be well known for earlier periods (New Kingdom, Third Intermediate Period, Late Period, and the first part of the Ptolemaic Period), it is still difficult to understand the last developments of the Book of the Dead because of the rarity of dated and well-preserved manuscripts. Nevertheless, recent studies have focused on that specific funerary literature, highlighting several representative sources and some of their structural features. Thus, based on concrete examples, this chapter aims to draw an evolving picture of the Book of the Dead corpus in the last years of its use.
The Book of the Dead Papyri in the Twenty-Sixth Dynasty
Authors: Gülden Svenja A.
Published: June 2023

This chapter provides an overview of the sources and composition of the Book of the Dead papyri of the Twenty-sixth Dynasty based on selected examples. The analysis focuses on the formal design of the manuscripts, which is mainly determined by format and layout. However, the choice of script as well as the combination and relationship of text and vignettes are also part of the formal design of Book of the Dead papyri. The selection of the Book of the Dead spells and their specific sequence is another distinctive feature of the papyrus manuscripts of the Twenty-sixth Dynasty. In an excursus, the history of the present-day numbering of the Book of the Dead spells is also described. Further topics are the provenance of the sources and the owners of the Book of the Dead papyri. Finally, the (stock) production of manuscripts and the question of whether Book of the Dead papyri were produced especially for one person or were pre-produced and individualized for the owner in a later step are discussed.
The Conservation of Book of the Dead Papyri
Authors: Krutzsch Myriam
Published: June 2023

The material condition of Book of the Dead papyri kept in ancient Egyptian collections and museums around the world is affected by historical treatments and the accompanying dissection of often several-meters-long scrolls out of convenience. The papyrus sections that came out from the dissection were afterward laminated onto bases of different materials. Today, it is necessary to correct the alterations and damage that has been done and, if possible, to repair them. This article will demonstrate how to proceed in order to correct papyrus alterations through several examples. Furthermore, observations regarding the papyrus material and its structure as well as further technical details will be illustrated.
Thematic Groups and Sequences of Spells
Authors: Weber Felicitas
Published: June 2023

More than two hundreds Book of the Dead chapters were available to be copied on papyrus, tomb walls, and other objects to ensure eternal existence for the deceased in the ancient Egyptian netherworld. Which chapters were finally chosen and how they were arranged depended not only on individual decisions, but also on the general zeitgeist and religious beliefs, of the time as well as on the personal taste of the owner. However, certain chapters tend to be grouped together in certain manners forming complex themes. Such common sequences are elucidated in this chapter, together with the general idea behind the composition of Book of the Dead manuscripts.
The International Legal Basis of Nuclear Security
Authors: Balci Yasemin
Published: June 2023

The chapter examines nuclear security from the perspective of international law. It is intended for those interested in the international legal basis of the subject area, whether they are legally trained or not. The chapter identifies treaties as the main source of international law on nuclear security. It examines the amended Convention on the Physical Protection of Nuclear Material (CPPNM) and International Convention for the Suppression of Acts of Nuclear Terrorism (ICSANT) as well as related obligations in other treaties and UN Security Council resolutions. The chapter also analyses how ‘soft law’ and judicial decisions form a part of the international legal basis. It discusses proposals to strengthen the international legal basis of nuclear security and addresses the importance of universalization and the relationship with national legal frameworks through legislative implementation of international obligations.
The Evolution of Global Nuclear Security Governance
Authors: Bowen Wyn Q. , Cottee Matthew , Tzinieris Sarah
Published: June 2023

The architecture of global nuclear security governance comprises a complex set of treaties, international agreements, policy instruments, and guidance documents—some of which are formal and legally binding, and others that are informal and dependent on state-level commitment for their application. These instruments are broadly designed to prevent, deter, and respond to non-state actor acquisition of nuclear material for malign purposes. The chapter provides an overview of the evolution of global nuclear security governance. Employing a chronological approach, the chapter charts the formulation of international instruments on nuclear security and seeks to shed light on the international negotiations and policy debates that preceded important developments in the governance architecture. As will become clear, the evolution of global nuclear security governance has often been driven by policy responses to perceived threats or gaps in existing structures.
Nuclear Security for Next-Generation Reactors
Authors: Aghara Sukesh K. , Peel Ross
Published: June 2023

Today’s operating nuclear power plant fleet is primarily composed of ageing Generation II reactors, these predominantly being in Organisation for Economic Co-operation and Development (OECD) countries. However, significant new build activity over the past two decades, primarily in Asia and in non-OECD countries more widely, is adding new Generation III and III+ reactors to a more globally distributed fleet. Previous construction, maintenance, and operational experience is now informing the development of the next generation of reactors, which are expected to be smaller and make use of novel technologies. To be operable in a free-market energy system, these novel nuclear power plants must be economically competitive with both large established nuclear power technologies and low-carbon energy generating options. Security accounts for a significant proportion of today’s nuclear power operating costs, including capital expenditures for expensive retrofits into existing plants. Consequently, to remain competitive, new approaches are needed to build security into the fabric of the plant during the design phase. The chapter introduces the evolutionary and innovative reactor designs (EID) under development. Detailed consideration of the many individual technologies is not feasible here; instead the chapter discusses some of the common elements relevant to many technologies, which can provide insights for the majority of EIDs, and considers the key areas that lead to changes in the security features of EIDs. It focuses on security-by-design approaches in the development of the next generation of nuclear reactors and addresses some safeguards-by-design elements where these link to security. It also covers the underlying frameworks of nuclear security and its suitability for EIDs.
Addressing the Confidence Gap in the Security of Military Nuclear Materials
Authors: Roecker Scott , Roth Nickolas
Published: June 2023

All weapons-useable nuclear materials and facilities with such materials must be protected from theft or attack. For decades, countries have worked together through bilateral government channels, multilateral groups, and international organizations to strengthen nuclear security around the world. Over time, countries have made significant progress on reducing the likelihood of nuclear material theft or sabotage. Despite significant accomplishments, these efforts have primarily focused on a small subsection of the global supply of nuclear materials. More than 80 per cent of the world’s stocks of nuclear weapons-useable materials exist within nuclear weapons (or nuclear submarines) and the programmes that develop, build, and dispose of them. Nuclear security cooperation has largely focused on nuclear materials in civilian use; for political, cultural, and security reasons, very little is known about military nuclear security in countries that possess military nuclear materials. These materials are largely set apart from international laws and institutions and beyond the reach of existing mechanisms for international nuclear security cooperation. Moreover, current geopolitical trends are making cooperation between countries with military nuclear materials more difficult. Yet, strengthening international confidence in security for military materials is a critical element of the nuclear non-proliferation regime. The chapter describes what military materials are, discusses the legal mechanisms and international institutions that support strengthening security for military materials around the world, identifies why confidence in military materials security is important, and provides recommendations for the further strengthening of security for military materials and increasing broader confidence in that security.
Open Source Intelligence and Investigative Techniques for Locating Radioactive Materials
Authors: Duitsman Michael , Kalinina-Pohl Margarita
Published: June 2023

Radioactive sources outside of regulatory control pose a wide range of safety and security threats to people and the environment. The chapter examines how traditional methods of administrative and physical searches to locate radioactive sources outside of regulatory control can be complemented by using open source intelligence (OSINT) techniques. The chapter discusses several types of open source data and analytical methods for locating radioactive sources outside of regulatory control and explains how the authors and others have used them as part of efforts to locate such material. A facility suspected to contain radioactive sources serves as an organizational hub for data and analysis. Different types of data, including satellite and ground truth imagery, academic and grey literature, news reports, and press releases are employed to learn about the facility, while social media provides information about current and former employees. The discussion of these data types is accompanied by examples and a discussion of the advantages and disadvantages of the various OSINT techniques. While open source data cannot replace traditional methods, it can play an invaluable role in supplementing additional information to national inventories of radioactive sources.
Prediction of GutCheckNEC and Its Relation to Severity of Illness and Measures of Deterioration in Necrotizing Enterocolitis
Authors: Gephart Sheila M. , Fleiner Michelle , Msowoya Amy , Rothers Janet
Published: June 2023

Background:

Necrotizing enterocolitis (NEC) risk has been shown to arise from multiple sources and risk awareness may be supported using bedside tools.

Purpose:

The purpose of this research was to examine the extent to which GutCheckNEC was associated with scores for clinical deterioration, severity of illness, and clinical outcome, and further to examine how scores might improve NEC prediction.

Methods:

A retrospective, correlational case-control study with infant data from 3 affiliated neonatal intensive care units was conducted.

Results:

Of 132 infants (44 cases, 88 controls), most were 28 weeks of gestation at birth and less (74%). Median age at NEC onset was 18 days (range: 6-34 days), with two-thirds diagnosed before 21 days. At 68 hours of life, higher GutCheckNEC scores were associated with NEC requiring surgery or resulting in death (relative risk ratio [RRR] = 1.06, P = .036), associations that persisted at 24 hours prior to diagnosis (RRR = 1.05, P = .046), and at the time of diagnosis (RRR = 1.05, P = .022) but showed no associations for medical NEC. GutCheckNEC scores were significantly correlated with pediatric early warning scores (PEWS) (r > 0.30; P < .005) and SNAPPE-II scores (r > 0.44, P < .0001). Increasing numbers of clinical signs and symptoms were positively associated with GutCheckNEC and PEWS at the time of diagnosis (r = 0.19, P = .026; and r = 0.25, P = .005, respectively).

Implications for Practice and Research:

GutCheckNEC provides structure to streamline assessment and communication about NEC risk. Yet, it is not intended to be diagnostic. Research is needed on how GutCheckNEC impacts timely recognition and treatment.
Comparing Patient-Reported Outcomes, Complications, Readmissions, and Revisions in Posterior Lumbar Fusion With, Versus Without, an Interbody Device
Authors: Steinle Anthony M. , Vaughan Wilson E. , Croft Andrew J. , Hymel Alicia , Pennings Jacquelyn S. , Chanbour Hani , Asher Anthony , Gardocki Raymond , Zuckerman Scott L. , Abtahi Amir M. , Stephens Byron F.
Published: June 2023

Study Design.

Retrospective analysis on prospectively collected data.

Objectives.

To compare posterior lumbar fusions with versus without an interbody in: 1) patient-reported outcomes (PROs) at 1 year, and 2) postoperative complications, readmission, and reoperations.

Summary of Background Data.

Elective lumbar fusion is commonly used to treat various lumbar pathologies. Two common approaches for open posterior lumbar fusion include posterolateral fusion (PLF) alone without an interbody and with an interbody through techniques like the transforaminal lumbar interbody fusion (TLIF). Whether fusion with or without an interbody leads to better outcomes remains an area of active research.

Methods.

The Lumbar Module of the Quality Outcomes Database (QOD) was queried for adults undergoing elective primary posterior lumbar fusion with or without an interbody. Covariates included demographic variables, comorbidities, primary spine diagnosis, operative variables, and baseline patient-reported outcomes (PROs), including Oswestry Disability Index (ODI), North American Spine Society (NASS) satisfaction index, numeric rating scale (NRS)-back/leg pain, and Euroqol 5-Dimension (EQ-5D). Outcomes included complications, reoperations, readmissions, return to work/activities, and PROs. Propensity score matching and linear regression modeling were used to estimate the average treatment effect on the treated (ATT) in order to assess the impact of interbody use on patient outcomes.

Results.

After propensity matching, there were 1,044 interbody patients and 215 PLF patients. ATT analysis showed that having an interbody or not had no significant impact on any outcome of interest, including 30-day complications and reoperations, 3-month readmissions, 12-month return to work, and 12-month PROs.

Conclusion.

There were no discernible differences in outcomes between patients undergoing PLF alone versus with an interbody in elective posterior lumbar fusion. These results add to the growing body of evidence that posterior lumbar fusions with and without an interbody appear to have similar outcomes up to one year postoperatively when treating degenerative lumbar spine conditions.
Associations between long-term aircraft noise exposure, cardiovascular disease, and mortality in US cohorts of female nurses
Authors: Grady Stephanie T. , Hart Jaime E. , Laden Francine , Roscoe Charlotte , Nguyen Daniel D. , Nelson Elizabeth J. , Bozigar Matthew , VoPham Trang , Manson JoAnn E. , Weuve Jennifer , Adar Sara D. , Forman John P. , Rexrode Kathryn , Levy Jonathan I. , Peters Junenette L.
Published: June 2023

Background:

There is limited research examining aircraft noise and cardiovascular disease (CVD) risk. The objective of this study was to investigate associations of aircraft noise with CVD among two US cohorts, the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII).

Methods:

Between 1994 and 2014, we followed 57,306 NHS and 60,058 NHSII participants surrounding 90 airports. Aircraft noise was modeled above 44 A-weighted decibels (dB(A)) and linked to geocoded addresses. Based on exposure distributions, we dichotomized exposures at 50 dB(A) and tested sensitivity of this cut-point by analyzing aircraft noise as categories (<45, 45–49, 50–54, ≥55) and continuously. We fit cohort-specific Cox proportional hazards models to estimate relationships between time-varying day-night average sound level (DNL) and CVD incidence and CVD and all-cause mortality, adjusting for fixed and time-varying individual- and area-level covariates. Results were pooled using random effects meta-analysis.

Results:

Over 20 years of follow-up, there were 4529 CVD cases and 14,930 deaths. Approximately 7% (n = 317) of CVD cases were exposed to DNL ≥50 dB(A). In pooled analyses comparing ≥50 with <50 dB(A), the adjusted hazard ratio for CVD incidence was 1.00 (95% confidence interval: 0.89, 1.12). The corresponding adjusted hazard ratio for all-cause mortality was 1.02 (95% confidence interval: 0.96, 1.09). Patterns were similar for CVD mortality in NHS yet underpowered.

Conclusions:

Among participants in the NHS and NHSII prospective cohorts who generally experience low exposure to aircraft noise, we did not find adverse associations of aircraft noise with CVD incidence, CVD mortality, or all-cause mortality.
Dizziness and Pain After Temporal Augmentation With Hyaluronic Acid
Authors: Zhuang Jun , Zheng Qiaoyuan , Hu Jintian
Published: June 2023

Hyaluronic acid is a commonly used soft tissue filler. However, it has been associated with numerous complications including skin necrosis, loss of vision, and cerebral infarction. In this article, the authors have reported the case of a 25-year-old woman who presented with significant dizziness and pain in the temporal and intrahairline region after undergoing hyaluronic acid augmentation of the temple and inner temporal hairline regions. Subsequently, the patient received 4 doses of a hyaluronidase injection to dissolve the emboli. She demonstrated improvement in clinical symptoms after emboli dissolution. During the 10-month posttreatment follow-up, the patient experienced gradual relief from pain and dizziness. The use of hyaluronic acid fillers should be limited in the intrahairline region as the resulting complications can be difficult to manage.
Learning Curve Analysis of Full-Length Costal Cartilage Harvesting by Plastic Surgery Residents: A Retrospective Study
Authors: Guo Junsheng , Zhang Xulong , Xu Yihao , Zheng Ruobing , You Jianjun , Fan Fei , Wang Huan
Published: June 2023

Costal cartilage harvesting (CCH) is a fundamental skill for plastic surgery residents to master. Understanding the learning process is essential for optimizing training programs and ensuring patient safety. Previous research on learning curves has been limited. A retrospective study was conducted on patients who underwent CCH between January 2018 and December 2022. The learning process of 14 inexperienced residents was analyzed using the curve-fitting method, with operative time (OT) and complication rates as outcome measured. Data were compared with 4 attending surgeons who also performed CCH. Resident OTs decreased as experience grew, with the bi-exponential model fitting best. After 10 to 20 cases, the average OT decreased to around 40 minutes. By extrapolation, novice residents require ~50 cases to achieve a plateau of OT similar to the attending surgeons, around 27 minutes. Most complications of the resident group occurred within the first 10 to 20 cases, and the complication rate of attending surgeons was <1%. Harvesting on the left side and a higher body mass index resulted in longer OTs for residents. Harvesting the seventh rib required significantly more time for both residents and attending surgeons. The learning curve for CCH shows that 10 to 20 cases are necessary for residents to perform safely and efficiently. Training should progress gradually, starting with longer incisions and leaner patients, then moving to smaller incisions and more challenging cases.

Level of Evidence:

Level IV.
Evaluation of Vitamin D-enriched Bone Graft in Surgically-induced Critical-sized Bone Defects: An experimental study
Authors: Markopoulos Georgios , Agrogiannis George , Perrea Despoina N. , Iliopoulos Dimitrios C. , Nikolaou Vasileios S.
Published: June 2023

Background:

Restoration of bone defects in the craniac vault may require the use of autografts, allografts, xenografts, or synthetic grafts. There are promising data that vitamin D may play a positive role in graft incorporation. The purpose of the present study is the evaluation of the impact of vitamin D addition to human-derived bone grafts in the healing of critical-sized bone defects in porcine skulls.

Materials and Methods:

Four identical critical-sized defects were created in the calvaria of 8 adult Landrace Large White pigs. The first defect was left blank as control, the second defect was filled with human-derived bone graft, the third defect was filled with human-derived bone graft enriched with a low concentration of vitamin D (2 mg/mL), and the fourth defect was filled with human-derived bone graft enriched with a high concentration of vitamin D (10 mg/mL). The animals were sacrificed after 12 weeks. Harvested tissue specimens were qualitatively evaluated by histology. New bone formation (bone volume/tissue volume) was quantitatively measured by histomorphometry.

Results:

Signs of bone formation were evident in all bone sockets. Mean values of the bone volume/tissue volume of the 4 defects were 10.91%, 11.05%, 10.40% and 10.87% respectively, at 12 weeks. In 5 animals, high concentration of vitamin D caused a significant improvement in bone formation in relation to controls. In 3 animals, a high concentration of vitamin D was associated with decreased bone formation compared with controls. No statistical difference was observed in the graft healing among the 4 graft sites (P > 0.05).

Conclusions:

The results of this study have shown that the addition of vitamin D to human-derived bone grafts does not have a significant effect on bone formation and graft incorporation in critical-sized bone defects of the porcine calvaria. Further high-quality studies are needed to fully elucidate the role of vitamin D in bone formation and bone graft union.
Prophages and plasmids can display opposite trends in the types of accessory genes they carry
Authors: Takeuchi Nobuto , Hamada-Zhu Sophia , Suzuki Haruo
Published: June 2023

Mobile genetic elements (MGEs), such as phages and plasmids, often possess accessory genes encoding bacterial functions, facilitating bacterial evolution. Are there rules governing the arsenal of accessory genes MGEs carry? If such rules exist, they might be reflected in the types of accessory genes different MGEs carry. To test this hypothesis, we compare prophages and plasmids with respect to the frequencies at which they carry antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) in the genomes of 21 pathogenic bacterial species using public databases. Our results indicate that prophages tend to carry VFGs more frequently than ARGs in three species, whereas plasmids tend to carry ARGs more frequently than VFGs in nine species, relative to genomic backgrounds. In
Escherichia coli
, where this prophage–plasmid disparity is detected, prophage-borne VFGs encode a much narrower range of functions than do plasmid-borne VFGs, typically involved in damaging host cells or modulating host immunity. In the species where the above disparity is not detected, ARGs and VFGs are barely found in prophages and plasmids. These results indicate that MGEs can differentiate in the types of accessory genes they carry depending on their infection strategies, suggesting a rule governing horizontal gene transfer mediated by MGEs.
Comparable Outcomes for Exclusive Lipofilling and Lipofilling-Implant Combination in Breast Reconstruction: A Retrospective Cohort Study
Authors: Razzouk Kais , Fitoussi Alfred , Tabrizi Arash Rafii
Published: June 2023

Background

Autologous fat grafting combined with prosthesis placement has become a widely accepted standard for breast reconstruction. However, a growing trend toward exclusive lipofilling-based reconstruction (LBR) is emerging. In this retrospective study, we compared the surgical and cosmetic outcomes of LBR to combined breast reconstruction (CBR) using fat grafting in conjunction with prosthetic placement.

Methods

This single-center retrospective cohort study included 170 patients who underwent mastectomy between 2014 and 2018 and received either LBR or CBR. The surgical parameters and outcomes were compared between the two groups.

Additionally, the cosmetic outcome was evaluated using a Likert-type ordinal scale by the patients, surgeon, and nurse.

Results

The study included a total of 170 patients, with 91 patients receiving LBR and 79 patients receiving CBR in combination with prosthetic placement. Patients who received exclusive lipofilling had more sessions on average than those who received prosthetic placement (3.7 lipofilling sessions vs. 2.17 sessions). Additionally, the volume of injected fat was significantly higher in the lipofilling group. No reconstruction failures were reported in either group. Patient, surgeon, and nurse satisfaction scores were high, with an average score of 4.7/5, 4.8/5, and 4.8/5, respectively, at 24 months of follow-up.

Conclusion

In this follow-up study, we demonstrate that exclusive lipofilling results in satisfactory cosmetic outcomes with a low rate of complications. This minimally invasive approach to breast reconstruction can serve as a viable alternative to flap and prosthetic-based reconstruction.