Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences.

We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.

Increase in Standardized Management of Neonates with Hypoxic-Ischemic Encephalopathy Since Implementation of a Patient Register.

The Swiss National Asphyxia and Cooling Register was implemented in 2011. This study assessed quality indicators of the cooling process and (short-term) outcomes of neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) longitudinally over time in Switzerland. This is a multicenter national retrospective cohort study of prospectively collected register data. Quality indicators were defined for longitudinal comparison (2011-2014 vs. 2015-2018) of processes of TH and (short-term) outcomes of neonates with moderate-to-severe HIE. Five hundred seventy neonates receiving TH in 10 Swiss cooling centers were included (2011-2018). Four hundred forty-nine (449/570; 78.8%) neonates with moderate-to-severe HIE received TH according to the Swiss National Asphyxia and Cooling Register Protocol. Quality indicators of processes of TH improved in 2015-2018 (compared with 2011-2014): less passive cooling (p = 0.013), shorter time to reach target temperature (p = 0.002), and less over- or undercooling (p < 0.001). In 2015-2018, adherence to performing a cranial magnetic resonance imaging after rewarming improved (p < 0.001), whereas less cranial ultrasounds were performed on admission (p = 0.012). With regard to quality indicators of short-term outcomes, persistent pulmonary hypertension of the neonate was reduced (p = 0.003), and there was a trend toward less coagulopathy (p = 0.063) in 2015-2018. There was no statistically significant change in the remaining processes and outcomes. The Swiss National Asphyxia and Cooling Register is well implemented with good overall adherence to the treatment protocol. Management of TH improved longitudinally. Continuous reevaluation of register data is desirable for quality assessment, benchmarking, and maintaining international evidence-based quality standards.

Genome sequence, comparative analysis and haplotype structure of the domestic dog.

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.

Process variations between Swiss units treating neonates with hypoxic-ischemic encephalopathy and their effect on short-term outcome.

OBJECTIVE: To compare therapeutic hypothermia (TH) treatment of term and near-term neonates with hypoxic-ischemic encephalopathy (HIE) between neonatal units. STUDY DESIGN: Population-based, retrospective analysis of TH initiation and maintenance, and of diagnostic imaging. The comparison between units was based on crude data analysis, indirect standardization, and adjusted logistic regression. RESULTS: TH was provided to 570 neonates with HIE between 2011 and 2018 in 10 Swiss units. We excluded 121 off-protocol cooled neonates to avoid selection bias. Of the remaining 449 neonates, the outcome was favorable to international benchmarks, but there were large unit-to-unit variations in baseline perinatal data and TH management. A total of 5% neonates did not reach target temperature within 7 h (3-10% between units), and 29% experienced over- or undercooling (0-38%). CONCLUSION: Although the neonates had favorable short-term outcomes, areas for improvement remain for Swiss units in both process and outcome measures.

Centre-specific differences in short-term outcomes in neonates with hypoxic-ischaemic encephalopathy.

AIMS OF THE STUDY: To investigate and compare the centre-specific short-term outcome indicators seizures, arterial hypotension, infection and mortality during therapeutic hypothermia until discharge from the neonatal/paediatric intensive care unit in term and near-term neonates with hypoxic-ischaemic encephalopathy (HIE) registered in the Swiss National Asphyxia and Cooling Register between 2011 and 2018. METHODS: Retrospective analysis of prospectively collected national register data between 1 January 2011 and 31 December 2018. Pregnancy, maternal, delivery and neonatal characteristics were compared between the centres. Four short-term outcomes were defined: seizures, arterial hypotension, infection and mortality. The outcome indicators were defined as stated in the protocol of the Swiss National Asphyxia and Cooling Register. Descriptive analyses of the de-identified centre to centre analysis were performed, and standardised observed-to-expected values (risk adjusted for male sex, small for gestational age, Sarnat score on admission, pregnancy/delivery complications) of each centre were compared using with the entire network indirectly standardised mortality/morbidity ratio charts. RESULTS: 570 cooled neonates with HIE receiving therapeutic hypothermia in 10 different centres were included. Clinical or subclinical seizures were reported in a median of 32% (range 17–49%). Arterial hypotension occurred in a median of 62% (range 30–90%). Median infection rate was 10% (range 0–31%). Median mortality rate until discharge was 14% (range 0–25%). CONCLUSIONS: Short-term outcome indicators of seizures, arterial hypotension, infection and mortality showed significant differences in incidence between the centres. These data will help to establish benchmarks for the assessed outcome measures. Benchmarking is a continuous need with the ultimate goal of improving modifiable short-term outcomes in neonates with HIE.

Long-term monitoring data from a naturally ventilated office building.

Data was collected in the field, from an office building located in Frankfurt, Germany, over the period of 4 years. The building was designed as a low-energy building and featured natural ventilation for individual control of air quality as well as buoyancy-driven night ventilation in combination with a central atrium as a passive cooling strategy. The monitored data include in total 116 data points related to outdoor and indoor environmental data, energy related data, and data related to occupancy and occupant behaviour. Data points representing a state were logged with the real timestamp of the event taking place, all other data points were recorded in 10 minute intervals. Data were collected in 17 cell offices with a size of ~20 m2, facing either east or west). Each office has one fixed and two operable windows, internal top light windows between office and corridor (to allow for night ventilation into the atrium) and sun protection elements (operated both manually and automatically). Each office is occupied by one or two persons.

ALLPATHS: de novo assembly of whole-genome shotgun microreads.

New DNA sequencing technologies deliver data at dramatically lower costs but demand new analytical methods to take full advantage of the very short reads that they produce. We provide an initial, theoretical solution to the challenge of de novo assembly from whole-genome shotgun "microreads." For 11 genomes of sizes up to 39 Mb, we generated high-quality assemblies from 80x coverage by paired 30-base simulated reads modeled after real Illumina-Solexa reads. The bacterial genomes of Campylobacter jejuni and Escherichia coli assemble optimally, yielding single perfect contigs, and larger genomes yield assemblies that are highly connected and accurate. Assemblies are presented in a graph form that retains intrinsic ambiguities such as those arising from polymorphism, thereby providing information that has been absent from previous genome assemblies. For both C. jejuni and E. coli, this assembly graph is a single edge encompassing the entire genome. Larger genomes produce more complicated graphs, but the vast majority of the bases in their assemblies are present in long edges that are nearly always perfect. We describe a general method for genome assembly that can be applied to all types of DNA sequence data, not only short read data, but also conventional sequence reads.

Hemoptise maciça / Massive hemoptysis

Os autores revisam a literatura e relatam parte de sua experiência sobre o tratamento da hemoptise maciça. Adotam um conceito menos matemático e mais fisiológico para o sangramento maciço, enfatizando a necessidade de se estabelecer uma rotina que possa ser executada rápida e eficientemente. Destacam o papel da embolizaçäo seletiva das artérias brônquicas, especialmente para os casos näo cirúrgicos. Propöem a cirurgia de ressecçäo pulmonar com a única forma definitiva de tratamento