Tropical methane emissions: A revised view from SCIAMACHY onboard ENVISAT

Methane retrievals from near-infrared spectra recorded by the SCIAMACHY instrument onboard ENVISAT hitherto suggested unexpectedly large tropical emissions. Even though recent studies confirm substantial tropical emissions, there were indications for an unresolved error in the satellite retrievals. Here we identify a retrieval error related to inaccuracies in water vapor spectroscopic parameters, causing a substantial overestimation of methane correlated with high water vapor abundances. We report on the overall implications of an update in water spectroscopy on methane retrievals with special focus on the tropics where the impact is largest. The new retrievals are applied in a four-dimensional variational (4D-VAR) data assimilation system to derive a first estimate of the impact on tropical CH_4 sources. Compared to inversions based on previous SCIAMACHY retrievals, annual tropical emission estimates are reduced from 260 to about 201 Tg CH_4 but still remain higher than previously anticipated

Genetic Evaluation in a Cohort of 126 Dutch Pulmonary Arterial Hypertension Patients

Pulmonary arterial hypertension (PAH) is a severe, life-threatening disease, and in some cases is caused by genetic defects. This study sought to assess the diagnostic yield of genetic testing in a Dutch cohort of 126 PAH patients. Historically, genetic testing in the Netherlands consisted of the analysis of BMPR2 and SMAD9. These genes were analyzed in 70 of the 126 patients. A (likely) pathogenic (LP/P) variant was detected in 22 (31%) of them. After the identification of additional PAH associated genes, a next generation sequencing (NGS) panel consisting of 19 genes was developed in 2018. Additional genetic testing was offered to the 48 BMPR2 and SMAD9 negative patients, out of which 28 opted for NGS analysis. In addition, this gene panel was analyzed in 56 newly identified idiopathic (IPAH) or pulmonary veno occlusive disease (PVOD) patients. In these 84 patients, NGS panel testing revealed LP/P variants in BMPR2 (N = 4), GDF2 (N = 2), EIF2AK4 (N = 1), and TBX4 (N = 3). Furthermore, 134 relatives of 32 probands with a LP/P variant were tested, yielding 41 carriers. NGS panel screening offered to IPAH/PVOD patients led to the identification of LP/P variants in GDF2, EIF2AK4, and TBX4 in six additional patients. The identification of LP/P variants in patients allows for screening of at-risk relatives, enabling the early identification of PAH

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

Publisher Correction: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

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Criteria for inclusion of vaccinations in public programmes

As more and more new vaccines are developed and brought to the market, governments have to make decisions about which vaccinations to include in public programmes. This paper describes the experience in the Netherlands in developing a framework for assessing whether a vaccination should be included in the National Immunization Programme (NIP). Bearing in mind the public nature, the factors that determine a vaccine's suitability for inclusion in a communal vaccination programme have been translated into seven selection criteria, grouped under five thematic headings: seriousness and extent of the disease burden, effectiveness and safety of the vaccination, acceptability of the vaccination, efficiency of the vaccination, and priority of the vaccination. The seven criteria and the explanation of them provide a framework for the systematic examination of arguments for and against the inclusion and prioritisation of particular vaccinations. As an illustration, the vaccinations currently provided in the Netherlands through public programmes as well as 23 'candidate' vaccinations are assessed against the seven criteria. The proposed assessment framework including the selection criteria can take full account of the values and specificities as they may differ between situations and countries; the transparency of the approach may help to clarify which elements of the assessment are pivotal in specific situations. Using the criteria furthers a trustworthy, transparent and accountable process of decision-making about inclusion of new vaccinations in public vaccination programmes and may help to retain public confidence. © 2010 Elsevier Ltd. All rights reserved