Broncho-alveolar lavage fluid recovery correlates with airway neutrophilia in lung transplant patients

SummaryBroncho-alveolar lavage (BAL) is important to assess airway inflammation. There is debate about the volume instilled, but the variation of BAL fluid recovery (BFR) has received little attention. We investigated the association between BFR and rejection/infection status after lung transplantation (LTx).We combined clinical findings, FEV1, transbronchial biopsies and BAL analysis (BFR, interleukin-8 (IL8), cell counts, microbiology) of 115 samples/LTx patients. The patients were divided into 4 groups: stable (subdivided in colonized and non-colonized), acute rejection (AR), Bronchiolitis Obliterans Syndrome (BOS) and infection.BFR was significantly lower in AR, BOS and infection, and correlated with the severity of AR and BOS. A 10ml decrease of BFR was associated with a FEV1 decrease of 4.4% and a %neutrophils and IL8 increase of 9.6% and 9.7pg/ml, respectively. Colonized stable patients had no significant differences in airway inflammation, FEV1 and BFR compared to the non-colonized stable patients.We conclude that a low BFR is an indicator of lung rejection or infection. BFR variation is related to airway obstruction and neutrophilic inflammation, which can cause an increased compliance of the airway wall, making it more collapsible. Airway colonization in stable patients had no effect on airway inflammatory parameters, BFR and FEV1

Efficient pairwise RNA structure prediction and alignment using sequence alignment constraints

BACKGROUND: We are interested in the problem of predicting secondary structure for small sets of homologous RNAs, by incorporating limited comparative sequence information into an RNA folding model. The Sankoff algorithm for simultaneous RNA folding and alignment is a basis for approaches to this problem. There are two open problems in applying a Sankoff algorithm: development of a good unified scoring system for alignment and folding and development of practical heuristics for dealing with the computational complexity of the algorithm. RESULTS: We use probabilistic models (pair stochastic context-free grammars, pairSCFGs) as a unifying framework for scoring pairwise alignment and folding. A constrained version of the pairSCFG structural alignment algorithm was developed which assumes knowledge of a few confidently aligned positions (pins). These pins are selected based on the posterior probabilities of a probabilistic pairwise sequence alignment. CONCLUSION: Pairwise RNA structural alignment improves on structure prediction accuracy relative to single sequence folding. Constraining on alignment is a straightforward method of reducing the runtime and memory requirements of the algorithm. Five practical implementations of the pairwise Sankoff algorithm – this work (Consan), David Mathews' Dynalign, Ian Holmes' Stemloc, Ivo Hofacker's PMcomp, and Jan Gorodkin's FOLDALIGN – have comparable overall performance with different strengths and weaknesses

Exploring gastrointestinal variables affecting drug and formulation behavior: methodologies, challenges and opportunities

Various gastrointestinal (GI) factors affect drug and formulation behavior after oral administration, including GI transfer, motility, pH and GI fluid volume and composition. An in-depth understanding of these physiological and anatomical variables is critical for a continued progress in oral drug development. In this review, different methodologies (invasive versus non-invasive) to explore the impact of physiological variables on formulation behavior in the human GI tract are presented, revealing their strengths and limitations. The techniques mentioned allow for an improved understanding of the role of following GI variables: gastric emptying (magnetic resonance imaging (MRI), scintigraphy, acetaminophen absorption technique, ultrasonography, breath test, intraluminal sampling and telemetry), motility (MRI, small intestinal/colonic manometry and telemetry), GI volume changes (MRI and ultrasonography), temperature (telemetry) and intraluminal pH (intraluminal sampling and telemetry)

A many-analysts approach to the relation between religiosity and well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

A Many-analysts Approach to the Relation Between Religiosity and Well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β = 0.120). For the second research question, this was the case for 65% of the teams (median reported β = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

Safety and efficacy of bridging to lung transplantation with antifibrotic drugs in idiopathic pulmonary fibrosis: a case series

Following recent approval of pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF), questions arise about the use of these antifibrotics in patients awaiting lung transplantation (LTx).status: publishe

Interactions between the introduction of a “covid pass” and consciously risking contracting covid

Er wordt in Europa gewerkt aan de introductie van een digitaal paspoort1 op basis waarvan mensen extra vrijheden kunnen krijgen na (a) volledige vaccinatie, (b) een recente negatieve PCR-test en (c) een aantoonbaar (recent) doorgemaakte infectie. Indien ook een aantoonbaar doorgemaakte infectie met het coronavirus tot meer vrijheden kan leiden, zou dit door sommigen ervaren kunnen worden als een reden om juist wél besmet te raken – zeker zo lang zij nog niet de mogelijkheid hebben om zich te laten vaccineren (of indien ze zich liever niet willen laten vaccineren). In deze memo staat daarom de volgende vraag centraal: Als een aantoonbaar doorlopen infectie met het coronavirus tot meer vrijheden leidt (‘coronapaspoort’), kan dit ertoe leiden dat sommige mensen bewust een besmetting opzoeken om op die manier meer vrijheden te kunnen krijgen? Welke factoren zijn hierbij van invloed

Interactions between the introduction of a “covid pass” and consciously risking contracting covid

Er wordt in Europa gewerkt aan de introductie van een digitaal paspoort1 op basis waarvan mensen extra vrijheden kunnen krijgen na (a) volledige vaccinatie, (b) een recente negatieve PCR-test en (c) een aantoonbaar (recent) doorgemaakte infectie. Indien ook een aantoonbaar doorgemaakte infectie met het coronavirus tot meer vrijheden kan leiden, zou dit door sommigen ervaren kunnen worden als een reden om juist wél besmet te raken – zeker zo lang zij nog niet de mogelijkheid hebben om zich te laten vaccineren (of indien ze zich liever niet willen laten vaccineren). In deze memo staat daarom de volgende vraag centraal: Als een aantoonbaar doorlopen infectie met het coronavirus tot meer vrijheden leidt (‘coronapaspoort’), kan dit ertoe leiden dat sommige mensen bewust een besmetting opzoeken om op die manier meer vrijheden te kunnen krijgen? Welke factoren zijn hierbij van invloed

Determinants of survival in lung transplantation patients with idiopathic pulmonary fibrosis: a retrospective cohort study

Survival after lung transplantation (LTx) for idiopathic pulmonary fibrosis (IPF) is worse compared to other indications for LTx. We investigated the effect of several pretransplant variables including the use of pretransplant corticosteroids (CS) on post-transplant graft and chronic lung allograft dysfunction (CLAD)-free survival and functional testing (maximum inspiratory and expiratory pressure, six-minute walk test, quadriceps and hand pinch force) in a small cohort of IPF patients. We retrospectively compared two groups of IPF patients (n = 36 on CS vs. n = 18 not on CS) who underwent LTx between 2000 and 2016. Analysis of 54 IPF-LTx patients showed no significant effect on graft survival or functional tests except for maximum inspiratory pressure (P = 0.033) between these two groups (all LTx patients, CS vs. no CS). Regression analysis showed significant impact of procedure with a hazard ratio of 0.423 (CI 95% 0.194, 0.924) favoring sequential single LTx (SSLTx) compared to single lung transplantation (SLTx). When analyzing only the 40 SSLTx patients, corticosteroid-free patients showed significantly better graft survival compared to patients on CS (P = 0.045) and CLAD-free survival (P = 0.019). The possible detrimental effect of corticosteroid therapy before LTx was demonstrated in this cohort of SSLTx patients, which questions the use of corticosteroids in a pretransplantation setting.status: publishe

Outcome of lung transplantation in non-idiopathic pulmonary fibrosis interstitial lung disease

Lung transplantation remains the only curative treatment option for selected patients with end-stage interstitial lung disease (ILD). Candidate selection is impeded by patient heterogeneity, particularly in the subgroup of non-idiopathic pulmonary fibrosis (non-IPF) interstitial lung diseases. We performed a descriptive analysis of all non-IPF ILD patients who underwent lung transplantation in our center between July 1991 and November 2016 (n = 129) and searched for pre-transplant variables correlating with graft loss and chronic lung allograft dysfunction (CLAD). Our study cohort was characterized by a significantly affected medical condition, an extensive pre-transplant corticosteroid use (73.8%), and a high prevalence of pulmonary hypertension (55.7%). Earlier year of transplantation (P = .004), higher bilirubin level (P < .0001), older recipient age (P = .04), and smaller recipient height (P = .02) were found to be associated with earlier graft loss in multivariate analysis. Moreover, pre-transplant corticosteroid treatment tended to be related to earlier graft loss (P = .06), while pulmonary hypertension did not significantly correlate. None of the pre-transplant variables were shown to be associated with CLAD development. Ongoing research is required to further explore this diverse patient population and the pre-transplant variables determining their post-transplant outcome.status: publishe