Search

Primordial Black Holes (PBHs) are gravitationally collapsed objects that may have been created by density fluctuations in the early universe and could have arbitrarily small masses down to the Planck scale. Hawking showed that due to quantum effects, a black hole has a temperature inversely proportional to its mass and will emit all species of fundamental particles thermally. PBHs with initial masses of ∼5.0 × 1014 g should be expiring in the present epoch with bursts of high-energy particles, including gamma radiation in the GeV-TeV energy range. The Milagro high energy observatory, which operated from 2000 to 2008, is sensitive to the high end of the PBH evaporation gamma-ray spectrum. Due to its large field-of-view, more than 90% duty cycle and sensitivity up to 100 TeV gamma rays, the Milagro observatory is well suited to perform a search for PBH bursts. Based on a search on the Milagro data, we report new PBH burst rate density upper limits over a range of PBH observation times. In addition, we report the sensitivity of the Milagro successor, the High Altitude Water Cherenkov (HAWC) observatory, to PBH evaporation events.

This paper reports the results from three targeted searches of Milagro TeV sky maps: two extragalactic point source lists and one pulsar source list. The first extragalactic candidate list consists of 709 candidates selected from the Fermi-LAT 2FGL catalog. The second extragalactic candidate list contains 31 candidates selected from the TeVCat source catalog that have been detected by imaging atmospheric Cherenkov telescopes (IACTs). In both extragalactic candidate lists Mkn 421 was the only source detected by Milagro. This paper presents the Milagro TeV flux for Mkn 421 and flux limits for the brighter Fermi-LAT extragalactic sources and for all TeVCat candidates. The pulsar list extends a previously published Milagro targeted search for Galactic sources. With the 32 new gamma-ray pulsars identified in 2FGL, the number of pulsars that are studied by both Fermi-LAT and Milagro is increased to 52. In this sample, we find that the probability of Milagro detecting a TeV emission coincident with a pulsar increases with the GeV flux observed by the Fermi-LAT in the energy range from 0.1 GeV to 100 GeV. © 2014 Elsevier B.V. All rights reserved.

TeV-flaring activity with timescales as short as tens of minutes and an orphan TeV flare have been observed from the blazar Markarian 421 (Mrk 421). The TeV emission from Mrk 421 is believed to be produced by leptonic synchrotron self-Compton (SSC) emission. In this scenario, correlations between the X-ray and the TeV fluxes are expected, TeV orphan flares are hardly explained, and the activity (measured as duty cycle) of the source at TeV energies is expected to be equal to or less than that observed in X-rays if only SSC is considered. To estimate the TeV duty cycle of Mrk 421 and to establish limits on its variability at different timescales, we continuously observed Mrk 421 with the Milagro observatory. Mrk 421 was detected by Milagro with a statistical significance of 7.1 standard deviations between 2005 September 21 and 2008 March 15. The observed spectrum is consistent with previous observations by VERITAS. We estimate the duty cycle of Mrk 421 for energies above 1 TeV for different hypotheses of the baseline flux and for different flare selections and we compared our results with the X-ray duty cycle estimated by Resconi et al. The robustness of the results is discussed. © 2014. The American Astronomical Society. All rights reserved..

Milagrito, a detector sensitive to gamma-rays at TeV energies, monitored thenorthern sky during the period February 1997 through May 1998. With a largefield of view and high duty cycle, this instrument was used to perform a searchfor TeV counterparts to gamma-ray bursts. Within the Milagrito field of view 54gamma-ray bursts at keV energies were observed by the Burst And TransientSatellite Experiment (BATSE) aboard the Compton Gamma-Ray Observatory. Thispaper describes the results of a preliminary analysis to search for TeVemission correlated with BATSE detected bursts. Milagrito detected an excess ofevents coincident both spatially and temporally with GRB 970417a, with chanceprobability $2.8 \times 10^{-5}$ within the BATSE error radius. No othersignificant correlations were detected. Since 54 bursts were examined thechance probability of observing an excess with this significance in any ofthese bursts is $1.5 \times 10^{-3}$. The statistical aspects and physicalimplications of this result are discussed.

Milagrito, a detector sensitive to gamma-rays at TeV energies, monitored thenorthern sky during the period February 1997 through May 1998. With a largefield of view and high duty cycle, this instrument was used to perform a searchfor TeV counterparts to gamma-ray bursts. Within the Milagrito field of view 54gamma-ray bursts at keV energies were observed by the Burst And TransientSatellite Experiment (BATSE) aboard the Compton Gamma-Ray Observatory. Thispaper describes the results of a preliminary analysis to search for TeVemission correlated with BATSE detected bursts. Milagrito detected an excess ofevents coincident both spatially and temporally with GRB 970417a, with chanceprobability $2.8 \times 10^{-5}$ within the BATSE error radius. No othersignificant correlations were detected. Since 54 bursts were examined thechance probability of observing an excess with this significance in any ofthese bursts is $1.5 \times 10^{-3}$. The statistical aspects and physicalimplications of this result are discussed.

Previous works have shown that water Cherenkov detectors have superiorsensitivity to those of scintillation counters as applied to detectingextensive air showers (EAS). This is in large part due to their much highersensitivity to EAS photons which are more than five times more numerous thanEAS electrons. Large area water Cherenkov detectors can be constructedrelatively cheaply and operated reliably. A sparse detector array has beendesigned which uses these types of detectors to substantially increase the areaover which the Milagro Gamma Ray Observatory collects EAS information.Improvements to the Milagro detector's performance characteristics andsensitivity derived from this array and preliminary results from a prototypearray currently installed near the Milagro detector will be presented.

The Milagro detector is an air shower array which uses the water Cherenkovtechnique and is capable of continuously monitoring the sky at energies near 1TeV. The detector consists of 20000 metric tons of pure water instrumented with723 photo-multiplier tubes (PMTs). The PMTs are arranged in a two-layerstructure on a lattice of 3 m spacing covering 5000 $m^2$ area. The directionof the shower is determined from the relative timing of the PMT signals,necessitating a common time reference and amplitude slewing corrections toimprove the time resolution. The calibration system to provide these consistsof a pulsed laser driving 30 diffusing light sources deployed in the pond toallow cross-calibration of the PMTs. The system is capable of calibrating timesand the pulse-heights from the PMTs using the time-over-threshold technique.The absolute energy scale is provided using single muons passing through thedetector. The description of the calibration system of the Milagro detector andits prototype Milagrito will be presented.

The Milagro Gamma Ray Observatory is the world's first large-area waterCherenkov detector capable of continuously monitoring the sky at TeV energies.Located in northern New Mexico, Milagro will perform an all sky survey of theNorthern Hemisphere at energies between ~250 GeV and 50 TeV. With a high dutycycle, large detector area (~5000 square meters), and a wide field-of-view (~1sr), Milagro is uniquely capable of searching for transient and DC sources ofhigh-energy gamma-ray emission. Milagro has been operating since February,1999. The current status of the Milagro Observatory and initial results will bediscussed.

Milagrito, a prototype for the Milagro detector, operated for 15 months in1997-8 and collected 8.9 billion events. It was the first extensive air shower(EAS) array sensitive to showers intiated by primaries with energy below 1 TeV.The shadows of the sun and moon observed with cosmic rays can be used to studysystematic pointing shifts and measure the angular resolution of EAS arrays.Below a few TeV, the paths of cosmic rays coming toward the earth are bent bythe helio- and geo-magnetic fields. This is expected to distort and displacethe shadows of the sun and the moon. The moon shadow, offset from the nominal(undeflected) position, has been observed with high statistical significance inMilagrito. This can be used to establish energy calibrations, as well as tosearch for the anti-matter content of the VHE cosmic ray flux. The shadow ofthe sun has also been observed with high significance.

The Milagrito water Cherenkov telescope operated for over a year. The mostprobable gamma-ray energy was ~1 TeV and the trigger rate was as high as 400Hz. We have developed an efficient technique for searching the entire sky forshort duration bursts of TeV photons. Such bursts may result from "traditional"gamma-ray bursts that were not in the field-of-view of any other instruments,the evaporation of primordial black holes, or some as yet undiscoveredphenomenon. We have begun to search the Milagrito data set for bursts ofduration 10 seconds. Here we will present the technique and the expectedresults. Final results will be presented at the conference.

Solar Energetic Particles from the 6 November 1997 solar flare/CME(coronalmass ejection) with energies exceeding 10 GeV have been detected by Milagrito,a prototype of the Milagro Gamma Ray Observatory. While particle accelerationbeyond 1 GeV at the Sun is well established, few data exist for protons or ionsbeyond 10 GeV. The Milagro observatory, a ground based water Cherenkov detectordesigned for observing very high energy gamma ray sources, can also be used tostudy the Sun. Milagrito, which operated for approximately one year in 1997/98,was sensitive to solar proton and neutron fluxes above ~5- 10 GeV. Milagritooperated in a scaler mode, which was primarily sensitive to muons, low energyphotons, and electrons, and the detector operated in a mode sensitive toshowers and high zenith angle muons. In its scaler mode, Milagrito registered arate increase coincident with the 6 November 1997 ground level event observedby Climax and other neutron monitors. A preliminary analysis suggests thepresence of >10 GeV particles.

The Milagro water Cherenkov detector near Los Alamos, New Mexico, has beenoperated as a sky monitor at energies of a few TeV between February 1997 andApril 1998. Serving as a test run for the full Milagro detector, Milagrito hastaken data during the strong and long-lasting 1997 flare of Mrk 501. We presentresults from the analysis of Mrk 501 and compare the excess and backgroundrates with expectations from the detector simulations.

Observing gamma ray bursts (GRBs) in the TeV energy range can be extremelyvaluable in providing insight to GRB radiation mechanisms and in constrainingsource distances. The Milagrito detector was an air shower array which used thewater Cherenkov technique to search for TeV sources. Data from this detectorwas analyzed to look for a TeV component of GRBs coincident with low energy-rays detected by the BATSE instrument on the Compton Gamma Ray Observatory. Asample of 54 BATSE GRBs which were in the field of view of the Milagritodetector during its lifetime (February 1997 to May 1998) was used.

The Milagrito water Cherenkov detector in the Jemez Mountains near LosAlamos, New Mexico took data from February 1997 to April 1998. Milagrito servedas a prototype for the larger Milagro detector, which has just begunoperations. Milagrito was the first large-aperture gamma-ray detector withsensitivity to gamma rays below 1 TeV. We report here on a search for steadyemission from point sources over most of the northern sky using data fromMilagrito.

Background: Achieving competence in clinical skills requires various resources and preparation time for undergraduate nursing students. Intentional opportunities should be created for student nurses to experience meaningful encounters in the clinical skills laboratory (CSL) to broaden their knowledge and competence. Therefore, factors that influence the competence in clinical learning in a CSL were explored., Aim: This study aimed to explore and describe the perceptions of nursing students regarding factors influencing their learning in a CSL., Setting: The study was conducted at a School of Nursing at a university in the Western Cape province., Methods: A qualitative descriptive design was adopted. Purposive sampling was used to select participants for this study based on specific inclusion and exclusion criteria. Following the attainment of ethical clearance, 10 focus group interviews were undertaken to explore the perceptions of nursing students regarding factors influencing their learning in a CSL. The focus group sessions continued until data saturation was established. Data were analysed using a thematic analysis process., Results: Three major themes emerged from the data analysis that was explored to make the following recommendations: physical environment, psychosocial environment and organisational environment., Conclusion: The results of this study highlighted the necessity for implementing interventions to enhance specific elements within the CSL, aiming to foster high-quality clinical learning experiences for nursing students., Contribution: Areas were identified within the CSL environment that requires enhancement to ensure the provision of quality clinical learning, thereby enabling student nurses to attain clinical competence., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

The FRESHAIR4Life study aims to reduce the non-communicable disease (NCD) burden by implementing preventive interventions targeting adolescents' exposure to tobacco use and air pollution (AP) worldwide. This paper presents the FRESHAIR4Life methodology and initial rapid review results. The rapid review, using various databases and PubMed, aimed to guide decision-making on risk factor focus, target areas, and populations. It showed variable NCD mortality rates related to tobacco use and AP across the participating countries, with tobacco as the main risk factor in the Kyrgyz Republic, Greece, and Romania, and AP prevailing in Pakistan and Uganda. Adolescent exposure levels, sources, and correlates varied. The study will continue with an in-depth situational analysis to guide the selection, adaptation, and integration of evidence-based interventions into the FRESHAIR4Life prevention package. This package will be implemented, evaluated, assessed for cost-effectiveness, and iteratively refined. The research places a strong emphasis on co-creation, capacity building, and comprehensive communication and dissemination., (© 2024. The Author(s).)

Increasingly, dry conifer forest restoration has focused on reestablishing horizontal and vertical complexity and ecological functions associated with frequent, low-intensity fires that characterize these systems. However, most forest inventory approaches lack the resolution, extent, or spatial explicitness for describing tree-level spatial aggregation and openings that were characteristic of historical forests. Uncrewed aerial system (UAS) structure from motion (SfM) remote sensing has potential for creating spatially explicit forest inventory data. This study evaluates the accuracy of SfM-estimated tree, clump, and stand structural attributes across 11 ponderosa pine-dominated stands treated with four different silvicultural prescriptions. Specifically, UAS-estimated tree height and diameter-at-breast-height (DBH) and stand-level canopy cover, density, and metrics of individual trees, tree clumps, and canopy openings were compared to forest survey data. Overall, tree detection success was high in all stands (F-scores of 0.64 to 0.89), with average F-scores > 0.81 for all size classes except understory trees (< 5.0 m tall). We observed average height and DBH errors of 0.34 m and - 0.04 cm, respectively. The UAS stand density was overestimated by 53 trees ha -1 (27.9%) on average, with most errors associated with understory trees. Focusing on trees > 5.0 m tall, reduced error to an underestimation of 10 trees ha -1 (5.7%). Mean absolute errors of bole basal area, bole quadratic mean diameter, and canopy cover were 11.4%, 16.6%, and 13.8%, respectively. While no differences were found between stem-mapped and UAS-derived metrics of individual trees, clumps of trees, canopy openings, and inter-clump tree characteristics, the UAS method overestimated crown area in two of the five comparisons. Results indicate that in ponderosa pine forests, UAS can reliably describe large- and small-grained forest structures to effectively inform spatially explicit management objectives., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Persons living with dementia (PLWD) may experience communication difficulties that impact their ability to process written and pictorial information. Patient-facing education may help promote discontinuation of potentially inappropriate medications for older adults without dementia, but it is unclear how to adapt this approach for PLWD. Our objective was to solicit feedback from PLWD and their care partners to gain insights into the design of PLWD-facing deprescribing intervention materials and PLWD-facing education material more broadly., Methods: We conducted 3 successive focus groups with PLWD aged ≥ 50 (n = 12) and their care partners (n = 10) between December 2022 and February 2023. Focus groups were recorded and transcripts were analyzed for overarching themes., Results: We identified 5 key themes: [1] Use images and language consistent with how PLWD perceive themselves; [2] Avoid content that might heighten fear or anxiety; [3] Use straightforward delivery with simple language and images; [4] Direct recipients to additional information; make the next step easy; and [5] Deliver material directly to the PLWD., Conclusion: PLWD-facing educational material should be addressed directly to PLWD, using plain, non-threatening and accessible language with clean, straightforward formatting., (© 2024. The Author(s).)

Blood products are likely to be critical components of the medical response to nuclear detonation, as the hematopoietic subsyndrome of acute radiation syndrome (H-ARS) includes depletion of platelets and red blood cells that can lead to lethal hemorrhage and anemia. There is, however, only limited clinical information on the use of blood products to treat H-ARS. As currently configured, the US blood supply cannot meet the predicted surge in blood product demand that is likely to occur short-term and possibly long-term in the event of a large nuclear detonation. As part of the Administration for Strategic Preparedness and Response within the US Department of Health and Human Services, the Biomedical Advanced Research and Development Authority (BARDA) is addressing this preparedness gap by supporting the development of novel blood products and devices with characteristics that improve blood product storage and use in austere operational environments. The US Food and Drug Administration's Center for Drug Evaluation and Research (CDER) recently issued draft guidance on the development of drugs and biologics regulated by CDER to prevent or treat Acute Radiation Syndrome under the provisions of the "Animal Rule." The commentary provided here discusses the unique regulatory scheme for transfusion components and blood products regulated as biological drugs by Center for Biologics Evaluation and Research, including the ambiguity surrounding the evidentiary requirements for their approval for H-ARS, and whether, under certain circumstances, a specific H-ARS indication is necessary if relevant commercial indications are approved., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Purpose: To summarize presentations and discussions from the 2022 trans-agency workshop titled "Overlapping science in radiation and sulfur mustard (SM) exposures of skin and lung: Consideration of models, mechanisms, organ systems, and medical countermeasures.", Methods: Summary on topics includes: (1) an overview of the radiation and chemical countermeasure development programs and missions; (2) regulatory and industry perspectives for drugs and devices; 3) pathophysiology of skin and lung following radiation or SM exposure; 4) mechanisms of action/targets, biomarkers of injury; and 5) animal models that simulate anticipated clinical responses., Results: There are striking similarities between injuries caused by radiation and SM exposures. Primary outcomes from both types of exposure include acute injuries, while late complications comprise chronic inflammation, oxidative stress, and vascular dysfunction, which can culminate in fibrosis in both skin and lung organ systems. This workshop brought together academic and industrial researchers, medical practitioners, US Government program officials, and regulators to discuss lung-, and skin- specific animal models and biomarkers, novel pathways of injury and recovery, and paths to licensure for products to address radiation or SM injuries., Conclusions: Regular communications between the radiological and chemical injury research communities can enhance the state-of-the-science, provide a unique perspective on novel therapeutic strategies, and improve overall US Government emergency preparedness.

BackgroundContact tracing has been a key component of COVID-19 outbreak control. Backward contact tracing (BCT) aims to trace the source that infected the index case and, thereafter, the cases infected by the source. Modelling studies have suggested BCT will substantially reduce SARS-CoV-2 transmission in addition to forward contact tracing.AimTo assess the feasibility and impact of adding BCT in practice.MethodsWe identified COVID-19 cases who were already registered in the electronic database between 19 February and 10 March 2021 for routine contact tracing at the Public Health Service (PHS) of Rotterdam-Rijnmond, the Netherlands (pop. 1.3 million). We investigated if, through a structured questionnaire by dedicated contact tracers, we could trace additional sources and cases infected by these sources. Potential sources identified by the index were approached to trace the source's contacts. We evaluated the number of source contacts that could be additionally quarantined.ResultsOf 7,448 COVID-19 cases interviewed in the study period, 47% (n = 3,497) indicated a source that was already registered as a case in the PHS electronic database. A potential, not yet registered source was traced in 13% (n = 979). Backward contact tracing was possible in 62 of 979 cases, from whom an additional 133 potential sources were traced, and four were eligible for tracing of source contacts. Two additional contacts traced had to stay in quarantine for 1 day. No new COVID-19 cases were confirmed.ConclusionsThe addition of manual BCT to control the COVID-19 pandemic did not provide added value in our study setting.

The hematopoietic system is highly sensitive to ionizing radiation. Damage to the immune system may result in opportunistic infections and hemorrhage, which could lead to mortality. Inflammation triggered by tissue damage can also lead to additional local or widespread tissue damage. The immune system is responsible for tissue repair and restoration, which is made more challenging when it is in the process of self-recovery. Because of these challenges, the Radiation and Nuclear Countermeasures Program (RNCP) and the Basic Immunology Branch (BIB) under the Division of Allergy, Immunology, and Transplantation (DAIT) within the National Institute of Allergy and Infectious Diseases (NIAID), along with partners from the Biomedical Advanced Research and Development Authority (BARDA), and the Radiation Injury Treatment Network (RITN) sponsored a two-day meeting titled Immune Dysfunction from Radiation Exposure held on September 9-10, 2020. The intent was to discuss the manifestations and mechanisms of radiation-induced immune dysfunction in people and animals, identify knowledge gaps, and discuss possible treatments to restore immune function and enhance tissue repair after irradiation.

Wildfires are a global crisis, but current fire models fail to capture vegetation response to changing climate. With drought and elevated temperature increasing the importance of vegetation dynamics to fire behavior, and the advent of next generation models capable of capturing increasingly complex physical processes, we provide a renewed focus on representation of woody vegetation in fire models. Currently, the most advanced representations of fire behavior and biophysical fire effects are found in distinct classes of fine-scale models and do not capture variation in live fuel (i.e. living plant) properties. We demonstrate that plant water and carbon dynamics, which influence combustion and heat transfer into the plant and often dictate plant survival, provide the mechanistic linkage between fire behavior and effects. Our conceptual framework linking remotely sensed estimates of plant water and carbon to fine-scale models of fire behavior and effects could be a critical first step toward improving the fidelity of the coarse scale models that are now relied upon for global fire forecasting. This process-based approach will be essential to capturing the influence of physiological responses to drought and warming on live fuel conditions, strengthening the science needed to guide fire managers in an uncertain future., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Microbially-induced corrosion is the acceleration of corrosion induced by bacterial biofilms. The bacteria in the biofilms oxidize metals on the surface, especially evident with iron, to drive metabolic activity and reduce inorganic species such as nitrates and sulfates. Coatings that prevent the formation of these corrosion-inducing biofilms significantly increase the service life of submerged materials and significantly decrease maintenance costs. One species in particular, a member of the Roseobacter clade, Sulfitobacter sp., has demonstrated iron-dependent biofilm formation in marine environments. We have found that compounds that contain the galloyl moiety can prevent Sulfitobacter sp. biofilm formation by sequestering iron, thus making a surface unappealing for bacteria. Herein, we have fabricated surfaces with exposed galloyl groups to test the effectiveness of nutrient reduction in iron-rich media as a non-toxic method to reduce biofilm formation.

Over the past several decades, the management of historically frequent-fire forests in the western United States has received significant attention due to the linked ecological and social risks posed by the increased occurrence of large, contiguous patches of high-severity fire. As a result, efforts are underway to simultaneously reduce potential fire and fuel hazards and restore characteristics indicative of historical forest structures and ecological processes that enhance the diversity and quality of wildlife habitat across landscapes. Despite widespread agreement on the need for action, there is a perceived tension among scientists concerning silvicultural treatments that modify stands to optimally reduce potential fire behavior (fuel hazard reduction) versus those that aim to emulate historical forest structures and create structurally complex stands (restoration). In this work, we evaluated thinning treatments in the Black Hills National Forest that exemplify the extremes of a treatment continuum that ranges from fuel hazard reduction to restoration. The goal of this work was to understand how the differing three-dimensional stand structures created by these treatment approaches altered potential fire behavior. Our results indicate that restoration treatments created higher levels of vertical and horizontal structural complexity than the fuel hazard reduction treatments but resulted in similar reductions to potential crown fire behavior. There were some trade-offs identified as the restoration treatments created larger openings, which generated faster mean rates of fire spread; however, these increased spread rates did not translate to higher levels of canopy consumption. Overall, our results suggest that treatments can create vertical and horizontal complexity desired for restoration and wildlife habitat management while reducing fire hazard and that they can be used in concert with traditional fuel hazard reduction treatments to reduce landscape scale fire risk. We also provide some suggestions to land managers seeking to design and implement prescriptions that emulate historical structures and enhance forest complexity., (© 2022 The Authors. Ecological Applications published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

2·6 billion people rely on solid fuels for cooking or heating. Accelerating access to cleaner solutions is crucial to reduce the negative effects of solid fuel use. Despite abundant evidence on how to implement these solutions, previous attempts have been disappointing. An overview of the evidence is missing and the translation of the evidence into practice is poor. We conducted an umbrella review using eight databases to: consolidate evidence on the factors that influence the implementation of improved solid fuel cookstoves and clean fuels in low-income and middle-income countries; weigh the level of confidence in existing evidence; and develop two practical implementation strategy tools. We identified 31 relevant reviews (13 systematic reviews and 18 narrative reviews) that covered over 479 primary studies. We found 15 implementation factors supported by the highest level of evidence. Regarding improved solid fuel cookstoves, these factors included: cost; knowledge and beliefs about the innovation; and compatibility. For clean fuels these factors included: cost; knowledge and beliefs about the innovation; and external policy and incentives. The factors were synthesised into the Cleaner Cookstove Implementation Tool and the Clean Fuel Implementation Tool. These tools can be used to optimise the implementation of cleaner cooking solutions, thereby improving health, environmental, climate, and gender equity outcomes., Competing Interests: Declaration of interests EABo is part-time employed at the Dutch Spark for Clean Cooking Solutions. Other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Macrolide resistance in Mycoplasma genitalium is emerging globally. There is paucity of data from sub-Saharan Africa where syndromic management is used to treat sexually transmitted infections (STIs). We conducted a molecular epidemiological study to determine the prevalence of azithromycin resistance and epidemic diversity of M. genitalium infections in South Africa., Methods: We analysed 90 M. genitalium -positive specimens that had been collected consecutively from men and women (50% symptomatic) from geographically diverse communities across the northern part of South Africa between 2015 and 2019. Melting curve analysis followed by targeted sequencing of the 23S rRNA gene was performed to detect azithromycin resistance. Molecular typing was done through single nucleotide polymorphism (SNP) analysis of the MG191 gene and short tandem repeats (STR) assessment of the MG309 gene. An overview of all published M. genitalium sequence types was generated and novel sequence types identified in this study were allocated numbers accordingly., Results: Azithromycin resistance was detected in 1/90 M. genitalium -positive specimens (1.1%; 95% CI 0% to 3.3%) as conferred by A2071G mutation; this strain also harboured a C234T mutation in the parC gene with wild type gyrA gene. SNP typing and STR assessment was successful in 38/90 specimens (42%) and showed a genetically diverse epidemic, without geographic clustering, with eight novel sequence types identified., Conclusion: This is the first study that determines resistance in M. genitalium infection since introduction of azithromycin in the syndromic management regimen for STIs in South Africa in 2015. Despite a well-established epidemic, azithromycin-resistant M. genitalium infection is still uncommon in the public healthcare sector. However, it has the potential to undermine the effectiveness of syndromic management. Introduction of molecular diagnostics and continuous surveillance are warranted for early detection emergence of resistance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Ionizing radiation can cause devastating injuries including hemorrhage, immune suppression, increased susceptibility to infection, and death. Medical countermeasures (MCMs) that address and mitigate radiation-induced injuries are the most important tools for countering the consequences of radiation exposure. Likewise, in matters of public health security, the development and advancement of radiological MCMs are fundamental for establishing an effective response to radiological and nuclear threats. United States Government agencies such as the Biomedical Advanced Research and Development Authority (BARDA), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Aeronautics and Space Administration (NASA) have dedicated significant efforts to advance the development of MCMs to treat radiation injury and facilitate their introduction into the public sphere. Due to the severe nature of radiation injuries, clinical trials are unethical. Therefore, nonclinical models that accurately replicate clinical manifestations of ionizing radiation injury observed in humans are essential to MCM advancement. The most frequently used nonclinical models of radiation injury are rodents and non-human primates (NHPs). These species reproduce many aspects of human disease caused by ionizing radiation and have been pivotal for the development and licensure of radiological MCMs. Despite these successes, model drawbacks have prompted the exploration and development of additional nonclinical models. Minipigs and rabbits show promise as acceptable models of radiation injury and demonstrate the potential to contribute significantly to MCM advancement. This collection of research showcases the capabilities of minipigs and rabbits in mirroring clinically relevant aspects of radiation-induced disease and documents the potential value these models may hold for radiological and nuclear MCM research. Together, these government-funded studies represent advances in radiological MCM development that can facilitate the emergence of cutting-edge technologies.

Tree spatial patterns in dry coniferous forests of the western United States, and analogous ecosystems globally, were historically aggregated, comprising a mixture of single trees and groups of trees. Modern forests, in contrast, are generally more homogeneous and overstocked than their historical counterparts. As these modern forests lack regular fire, pattern formation and maintenance is generally attributed to fire. Accordingly, fires in modern forests may not yield historically analogous patterns. However, direct observations on how selective tree mortality among pre-existing forest structure shapes tree spatial patterns is limited. In this study, we (a) simulated fires in historical and contemporary counterpart plots in a Sierra Nevadan mixed-conifer forest, (b) estimated tree mortality, and (c) examined tree spatial patterns of live trees before and after fire, and of fire-killed trees. Tree mortality in the historical period was clustered and density-dependent, because trees were aggregated and segregated by tree size before fire. Thus, fires maintained an aggregated distribution of tree groups. Tree mortality in the contemporary period was widespread, except for dispersed large trees, because most trees were a part of large, interconnected tree groups. Thus, postfire tree patterns were more uniform and devoid of moderately sized tree groups. Postfire tree patterns in the historical period, unlike the contemporary period, were within the historical range of variability identified for the western United States. This divergence suggests that decades of forest dynamics without significant disturbances have altered the historical means of pyric pattern formation. Our results suggest that ecological silvicultural treatments, such as forest restoration thinnings, which emulate qualities of historical forests may facilitate the reintroduction of fire as a means to reinforce forest structural heterogeneity., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Purpose: In the wake of a nuclear detonation, individuals with acute radiation syndrome will be a significant source of morbidity and mortality. Mathematical modeling can compare response strategies developed for real-world chaotic conditions after a nuclear blast in order to identify optimal strategies for administering effective treatment to these individuals. To maximize responders' abilities to save lives it is critical to understand how treatment efficacy is impacted by real-world conditions and levels of supportive care. To illustrate the importance of these factors, we developed a mathematical model of cytokine administration 24 h after the blast with varying levels of supportive care described in the primary literature. Conclusion: The results highlight the proportionally higher life-saving benefit of administering cytokines to individuals with a moderate to high dose of radiation exposure, compared to those with a lower dose. However, the fidelity of mathematical models is dependent on the primary data informing them. We describe the data needed to fully explore the impact of timing, dosage, and fractional benefit of cytokines and supportive care treatment in non-optimal situations that could be seen after a nuclear detonation. Studies addressing these types of knowledge gaps are essential to evaluating the relative efficacy of countermeasures to refine existing plans and help develop new strategies and priorities.

We report the development of a new class of "water-in-salt" electrolytes based on UV photopolymerized acrylic polymers. Incorporation of "water-in-bisalt" in a polymer matrix reduces water activity, expands the electrochemical stability window to 4.1 V, and dramatically improves cycle life in full cells with lithium titanate anodes compared to liquid water-based electrolytes.

Objectives: To determine the unmet need for care and barriers for consulting sexually transmitted infection (STI) services at six primary healthcare (PHC) facilities in rural South Africa., Methods: Cross-sectional study using three community-based strategies to mobilise adult individuals with STI-associated symptoms to access care. Participants were mobilised through clinic posters and referral by community healthcare workers (CHWs) and traditional leaders after training. Men with male urethritis syndrome and women with vaginal discharge syndrome were mobilised to visit participating PHC facilities on two designated days when an expert team visited the facility. Questionnaires were completed and HIV rapid tests offered. The minimal unmet need for care of individuals with STI-associated symptoms was calculated by dividing the number of cases over the adult catchment population of each PHC facility., Results: We successfully mobilised 177 symptomatic individuals: 134 (76%) women and 43 (24%) men. The estimated minimal unmet need for STI care was 1:364 (95% CI 1:350-1:380) individuals in this region; the rate was higher in village than township facilities, and among women. Mobilisation through clinic posters (57%) and by CHWs (23%) was most successful. Three-quarters of individuals (132/177) reported symptoms that had been present for >30 days; 49% (87/177) had symptoms >6 months. In addition, we identified 14 individuals with untreated HIV infection amounting to a 7% HIV testing yield. Lack of awareness of symptoms (34%), and disappointment in care due to persistent (23%) or recurrent (15%) symptoms after previous treatment, or disappointment with health services in general during previous visit(s) for any reason (10%) was the most common reasons for not consulting health care., Conclusions: We demonstrate a high unmet need for care of individuals with STI-associated symptoms in rural South Africa that requires urgent attention. A multidisciplinary approach that creates service demand through community awareness and information provision by healthcare workers combined with strengthening the quality of STI services is required to improve reproductive health and prevent complications of untreated STIs in this population., (© 2019 John Wiley & Sons Ltd.)

Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are two perfluoroalkyl substances that have been shown to result in several adverse health effects, including birth defects, kidney/testicular cancer, as well as liver and thyroid damage. The surfactant nature of PFOS and PFOA in water makes these compounds extremely difficult to remove from drinking water. In this paper, an efficient method to remove PFOS and PFOA from drinking water using linear fluorinated silane-functionalized aluminum oxide hydroxide (γ-AlOOH) nanowhiskers was developed. Filters functionalized with linear fluorinated silanes containing 13-17 fluorine atoms were able to remove >90% of the PFOS/PFOA at a very high flux of 1223 L/m 2 ·h. However, due to the hydrophobicity of these linear fluorinated silanes, high pressure drop was also noted across the membrane thickness during the filtration process. To reduce the back-pressure drop, linear fluorinated silanes with appended hydrophilic poly(ethylene glycol) units were synthesized, and it was further demonstrated that the new hydrophilic linear fluorinated silane dramatically reduced the pressure drop of the γ-AlOOH filter while maintaining 99.9% PFOS and PFOA reduction. Adsorption tests were performed to understand the removal mechanism., Competing Interests: The authors declare no competing financial interest.

The bone marrow microenvironment (BMME) contributes to the regulation of hematopoietic stem cell (HSC) function, though its role in age-associated lineage skewing is poorly understood. Here we show that dysfunction of aged marrow macrophages (Mφs) directs HSC platelet-bias. Mφs from the marrow of aged mice and humans exhibited an activated phenotype, with increased expression of inflammatory signals. Aged marrow Mφs also displayed decreased phagocytic function. Senescent neutrophils, typically cleared by marrow Mφs, were markedly increased in aged mice, consistent with functional defects in Mφ phagocytosis and efferocytosis. In aged mice, Interleukin 1B (IL1B) was elevated in the bone marrow and caspase 1 activity, which can process pro-IL1B, was increased in marrow Mφs and neutrophils. Mechanistically, IL1B signaling was necessary and sufficient to induce a platelet bias in HSCs. In young mice, depletion of phagocytic cell populations or loss of the efferocytic receptor Axl expanded platelet-biased HSCs. Our data support a model wherein increased inflammatory signals and decreased phagocytic function of aged marrow Mφs induce the acquisition of platelet bias in aged HSCs. This work highlights the instructive role of Mφs and IL1B in the age-associated lineage-skewing of HSCs, and reveals the therapeutic potential of their manipulation as antigeronic targets.

Background: The burden of sexually transmitted infections (STIs) in areas of sub-Saharan Africa with poor access to health care services is not well documented. In remote areas of South Africa, we investigated the prevalence of STIs and approaches to providing STI services through a mobile clinic., Methods: We recruited 251 adult women visiting a mobile clinic that normally provides general health education and screening services, but not STI care. Clinical and sexual history was obtained and vaginal specimens were tested for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium infection and for Candida albicans and bacterial vaginosis., Results: Laboratory test was positive for 133 (53%) of 251 women for at least 1 STI: C. trachomatis was observed in 52 (21%) women, N. gonorrhoeae in 39 (16%) women, T. vaginalis in 81 (32%) women and M. genitalium in 21 (8%) women. Eighty-one (32%) women met the criteria for vaginal discharge syndrome, of which 58% (47/81) would have been treated accurately. Among asymptomatic women 84 (49%) of 170 were diagnosed with an STI but untreated under the syndromic approach. We could not identify factors associated with asymptomatic STI infection., Conclusions: There is a high unmet need for STI care in rural South African settings with poor access to health care services. Provision of STI services in a mobile clinic using the syndromic management approach provides a useful approach, but would have to be enhanced by targeted diagnostics to successfully address the burden of infection.

Hematopoiesis in land dwelling vertebrates and marine mammals occurs within the bone marrow, continually providing mature progeny over the course of an organism's lifetime. This conserved dependency highlights the critical relationship between these two organs, yet the skeletal and hematopoietic systems are often thought of as separate. In fact, data are beginning to show that skeletal disease pathogenesis influences hematopoiesis and viceversa, offering novel opportunities to approach disease affecting bone and blood. With a growing global population of aged individuals, interest has focused on cell autonomous changes in hematopoietic and skeletal systems that result in dysfunction. The purpose of this review is to summarize the literature on aging effects in both fields, and provide critical examples of organ cross-talk in the aging process., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study from South Africa highlights the importance of rectal Trichomonas vaginalis infection as a sexually transmitted infection among men who have sex with men (MSM). We report seven MSM presenting with rectal T. vaginalis infection. Two men presented with symptoms of proctitis; 5/7 had urethral coinfection with T. vaginalis. Rectal T. vaginalis infection should be considered in MSM in areas where genital infection is endemic.

Essentials Perioperative thrombosis is a major cause of morbidity and mortality in congenital heart disease. Neonates and infants undergoing repair of congenital heart lesions were prospectively followed. Elevated von Willebrand factor (VWF) to ADAMTS-13 activity ratios typified the postoperative period. Thrombosis was associated with preoperative VWF activity and cryoprecipitate transfusion SUMMARY: Background The surgical repair of congenital heart malformations is frequently complicated by perioperative thrombosis of unclear etiology. An imbalance between von Willebrand factor (VWF) and ADAMTS-13 is an emerging variable in thrombosis. Objectives To describe perioperative changes to VWF, ADAMTS-13 and NETosis, and evaluate clinical and biochemical associations with postoperative thrombosis. Methods Neonates and infants undergoing palliation or definitive surgical repair of congenital heart malformations were recruited (n = 133). Preoperative and postoperative plasma levels of VWF, ADAMTS-13 and markers of NETosis were determined. Patients were followed for up to 30 days for the occurrence of thrombosis. Univariate and multivariate logistic regression analyses were conducted to identify variables associated with thrombosis. Results We identified significant postoperative increases in VWF activity, VWF level, DNA-histone complexes and cell-free DNA with an overall decrease in ADAMTS-13 activity. Patients experiencing postoperative thrombotic events (9%) were characterized by surgery performed at a lower intraoperative temperature, higher preoperative lactic acid levels, and higher preoperative VWF activity and level. A multivariate logistic regression model identified preoperative VWF activity (odds ratio (OR) 8.39 per IU mL -1 , 95% confidence interval [CI] 1.73-40.55) and transfusion of cryoprecipitate (OR 1.10 per mL kg -1 , 95% CI 1.03-1.17) as being associated with thrombosis. Conclusions Pediatric patients undergoing surgical repair of congenital heart malformations are exposed to high levels of VWF with diminished or minimal change to ADAMTS-13 in the immediate postoperative period. Elevated preoperative VWF activity is associated with postoperative thrombosis in pediatric congenital heart disease., (© 2017 International Society on Thrombosis and Haemostasis.)

Notch signaling is critical for osteoblastic differentiation; however, the specific contribution of individual Notch ligands is unknown. Parathyroid hormone (PTH) regulates the Notch ligand Jagged1 in osteoblastic cells. To determine if osteolineage Jagged1 contributes to bone homeostasis, selective deletion of Jagged1 in osteolineage cells was achieved through the presence of Prx1 promoter-driven Cre recombinase expression, targeting mesenchymal stem cells (MSCs) and their progeny (PJag1 mice). PJag1 mice were viable and fertile and did not exhibit any skeletal abnormalities at 2 weeks of age. At 2 months of age, however, PJag1 mice had increased trabecular bone mass compared to wild-type (WT) littermates. Dynamic histomorphometric analysis showed increased osteoblastic activity and increased mineral apposition rate. Immunohistochemical analysis showed increased numbers of osteocalcin-positive mature osteoblasts in PJag1 mice. Also increased phenotypically defined Lin - /CD45 - /CD31 - /Sca1 - /CD51 + osteoblastic cells were measured by flow cytometric analysis. Surprisingly, phenotypically defined Lin - /CD45 - /CD31 - /Sca1 + /CD51 + MSCs were unchanged in PJag1 mice as measured by flow cytometric analysis. However, functional osteoprogenitor (OP) cell frequency, measured by Von Kossa + colony formation, was decreased, suggesting that osteolineage Jagged1 contributes to maintenance of the OP pool. The trabecular bone increases were not due to osteoclastic defects, because PJag1 mice had increased bone resorption. Because PTH increases osteoblastic Jagged1, we sought to understand if osteolineage Jagged1 modulates PTH-mediated bone anabolism. Intermittent PTH treatment resulted in a significantly greater increase in BV/TV in PJag1 hind limbs compared to WT. These findings demonstrate a critical role of osteolineage Jagged1 in bone homeostasis, where Jagged1 maintains the transition of OP to maturing osteoblasts. This novel role of Jagged1 not only identifies a regulatory loop maintaining appropriate populations of osteolineage cells, but also provides a novel approach to increase trabecular bone mass, particularly in combination with PTH, through modulation of Jagged1. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

In vitro evidence suggests that the bone marrow microenvironment (BMME) is altered in myelodysplastic syndromes (MDSs). Here, we study the BMME in MDS in vivo using a transgenic murine model of MDS with hematopoietic expression of the translocation product NUP98-HOXD13 (NHD13). This model exhibits a prolonged period of cytopenias prior to transformation to leukemia and is therefore ideal to interrogate the role of the BMME in MDS. In this model, hematopoietic stem and progenitor cells (HSPCs) were decreased in NHD13 mice by flow cytometric analysis. The reduction in the total phenotypic HSPC pool in NHD13 mice was confirmed functionally with transplantation assays. Marrow microenvironmental cellular components of the NHD13 BMME were found to be abnormal, including increases in endothelial cells and in dysfunctional mesenchymal and osteoblastic populations, whereas megakaryocytes were decreased. Both CC chemokine ligand 3 and vascular endothelial growth factor, previously shown to be increased in human MDS, were increased in NHD13 mice. To assess whether the BMME contributes to disease progression in NHD13 mice, we performed transplantation of NHD13 marrow into NHD13 mice or their wild-type (WT) littermates. WT recipients as compared with NHD13 recipients of NHD13 marrow had a lower rate of the combined outcome of progression to leukemia and death. Moreover, hematopoietic function was superior in a WT BMME as compared with an NHD13 BMME. Our data therefore demonstrate a contributory role of the BMME to disease progression in MDS and support a therapeutic strategy whereby manipulation of the MDS microenvironment may improve hematopoietic function and overall survival., (© 2016 by The American Society of Hematology.)