Replication Data for: Wide lag time distributions break a trade-off between reproduction and survival in bacteria

Code and text file with parameter values to replicate simulations presented in Figure 6 of the paper. The code produces two files per replicate with the values of the traits u and v in the population over evolutionary time. The parameters can be adjusted in the text file and are: K = carrying capacity; n0= initial size of the population at the start of a growth cycle; doubrate= doubling rate; u0= initial value of u for all individuals in the population; v0= initial value of v for all individuals in the population; u= mutation rate; mutsize= size of a mutational step; numrep= number of evolutionary replicates to run; numcycles = number of growth cycles per replicate (the default is to run each simulation until >95% of the individuals have u=0 but the simulations can also be run for a fixed number of growth cycles per replicate which is set by this parameter. To use this option go to lines 71-72 of the code and change accordingly)

Microcirculatory alterations in critically ill COVID-19 patients analyzed using artificial intelligence

Abstract Background The sublingual microcirculation presumably exhibits disease-specific changes in function and morphology. Algorithm-based quantification of functional microcirculatory hemodynamic variables in handheld vital microscopy (HVM) has recently allowed identification of hemodynamic alterations in the microcirculation associated with COVID-19. In the present study we hypothesized that supervised deep machine learning could be used to identify previously unknown microcirculatory alterations, and combination with algorithmically quantified functional variables increases the model’s performance to differentiate critically ill COVID-19 patients from healthy volunteers. Methods Four international, multi-central cohorts of critically ill COVID-19 patients and healthy volunteers (n = 59/n = 40) were used for neuronal network training and internal validation, alongside quantification of functional microcirculatory hemodynamic variables. Independent verification of the models was performed in a second cohort (n = 25/n = 33). Results Six thousand ninety-two image sequences in 157 individuals were included. Bootstrapped internal validation yielded AUROC(CI) for detection of COVID-19 status of 0.75 (0.69–0.79), 0.74 (0.69–0.79) and 0.84 (0.80–0.89) for the algorithm-based, deep learning-based and combined models. Individual model performance in external validation was 0.73 (0.71–0.76) and 0.61 (0.58–0.63). Combined neuronal network and algorithm-based identification yielded the highest externally validated AUROC of 0.75 (0.73–0.78) (P < 0.0001 versus internal validation and individual models). Conclusions We successfully trained a deep learning-based model to differentiate critically ill COVID-19 patients from heathy volunteers in sublingual HVM image sequences. Internally validated, deep learning was superior to the algorithmic approach. However, combining the deep learning method with an algorithm-based approach to quantify the functional state of the microcirculation markedly increased the sensitivity and specificity as compared to either approach alone, and enabled successful external validation of the identification of the presence of microcirculatory alterations associated with COVID-19 status

Factors associated with self-reported pain and hand function following dorsal wrist ganglion excision

This study aimed to analyse which factors contribute to pain and limited hand function after dorsal wrist ganglion excision. We included 308 patients who underwent surgery between September 2017 and August 2021. Patients completed baseline questionnaires and the patient-rated wrist/hand evaluation questionnaire at baseline and 3 months postoperatively. We observed an improvement in postoperative pain and hand function, but individual outcomes were highly variable. We performed stepwise linear regression analyses to examine which patient characteristics, disease characteristics and psychological factors were associated with postoperative pain and hand function. Higher postoperative pain intensity was associated with recurrence following previous surgery, treatment of the dominant hand, higher baseline pain intensity, lower credibility the patient attributes to the treatment and longer symptom duration. Worse hand function was associated with recurrence following prior surgery, worse baseline hand function and lower treatment credibility. Clinicians should take these findings into account during patient counselling and expectation management.Level of evidence: I

Inter-observer variability in target delineation increases during adaptive treatment of head-and-neck and lung cancer

Introduction: Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC]. Material and methods: Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases each. Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnaire. Results: Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample (p-value range .063–.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment. Conclusion: IOV in target volume delineation increases during treatment, where a disparity in institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needed

Additional file 6 of Whole-genome sequence-informed MALDI-TOF MS diagnostics reveal importance of Klebsiella oxytoca group in invasive infections: a retrospective clinical study

Additional file 6: Table S4. Reproducibility of detection for the predicted ribosomal subunits in MALDI-TOF mass spectra acquired in 4 different centers

Additional file 4 of Worldwide clinical practices in perioperative antibiotic therapy for lung transplantation

Additional file 4. Answers to Case 2

Additional file 4 of Whole-genome sequence-informed MALDI-TOF MS diagnostics reveal importance of Klebsiella oxytoca group in invasive infections: a retrospective clinical study

Additional file 4: Table S2. Cellular fatty acid composition of 11 Klebsiella spp. strains

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Abstract Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so