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The fungal pathogen ) forms yeast cells of different sizes and morphological characteristics during infection. These features are usually not seen in standard laboratory conditions. Here, we describe cell morphologies when is grown in human plasma-like medium at 37°C, 5% CO . We observed mixed-size populations of cells less than 1 µm up to 16.8 µm in cell diameter, increased capsule size, high chitin, and DNA content in larger cells. Our findings show that serum is not required for human plasma-like medium (HPLM)-induced cellular heterogeneity. Thus, this new method offers an opportunity to investigate factors of that mediate pathogenesis or host-pathogen interactions in a physiologically relevant setting.IMPORTANCEWe provide a description of new culture condition using the human plasma-like medium that supports the formation of the full range of cell morphologies of .

A problemática da gestão ineficiente dos resíduos sólidos urbanos no Brasil conduziu à elaboração da Lei 12.305/2010, a qual acarretou na desativação de diversos empreendimentos que não conseguiram se adequar a nova legislação. O objetivo desse estudo foi diagnosticar a situação da Central de Triagem e Compostagem com Aterro Sanitário durante sua operação e após a sua desativação no município de Planalto, a fim de verificar sua adequação a legislação vigente e as razões que conduziram a sua desativação. Diante disso, foram realizadas coletas de dados junto à prefeitura e visitas ao empreendimento antes de sua desativação, onde avaliou-se a existência de cercas, sinalização, guarita/portaria, balança, acessos, iluminação e comunicação, instalações de apoio operacional, impermeabilização da base e laterais, drenagem, coleta seletiva e educação ambiental, espalhamento e compactação do resíduo, tratamento do lixiviado, proximidade da área com nascentes e águas superficiais, presença de animais e pessoas e monitoramento da área. Após a desativação da Central de Triagem e Compostagem com Aterro Sanitário, realizou-se novamente uma visita para verificação dos seguintes parâmetros: plano de recuperação, remoção dos resíduos, recuperação executada na área, coleta e tratamento do lixiviado e gás, monitoramento e manutenção da recuperação. Verificou-se a precariedade das instalações do local durante sua operação e após sua desativação, as causas da desativação do empreendimento e as técnicas de recuperação aplicadas, sendo que a mesma se apresenta de forma insuficiente e inadequada, visto que os resíduos depositados continuam poluindo por meio do chorume gerado na decomposição dos mesmos.

The fungal pathogen Cryptococcus neoformans (C. neoformans) forms yeast cells of different sizes and morphological characteristics during infection. These features are usually not seen in standard laboratory in vitro conditions. Here, we describe in vivo cell morphologies when C. neoformans is grown in human plasma-like medium at 37°C-5% CO2. We observed mixed-size populations of cells less than 1 μm up to 16.8 μm cell diameter, increased capsule size, high chitin and DNA content in larger cells. Our findings show serum is not required for HPLM-induced C. neoformans cellular heterogeneity. Thus, this new method offers an opportunity to investigate factors of C. neoformans that mediate pathogenesis or host-pathogen interactions in a physiologically relevant setting. Description of new in vitro culture condition using the human plasma-like medium that supports the formation of the full range of in vivo cell morphologies of C. neoformans.

The problem of the inefficient management of municipal solid waste in Brazil led to the elaboration of the Law 12,305/2010, which resulted in the deactivation of several projects that have failed to adapt to the new legislation. The aim of this study was to diagnose the situation of the Screening and Composting Central with landfill during its operation and after its deactivation in the municipality of Planalto, in order to verify its suitability to the current legislation and the reasons that led to its deactivation. Thus, data collection was carried out along with the city prefecture as well as visits to the project prior to its deactivation, where the existence of fences, signs, gatehouse/concierge, balance, access, lighting and communication, operational support facilities, bottom and lateral impermeabilization, drainage, selective waste collection and environmental education, spreading and compacting of the waste, treatment of leachate, proximity to the area with water sources and surface water, the presence of animals and people and area monitoring were evaluated. After the deactivation of the Screening and Composting Central with landfill, another visit was conducted in order to check the following parameters: recovery plan, waste removal, recovery performed in the area, collection and treatment of leachate and gas, monitoring and maintenance of the recovery. It could be verified precariousness of local facilities during its operation and after its deactivation, the causes of closure and the recovery techniques applied, appears to be insufficient and inadequately, since the deposited waste continues to pollute through the leachate generated in their decomposition. Keywords: Solid Waste; NPSW; Inadequate Disposal; Landfill. A problematica da gestao ineficiente dos residuos solidos urbanos no Brasil conduziu a elaboracao da Lei 12.305/2010, a qual acarretou na desativacao de diversos empreendimentos que nao conseguiram se adequar a nova legislacao. O objetivo desse estudo foi diagnosticar a situacao da Central de Triagem e Compostagem com Aterro Sanitario durante sua operacao e apos a sua desativacao no municipio de Planalto, a fim de verificar sua adequacao a legislacao vigente e as razoes que conduziram a sua desativacao. Diante disso, foram realizadas coletas de dados junto a prefeitura e visitas ao empreendimento antes de sua desativacao, onde avaliou-se a existencia de cercas, sinalizacao, guarita/portaria, balanca, acessos, iluminacao e comunicacao, instalacoes de apoio operacional, impermeabilizacao da base e laterais, drenagem, coleta seletiva e educacao ambiental, espalhamento e compactacao do residuo, tratamento do lixiviado, proximidade da area com nascentes e aguas superficiais, presenca de animais e pessoas e monitoramento da area. Apos a desativacao da Central de Triagem e Compostagem com Aterro Sanitario, realizou-se novamente uma visita para verificacao dos seguintes parametros: plano de recuperacao, remocao dos residuos, recuperacao executada na area, coleta e tratamento do lixiviado e gas, monitoramento e manutencao da recuperacao. Verificou-se a precariedade das instalacoes do local durante sua operacao e apos sua desativacao, as causas da desativacao do empreendimento e as tecnicas de recuperacao aplicadas, sendo que a mesma se apresenta de forma insuficiente e inadequada, visto que os residuos depositados continuam poluindo por meio do chorume gerado na decomposicao dos mesmos. Palavras-chave: Residuos Solidos; PNRS; Disposicao Inadequada; Aterro Sanitario. El problema de la gestion ineficiente de los residuos solidos urbanos en Brasil llevo a la elaboracion de la Ley 12.305/2010, la cual ha resuelto en la desactivacion de varios proyectos que no han logrado adaptarse a la nueva legislacion. El objetivo de este estudio fue diagnosticar la situacion de la central de clasificacion y compostaje con vertedero durante su operacion y despues de su desactivacion en el municipio de Planalto, con el fin de verificar su adecuacion a la legislacion vigente y las razones que llevaron a su desactivacion. Por lo tanto, se llevaron a cabo recolecciones de datos con el ayuntamiento municipal y visitas al proyecto antes de su desactivacion, donde se evaluo la existencia de vallas, senales, puerta de entrada/conserje, escala, el acceso, la iluminacion y la comunicacion, medios de apoyo operativo, impermeabilizacion de la base y lateral, el drenaje, la recogida selectiva y la educacion ambiental, el esparcimiento y compactacion de los residuos, el tratamiento de los lixiviados, la proximidad a la zona con manantiales y aguas superficiales, la presencia de animales y personas y el control de la zona. Despues de la desactivacion de la central de clasificacion y compostaje con vertedero, nuevamente se llevo a cabo una visita para comprobar los siguientes parametros: plan de recuperacion, eliminacion de residuos, la recuperacion se realiza en la zona, recogida y tratamiento de lixiviados y gases, monitoreo y mantenimiento de la recuperacion. Se verifico la precariedad de las instalaciones locales durante la operacion y despues de su desactivacion, las causas de la desactivacion del emprendimiento y las tecnicas de recuperacion aplicadas, siendo que la misma se presenta de manera insuficiente y inapropiada, visto que los residuos depositados siguen poluindo por medio del lixiviado generado en la descomposicion de los mismos. Palabras clave: Residuos Solidos; PNRS; Provision inadecuada; Vertedero.

The problem of the inefficient management of municipal solid waste in Brazil led to the elaboration of the Law 12,305/2010, which resulted in the deactivation of several projects that have failed to adapt to the new legislation. The aim of this study was to diagnose the situation of the Screening and Composting Central with landfill during its operation and after its deactivation in the municipality of Planalto, in order to verify its suitability to the current legislation and the reasons that led to its deactivation. Thus, data collection was carried out along with the city prefecture as well as visits to the project prior to its deactivation, where the existence of fences, signs, gatehouse/concierge, balance, access, lighting and communication, operational support facilities, bottom and lateral impermeabilization, drainage, selective waste collection and environmental education, spreading and compacting of the waste, treatment of leachate, proximity to the area with water sources and surface water, the presence of animals and people and area monitoring were evaluated. After the deactivation of the Screening and Composting Central with landfill, another visit was conducted in order to check the following parameters: recovery plan, waste removal, recovery performed in the area, collection and treatment of leachate and gas, monitoring and maintenance of the recovery. It could be verified precariousness of local facilities during its operation and after its deactivation, the causes of closure and the recovery techniques applied, appears to be insufficient and inadequately, since the deposited waste continues to pollute through the leachate generated in their decomposition.

Protein sequences preserved in two Quaternary taxa, Macrauchenia and Toxodon , resolve the evolutionary history of South American native ungulates. South American ungulates demystified When Charles Darwin first unearthed the remains of the South American native ungulates — herbivorous mammals that evolved in isolation on the South American continent for tens of millions of years — he declared them “the strangest animals ever discovered”. Their origins are obscured by rampant convergence of morphology, and work with ancient DNA has been similarly frustrating. Ian Barnes and colleagues have circumvented these problems by screening protein sequences preserved in two Quaternary taxa, Macrauchenia and Toxodon , to show that their closest relatives among other mammals are the Perissodactyls (odd-toed ungulates such as horses and rhinos) rather than among the Afrotheres (elephants, sirenians and allies). No large group of recently extinct placental mammals remains as evolutionarily cryptic as the approximately 280 genera grouped as ‘South American native ungulates’. To Charles Darwin 1 , 2 , who first collected their remains, they included perhaps the ‘strangest animal[s] ever discovered’. Today, much like 180 years ago, it is no clearer whether they had one origin or several, arose before or after the Cretaceous/Palaeogene transition 66.2 million years ago 3 , or are more likely to belong with the elephants and sirenians of superorder Afrotheria than with the euungulates (cattle, horses, and allies) of superorder Laurasiatheria 4 , 5 , 6 . Morphology-based analyses have proved unconvincing because convergences are pervasive among unrelated ungulate-like placentals. Approaches using ancient DNA have also been unsuccessful, probably because of rapid DNA degradation in semitropical and temperate deposits. Here we apply proteomic analysis to screen bone samples of the Late Quaternary South American native ungulate taxa Toxodon (Notoungulata) and Macrauchenia (Litopterna) for phylogenetically informative protein sequences. For each ungulate, we obtain approximately 90% direct sequence coverage of type I collagen α1- and α2-chains, representing approximately 900 of 1,140 amino-acid residues for each subunit. A phylogeny is estimated from an alignment of these fossil sequences with collagen (I) gene transcripts from available mammalian genomes or mass spectrometrically derived sequence data obtained for this study. The resulting consensus tree agrees well with recent higher-level mammalian phylogenies 7 , 8 , 9 . Toxodon and Macrauchenia form a monophyletic group whose sister taxon is not Afrotheria or any of its constituent clades as recently claimed 5 , 6 , but instead crown Perissodactyla (horses, tapirs, and rhinoceroses). These results are consistent with the origin of at least some South American native ungulates 4 , 6 from ‘condylarths’, a paraphyletic assembly of archaic placentals. With ongoing improvements in instrumentation and analytical procedures, proteomics may produce a revolution in systematics such as that achieved by genomics, but with the possibility of reaching much further back in time.

The extinct ‘New World stilt-legged’, or NWSL, equids constitute a perplexing group of Pleistocene horses endemic to North America. Their slender distal limb bones resemble those of Asiatic asses, such as the Persian onager. Previous palaeogenetic studies, however, have suggested a closer relationship to caballine horses than to Asiatic asses. Here, we report complete mitochondrial and partial nuclear genomes from NWSL equids from across their geographic range. Although multiple NWSL equid species have been named, our palaeogenomic and morphometric analyses support the idea that there was only a single species of middle to late Pleistocene NWSL equid, and demonstrate that it falls outside of crown group Equus. We therefore propose a new genus, Haringtonhippus, for the sole species H. francisci. Our combined genomic and phenomic approach to resolving the systematics of extinct megafauna will allow for an improved understanding of the full extent of the terminal Pleistocene extinction event. The horse family – which also includes zebras, donkeys and asses – is often featured on the pages of textbooks about evolution. All living horses belong to a group, or genus, called Equus. The fossil record shows how the ancestors of these animals evolved from dog-sized, three-toed browsers to larger, one-toed grazers. This process took around 55 million years, and many members of the horse family tree went extinct along the way. Nevertheless, the details of the horse family tree over the past 2.5 million years remain poorly understood. In North America, horses from this period – which is referred to as the Pleistocene – have been classed into two major groups: stout-legged horses and stilt-legged horses. Both groups became extinct near the end of the Pleistocene in North America, and it was not clear how they relate to one another. Based on their anatomy, many scientists suggested that stilt-legged horses were most closely related to modern-day asses living in Asia. Yet, other studies using ancient DNA placed the stilt-legged horses closer to the stout-legged horses. Heintzman et al. set out to resolve where the stilt-legged horses sit within the horse family tree by examining more ancient DNA than the previous studies. The analyses showed that the stilt-legged horses were much more distinct than previously thought. In fact, contrary to all previous findings, these animals actually belonged outside of the genus Equus. Heintzman et al. named the new genus for the stilt-legged horses Haringtonhippus, and showed that all stilt-legged horses belonged to a single species within this genus, Haringtonhippus francisci. Together these new findings provide a benchmark for reclassifying problematic fossil groups across the tree of life. A similar approach could be used to resolve the relationships in other problematic groups of Pleistocene animals, such as mammoths and bison. This would give scientists a more nuanced understanding of evolution and extinction during this period.

Background To identify the strategies and contextual factors that enable optimal engagement of patients in the design, delivery, and evaluation of health services. Methods We searched MEDLINE, EMBASE, CINAHL, Cochrane, Scopus, PsychINFO, Social Science Abstracts, EBSCO, and ISI Web of Science from 1990 to 2016 for empirical studies addressing the active participation of patients, caregivers, or families in the design, delivery and evaluation of health services to improve quality of care. Thematic analysis was used to identify (1) strategies and contextual factors that enable optimal engagement of patients, (2) outcomes of patient engagement, and (3) patients’ experiences of being engaged. Results Forty-eight studies were included. Strategies and contextual factors that enable patient engagement were thematically grouped and related to techniques to enhance design, recruitment, involvement and leadership action, and those aimed to creating a receptive context. Reported outcomes ranged from educational or tool development and informed policy or planning documents (discrete products) to enhanced care processes or service delivery and governance (care process or structural outcomes). The level of engagement appears to influence the outcomes of service redesign—discrete products largely derived from low-level engagement (consultative unidirectional feedback)—whereas care process or structural outcomes mainly derived from high-level engagement (co-design or partnership strategies). A minority of studies formally evaluated patients’ experiences of the engagement process ( n  = 12; 25%). While most experiences were positive—increased self-esteem, feeling empowered, or independent—some patients sought greater involvement and felt that their involvement was important but tokenistic, especially when their requests were denied or decisions had already been made. Conclusions Patient engagement can inform patient and provider education and policies, as well as enhance service delivery and governance. Additional evidence is needed to understand patients’ experiences of the engagement process and whether these outcomes translate into improved quality of care. Registration N/A (data extraction completed prior to registration on PROSPERO).

Immune checkpoint inhibitors (ICI) are increasingly used in cancer therapy. Elevated liver enzymes frequently occur in patients treated with ICI but evaluation is poorly described. We sought to better understand causes of liver enzyme elevation, investigation and management. Patients treated with anti-PD-1, PDL-1 or CTLA-4 therapy in Phase I/II clinical trials between August 2012 and December 2018 were included. Clinical records of patients with significant liver enzyme elevations were retrospectively reviewed. Of 470 ICI-treated patients, liver enzyme elevation occurred in 102 (21.6%), attributed to disease progression (56; 54.9%), other drugs/toxins (7; 6.9%), other causes (22; 21.6%) and ICI immunotoxicity (17; 16.7%; 3.6% of total cohort). Immunotoxicity was associated with higher peak ALT than other causes of enzyme elevation (N = 17; M = 217, 95% CI 145-324 for immunotoxicity, N = 103; M = 74, 95% CI 59-92 for other causes; ratio of means 0.34, 95% CI 0.19-0.60, p = <0.001) and higher ALT:AST ratio (M = 1.27, 95% CI 0.78-2.06 for immunotoxicity, M = 0.69, 95% CI 0.59-0.80 for other causes, ratio of means 0.54, 95% CI 0.36-0.82, p = 0.004). Immunotoxicity was more often seen in patients with prior CPI exposure (41.2% of immunotoxicity vs 15.9% of patients without, p = 0.01), anti-CTLA-4 -containing ICI treatments (29.4% of immunotoxicity vs 6.8% of patients without, p = <0.001) and other organ immunotoxicity (76.5% of immunotoxicity vs 19.2% of patients without, p = <0.001). Cause for enzyme elevation was established in most patients after non-invasive investigation. Liver biopsy was reserved for four patients with atypical treatment response. Liver enzyme elevation is common in patients receiving ICI, but often has a cause other than immunotoxicity. A biochemical signature with higher ALT and ALT/AST ratio, a history of prior ICI exposure and other organ immunotoxicities may help to identify patients at a higher likelihood of immunotoxicity. Liver biopsy can be safely deferred in most patients. We propose an approach to diagnostic evaluation in patients with liver enzyme elevations following ICI exposure.

Variable harlequin frogs Atelopus varius have declined significantly throughout their range as a result of infection with the fungal pathogen Batrachochytrium dendrobatidis (Bd). The Panama Amphibian Rescue and Conservation Project maintains an ex situ population of this Critically Endangered species. We conducted a release trial with surplus captive-bred A. varius individuals to improve our ability to monitor frog populations post-release, observe dispersal patterns after freeing them into the wild and learn about threats to released frogs, as well as to determine whether natural skin toxin defences of frogs could be restored inside mesocosms in the wild and to compare Bd dynamics in natural amphibian communities at the release site vs a non-release site. The 458 released frogs dispersed rapidly and were difficult to re-encounter unless they carried a radio transmitter. No frog was seen after 36 days following release. Thirty frogs were fitted with radio transmitters and only half were trackable by day 10. Tetrodotoxin was not detected in the skins of the frogs inside mesocosms for up to 79 days. Bd loads in other species present at sites were high prior to release and decreased over time in a pattern probably driven by weather. No differences were observed in Bd prevalence between the release and non-release sites. This trial showed that refinements of our methods and approaches are required to study captive Atelopus frogs released into wild conditions. We recommend continuing release trials of captive-bred frogs with post-release monitoring methods, using an adaptive management framework to advance the field of amphibian reintroduction ecology.