Inherited cancer predisposing mutations in patients with therapy-related myeloid neoplasms.

Some patients with therapy-related myeloid neoplasms (t-MN) may have unsuspected inherited cancer predisposition syndrome (CPS). We propose a set of clinical criteria to identify t-MN patients with high risk of CPS (HR-CPS). Among 225 t-MN patients with an antecedent non-myeloid malignancy, our clinical criteria identified 52 (23%) HR-CPS patients. Germline whole-exome sequencing identified pathogenic or likely pathogenic variants in 10 of 27 HR-CPS patients compared to 0 of 9 low-risk CPS patients (37% vs. 0%, p = 0.04). These simple clinical criteria identify t-MN patients most likely to benefit from genetic testing for inherited CPS.

Retaining natural vegetation to safeguard biodiversity and humanity.

Global efforts to deliver internationally agreed goals to reduce carbon emissions, halt biodiversity loss, and retain essential ecosystem services have been poorly integrated. These goals rely in part on preserving natural (e.g., native, largely unmodified) and seminatural (e.g., low intensity or sustainable human use) forests, woodlands, and grasslands. To show how to unify these goals, we empirically derived spatially explicit, quantitative, area-based targets for the retention of natural and seminatural (e.g., native) terrestrial vegetation worldwide. We used a 250-m-resolution map of natural and seminatural vegetation cover and, from this, selected areas identified under different international agreements as being important for achieving global biodiversity, carbon, soil, and water targets. At least 67 million km2 of Earth's terrestrial vegetation (∼79% of the area of vegetation remaining) required retention to contribute to biodiversity, climate, soil, and freshwater conservation objectives under 4 United Nations' resolutions. This equates to retaining natural and seminatural vegetation across at least 50% of the total terrestrial (excluding Antarctica) surface of Earth. Retention efforts could contribute to multiple goals simultaneously, especially where natural and seminatural vegetation can be managed to achieve cobenefits for biodiversity, carbon storage, and ecosystem service provision. Such management can and should co-occur and be driven by people who live in and rely on places where natural and sustainably managed vegetation remains in situ and must be complemented by restoration and appropriate management of more human-modified environments if global goals are to be realized.

Retención de la vegetación natural para salvaguardar la biodiversidad y la humanidad Resumen Hoy en día hay muy poca integración de los esfuerzos mundiales para alcanzar los objetivos internacionales de reducción de las emisiones de carbono, impedimento de la pérdida de biodiversidad y conservación de los servicios ambientales esenciales. Estos objetivos dependen parcialmente de la conservación de los bosques, selvas y praderas naturales (por ejemplo, nativos y en su mayoría sin alteraciones) y seminaturales (por ejemplo, de uso humano sostenible o de baja intensidad). Obtuvimos de manera empírica objetivos espacialmente explícitos, cuantitativos y basados en áreas para la conservación de la vegetación terrestre natural y seminatural (por ejemplo, nativa) en todo el mundo para mostrar cómo unificar los objetivos internacionales. Usamos un mapa de 250 m de resolución de la cubierta vegetal natural y seminatural y, a partir de él, seleccionamos las áreas identificadas como importantes en diferentes acuerdos internacionales para alcanzar los objetivos globales de biodiversidad, carbono, suelo y agua. Al menos 67 millones de km2 de la vegetación terrestre de la Tierra (∼79% de la superficie de vegetación restante) requieren ser conservados para contribuir a los objetivos de conservación de la biodiversidad, el clima, el suelo y el agua dulce en virtud de cuatro de las resoluciones de las Naciones Unidas. Esto equivale a conservar la vegetación natural y seminatural en al menos el 50% de la superficie terrestre total de la Tierra (sin contar a la Antártida). Los esfuerzos de retención podrían contribuir a alcanzar múltiples objetivos simultáneamente, especialmente en donde la vegetación natural y seminatural puede gestionarse para lograr beneficios colaterales para la biodiversidad, el almacenamiento de carbono y la provisión de servicios ambientales. Esta gestión puede y debe ser impulsada y llevada a cabo por las personas que viven en y dependen de los lugares donde la vegetación natural y gestionada de forma sostenible permanece in situ y debe complementarse con la restauración y la gestión adecuada de entornos modificados por el hombre si se quieren alcanzar los objetivos globales.

Hotspots of human impact on threatened terrestrial vertebrates.

Conserving threatened species requires identifying where across their range they are being impacted by threats, yet this remains unresolved across most of Earth. Here, we present a global analysis of cumulative human impacts on threatened species by using a spatial framework that jointly considers the co-occurrence of eight threatening processes and the distribution of 5,457 terrestrial vertebrates. We show that impacts to species are widespread, occurring across 84% of Earth's surface, and identify hotspots of impacted species richness and coolspots of unimpacted species richness. Almost one-quarter of assessed species are impacted across >90% of their distribution, and approximately 7% are impacted across their entire range. These results foreshadow localised extirpations and potential extinctions without conservation action. The spatial framework developed here offers a tool for defining strategies to directly mitigate the threats driving species' declines, providing essential information for future national and global conservation agendas.

Correction: Hotspots of human impact on threatened terrestrial vertebrates.

[This corrects the article DOI: 10.1371/journal.pbio.3000158.].

Role of Secondary Organic Matter on Soot Particle Toxicity in Reconstituted Human Bronchial Epithelia Exposed at the Air-Liquid Interface.

Secondary organic matter (SOM) formed from gaseous precursors constitutes a major mass fraction of fine particulate matter. However, there is only limited evidence on its toxicological impact. In this study, air-liquid interface cultures of human bronchial epithelia were exposed to different series of fresh and aged soot particles generated by a miniCAST burner combined with a micro smog chamber (MSC). Soot cores with geometric mean mobility diameters of 30 and 90 nm were coated with increasing amounts of SOM, generated from the photo-oxidation of mesitylene and ozonolysis of α-pinene. At 24 h after exposure, the release of lactate dehydrogenase (LDH), indicating cell membrane damage, was measured and proteome analysis, i.e. the release of 102 cytokines and chemokines to assess the inflammatory response, was performed. The data indicate that the presence of the SOM coating and its bioavailability play an important role in cytotoxicity. In particular, LDH release increased with increasing SOM mass/total particle mass ratio, but only when SOM had condensed on the outer surface of the soot cores. Proteome analysis provided further evidence for substantial interference of coated particles with essential properties of the respiratory epithelium as a barrier as well as affecting cell remodeling and inflammatory activity.

A Four Carbon Organonitrate as a Significant Product of Secondary Isoprene Chemistry.

Oxidation of isoprene by nitrate radicals (NO3) or by hydroxyl radicals (OH) under high NOx conditions forms a substantial amount of organonitrates (ONs). ONs impact NOx concentrations and consequently ozone formation while also contributing to secondary organic aerosol. Here we show that the ONs with the chemical formula C4H7NO5 are a significant fraction of isoprene-derived ONs, based on chamber experiments and ambient measurements from different sites around the globe. From chamber experiments we found that C4H7NO5 isomers contribute 5%-17% of all measured ONs formed during nighttime and constitute more than 40% of the measured ONs after further daytime oxidation. In ambient measurements C4H7NO5 isomers usually dominate both nighttime and daytime, implying a long residence time compared to C5 ONs which are removed more rapidly. We propose potential nighttime sources and secondary formation pathways, and test them using a box model with an updated isoprene oxidation scheme.

Management and outcomes of esophageal perforation.

BACKGROUND: Esophageal perforation is a morbid condition and remains a therapeutic challenge. We report the outcomes of a large institutional experience with esophageal perforation and identify risk factors for morbidity and mortality. METHODS: A retrospective analysis was conducted on 142 patients who presented with a thoracic or gastroesophageal junction esophageal perforation from 1995 to 2020. Baseline characteristics, operative or interventional strategies, and outcomes were analyzed by etiology of the perforation and management approach. Multivariable cox and logistic regression models were constructed to identify predictors of mortality and morbidity. RESULTS: Overall, 109 (77%) patients underwent operative intervention, including 80 primary reinforced repairs and 21 esophagectomies and 33 (23%) underwent esophageal stenting. Stenting was more common in iatrogenic (27%) and malignant (64%) perforations. Patients who presented with a postemetic or iatrogenic perforation had similar 90-day mortality (16% and 16%) and composite morbidity (51% and 45%), whereas patients who presented with a malignant perforation had a 45% 90-day mortality and 45% composite morbidity. Risk factors for mortality included age >65 years (hazard ratio [HR] 1.89 [1.02-3.26], P = 0.044) and a malignant perforation (HR 4.80 [1.31-17.48], P = 0.017). Risk factors for composite morbidity included pleural contamination (odds ratio [OR] 2.06 [1.39-4.43], P = 0.046) and sepsis (OR 3.26 [1.44-7.36], P = 0.005). Of the 33 patients who underwent stent placement, 67% were successfully managed with stenting alone and 30% required stent repositioning. CONCLUSIONS: Risk factors for morbidity and mortality after esophageal perforation include advanced age, pleural contamination, septic physiology, and malignant perforation. Primary reinforced repair remains a reasonable strategy for patients with an esophageal perforation from a benign etiology.

Vertical profile of particle hygroscopicity and CCN effectiveness during winter in Beijing: insight into the hygroscopicity transition threshold of black carbon.

The hygroscopicity and ability of aerosol particles to act as cloud condensation nuclei (CCN) is important in determining their lifetime and role in aerosol-cloud interactions, thereby influencing cloud formation and climate. Previous studies have used the aerosol hygroscopic properties measured at the ground to evaluate the influence on cloud formation in the atmosphere, which may introduce uncertainty associated with aerosol hygroscopicity variability with altitude. In this study, the CCN behaviour and hygroscopic properties of daily filter collections of PM2.5 from three different heights (8, 120, 260 m) on a tower in Beijing were determined in the laboratory using water, water/methanol and methanol as the atomization solvents. Whilst there was substantial temporal variability in particle concentration and composition, there was little obvious difference in aerosol CCN and hygroscopic behaviour at different heights, although the planetary boundary layer height (PBLH) reduced to below the tower height during the nighttime, suggesting that use of surface hygroscopicity measurements is sufficient for the estimation of aerosol particle activation in clouds. Additionally, the critical coating thickness (in terms of mass ratio of coating/refractory BC, MRc) defining the BC transition between being hydrophobic to hydrophilic, was determined by combining hygroscopic tandem differential mobility analyser (H-TDMA), centrifugal particle mass analyzer (CPMA) and single particle soot photometer (SP2) measurements. The MRc of 250 nm BC-containing particles increased from a background value of between 0.8 and 1.6 to around 4.6 at the onset of the growth event of nanoparticles, decreasing monotonically back to the background level as the event progressed. This indicates that large particles do not act as an effective pre-existing condensation sink of the hygroscopic vapours during the nanoparticle growth events, leading to the 250 nm BC particles requiring more coating materials to transition between being hydrophobic and hydrophilic. These findings show that large particles may be less important in suppressing the new particle formation and subsequent growth in the atmosphere.

Using highly time-resolved online mass spectrometry to examine biogenic and anthropogenic contributions to organic aerosol in Beijing.

Organic aerosols, a major constituent of fine particulate mass in megacities, can be directly emitted or formed from secondary processing of biogenic and anthropogenic volatile organic compound emissions. The complexity of volatile organic compound emission sources, speciation and oxidation pathways leads to uncertainties in the key sources and chemistry leading to formation of organic aerosol in urban areas. Historically, online measurements of organic aerosol composition have been unable to resolve specific markers of volatile organic compound oxidation, while offline analysis of markers focus on a small proportion of organic aerosol and lack the time resolution to carry out detailed statistical analysis required to study the dynamic changes in aerosol sources and chemistry. Here we use data collected as part of the joint UK-China Air Pollution and Human Health (APHH-Beijing) collaboration during a field campaign in urban Beijing in the summer of 2017 alongside laboratory measurements of secondary organic aerosol from oxidation of key aromatic precursors (1,3,5-trimethyl benzene, 1,2,4-trimethyl benzene, propyl benzene, isopropyl benzene and 1-methyl naphthalene) to study the anthropogenic and biogenic contributions to organic aerosol. For the first time in Beijing, this study applies positive matrix factorisation to online measurements of organic aerosol composition from a time-of-flight iodide chemical ionisation mass spectrometer fitted with a filter inlet for gases and aerosols (FIGAERO-ToF-I-CIMS). This approach identifies the real-time variations in sources and oxidation processes influencing aerosol composition at a near-molecular level. We identify eight factors with distinct temporal variability, highlighting episodic differences in OA composition attributed to regional influences and in situ formation. These have average carbon numbers ranging from C5-C9 and can be associated with oxidation of anthropogenic aromatic hydrocarbons alongside biogenic emissions of isoprene, α-pinene and sesquiterpenes.

Renewable energy development threatens many globally important biodiversity areas.

Transitioning from fossil fuels to renewable energy is fundamental for halting anthropogenic climate change. However, renewable energy facilities can be land-use intensive and impact conservation areas, and little attention has been given to whether the aggregated effect of energy transitions poses a substantial threat to global biodiversity. Here, we assess the extent of current and likely future renewable energy infrastructure associated with onshore wind, hydropower and solar photovoltaic generation, within three important conservation areas: protected areas (PAs), Key Biodiversity Areas (KBAs) and Earth's remaining wilderness. We identified 2,206 fully operational renewable energy facilities within the boundaries of these conservation areas, with another 922 facilities under development. Combined, these facilities span and are degrading 886 PAs, 749 KBAs and 40 distinct wilderness areas. Two trends are particularly concerning. First, while the majority of historical overlap occurs in Western Europe, the renewable electricity facilities under development increasingly overlap with conservation areas in Southeast Asia, a globally important region for biodiversity. Second, this next wave of renewable energy infrastructure represents a ~30% increase in the number of PAs and KBAs impacted and could increase the number of compromised wilderness areas by ~60%. If the world continues to rapidly transition towards renewable energy these areas will face increasing pressure to allow infrastructure expansion. Coordinated planning of renewable energy expansion and biodiversity conservation is essential to avoid conflicts that compromise their respective objectives.

Characterizing the Particle Composition and Cloud Condensation Nuclei from Shipping Emission in Western Europe.

Commercial shipping is considered as an important source of air pollution and cloud condensation nuclei (CCN). To assess the climatic and environmental impacts of shipping, detailed characterization of ship plumes near the point of emission and understanding of ship plume evolution further downwind are essential. This airborne measurement study presents the online characterization of particulate phase ship emissions in the region of Western Europe in 2019 prior to new international sulfur emission controls becoming enacted. More than 30 ships from both the sulfur emission control area (SECA) in the English Channel and the open sea (OS) are measured and compared. Ships within the SECA emitted much less sulfate (SO4) compared with those at OS. When shifted to a lower apparent fuel sulfur content (FSC) at similar engine loads, the peak of the fresh ship emitting the particle number size distribution shifted from around 60-80 nm in diameter to below 40 nm in diameter. The emission factors (EFs) of sulfate are predicted to decrease by around 94% after the 2020 regulation on ship sulfur emission in the open ocean. The EFs of refractory black carbon (rBC) and organic compounds (Org) do not appear to be directly affected by the lower sulfur contents. The total number concentration for condensation nuclei (CN) >2.5 nm and >0.1 µm are predicated to be reduced by 69 and 56%, respectively. Measured plume evolution results indicate that the S(IV) to S(VI) conversion rate was around 23.4% per hour at the beginning of plume evolution, and the CCN and CN >2.5 nm ratio increased with plume age primarily due to condensation and coagulation. We estimate that the new sulfur emission regulation will lead to a reduction of more than 80% in CCN from fresh ship emissions. The ship-emitted EFs results presented here will also inform emission inventories, policymaking, climate, and human health studies.

Stepwise unfolding supports a subunit model for vertebrate kinetochores.

During cell division, interactions between microtubules and chromosomes are mediated by the kinetochore, a proteinaceous structure located at the primary constriction of chromosomes. In addition to the centromere histone centromere protein A (CENP-A), 15 other members of the constitutive centromere associated network (CCAN) participate in the formation of a chromatin-associated scaffold that supports kinetochore structure. We performed a targeted screen analyzing unfolded centrochromatin from CENP-depleted chromosomes. Our results revealed that CENP-C and CENP-S are critical for the stable folding of mitotic kinetochore chromatin. Multipeak fitting algorithms revealed the presence of an organized pattern of centrochromatin packing consistent with arrangement of CENP-A-containing nucleosomes into up to five chromatin "subunits"-each containing roughly 20-30 nucleosomes. These subunits could be either layers of a boustrophedon or small loops of centromeric chromatin.

Bilateral giant retinal tears in Osteogenesis Imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare primarily autosomal dominant condition in which the connective tissues of bones, ligaments and sclerae do not form properly. Typically, mutations in COL1A1 and COL1A2 genes lead to the defective formation or quantity of type I collagen, the principle matrix in these tissues. Molecular genetic studies have now elucidated multiple genetic subtypes of the disorder but little literature exists on the risk of retinal tears and detachments in OI. CASE PRESENTATION: We report the first case of a child with a rare recessive type of OI, subtype VIII, resulting from a P3H1 (also known as LEPRE1) gene mutation presenting with bilateral giant retinal tears and the surgical challenges encountered in performing retinal detachment repair due to scleral thinning. The P3H1 gene encodes for prolyl 3-hydroxylase 1 which is involved in the post-translational modification of not only collagen type I but also types II and V which when mutated may result in pathological posterior vitreous detachment (PVD) and giant retinal tear detachments. CONCLUSIONS: Genetic analyses are increasingly important in such cases and may guide patient monitoring and potential prophylactic treatment, known to significantly reduce the probability of giant retinal tear detachments in other high-risk collagenopathies such as Stickler Syndrome Type I.

Gaps and opportunities for the World Heritage Convention to contribute to global wilderness conservation.

Wilderness areas are ecologically intact landscapes predominantly free of human uses, especially industrial-scale activities that result in substantial biophysical disturbance. This definition does not exclude land and resource use by local communities who depend on such areas for subsistence and bio-cultural connections. Wilderness areas are important for biodiversity conservation and sustain key ecological processes and ecosystem services that underpin planetary life-support systems. Despite these widely recognized benefits and values of wilderness, they are insufficiently protected and are consequently being rapidly eroded. There are increasing calls for multilateral environmental agreements to make a greater and more systematic contribution to wilderness conservation before it is too late. We created a global map of remaining terrestrial wilderness following the established last-of-the-wild method, which identifies the 10% of areas with the lowest human pressure within each of Earth's 62 biogeographic realms and identifies the 10 largest contiguous areas and all contiguous areas >10,000 km2 . We used our map to assess wilderness coverage by the World Heritage Convention and to identify gaps in coverage. We then identified large nationally designated protected areas with good wilderness coverage within these gaps. One-quarter of natural and mixed (i.e., sites of both natural and cultural value) World Heritage Sites (WHS) contained wilderness (total of 545,307 km2 ), which is approximately 1.8% of the world's wilderness extent. Many WHS had excellent wilderness coverage, for example, the Okavango Delta in Botswana (11,914 km2 ) and the Central Suriname Nature Reserve (16,029 km2 ). However, 22 (35%) of the world's terrestrial biorealms had no wilderness representation within WHS. We identified 840 protected areas of >500 km2 that were predominantly wilderness (>50% of their area) and represented 18 of the 22 missing biorealms. These areas offer a starting point for assessing the potential for the designation of new WHSs that could help increase wilderness representation on the World Heritage list. We urge the World Heritage Convention to ensure that the ecological integrity and outstanding universal value of existing WHS with wilderness values are preserved.

Reach and messages of the world's largest ivory burn.

Recent increases in ivory poaching have depressed African elephant populations. Successful enforcement has led to ivory stockpiling. Stockpile destruction is becoming increasingly popular, and most destruction has occurred in the last 5 years. Ivory destruction is intended to send a strong message against ivory consumption, both in promoting a taboo on ivory use and catalyzing policy change. However, there has been no effort to establish the distribution and extent of media reporting on ivory destruction events globally. We analyzed media coverage of the largest ivory destruction event in history (Kenya, 30 April 2016) across 11 nation states connected to ivory trade. We used an online-media crawling tool to search online media outlets and subjected 5 of the largest print newspapers (by circulation) in 5 nations of interest to content analysis. Most online news on the ivory burn came from the United States (81% of 1944 articles), whereas most of the print news articles came from Kenya (61% of 157 articles). Eighty-six to 97% of all online articles reported the burn as a positive conservation action, whereas 4-50% discussed ivory burning as having a negative impact on elephant conservation. Most articles discussed law enforcement and trade bans as effective for elephant conservation. There was more relative search interest globally in the 2016 Kenyan ivory burn than any other burn in 5 years. Ours is the first attempt to track the reach of media coverage relative to an ivory burn and provides a case study in tracking the effects of a conservation-marketing event.

Light Absorption Enhancement of Black Carbon Aerosol Constrained by Particle Morphology.

The radiative forcing of black carbon aerosol (BC) is one of the largest sources of uncertainty in climate change assessments. Contrasting results of BC absorption enhancement ( Eabs) after aging are estimated by field measurements and modeling studies, causing ambiguous parametrizations of BC solar absorption in climate models. Here we quantify Eabs using a theoretical model parametrized by the complex particle morphology of BC in different aging scales. We show that Eabs continuously increases with aging and stabilizes with a maximum of ∼3.5, suggesting that previous seemingly contrast results of Eabs can be explicitly described by BC aging with corresponding particle morphology. We also report that current climate models using Mie Core-Shell model may overestimate Eabs at a certain aging stage with a rapid rise of Eabs, which is commonly observed in the ambient. A correction coefficient for this overestimation is suggested to improve model predictions of BC climate impact.

Online Chemical Characterization of Food-Cooking Organic Aerosols: Implications for Source Apportionment.

Food-cooking organic aerosols (COA) are one of the primary sources of submicron particulate matter in urban environments. However, there are still many questions surrounding source apportionment related to instrumentation as well as semivolatile partitioning because COA evolve rapidly in the ambient air, making source apportionment more complex. Online measurements of emissions from cooking different types of food were performed in a laboratory to characterize particles and gases. Aerosol mass spectrometer (AMS) measurements showed that the relative ionization efficiency for OA was higher (1.56-3.06) relative to a typical value of 1.4, concluding that AMS is over-estimating COA and suggesting that previous studies likely over-estimated COA concentrations. Food-cooking mass spectra were generated using AMS, and gas and particle food markers were identified with filter inlets for gases and aerosols-chemical ionization mass spectrometer (CIMS) measurements to be used in future food cooking-source apportionment studies. However, there is a considerable variability in both gas and particle markers, and dilution plays an important role in the particle mass budget, showing the importance of using these markers with caution during receptor modeling. These findings can be used to better understand the chemical composition of COA, and they provides useful information to be used in future source-apportionment studies.

Mixing State of Carbonaceous Aerosols of Primary Emissions from "Improved" African Cookstoves.

Designs of "improved" stoves are introduced recently to benefit the solid fuel consumption of cooking activities in developing countries, but the uncertainties concerning the combustion processes and particulate emissions remain poorly characterized. To help understand this, combustion in three examples of "improved" African cookstoves was investigated in the laboratory. A typical European heating stove was included for comparison purpose. Detailed aerosol emissions were studied in real-time with an Aerosol Mass Spectrometer and Single Particle Soot Photometer, to explore interactions between black carbon (BC) and organic carbon aerosols, which were parametrized according to modified combustion efficiency (MCE), a common metric used within the atmospheric emission community. Greater than 50% of the total organic matter (OM) was found in BC-containing particles when MCE was >0.95 for dry oak and coal fuels, whereas at lower MCE, over 80% of the total OM for most of the fuels existed in particles without detectable BC. When the OM mass fraction of total particulate matter (PM1) > 0.9, the mass ratio of OM to refractory BC in BC-containing particles was about 2-3, but only ∼0.8 when OM mass fraction <0.9. These findings are not currently included in models and such information should be considered in the future emission scenarios.