Summary
Aim : The gastrointestinal transit of sequentially administered capsules was investigated in relation to the availability of fluid along the intestinal lumen by magnetic resonance imaging.
...Methods : Water‐sensitive magnetic resonance imaging was performed on 12 healthy subjects during fasting and 1 h after a meal. Specifiable non‐disintegrating capsules were administered at 7, 4 and 1 h prior to imaging.
Results : While food intake reduced the mean fluid volumes in the small intestine (105 ± 72 mL vs. 54 ± 41 mL, P < 0.01) it had no significant effect on the mean fluid volumes in the colon (13 ± 12 mL vs. 18 ± 26 mL). The mean number of separated fluid pockets increased in both organs after meal (small intestine: 4 vs. 6, P < 0.05; large intestine: 4 vs. 6, P < 0.05). The distribution of capsules between the small and large intestine was strongly influenced by food (colon: 3 vs. 17 capsules, P < 0.01).
Conclusions : The results show that fluid is not homogeneously distributed along the gut, which likely contributes to the individual variability of drug absorption. Furthermore, transport of fluid and solids through the ileocaecal valve is obviously initiated by a meal‐induced gastro‐ileocaecal reflex.
The demand for cooling devices has increased during the last years and this trend will continue. Adsorption‐driven chillers (ADCs) using water as the working fluid and low temperature waste energy ...for regeneration are an environmentally friendly alternative to currently employed cooling devices and can concurrently help to dramatically decrease energy consumption. Due to the ideal water sorption behavior and proven lifetime stability of Al(OH)(m‐BDC) ∙ x H2O (m‐BDC2− = 1,3‐benzenedicarboxylate), also denoted CAU‐10‐H, a green very robust synthesis process under reflux, with high yields up to 95% is developed and scaled up to 12 kg‐scale. Shaping of the adsorbent is demonstrated, which is important for an application. Thus monoliths and coatings of CAU‐10‐H are produced using a water‐based binder. The composites are thoroughly characterized toward their mechanical stability and water sorption behavior. Finally a full‐scale heat exchanger is coated and tested under ADC working conditions. Fast adsorption dynamic leads to a high power output and a good power density. A low regeneration temperature of only 70 °C is demonstrated, allowing the use of low temperature sources like waste heat and solar thermal collectors.
Metal–organic frameworks (MOFs) can be implemented as active materials in adsorption‐driven chillers. Therefore a green robust synthesis for the Al‐MOF CAU‐10‐H, scalable to 12 kg‐scale, is developed. Monoliths and coatings are produced using a water‐based binder and are investigated as composite material. Finally a full‐scale heat exchanger is coated and measured under adsorption‐driven chiller working conditions.
To establish a reliable machine learning model to predict malignancy in breast lesions identified by ultrasound (US) and optimize the negative predictive value to minimize unnecessary ...biopsies.PURPOSETo establish a reliable machine learning model to predict malignancy in breast lesions identified by ultrasound (US) and optimize the negative predictive value to minimize unnecessary biopsies.We included clinical and ultrasonographic attributes from 1526 breast lesions classified as BI-RADS 3, 4a, 4b, 4c, 5, and 6 that underwent US-guided breast biopsy in four institutions. We selected the most informative attributes to train nine machine learning models, ensemble models and models with tuned threshold to make inferences about the diagnosis of BI-RADS 4a and 4b lesions (validation dataset). We tested the performance of the final model with 403 new suspicious lesions.METHODSWe included clinical and ultrasonographic attributes from 1526 breast lesions classified as BI-RADS 3, 4a, 4b, 4c, 5, and 6 that underwent US-guided breast biopsy in four institutions. We selected the most informative attributes to train nine machine learning models, ensemble models and models with tuned threshold to make inferences about the diagnosis of BI-RADS 4a and 4b lesions (validation dataset). We tested the performance of the final model with 403 new suspicious lesions.The most informative attributes were shape, margin, orientation and size of the lesions, the resistance index of the internal vessel, the age of the patient and the presence of a palpable lump. The highest mean negative predictive value (NPV) was achieved with the K-Nearest Neighbors algorithm (97.9%). Making ensembles did not improve the performance. Tuning the threshold did improve the performance of the models and we chose the algorithm XGBoost with the tuned threshold as the final one. The tested performance of the final model was: NPV 98.1%, false negative 1.9%, positive predictive value 77.1%, false positive 22.9%. Applying this final model, we would have missed 2 of the 231 malignant lesions of the test dataset (0.8%).RESULTSThe most informative attributes were shape, margin, orientation and size of the lesions, the resistance index of the internal vessel, the age of the patient and the presence of a palpable lump. The highest mean negative predictive value (NPV) was achieved with the K-Nearest Neighbors algorithm (97.9%). Making ensembles did not improve the performance. Tuning the threshold did improve the performance of the models and we chose the algorithm XGBoost with the tuned threshold as the final one. The tested performance of the final model was: NPV 98.1%, false negative 1.9%, positive predictive value 77.1%, false positive 22.9%. Applying this final model, we would have missed 2 of the 231 malignant lesions of the test dataset (0.8%).Machine learning can help physicians predict malignancy in suspicious breast lesions identified by the US. Our final model would be able to avoid 60.4% of the biopsies in benign lesions missing less than 1% of the cancer cases.CONCLUSIONMachine learning can help physicians predict malignancy in suspicious breast lesions identified by the US. Our final model would be able to avoid 60.4% of the biopsies in benign lesions missing less than 1% of the cancer cases.
High-resolution large-eddy simulation is used to investigate the mean and turbulence properties of a separated flow in a channel constricted by periodically distributed hill-shaped protrusions on one ...wall that obstruct the channel by 33% of its height and are arranged 9 hill heights apart. The geometry is a modification of an experimental configuration, the adaptation providing an extended region of post-reattachment recovery and allowing high-quality simulations to be performed at acceptable computing costs. The Reynolds number, based on the hill height and the bulk velocity above the crest is 10595. The simulated domain is streamwise as well as spanwise periodic, extending from one hill crest to the next in the streamwise direction and over 4.5 hill heights in the spanwise direction. This arrangement minimizes uncertainties associated with boundary conditions and makes the flow an especially attractive generic test case for validating turbulence closures for statistically two-dimensional separation. The emphasis of the study is on elucidating the turbulence mechanisms associated with separation, recirculation reattachment, acceleration and wall proximity. Hence, careful attention has been paid to resolution, and a body-fitted, low-aspect-ratio, nearly orthogonal numerical grid of close to 5 million nodes has been used. Unusually, the results of two entirely independent simulations with different codes for identical flow and numerical conditions are compared and shown to agree closely. Results are included for mean velocity, Reynolds stresses, anisotropy measures, spectra and budgets for the Reynolds stresses. Moreover, an analysis of structural characteristics is undertaken on the basis of instantaneous realizations, and links to features observed in the statistical results are identified and interpreted. Among a number of interesting features, a distinct ‘splatting’ of eddies on the windward hill side following reattachment is observed, which generates strong spanwise fluctuations that are reflected, statistically, by the spanwise normal stress near the wall exceeding that of the streamwise stress by a substantial margin, despite the absence of spanwise strain.
Transition state theory suggests that enzymatic rate acceleration (k cat/k non) is related to the stabilization of the transition state for a given reaction. Chemically stable analogues of a ...transition state complex are predicted to convert catalytic energy into binding energy. Because transition state stabilization is a function of catalytic efficiency, differences in substrate specificity can be exploited in the design of tight-binding transition state analogue inhibitors. Coformycin and 2‘-deoxycoformycin are natural product transition state analogue inhibitors of adenosine deaminases (ADAs). These compounds mimic the tetrahedral geometry of the ADA transition state and bind with picomolar dissociation constants to enzymes from bovine, human, and protozoan sources. The purine salvage pathway in malaria parasites is unique in that Plasmodium falciparum ADA (PfADA) catalyzes the deamination of both adenosine and 5‘-methylthioadenosine. In contrast, neither human adenosine deaminase (HsADA) nor the bovine enzyme (BtADA) can deaminate 5‘-methylthioadenosine. 5‘-Methylthiocoformycin and 5‘-methylthio-2‘-deoxycoformycin were synthesized to be specific transition state mimics of the P. falciparum enzyme. These analogues inhibited PfADA with dissociation constants of 430 and 790 pM, respectively. Remarkably, they gave no detectable inhibition of the human and bovine enzymes. Adenosine deamination is involved in the essential pathway of purine salvage in P. falciparum, and prior studies have shown that inhibition of purine salvage results in parasite death. Inhibitors of HsADA are known to be toxic to humans, and the availability of parasite-specific ADA inhibitors may prevent this side-effect. The potent and P. falciparum-specific inhibitors described here have potential for development as antimalarials without inhibition of host ADA.
Large eddy simulations are presented for the flow in a periodic channel segment, which is laterally constricted by hill-shaped obstructions on one wall, having a height of 33% of the unconstricted ...channel. The Reynolds number, based on channel height, is 21,560. Massive separation thus arises on the hills’ leeward sides, the length of which is about 50% of that of the periodic segment. After reattachment, the flow is allowed to recover over about 30% of the segment length before being strongly accelerated over the windward side of the next hill. The principal challenge of this flow arises from the separation on the curved hill surface and the fact that the reattachment point, and hence the whole flow, are highly sensitive to the separation process. Simulations were performed with three grids, six subgrid-scale models and eight practices of approximating the near-wall region in simulations on the two coarser grids. These were supported by wall-resolved and wall-function simulations for fully-developed channel flow. The principal objective is to identify the sensitivity of the predictive accuracy to resolution and modelling issues. Coarse-grid simulations are judged by reference to data derived from two independent highly-resolved simulations obtained over identical meshes of close to 5 million nodes. Similarly, coarser-grid simulations were also performed with the two codes to enhance confidence in the results. The principal message emerging from the simulations is that grid resolution, especially in the streamwise direction around the mean separation position, has a very strong influence on the reattachment behaviour and hence the whole flow. This has serious implications for even more challenging high-Reynolds-number cases in which separation occurs from gently curved surfaces. The near-wall treatment, including the details of the numerical implementation of the wall laws, is also shown to be influential, most prominently on the coarsest grid. The application of the no-slip conditions at the wall at which separation occurs is found to cause substantial errors, especially in conjunction with poor streamwise resolution, even if the wall-nearest grid nodes are within the semi-viscous sublayer, in the range 5≲
y
+≲15. The sensitivity to subgrid-scale modelling is shown to be more modest, with those models returning relatively low subgrid-scale viscosity giving the closest accord with the highly-resolved simulation.
Exercise modulates metabolism and the gut microbiome. Brief exposure to low mT‐range pulsing electromagnetic fields (PEMFs) was previously shown to accentuate in vitro myogenesis and ...mitochondriogenesis by activating a calcium‐mitochondrial axis upstream of PGC‐1α transcriptional upregulation, recapitulating a genetic response implicated in exercise‐induced metabolic adaptations. We compared the effects of analogous PEMF exposure (1.5 mT, 10 min/week), with and without exercise, on systemic metabolism and gut microbiome in four groups of mice: (a) no intervention; (b) PEMF treatment; (c) exercise; (d) exercise and PEMF treatment. The combination of PEMFs and exercise for 6 weeks enhanced running performance and upregulated muscular and adipose Pgc‐1α transcript levels, whereas exercise alone was incapable of elevating Pgc‐1α levels. The gut microbiome Firmicutes/Bacteroidetes ratio decreased with exercise and PEMF exposure, alone or in combination, which has been associated in published studies with an increase in lean body mass. After 2 months, brief PEMF treatment alone increased Pgc‐1α and mitohormetic gene expression and after >4 months PEMF treatment alone enhanced oxidative muscle expression, fatty acid oxidation, and reduced insulin levels. Hence, short‐term PEMF treatment was sufficient to instigate PGC‐1α‐associated transcriptional cascades governing systemic mitohormetic adaptations, whereas longer‐term PEMF treatment was capable of inducing related metabolic adaptations independently of exercise.
Three hexamethylenetetramine (HMTA) metal nitrate complexes such as M(H
2
O)
4
(H
2
O-HMTA)
2
(NO
3
)·4H
2
O (where
M
=Co, Ni and Zn) have been prepared and characterized by X-ray crystallography. ...Their thermal decomposition have been studied by using dynamic, isothermal thermogravimery (TG) and differential thermal analysis (DTA). Kinetics of thermal decomposition was undertaken by applying model-fitting as well as isoconversional methods. The possible pathways of thermolysis have also been proposed. Ignition delay measurements have been carried out to investigate the response of these complexes under condition of rapid heating.
Preservation of the hip joint function by treatment of the avascular necrosis of the femoral head in adults or at least avoiding progression.
Avascular necrosis of the femoral head in adults in ...Steinberg stages I-III. In patients with Steinberg stage IVa (subchondral collapse ≤ 15% of the articular surface, depression < 2 mm) hip joint salvage therapy in early stages of femoral head collapse.
Manifest osteoarthritis of the hip joint. Joint infection. Relative contraindications: subchondral collapse > 15% of the articular surface or depression > 2 mm (Steinberg stage IVb and above). Persisting risk factors for a progression of avascular necrosis (e.g., alcohol abuse, chemotherapy, local irradiation, high-dose cortisone therapy) and obesity (BMI > 40).
Arthroscopy of the hip joint in case of cartilage defects and/or potential collapse of the femoral head. Without collapse of the femoral head and absence of severe damage of the cartilage: core decompression using a guiding sleeve through a lateral approach (Steinberg II, III). Subsequently curettage of the necrotic area through a central drill hole and insertion of autogenic bone cylinders using an OATS harvester (Steinberg II b/c, III b/c). In Steinberg stage IVa, reconstruction of the outline of the femoral head is attempted by reduction of the impressed portion (under intraoperative fluoroscopy).
Limited weight bearing (10 kg) of the operated leg for 6 weeks. In cases of large necrotic defects located directly beneath the subchondral bone (Steinberg IIIc) as well as subchondral collapse with flattening of the femoral head (Steinberg IVa) limited weight bearing (10 kg) for 12 weeks.
Early results of femoral head preserving therapy in 53 patients (56 hips, consecutively treated between June 2004 and December 2009) after 33 ± 20 months: success rate (no arthroplasty, no reoperation, no radiological progress associated with clinical symptoms) 86% for patients treated with Steinberg stages I-III. Failure of the head preserving therapy with concern to the mentioned criteria depending on the initial Steinberg stage: 0 (0%) for stage I, 2 (10%) for stage II, 3 (25%) for stage III, and 4 (31%) for stage IVa.
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