A kinetic study of mechanically activated atom exchange: the effect of milling frequency and ball mass.

This study investigates the mechanochemical reaction of hydrogen isotope exchange between solid benzoic acid and liquid heavy water. The systematic change of milling conditions revealed that the reaction rate scales with the milling frequency and the mass of the milling balls. The ball size being always the same, faster reactions stem from the use of higher milling frequencies and heavier balls. The kinetic curves are described by a kinetic model that accounts for the statistical, deformational and chemical factors involved in mechanochemical transformations. The results indicate that the reaction is driven by the generation of a new interface area caused by the deformation of the solid reactants.

Mechanochemical ignition of self-propagating reactions in equimolar Al-Ni powder mixtures and multilayers.

This work addresses a long standing question in the field of mechanochemistry, namely the role of mesostructure in the initiation of self-propagating high-temperature reactions in exothermic chemical systems, commonly referred to as ignition. In an attempt to find robust evidence in this regard, we compare the ignition behaviour of equimolar Al-Ni powder mixtures and equimolar Al-Ni multilayers. To achieve the best possible control of experimental conditions and allowing high reproducibility, we used elemental powders sieved in the range between 20 µm and 44 µm, and multilayers with bi-layer thickness between 10 nm and 800 nm. We carried out systematic ball milling experiments involving pristine powder mixtures and multilayers as well as a mix of pristine material and material prone to ignition suitably prepared. Experimental findings suggest that pristine powder mixtures and multilayers with bi-layer thickness of 240 nm have analogous ignition behaviour. Along the same lines, data suggest that pristine powder mixtures undergo ignition when they attain a mesostructure similar to that of multilayers with bi-layer thickness of 10 nm.

Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project.

BACKGROUND: A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating. Knowing which tools are most effective remains unclear. To evaluate the performance of computational methods, and to encourage innovation in method development, we designed a Critical Assessment of Genome Interpretation (CAGI) community challenge to place variant prioritization models head-to-head in a real-life clinical diagnostic setting. METHODS: We utilized genome sequencing (GS) data from families sequenced in the Rare Genomes Project (RGP), a direct-to-participant research study on the utility of GS for rare disease diagnosis and gene discovery. Challenge predictors were provided with a dataset of variant calls and phenotype terms from 175 RGP individuals (65 families), including 35 solved training set families with causal variants specified, and 30 unlabeled test set families (14 solved, 16 unsolved). We tasked teams to identify causal variants in as many families as possible. Predictors submitted variant predictions with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on the rank position of causal variants, and the maximum F-measure, based on precision and recall of causal variants across all EPCR values. RESULTS: Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performers recalled causal variants in up to 13 of 14 solved families within the top 5 ranked variants. Newly discovered diagnostic variants were returned to two previously unsolved families following confirmatory RNA sequencing, and two novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant in an unsolved proband with phenotypes consistent with asparagine synthetase deficiency. CONCLUSIONS: Model methodology and performance was highly variable. Models weighing call quality, allele frequency, predicted deleteriousness, segregation, and phenotype were effective in identifying causal variants, and models open to phenotype expansion and non-coding variants were able to capture more difficult diagnoses and discover new diagnoses. Overall, computational models can significantly aid variant prioritization. For use in diagnostics, detailed review and conservative assessment of prioritized variants against established criteria is needed.

Mechanochemically Induced Solid-State Transformations of Levofloxacin.

Levofloxacin hemihydrate (LVXh) is a complex fluoroquinolone drug that exists in both hydrated and anhydrous/dehydrated forms. Due to the complexity of such a compound, the primary aim of this study was to investigate the amorphization capabilities and solid-state transformations of LVXh when exposed to mechanical treatment using ball milling. Spray drying was utilized as a comparative method for investigating the capabilities of complete LVX amorphous (LVXam) formation. The solid states of the samples produced were comprehensively characterized by powder X-ray diffraction, thermal analysis, infrared spectroscopy, Rietveld method, and dynamic vapor sorption. The kinetics of the process and the quantification of phases at different time points were conducted by Rietveld refinement. The impact of the different mills, milling conditions, and parameters on the composition of the resulting powders was examined. A kinetic investigation of samples produced using both mills disclosed that it was in fact possible to partially amorphize LVXh upon mechanical treatment. It was discovered that LVXh first transformed to the anhydrous/dehydrated form γ (LVXγ), as an intermediate phase, before converting to LVXam. The mechanism of LVXam formation by ball milling was successfully revealed, and a new method of forming LVXγ and LVXam by mechanical forces was developed. Spray drying from water depicted that complete amorphization of LVXh was possible. The amorphous form of LVX had a glass transition temperature of 80 °C. The comparison of methods highlighted that the formation of LVXam is thus both mechanism- and process-dependent. Dynamic vapor sorption studies of both LVXam samples showed comparable stability properties and crystallized to the most stable hemihydrate form upon analysis. In summary, this work contributed to the detailed understanding of solid-state transformations of essential fluoroquinolones while employing greener and more sustainable manufacturing methods.

Machine Learning-Supported Diagnosis of Small Blue Round Cell Sarcomas Using Targeted RNA Sequencing.

Small blue round cell sarcomas (SBRCSs) are a heterogeneous group of tumors with overlapping morphologic features but markedly varying prognosis. They are characterized by distinct chromosomal alterations, particularly rearrangements leading to gene fusions, whose detection currently represents the most reliable diagnostic marker. Ewing sarcomas are the most common SBRCSs, defined by gene fusions involving EWSR1 and transcription factors of the ETS family, and the most frequent non-EWSR1-rearranged SBRCSs harbor a CIC rearrangement. Unfortunately, currently the identification of CIC::DUX4 translocation events, the most common CIC rearrangement, is challenging. Here, we present a machine-learning approach to support SBRCS diagnosis that relies on gene expression profiles measured via targeted sequencing. The analyses on a curated cohort of 69 soft-tissue tumors showed markedly distinct expression patterns for SBRCS subgroups. A random forest classifier trained on Ewing sarcoma and CIC-rearranged cases predicted probabilities of being CIC-rearranged >0.9 for CIC-rearranged-like sarcomas and <0.6 for other SBRCSs. Testing on a retrospective cohort of 1335 routine diagnostic cases identified 15 candidate CIC-rearranged tumors with a probability >0.75, all of which were supported by expert histopathologic reassessment. Furthermore, the multigene random forest classifier appeared advantageous over using high ETV4 expression alone, previously proposed as a surrogate to identify CIC rearrangement. Taken together, the expression-based classifier can offer valuable support for SBRCS pathologic diagnosis.

Critical assessment of variant prioritization methods for rare disease diagnosis within the Rare Genomes Project.

Background: A major obstacle faced by rare disease families is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years, and causal variants are identified in under 50%. The Rare Genomes Project (RGP) is a direct-to-participant research study on the utility of genome sequencing (GS) for diagnosis and gene discovery. Families are consented for sharing of sequence and phenotype data with researchers, allowing development of a Critical Assessment of Genome Interpretation (CAGI) community challenge, placing variant prioritization models head-to-head in a real-life clinical diagnostic setting. Methods: Predictors were provided a dataset of phenotype terms and variant calls from GS of 175 RGP individuals (65 families), including 35 solved training set families, with causal variants specified, and 30 test set families (14 solved, 16 unsolved). The challenge tasked teams with identifying the causal variants in as many test set families as possible. Ranked variant predictions were submitted with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on rank position of true positive causal variants and maximum F-measure, based on precision and recall of causal variants across EPCR thresholds. Results: Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performing teams recalled the causal variants in up to 13 of 14 solved families by prioritizing high quality variant calls that were rare, predicted deleterious, segregating correctly, and consistent with reported phenotype. In unsolved families, newly discovered diagnostic variants were returned to two families following confirmatory RNA sequencing, and two prioritized novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant, in an unsolved proband with phenotype overlap with asparagine synthetase deficiency. Conclusions: By objective assessment of variant predictions, we provide insights into current state-of-the-art algorithms and platforms for genome sequencing analysis for rare disease diagnosis and explore areas for future optimization. Identification of diagnostic variants in unsolved families promotes synergy between researchers with clinical and computational expertise as a means of advancing the field of clinical genome interpretation.

Mechanochemical Reactions from Individual Impacts to Global Transformation Kinetics.

Typically induced by the mechanical processing of powders in ball mills, mechanochemical transformations are considered to result from the application of mechanical force to solid reactants. However, the undeniable deep connection between the dynamic compaction of powders during impacts and the overall transformation degree has yet to be disclosed. In the present work, we show that the square planar bis(dibenzoylmethanato)NiII coordination compound undergoes trimerization when its powder experiences even a single ball impact. Based on systematic experiments with individual ball impacts and analysis by Raman spectroscopy, we provide here quantitative mapping of the transformation in the powder compact and deduce bulk reaction kinetics from multiple individual impacts.

Mechanochemical effects underlying the mechanically activated catalytic hydrogenation of carbon monoxide.

In this work, we highlight and measure the intensity of mechanochemical effects at work in the hydrogenation of carbon monoxide by comparing the activity of a supported Co-Fe catalyst subjected, respectively, to ball milling and simple powder agitation. Paying due regard to the discontinuous nature of ball milling, we show that mechanochemical hydrogenation proceeds at significantly higher rate and disclose its connection with individual impacts. Experimental evidence suggests that the enhanced catalytic activity we observe can be ascribed to local processes affecting the amount of powder that gets involved in individual impacts.

Extending the Hammett correlation to mechanochemical reactions.

Using Raman in situ monitoring and mechanochemistry-specific kinetic analysis, we find a correlation between the reaction probability and the Hammett constants in a model mechanochemical reaction of imine formation, indicating that the body of knowledge developed in physical-organic chemistry could be transferable to ball milling reactions in the solid state.

Mechanochemical reaction kinetics scales linearly with impact energy.

Inelastic collisions of the milling media in ball milling provide energy to the reaction mixture required for chemical transformations. However, movement of the milling media also results in physical mixing of reactants, which may enable a chemical reaction too. Separating the two contributions is challenging and gaining a direct insight into the purely mechanochemically driven reactivity is accordingly hindered. Here, we have applied in situ reaction monitoring by Raman spectroscopy to a suitable, purely mechanically activated, chemical reaction and combined kinetic analysis with numerical simulations to access experimentally unattainable milling parameters. The breadth of milling conditions allows us to establish a linear relationship between the reaction rate and the energy dose received by the sample. Consequently, different kinetic profiles in time scale to the same profile when plotted against the energy dose, which increases with the ball mass, the average ball velocity and the frequency of impacts, but decreases with the hardness of the milling media due to more elastic collisions. The fundamental relationship between kinetics and energy input provides the basis for planning and optimisation of mechanochemical reactions and is essential for transferability of mechanochemical reactions across different milling platforms.

Chemical effects induced by the mechanical processing of granite powder.

Starting from 1970s, the use of mechanical forces to induce chemical transformations has radically changed vast areas of metallurgy and materials science. More recently, mechanochemistry has expanded to core sectors of chemistry, showing the promise to deeply innovate chemical industry while enhancing its sustainability and competitiveness. We are still far, however, from unveiling the full potential of mechanical activation. This study marks a step forward in this direction focusing on the chemical effects induced on the surrounding gaseous phase by the mechanical processing of granite. We show that fracturing granite blocks in oxygen can result in the generation of ozone. The refinement of coarse granite particles and the friction between fine ones are also effective in this regard. Combining experimental evidence related to the crushing of large granite samples by uniaxial compression and the ball milling of coarse and fine granite powders, we develop a model that relates mechanochemical ozone generation to the surface area effectively affected by fracture and frictional events taking place during individual impacts. We also extend the investigation to gaseous phases involving methane, oxygen, benzene and water, revealing that chemical transformations occur as well.

A phenomenological kinetic equation for mechanochemical reactions involving highly deformable molecular solids.

With its ability to enable solvent-free chemical reactions, mechanochemistry promises to open new and greener synthetic routes to chemical products of industrial interest. Its practical exploitation requires understanding the relationships between processing variables, powders' mechanical behaviour, and chemical reactivity. To this aim, rationalizing experimental kinetics is of paramount importance. In this work, we propose a phenomenological kinetic model that could help experimentalists to disentangle the mechanical, chemical, and statistical factors underlying mechanochemical reactions. The model takes into account the statistical nature of ball milling and relates the global kinetic curve that can be obtained experimentally to the deformation and chemical processes that occur on the mesoscopic and microscopic scales during individual impacts. We show that our model equations can satisfactorily best fit experimental datasets, providing information on the underlying mechanochemistry.

Prebiotic Therapy with Inulin Associated with Low Protein Diet in Chronic Kidney Disease Patients: Evaluation of Nutritional, Cardiovascular and Psychocognitive Parameters.

A relationship between dysbiotic gut microbiome and chronic kidney disease (CKD) has been recently documented; it contributes to CKD-related complications, including cardiovascular disease. Aim: We tested how a low-protein diet (LPD)-with or without oral inulin supplementation as a prebiotic-modulates some inflammatory, atherosclerosis and endothelial dysfunction indices and nutritional markers, as well as psychocognitive functions in CKD patients. We conducted a prospective, case-control study on CKD patients on conservative therapy, divided in two groups: the intervention group treated with LPD (0.6 g/kg/day) plus inulin (19 g/day) and a control group treated with LPD without inulin, for six consecutive months. Clinical and hematochemical parameters as well as instrumental, and psychocognitive assessments (by SF-36 survey and MMSE, HAM-D, BDI-II) were recorded in all the participants at baseline (T0), at three months (T1) and at six months (T2). A total of 41 patients were enrolled: 18 in the intervention group and 23 in the control group. At T2, in both groups, we observed a significant reduction of serum nitrogen and phosphorus (p ≤ 0.01) and serum uric acid (p ≤ 0.03), and an improvement in metabolic acidosis (bicarbonates, p ≤ 0.01; base excess, p ≤ 0.02). Moreover, at T2 the intervention group showed a reduction in serum insulin (p = 0.008) and fasting glucose levels (p = 0.022), HOMA-IR (p = 0.004), as well as lower total serum cholesterol (p = 0.012), triglycerides (p = 0.016), C-reactive protein (p = 0.044) and homocysteine (p = 0.044) and higher HDL (p < 0.001) with respect to baseline. We also observed a significant amelioration of some quality of life and functional status indices (SF-36 survey) among the intervention group compared to controls, without a significant improvement in the cognitive state (MMSE). On the other hand, an amelioration in mood (by HAM-D and BDI-II) was found in the intervention group and in controls (only by BID-II). In conclusion, LPD in association with oral inulin supplementation improved glycemic and lipid metabolism and ameliorated the systemic inflammatory state, likely reducing cardiovascular risk in CKD patients and this may represent a promising therapeutic option, also improving quality of life and mood.

Kinetics of mechanochemical transformations.

The use of mechanical forces to activate and drive chemical transformations in solid particulate is attracting remarkable interest in the light of its promising application in a wide spectrum of strategic areas ranging from materials science to fine chemical synthesis and pharmaceutical ingredient production. The capability of enabling solventless processes and fabricating unique materials inaccessible otherwise has made mechanochemistry one of the ten chemical innovations with the highest potential of changing the world. As in the past, so again now, the development of reliable technologies based on mechanochemical transformations cannot be separated from the understanding of the underlying mechanisms, their description and their control. To this aim, in this work we propose a kinetic model that relates macroscopic and microscopic scales while accounting for the statistical nature of the mechanical processing of powder. We discuss several specific case studies and develop the pertinent kinetic equations, showing how they can be used to best fit the experimental data and obtain insight into the microscopic features of mechanical activation.

Urinary [TIMP-2] × [IGFBP7] and serum procalcitonin to predict and assess the risk for short-term outcomes in septic and non-septic critically ill patients.

BACKGROUND: Biomarkers can play a critical role by facilitating diagnosis and stratification of disease, as well as assessment or prediction of disease severity. Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 product ([TIMP-2] × [IGFBP7]) predict the development and progression of AKI and recently procalcitonin (PCT), a widely used biomarker for sepsis diagnosis and management, has been associated with AKI occurrence in ICU patients. To assess combinations of [TIMP-2] × [IGFBP7] and PCT results for prediction and risk stratification of short-term outcomes in septic and non-septic patients, a retrospective cohort analysis of critically ill patients was performed in a multidisciplinary ICU. ROC curve analysis was used in order to evaluate predictive performance of combined results of [TIMP-2] × [IGFBP7] and PCT at the time of admission for AKI development. To verify the utility of adding [TIMP-2] × [IGFBP7] and PCT results for risk assessment, we evaluated the predictive value of having a single-marker positivity compared to a double-marker positivity using the widely used cut-off of 0.3 (ng/mL)2/1000 for [TIMP-2] × [IGFBP7] and 0.5 µg/L for PCT. Risk assessment for AKI occurrence within 48 h, acute kidney disease (AKD) and mortality at 7 days was performed by logistic/Cox regression analysis. RESULTS: 433 patients were analysed, of whom 168 had AKI within 48 h (93 septic and 65 non-septic patients). Combination of [TIMP-2] × [IGFBP7] and PCT showed a good predictive ability for AKI occurrence (AUC 0.81, 95% CI 0.77-0.86, p < 0.001, Sens 78%, Spec 73%). Combinations of biomarkers increased the odd ratios (OR) considerably. A single-marker positivity showed a fourfold risk increase, while the double-marker positivity a 26-fold risk increase for AKI occurrence. Moreover, the double-marker positivity showed an elevated risk for AKD at 7 days in non-septic patients (OR 15.9, 95% CI 3,21-73,57, p < 0.001) and for mortality within 7 days in septic patients (HR 4.1, 95% CI 1.4-11.8, p = 0.001). CONCLUSIONS: Although combining the results of [TIMP-2] × [IGFBP7] and PCT may be a useful tool to identify and stratify ICU patients at high risk for septic AKI and short-term adverse outcomes, data should be confirmed in a large prospective study.

α-lipoic acid in patients with autosomal dominant polycystic kidney disease.

OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease characterized by multiple and bilateral cystic dilation of renal tubules. Hypertension, endothelial dysfunction, systemic inflammation, and accelerated atherosclerosis are alterations found at a very early stage of the disease and are responsible for increasing both cardiovascular risks and progression toward end-stage renal disease. The aim of the study was to evaluate the effects of the use of 1.6 g α-lipoic acid (ALA) daily for 3 and 6 on the main markers of systemic inflammation, endothelial dysfunction, and atherosclerosis, as well as on nutritional, cardiovascular, and psychocognitive parameters, in ADPKD patients with CKD stage G2/G3 Kidney Disease Improving Global Outcomes chronic kidney disease (KDIGO) compared to controls. METHODS: This was a controlled, longitudinal, prospective, interventional study with 59 patients with ADPKD. Of the patients, 33 were treated with ALA (1.6 g/d) for 6 mo and 26 were controls. Clinical, laboratory (inflammation and metabolic indexes), instrumental parameters (intima media thickness (IMT), renal resistive index (RRI), flow-mediated dilation (FMD), ankle-brachial index (ABI), and psycho-cognitive tests (Mini-Mental State Examination [MMSE], Hamilton Depression Rating Scale [HAM-D], Beck Depression Inventory-II [BDI-II]) were evaluated at baseline (T0), 3 mo (T1), and 6 mo (T2). RESULTS: Patients treated with ALA at T1 and T2 showed a significant reduction in serum glucose, insulin, homeostatic model assessment-insulin resistance, and serum uric acid (P = 0.013, P = 0.002, P = 0.002, P <0.001; respectively) and significantly higher values of base excess (P < 0.001), compared with the control group. Moreover, the results showed a significant increase in bicarbonates (P = 0.009) and FMD (P < 0.001), and a significant reduction of C-reactive protein (P <0.001) and RRI (P = 0.013). On the other hand, we did not assess a significant difference in IMT and ABI at T1 and T2. Psychocognitive tests (BDI-II, HAM-D, and MMSE) were significantly improved (P = 0.007, P < 0.001, P < 0.001; respectively) in patients treated with ALA for 6 mo compared with the control group. A significant difference in nicotinamide adenine dinucleotide phosphate oxidase 2 concentrations was observed between T0 and T2 only in ADPKD patients treated with ALA (P = 0.039, P = 0.039; respectively), although we did not find a significant difference in interleukin-6, interleukin -1ß, and tumor necrosis factor-α concentrations in either group. CONCLUSIONS: We suggest an early and careful monitoring of traditional and non-traditional cardiovascular risk factors in patients with ADPKD. Moreover, we suggest the use of ALA, an anti-inflammatory and antioxidant nutraceutical with few side effects. Additionally, it is important to evaluate the cognitive abilities, psychological health, and quality of life of patients with ADPKD, especially at the early stage of disease.

Routine Adoption of Urinary [IGFBP7]∙[TIMP-2] to Assess Acute Kidney Injury at Any Stage 12 hours After Intensive Care Unit Admission: a Prospective Cohort Study.

The urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]∙[IGFBP7]) have been introduced to improve risk prediction of severe acute kidney injury (AKI) within 12 hours of measurement. We performed a prospective cohort study to evaluate if the predictive value of [TIMP-2]∙[IGFBP7] for AKI might continue after 12 hours. We enrolled 442 critically ill adult patients from June to December 2016. Urine samples were collected at admission for [TIMP-2]∙[IGFBP7] measurement. Baseline patient characteristics were recorded including patients' demographics, prior health history, and the main reason for admission to build a logistic regression model to predict AKI. AKI occurrence differed between patients with [TIMP-2]∙[IGFBP7] ≤0.3 and >0.3 (ng/ml)2/1000 (31.9% and 68.10% respectively; p < 0.001). Patients with AKI had higher biomarker values compared to those without AKI (0.66 (0.21-2.84) vs 0.22 (0.08-0.63) (ng/ml)2/1000; p < 0.001). [TIMP-2]∙[IGFBP7] at ICU admission had a lower performance in predicting AKI at any stage within 48 hours and 7 days after measurement (area under the receiver operating characteristic curve (AUC) equal to 0.70 (95%CI 0.65-0.76), AUC 0.68 (95%CI 0.63-0.73)). In the logistic regression model, 0.1 (ng/ml)2/1000-unit increment was likely to increase the risk of AKI by 2% (p = 0.002).

The Relationships between Physical Activity, Self-Efficacy, and Quality of Life in People with Multiple Sclerosis.

Regular physical activity (PA) can enhance the physical and mental health of people with Multiple Sclerosis (MS) because of its impact on muscular strength, mobility, balance, walking, fatigue, pain and health-related quality of life (HRQoL). Previous studies have hypothesized that the relationship between PA and HRQoL is mediated by self-efficacy. The aim of this research is to evaluate whether self-efficacy in goal setting and self-efficacy in the management of symptoms, mediate the relationship between PA and HRQoL, in a similar way to exercise self-efficacy. A sample of 28 participants with MS (18 females) and different levels of physical activity have been recruited and completed the following measures: a) physical activity (GLTEQ); b) health-related quality of life (SF-12); c) self-efficacy in the management of Multiple Sclerosis (SEMS) and, d) exercise self-efficacy (EXSE). The statistical analysis highlighted that self-efficacy in goal setting mediated the relationship between PA and mental health better than exercise self-efficacy. Our findings suggest that self-efficacy in goal setting can contribute to the adoption and maintenance of regular physical activity for long-lasting times, supporting and increasing the mental quality of life of people suffering from MS.

Phenomenological Inferences on the Kinetics of a Mechanically Activated Knoevenagel Condensation: Understanding the "Snowball" Kinetic Effect in Ball Milling.

We focus on understanding the kinetics of a mechanically activated Knoevenagel condensation conducted in a ball mill, that is characterized by sigmoidal kinetics and the formation of a rubber-like cohesive intermediate state coating the milling ball. The previously described experimental findings are explained using a phenomenological kinetic model. It is assumed that reactants transform into products already at the very first collision of the ball with the wall of the jar. The portion of reactants that are transformed into products during each oscillation is taken to be a fraction of the amount of material that is trapped between the ball and the wall of the jar. This quantity is greater when the reaction mixture transforms from its initial powder form to the rubber-like cohesive coating on the ball. Further, the amount of reactants processed in each collision varies proportionally with the total area of the layer coating the ball. The total area of this coating layer is predicted to vary with the third power of time, thus accounting for the observed dramatic increase of the reaction rate. Supporting experiments, performed using a polyvinyl acetate adhesive as a nonreactive but cohesive material, confirm that the coating around the ball grows with the third power of time.

Development and validation of quick Acute Kidney Injury-score (q-AKI) to predict acute kidney injury at admission to a multidisciplinary intensive care unit.

AKI is associated with increased risk of death, prolonged length of stay and development of de-novo chronic kidney disease. The aim of our study is the development and validation of prediction models to identify the risk of AKI in ICU patients up to 7 days. We retrospectively recruited 692 consecutive patients admitted to the ICU at San Bortolo Hospital (Vicenza, Italy) from 1 June 2016 to 31 March 2017: 455 patients were treated as the derivation group and 237 as the validation group. Candidate variables were selected based on a literature review and expert opinion. Admission eGFR< 90 ml/min /1.73 mq (OR 2.78; 95% CI 1.78-4.35; p<0.001); SOFAcv ≥ 2 (OR 2.23; 95% CI 1.48-3.37; p<0.001); lactate ≥ 2 mmol/L (OR 1.81; 95% CI 1.19-2.74; p = 0.005) and (TIMP-2)•(IGFBP7) ≥ 0.3 (OR 1.65; 95% CI 1.08-2.52; p = 0.019) were significantly associated with AKI. For the q-AKI score, we stratified patients into different AKI Risk score levels: 0-2; 3-4; 5-6; 7-8 and 9-10. In both cohorts, we observed that the proportion of AKI patients was higher in the higher score levels.