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Platelet transfusion refractoriness is a serious clinical concern that complicates the management of thrombocytopenic patients. Previous studies have suggested a potential role for both complement and platelet activation based on in vitro analyses of platelet concentrates. In this study, the post-transfusion platelet response, as indicated by the corrected count increment at 1 and 24 h after prophylactic platelet transfusions, respectively, was correlated with the 1 h post-transfusion Δconcentration (1 h post-transfusion – pretransfusion) of complement and platelet activation biomarkers. The study was registered as a clinical trial at ClinicalTrials.gov (identifier: NCT02601131) and patients were recruited during inpatient care in the hematological department. Soluble terminal complement complexes, soluble P-selectin and soluble CD40 ligand were analyzed. Confirmed alloimmunized patients were excluded. Included subjects were either given platelet transfusions (n = 43) and categorized into four clinical study groups or included in a non-transfused control group (n = 10). In total, 54 transfusions were included. No transfusion-mediated complement activation was observed. The transfusions were associated with a significant increase in the concentration of soluble P-selectin (p < .001), primarily corresponding to the passive infusion of soluble P-selectin-containing plasma residuals. The Δconcentration of soluble P-selectin was, however, not significantly correlated with the corrected count increments. Thus, significant correlations between biomarkers of complement and platelet activation and the post-transfusion platelet response could not be demonstrated in this study.

Abstract Background and objectives Several thrombin generation tests are available but few have been directly compared. Our primary aim was to investigate the correlation of two thrombin generation tests, thrombin generation assay-calibrated automated thrombogram (TGA-CAT) and INNOVANCE ETP, to factor VIII levels (FVIII:C) in a group of patients with hemophilia A. The secondary aim was to investigate inter-laboratory variation for the TGA-CAT method. Methods Blood samples were taken from 45 patients with mild, moderate and severe hemophilia A. The TGA-CAT method was performed at both centers while the INNOVANCE ETP was only performed at the Stockholm center. Correlation between parameters was evaluated using Spearman´s rank correlation test. For determination of the TGA-CAT inter-laboratory variability Bland-Altman plots was used. Results The correlation for the INNOVANCE ETP and TGA-CAT methods with FVIII:C in persons with hemophilia (PWH) was r=0,701 and r=0,734 respectively. The correlation between the two methods was r=0,546. When dividing the study material into disease severity groups (mild, moderate and severe) based on FVIII levels, both methods fail to discriminate between them. The variability of the TGA-CAT results performed at the two centers was reduced after normalization, before normalization 29% of values showed less than ±10% difference while after normalization the number increased to 41%. Conclusions Both methods correlate in an equal manner to FVIII:C in PWH but show a poor correlation to each other. The level of agreement for the TGA-CAT method was poor though slightly improved after normalization of data. Further improvement of standardization of these methods is warranted.

Evolutionary molecular studies of island radiations may lead to insights in the role of vicariance, founder events, population size and drift in the processes of population differentiation. We evaluate the degree of population genetic differentiation and fixation of the Canary Islands blue tit subspecies complex using microsatellite markers and aim to get insights in the population history using coalescence based methods. The Canary Island populations were strongly genetically differentiated and had reduced diversity with pronounced fixation including many private alleles. In population structure models, the relationship between the central island populations (La Gomera, Tenerife and Gran Canaria) and El Hierro was difficult to disentangle whereas the two European populations showed consistent clustering, the two eastern islands (Fuerteventura and Lanzarote) and Morocco weak clustering, and La Palma a consistent unique lineage. Coalescence based models suggested that the European mainland forms an outgroup to the Afrocanarian population, a split between the western island group (La Palma and El Hierro) and the central island group, and recent splits between the three central islands, and between the two eastern islands and Morocco, respectively. It is clear that strong genetic drift and low level of concurrent gene flow among populations have shaped complex allelic patterns of fixation and skewed frequencies over the archipelago. However, understanding the population history remains challenging; in particular, the pattern of extreme divergence with low genetic diversity and yet unique genetic material in the Canary Island system requires an explanation. A potential scenario is population contractions of a historically large and genetically variable Afrocanarian population, with vicariance and drift following in the wake. The suggestion from sequence-based analyses of a Pleistocene extinction of a substantial part of North Africa and a Pleistocene/Holocene eastward re-colonisation of western North Africa from the Canaries remains possible.

Intratumoral heterogeneity drives cancer progression and influences treatment outcomes. The mechanisms underlying how cellular subpopulations communicate and cooperate to impact progression remain largely unknown. Here, we use collective invasion as a model to deconstruct processes underlying non-small cell lung cancer subpopulation cooperation. We reveal that collectively invading packs consist of heterogeneously cycling and non-cycling subpopulations using distinct pathways. We demonstrate that the follower subpopulation secretes transforming growth factor beta one (TGF-β1) to stimulate divergent subpopulation responses-including proliferation, pack cohesion, and JAG1-dependent invasion-depending on cellular context. While isolated followers maintain proliferation in response to TGF-β1, isolated leaders enter a quiescence-like cellular state. In contrast, leaders within a heterogeneous population sustain proliferation to maintain subpopulation proportions. In vivo, both leader and follower subpopulations are necessary for macro-metastatic disease progression. Taken together, these findings highlight that intercellular communication preserves tumor cell heterogeneity and promotes collective behaviors such as invasion and tumor progression., Competing Interests: Declaration of interests The authors declare no competing interests with this work., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

In the evolving landscape of crisis leadership and emergency management, artificial intelligence (AI) emerges as a potentially transformative force with far-reaching implications. Utilizing the POP-DOC Loop, a comprehensive framework for crisis leadership analysis and decision-making, this paper delves into the diverse roles that AI is poised to play in shaping the future of crisis planning and response. The POP-DOC Loop serves as a structured methodology, encompassing key elements such as information gathering, contextual analysis informed by social determinants, enhanced predictive modeling, guided decision-making, strategic action implementation, and appropriate communication. Rather than offer definitive predictions, this review aims to catalyze exploration and discussion, equipping researchers and practitioners to anticipate future contingencies. The paper concludes by examining the limitations and challenges posed by AI within this specialized context.

The current hyper-volatile, -uncertain, -complex, and -ambiguous (VUCA) threat environment demands a more cohesive support structure for crisis leaders who may be faced with crises of increasing magnitude and frequency and, in some instances, multiple crisis events simultaneously. The project team investigates the perceptions of crisis leaders regarding establishing a crisis leader advisor position for crisis leaders to benefit from their experience while prosecuting crisis response activities. The team linked hyper-VUCA crises, crisis response frameworks, meta-leadership, crisis leader attributes, and advisor attributes. The overall goal of the project is to increase the ability of the crisis leaders to more effectively and efficiently navigate crisis events resulting in more efficient and effective response and recovery. Three research questions were developed to assess the following: thoughts of integrating a crisis leader advisor position; development of a crisis leader advisor certification program; and attributes of crisis leader advisors. A qualitative research methodology using a phenomenological approach was employed. Forty-one participants were purposefully selected and administered a short, on-line survey consisting of 11 questions. Data were analyzed using percentage analysis,weighted sums, and inductive thematic analysis. The project team found an overwhelming support for the crisis leader advisor position and the crisis leader advisor certification program. Additionally, experience and trustworthiness ranked among the top sought after attributes of a crisis leader advisor. The team recommendations included (1) implement a crisis leaders advisor guide/framework; (2) create a formal crisis leader advisor position in national incident management system; (3) implement a crisis leader advisor certification framework; (4) benchmark established advisor programs; and (5) implement a framework to match leaders and advisors.

Background: Effective medical therapies are lacking for the treatment of neurofibromatosis type 1-related plexiform neurofibromas, which are characterized by elevated RAS-mitogen-activated protein kinase (MAPK) signaling., Methods: We conducted a phase 1 trial of selumetinib (AZD6244 or ARRY-142886), an oral selective inhibitor of MAPK kinase (MEK) 1 and 2, in children who had neurofibromatosis type 1 and inoperable plexiform neurofibromas to determine the maximum tolerated dose and to evaluate plasma pharmacokinetics. Selumetinib was administered twice daily at a dose of 20 to 30 mg per square meter of body-surface area on a continuous dosing schedule (in 28-day cycles). We also tested selumetinib using a mouse model of neurofibromatosis type 1-related neurofibroma. Response to treatment (i.e., an increase or decrease from baseline in the volume of plexiform neurofibromas) was monitored by using volumetric magnetic resonance imaging analysis to measure the change in size of the plexiform neurofibroma., Results: A total of 24 children (median age, 10.9 years; range, 3.0 to 18.5) with a median tumor volume of 1205 ml (range, 29 to 8744) received selumetinib. Patients were able to receive selumetinib on a long-term basis; the median number of cycles was 30 (range, 6 to 56). The maximum tolerated dose was 25 mg per square meter (approximately 60% of the recommended adult dose). The most common toxic effects associated with selumetinib included acneiform rash, gastrointestinal effects, and asymptomatic creatine kinase elevation. The results of pharmacokinetic evaluations of selumetinib among the children in this trial were similar to those published for adults. Treatment with selumetinib resulted in confirmed partial responses (tumor volume decreases from baseline of ≥20%) in 17 of the 24 children (71%) and decreases from baseline in neurofibroma volume in 12 of 18 mice (67%). Disease progression (tumor volume increase from baseline of ≥20%) has not been observed to date. Anecdotal evidence of decreases in tumor-related pain, disfigurement, and functional impairment was observed., Conclusions: Our early-phase data suggested that children with neurofibromatosis type 1 and inoperable plexiform neurofibromas benefited from long-term dose-adjusted treatment with selumetinib without having excess toxic effects. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01362803 .).

Symptomatic heterotopic ossification of abdominal surgical incisions is a rare occurrence. We present a 67-year-old man with severe discomfort caused by heterotopic ossification extending from the xiphoid to the umbilicus. The patient underwent an abdominal aortic aneurysm repair 3 years before our treatment. A 13 × 3.5 cm ossified lesion was excised. The resulting midline defect was closed using component separation and inlay Strattice. Tension-free midline adaptation of the recti muscles was achieved. A computed tomography scan of the abdomen 6 months after the surgery showed no recurrence or hernias. Heterotopic ossification in symptomatic patients has previously been treated with excision and primary closure. We believe that tension-free repair is important to prevent recurrence. Acellular dermal matrix may add to this effect and also compartmentalize the process.

This article reports on the design, evaluation framework, and results from the Meta-Leadership Summit for Preparedness Initiative. The Meta-Leadership Summit for Preparedness was a 5-year initiative based on the premise that national preparedness and emergency response is not solely the responsibility of government. From 2006 to 2011, 36 Meta-Leadership Summits were delivered in communities across the country. Summits were customized, 10-hour leadership development, networking, and community action planning events. They included participation from targeted federal, state, local, nonprofit/philanthropic, and private sector leaders who are directly involved in decision making during a major community or state-wide emergency. A total of 4,971 government, nonprofit, and business leaders attended Meta-Leadership Summits; distribution of attendees by sector was balanced. Ninety-three percent of respondents reported the summit was a valuable use of time, 91% reported the overall quality as "good" or "outstanding," and 91% would recommend the summit to their colleagues. In addition, approximately 6 months after attending a summit, 80% of respondents reported that they had used meta-leadership concepts or principles. Of these, 93% reported that using meta-leadership concepts or principles had made a positive difference for them and their organizations. The Meta-Leadership Summit for Preparedness Initiative was a value-added opportunity for communities, providing the venue for learning the concepts and practice of meta-leadership, multisector collaboration, and resource sharing with the intent of substantively improving preparedness, response, and recovery efforts.

Objective: Survey instruments for evaluating public health preparedness have focused on measuring the structure and capacity of local, state, and federal agencies, rather than linkages among structure, process, and outcomes. To focus evaluation on the latter, we evaluated the linkages among individuals, organizations, and systems using the construct of "connectivity" and developed a measurement instrument., Methods: Results from focus groups of emergency preparedness first responders generated 62 items used in the development sample of 187 respondents. Item reduction and factors analyses were conducted to confirm the scale's components., Results: The 62 items were reduced to 28. Five scales explained 70% of the total variance (number of items, percent variance explained, Cronbach's alpha) including connectivity with the system (8, 45%, 0.94), coworkers (7, 7%, 0.91), organization (7, 12%, 0.93), and perceptions (6, 6%, 0.90). Discriminant validity was found to be consistent with the factor structure., Conclusion: We developed a Connectivity Measurement Tool for the public health workforce consisting of a 34-item questionnaire found to be a reliable measure of connectivity with preliminary evidence of construct validity.

Effective emergency preparedness and response requires leadership that can accomplish perceptive coordination and communication amongst diverse agencies and sectors. Nevertheless, operating within their specified scope of authority, preparedness leaders in characteristic bureaucratic fashion often serve to bolster the profile and import of their own organization, thereby creating a silo effect that interferes with effective systemwide planning and response. This article describes a strategy to overcome traditional silo thinking: "meta-leadership," overarching leadership that intentionally connects the purposes and work of different organizations or organizational units. Thinking and operating beyond their immediate scope of authority, meta-leaders provide guidance, direction, and momentum across organizational lines that develop into a shared course of action and a commonality of purpose among people and agencies that are doing what may appear to be very different work. Meta-leaders are able to imaginatively and effectively leverage system assets, information, and capacities, a particularly critical function for organizations with emergency preparedness responsibilities that are constrained by ingrained bureaucratic patterns of behavior.

Over the past two decades, physicians have suffered declines in real income, community standing, and of collegiality. Physicians must not view themselves solely as victims of the sweeping changes in current medical care delivery. They have both the opportunity and the duty to reassert their true role as compassionate conveyors of the science and the art of medicine. This article explores the historic trends that have led to our current state. It also explores the exciting possibilities open to doctors to assume a renewed elevated status that both they and their patients yearn for.

The "bygone" doctor practiced in the good old days under a relatively uncomplicated, clearly defined system. Physicians could afford to be independent. To survive in practice today, say the authors of "Renegotiating Health Care: Resolving Conflict to Build Collaboration," physicians must adapt to change or the health-care market will pass them by. Today's "evolving" doctor is a partner, contributing to and deriving benefit through collaborative patient-care networks, physician practice organizations, and medical services organizations. Historical rivalries have been forgotten as hospitals, insurers, and physicians seek and achieve innovative alliances. Still, resistance to these plans runs strong. The following story typifies one dilemma that faces physicians today. It concerns a hypothetical group practice that must decide whether to form a capitated individual practice association.

As the health-care revolution continues, bargaining skills have become more crucial for doctors than ever before. If you want your practice to thrive, you must regularly negotiate with colleagues, practice administrators, allied health professionals, managed-care plans, business groups, hospitals, and the government. Yet medical schools and residency programs devote little if any time to negotiating skills. The "golden days," when physicians could afford to be mavericks, are over. Doctors must develop a new collaborative outlook to be successful and happy in their careers, says Leonard J. Marcus, Ph.D., lead author of the book "Renegotiating Health Care: Resolving conflict to Build Collaboration." He and his co-authors often conduct seminars for health professionals on improving bargaining skills. The following excerpt concerns the role of conflict in negotiation, and how to resolve it.

A rich body of knowledge spans organizational topics relevant to the practice, conceptual development and planning of social work health care services. At a time when health care organizations are experiencing major changes in their structure and financing; organizational research informs both the system adjustments and leadership which social work can offer the health care field. Organizational research on health care social work is grouped into three categories: management and administrative issues; interprofessional and interorganizational relations; and service delivery topics. Within each category, the major issues are presented with single site and multi-site research reviewed. Recommendations to improve the contributions of this body of research include greater attention to methodological rigor in designing and implementing research projects.

Economic pressures and the advent of prospective payment systems have heightened the importance of effective discharge planning. In this examination of the organizational dimension of the discharge process, a conceptual approach for understanding complex organizations is outlined and strategies for negotiating multifaceted systems are presented.