FLEXBAR: flexible barcode and adapter processing for next-generation sequencing platforms

Quantitative and systems biology approaches benefit from the unprecedented depth of next-generation sequencing. A typical experiment yields millions of short reads, which oftentimes carry particular sequence tags. These tags may be: (a) specific to the sequencing platform and library construction method (e.g., adapter sequences); (b) have been introduced by experimental design (e.g., sample barcodes); or (c) constitute some biological signal (e.g., splice leader sequences in nematodes). Our software FLEXBAR enables accurate recognition, sorting and trimming of sequence tags with maximal flexibility, based on exact overlap sequence alignment. The software supports data formats from all current sequencing platforms, including color-space reads. FLEXBAR maintains read pairings and processes separate barcode reads on demand. Our software facilitates the fine-grained adjustment of sequence tag detection parameters and search regions. FLEXBAR is a multi-threaded software and combines speed with precision. Even complex read processing scenarios might be executed with a single command line call. We demonstrate the utility of the software in terms of read mapping applications, library demultiplexing and splice leader detection. FLEXBAR and additional information is available for academic use from the website: http://sourceforge.net/projects/flexbar/

A Constraint-based Mission Planning Approach for Reconfigurable Multi-Robot Systems

The application of reconfigurable multi-robot systems introduces additional degrees of freedom to design robotic missions compared to classical multi-robot systems. To allow for autonomous operation of such systems, planning approaches have to be investigated that cannot only cope with the combinatorial challenge arising from the increased flexibility of modular systems, but also exploit this flexibility to improve for example the safety of operation. While the problem originates from the domain of robotics it is of general nature and significantly intersects with operations research. This paper suggests a constraint-based mission planning approach, and presents a set of revised definitions for reconfigurable multi-robot systems including the representation of the planning problem using spatially and temporally qualified resource constraints. Planning is performed using a multi-stage approach and a combined use of knowledge-based reasoning, constraint-based programming and integer linear programming. The paper concludes with the illustration of the solution of a planned example mission

Multi-Parton Interactions at the LHC

We review the recent progress in the theoretical description and experimental observation of multiple parton interactions. Subjects covered include experimental measurements of minimum bias interactions and of the underlying event, models of soft physics implemented in Monte Carlo generators, developments in the theoretical description of multiple parton interactions and phenomenological studies of double parton scattering. This article stems from contributions presented at the Helmholtz Alliance workshop on "Multi-Parton Interactions at the LHC", DESY Hamburg, 13-15 September 2010.Comment: 68 page

Are social conflicts at work associated with depressive symptomatology? Results from the population-based LIFE-Adult-Study

Background Psychosocial stressors in the workplace can be detrimental to mental health. Conflicts at work, e.g. aggression, hostility or threats from coworkers, supervisors or customers, can be considered a psychosocial stressor, possibly increasing risk for depressive symptoms. Existing studies, however, differ in the assessment of social conflicts, i.e. as individual- or job-level characteristics. Here, we investigated the association between conflicts at work assessed as objective job characteristics, and depressive symptomatology, using data from a large population-based sample. Additionally, we investigated gender differences and the impact of personality traits and social resources. Methods We used data from the population-based LIFE-Adult-Study from Leipzig, Germany. Information on conflicts at work, assessed as job characteristics, were drawn from the Occupational Information Network, depressive symptoms were assessed via the Center for Epidemiological Studies Depression Scale. Multilevel linear regression models with individuals and occupations as levels of analysis were applied to investigate the association between conflicts at work and depressive symptoms. Results Our sample included 2164 employed adults (age: 18–65 years, mean: 49.3, SD: 7.9) in 65 occupations. No association between conflicts s at work and depressive symptomatology was found (men: b = − 0.14; p = 0.74, women: b = 0.17, p = 0.72). Risk for depression was mostly explained by individual-level factors like e.g. neuroticism or level of social resources. The model showed slightly higher explanatory power in the female subsample. Conclusion Conflicts at work, assessed as objective job characteristics, were not associated with depressive symptoms. Possible links between interpersonal conflict and impaired mental health might rather be explained by subjective perceptions of social stressors and individual coping styles

Heart failure is independently associated with white matter lesions: Insights from the population-based LIFE-Adult Study

Aims: White matter lesions (WML) are common structural alterations in the white matter of the brain and their prevalence increases with age. They are associated with cerebral ischaemia and cognitive dysfunction. Patients with heart failure (HF) are at risk for cognitive decline. We hypothesized that the presence and duration of HF are associated with WML. Methods and results: The LIFE-Adult Study is a population-based study of 10 000 residents of Leipzig, Germany. WML were quantitated in 2490 participants who additionally underwent cerebral MRI using the Fazekas score. Mean age was 64 years, and 46% were female; 2156 (86.6%) subjects had Fazekas score of 0-1, and 334 (13.4%) had Fazekas score of 2-3. Thirty participants had a medical history of HF, 1019 had hypertension, and 51 had a history of stroke. Median left ventricular ejection fraction of the participants with HF was 57% (interquartile ranges 54-62). Age, troponin T, NT-proBNP, body mass index, history of acute myocardial infarction, stroke, HF, and diabetes were positively associated with WML in univariate analysis. On multivariate analysis, age, hypertension, stroke, and HF were independently associated with WML. The odd's ratio for the association of WML (Fazekas 2-3) with HF was 2.8 (95% CI 1.2-6.5; P = 0.019). WML increased with longer duration of HF (P = 0.036 for trend). Conclusions: In addition to age, hypertension, and stroke, the prevalence and duration of HF are independently associated with WML. This observation sets the stage to investigate the prognostic value of WML in HF and the impact of HF therapies on WML

Early prediction of severe retinopathy of prematurity requiring laser treatment using physiological data

Background Early risk stratification for developing retinopathy of prematurity (ROP) is essential for tailoring screening strategies and preventing abnormal retinal development. This study aims to examine the ability of physiological data during the first postnatal month to distinguish preterm infants with and without ROP requiring laser treatment. Methods In this cohort study, preterm infants with a gestational age <32 weeks and/or birth weight <1500 g, who were screened for ROP were included. Differences in the physiological data between the laser and non-laser group were identified, and tree-based classification models were trained and independently tested to predict ROP requiring laser treatment. Results In total, 208 preterm infants were included in the analysis of whom 30 infants (14%) required laser treatment. Significant differences were identified in the level of hypoxia and hyperoxia, oxygen requirement, and skewness of heart rate. The best model had a balanced accuracy of 0.81 (0.72–0.87), a sensitivity of 0.73 (0.64–0.81), and a specificity of 0.88 (0.80–0.93) and included the SpO2/FiO2 ratio and baseline demographics (including gestational age and birth weight). Conclusions Routinely monitored physiological data from preterm infants in the first postnatal month are already predictive of later development of ROP requiring laser treatment, although validation is required in larger cohorts. Impact Routinely monitored physiological data from the first postnatal month are predictive of later development of ROP requiring laser treatment, although model performance was not significantly better than baseline characteristics (gestational age, birth weight, sex, multiple birth, prenatal glucocorticosteroids, route of delivery, and Apgar scores) alone. A balanced accuracy of 0.81 (0.72–0.87), a sensitivity of 0.73 (0.64–0.81), and a specificity of 0.88 (0.80–0.93) was achieved with a model including the SpO2/FiO2 ratio and baseline characteristics. Physiological data have potential to play a significant role for future ROP prediction and provide opportunities for early interventions to protect infants from abnormal retinal development

Preterm white matter injury : ultrasound diagnosis and classification

White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential neuroimaging in preterm infants, and is reliable for the diagnosis of cystic periventricular leukomalacia. Although magnetic resonance imaging is superior to CUS in detecting the diffuse and more subtle forms of WMI that prevail in very premature infants surviving nowadays, recent improvement in the quality of neonatal CUS imaging has broadened the spectrum of preterm white matter abnormalities that can be detected with this technique. We propose a structured CUS assessment of WMI of prematurity that seeks to account for both cystic and non-cystic changes, as well as signs of white matter loss and impaired brain growth and maturation, at or near term equivalent age. This novel assessment system aims to improve disease description in both routine clinical practice and clinical research. Whether this systematic assessment will improve prediction of outcome in preterm infants with WMI still needs to be evaluated in prospective studies

Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial

Background Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice. Methods In this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002. Findings We recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86–1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention. Interpretation Enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants. Funding UK National Institute for Health Research Health Technology Assessment programme (10/57/49)

Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial

Background Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice. Methods In this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002. Findings We recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86–1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention. Interpretation Enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants. Funding UK National Institute for Health Research Health Technology Assessment programme (10/57/49)