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BackgroundSurvival after childhood cancer has improved to more than 80% during the last few years, leading to an increased number of childhood cancer survivors. Cancer itself, or its treatment, may cause chronic health conditions, including somatic and mental sequelae, which may affect survivors’ health-related quality of life (HRQoL). ObjectiveThe project PanCareLIFE aims to establish a large database with comprehensive data on childhood cancer survivors from different European countries, including data on HRQoL. Within PanCareLIFE, this study aims to describe HRQoL in survivors, investigate predictors of HRQoL, and describe the association of HRQoL with hearing and female fertility impairment. This paper describes the design of the HRQoL study, the origin of data, strategies for data collection, and sampling characteristics of survivors from each contributing country. MethodsA total of 6 institutions from 5 European countries (the Czech Republic, France, Germany, the Netherlands, and Switzerland) provided data on HRQoL assessed with the Short Form 36 and on relevant predictors. The central PanCareLIFE data center aggregated the data and harmonized the variables between the institutions. Survivors were eligible if they received a diagnosis of cancer according to the 12 main groups of the International Classification of Childhood Cancer, 3rd edition, or Langerhans cell histiocytosis; were aged ≤18 years at the time of diagnosis; were residents of the respective country at the time of diagnosis; had survived ≥5 years after cancer diagnosis; were aged ≥18 years at the time of the questionnaire survey; and did not refuse to registration in the national or local childhood cancer cohort. ResultsWe identified 24,993 eligible survivors. Of those, 19,268 survivors received a questionnaire and 9871 survivors participated, resulting in response rates of 9871/24,993 (39.50%) of eligible survivors and of 9871/19,268 (51.23%) invited survivors. Most participants were diagnosed with cancer between the ages of 10 and 14 years (3448/9871, 34.93%) or

Monitoring changes in glacial dynamics is essential for understanding the environmental response to accelerated climate warming in the Arctic. However, geodetic surveys in polar regions continue to present considerable challenges because of the harsh environmental conditions and the polar night. This study records a 14-year-long time series (2006–2019) of global navigation satellite system (GNSS) surveys of the positions of 16 ablation stakes distributed across Hansbreen, a tidewater glacier in southern Svalbard. The measurements were conducted with an exceptionally high temporal resolution, from about 1 week to about 1 month, and covering altitudes ranging from 20 to 490 m a.s.l. The position of one stake was surveyed every day. The primary data products consist of the stake coordinates and velocities. Time series of annual and seasonal velocities are also provided. This dataset may be a subject of further studies of glacier dynamics in relation to the long-term and seasonal impact of climate change on ice flow in the region. It also offers unique material for tuning numerical models of glacier dynamics and for validating satellite-derived products such as velocity and digital elevation models. The dataset described here has been made publicly available through the Zenodo repository: https://doi.org/10.5281/zenodo.8289380 (Błaszczyk et al., 2023).

IntroductionThis study evaluated changes in the white matter of the brain and psychological health variables, resulting from a neuroscience-based mindfulness intervention, the Training for Awareness, Resilience, and Action (TARA), in a population of healthy adolescents.MethodsA total of 100 healthy adolescents (57 female, age ranges 14–18 years) were randomized into the 12-week TARA intervention or a waitlist-control group. All participants were imaged with diffusion MRI to quantify white matter connectivity between brain regions. Imaging occurred at baseline/randomization and after 12 weeks of baseline (pre- and post-intervention in the TARA group). We hypothesized that structural connectivity in the striatum and interoceptive networks would increase following the TARA intervention, and that, this increased connectivity would relate to psychological health metrics from the Strengths and Difficulties Questionnaire (SDQ) and the Insomnia Severity Index (ISI). The TARA intervention and all assessments, except for the MRIs, were fully remotely delivered using secure telehealth platforms and online electronic data capture systems.ResultsThe TARA intervention showed high consistency, tolerability, safety, recruitment, fidelity, adherence, and retention. After 12 weeks, the TARA group, but not controls, also demonstrated significantly improved sleep quality (p = 0.02), and changes in the right putamen node strength were related to this improved sleep quality (r = −0.42, p = 0.006). Similarly, the TARA group, but not controls, had significantly increased right insula node strength related to improved emotional well-being (r = −0.31, p = 0.04). Finally, we used the network-based statistics to identify a white matter interoception network that strengthened following TARA (p = 0.009).DiscussionThese results suggest that the TARA mindfulness-based intervention in healthy adolescents is feasible and safe, and it may act to increase structural connectivity strength in interoceptive brain regions. Furthermore, these white matter changes are associated with improved adolescent sleep quality and emotional well-being. Our results suggest that TARA could be a promising fully remotely delivered intervention for improving psychological well-being in adolescents. As our findings suggest that TARA affects brain regions in healthy adolescents, which are also known to be altered during depression in adolescents, future studies will examine the effects of TARA on depressed adolescents.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT04254796.

The Svalbard archipelago is particularly sensitive to climate change due to the relatively low altitude of its main ice fields and its geographical location in the higher North Atlantic, where the effect of Arctic amplification is more significant. The largest temperature increases have been observed during winter, but increasing summer temperatures, above the melting point, have led to increased glacier melt. Here, we evaluate the impact of this increased melt on the preservation of the oxygen isotope (δ18O) signal in firn records. δ18O is commonly used as a proxy for past atmospheric temperature reconstructions, and, when preserved, it is a crucial parameter to date and align ice cores. By comparing four different firn cores collected in 2012, 2015, 2017 and 2019 at the top of the Holtedahlfonna ice field (1100 m a.s.l.), we show a progressive deterioration of the isotope signal, and we link its degradation to the increased occurrence and intensity of melt events. Our findings indicate that, starting from 2015, there has been an escalation in melting and percolation resulting from changes in the overall atmospheric conditions. This has led to the deterioration of the climate signal preserved within the firn or ice. Our observations correspond with the model's calculations, demonstrating an increase in water percolation since 2014, potentially reaching deeper layers of the firn. Although the δ18O signal still reflects the interannual temperature trend, more frequent melting events may in the future affect the interpretation of the isotopic signal, compromising the use of Svalbard ice cores. Our findings highlight the impact and the speed at which Arctic amplification is affecting Svalbard's cryosphere.

We describe the annual pattern of frontal ablation driven by submarine melting mechanisms at the Hansbreen terminus: these are reflected in the intensity and spatial distribution of calving events. Analysis of time-lapse images of the Hansbreen front in conjunction with oceanographic and meteorological data shows that calving intensity is driven primarily by seawater temperature. Regression analysis also highlights the importance of air temperature, which we take to be a proxy for surface ablation and subglacial discharge. This, combined with seasonal changes in ice cliff tortuosity and the increasing significance of wave motion outside the ablation season, enabled us to determine seasonal changes in the mechanisms of ice cliff undercutting by submarine melting. While submarine melting controlled by estuarine circulation primarily drives frontal ablation in summer, wave-driven melting at the waterline is more important outside the ablation season. During winter, ice cliff undercutting by melting is suspended by low seawater temperature, negligible subglacial water discharge and sea-ice cover. The most intense frontal ablation, recorded in summer, was related to higher sea temperature and vigorous estuarine circulation.

Introduction In utero gene editing (IUGE) is a potential treatment for inherited diseases that takes advantage of normal fetal developmental properties to institute the therapy before the onset of pathology. [...], In utero gene editing (IUGE) is a potential treatment for inherited diseases that cause pathology before or soon after birth. Preexisting immunity to adeno-associated virus (AAV) vectors and Cas9 endonuclease may limit postnatal gene editing. The tolerogenic fetal immune system minimizes a fetal immune barrier to IUGE. However, the ability of maternal immunity to limit fetal gene editing remains a question. We investigated whether preexisting maternal immunity to AAV or Cas9 impairs IUGE. Using a combination of fluorescent reporter mice and a murine model of a metabolic liver disease, we demonstrated that maternal anti-AAV IgG antibodies were efficiently transferred from dam to fetus and impaired IUGE in a maternal titer-dependent fashion. By contrast, maternal cellular immunity was inefficiently transferred to the fetus, and neither maternal cellular nor humoral immunity to Cas9 impaired IUGE. Using human umbilical cord and maternal blood samples collected from mid- to late-gestation pregnancies, we demonstrated that maternal-fetal transmission of anti-AAV IgG was inefficient in midgestation compared with term, suggesting that the maternal immune barrier to clinical IUGE would be less relevant at midgestation. These findings support immunologic advantages for IUGE and inform maternal preprocedural testing protocols and exclusion criteria for future clinical trials.

In response to the COVID-19 pandemic, chemical engineering departments from around the world shifted their course offerings from in-person to online almost instantaneously. The AIChE Education Division immediately responded to this educational shift by developing five Virtual Communities of Practice (VCPs) that allowed faculty to share experiences and best practices as well as provide a network for emotional support. Community creation, methods and materials shared, and surveys related to the impact of this initiative will be discussed.

BackgroundAlthough many surveys have been conducted on patients accessing their own health records in recent years, there is a limited amount of nationwide cross-country data available on patients’ views and preferences. To address this gap, an international survey of patient users was conducted in the Nordic eHealth project, NORDeHEALTH. ObjectiveWe aimed to investigate the sociodemographic characteristics and experiences of patients who accessed their electronic health records (EHRs) through national patient portals in Norway, Sweden, Finland, and Estonia. MethodsA cross-sectional web-based survey was distributed using the national online health portals. The target participants were patients who accessed the national patient portals at the start of 2022 and who were aged ≥15 years. The survey included a mixture of close-ended and free-text questions about participant sociodemographics, usability experience, experiences with health care and the EHR, reasons for reading health records online, experience with errors, omissions and offense, opinions about security and privacy, and the usefulness of portal functions. In this paper, we summarized the data on participant demographics, past experience with health care, and the patient portal through descriptive statistics. ResultsIn total, 29,334 users completed the survey, of which 9503 (32.40%) were from Norway, 13,008 (44.35%) from Sweden, 4713 (16.07%) from Finland, and 2104 (7.17%) from Estonia. National samples were comparable according to reported gender, with about two-thirds identifying as women (19,904/29,302, 67.93%). Age distributions were similar across the countries, but Finland had older users while Estonia had younger users. The highest attained education and presence of health care education varied among the national samples. In all 4 countries, patients most commonly rated their health as “fair” (11,279/29,302, 38.48%). In Estonia, participants were more often inclined to rate their health positively, whereas Norway and Sweden had the highest proportion of negative health ratings. Across the whole sample, most patients received some care in the last 2 years (25,318/29,254, 86.55%). Mental health care was more common (6214/29,254, 21.24%) than oncological care (3664/29,254, 12.52%). Overall, most patients had accessed their health record “2 to 9 times” (11,546/29,306, 39.4%), with the most frequent users residing in Sweden, where about one-third of patients accessed it “more than 20 times” (4571/13,008, 35.14%). ConclusionsThis is the first large-scale international survey to compare patient users’ sociodemographics and experiences with accessing their EHRs. Although the countries are in close geographic proximity and demonstrate similar advancements in giving their residents online records access, patient users in this survey differed. We will continue to investigate patients’ experiences and opinions about national patient-accessible EHRs through focused analyses of the national and combined data sets from the NORDeHEALTH 2022 Patient Survey.

Although fully automated volumetric approaches for monitoring brain tumor response have many advantages, most available deep learning models are optimized for highly curated, multi-contrast MRI from newly diagnosed gliomas, which are not representative of post-treatment cases in the clinic. Improving segmentation for treated patients is critical to accurately tracking changes in response to therapy. We investigated mixing data from newly diagnosed (n = 208) and treated (n = 221) gliomas in training, applying transfer learning (TL) from pre- to post-treatment imaging domains, and incorporating spatial regularization for T2-lesion segmentation using only T2 FLAIR images as input to improve generalization post-treatment. These approaches were evaluated on 24 patients suspected of progression who had received prior treatment. Including 26% of treated patients in training improved performance by 13.9%, and including more treated and untreated patients resulted in minimal changes. Fine-tuning with treated glioma improved sensitivity compared to data mixing by 2.5% (p < 0.05), and spatial regularization further improved performance when used with TL by 95th HD, Dice, and sensitivity (6.8%, 0.8%, 2.2%; p < 0.05). While training with ≥60 treated patients yielded the majority of performance gain, TL and spatial regularization further improved T2-lesion segmentation to treated gliomas using a single MR contrast and minimal processing, demonstrating clinical utility in response assessment.

Measurement(s) snow cover, snow stratigraphy Technology Type(s) snow pit analyses, automatic weather stations Factor Type(s) Hansbreen Sample Characteristic - Environment seasonal snow cover, cryosphere, polar environment Sample Characteristic - Location glacier, Hansbreen, Hornsund, Spitsbergen, Svalbard, Arctic

Dust particles from high latitudes have a potentially large local, regional, and global significance to climate and the environment as short-lived climate forcers, air pollutants, and nutrient sources. Identifying the locations of local dust sources and their emission, transport, and deposition processes is important for understanding the multiple impacts of high-latitude dust (HLD) on the Earth's systems. Here, we identify, describe, and quantify the source intensity (SI) values, which show the potential of soil surfaces for dust emission scaled to values 0 to 1 concerning globally best productive sources, using the Global Sand and Dust Storms Source Base Map (G-SDS-SBM). This includes 64 HLD sources in our collection for the northern (Alaska, Canada, Denmark, Greenland, Iceland, Svalbard, Sweden, and Russia) and southern (Antarctica and Patagonia) high latitudes. Activity from most of these HLD sources shows seasonal character. It is estimated that high-latitude land areas with higher (SI ≥0.5), very high (SI ≥0.7), and the highest potential (SI ≥0.9) for dust emission cover >1 670 000 km2, >560 000 km2, and >240 000 km2, respectively. In the Arctic HLD region (≥60∘ N), land area with SI ≥0.5 is 5.5 % (1 035 059 km2), area with SI ≥0.7 is 2.3 % (440 804 km2), and area with SI ≥0.9 is 1.1 % (208 701 km2). Minimum SI values in the northern HLD region are about 3 orders of magnitude smaller, indicating that the dust sources of this region greatly depend on weather conditions. Our spatial dust source distribution analysis modeling results showed evidence supporting a northern HLD belt, defined as the area north of 50∘ N, with a “transitional HLD-source area” extending at latitudes 50–58∘ N in Eurasia and 50–55∘ N in Canada and a “cold HLD-source area” including areas north of 60∘ N in Eurasia and north of 58∘ N in Canada, with currently “no dust source” area between the HLD and low-latitude dust (LLD) dust belt, except for British Columbia. Using the global atmospheric transport model SILAM, we estimated that 1.0 % of the global dust emission originated from the high-latitude regions. About 57 % of the dust deposition in snow- and ice-covered Arctic regions was from HLD sources. In the southern HLD region, soil surface conditions are favorable for dust emission during the whole year. Climate change can cause a decrease in the duration of snow cover, retreat of glaciers, and an increase in drought, heatwave intensity, and frequency, leading to the increasing frequency of topsoil conditions favorable for dust emission, which increases the probability of dust storms. Our study provides a step forward to improve the representation of HLD in models and to monitor, quantify, and assess the environmental and climate significance of HLD.

Luks, Andrew M., Thomas G. DeLoughery, Jeffrey H. Gertsch, and Suzy Stokes. Clinical conundrum: return to high altitude after cerebral venous sinus thrombosis. High Alt Med Biol. 25:337–341, 2024. [ABSTRACT FROM AUTHOR]

Introduction Documentation of the cause of death is important for local and national epidemiology as well as for research and public health funding allocation. Despite this, many physicians lack the skills necessary to accurately complete a death certificate. Methods We created a 45-minute virtual workshop to improve skills in completing death certificates. Participants examined the role of death certificates in disease epidemiology and resource allocation for research and public health interventions, reviewed the components of a death certificate, and practiced correcting and filling out death certificates from actual patient cases. To assess the workshop, participants completed sample death certificates immediately before and after the workshop for two representative cases. Results Thirty-six internal medicine residents (17 PGY 1s, 12 PGY 2s, and seven PGY 3s) completed the workshop. Prior to the workshop, 89% of the sample death certificates contained one or more errors, compared with 46% postworkshop. Major errors, such as incorrect categorization of a cause of death, decreased from 58% preworkshop to 17% postworkshop. Learners expressed discomfort after realizing they had made errors in completing previous death certificates and noted a desire for continuing education and reference materials on this topic. Discussion Death certification is a key competency for physicians. Our virtual workshop improved participants’ skills in completing death certificates. Although a significant number of errors remained after the workshop, most of these residual errors were minor and would not affect cause-of-death reporting. The durability of these improvements over time requires further study.

For often unclear reasons, the survival times of critically buried avalanche victims vary widely from minutes to hours. Individuals can survive and sustain organ function if they can breathe under the snow and maintain sufficient delivery of oxygen and efflux of carbon dioxide. We review the physiological responses of humans to critical avalanche burial, a model which shares similarities and differences with apnoea and accidental hypothermia. Within a few minutes of burial, an avalanche victim is exposed to hypoxaemia and hypercapnia, which have important effects on the respiratory and cardiovascular systems and pose a major threat to the central nervous system. As burial time increases, an avalanche victim also develops hypothermia. Despite progressively reduced metabolism, reduced oxygen and increased carbon dioxide tensions may exacerbate the pathophysiological consequences of hypothermia. Hypercapnia seems to be the main cause of cardiovascular instability, which, in turn, is the major reason for reduced cerebral oxygenation despite reductions in cerebral metabolic activity caused by hypothermia. 'Triple H syndrome' refers to the interaction of hypoxia, hypercapnia and hypothermia in a buried avalanche victim. Future studies should investigate how the respiratory gases entrapped in the porous snow structure influence the physiological responses of buried individuals and how haemoconcentration, blood viscosity and cell deformability affect blood flow and oxygen delivery. Attention should also be devoted to identifying strategies to prolong avalanche survival by either mitigating hypoxia and hypercapnia or reducing core temperature so that neuroprotection occurs before the onset of cerebral hypoxia. [ABSTRACT FROM AUTHOR]

Luks AM, Grissom CK. Evaluation and Management of the Individual with Recurrent HAPE. High Alt Med Biol. 25:238–246, 2024. Individuals with a history of acute altitude illness often seek recommendations from medical providers on how to prevent such problems on future ascents to high elevation. Although many of these cases can be managed with pharmacologic prophylaxis and counseling about the appropriate rate of ascent alone, there are some situations in which further diagnostic evaluation may also be warranted. One such situation is the individual with recurrent episodes of high altitude pulmonary edema (HAPE), as one of several predisposing factors may be present that warrants additional interventions beyond pharmacologic prophylaxis and slow ascent and may even preclude future travel to high altitude. This review considers this situation in greater detail. Structured around the case of an otherwise healthy 27-year-old individual with recurrent episodes of HAPE who would like to climb Denali (6,190 m), the review examines the known risk factors for disease and then provides guidance regarding when and how to evaluate such individuals and appropriate steps to prevent HAPE on further ascents to high elevation. Except in rare circumstances, a history of recurrent HAPE does not preclude further ascent to high elevation, as a multipronged approach including pharmacologic prophylaxis, careful planning about the rate of ascent, and the degree of physical effort and other strategies, such as preacclimatization, staged ascent, and use of hypoxic tents, can be employed to reduce the risk of recurrence with future travel. [ABSTRACT FROM AUTHOR]

Winter tourism can generate environmental pollution and affect microbial ecology in mountain ecosystems. This could stimulate the development of antibiotic resistance in snow and its dissemination through the atmosphere and through snow melting. Despite these potential impacts, the effect of winter tourism on the snow antibiotic resistome remains to be elucidated. In this study, snow samples subjected to different levels of anthropogenic activities and surrounding forest were obtained from the Sudety Mountains in Poland to evaluate the impact of winter tourism on snow bacteria using a metagenomic approach. Bacterial community composition was determined by the sequencing of the V3-V4 hypervariable region of the 16S rRNA gene and the composition of the antibiotic resistome was explored by metagenomic sequencing. Whereas environmental factors were the main drivers of bacterial community and antibiotic resistome composition in snow, winter tourism affected resistome composition in sites with similar environmental conditions. Several antibiotic resistance genes (ARGs) showed a higher abundance in sites subjected to human activities. This is the first study to show that anthropogenic activities may influence the antibiotic resistome in alpine snow. Our results highlight the need to survey antibiotic resistance development in anthropogenically polluted sites.

CASE PRESENTATION: A seven-year-old male presented to the pediatric emergency department with one day of abdominal pain. His physical exam was significant for rebound, guarding, and tenderness in the right lower quadrant, and his labs demonstrated a leukocytosis. Both a point-of-care ultrasound and radiology-performed ultrasound were concerning for acute appendicitis with a periappendiceal abscess, but on emergent laparoscopy the patient was found to have an infected urachal cyst. DISCUSSION: Infected urachal remnants are a rare but important cause of pediatric abdominal pain. In this case, inflammation surrounding the patient’s midline urachal cyst triggered a serositis that involved the appendix and pulled the cyst to the right. This created a clinical and radiologic presentation similar to appendicitis. This atypical presentation of an already rare anomaly highlights the importance of maintaining a broad differential during the work-up of pediatric abdominal pain.

BackgroundAdvances in Molecular Therapy have made gene editing through systemic or topical administration of reagents a feasible strategy to treat genetic diseases in a rational manner. Encapsulation of therapeutic agents in nanoparticles can improve intracellular delivery of therapeutic agents, provided that the nanoparticles are efficiently taken up within the target cells. In prior work we had established proof-of-principle that nanoparticles carrying gene editing reagents can mediate site-specific gene editing in fetal and adult animals in vivo that results in functional disease improvement in rodent models of β-thalassemia and cystic fibrosis. Modification of the surface of nanoparticles to include targeting molecules (e.g. antibodies) holds the promise of improving cellular uptake and specific cellular binding.Methods and findingsTo improve particle uptake for diseases of the airway, like cystic fibrosis, our group tested the impact of nanoparticle surface modification with cell surface marker antibodies on uptake in human bronchial epithelial cells in vitro. Binding kinetics of antibodies (Podoplanin, Muc 1, Surfactant Protein C, and Intracellular Adhesion Molecule-1 (ICAM)) were determined to select appropriate antibodies for cellular targeting. The best target-specific antibody among those screened was ICAM antibody. Surface conjugation of nanoparticles with antibodies against ICAM improved cellular uptake in bronchial epithelial cells up to 24-fold.ConclusionsThis is a first demonstration of improved nanoparticle uptake in epithelial cells using conjugation of target specific antibodies. Improved binding, uptake or specificity of particles delivered systemically or to the luminal surface of the airway would potentially improve efficacy, reduce the necessary dose and thus safety of administered therapeutic agents. Incremental improvement in the efficacy and safety of particle-based therapeutic strategies may allow genetic diseases such as cystic fibrosis to be cured on a fundamental genetic level before birth or shortly after birth.

Remarkable developments in the fields of earth observation (EO) satellites and remote sensing (RS) technology over the past four decades have substantially contributed to spatial, spectral, and temporal sampling [...]

This paper explores the potential of ground-penetrating radar (GPR) monitoring for an advanced understanding of snow cover processes and structure. For this purpose, the study uses the Hansbreen (SW Spitsbergen) records that are among the longest and the most comprehensive snow-cover GPR monitoring records available on Svalbard. While snow depth (HS) is frequently the only feature derived from high-frequency radio-echo sounding (RES), this study also offers an analysis of the physical characteristics (grain shape, size, hardness, and density) of the snow cover structure. We demonstrate that, based on GPR data (800 MHz) and a single snow pit, it is possible to extrapolate the detailed features of snow cover to the accumulation area. Field studies (snow pits and RES) were conducted at the end of selected accumulation seasons in the period 2008–2019, under dry snow conditions and HS close to the maximum. The paper shows that although the snow cover structure varies in space and from season to season, a single snow pit site can represent the entire center line of the accumulation zone. Numerous hard layers (HLs) (up to 30% of the snow column) were observed that reflect progressive climate change, but there is no trend in quantity, thickness, or percentage contribution in total snow depth in the study period. HLs with strong crystal bonds create a “framework” in the snowpack, which reduces compaction and, consequently, the ice formation layers slow down the rate of snowpack metamorphosis. The extrapolation of snow pit data through radar profiling is a novel solution that can improve spatial recognition of snow cover characteristics and the accuracy of calculation of snow water equivalent (SWE).