Ground truth labels challenge the validity of sepsis consensus definitions in critical illness

Background Sepsis is the leading cause of death in the intensive care unit (ICU). Expediting its diagnosis, largely determined by clinical assessment, improves survival. Predictive and explanatory modelling of sepsis in the critically ill commonly bases both outcome definition and predictions on clinical criteria for consensus definitions of sepsis, leading to circularity. As a remedy, we collected ground truth labels for sepsis. Methods In the Ground Truth for Sepsis Questionnaire (GTSQ), senior attending physicians in the ICU documented daily their opinion on each patient’s condition regarding sepsis as a five-category working diagnosis and nine related items. Working diagnosis groups were described and compared and their SOFA-scores analyzed with a generalized linear mixed model. Agreement and discriminatory performance measures for clinical criteria of sepsis and GTSQ labels as reference class were derived. Results We analyzed 7291 questionnaires and 761 complete encounters from the first survey year. Editing rates for all items were > 90%, and responses were consistent with current understanding of critical illness pathophysiology, including sepsis pathogenesis. Interrater agreement for presence and absence of sepsis was almost perfect but only slight for suspected infection. ICU mortality was 19.5% in encounters with SIRS as the “worst” working diagnosis compared to 5.9% with sepsis and 5.9% with severe sepsis without differences in admission and maximum SOFA. Compared to sepsis, proportions of GTSQs with SIRS plus acute organ dysfunction were equal and macrocirculatory abnormalities higher (p < 0.0001). SIRS proportionally ranked above sepsis in daily assessment of illness severity (p < 0.0001). Separate analyses of neurosurgical referrals revealed similar differences. Discriminatory performance of Sepsis-1/2 and Sepsis-3 compared to GTSQ labels was similar with sensitivities around 70% and specificities 92%. Essentially no difference between the prevalence of SIRS and SOFA ≥ 2 yielded sensitivities and specificities for detecting sepsis onset close to 55% and 83%, respectively. Conclusions GTSQ labels are a valid measure of sepsis in the ICU. They reveal suspicion of infection as an unclear clinical concept and refute an illness severity hierarchy in the SIRS-sepsis-severe sepsis spectrum. Ground truth challenges the accuracy of Sepsis-1/2 and Sepsis-3 in detecting sepsis onset. It is an indispensable intermediate step towards advancing diagnosis and therapy in the ICU and, potentially, other health care settings.

In Vivo Accelerator-Based Boron Neutron Capture Therapy for Spontaneous Tumors in Large Animals: Case Series

(1) Background: accelerator-based neutron sources are a new frontier for BNCT but many technical issues remain. We aimed to study such issues and results in larger-animal BNCT (cats and dogs) with naturally occurring, malignant tumors in different locations as an intermediate step in translating current research into clinical practice. (2) Methods: 10 pet cats and dogs with incurable, malignant tumors that had no treatment alternatives were included in this study. A tandem accelerator with vacuum insulation was used as a neutron source. As a boron-containing agent, 10B-enriched sodium borocaptate (BSH) was used at a dose of 100 mg/kg. Animal condition as well as tumor progression/regression were monitored. (3) Results: regression of tumors in response to treatment, improvements in the overall clinical picture, and an increase in the estimated duration and quality of life were observed. Treatment-related toxicity was mild and reversible. (4) Conclusions: our study contributes to preparations for human BNCT clinical trials and suggests utility for veterinary oncology.

Hallucinogens, alcohol and shifting leadership strategies in the ancient Peruvian Andes

In the pre-Columbian Andes, the use of hallucinogens during the Formative period (900–300 BC) often supported exclusionary political strategies, whereas, during the Late Horizon (AD 1450–1532), Inca leaders emphasised corporate strategies via the mass consumption of alcohol. Using data from Quilcapampa, the authors argue that a shift occurred during the Middle Horizon (AD 600–1000), when beer made from Schinus molle was combined with the hallucinogen Anadenanthera colubrina. The resulting psychotropic experience reinforced the power of the Wari state, and represents an intermediate step between exclusionary and corporate political strategies. This Andean example adds to the global catalogue documenting the close relationship between hallucinogens and social power.

The Modified Procedure of Totally Tubeless PNL

Mini percutaneous nephrolithotomy (mPNL) is a standard treatment for kidney stones larger than 1.5 cm, with the placement of a nephrostomy drainage at the end of it, which is considered the standard procedure, but tubeless/ totally tubeless mPNL techniques reduce postoperative discomfort in patients and shorten hospital stays. The aim of article was to compare the efficacy and safety of our proposed modified method of totally tubeless mPNL with control of the parenchymal canal, with existing methods of tubeless/totally tubeless mPNL. Novelty of the study presented by modified method of totally tubeless mPNL. During the period from 2018 to 2020 we performed 486 mPNL were performed in our clinic in total, among which 63 (12.9%) patients underwent tubeless PNL. Patients whose surgeries ended with using tubeless techniques were divided into three groups: Group I – 22 patients who had tubeless mPNL (with ureteral stent), Group II (20 patients) – totally tubeless mPNL with a safety thread (the proposed procedure), Group III (21 patients) – totally tubeless mPNL. In all three groups, the access point was most often made through the lower group of renal calyces: Group I – 12 (54.5%), Group II – 14 (70.0%), Group III – 13 (61.9%); then through the middle calyx: Group I – 8 (36.4%), Group II – 6 (30.0%), Group III – 7 (33.3%); and the upper calyx: Group І – 2 (9.1%), Group ІІ – 0%, Group ІІІ – 1 (4.8%), no differences in the distribution of access points between groups were found (p=0.67). There were no differences in the distribution of tract sizes between the groups (p=0.95) with tract dilatation to 16.5/17.5 Fr was performed most often: Group I – 12 (54.5%), in Group II – 11 (55.0%) and Group III – 11 (52.4%). The mean duration of surgery in Group I was 83.0±22.9 min, in Group II – 74.9±13.6 min, in Group III – 72.6±12.0 min (p=0.47). This study confirms the high effectiveness of totally tubeless mPNL. The proposed modification to perform totally tubeless mPNL allows you to have permanent postoperative control over the parenchymal channel and in case of postoperative bleeding it enables you to immediately insert nephrostomy drainage through the safety thread. Study contributes to practical methods as an intermediate step for surgeons who are considering transition to a totally tubeless PCNL technique.

An Algebraic Approach to Clustering and Classification with Support Vector Machines

In this note, we propose a novel classification approach by introducing a new clustering method, which is used as an intermediate step to discover the structure of a data set. The proposed clustering algorithm uses similarities and the concept of a clique to obtain clusters, which can be used with different strategies for classification. This approach also reduces the size of the training data set. In this study, we apply support vector machines (SVMs) after obtaining clusters with the proposed clustering algorithm. The proposed clustering algorithm is applied with different strategies for applying SVMs. The results for several real data sets show that the performance is comparable with the standard SVM while reducing the size of the training data set and also the number of support vectors.

Effect of Exercise Training On Autophagic Process in White Adipose Tissue of High Fat Diet-Induced Obese Mice

Background. Some studies have established a relationship between obesity and the autophagic process in adipose tissue. This study aimed to investigate the effect of exercise training on the autophagic process in white adipose tissue (WAT) of high fat diet-induced obese mice.Methods and Results. C57BL/6 mice were assigned into three groups included: 1) Control 2), High-Fat Diet-induced Obesity (HFD-Ob), and 3) High-Fat Diet with Exercise Training (HFD-Ex). The subjects of HFD-Ob were fed a high-fat diet for 14 weeks. The mice of HFD-Ex had eight weeks of endurance training on a treadmill in addition to having the HFD. The Real-Time–PCR and western blot methods were used to measure the mRNA and protein levels of markers of the autophagic process. HFD caused an upregulation in the factors of the autophagosome formation, including ATG5 and ATG7, LC3, and the exercise training could augment the upregulation. Further, the training program prevented the change in LAMP2 expression (a marker of autophagolysosome), which being reduced by HFD. The lysosomal clearance factors (CTSB and CTSL) were raised in HFD-Ob and differently changed in HFD-Ex.Conclusion. HFD-induced obesity promoted the early and last steps of autophagy whereas defected the intermediate-step of it. Interestingly, the exercise training enhanced the early phase of autophagy, which being increased by HFD. Further, the training program could modify the rising effect of HFD on the last step of autophagy. It seems that a part of the protective effect of exercise training on obesity-related complications may be mediated by modulating the autophagic process in white adipose tissue.

Multi-Step Crystallization and Chemical Evolution of Sodium Yttrium Fluoride

Two-step crystallization mechanisms based on spinodal decomposition followed by nucleation are commonly observed both in the laboratory and in nature. While this pathway may require chemical reactions, subsequent nucleation and growth are often considered as separate, discrete events from the reaction itself. Recent work has also shown a distinct intermediate step involving the formation of an amorphous aggregate. Here we report a novel four-step mechanism in the aqueous synthesis of sodium yttrium fluoride involving 1) the segregation of aqueous ions into a dense liquid phase, 2) the formation of an amorphous aggregate, 3) nucleation of a cubic YF3 phase, and 4) subsequent solid-state diffusion of sodium and fluoride ions to form a final NaYF4 phase. The final step involves a continuous, gradual change of the solid phase’s chemical stoichiometry from YF3 toward NaYF4. Unlike previously studied nucleation and growth mechanisms, the stoichiometry of the final solid phase evolves throughout the crystallization process rather than being determined at nucleation. This novel four-step mechanism provides a new perspective into the nucleation and growth of many other crystalline materials given the ubiquity of nonstoichiometric compounds in nature.

15-year survivorship analysis of an interspinous device in surgery for single-level lumbar disc herniation

Background Interspinous devices have been introduced as alternatives to decompression or fusion in surgery for degenerative lumbar diseases. This study aimed to investigate 15-year survivorship and risk factors for reoperation of a Device for Intervertebral Assisted Motion (DIAM) in surgery for 1-level lumbar disc herniation (LDH). Methods A total of 94 patients (54 men and 40 women) underwent discectomy and DIAM implantation for 1-level LDH, with a mean follow-up of 12.9 years (range, 6.3–15.3 years). The mean age was 46.2 years (range, 21–65 years). Sixty-two patients underwent DIAM implantation for L4–5, 27 for L5–6, and 5 for L3–4. Reoperations due to any reason associated with DIAM implantation level or adjacent levels were defined as failure and used as the end point of determining survivorship. Results During the 15-year follow-up, 8 patients (4 men and 4 women) underwent reoperation due to recurrence of LDH at the DIAM implantation level, a reoperation rate of 8.5%. The mean time to reoperation was 6.5 years (range, 0.8–13.9 years). Kaplan-Meier analysis showed a cumulative survival rate of the DIAM implantation of 97% at 5 years, 93% at 10 years, and 92% at 15 years after surgery; the cumulative reoperation rate of the DIAM implantation was 3% at 5 years, 7% at 10 years, and 8% at 15 years after surgery. Mean survival time was predicted to be 14.5 years (95% CI, 13.97–15.07). The log-rank test and Cox proportional hazard model showed that age, sex, and location did not significantly affect the reoperation rate of DIAM implantation. Conclusions Our results showed that DIAM implantation significantly decreased reoperation rate for LDH in the 15-year survivorship analysis. We suggest that DIAM implantation could be considered a useful intermediate step procedure for LDH surgery. To the best of our knowledge, this is the longest follow-up study in which surgical outcomes of interspinous device surgery were reported.

Evolution of a Polydisperse Ensemble of Ellipsoidal Crystals with Fluctuating Growth Rates in Supercooled Melts

In this paper, an analytical solution to the model of the evolution of ellipsoidal crystals with fluctuating growth rates at the intermediate step of bulk phase transition is presented. A complete system of integrodifferential equations describing the problem was derived and analytically solved using the Laplace integral method. The kinetics of supercooling removal in melts has been found. The particle-volume distribution function represents a pike-shaped curve decreasing its maximum with time. It is demonstrated the differences in the distribution function for ellipsoidal and spherical crystals.

ShapeFit: extracting the power spectrum shape information in galaxy surveys beyond BAO and RSD

In the standard (classic) approach, galaxy clustering measurements from spectroscopic surveys are compressed into baryon acoustic oscillations and redshift space distortions measurements, which in turn can be compared to cosmological models. Recent works have shown that avoiding this intermediate step and fitting directly the full power spectrum signal (full modelling) leads to much tighter constraints on cosmological parameters. Here we show where this extra information is coming from and extend the classic approach with one additional effective parameter, such that it captures, effectively, the same amount of information as the full modelling approach, but in a model-independent way. We validate this new method (ShapeFit) on mock catalogs, and compare its performance to the full modelling approach finding both to deliver equivalent results. The ShapeFit extension of the classic approach promotes the standard analyses at the level of full modelling ones in terms of information content, with the advantages of i) being more model independent; ii) offering an understanding of the origin of the extra cosmological information; iii) allowing a robust control on the impact of observational systematics.