bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Spillover of Antimicrobial Resistance to Untreated Children 7–12 Years Old After Mass Drug Administration of Azithromycin for Child Survival in Niger: A Secondary Analysis of the MORDOR Cluster-Randomized Trial
Authors: Peterson Brittany , Arzika Ahmed M , Amza Abdou , Maliki Ramatou , Karamba Alio Mankara , Moussa Mariama , Kemago Mariama , Liu Zijun , Houpt Eric , Liu Jie , Pholwat Suporn , Doan Thuy , Porco Travis C , Keenan Jeremy D , Lietman Thomas M , O’Brien Kieran S
Published: May 2024

Background

The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aimed to understand the risk of spillover of antibiotic resistance to nontarget groups in these programs.

Methods

Data were used from a cluster-randomized trial comparing the effects of biannual azithromycin and placebo distribution to children 1–59 months old on child mortality rates. Nasopharyngeal samples from untreated children 7–12 years old were tested for genetic determinants of macrolide resistance (primary outcome) and resistance to other antibiotic classes (secondary outcomes). Linear regression was used to compare the community-level mean difference in prevalence by arm at the 24-month time point, adjusting for baseline prevalence.

Results

A total of 1103 children 7–12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). The adjusted mean differences in the prevalence of resistance determinants for macrolides, β-lactams, and tetracyclines were 3.4% (95% confidence interval, −4.1% to 10.8%; P = .37), −1.2% (−7.9% to 5.5%; P = .72), and −3.3% (−9.5% to 2.8%; P = .61), respectively.

Conclusions

We were unable to demonstrate a statistically significant increase in macrolide resistance determinants in untreated groups in an azithromycin mass drug administration program. While the result might be consistent with a small spillover effect, this study was not powered to detect such a small difference. Larger studies are warranted to better quantify the potential for spillover effects within these programs.
Pulmonary artery pressure monitoring in chronic heart failure: effects across clinically relevant subgroups in the MONITOR-HF trial
Authors: Clephas Pascal R D , Zwartkruis Victor W , Malgie Jishnu , van Gent Marco W F , Brunner-La Rocca Hans-Peter , Szymanski Mariusz K , van Halm Vokko P , Handoko M Louis , Kok Wouter E M , Asselbergs Folkert W , van Kimmenade Roland R J , Manintveld Olivier C , van Mieghem Nicolas M D A , Beeres Saskia L M A , Post Marco C , Borleffs C Jan Willem , Tukkie Raymond , Mosterd Arend , Linssen Gerard C M , Spee Ruud F , Emans Mireille E , Smilde Tom D J , van Ramshorst Jan , Kirchhof Charles J H J , Feenema-Aardema Margriet W , da Fonseca Carlos A , van den Heuvel Mieke , Hazeleger Ronald , van Eck Martijn , van Heerebeek Loek , Boersma Eric , Rienstra Michiel , de Boer Rudolf A , Brugts Jasper J
Published: May 2024

Background and Aims

In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups.

Methods

The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronization therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life-, clinical-, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented.

Results

The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were non-significant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = .03; adjusted Pinteraction = .33) and diabetics (Pinteraction = .01; adjusted Pinteraction = .06) were observed. However, these interaction effects did not persist after adjusting for multiple testing.

Conclusions

This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.
Understanding evolutionary rescue and parallelism in response to environmental stress
Authors: Freitas Osmar , Campos Paulo R A
Published: May 2024

Evolutionary rescue, the process by which populations facing environmental stress avoid extinction through genetic adaptation, is a critical area of study in evolutionary biology. The order in which mutations arise and get established will be relevant to the population’s rescue. This study investigates the degree of parallel evolution at the genotypic level between independent populations facing environmental stress and subject to different demographic regimes. Under density regulation, 2 regimes exist: In the first, the population can restore positive growth rates by adjusting its population size or through adaptive mutations, whereas in the second regime, the population is doomed to extinction unless a rescue mutation occurs. Analytical approximations for the likelihood of evolutionary rescue are obtained and contrasted with simulation results. We show that the initial level of maladaptation and the demographic regime significantly affect the level of parallelism. There is an evident transition between these 2 regimes. Whereas in the first regime, parallelism decreases with the level of maladaptation, it displays the opposite behavior in the rescue/extinction regime. These findings have important implications for understanding population persistence and the degree of parallelism in evolutionary responses as they integrate demographic effects and evolutionary processes.
Cognitive and Emotional Factors Influencing the Incorporation of Advice Into Decision Making Across the Adult Lifespan
Authors: Leon Tarren , Weidemann Gabrielle , Kneebone Ian I , Bailey Phoebe E
Published: May 2024

Objectives

The present study sought to investigate the influence of advice on decision making in older age, as well as the potential influence of depressive symptoms and age-related differences in the cognitively demanding emotion regulation on advice-taking.

Method

A nonclinical sample (N = 156; 50% female; 47 young: M age = 29.87, standard deviation [SD] = 5.58; 54 middle-aged: M age = 50.91, SD = 7.13; 55 older: M age = 72.51, SD = 5.33) completed a judge–advisor task to measure degree of advice-taking, as well as measures of fluid intelligence, depressive symptoms, confidence, perceived advice accuracy, and emotion regulation.

Results

Age did not influence degree of advice-taking. Greater depressive symptoms were associated with more reliance on advice, but only among individuals who identified as emotion regulators. Interestingly, older age was associated with perceiving advice to be less accurate.

Discussion

The study contributes to the sparse literature on advice-taking in older age. Cognitive and emotional factors influence the degree to which advice is incorporated into decision making in consistent ways across the adult lifespan. A key difference is that older adults take as much advice as younger adults despite perceiving the advice to be less accurate.
Freedom of speech, news and the classical republican tradition in seventeenth-century England
Authors: Gianoutsos Jamie
Published: May 2024

This article examines how printed newsbooks shaped conceptions of freedom of speech and the classical republican tradition in Britain. After exploring the persistent concern of parliamentary and then royalist newsbooks to provide true information to the public, the article considers how newsbooks increasingly condemned press control and state secrecy as tyrannical. Its final sections explore the contributions of Marchamont Nedham and examine how John Streater significantly advanced arguments for free speech as a foundational liberty for the free state, developing earlier claims in newsbooks. The article suggests that the invention of printed news encouraged more populist strands of classical republicanism.
The role of community pharmacists as oral health advisors in the management of oral effects of asthma medications: an exploratory survey
Authors: Ho Alex Vy Luan , Lau Isabel , Davidson Michelle , Nimmo Alan , Croker Felicity Ann
Published: May 2024

Objectives

To investigate community pharmacists’ attitudes, confidence, practice, knowledge, and barriers towards the management of oral side effects of asthma medications.

Methods

A paper-based questionnaire was developed from previous research, trialled, and validated. Convenience sampling through web search was used to identify pharmacy practices across Cairns, Queensland, Australia. Practices were contacted by email and phone before hand-delivering and collecting questionnaires.

Key findings

Thirty eight community pharmacist responses were descriptively analysed. Community pharmacists surveyed within the Cairns region feel that it is within their role to help manage the side effects of asthma medications. Many feel this is best conveyed during inhaler dispensing and instruction. Current advice is more prompted rather than preventative. Pharmacists routinely advise patients of mouth-rinsing following inhaler use, however the link to preventing side effects is not clearly communicated. Pharmacists are confident in recognizing and managing common side effects such as oral thrush and dry mouth, but fewer are aware of dental decay and gingivitis. Many identify a lack of guidelines as the largest barrier to providing preventive oral health advice.

Conclusions

Cairns community pharmacists already self-perceive their role in the management of oral side effects of asthma medications. Advice given to patients is practical but does not clearly convey the causative associations between asthma medications and their potential oral side effects. Patient education is prompted more by enquiry rather than a preventative approach. The development of standardized practice protocols and integration within undergraduate degrees or continuing education may benefit the community–pharmacist delivered care.
Financial Crimes as ‘Serious Non-Political Crimes’: Consequences for the Concepts of Seriousness and Unworthiness in Exclusion Law
Authors: Guiot Juliette
Published: May 2024

Financial crimes were recently recognized by the Conseil d’État, France’s supreme administrative court, as ‘serious non-political crimes’ for the purposes of exclusion under article 1F(b) of the Refugee Convention. Such an extension of the scope of article 1F(b) raises questions regarding the seriousness threshold of article 1F(b) and its link to bodily harm. A first approach would be to establish the indirect relationship between financial crimes and bodily harm. Another approach would be to discard the concept of bodily harm as being pivotal in understanding the scope of the exclusion clauses. This second solution would have crucial implications for the theoretical underpinnings of the exclusion clauses of article 1F of the Refugee Convention, namely on the concept of unworthiness. In this regard, the recognition of financial crimes as rendering an asylum seeker unworthy of protection highlights the link between exclusion and moral and societal concerns.
Serological Evidence of Mpox Virus Infection During Peak Mpox Transmission in New York City, July to August 2022
Authors: Pathela Preeti , Townsend Michael B , Kopping Erik J , Tang Jennifer , Navarra Terese , Priyamvada Lalita , Carson William C , Panayampalli S Satheshkumar , Fowler Randal C , Kyaw Nang , Hughes Scott , Jamison Kelly
Published: May 2024

Background

The extent to which infections may have been undetected in an epicenter of the 2022 mpox outbreak is unknown.

Methods

A serosurvey (July and August 2022) assessed the seroprevalence and correlates of mpox infection among a diverse sample of asymptomatic patients with no prior mpox diagnoses and no known histories of smallpox or mpox vaccination. We present seropositivity stratified by participant characteristics collected via survey.

Results

Two-thirds of 419 participants were cismen (281 of 419), of whom 59.1% (166 of 281) reported sex with men (MSM). The sample also included 109 ciswomen and 28 transgender/gender nonconforming/nonbinary individuals. Overall seroprevalence was 6.4% (95% confidence interval [CI], 4.1%–8.8%); 3.7% among ciswomen (95% CI, 1.0%–9.1%), 7.0% among cismen with only ciswomen partners (95% CI, 2.0%–11.9%), and 7.8% among MSM (95% CI, 3.7%–11.9%). There was little variation in seroprevalence by race/ethnicity, age group, HIV status, or number of recent sex partners. No participants who reported close contact with mpox cases were seropositive. Among participants without recent mpox-like symptoms, 6.3% were seropositive (95% CI, 3.6%–9.0%).

Conclusions

Approximately 1 in 15 vaccine-naive people in our study had antibodies to mpox during the height of the NYC outbreak, indicating the presence of asymptomatic infections that could contribute to ongoing transmission.
Widespread horizontal gene transfer between plants and bacteria
Authors: Haimlich Shelly , Fridman Yulia , Khandal Hitaishi , Savaldi-Goldstein Sigal , Levy Asaf
Published: May 2024

Plants host a large array of commensal bacteria that interact with the host. The growth of both bacteria and plants is often dependent on nutrients derived from the cognate partners, and the bacteria fine-tune host immunity against pathogens. This ancient interaction is common in all studied land plants and is critical for proper plant health and development. We hypothesized that the spatial vicinity and the long-term relationships between plants and their microbiota may promote cross-kingdom horizontal gene transfer (HGT), a phenomenon that is relatively rare in nature. To test this hypothesis, we analyzed the Arabidopsis thaliana genome and its extensively sequenced microbiome to detect events of horizontal transfer of full-length genes that transferred between plants and bacteria. Interestingly, we detected 75 unique genes that were horizontally transferred between plants and bacteria. Plants and bacteria exchange in both directions genes that are enriched in carbohydrate metabolism functions, and bacteria transferred to plants genes that are enriched in auxin biosynthesis genes. Next, we provided a proof of concept for the functional similarity between a horizontally transferred bacterial gene and its Arabidopsis homologue in planta. The Arabidopsis DET2 gene is essential for biosynthesis of the brassinosteroid phytohormones, and loss of function of the gene leads to dwarfism. We found that expression of the DET2 homologue from Leifsonia bacteria of the Actinobacteria phylum in the Arabidopsis det2 background complements the mutant and leads to normal plant growth. Together, these data suggest that cross-kingdom HGT events shape the metabolic capabilities and interactions between plants and bacteria.
Transcriptome analysis reveals the role of long noncoding RNAs in specific deposition of inosine monphosphate in Jingyuan chickens
Authors: Zhao Wei , Cai Zhengyun , Jiang Qiufei , Zhang Juan , Yu Baojun , Feng Xiaofang , Fu Xi , Zhang Tong , Hu Jiahuan , Gu Yaling
Published: May 2024

Inosine monphosphate (IMP) is one of the important indicators for evaluating meat flavor, and long noncoding RNAs (lncRNAs) play an important role in its transcription and post-transcriptional regulation. Currently, there is little information about how lncRNA regulates the specific deposition of IMP in chicken muscle. In this study, we used transcriptome sequencing to analyze the lncRNAs of the breast and leg muscles of the Jingyuan chicken and identified a total of 357 differentially expressed lncRNAs (DELs), of which 158 were up-regulated and 199 were down-regulated. There were 2,203 and 7,377 cis- and trans-regulated target genes of lncRNAs, respectively, and we identified the lncRNA target genes that are involved in NEGF signaling pathway, glycolysis/glucoseogenesis, and biosynthesis of amino acids pathways. Meanwhile, 621 pairs of lncRNA-miRNA-mRNA interaction networks were constructed with target genes involved in purine metabolism, fatty acid metabolism, and biosynthesis of amino acids. Next, three interacting meso-networks gga-miR-1603-LNC_000324-PGM1, gga-miR-1768-LNC_000324-PGM1, and gga-miR-21-LNC_011339-AMPD1 were identified as closely associated with IMP-specific deposition. Both differentially expressed genes (DEGs) PGM1 and AMPD1 were significantly enriched in IMP synthesis and metabolism-related pathways, and participated in the anabolic process of IMP in the form of organic matter synthesis and energy metabolism. This study obtained lncRNAs and target genes affecting IMP-specific deposition in Jingyuan chickens based on transcriptome analysis, which deepened our insight into the role of lncRNAs in chicken meat quality.
Considerations on the evolutionary biology and functions of eosinophils: what the “haeckel”?
Authors: Ackerman Steven J , Stacy Nicole I
Published: May 2024

The origins and evolution of the eosinophilic leukocyte have received only scattered attention since Paul Ehrlich first named this granulocyte. Studies suggest that myeloperoxidase, expressed by granulocytes, and eosinophil peroxidase diverged some 60 to 70 million years ago, but invertebrate to vertebrate evolution of the eosinophil lineage is unknown. Vertebrate eosinophils have been characterized extensively in representative species at light microscopic, ultrastructural, genetic, and biochemical levels. Understanding of eosinophil function continues to expand and includes to date regulation of “Local Immunity And/Or Remodeling/Repair” (the so-called LIAR hypothesis), modulation of innate and adaptive immune responses, maintenance of tissue and metabolic homeostasis, and, under pathologic conditions, inducers of tissue damage, repair, remodeling, and fibrosis. This contrasts with their classically considered primary roles in host defense against parasites and other pathogens, as well as involvement in T-helper 2 inflammatory and immune responses. The eosinophils’ early appearance during evolution and continued retention within the innate immune system across taxa illustrate their importance during evolutionary biology. However, successful pregnancies in eosinophil-depleted humans/primates treated with biologics, host immune responses to parasites in eosinophil-deficient mice, and the absence of significant developmental or functional abnormalities in eosinophil-deficient mouse strains under laboratory conditions raise questions of the continuing selective advantages of the eosinophil lineage in mammals and humans. The objectives of this review are to provide an overview on evolutionary origins of eosinophils across the animal kingdom, discuss some of their main functions in the context of potential evolutionary relevance, and highlight the need for further research on eosinophil functions and functional evolution.
Ethical Problems of Observational Studies and Big Data Compared to Randomized Trials
Authors: Raymond Jean , Fahed Robert , Darsaut Tim E
Published: May 2024

The temptation to use prospective observational studies (POS) instead of conducting difficult trials (RCTs) has always existed, but with the advent of powerful computers and large databases, it can become almost irresistible. We examine the potential consequences, were this to occur, by comparing two hypothetical studies of a new treatment: one RCT, and one POS. The POS inevitably submits more patients to inferior research methodology. In RCTs, patients are clearly informed of the research context, and 1:1 randomized allocation between experimental and validated treatment balances risks for each patient. In POS, for each patient, the risks of receiving inferior treatment are impossible to estimate. The research context and the uncertainty are down-played, and patients and clinicians are at risk of becoming passive research subjects in studies performed from an outsider’s view, which potentially has extraneous objectives, and is conducted without their explicit, autonomous, and voluntary involvement and consent.
Impairment Arguments, Interests, and Circularity
Authors: Napier Stephen
Published: May 2024

A common justification for abortion rights is that the death of the fetus does not violate any of the fetus’s time-relative interests. The time-relative interest account (TRIA) of harm and wrongdoing tells us that a necessary condition for harming someone is that his or her time-relative interests are frustrated. Regarding the justification for abortion, this account falls prey to impairment arguments. Impairment arguments entertain cases of prenatal injury, such as the mother using illicit drugs that disable the child. The intuition is that the child who is born with such disabilities is harmed by the mother’s drug use. But it is unclear what time-relative interest is violated in cases of prenatal harm. Typical responses to impairment arguments point out that the abortion case is different because the child does not exist to experience such harms; but in prenatal injury + survival cases, the child does live to experience those harms. Thus, the TRIA justification for abortion is not impugned by impairment counter-examples. This article argues that this response to impairment arguments is viciously circular. The response must say that so long as you kill the child, no harm is done. But this assumes that killing itself is morally inconsequential and is not itself a case of harm. The response to impairment arguments, then, assumes the permissibility of abortion.
Wildfire Management Strategy and Its Relation to Operational Risk
Authors: Noonan-Wright Erin , Seielstad Carl
Published: May 2024

Changes to US wildfire policy in 2009 blurred the distinction between fires managed for resource benefits and fires with primarily suppression objectives, making management strategies difficult to track. Here, qualitative text is coded from a sample of 282 Wildland Fire Decision Support System Relative Risk Assessments completed on wildfires between 2010 and 2017 to examine the prevalence of different strategies and their associations with risk. Suppression is used most, associated with high risk. Managers discuss intent to suppress even when it is untenable. Monitoring, confine, or point protection are used much less commonly and when risk is low. The Southwest region discusses a diversity of strategies, leveraging landscape barriers from past management to support them; the Northwest discusses suppression or monitoring and rarely links strategy selection to barriers. Based on associations between physical barriers to fire spread, risk, and strategy, creating more barriers may provide a path forward to better implement fire policy.

Study Implications: Systematic analysis of text data in wildfire decision documents provides insights into how fires are managed. Most wildfires are still aggressively suppressed despite federal fire policy promoting the use of fire to enhance resources. When managers discuss risk during wildfires, it is evident that physical barriers to fire spread (e.g., rivers, roads, trails, rocky scree), including mechanical fuel treatments, prescribed fires, and previous wildfires, are important factors in operational fire planning. However, management strategies promoting the use of wildfire to enhance ecological resiliency or reduce transmission of future fires to values are used sparingly. Southwest fire managers are relying on past wildfires, fuel treatments, and prescribed fires more so than the Northwest to engage in a full spectrum of fire management strategies. This finding suggests that, at least in some geographies, ongoing investments in fuels management will pay dividends in reducing risk and broadening opportunities to meet federal policy goals.
Constraints on Mechanical Fuel Reduction Treatments in United States Forest Service Wildfire Crisis Strategy Priority Landscapes
Authors: Woolsey George A , Tinkham Wade T , Battaglia Mike A , Hoffman Chad M
Published: May 2024

The USDA Forest Service recently launched a Wildfire Crisis Strategy outlining objectives to safeguard communities and other values at risk by substantially increasing the pace and scale of fuel reduction treatment. This analysis quantified layered operational constraints to mechanical fuel reduction treatments, including existing vegetation, protected areas, steep slopes, and administrative boundaries in twenty-one prioritized landscapes. Results suggest that achieving the objective to treat 20%–40% of high-risk area is unlikely in most landscapes under a business-as-usual approach to mechanical fuel reduction treatments. Increased investment in steep-slope systems and expanded road access opens sufficient acreage to meet treatment objectives in eighteen of twenty-one priority landscapes. Achieving treatment objectives in the remaining three landscapes will require both increased investment to overcome physical constraints and navigating administrative complexities within reserved land allocations to implement fuels treatments at the pace and scale needed to moderate fire risk to communities.

Study Implications: Legal, operational, and administrative factors have hindered the implementation of proposed wildland fire risk reduction management actions. Investing in steep-slope systems, expanding use of temporary roads, and revising administrative rules to allow for appropriately tailored mechanical thinning in special conservation areas are possible ways to meet fuel reduction treatment objectives of the USDA Forest Service Wildfire Crisis Strategy in twenty-one landscapes across the western United States. Broadening the land base available for mechanical treatment allows for flexibility to develop treatment plans that optimize across the multiple dimensions of effective landscape-scale fuel treatment design and restore fire as a key ecosystem process.
Risk Analysis of Respiratory Syncytial Virus Among Infants in the United States by Birth Month
Authors: Gantenberg Jason R , van Aalst Robertus , Bhuma Monika Reddy , Limone Brendan , Diakun David , Smith David M , Nelson Christopher B , Bengtson Angela M , Chaves Sandra S , La Via William V , Rizzo Christopher , Savitz David A , Zullo Andrew R
Published: May 2024

Background

Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality among US infants. A child’s calendar birth month determines their age at first exposure(s) to RSV. We estimated birth month-specific risk of medically attended (MA) RSV lower respiratory tract infection (LRTI) among infants during their first RSV season and first year of life (FYOL).

Methods

We analyzed infants born in the USA between July 2016 and February 2020 using three insurance claims databases (two commercial, one Medicaid). We classified infants’ first MA RSV LRTI episode by the highest level of care incurred (outpatient, emergency department, or inpatient), employing specific and sensitive diagnostic coding algorithms to define index RSV diagnoses. In our main analysis, we focused on infants’ first RSV season. In our secondary analysis, we compared the risk of MA RSV LRTI during infants’ first RSV season to that of their FYOL.

Results

Infants born from May through September generally had the highest risk of first-season MA RSV LRTI—approximately 6–10% under the specific RSV index diagnosis definition and 16–26% under the sensitive. Infants born between October and December had the highest risk of RSV-related hospitalization during their first season. The proportion of MA RSV LRTI events classified as inpatient ranged from 9% to 54% (specific) and 5% to 33% (sensitive) across birth month and comorbidity group. Through the FYOL, the overall risk of MA RSV LRTI is comparable across birth months within each claims database (6–11% under the specific definition, 17–30% under the sensitive), with additional cases progressing to care at outpatient or ED settings.

Conclusions

Our data support recent national recommendations for the use of nirsevimab in the USA. For infants born at the tail end of an RSV season who do not receive nirsevimab, a dose administered prior to the onset of their second RSV season could reduce the incidence of outpatient- and ED-related events.
Moderately hypofractionated proton beam therapy for localized prostate cancer: 5-year outcomes of a phase II trial
Authors: Murakami Motohiro , Ishikawa Hitoshi , Sekino Yuta , Nishiyama Hiroyuki , Suzuki Hiroyoshi , Sugahara Shinji , Iizumi Takashi , Mizumoto Masashi , Okumura Toshiyuki , Keino Naoto , Iizumi Yuichi , Hashimoto Koichi , Gosho Masahiko , Sakurai Hideyuki
Published: May 2024

The usefulness of moderately hypofractionated radiotherapy for localized prostate cancer has been extensively reported, but there are limited studies on proton beam therapy (PBT) using similar hypofractionation schedules. The aim of this prospective phase II study is to confirm the safety of a shortened PBT course using 70 Gy relative biological effectiveness (RBE) in 28 fractions. From May 2013 to June 2015, 102 men with localized prostate cancer were enrolled. Androgen deprivation therapy was administered according to risk classification. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. Of the 100 patients ultimately evaluated, 15 were classified as low risk, 43 as intermediate risk, and 42 as high risk. The median follow-up time of the surviving patients was 96 months (range: 60–119 months). The 5-year cumulative incidences of grade 2 gastrointestinal/genitourinary adverse events were 1% (95% CI: 0.1–6.9) and 4% (95% CI: 1.5–10.3), respectively; no grade ≥ 3 gastrointestinal/genitourinary adverse events were observed. The current study revealed a low incidence of late adverse events in prostate cancer patients treated with moderately hypofractionated PBT of 70 Gy (RBE) in 28 fractions, indicating the safety of this schedule.
Hemostatic Evaluation of Refrigerated Whole Blood Stored 7 Days Post-Expiration
Authors: Greene Nicholas A , McIntosh Colby S , Meledeo Michael A , Reddoch-Cardenas Kristin M
Published: May 2024

Introduction

The United States Army has shifted doctrine to focus on large-scale combat operations against peer to near-peer adversaries. Future conflicts could result in a limited supply chain, leaving medical providers with only expired blood products for treatment of hemorrhagic shock. This study evaluated quality, function, and safety metrics of whole blood stored for 1 week past regulated expiration (i.e., 35 days, in CPDA-1).

Materials and Methods

Whole blood units (n = 6) were collected in citrate phosphate dextrose adenine-1 (CPDA-1) anticoagulant and stored refrigerated for up to 42 days. Units were sampled on days 35, 37, 39, and 42 of storage and evaluated for the following: complete blood count, blood metabolism and chemistries, clotting dynamics, and presence of bacteria.

Results

The majority of evaluated parameters fell outside of normal clinical ranges beginning at day 35 of storage. At 42 days, blood pH was 6.58 ± 0.038, hemolysis was significantly increased (P = .037 vs day 35), and bacterial contamination was not evident. Glucose levels continuously dropped during extended storage. K+ was significantly increased at day 42 compared to day 35 (P = .010). A significant reduction in clot strength, factor V activity, and factor VIII activity was evident beginning at day 39 of storage.

Conclusions

Storage of whole blood out to 42 days results in a continuous decline in function, but further in vivo safety studies should be performed to determine if the benefits of expired blood outweigh the risks. Other methods to safely extend storage of whole blood that maintain hemostatic function and preserve safety should be investigated, with emphasis placed on methods that reduce potassium leak and/or hemolysis.
Pilot Study: Developing Curriculum to Prepare Fourth-Year Medical Students Applying for OBGYN Residency Within the Defense Health Agency
Authors: Wright Danielle , Boedeker David , Ulfers Alexander , Peterson Logan
Published: May 2024

Background

Obstetrics and gynecology (OBGYN) is becoming increasingly competitive among medical specialties. As a result, many medical schools have frameworks to help their students increase their competitiveness to maximize chances of a successful match. However, “boot camps” have traditionally been geared toward the transition to intern year and not to sub-internships during the fourth year of medical school. We aimed to develop a boot camp for rising fourth-year medical students planning to apply into OBGYN before the initiation of their sub-internships and interview season.

Methods

Sixteen students enrolled in this course led by faculty OBGYNs at our institution. We utilized a combination of mentorship, coaching, and education to achieve applicant success. The curriculum included formal lectures, surgical skills training, and focused feedback from our applicant development committee.

Results

Our response rate was 100% and 94% for the pre-intervention and post-intervention survey, respectively. Before the intervention, the majority of participants felt either neutral (47.4%) or unprepared (21.1%) regarding their knowledge before their sub-internships. However, after the intervention, all reported feeling more prepared for their rotations. All respondents either agreed (60%) or strongly agreed (40%) that the course increased their confidence in performing well on audition rotations. Our match rate increased from 62% for the class of 2022 (before this intervention) to 75% for the class of 2023.

Discussion

In light of the increasing residency match competitiveness, it is crucial to investigate programs that can assist students in developing stronger applications. This reproducible intervention utilizes few resources and can be implemented at most medical schools to better support their OBGYN applicants.
The Association Between Grip Strength, Upper Body Power, and Limb Dominance in a Military Population
Authors: Silder Amy , Zifchock Rebecca , Brown Luke , Sessoms Pinata , Jones Douglas
Published: May 2024

Introduction

Military service members rely on upper body strength and power to accomplish tasks such as carrying heavy weapons and gear, rappelling, combat grappling, and marksmanship. Early identification of the factors that lead to reduced upper body strength and power would enable leadership to predict and mitigate aspects that decrease military operational readiness and increase injury risk. The purpose of this study was to investigate the relationship between grip strength and upper body power in U.S. Infantry Marines. We hypothesized that dominant arm grip strength would show a strong positive correlation with upper body power and that the dominant arm would be more powerful than the non-dominant arm.

Materials and Methods

A total of 120 U.S. Marines completed 3 maximum effort isometric grip strength trials with their dominant hand and 3 maximum effort ballistic pushups on a ForceDecks force plate system. Force plate data were used to estimate pushup height and peak power. Maximum grip strength, pushup height, and peak power across the 3 trials were used for analysis. Pearson’s correlation was used to test for associations between peak power, pushup height, and grip strength. Paired t-tests were used to test for differences in peak power between the dominant and non-dominant arms.

Results

A very weak correlation was found between grip strength and upper body power, but there was no relationship between grip strength and pushup height. Additionally, there were no significant differences in upper body power between the dominant and non-dominant arms.

Conclusions

The results of this study suggest that grip strength is not predictive of upper body power and cannot be used as a stand-alone measure of physical readiness in a military unit. These findings do not, however, degrade the potential of both measures to predict and inform health status and physical readiness. Future prospective research should be conducted to determine if either of these measures can be used as indicators of performance and/or injury susceptibility and if limb dominance plays a role in injury incidence within the upper extremity.
Eccentric orbits in disc-embedded EMRIs : orbital evolution and observability trend in LISA
Authors: Basu Prasad , Chatterjee Sangita , Mondal Soumen
Published: May 2024

The purpose of this work is to study the orbital evolution under the combined effect of disc-drag and GW-emission for E/IMRIs endowed with accretion disc. We study the dependence of disc-torque and GW-torque on the orbital-parameters of compact companions. We employ a semirelativistic technique to study E/IMRI-dynamics evolving under most general elliptical-orbits in the equatorial plane and assume natural transonic-disc in the Kerr space–time around a supermassive black hole (SMBH). To conduct an accurate investigation, we fix the disc attributes and alter orbital-parameters, mass-ratio of E/IMRIs and spin of SMBH. We notice that high-eccentric orbits with smaller semimajor axis exhibit a more prominent impact of accretion-drag on the companion-dynamics. The magnitude of disc-torque is greater and almost one order higher in retrograde-spins than prograde-spins. We identify the best fitted orbital parameters, which can potentially enhance detectability of accretion-disc effect on the observed GW-signal. Prioritizing such orbital-configuration, we obtain substantial impact on the dephasing for maximum disc-torque and high signal-to-noise-ratio (SNR) in emitted signals. Employing a threshold-SNR (>8), we finally identify the detectability trend of those systems in LISA-band. A key aspect of our findings is the ability to constrain the orbital parameters by GW-detection and estimate orbital-ellipticity or other orbital-characteristics by comparing two SNRs. Hence, the study will be important in understanding the orbital-evolution, predicting orbital-configuration, and finding detectability for such gas-rich E/IMRIs. The predictions of E/IMRI formation pathways from ground and more certainly from future space-borne detectors, would also be possible from the likelihood of such eccentric-E/IMRIs in the sky.
Characteristics and Outcome of Vascular Graft Infections: A Risk Factor and Survival Analysis
Authors: Stockschläder Leonie , Margaryan Donara , Omran Safwan , Schomaker Martin , Greiner Andreas , Trampuz Andrej
Published: May 2024

Background

Vascular graft infection (VGI) is a serious complication after implantation of arterial vascular grafts. Optimal surgical and pathogen-specific antimicrobial treatment regimens for VGI are largely unknown. We evaluated patients with arterial VGI according to onset, location, microbiological and imaging characteristics, and surgical and antimicrobial treatment and performed an outcome evaluation.

Methods

Consecutive patients with VGI treated in 2 hospitals from 2010 through 2020 were retrospectively analyzed. Uniform definition criteria and standardized outcome evaluation were applied. Logistic regression was used for multiple analysis; survival analysis was performed with Kaplan-Meier analysis and a log-rank test.

Results

Seventy-eight patients with VGI were included: 30 early-onset cases (<8 weeks after graft implantation) and 48 late-onset cases, involving 49 aortic and 29 peripheral grafts. The median time from initial implantation to diagnosis of VGI was significantly longer in aortic than peripheral VGIs (363 vs 56 days, P = .018). Late-onset VGI (odds ratio [OR], 7.3; P = .005) and the presence of surgical site infection/complication (OR, 8.21; P = .006) were independent risk factors for treatment failure. Surgical site infection/complication was associated with a higher risk for early-onset VGI (OR, 3.13; P = .040). Longer infection-free survival was observed in cases where the infected graft was surgically removed (P = .037).

Conclusions

This study underlines the importance of timely diagnosis of VGI and preventing surgical site infections/complications at graft implantation. It highlights the complexity of infection eradication, especially for late-onset infections, and the importance of adequate antimicrobial and surgical treatment.
In-home TB Testing Using GeneXpert Edge is Acceptable, Feasible, and Improves the Proportion of Symptomatic Household Contacts Tested for TB: A Proof-of-Concept Study
Authors: Medina-Marino Andrew , Bezuidenhout Dana , Bezuidenhout Charl , Facente Shelley N , Fourie Bernard , Shin Sanghyuk S , Penn-Nicholson Adam , Theron Grant
Published: May 2024

Background

Household contact investigations are effective for finding tuberculosis (TB) cases but are hindered by low referral uptake for clinic-based evaluation and testing. We assessed the acceptability and feasibility of in-home testing of household contacts (HHC) using the GeneXpert Edge platform.

Methods

We conducted a 2-arm, randomized study in Eastern Cape, South Africa. HHCs were verbally assessed using the World Health Organization-recommended 4-symptom screen. Households with ≥1 eligible symptomatic contact were randomized. Intervention households received in-home GeneXpert MTB/RIF molecular testing. GeneXpert-positive HHCs were referred for clinic-based treatment. Standard-of-care households were referred for clinic-based sputum collection and testing. We defined acceptability as agreeing to in-home testing and feasibility as generation of valid Xpert MTB/RIF results. The proportion and timeliness of test results received was compared between groups.

Results

Eighty-four households were randomized (n = 42 per arm). Of 100 eligible HHCs identified, 98/100 (98%) provided consent. Of 51 HHCs allocated to the intervention arm, all accepted in-home testing; of those, 24/51 (47%) were sputum productive and 23/24 (96%) received their test results. Of 47 HCCs allocated to standard-of-care, 7 (15%) presented for clinic-based TB evaluation, 6/47 (13%) were tested, and 4/6 (67%) returned for their results. The median (interquartile range) number of days from screening to receiving test results was 0 (0) and 16.5 (11-15) in the intervention and standard-of-care arms, respectively.

Conclusions

In-home testing for TB was acceptable, feasible, and increased HHCs with a molecular test result. In-home testing mitigates a major limitation of household contact investigations (dependency on clinic-based referral), revealing new strategies for enhancing early case detection.
Oncology drug pricing: potential Medicare savings on cancer-directed and supportive care medications through the Mark Cuban cost plus drug model
Authors: Bouvette Max J , Lam Anh B , Bouvette Christopher , Ayanambakkam Adanma , Nipp Ryan D
Published: May 2024

Prescription drug costs within oncology remain a challenge for many patients with cancer. The Mark Cuban Cost Plus Drug Company (MCCPDC) launched in 2022, aiming to provide transparently priced medications at reduced costs. In this study, we sought to describe the potential impact of MCCPDC on Medicare Part-D oncology spending related to cancer-directed (n = 7) and supportive care (n = 26) drugs. We extracted data for drug-specific Part-D claims and spending for 2021. Using 90-count purchases from MCCPDC, we found potential Part-D savings of $857.8 million (91% savings) across the 7 cancer-directed drugs and $28.7 million (67% savings) across 21/26 (5/26 did not demonstrate savings) supportive care drugs. Collectively, our findings support that alternative purchasing models like MCCPDC may promote substantial health care savings.
Speaking of ‘violence’: Figleaf use in sexualized violence contexts
Authors: Kenyon Madeleine
Published: May 2024

In this project, I develop the concept of a sexualized violence figleaf, a speech mechanism often used in sexualized violence discourse to dismiss or characterize assault as some other kind of thing: a misunderstanding, a change of heart by the victim, a mischaracterization of the perpetrator, or any other number of things which are not rape, or violence. Sexualized violence figleaves are an extension of Jennifer Saul's work on racial and gender figleaves, as the underlying mechanics of the utterance track those of Saul's figleaves. In other words, I am developing a figleaf variant, showing that this conceptual tool is useful for analysing utterances beyond racist, sexist, and conspiracist speech, upon which Saul focuses. Rather, bringing figleaves into the realm of sexualized violence discourse illuminates features of the discourse which are often obscured by the prevalence of strong social intuitions about rapists and their corresponding character.
Understanding the contents and gaps in sexual and reproductive health toolkits designed for adolescence and young adults: a scoping review
Authors: Castleton Patience , Meherali Salima , Memon Zahid , Lassi Zohra S
Published: May 2024

Introduction

Adolescence is a crucial stage of physical and sexual maturation and development and a period in which understanding sexual and reproductive health (SRH) is important. SRH interventions and toolkits provide a range of valuable resources and information to young people, educators, and members of the community on numerous topics, including contraception and puberty.

Objectives

The usefulness and reliability of these available toolkits have not been previously studied, thus limiting our understanding of their appropriateness and contents. Hence, this scoping review aimed to synthesize the available toolkits aimed at the SRH of adolescents and young adults to understand the contents, design, and information gaps.

Methods

A systematic search was conducted of 6 medical databases and 12 gray literature sites. Sixteen toolkits published globally before May 2023 were included in our review.

Results

The majority of toolkits (n = 12) contained information related to general SRH knowledge and contraception, whereas only 3 contained information on teenage pregnancy. We found that aiming the toolkits toward educators and health care workers was a favorable design over targeting adolescents and young adults directly and that vulnerable youth—including LGBTQI+ (lesbian, gay, bisexual, transgender, queer or questioning, asexual or allied, intersex, and additional identities) and youth from humanitarian settings—were not well represented.

Conclusion

We identified key gaps in the inclusion of information in a range of SRH topics, such as LGBTQI+ sexuality, teenage pregnancy, and safe abortion, in the currently available SRH toolkits and their lack of applicability in a global context. Furthermore, we provide recommendations for areas of improvement to encourage adolescents’ agency in their SRH education.
Unlocking Precision in Callose Staining: Unveiling the Role of Sirofluor
Authors: Conrath Uwe
Published: May 2024

Callose is a vital component in plant biology, contributing to essential processes like pollen maturation and defense against pathogens. However, misconceptions surrounding callose staining persist, particularly regarding the role of aniline blue. It is now known that commercial aniline blue contains sirofluor, and it is this fluorophore, rather than aniline blue itself, that is responsible for the observed fluorescence during callose detection.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .