We review the state of the art in the formulation, implementation, and performance of so-called high-order/low-order (HOLO) algorithms for challenging multiscale problems. HOLO algorithms attempt to ...couple one or several high-complexity physical models (the high-order model, HO) with low-complexity ones (the low-order model, LO). The primary goal of HOLO algorithms is to achieve nonlinear convergence between HO and LO components while minimizing memory footprint and managing the computational complexity in a practical manner. Key to the HOLO approach is the use of the LO representations to address temporal stiffness, effectively accelerating the convergence of the HO/LO coupled system. The HOLO approach is broadly underpinned by the concept of nonlinear elimination, which enables segregation of the HO and LO components in ways that can effectively use heterogeneous architectures. The accuracy and efficiency benefits of HOLO algorithms are demonstrated with specific applications to radiation transport, gas dynamics, plasmas (both Eulerian and Lagrangian formulations), and ocean modeling. Across this broad application spectrum, HOLO algorithms achieve significant accuracy improvements at a fraction of the cost compared to conventional approaches. It follows that HOLO algorithms hold significant potential for high-fidelity system scale multiscale simulations leveraging exascale computing.
EUS-guided fine-needle aspiration biopsy (EUS-FNA) is used increasingly for the diagnosis of mediastinal, biliopancreatic, and gastric tumors. However, little is known about EUS-FNA in hepatic ...lesions and the best method for tissue analysis. We assessed EUS-FNA combined with histological and cytological evaluation in selected patients.
41 patients (66 +/- 7 years) were prospectively studied, 33 of whom had clinical findings suggestive of liver malignancies. Selection for EUS-FNA was based on an increased risk of bleeding from percutaneous biopsy (coagulopathy, cirrhosis, ascites, aspirin intake; n = 15), presence of small liver tumors < 2 cm (n = 12), or liver lesions found incidentally (n = 14). Transgastric EUS-FNA of lesions located in accessible liver segments was performed using the Hitachi FG-34UX longitudinal echo endoscope and a 22-G aspiration needle. Specimens were submitted separately for standard cytological and histological evaluation. In the case of malignancies, findings at surgery with histological examination, endoscopy, or computed tomography (CT)-guided biopsy of the primary cancer served as reference results (n = 33), while in benign disorders, a combination of imaging studies (Magnetic Resonance Tomography , scintigraphy) and the clinical follow-up, as summarized in the physician's report, was used as reference.
EUS-FNA provided appropriate biopsy specimens in 40/41 patients. It was not possible to aspirate sufficient material in one patient. On average, 1.4 needle passes were necessary to obtain sufficient amounts of tissue. With regard to malignancy, the combination of histological and cytological examination had a sensitivity of 94%, specificity of 100%, negative predictive value (NPV) of 78%, and positive predictive value (PPV) of 100%. Tissue diagnoses were in agreement in 27/41 patients (65%). In the remaining patients, only the cytological examination identified six lesions correctly, while the histological assessment was correct in another seven patients. Malignant lesions were correctly identified by cytology in 24/33 (73%) patients, while histology alone was diagnostic for malignancy in 27/33 (82%) patients. When both modalities were combined, 31 out of 33-malignancies (94%) were correctly diagnosed. Minor complications occurred in two patients and consisted of self-limiting local bleeding.
EUS-FNA of liver tumors is a powerful, reliable, and safe procedure for the diagnosis of malignant liver lesions. Optimal diagnostic results are achieved by combining cytological with histological assessment. Hence, EUS-FNA is an alternative to percutaneous biopsy, particularly in patients at risk of bleeding or with small lesions of the liver.
Mitochondria are important in the function and control of Crassulacean acid metabolism (CAM) during organic acid accumulation at night and acid decarboxylation in the day. In plants of the malic ...enzyme-(ME) type and the phosphoenolpyruvate carboxykinase- (PEPCK) type, mitochondria may exert their role in the control of the diurnal rhythm of malic and citric acids to a differential degree. In plants of both CAM types, the oxidative capacity of mitochondria, as well as the activity of CAM-linked mitochondrial enzymes, and of the alternative and the rotenone-resistant pathways of substrate oxidation were compared. Furthermore, a C₃ succulent was included, as well as both C₃ and CAM forms ofMesembryanthemum crystallinumduring a salt-induced C₃-to-CAM shift. Mitochondria of PEPCK-type CAM plants exhibited a lower activity of malate oxidation, ratio of malate to succinate oxidation, and activity of mitochondrial NAD-ME. With the exception ofKalanchoë daigremontiana, leaf mitochondria of all other CAM species were highly sensitive to cyanide (80–100%), irrespective of the oxidant used. This indicates that the alternative oxidase is not of general importance in CAM. By contrast, rotenone-insensitive substrate oxidation was very high (50–90%) in all CAM species. This is the first comparison of the rotenone-insensitive pathway of respiration in plants with different CAM-types. The results of this study confirm that mitochondria are involved in the control of CAM to different degrees in the two CAM types, and they highlight the multiple roles of mitochondria in CAM.
Abstract:
Epidermal hydathodes were found on leaves of 46 of 48 species of CRASSULA collected from the Namib Desert in southern Africa. The possibility that these structures might allow the ...absorption of surface water was investigated in 27 species (including subspecies). The presence of hydathodes on leaf epidermi correlated, in most cases, with increases in leaf thickness and enhanced rates of nocturnal, and sometimes diurnal, CO
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uptake following wetting of the leaves during the night. The precise nature of these responses varied depending on the species. In addition, wetting only the older leaves on the lower portion of the shoot of C. TETRAGONA ssp. ACUTIFOLIA not only resulted in increased thickness of these leaves, but also effected an increase in leaf thickness and stimulation of CO
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uptake rates in the distal, younger portion of the shoot that was not wetted. Overall, foliar hydathodes were implicated in the absorption of surface water in many species of CRASSULA such that the ecophysiology of these desert succulents was positively affected. Although rainfall in the Namib Desert is infrequent, surface wetting of the leaves is a more common occurrence as a result of nighttime dew or fog deposition. Presumably, species with hydathodes benefit directly from this source of moisture. These findings have important implications in understanding a relatively unexplored adaptation of some xerophytes to an extremely arid environment.
Since the introduction in 2001 of M2A video capsule imaging of the small bowel in humans, this technique has been used increasingly in patients with disorders of the small bowel. In particular the ...assessment of small obscure gastrointestinal bleeding sources and the detection of shallow inflammatory lesions in the small bowel, have been greatly facilitated by this novel imaging procedure. We report two cases of patients with obscure gastrointestinal bleeding, in whom normal passage of the capsule through the antroduodenal junction was inhibited. This was because of delayed gastric emptying in both patients, which was presumably caused by functional impairment of pyloric motility. To facilitate capsule transport into the small bowel, after swallowing the capsule each patient underwent unsedated upper gastrointestinal endoscopy during which the capsule was grasped with a polypectomy snare, directly transported through the pylorus, and finally released upon arrival in the second portion of the duodenum. Capsule recordings revealed the source of bleeding in both patients and their medical or surgical treatment was subsequently escalated. Capsule imaging of the small bowel facilitated by esophagogastroduodenoscopy (EGD) is safe, and can be applied when patients have functional disorders of pyloric motility.
Surface incorporation of a liming agent in combination with compost or biosolids is a proven way to revegetate acidic minespoils, but little is known about the effect of the surface amendments on ...subsoil chemistry. We conducted a greenhouse column experiment to investigate how different surface amendments affected plant growth and subsoil chemistry in highly acidic minespoil material. Columns were filled with shale minespoil material (pH ≈ 2.5), amended with CaCO3, CaSO4·2H2O (gypsum), and two rates of compost, and seeded with birdsfoot trefoil (Lotus corniculatus L.) and ‘Kentucky 31’ tall fescue (Festuca arundinacea Schreb.). We measured leachate and plant growth over a 170-d period with extensive irrigation. Without CaCO3, plants could only grow at the high compost rate (68.8 g kg−1), even though the soil pH in those treatments was below 3.5, indicating the capability of natural organic matter to detoxify Al3+ by forming Al–organic matter complexes. Compost had no effect on the subsoil. When CaCO3 or gypsum was added to the surface, extractable Ca increased in the subsoil, but there was no relevant increase in subsoil pH. Even in the first 5 cm of subsoil material, extractable Al did not decrease very much, possibly because a jurbanite-like solid phase controlled subsoil Al3+ activities. During the reclamation of highly acidic minespoil material one should therefore not expect significant effects of the surface treatment on the untreated subsoil. A sufficient root zone would have to be achieved by incorporating the liming agent down to the desired rooting depth.
onitoring CAR transgene level in peripheral blood post tisa-cel infusion provides data on CAR-T cell expansion and persistence. We analyzed the impact of CAR persistence and B-cell aplasia on DOR in ...pts treated with tisa-cel. Transgene levels measured by qPCR were available from trials in r/r ALL (ELIANA, ENSIGN, NCT03123939, NCT01626495), DLBCL (JULIET), FL (ELARA), and long-term follow-up study (NCT02445222). Impact of duration of Tloss (time when transgene levels first dropped to <50 copies/µg DNA LLOQ after maximal expansion) and ongoing persistence beyond 1 year along with time to B-cell recovery (ALL: >1% CD19+ B-cells/WBC or >3% CD19+ B-cells/lymphocytes) on DOR/relapse were investigated
Long-term CAR persistence in tisa-cel-treated pts was observed for up to 9, 6, and 2.5 years for ALL, DLBCL, and FL, respectively, reflecting differing length of follow-up due to initiation of trials. In ALL, pts who lost transgene in ≤6 or 6-12 months (mo) had shorter DOR vs pts with persistent transgene (Fig). In ALL, median Tloss was 27.4, 18.2, 9.7, and 18 mo for ongoing CR >12 mo, CR pts between 6-12 mo, relapsed pts <12 mo, and relapsed pts >12 mo, respectively. In pts who lost transgene ≤6 mo, durable responses for ≥12 mo were maintained in some pts — ALL: 29%; DLBCL: 15%; FL: 50%. Among ALL-relapsed pts, 17/26 (65%) with Tloss at <6 mo showed B-cell recovery; 6 pts had Tloss at <6 mo and B-cell recovery but maintained response for ≥12 mo. In ALL, NGS MRD ≤6 mo to 1 year post infusion may be a more reliable predictor of potential relapse than B-cell recovery (Pulsipher MA et al., 2022). Median time to B-cell recovery was 266 days in relapsed/censored pts ≤12 mo but was not reached for pts with ongoing response at 12 mo. Of ALL pts with CAR persistence, longer DOR observed in pts (with <50% blasts) prior to tisa-cel infusion vs pts with ≥50% blasts reflect more resistant high-risk ALL at study entry or greater potential for stochastic loss of CD19 in higher disease burden pts. Long-term sustained remission was observed in tisa-cel–treated pts in pivotal trials. A positive association between CAR persistence and durable responses across indications was demonstrated; however, some pts maintained durable responses despite early loss of transgene and/or early B-cell recovery. In DLBCL and FL, the transgene levels in blood may not represent levels at target sites including lymph nodes. Also, persistence or Tloss are dependent on the duration of follow-up and LLOQ
This study examines the influence of cultural regions on the interdependence between delegation of authority and other management control (MC) practices. In particular, we assess whether one of the ...central contentions of agency theory, that incentive contracting and delegation are jointly determined, holds in different cultural regions. Drawing on prior literature, we hypothesise that the MC practices that operate as a complement to delegation vary depending on societal values and preferences, and that MC practices other than incentive contracting will complement delegation in firms in non-Anglo cultural regions. Using data collected from 584 strategic business units across three Western cultural regions (Anglo, Germanic, Nordic), our results show that the interdependence between delegation and incentive contracting is confined to Anglo firms. In the Nordic and Germanic regions, we find that strategic and action planning participation operate as a complement to delegation, while delegation is also complemented by manager selection in Nordic firms. Overall, our study demonstrates that cultural values and preferences significantly influence MC interdependence, and suggests that caution needs to be taken in making cross-cultural generalisations about the complementarity of MC practices.
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