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Objectives: To identify clinical presentations that acted as harbingers for future sepsis hospitalizations in pediatric patients evaluated in the emergency department (ED) using the Symptom Disease Pair Analysis of Diagnostic Error (SPADE) methodology., Methods: We identified patients in the Pediatric Health Information Systems (PHIS) database admitted for sepsis between January 1, 2004 and December 31, 2023 and limited the study cohort to those patients who had an ED treat-and-release visit in the 30 days prior to admission. Using the look-back approach of the SPADE methodology, we identified the most common clinical presentations at the initial ED visit and used an observed to expected (O:E) analysis to determine which presentations were overrepresented. We then employed a graphical, temporal analysis with a comparison group to identify which overrepresented presentations most likely represented harbingers for future sepsis hospitalization., Results: We identified 184,157 inpatient admissions for sepsis, of which 15,331 hospitalizations (8.3 %) were preceded by a treat-and-release ED visit in the prior 30 days. Based on the O:E and temporal analyses, the presentations of fever and dehydration were both overrepresented in the study cohort and temporally clustered close to sepsis hospitalization. ED treat-and-release visits for fever or dehydration preceded 1.2 % of all sepsis admissions., Conclusions: In pediatric patients presenting to the ED, fever and dehydration may represent harbingers for future sepsis hospitalization. The SPADE methodology could be applied to the PHIS database to develop diagnostic performance measures across a wide range of pediatric hospitals., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Emotional intelligence (EI) is an asset in health professionals supporting resilience, job satisfaction, interprofessional collaboration, and improved health outcomes for patients. Emerging research in health professions education shows that self-reflection and peer feedback, simulation, and experiential learning may contribute to the development of EI. The evidence indicates that training should be incorporated longitudinally throughout the educational process with increasing complexity and challenge. Several contextual factors may support success, such as framing the learning activities as opportunities for growth, adequate faculty and instructor training, and establishment of trusting relationships., Competing Interests: The authors report no funding or conflicts of interest., (Copyright © 2024 Baylor University Medical Center.)

Dairy cows experiencing heat stress (HS) during the precalving portion of the transition period give birth to smaller calves and produce less milk and milk protein. Supplementation of rumen-protected methionine (RPM) has been shown to modulate protein, energy, and placenta metabolism, making it a potential candidate to ameliorate HS effects. We investigated the effects of supplementing RPM to transition cows under HS induced by electric heat blanket (EHB) on cow-calf performance. Six weeks before expected calving, 53 Holstein cows were housed in a tiestall barn and fed a control diet (CON, 2.2% Met of MP) or a CON diet supplemented with SmartamineM (MET, 2.6% Met of MP, Adisseo Inc., France). Four weeks precalving, all MET and half CON cows were fitted with an EHB. The other half of the CON cows were considered thermoneutral (TN), resulting in 3 treatments: CONTN (n = 19), CONHS (n = 17), and METHS (n = 17). Respiratory rate (RR), skin temperature (ST), and rectal temperature (RT) were measured thrice weekly and core body temperatures recorded biweekly. Postcalving BW and BCS were recorded weekly, and DMI was calculated and averaged weekly. Milk yield was recorded daily and milk components were analyzed every third DIM. Biweekly AA and weekly nonesterified fatty acids (NEFA), BHB, insulin, and glucose were measured from plasma. Calf birth weight and 24 h growth, thermoregulation, and hematology profile were measured and apparent efficiency of absorption (AEA) of immunoglobulins was calculated. Data were analyzed using the MIXED procedure of SAS with 2 preplanned orthogonal contrasts: CONTN versus the average of CONHS and METHS (C1) and CONHS versus METHS (C2). Relative to TN, EHB cows had increased RT during the postcalving weeks and increased RR and ST during the entire transition period. Body weight, BCS, DMI, and milk yield were not affected by the EHB or RPM. However, protein percentage and SNF were lower in CONHS, relative to METHS cows. At calving, METHS dams had higher glucose concentrations, relative to CONHS, and during the postcalving weeks, the EHB cows had lower NEFA concentrations than TN cows. Calf birthweight and AEA were reduced by HS, whereas RR was increased by HS. Calf withers height tended to be shorter and RT were lower in CONHS, compared with METHS heifers. Overall, RPM supplementation to transition cows reverts the negative effect of HS on blood glucose concentration at calving and milk protein percentage in the dams and increases wither height while decreasing RT in the calf., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Dairy cows experiencing heat stress (HS) during the pre-calving portion of the transition period give birth to smaller calves and produce less milk and milk protein. Supplementation of rumen-protected methionine (RPM) has been shown to modulate protein, energy, and placenta metabolism, making it a potential candidate to ameliorate HS effects. We investigated the effects of supplementing RPM to transition cows under HS induced by electric heat blanket (EHB) on cow-calf performance. Six weeks before expected calving, 53 Holstein cows were housed in a tie-stall barn and fed a control diet (CON, 2.2% Met of MP) or a CON diet supplemented with Smartamine®M (MET, 2.6% Met of MP, Adisseo Inc., France). Four weeks pre-calving, all MET and half CON cows were fitted with an EHB. The other half of the CON cows were considered thermoneutral (TN), resulting in 3 treatments: CONTN (n = 19), CONHS (n = 17), and METHS (n = 17). Respiratory rate (RR), skin temperature (ST), and rectal temperature (RT) were measured thrice weekly and core body temperatures recorded bi-weekly. Post-calving body weights (BW) and BCS were recorded weekly, and DMI was calculated and averaged weekly. Milk yield was recorded daily and milk components were analyzed every third DIM. Biweekly AA and weekly nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHB), insulin, and glucose were measured from plasma. Calf birth weight and 24 h growth, thermoregulation, and hematology profile were measured and apparent efficiency of absorption (AEA) of immunoglobulins was calculated. Data were analyzed using the MIXED procedure of SAS with 2 preplanned orthogonal contrasts: CONTN vs. the average of CONHS and METHS (C1) and CONHS vs. METHS (C2). Relative to TN, EHB cows had increased RT during the post-calving weeks and increased RR and ST during the entire transition period. Body weight, BCS, DMI, and milk yield were not impacted by the EHB or RPM. However, protein % and SNF were lower in CONHS, relative to METHS cows. At calving, METHS dams had higher glucose concentrations, relative to CONHS, and during the post-calving weeks, the EHB cows had lower NEFA concentrations than TN cows. Calf birthweight and AEA were reduced by HS, while RR was increased by HS. Calf withers height tended to be shorter and RT were lower in CONHS, compared with MTHS heifers. Overall, RPM supplementation to transition cows reverts the negative impact of HS on blood glucose concentration at calving and milk protein % in the dams and increases wither height while decreasing RT in the calf., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Pump thrombosis (PT) and related adverse complications contributed to the HeartWare Ventricular Assist Device (HVAD) market withdrawal. Many patients still receive lifelong support, with deficient PT surveillance based on pump power trends. Analysis of pump vibrations is better for detecting PT. Here, we investigated the feasibility of an extracorporeal accelerometer to detect PT from pump vibrations propagated out on the driveline., Methods: In a porcine HVAD model (n = 6), an accelerometer was attached to the pump as a reference and another to the driveline for comparisons of signals. In total, 59 thrombi were injected into the heart to induce PT, followed by intermittent thrombus washout maneuvers. Signals were compared visually in spectrograms and quantitatively in third harmonic saliences (S 3H ) by correlation analysis. Receiver operating characteristic curves expressed the method's outcome in sensitivity vs specificity, with the overall diagnostic performance in the area under the curve (AUC) score., Results: Five experiments had good driveline signal strength, with clear spectrographic relationships between the 2 accelerometers. Third harmonic driveline vibrations were visible 20 vs 30 times in the reference. The comparison in S 3H showed a strong correlation and yielded an AUC of 0.85. Notably, S 3H proved robust regarding noise and false PT detections., Conclusions: An extracorporeal accelerometer on the driveline can be a readily available method for accurate HVAD PT detection before an accelerometer integration with left ventricular assist device is feasible., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Nanoparticles represent one of the most important innovations in the medical field. Among nanocarriers, polymeric nanoparticles (PNPs) attracted much attention due to their biodegradability, biocompatibility, and capacity to increase efficacy and safety of encapsulated drugs. Another important improvement in the use of nanoparticles as delivery systems is the conjugation of a targeting agent that enables the nanoparticles to accumulate in a specific tissue. Despite these advantages, the clinical translation of therapeutic approaches based on nanoparticles is prevented by their interactions with blood proteins. In fact, the so-formed protein corona (PC) drastically alters the biological identity of the particles. Adsorbed activated proteins of the complement cascade play a pivotal role in the clearance of nanoparticles, making them more easily recognized by macrophages, leading to their rapid elimination from the bloodstream and limiting their efficacy. Since the mouse is the most used preclinical model for human disease, this work compared human and mouse PC formed on untargeted PNPs (uPNPs) and targeted PNPs (tPNPs), paying particular attention to complement activation., Results: Mouse and human serum proteins adsorbed differently to PNPs. The differences in the binding of mouse complement proteins are minimal, whereas human complement components strongly distinguish the two particles. This is probably due to the human origin of the Fc portion of the antibody used as targeting agent on tPNPs. tPNPs and uPNPs mainly activate complement via the classical and alternative pathways, respectively, but this pattern did not affect their binding and internalization in macrophages and only a limited consumption of the activity of the human complement system was documented., Conclusions: The results clearly indicate the presence of complement proteins on PNPs surface but partially derived from an unspecific deposition rather than an effective complement activation. The presence of a targeting antibody favors the activation of the classical pathway, but its absence allows an increased activation of the alternative pathway. This results in similar opsonization of both PNPs and similar phagocytosis by macrophages, without an impairment of the activity of circulating complement system and, consequently, not enhancing the susceptibility to infection., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The Two Weeks in the World research project has resulted in a dataset of 3087 clinically relevant bacterial genomes with pertaining metadata, collected from 59 diagnostic units in 35 countries around the world during 2020. A relational database is available with metadata and summary data from selected bioinformatic analysis, such as species prediction and identification of acquired resistance genes., (© 2023. Springer Nature Limited.)

Objectives: We sought to improve utilization of a sepsis care bundle and decrease 3- and 30- day sepsis-attributable mortality, as well as determine which care elements of a sepsis bundle are associated with improved outcomes., Methods: Children's Hospital Association formed a QI collaborative to Improve Pediatric Sepsis Outcomes (IPSO) (January 2017-March 2020 analyzed here). IPSO Suspected Sepsis (ISS) patients were those without organ dysfunction where the provider "intended to treat" sepsis. IPSO Critical Sepsis (ICS) patients approximated those with septic shock. Process (bundle adherence), outcome (mortality), and balancing measures were quantified over time using statistical process control. An original bundle (recognition method, fluid bolus < 20 min, antibiotics < 60 min) was retrospectively compared with varying bundle time-points, including a modified evidence-based care bundle, (recognition method, fluid bolus < 60 min, antibiotics < 180 min). We compared outcomes using Pearson χ-square and Kruskal Wallis tests and adjusted analysis., Results: Reported are 24 518 ISS and 12 821 ICS cases from 40 children's hospitals (January 2017-March 2020). Modified bundle compliance demonstrated special cause variation (40.1% to 45.8% in ISS; 52.3% to 57.4% in ICS). The ISS cohort's 30-day, sepsis-attributable mortality dropped from 1.4% to 0.9%, a 35.7% relative reduction over time (P < .001). In the ICS cohort, compliance with the original bundle was not associated with a decrease in 30-day sepsis-attributable mortality, whereas compliance with the modified bundle decreased mortality from 4.75% to 2.4% (P < .01)., Conclusions: Timely treatment of pediatric sepsis is associated with reduced mortality. A time-liberalized care bundle was associated with greater mortality reductions., (Copyright © 2023 by the American Academy of Pediatrics.)

Most new pathogens of humans and animals arise via switching events from distinct host species. However, our understanding of the evolutionary and ecological drivers of successful host adaptation, expansion, and dissemination are limited. Staphylococcus aureus is a major bacterial pathogen of humans and a leading cause of mastitis in dairy cows worldwide. Here we trace the evolutionary history of bovine S. aureus using a global dataset of 10,254 S. aureus genomes including 1,896 bovine isolates from 32 countries in 6 continents. We identified 7 major contemporary endemic clones of S. aureus causing bovine mastitis around the world and traced them back to 4 independent host-jump events from humans that occurred up to 2,500 y ago. Individual clones emerged and underwent clonal expansion from the mid-19th to late 20th century coinciding with the commercialization and industrialization of dairy farming, and older lineages have become globally distributed via established cattle trade links. Importantly, we identified lineage-dependent differences in the frequency of host transmission events between humans and cows in both directions revealing high risk clones threatening veterinary and human health. Finally, pangenome network analysis revealed that some bovine S. aureus lineages contained distinct sets of bovine-associated genes, consistent with multiple trajectories to host adaptation via gene acquisition. Taken together, we have dissected the evolutionary history of a major endemic pathogen of livestock providing a comprehensive temporal, geographic, and gene-level perspective of its remarkable success.

Background: A 56 US hospital collaborative, Improving Pediatric Sepsis Outcomes, has developed variables, metrics and a data analysis plan to track quality improvement (QI)-based patient outcomes over time. Improving Pediatric Sepsis Outcomes expands on previous pediatric sepsis QI efforts by improving electronic data capture and uniformity across sites., Methods: An expert panel developed metrics and corresponding variables to assess improvements across the care delivery spectrum, including the emergency department, acute care units, hematology and oncology, and the ICU. Outcome, process, and balancing measures were represented. Variables and statistical process control charts were mapped to each metric, elucidating progress over time and informing plan-do-study-act cycles. Electronic health record (EHR) abstraction feasibility was prioritized. Time 0 was defined as time of earliest sepsis recognition (determined electronically), or as a clinically derived time 0 (manually abstracted), identifying earliest physiologic onset of sepsis., Results: Twenty-four evidence-based metrics reflected timely and appropriate interventions for a uniformly defined sepsis cohort. Metrics mapped to statistical process control charts with 44 final variables; 40 could be abstracted automatically from multiple EHRs. Variables, including high-risk conditions and bedside huddle time, were challenging to abstract (reported in <80% of encounters). Size or type of hospital, method of data abstraction, and previous QI collaboration participation did not influence hospitals' abilities to contribute data. To date, 90% of data have been submitted, representing 200 007 sepsis episodes., Conclusions: A comprehensive data dictionary was developed for the largest pediatric sepsis QI collaborative, optimizing automation and ensuring sustainable reporting. These approaches can be used in other large-scale sepsis QI projects in which researchers seek to leverage EHR data abstraction., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Abstract: At the start of the COVID-19 pandemic, the US faced nationwide shortages of nasopharyngeal swabs due to both overwhelmed supply chains and an increase in demand. To address this shortfall, multiple 3D printed swabs were ultimately produced and sold for COVID-19 testing. In this work, we present a framework for mechanical and functional bench-testing of nasopharyngeal swabs using standard and widely available material testing equipment. Using this framework, we offer a comprehensive, quantitative comparison of the 3D printed swabs to benchmark their performance against traditional flocked swabs. The test protocols were designed to emulate the clinical use of the nasopharyngeal swabs and to evaluate potential failure modes. Overall, the 3D printed swabs performed comparably to, or outperformed, the traditional swabs in all mechanical tests. While traditional swabs outperformed some of the new 3D printed swabs in terms of sample uptake and retention, similar amounts of RNA were recovered from both 3D printed and traditional swabs., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021.)

We present a clinical imaging question focusing on a patient with a history of gross hematuria and an enhancing mass abutting the left renal collecting system. In patients with nondiagnostic cytology and imaging, upper tract urothelial carcinoma should be explored as a potential etiology prior to definitive surgical management., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Investigate clinical and system drivers of family satisfaction in the PICU., Design: Mixed methods qualitative and quantitative (observational) study. Qualitative interviews with families were performed as a pilot to inform modality of survey distribution based on family preferences. A validated pediatric satisfaction survey deployed to family members for 7 months with a corresponding chart review and administrative data collection., Setting: PICU in a tertiary children's hospital., Patients: Two hundred six families of patients admitted to the PICU more than 48 hours., Interventions: None., Measurements and Main Results: Families preferred surveys distributed electronically on a tablet in the PICU setting. The Pediatric Family Satisfaction-ICU survey was used to assess comfort with medical decision-making and communication with the care team. Capture rate of all eligible patients was 69.5% and response rate was 90.8%. Overall, 64.7% of respondents were highly satisfied, whereas over one third were not highly satisfied; families of Hispanic ethnicity (odds ratio of lower satisfaction of families with Hispanic ethnicity: 2.09; 95% CI, 1.01-4.33; p = 0.047) and high social stressors (odds ratio of higher satisfaction among high stressed subgroup: 0.49; 95% CI, 0.24-0.99; p = 0.047) reported statistically significant lower satisfaction. Additional free-text responses were identified in 21% of respondents, with the majority of comments indicating wishes for improvements clustered around communication with the medical team or sleeping environment of families and patients., Conclusions: High capture rates of family satisfaction in the PICU can be obtained with a PICU-specific survey, limiting barriers to completion by including family preferences, and distributing in the PICU setting. Less than two-third of PICU families are highly satisfied; patients of Hispanic ethnicity and those with high social stressors predict low satisfaction, whereas illness severity, age, and PICU length of stay did not have statistical significance. Local improvement teams can use this approach to drive enhanced satisfaction.

Background: Similar to the situation in other European countries, Danish wild boars may harbour a wide range of pathogens infectious to humans and domestic pigs. Although wild boars must be kept behind fences in Denmark, hunting and consumption of the meat may cause zoonotic transmission. Moreover, most infections of wild boars are transmissible to domestic pigs, which may have important economic consequences. The aim of this study was to investigate whether Danish wild boars were infected with bacteria and parasites transmissible to humans or domestic pigs: Brucella suis, methicillin-resistant Staphylococcus aureus (MRSA), Salmonella spp., Trichinella spp., lungworms and gastrointestinal parasites, especially Ascaris suum. This is the first study to investigate the prevalence of these important pathogens in Danish wild boars., Results: Wild boars from eight enclosures were analysed over a 5-year period. All tested wild boars were negative for B. suis (n = 240), MRSA (n = 244), Salmonella spp. (n = 115) and Trichinella spp. (n = 232), while eight parasite genera were identified in the faeces (n = 254): Ascaris suum, Capillaria sp., Cystoisospora suis, Eimeria spp., Metastrongylus sp. (lungworm), Strongyloides ransomi, Trichuris suis and strongylid eggs, i.e. strongyles not identified to the genera. Eimeria spp. and Metastrongylus sp. had the highest prevalence (92.3 and 79.5%, respectively) and were identified in wild boars from all eight enclosures, while the remaining parasite genera were present more sporadically., Conclusions: Wild boars from Denmark constitute a low risk of transmitting B. suis, MRSA, Salmonella spp. and Trichinella spp. to humans or domestic pigs, while economically important parasites transmissible to domestic pigs are highly prevalent in the wild boar population.

More than 55 million mink skins were produced globally in 2017. As a consequence, a large number of people are employed in mink production worldwide. In Denmark, farmed mink were found to constitute a reservoir of methicillin-resistant Staphylococcus aureus (MRSA) clonal complex (CC) 398 and 6000 mink farm workers in Denmark are potentially exposed to LA-MRSA CC398. The study aim was to elucidate the source of LA-MRSA CC398 in mink farms and to investigate possible transmission to humans. In total, 161 LA-MRSA CC398 isolates from mink (n = 65), mink feed (n = 16) and humans (n = 80) with reported contact to mink, were whole-genome sequenced and compared to 183 LA-MRSA CC398 isolates from Danish pigs and an international collection of 89 S. aureus CC398 isolates. Most of the mink-associated isolates clustered within the predominant LA-MRSA CC398 lineages circulating in the Danish pig production, supporting that pigs are a source of LA-MRSA CC398 in mink feed, mink, and mink farmers., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The incidence of clinical complications such as granuloma formation and sarcoidosis is often seen in black tattoos and may be associated with agglomeration of black pigment., Aim: To measure count and dimensions of agglomerates in black tattoo inks vs red inks and to compare old inks and new inks of identical brands., Method: Examination was performed by light microscopy (Olympus BX51 ™ ) with magnification 40X, immersion oil. Photographs (Jenoptik Gryphax RGB camera) were taken of each ink sample and analysed by ImageJ software; count, area, width, height, circumference and circularity index were measured. Agglomerates were defined as width and height of objects above 800 nm. Twenty-one new unopened black inks and 17 new unopened red inks were compared. Furthermore, five old black inks and five old red inks, that had been opened and stocked for over 2 years, were compared with new products of the same brands., Results: Black agglomerates were area wise and with respect to width, height and circumference significantly larger compared with red agglomerates and more circularly shaped. Count of agglomerates was lower in black inks than in red inks, in accordance with bigger dimensions of black agglomerates. Comparison of old and new inks indicated old inks have larger agglomerates but variable bottle size and storage conditions may have confounded results., Conclusion: Pigment agglomerates in black tattoo ink stock products were sized larger than agglomerates in red inks. Agglomerates found directly in black inks may predispose to granuloma formation in black tattoos causing sarcoid reaction., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Black tattoo reactions are suggested to be foreign body reactions manifested as papulo-nodular inflammation that is associated with active sarcoidosis., Aim: To study the morphology of black and red pigment agglomerates in skin biopsies from tattoo reactions, referenced to clinical diagnoses., Method: Agglomerate count, area, width, height, circumference and circularity were measured in 161 patients by light microscopy (Olympus BX51™); 161 unstained skin biopsies from 64 black tattoo reactions and 97 reactions in red tattoos with allergy. Images (Jenoptic Gryphax RGB camera) were taken through a 40× objective using immersion oil. Computerised analysis of agglomerates was performed using ImageJ software. Student t test, chi-square test, Fisher Exact test, ANOVA and Bonferroni tests were applied., Results: Comparison of black and red pigment agglomerates showed no overall differences in count, area, width, height or circumference. However, in black tattoo reactions, the count of agglomerates was higher in patients with sarcoidosis (P = .009) vs no sarcoidosis. Black agglomerates were more circular shaped as compared to red, P = .023. In red tattoo reactions, agglomerates in patients with allergic cross-reactivity were slightly more circular (P = .036) vs patients with milder allergy. The count of red agglomerates was lower in patients clinically typed excessive hyperkeratosis (P = .041) compared with other clinical types of allergy., Conclusion: Patients with reactions in black tattoos associated with sarcoidosis have increased count of pigment agglomerates vs those without associated sarcoidosis indicating that black pigment agglomeration is one among a number of factors triggering sarcoid tattoo complication. Circular shape of agglomerates may code for bioactivity., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this work, hydrogen isotopes in the form of protium and deuterium were rapidly desorbed from magnetic-hydride iron oxide-palladium (Fe 2 O 3 -Pd) hybrid nanomaterials using an alternating magnetic field (AFM). Palladium (Pd), a hydride material with a well-known hydrogen isotope effect, was deposited on an Fe 2 O 3 magnetic nanoparticle support by solution chemistries and used as a hydrogen isotope storage component. The morphological, structural, optical, and magnetic studies reveal that the Fe 2 O 3 -Pd nanoparticles are hybrid structures exhibiting both hydrogen isotope storage (Pd) and magnetic (Fe 2 O 3 ) properties. The hydrogen isotope sorption/desorption behavior of metal hydride-magnetic nanomaterials was assessed by isothermal pressure-composition response curves (isotherms). The amount and rate of hydrogen isotope gas release was tuned by simply adjusting the strength of the magnetic field strength applied. Protium and deuterium displayed similar loading capacities, namely, H/M 0.55 and H/M = 0.45, but different plateau pressures. Significant differences in the kinetics of release for protium and deuterium during magnetic heating were observed. A series of magnetically induced charge-discharge cycling experiments were conducted showing that this is a highly reproducible and robust process.

Background: Abortion is a major source of economic losses in cattle breeding. Abortion occurs due to a wide range of causes, but infections are the most frequently diagnosed. However, establishing an aetiological diagnosis remains challenging due to the large variety of bacteria, protozoa, viruses, and fungi that have been associated with abortion in cattle. Economic restraints limit the range of diagnostic methods available for routine diagnostics, and decomposition of the conceptus or lack of proper fetal and/or maternal samples further restrict the diagnostic success. In this study, we report recent diagnostic findings from bovine abortions in Denmark, a country that has a large dairy sector and is free from most infectious agents causing epizootic abortion in cattle. The aims of the study were: (i) to identify infectious causes of bovine abortion in Denmark, (ii) to categorise the diagnostic findings based on the level of diagnostic certainty, and (iii) to assess the diagnostic rate. Due to economic restraints, only a limited panel of routine diagnostic methods were available. Placentas and/or fetuses from mid- to late-term abortions and stillbirths (n = 162) were submitted to the Danish National Veterinary Institute between January 2015 and June 2017. The aborted materials were examined macroscopically, histologically, and by bacterial culture. Maternal blood samples were tested for bovine viral diarrhoea virus (BVDV) antibodies., Results: The likely aetiology of the abortion was diagnosed in 52 cases, resulting in a diagnostic rate of 33%. The most common cause was protozoal infection (19%) followed by infection with Trueperella pyogenes (3%), Staphylococcus aureus (2%), and non-haemolytic Escherichia coli (2%). Lesions in fetuses with a protozoal infection were consistent with neosporosis. In many cases (38%), inflammatory changes were found in the placenta and/or fetal organs but no specific aetiology was identified. Neither infection with Brucella spp. nor maternal BVDV antibodies were detected. The majority of submitting herds (92%) were each represented by fewer than three abortion cases over the study period., Conclusions: Protozoal infection, most likely neosporosis, was the most commonly diagnosed cause of abortion and the only one associated with potential epizootic abortion events. Despite using a reduced number of diagnostic methods in comparison to other abortion studies, the diagnostic rate of this study was within the range reported in an earlier Danish study, as well as in recent international studies. The low number of submitted cases per herd and the sparse anamnestic information provided at submission hampered conclusions on the potential epizootic character of the abortion events in question.

Alkylating chemotherapy is a central component of the management of glioblastoma (GBM). Among the factors that regulate the response to alkylation damage, NF-κB acts to both promote and block cytotoxicity. In this study, we used genome-wide expression analysis in U87 GBM to identify NF-κB-dependent factors altered in response to temozolomide and found the long noncoding RNA (lncRNA) MALAT1 as one of the most significantly upregulated. In addition, we demonstrated that MALAT1 expression was coregulated by p50 (p105) and p53 via novel κB- and p53-binding sites in the proximal MALAT1 coding region. Temozolomide treatment inhibited p50 recruitment to its cognate element as a function of Ser329 phosphorylation while concomitantly increasing p53 recruitment. Moreover, luciferase reporter studies demonstrated that both κB and p53 cis-elements were required for efficient transactivation in response to temozolomide. Depletion of MALAT1 sensitized patient-derived GBM cells to temozolomide cytotoxicity, and in vivo delivery of nanoparticle-encapsulated anti-MALAT1 siRNA increased the efficacy of temozolomide in mice bearing intracranial GBM xenografts. Despite these observations, in situ hybridization of GBM specimens and analysis of publicly available datasets revealed that MALAT1 expression within GBM tissue was not prognostic of overall survival. Together, these findings support MALAT1 as a target for chemosensitization of GBM and identify p50 and p52 as primary regulators of this ncRNA. SIGNIFICANCE: These findings identify NF-κB and p53 as regulators of the lncRNA MALAT1 and suggest MALAT1 as a potential target for the chemosensitization of GBM., (©2019 American Association for Cancer Research.)

The present study aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (core building unit) and L-lactide (GluN-LLA). Particles were made via electrohydrodynamic atomization. Prolonged release (for up to 14 days) of RIF from these particles is reported. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism in vitro and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) particles (reference materials) did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated that cell death correlates with an increase of particle concentration but is not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. The uptake of GluN-LLA particles is higher than those of their PLA counterparts. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and showed favorable long-term drug release behavior, which facilitated the killing of intracellular bacteria when compared to free RIF. The present studies suggest that these drug carrier materials are potentially very attractive candidates for the development of high-payload, sustained-release antibiotic/resorbable polymer particle systems for treating bacterial lung infections.

The aim of the present study was to identify the animal prevalence and environmental reservoir of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in mink farms. LA-MRSA on mink constitutes a human health hazard to farmers and farm workers, who handle the animals and are at risk of bites and scratches from colonized sites. The primary route of LA-MRSA colonization of mink is suspected to be by ingestion of contaminated pig by-products. We performed a cross-sectional study with repeated measurements during May-July 2017. A total of 644 mink carcasses (542 mink kits and 102 breeding animals) from five Danish farms were sampled. From each carcass, pharynx was swabbed and the right forepaw dissected. In addition, environmental samples covering feed, air, glove, cages (top and between) and nest boxes were collected on the farms. MRSA was selectively cultured from each sample and suspect colonies were assessed using matrix-assisted laser desorption ionisation (MALDI-TOF) for species confirmation. Further, from each farm, three isolates from mink and one isolate per positive environmental site were sent for whole genome sequencing. We isolated LA-MRSA from mink in four out of the five farms, but LA-MRSA bacterium was detected on all farms. On farms with LA-MRSA positive animals, the overall apparent animal prevalence ranged from 20% [13;29] CI95% to 29% [22;38] CI95% . LA-MRSA was isolated from kits before weaning, most likely due to a contaminated environment or transfer from the dam. Further, the apparent prevalence of LA-MRSA in kits tended to increase during the first months of age. On farms where LA-MRSA was isolated from mink, LA-MRSA was also isolated from the environment. LA-MRSA was isolated from all environmental sites tested (i.e. glove, on top of and between the cages and in the nest boxes), apart from air. The negative air samples contrast with the high concentrations of LA-MRSA in air found in the pig production. Hence, the risk of human exposure to LA-MRSA on mink-farms tends to be associated mainly with direct contact with contaminated environmental sites and the handling of colonized mink. All sequenced isolates were confirmed as LA-MRSA CC398 and genetically similar to clones previously isolated from the Danish pig production, supporting the hypothesis of LA-MRSA being transmitted by contaminated pig by-products., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We hypothesized that slow crystalloid resuscitation would result in less blood loss and a smaller hemoglobin decrease compared to a rapid resuscitation during uncontrolled hemorrhage., Methods: Anesthetized, splenectomized domestic swine underwent hepatic lobar hemitransection. Lactated Ringers was given at 150 or 20 mL/min IV (rapid vs. slow, respectively, N = 12 per group; limit of 100 mL/kg). Primary endpoints were blood loss and serum hemoglobin; secondary endpoints included survival, vital signs, coagulation parameters, and blood gases., Results: The slow group had a less blood loss (1.6 vs. 2.7 L, respectively) and a higher final hemoglobin concentration (6.0 vs. 3.4 g/dL)., Conclusions: Using a fixed volume of crystalloid resuscitation in this porcine model of uncontrolled intraabdominal hemorrhage, a slow IV infusion rate produced less blood loss and a smaller hemoglobin decrease compared to rapid infusion., Competing Interests: The authors have declared that no competing interests exist.

Capillaria plica is a parasitic nematode belonging to the family Capillariidae. The adult parasites reside in the urinary tract of wild and domestic canines. The infection is most often asymptomatic, but can cause a wide range of symptoms including urinary bladder inflammation, pollacisuria, dysuria and hematuria. Canines acquire the infection by ingesting the intermediate host, the earthworm (Lumbricidae). Epidemiological studies on C. plica infection in wildlife are few and only one previous Danish study examined the prevalence in red foxes, while studies on prevalence in other animals are limited. We examined the urine sediment or urinary bladder from 375 Raccoon dogs ( Nyctereutes procyonoides ), 247 red foxes ( Vulpes vulpes ), 20 beech martens ( Martes foina ), 16 wild mink ( Neovison vison ), 14 otters ( Lutra lutra ), nine European polecats ( Mustela putorius ), three European badgers ( Meles meles ) and one golden jackal ( Canis aureus ) received as a part of Danish wildlife surveillance. Capillaria plica was detected in 73.7% of red foxes, 20.0% of beech martens, 0.5% of raccoon dogs, and in the Golden jackal. Red foxes originating from all 5 regions of Denmark were infected, although with a significantly higher prevalence in the three regions in Jutland compared to Region Zealand.

In this study, heparin-loaded poly-ɛ-caprolactone (PCL) fibrous mats were prepared and characterized based on their physical, cytotoxic, thermal, and biological properties. The main objective of the work described here was to test the hypothesis that incorporation of heparin into a PCL carrier could serve as bio-compatible material capable of inhibiting Human Papillomavirus (HPV) infection. The idea of firmly anchoring heparin to capture soluble virus, vs. a slow heparin release to inhibit a virus in solution was tested. Thus, one material was produced via conventional heparin matrix encapsulation and electrohydrodynamic fiber processing in one step. A second type of material was obtained via heparin crosslinking. This was achieved by running a carbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling reaction on preformed PCL fibers. In vitro HPV16 L1 protein binding capacity studies were performed. Infectivity assays were done using HPV16 pseudoviruses (PsVs) carrying a GFP plasmid to directly test the ability of the fibrous mats to prevent internalization of HPV PsVs. The crosslinked heparin material presented a dissociation constant (Kd) value comparable to those found in the literature for different heparin-protein L1 peptide interactions. Both materials significantly reduced internalization of HPV PsVs, with a reduction of 94% of PsVs internalization when matrix encapsulated heparin-loaded material was present. Differences in performance between the two proposed structures are discussed., Competing Interests: The authors have declared that no competing interests exist.

We report Taenia ovis infection in Danish sheep for the first time. In spring 2016, the metacestode stage of T. ovis was at slaughter observed in heart muscles, diaphragm and skeletal muscles from approx. a third of all sheep from one specific farm localised in South Jutland. The diagnosis was confirmed by molecular typing of the mitochondrial cytochrome c oxidase I (cox1) gene. Three newly imported dogs were suspected but the definitive host was unidentifiable. The finding is not regulated in the meat control procedures. However, infected meat is usually condemned due to aesthetic reasons causing economic losses. Thus, finding of T. ovis is of concern to sheep meat producers in the area, as the infection could have spread further on to other farms., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Sepsis is a leading cause of morbidity and mortality in children worldwide. Barriers exist for timely recognition and management in emergency care settings. This 1-year quality improvement collaborative sought to reduce mortality from sepsis., Methods: Fifteen hospitals participated initially. We included children with a spectrum of illness from sepsis to septic shock. The intervention bundle focused on recognition, escalation of care, and the first hour of resuscitation. We conducted monthly learning sessions and disseminated data reports of site-specific and aggregated metrics to drive rapid cycle improvement., Results: Seven sites contributed enough data to be analyzed. Of the 1,173 pediatric patients in the total cohort, 506 presented with severe sepsis/septic shock. Quarterly data demonstrated a mean improvement in initial clinical assessment from 46% to 60% ( P < 0.001) and in adherence to the administration of first fluid bolus within 15 minutes from 38% to 46% ( P < 0.015). There was no statistically significant improvement in other process metrics. There was no statistically significant improvement in mortality for the total cohort (sepsis to septic shock) or either of the subgroups in either 3- or 30-day mortality., Conclusions: A quality improvement collaborative focused on improving timely recognition and management of pediatric sepsis to septic shock led to some process improvements but did not show improvement in mortality. Future national efforts should standardize definitions and processes of care for sepsis to septic shock, including the identification of a "time zero" for measuring the timeliness of treatment.

Background: Infectious skin disorders are not uncommon in mink. Such disorders are important as they have a negative impact on animal health and welfare as well as on the quality and value of the fur. This study presents the isolation of Arcanobacterium phocae from mink with severe skin lesions and other pathological conditions, and from wild seals and otters., Results: In 2015, A. phocae was isolated for the first time in Denmark from outbreaks of dermatitis in mink farms. The outbreaks affected at least 12 farms. Originating from these 12 farms, 23 animals cultured positive for A. phocae. The main clinical findings were necrotizing pododermatitis or dermatitis located to other body sites, such as the lumbar and cervical regions. A. phocae could be isolated from skin lesions and in nine animals also from liver, spleen and lung, indicating a systemic spread. The bacterium was also, for the first time in Denmark, detected in dead seals (n = 9) (lungs, throat or wounds) and otters (n = 2) (throat and foot)., Conclusions: An infectious skin disorder in mink associated with A. phocae has started to occur in Danish farmed mink. The origin of the infection has not been identified and it is still not clear what the pathogenesis or the port of entry for A. phocae infections are.

Background: For proper treatment of bacterial infections in mink, knowledge of the causative agents and their antimicrobial susceptibility patterns is crucial. The used antimicrobials are in general not registered for mink, i.e. most usage is "off-label". In this study, we report the patterns of antimicrobial resistance among pathogenic bacteria isolated from Danish mink during the period 2014-2016. The aim of this investigation was to provide data on antimicrobial resistance and consumption, to serve as background knowledge for new veterinary guidelines for prudent and optimal antimicrobial usage in mink., Results: A total number of 308 Escherichia coli isolates, 41 Pseudomonas aeruginosa, 36 Streptococcus canis, 30 Streptococcus dysgalactiae, 55 Staphylococcus delphini, 9 Staphylococcus aureus, and 20 Staphylococcus schleiferi were included in this study. Among E. coli, resistance was observed more frequently among the hemolytic isolates than among the non-hemolytic ones. The highest frequency of resistance was found to ampicillin, 82.3% and 48.0% of the hemolytic of the non-hemolytic isolates, respectively. The majority of the P. aeruginosa isolates were only sensitive to ciprofloxacin and gentamicin. Among the Staphylococcus spp., the highest occurrence of resistance was found for tetracycline. Regarding the nine S. aureus, one isolate was resistant to cefoxitin indicating it was a methicillin-resistant Staphylococcus aureus. Both β-hemolytic Streptococcus species showed high levels of resistance to tetracycline and erythromycin. The antimicrobial consumption increased significantly during 2007-2012, and fluctuated at a high level during 2012-2016, except for a temporary drop in 2013-2014. The majority of the prescribed antimicrobials were aminopenicillins followed by tetracyclines and macrolides., Conclusions: The study showed that antimicrobial resistance was common in most pathogenic bacteria from mink, in particular hemolytic E. coli. There is a need of guidelines for prudent use of antimicrobials for mink.

Background: The eruptions of Eyjafjallajökull (2010) and Grímsvötn (2011), Iceland, triggered immediate, international consideration of the respiratory health hazard of inhaling volcanic ash, and prompted the need to estimate the potential hazard posed by future eruptions of Iceland's volcanoes to Icelandic and Northern European populations., Methods: A physicochemical characterization and toxicological assessment was conducted on a suite of archived ash samples spanning the spectrum of past eruptions (basaltic to rhyolitic magmatic composition) of Icelandic volcanoes following a protocol specifically designed by the International Volcanic Health Hazard Network., Results: Icelandic ash can be of a respirable size (up to 11.3 vol.% < 4 μm), but the samples did not display physicochemical characteristics of pathogenic particulate in terms of composition or morphology. Ash particles were generally angular, being composed of fragmented glass and crystals. Few fiber-like particles were observed, but those present comprised glass or sodium oxides, and are not related to pathogenic natural fibers, like asbestos or fibrous zeolites, thereby limiting concern of associated respiratory diseases. None of the samples contained cristobalite or tridymite, and only one sample contained quartz, minerals of interest due to the potential to cause silicosis. Sample surface areas are low, ranging from 0.4 to 1.6 m 2  g -1 , which aligns with analyses on ash from other eruptions worldwide. All samples generated a low level of hydroxyl radicals (HO • ), a measure of surface reactivity, through the iron-catalyzed Fenton reaction compared to concurrently analyzed comparative samples. However, radical generation increased after 'refreshing' sample surfaces, indicating that newly erupted samples may display higher reactivity. A composition-dependent range of available surface iron was measured after a 7-day incubation, from 22.5 to 315.7 μmol m -2 , with mafic samples releasing more iron than silicic samples. All samples were non-reactive in a test of red blood cell-membrane damage., Conclusions: The primary particle-specific concern is the potential for future eruptions of Iceland's volcanoes to generate fine, respirable material and, thus, to increase ambient PM concentrations. This particularly applies to highly explosive silicic eruptions, but can also hold true for explosive basaltic eruptions or discrete events associated with basaltic fissure eruptions.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex (CC) 398 is widespread in the Danish pig production with around 90% of herds being positive. Since 2009, cases of CC398 LA-MRSA infections in Danish mink farmers have been observed. The objective of the study was to examine the presence of LA-MRSA in farmed mink. The investigation comprised three different sample types 1) clinical samples from carcasses submitted to the laboratory for diagnostic examination, 2) paws and pharyngeal swabs from healthy animals collected at pelting, and 3) feed samples from mink feed producers. In clinical samples, LA-MRSA was found in 34% of submissions and was most prevalent in samples from paws (33%) and pharynx (17%), followed by nasal and intestinal samples (each 13%), whereas it was never detected in perineal samples. LA-MRSA was found in healthy animals on 40% of the investigated farms, including paw samples (29%) and pharyngeal samples (16%). Twenty out of the 108 feed samples from feed producers were positive for LA-MRSA. The dominant spa-types were t034 and t011 associated to CC398, corresponding to the dominant spa-types detected in the Danish pig production, from which slaughter offal is used for mink feed. The spa-types, the high prevalence of LA-MRSA on paws and in pharynx, and its detection in feed samples, suggest feed as a possible source of LA-MRSA in mink., (Copyright © 2017 Elsevier B.V. All rights reserved.)

OBJECTIVE Adult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children. DESIGN Retrospective cohort SETTING Pediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitals PATIENTS Patients ≤18 years old ventilated for ≥1 day METHODS We identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models. RESULTS In total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on "pediatric VAC with antimicrobial use" (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test ("pediatric PVAP") occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls. CONCLUSIONS We propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes. Infect Control Hosp Epidemiol 2017;38:327-333.

Halicephalobus gingivalis is an opportunistic parasite which is known to cause fatal meningoencephalomyelitis primarily in equines but sporadically also in humans. In April 2014, laboratory examination of the head of a young dairy calf, euthanized due to severe central nervous system symptoms, revealed the presence of granulomatous to necrotizing encephalitis and myriads of nematodes in the brain lesion. Morphologically the parasites were identified as H. gingivalis. The diagnosis was confirmed by molecular analysis of the large subunit (LSU) rRNA and the small subunit (SSU) rRNA genes, revealing genetic variations of 0.5-4.4% and 0.7-8.6%, respectively, between the H. gingivalis isolated from the Danish calf and published isolates, collected worldwide from free-living and parasitic stages of the nematode. Clinical symptoms and histological changes indicated infection with H. gingivalis from another three calves in the herd. This is the first scientific publication of H. gingivalis induced meningoencephalomyelitis in ruminants. As ante mortem diagnosis is a major challenge, the infection may easily remain undiagnosed in cattle., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: To identify a pediatric ventilator-associated condition definition for use in neonates and children by exploring whether potential ventilator-associated condition definitions identify patients with worse outcomes., Design: Retrospective cohort study and a matched cohort analysis., Setting: Pediatric, cardiac, and neonatal ICUs in five U.S. hospitals., Patients: Children 18 years old or younger ventilated for at least 1 day., Interventions: None., Measurements and Main Results: We evaluated the evidence of worsening oxygenation via a range of thresholds for increases in daily minimum fraction of inspired oxygen (by 0.20, 0.25, and 0.30) and daily minimum mean airway pressure (by 4, 5, 6, and 7 cm H2O). We required worsening oxygenation be sustained for at least 2 days after at least 2 days of stability. We matched patients with a ventilator-associated condition to those without and used Cox proportional hazard models with frailties to examine associations with hospital mortality, hospital and ICU length of stay, and duration of ventilation. The cohort included 8,862 children with 10,209 hospitalizations and 77,751 ventilator days. For the fraction of inspired oxygen 0.25/mean airway pressure 4 definition (i.e., increase in minimum daily fraction of inspired oxygen by 0.25 or mean airway pressure by 4), rates ranged from 2.9 to 3.2 per 1,000 ventilator days depending on ICU type; the fraction of inspired oxygen 0.30/mean airway pressure 7 definition yielded ventilator-associated condition rates of 1.1-1.3 per 1,000 ventilator days. All definitions were significantly associated with greater risk of hospital death, with hazard ratios ranging from 1.6 (95% CI, 0.7-3.4) to 6.8 (2.9-16.0), depending on thresholds and ICU type. Each definition was associated with prolonged hospitalization, time in ICU, and duration of ventilation, among survivors. The advisory board of the study proposed using the fraction of inspired oxygen 0.25/mean airway pressure 4 thresholds to identify pediatric ventilator-associated conditions in ICUs., Conclusions: Pediatric patients with ventilator-associated conditions are at substantially higher risk for mortality and morbidity across ICUs, regardless of thresholds used. Next steps include identification of risk factors, etiologies, and preventative measures for pediatric ventilator-associated conditions.

Volcanic eruptions are common in Iceland and have caused health problems ever since the settlement of Iceland. Here we describe volcanic activity and the effects of volcanic gases and ash on human health in Iceland. Volcanic gases expelled during eruptions can be highly toxic for humans if their concentrations are high, irritating the mucus membranes of the eyes and upper respiratory tract at lower concentrations. They can also be very irritating to the skin. Volcanic ash is also irritating for the mucus membranes of the eyes and upper respiratory tract. The smalles particles of volcanic ash can reach the alveoli of the lungs. Described are four examples of volcanic eruptions that have affected the health of Icelanders. The eruption of Laki volcanic fissure in 1783-1784 is the volcanic eruption that has caused the highest mortality and had the greatest effects on the well-being of Icelanders. Despite multiple volcanic eruptions during the last decades in Iceland mortality has been low and effects on human health have been limited, although studies on longterm effects are lacking. Studies on the effects of the Eyjafjallajökul eruption in 2010 on human health showed increased physical and mental symptoms, especially in those having respiratory disorders. The Directorate of Health in Iceland and other services have responded promptly to recurrent volcanic eruptions over the last few years and given detailed instructions on how to minimize the effects on the public health. Key words: volcanic eruptions, Iceland, volcanic ash, volcanic gases, health effects, mortality. Correspondence: Gunnar Guðmundsson, ggudmund@landspitali.is.

Noncompressible truncal hemorrhage and brain injury currently account for most early mortality of warfighters on the battlefield. There is no effective treatment for noncompressible truncal hemorrhage, other than rapid evacuation to a surgical facility. The availability of an effective field treatment for noncompressible truncal hemorrhage could increase the number of warfighters salvaged from this frequently-lethal scenario. Our intent was to develop a porcine model of noncompressible truncal hemorrhage with a ∼ 50% one-hour mortality so that we could develop new treatments for this difficult problem. Normovolemic normothermic domestic swine (barrows, 3 months old, 34-36 kg) underwent one of three injury types through a midline incision: 1) central stellate injury (N = 6); 2) excision of a portal vein branch distal to the main PV trunk (N = 6); or 3) hemi-transection of the left lateral lobe of the liver at its base (N = 10). The one-hour mortality of these injuries was 0, 82, and 40%, respectively; the final mean arterial pressure was 65, 24, and 30 mm Hg, respectively; and the final hemoglobin was 8.3, 2.3, and 3.6 g/dL, respectively. Hemi-transection of the left lateral lobe of the liver appeared to target our desired mortality rate better than the other injury mechanisms.

Spirocerca lupi causes formation of nodules that may transform into sarcoma in the walls of aorta, esophagus and stomach of infected canids. In February 2013, post mortem examination of a red fox (Vulpes vulpes) hunted in Denmark revealed the presence of several nodules containing adult worms of Spirocerca sp. in the stomach and the omentum. The nodules largely consisted of fibrous tissue with infiltration of mononuclear cells, neutrophilic granulocytes and macrophages with hemosiderin deposition. Parasitological examination by three copromicroscopic methods, sedimentation, flotation with saturated sugar-salt solution, and sieving failed to detect eggs of Spirocerca sp. in feces collected from the colon. This is the first report of spirocercosis in Denmark, and may have been caused by a recent introduction by migrating paratenic or definitive host. Analysis of two overlapping partial sequences of the cox1 gene, from individual worms, revealed distinct genetic variation (7-9%) between the Danish worms and isolates of S. lupi from Europe, Asia and Africa. This was confirmed by phylogenetic analysis that clearly separated the Danish worms from other isolates of S. lupi. The distinct genetic differences of the current worms compared to other isolates of S. lupi may suggest the presence of a cryptic species within Spirocerca., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A network of extracellular signaling factors has previously been shown to act in concert to control the ovarian primordial to primary follicle transition. The current study was designed to investigate the roles of the endogenous bone morphogenetic protein (BMP) inhibitors Gremlin 1 (GREM1) and GREM2 in primordial follicle transition in the rat ovary. GREM1 and GREM2 treatments were found to reverse the effects of anti-Müllerian hormone (AMH) to inhibit follicle transition in a whole-ovary culture system. GREM1 reversed the effect of BMP4 to stimulate primordial follicle transition. Immunohistochemical studies showed that GREM2, but not GREM1, was present in primordial follicles suggesting that GREM2 may regulate primordial follicle transition in vivo. Co-immunoprecipitation studies indicated that GREM2 directly binds to AMH, as well as to BMP4. Transcriptome analyses of ovaries treated with GREM2 or GREM1 yielded negligible numbers of differentially expressed genes, suggesting that the immediate effects of GREM2 or GREM1 appear to be at the level of protein-protein interactions, rather than direct actions on the cells. A number of other ovarian growth factors were found to influence the expression of Grem2. Observations suggest that Grem2 is a part of the signaling network of growth factors that regulate the primordial to primary follicle transition. Insights into the regulatory networks affecting the pool of primordial follicles are important to understand the molecular basis for reproductive diseases such as primary ovarian insufficiency., (© 2014 Society for Reproduction and Fertility.)

Dyspnoea, a much less specific symptom of ischaemia than chest discomfort, is common among obese patients. Patients with dyspnoea often undergo stress testing as part of their evaluation. We sought to examine the yield of stress testing in non-elderly, obese, sedentary patients with dyspnoea on exertion (DOE) as a chief complaint.We reviewed stress echocardiograms carried out on 203 patients in a stress testing laboratory at a major tertiary care centre. Of these, 81 (40%) fell into a group that was at low risk for coronary artery disease (CAD) by clinical criteria. Ischaemia was detected in two patients in the low-risk group (2.5%), and these results were likely false positives. In the higher risk group, 9.0% of functional tests showed ischaemia; after further testing, 2.5% of the higher risk patients were found to have obstructive coronary lesions. Clinical follow-up was performed for a mean of 815 days. New obstructive coronary disease was detected in 1.6% of all patients, and these patients were from the higher risk group. In obese sedentary patients with DOE but otherwise at low risk of coronary disease stress testing is of very low yield. DOE is generally not an anginal equivalent in this patient population., (© 2014 The Authors. Clinical Obesity © 2014 International Association for the Study of Obesity.)

A major outbreak of canine distemper virus (CDV) in Danish farmed mink (Neovison vison) started in the late summer period of 2012. At the same time, a high number of diseased and dead wildlife species such as foxes, raccoon dogs, and ferrets were observed. To track the origin of the outbreak virus full-length sequencing of the receptor binding surface protein hemagglutinin (H) was performed on 26 CDV's collected from mink and 10 CDV's collected from wildlife species. Subsequent phylogenetic analyses showed that the virus circulating in the mink farms and wildlife were highly identical with an identity at the nucleotide level of 99.45% to 100%. The sequences could be grouped by single nucleotide polymorphisms according to geographical distribution of mink farms and wildlife. The signaling lymphocytic activation molecule (SLAM) receptor binding region in most viruses from both mink and wildlife contained G at position 530 and Y at position 549; however, three mink viruses had an Y549H substitution. The outbreak viruses clustered phylogenetically in the European lineage and were highly identical to wildlife viruses from Germany and Hungary (99.29% - 99.62%). The study furthermore revealed that fleas (Ceratophyllus sciurorum) contained CDV and that vertical transmission of CDV occurred in a wild ferret. The study provides evidence that wildlife species, such as foxes, play an important role in the transmission of CDV to farmed mink and that the virus may be maintained in the wild animal reservoir between outbreaks.

Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

An x-ray streak camera platform has been characterized and implemented for use at the National Ignition Facility. The camera has been modified to meet the experiment requirements of the National Ignition Campaign and to perform reliably in conditions that produce high electromagnetic interference. A train of temporal ultra-violet timing markers has been added to the diagnostic in order to calibrate the temporal axis of the instrument and the detector efficiency of the streak camera was improved by using a CsI photocathode. The performance of the streak camera has been characterized and is summarized in this paper. The detector efficiency and cathode measurements are also presented.

Objective: Most sudden cardiac deaths are due to cardiac arrhythmias, and abnormalities in the autonomic nervous system could underlie them. There is growing evidence that coronary heart disease is associated with alterations of fetal development as a result of variations in the processes of placentation that control fetal nutrition. We hypothesized that placental size would be associated with sudden cardiac death., Methods: We examined sudden cardiac death within the Helsinki Birth Cohort of 13 345 men and women., Results: One hundred eighty-seven (2.7%) men and 47 (0.7%) women had sudden unexplained cardiac death outside hospital. Sudden death was associated with a thin placenta, the hazard ratio being 1.47 [95% confidence interval (CI) 1.11-1.93, P = 0.006] for each g/cm(2) decrease in thickness. Sudden death was independently associated with poor educational attainment (P < 0.0001). Both of these associations were independent of socio-economic status in later life., Conclusion: Sudden death may be initiated by impaired development of the autonomic nervous system in utero as a result of shallow invasion of the spiral arteries in the maternal endometrium and consequent fetal malnutrition.

The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology.

The 39-day long eruption at the summit of Eyjafjallajökull volcano in April-May 2010 was of modest size but ash was widely dispersed. By combining data from ground surveys and remote sensing we show that the erupted material was 4.8±1.2·10¹¹ kg (benmoreite and trachyte, dense rock equivalent volume 0.18±0.05 km³). About 20% was lava and water-transported tephra, 80% was airborne tephra (bulk volume 0.27 km³) transported by 3-10 km high plumes. The airborne tephra was mostly fine ash (diameter <1000 µm). At least 7·10¹⁰ kg (70 Tg) was very fine ash (<28 µm), several times more than previously estimated via satellite retrievals. About 50% of the tephra fell in Iceland with the remainder carried towards south and east, detected over ~7 million km² in Europe and the North Atlantic. Of order 10¹⁰ kg (2%) are considered to have been transported longer than 600-700 km with <10⁸ kg (<0.02%) reaching mainland Europe.