Emergency managers are responsible for managing crises and disasters, and while their work is essential, it can be stressful and impact their mental health, particularly during the COVID-19 pandemic. This study aimed to examine the mental health of professional emergency managers and factors associated with their intent to leave the field before and during the COVID-19 pandemic. A total of 903 respondents completed an online survey assessing their secondary traumatic stress, emergency reaction strategies, organizational culture, age, length of time in primary position, the highest level of education as well as other metrics. The Secondary Traumatic Stress Scale (STSS) was used to determine scores of secondary traumatic stress symptoms, and the Emergency Reaction Questionnaire (ERQ) index was used to evaluate levels of predominant personality types and its tendency towards "fight or flight" reactions in emergency situations. Results revealed significant differences among respondents who reported considering leaving the field before or during the COVID-19 pandemic in terms of secondary traumatic stress scores, ERQ levels, perceived organizational culture (OC), age category, length of time in primary position, and the highest level of education (p < 0.05). Logistic regression analysis indicated that respondents with higher secondary traumatic stress scores, poorer organizational culture, younger age, less experience, and a bachelor's degree had nearly three times the odds of reporting considering leaving the field (p < 0.05). Additionally, respondents with a graduate degree had nearly four times the odds of reporting leaving the field (p < 0.05), while those who had directly managed between three and five disasters had nearly two times the odds of reporting and considering leaving the field (p < 0.05). These findings underscore the importance of addressing secondary traumatic stress, promoting positive organizational culture, and providing support for emergency managers now and in the future. By addressing the factors identified in this study, such as secondary traumatic stress symptoms, promoting positive organizational culture, and providing adequate support, emergency management organizations can improve the mental health and well-being of their personnel, reduce attrition rates, and ensure that they are better equipped to respond to future crises.

Background. Persons with a history of traumatic brain injury (TBI) may exhibit short- and long-term cognitive deficits as well as psychiatric symptoms. These symptoms often reflect functional anomalies in the brain that are not detected by standard neuroimaging. In this context, quantitative electroencephalography (qEEG) is more suitable to evaluate non-normative activity in a wide range of clinical settings. Method. We searched the literature using the "Medline" and "Web of Science" online databases. The search was concluded on February 23, 2023, and revised on July 12, 2023. It returned 134 results from Medline and 4 from Web of Science. We then applied the PRISMA method, which led to the selection of 31 articles, the most recent one published in March 2023. Results. The qEEG method can detect functional anomalies in the brain occurring immediately after and even years after injury, revealing in most cases abnormal power variability and increases in slow (delta and theta) versus decreases in fast (alpha, beta, and gamma) frequency activity. Moreover, other findings show that reduced beta coherence between frontoparietal regions is associated with slower processing speed in patients with recent mild TBI (mTBI). More recently, machine learning (ML) research has developed highly reliable models and algorithms for the detection of TBI, some of which are already integrated into commercial qEEG equipment. Conclusion. Accumulating evidence indicates that the qEEG method may improve the diagnosis and management of TBI, in many cases revealing long-term functional anomalies in the brain or even neuroanatomical insults that are not revealed by standard neuroimaging. While FDA clearance has been obtained only for some of the commercially available equipment, the qEEG method allows for systematic, cost-effective, non-invasive, and reliable investigations at emergency departments. Importantly, the automated implementation of intelligent algorithms based on multimodally acquired, clinically relevant measures may play a key role in increasing diagnosis reliability.

We read with great interest the article entitled “A Prospective, Randomized Study Comparing Closed-Incision Negative-Pressure Wound Therapy with Standard Care in Immediate Breast Reconstruction” by Pieszko et al.1 in Plastic and Reconstructive Surgery. The authors assessed the impact of closed-incision negative-pressure wound therapy versus standard dressings after immediate breast reconstruction on surgical-site complications, superficial skin temperature, skin elasticity, and subjective scar quality, to determine the potential benefit of prophylactic closed-incision negative-pressure wound application. There is growing evidence that negative-pressure therapy on closed wounds can reduce complication rates following surgery. The authors showed that application of closed-incision negative-pressure on the wound correlated with a significant decrease in surgical-site complications within 1 year of immediate breast reconstruction. Active smoking status was not significant between the two groups, yet the actual number of smokers in the standard dressing group was over twice the size. Radiotherapy was the most important risk factor for developing surgical-site complications, as previously reported in the literature.2 There is some heterogenicity between the cohorts that is not represented by sufficient statistical significance but raises questions and may be a potential source of bias. In direct conjunction with the above-mentioned factors, the small sample size in this study may potentially compromise the validity of the conclusions that can be drawn and makes it prone to bias. However, these findings correlate with previous studies focused on bilateral breast reduction mammaplasty showing fewer complications in favor of the negative-pressure wound therapy–treated sites.3,4 The authors performed scar assessment based on the average coefficient of elasticity, and superficial skin temperature. The authors found more elastic scar tissue and superficial skin temperature to be significantly higher in the closed-incision negative-pressure wound therapy group. Tanaydin et al. measured scar viscoelasticity in 32 women undergoing bilateral breast reduction mammaplasty. They reported that skin viscoelasticity measurements did not show significant improvement in negative-pressure therapy compared with fixation strips.3 In contrast, Nagata et al. reported that scars treated with negative-pressure therapy are softer as measured with a scanning acoustic microscope (a technique used to measure tissue elasticity), which correlates with the results found by the authors.5 The effect of negative-pressure therapy on scar elasticity in breast reconstruction remains controversial, and further studies are needed to better define how negative-pressure wound therapy affects scar elasticity in breast reconstruction. It is well known that lower temperatures improve angiogenesis and wound healing.6 In contrast, Muenchow et al. demonstrated a significant increase in skin microcirculation parameters when a negative-pressure dressing was applied. The authors assessed local blood flow, capillary-venous oxygen saturation, blood flow velocity, and the relative amount of hemoglobin using a combined tissue laser/photospectrometry technique. However, no mention of superficial skin temperature was made.7 Further studies are needed to assess whether higher skin temperatures benefit scar formation during negative-pressure wound therapy. We would appreciate it if the authors would perform some noninvasive quantitative measurements of scar properties, such as digital photography with image analysis.8 According to the Patient and Observer Scar Assessment Scale v2.0, subjective scar outcomes in both groups were comparable in this study. This represents a reliable and valid scar assessment scale that measures scar quality from two perspectives; however, one of the major limitations of this particular outcome is that neither patients nor assessing physicians were blinded to the type of dressing used in this study. We would appreciate it if the authors would record the postoperative satisfaction of patients, which should be combined with the surgeon’s professional evaluation. Breast reconstruction is an expensive procedure that is usually paid for by the patient’s insurance. Using a disposable device adds an extra cost to the operation. We would appreciate a cost analysis assessment of vacuum-assisted closure therapy versus standard wound care.9 This analysis would determine the real cost-effectiveness of single-use vacuum-assisted closure therapy in this patient population. In conclusion, and despite some minor methodologic limitations inherent in clinical research, the authors provided useful data that add to the current body of scholarly literature on vacuum-assisted closure therapy and breast reconstruction, and the results are promising. We expect further long-term, large-sample studies that support the authors’ findings in the near future. DISCLOSURE The authors have no financial interest to declare in relation to the content of this Discussion or of the associated article.

Adeno-associated virus (AAV) vectors have emerged as the leading delivery platforms for gene therapy. Throughout the life cycle of the virions, the capsid vector carries out diverse functions, ranging from cell surface receptor engagement, cellular entry, endosomal escape, nuclear import to new particle packaging, and assembly. Each of these steps is mediated by exquisite structure features of the viral capsid and its interaction with viral genome, Rep proteins, and cellular organelle and apparatus. In this brief review, we provide an overview of results from over a decade of extensive biophysical studies of the capsid employing various techniques. The remaining unaddressed questions and perspective are also discussed. The detailed understanding of the structure and function interplay would provide insight to the strategy for improving the efficacy and safety of the viral vectors.

Dimethyl fumarate (DMF) showed favorable benefit-risk in patients with relapsing-remitting multiple sclerosis (MS) in phase 3 DEFINE and CONFIRM trials and in the ENDORSE extension study. Disease activity can differ in younger patients with MS compared with the overall population. Randomized patients received DMF 240mg twice daily or placebo (PBO; years 0-2 DEFINE/CONFIRM), then DMF (years 3-10; continuous DMF/DMF or PBO/DMF; ENDORSE); maximum follow-up (combined studies) was 13years. This integrated post hoc analysis evaluated safety and efficacy of DMF in a subgroup of young adults aged 18-29years. Of 1736 patients enrolled in ENDORSE, 125 were young adults, 86 treated continuously with DMF (DMF/DMF) and 39 received delayed DMF (PBO/DMF) in DEFINE/CONFIRM. Most (n = 116 [93%]) young adults completed DMF treatment in DEFINE/CONFIRM. Median (range) follow-up time in ENDORSE was 6.5 (2.0-10.0) years. Young adults entering ENDORSE who had been treated with DMF in DEFINE/CONFIRM had a model-based Annualized Relapse Rate (ARR; 95% CI) of 0.24 (0.16-0.35) vs. 0.56 (0.35-0.88) in PBO patients. ARR remained low in ENDORSE: 0.07 (0.01-0.47) at years 9-10 (DMF/DMF group). At year 10 of ENDORSE, EDSS scores were low in young adults: DMF/DMF, 1.9 (1.4); PBO/DMF, 2.4 (1.6). At ~ 7years, the proportion of young adults with no confirmed disability progresion was 81% for DMF/DMF and 72% for PBO/DMF. Patient-reported outcomes (PROs) (SF-36 and EQ-5D) generally remained stable during ENDORSE. The most common adverse events (AEs) in young adults during ENDORSE were MS relapse (n = 53 [42%]). Most AEs were mild (n = 20 [23.3%], n = 7 [17.9%]) to moderate (n = 45 [52.3%], n = 23 [59.0%]) in the DMF/DMF and PBO/DMF groups, respectively. The most common serious AE (SAE) was MS relapse (n = 19 [15%]). The data support a favorable benefit-risk profile of DMF in young adults, as evidenced by well-characterized safety, sustained efficacy, and stable PROs. Clinical trials.gov, DEFINE (NCT00420212), CONFIRM (NCT00451451), and ENDORSE (NCT00835770).

Anaplastic lymphoma kinase (ALK) aberrations have been identified in pediatric-type infant gliomas, but their occurrence across age groups, functional effects, and treatment response has not been broadly established. We performed a comprehensive analysis of ALK expression and genomic aberrations in both newly generated and retrospective data from 371 glioblastomas (156 adult, 205 infant/pediatric, and 10 congenital) with in vitro and in vivo validation of aberrations. ALK aberrations at the protein or genomic level were detected in 12% of gliomas (45/371) in a wide age range (0-80 years). Recurrent as well as novel ALK fusions (LRRFIP1-ALK, DCTN1-ALK, PRKD3-ALK) were present in 50% (5/10) of congenital/infant, 1.4% (3/205) of pediatric, and 1.9% (3/156) of adult GBMs. ALK fusions were present as the only candidate driver in congenital/infant GBMs and were sometimes focally amplified. In contrast, adult ALK fusions co-occurred with other oncogenic drivers. No activating ALK mutations were identified in any age group. Novel and recurrent ALK rearrangements promoted STAT3 and ERK1/2 pathways and transformation in vitro and in vivo. ALK-fused GBM cellular and mouse models were responsive to ALK inhibitors, including in patient cells derived from a congenital GBM. Relevant to the treatment of infant gliomas, we showed that ALK protein appears minimally expressed in the forebrain at perinatal stages, and no gross effects on perinatal brain development were seen in pregnant mice treated with the ALK inhibitor ceritinib. These findings support use of brain-penetrant ALK inhibitors in clinical trials across infant, pediatric, and adult GBMs. See related commentary by Mack and Bertrand, p. 2567.

The Functional Safety Standards Committee (FSSC) turned one year old. This article describes the FSSC results both in terms of sponsorship of IEEE Computer Society safety-related standards (for example, IEEE P2851) and of nurturing new initiatives.