Temperature-dependent benefits of bacterial exposure in embryonic development of Daphnia magna resting eggs

The environments in which animals develop and evolve are profoundly shaped by bacteria, which affect animals both indirectly through their role in biogeochemical processes and directly through antagonistic or beneficial interactions. The outcomes of these activities can differ according to environmental context. In a series of laboratory experiments with diapausing eggs of the water flea Daphnia magna, we manipulated two environmental parameters, temperature and presence of bacteria, and examined their effect on development. At elevated temperatures (≥ 26 °C), resting eggs developing without live bacteria had reduced hatching success and correspondingly higher rates of severe morphological abnormalities compared with eggs with bacteria in their environment. The beneficial effect of bacteria was strongly reduced at 20 °C. Neither temperature nor the presence of bacteria affected directly developing parthenogenetic eggs. The mechanistic basis of this effect of bacteria on development is unclear, but these results highlight the complex interplay of biotic and abiotic factors influencing animal development after diapause

Resource use and outcome in critically ill patients with hematological malignancy: a retrospective cohort study

INTRODUCTION: The paucity of data on resource use in critically ill patients with hematological malignancy and on these patients' perceived poor outcome can lead to uncertainty over the extent to which intensive care treatment is appropriate. The aim of the present study was to assess the amount of intensive care resources needed for, and the effect of treatment of, hemato-oncological patients in the intensive care unit (ICU) in comparison with a nononcological patient population with a similar degree of organ dysfunction. METHODS: A retrospective cohort study of 101 ICU admissions of 84 consecutive hemato-oncological patients and 3,808 ICU admissions of 3,478 nononcological patients over a period of 4 years was performed. RESULTS: As assessed by Therapeutic Intervention Scoring System points, resource use was higher in hemato-oncological patients than in nononcological patients (median (interquartile range), 214 (102 to 642) versus 95 (54 to 224), P < 0.0001). Severity of disease at ICU admission was a less important predictor of ICU resource use than necessity for specific treatment modalities. Hemato-oncological patients and nononcological patients with similar admission Simplified Acute Physiology Score scores had the same ICU mortality. In hemato-oncological patients, improvement of organ function within the first 48 hours of the ICU stay was the best predictor of 28-day survival. CONCLUSION: The presence of a hemato-oncological disease per se is associated with higher ICU resource use, but not with increased mortality. If withdrawal of treatment is considered, this decision should not be based on admission parameters but rather on the evolutional changes in organ dysfunctions

Earth Virtualization Engines -- A Technical Perspective

Participants of the Berlin Summit on Earth Virtualization Engines (EVEs) discussed ideas and concepts to improve our ability to cope with climate change. EVEs aim to provide interactive and accessible climate simulations and data for a wide range of users. They combine high-resolution physics-based models with machine learning techniques to improve the fidelity, efficiency, and interpretability of climate projections. At their core, EVEs offer a federated data layer that enables simple and fast access to exabyte-sized climate data through simple interfaces. In this article, we summarize the technical challenges and opportunities for developing EVEs, and argue that they are essential for addressing the consequences of climate change

Swiss public health measures associated with reduced SARS-CoV-2 transmission using genome data

Genome sequences from evolving infectious pathogens allow quantification of case introductions and local transmission dynamics. We sequenced 11,357 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Switzerland in 2020 - the sixth largest effort globally. Using a representative subset of these data, we estimated viral introductions to Switzerland and their persistence over the course of 2020. We contrasted these estimates with simple null models representing the absence of certain public health measures. We show that Switzerland's border closures de-coupled case introductions from incidence in neighboring countries. Under a simple model, we estimate an 86-98% reduction in introductions during Switzerland's strictest border closures. Furthermore, the Swiss 2020 partial lockdown roughly halved the time for sampled introductions to die out. Last, we quantified local transmission dynamics once introductions into Switzerland occurred, using a phylodynamic model. We found that transmission slowed 35-63% upon outbreak detection in summer 2020, but not in fall. This finding may indicate successful contact tracing over summer before overburdening in fall. The study highlights the added value of genome sequencing data for understanding transmission dynamics

Earth Virtualization Engines: a technical perspective

Participants of the Berlin Summit on Earth Virtualization Engines (EVEs) discussed ideas and concepts to improve our ability to cope with climate change. EVEs aim to provide interactive and accessible climate simulations and data for a wide range of users. They combine high-resolution physics-based models with machine learning techniques to improve the fidelity, efficiency, and interpretability of climate projections. At their core, EVEs offer a federated data layer that enables simple and fast access to exabyte-sized climate data through simple interfaces. In this article, we summarize the technical challenges and opportunities for developing EVEs, and argue that they are essential for addressing the consequences of climate change

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Erectile function preservation after salvage radiation therapy for biochemically recurrent prostate cancer after prostatectomy: Five-year results of the SAKK 09/10 randomized phase 3 trial.

OBJECTIVES To evaluate effects of dose intensified salvage radiotherapy (sRT) on erectile function in biochemically recurrent prostate cancer (PC) after radical prostatectomy (RP). MATERIALS AND METHODS Eligible patients had evidence of biochemical failure after RP and a PSA at randomization of ≤ 2 ng/ml. Erectile dysfunction (ED) was investigated as secondary endpoint within the multicentre randomized trial (February 2011 to April 2014) in patients receiving either 64 Gy or 70 Gy sRT. ED and quality of life (QoL) were assessed using CTCAE v4.0 and the EORTC QoL questionnaires C30 and PR25 at baseline and up to 5 years after sRT. RESULTS 344 patients were evaluable. After RP 197 (57.3 %) patients had G0-2 ED while G3 ED was recorded in 147 (42.7 %) patients. Subsequently, sexual activity and functioning was impaired. 5 years after sRT, 101 (29.4 %) patients noted G0-2 ED. During follow-up, 44.2 % of patients with baseline G3 ED showed any improvement and 61.4 % of patients with baseline G0-2 ED showed worsening. Shorter time interval between RP and start of sRT (p = 0.007) and older age at randomization (p = 0.005) were significant predictors to more baseline ED and low sexual activity in the long-term. Age (p = 0.010) and RT technique (p = 0.031) had a significant impact on occurrence of long-term ED grade 3 and worse sexual functioning. During follow-up, no differences were found in erectile function, sexual activity, and sexual functioning between the 64 Gy and 70 Gy arm. CONCLUSION ED after RP is a known long-term side effect with significant impact on patients' QoL. ED was further affected by sRT, but dose intensification of sRT showed no significant impact on erectile function recovery or prevalence of de novo ED after sRT. Age, tumor stage, prostatectomy and RT-techniques, nerve-sparing and observation time were associated with long-term erectile function outcome.ClinicalTrials.gov. Identifier: NCT01272050

Adherence to Contouring and Treatment Planning Requirements Within a Multicentric Trial: Results of the Quality Assurance of the SAKK 09/10 trial

PURPOSE To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent prostate cancer after prostatectomy. METHODS AND MATERIALS Within the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) 09/10 trial testing 64-Gy versus 70-Gy salvage RT, a central collection of treatment plans was performed and thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events version 4.0) and freedom from biochemical progression (FFBP) were investigated. RESULTS The treatment plans for 344 patients treated between February 2011 and April 2014 depicted important deviations from the EORTC guidelines and the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (eg, prostate bed in 48.8%, rectal wall [RW] in 41%). In addition, variations in clinical target volume (CTV) and planning target volume (PTV) occurred frequently (eg, CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥2 gastrointestinal acute toxicity when the CTV did not overlap the RW versus when the CTV overlapped the RW (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.85; P = .014), and a higher rate of grade ≥2 late genitourinary (GU) toxicity when the CTV overlapped the RW (OR, 2.58; 95% CI, 1.17-5.72; P = .019). A marginally significant lower risk of grade ≥2 late GU toxicity was observed when the prostate bed did not overlap versus did overlap the RW (OR, 0.51; 95% CI, 0.25-1.03; P = .06). In addition, a marginally significant decrease in FFBP was observed in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed (hazard ratio, 1.44; 95% CI, 0.96-2.17; P = .07). CONCLUSIONS Despite a thorough QA program, the central review of a phase 3 trial showed limited adherence to treatment protocol recommendations, which was associated with a higher risk of toxicity by means of acute or late gastrointestinal or GU toxicity and showed a trend toward worse FFBP. Data from this QA review might help to refine future QA programs and prostate bed delineation guidelines

Adherence to contouring and treatment planning requirements within a multicentric trial -results of the quality assurance of the SAKK 09/10 trial.

PURPOSE To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase III randomized "XXXX-Anonymized for Review" trial in biochemically recurrent prostate cancer (PC) patients after prostatectomy. METHODS AND MATERIALS Within the "XXXX-Anonymized for Review" trial testing 64Gy versus 70Gy salvage RT, a central collection of treatment plans were performed, which were thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs. no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events (CTCAE) v4.0) and freedom from biochemical progression (FFBP) were investigated. RESULTS The treatment plans of 344 patients treated between February 2011 and April 2014 depicted important deviations to the EORTC guidelines and to the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (e.g., prostate bed (PB) in 48.8%, rectal wall (RW) in 41%). In addition, variations in clinical (CTV) - and planning target volume (PTV) occurred frequently (e.g., CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥ 2 gastrointestinal (GI) acute toxicity when CTV not overlapped RW vs. CTV overlapping RW, (OR 0.43; CI [0.22, 0.85]; p= 0.014), and a higher rate of grade ≥ 2 late genitourinary (GU) toxicity in case of the CTV overlapped with RW, (OR 2.58; CI [1.17, 5.72]; p= 0.019). A marginally significant lower risk of grade ≥ 2 late GU toxicity in patients when PB not overlapping RW versus overlapping RW was observed (OR 0.51; CI [0.25, 1.03]; p= 0.06). In addition, a marginally significant decrease of FFBP in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed, (HR 1.44; CI [0.96, 2.17]; p= 0.07) was observed. CONCLUSIONS Despite a thorough QA program, the central review of a phase-III trial showed limited adherence to treatment protocol recommendations which was associated with a higher risk of toxicity by means of acute or late GI or GU toxicity and showed a trend towards worse FFBP. Data from this QA review may help refine future QA programs and prostate bed delineation guidelines