Location Of Sites Research Articles

Flow boiling heat transfer enhancement of R134a in additively manufactured minichannels with microengineered surfaces

Additive manufacturing (AM) of metal components has opened new frontiers in heat transfer applications owing to its wide design freedom, which enables previously unexplored geometries with enhanced thermal performance to be developed. Open minichannels, on the other hand, consist of an extra manifold situated above the common flow channels, have been demonstrated to effectively reduce pressure drop and two-phase flow instability by mitigating backflow and maldistribution. In this paper, we synergized open minichannel design methodology with an ultrascalable surface microstructuring method for AM AlSi10Mg to improve flow boiling heat transfer performance of R134a. Experiments were conducted at the refrigerant mass flow rates (ṁ) of 0.005 kg/s to 0.01 kg/s (corresponding to mass fluxes of 73 to 146 kg/m2⋅s), and effective heat fluxes (qeff) of 1.8 kW/m2 to 141 kW/m2, by supplying 2 ℃ subcooled liquid to the minichannel inlet at saturation pressure (Psat) of 7.27 bar. The effects of heat flux, nucleation site density, mass flow rate and location of nucleation sites on the harmonic-average heat transfer coefficient (have) and pressure drop (ΔP) along the flow direction are investigated and compared against a conventionally manufactured (Al6061) counterpart. Our results show that the proposed etching process significantly improves the cooling performance of AM microstrucured minichannels, resulting in 210% higher have than Al6061 with negligible pressure drop penalty. The flow visualization results reveal a sequential order of nucleation site activation with increasing heat flux for microstructured open minichannels, which starts from the top of fins, followed by the corners and other three surfaces within the channels. This also results in the non-negligible effects of mass flow rate on cooling performance for microstructured minichannels, with approximately 10%–66% higher have at the lowest mass flow rate. Besides, the pressure drop penalty resulting from plain AM rough surface is also reduced by up to 13% through the proposed microstructuring process. In all, this work not only successfully identifies the dominant mechanisms in AM microstructured open minichannels, but it also provides useful minichannel design guidelines for high-performance two-phase cooling devices by AM.

Accuracy of gravity based automatic infusion system applied to chemoport for intravenous infusion.

191 Background: When a vesicant drug is administered to the peripheral vein, a gravity drip method rather than an peristaltic infusion pump is recommended. In addition, it is reported that the gravity based pump has less particle generation than the peristaltic pump that injects fluid through constant peristaltic movement. However, it is pointed out that the disadvantage of gravity based pump is that the rate of administration can easily change according to the change in the location of the injection site. We evaluate the accuracy of new gravity based pump (pressure-sensitive speed control fluid injection device, Accudrip made by Hanvit MD ) at various injection rates and hanging heights common to hospital settings. Methods: The accuracy and safety of the intravenous (IV) flow controller were evaluated for patients receiving IV chemotherapy in the oncology department. It was verified whether the accurate injection rate could be maintained even in various fluid heights, fluid amounts, and types of anticancer drugs that could affect the injection rate. Various anticancer drugs, including immune checkpoint inhibitor, were mixed with 250 ml/500 ml of normal saline and administered for 30 min/60 min, and glucose 500 ml/1000 ml was administered for 60 min/120 min to measure accuracy, each progressed 25 times. Medical staff were surveyed on the ease and limitations of medical practice for each peristaltic infusion pump and new gravity based pump. In addition, side effects occurring in patients during fluid administration were recorded. Results: The mean degree of error in the estimated end time of gravity based automatic infusion system was 3.09% (2.09 ~ 4.10). The error of the gravity based automatic infusion system was statistically significant depending on the patient age (p=.001) and the infusion time (p=.016), but the degree of error according to the type of fluids (p=.302) and fluid concentration (p=.844) was not statistically significant. Among the subjects of the study, nurses' satisfaction with the application of gravity based pump was 4.10 (±0.62) out of 5, and among the general characteristics of nurses, age ( p<.078), and working department (p<.91) did not show a statistically significant difference, but work experience ( p <.021) showed a statistically significant difference. Conclusions: The accuracy of Gravity based automatic infusion system was determined because the degree of error in the expected end time of infusion was not significant according to the infusion variable. In a survey of nurses who have used gravity based pump directly, it was found that the ease of use and satisfaction were similar to those of the conventional peristaltic pump. These findings will contribute greatly to the precise drug administration (over or under-administration) and minimization of adverse events in real-world hospital settings.

Intratumoral Chemotherapy: The Effects of Drug Concentration and Dose Apportioning on Tumor Cell Injury.

The addition of intravenous (i.v.) chemotherapy to i.v. immunotherapy for patients with lung cancer results in improved overall survival but is limited by synergistic side effects and an unknown, highly variable final cytotoxic dose within the tumor. The synergy between i.v. chemo- and immunotherapies is hypothesized to occur as a result of cell injury caused by chemotherapy, a mechanism demonstrated to drive antigen presentation within the tumor microenvironment. Intratumoral delivery of chemotherapy may thus be optimized to maximize tumor cell injury. To assess the balance between the damage versus the death of tumor cells, we developed a computational model of intratumoral dynamics within a lung cancer tumor for three different chemotherapy agents following direct injection as a function of location and number of injection sites. We based the model on the morphology of a lung tumor obtained from a thoracic CT scan. We found no meaningful difference in the extent of tumor cell damage between a centrally injected versus peripherally injected agent, but there were significant differences between a single injection versus when the total dose was apportioned between multiple injection sites. Importantly, we also found that the standard chemotherapeutic concentrations used for intravenous administration were effective at causing cell death but were too high to generate significant cell injury. This suggests that to induce maximal tumor cell injury, the optimal concentration should be several orders of magnitude lower than those typically used for intravenous therapy.

Prefeasibility study on optimal site location for Power‐to‐X: An experiment for the Danish energy system

Denmark has set ambitious goals to cut greenhouse gas emissions by 70 % by the year 2030, and in an effort to reach this, the Danish Energy Agency has proposed a Power-to-X strategy that involves an overall capacity target of 6 GW of electrolysis by 2030. The objective of the following study was to identify the optimal site location for siting an electrolyser for Power-to-X as a prefeasibility analysis. The results indicated that Jammerbugt was an ideal area, for an add on solution to an already existing wind turbine, with 1303 h of excess wind energy available for Power-to-X. A financial analysis showed that there was an NPV of - €126,032 after a 20-year period, which improves with a theoretical 20 % governmental subsidy to €16,662. Therefore, it was found that Power-to-X is still currently reliant on governmental support as a viable business case. The study's findings highlight the importance of this support for Power-to-X to be a viable business case, such as the decision to allocate 1.25 billion DKK for hydrogen production by 2030.

Histopathological and phylogenetic description of an Amazonian cnidaria microparasite Myxobolus rousseauxii n. sp. infecting the gill arches of Brachyplatystoma rousseauxii (Siluriformes)

From genus Myxobolus, cnidarians of Myxozoa class, is well known for infecting economically important fish species and, as result, relevant losses in aquaculture production can be observed. They are present in a big range of fish in its natural habitat, including the migratory Brachyplatystoma rousseauxii catfish. This study aimed is to develop an integrative characterization of a new species of Myxobolus, located in B. rousseauxii's gills. To accomplish this, 30 specimens of B. rousseauxii catfish were collected from Mosqueiro Island in Pará, Brazil; necropsied and analyzed for morphology, histology and molecular characteristics. Cysts with conjunctival capsule development made up of fibroblasts were observed at the gill arches; such proliferation caused bone tissue loss and cartilage compression. The cysts contained Myxobolus myxospores measuring 9.9 μm of length and 9.6 μm of width, whereas polar capsules were 5.4 μm long and 3.4 μm wide, with 8 to 9 coils of polar tubules. Phylogenetic analyses revealed that new species were included in a subclade alongside species from the same geographic location and infection site that infect Siluriformes fish. Morphological and molecular differences revealed that Myxobolus spp. parasite-host associations through histopathology supporting the designation of a new M. rousseauxii n. sp. species in B. rousseauxii, a commercially important fish.

The Role of Talus Pile Mobility in Valley Widening Processes and the Development of Wide Bedrock Valleys, Buffalo River, AR

AbstractValley width is largely controlled by lithology and upstream drainage area, but little work has focused on identifying the processes through which valleys widen. Bedrock valleys widen by first laterally eroding bedrock valley walls, followed by the collapse of overlying bedrock material that must then be transported away from the valley wall before the valley can continue widening. We hypothesize that talus piles that cannot be transported by the river protect the valley wall and slow valley widening, while talus piles that are rapidly transported allow for uninterrupted valley widening. We used field measurements from 40 locations in both wide and narrow valleys along the Buffalo River, AR to test this hypothesis. Our data show that wide valleys tend to have fewer talus piles and smaller talus grain sizes, whereas talus in narrow valleys is larger in size and more continuous along valley walls. We calculated potential talus block entrainment at each site location and found that talus blocks in wide valleys are potentially entrained and moved away from valley walls during moderate and large flood events, whereas talus blocks in narrow valleys are very rarely moved. Our results show that the potential transport of talus piles protecting bedrock valley walls from widening is controlled by the block size of collapsed bedrock wall material relative to stream competency. Our results also suggest that persistence versus mobility of collapsed talus piles is an important process in the development of wide bedrock valleys.

Improved Robustness for Deep Learning-based Segmentation of Multi-Center Myocardial Perfusion MRI Datasets Using Data Adaptive Uncertainty-guided Space-time Analysis

Fully automatic analysis of myocardial perfusion MRI datasets enables rapid and objective reporting of stress/rest studies in patients with suspected ischemic heart disease. Developing deep learning techniques that can analyze multi-center datasets despite limited training data and variations in software (pulse sequence) and hardware (scanner vendor) is an ongoing challenge. Datasets from 3 medical centers acquired at 3T (n = 150 subjects; 21,150 first-pass images) were included: an internal dataset (inD; n = 95) and two external datasets (exDs; n = 55) used for evaluating the robustness of the trained deep neural network (DNN) models against differences in pulse sequence (exD-1) and scanner vendor (exD-2). A subset of inD (n = 85) was used for training/validation of a pool of DNNs for segmentation, all using the same spatiotemporal U-Net architecture and hyperparameters but with different parameter initializations. We employed a space-time sliding-patch analysis approach that automatically yields a pixel-wise "uncertainty map" as a byproduct of the segmentation process. In our approach, dubbed Data Adaptive Uncertainty-Guided Space-time (DAUGS) analysis, a given test case is segmented by all members of the DNN pool and the resulting uncertainty maps are leveraged to automatically select the "best" one among the pool of solutions. For comparison, we also trained a DNN using the established approach with the same settings (hyperparameters, data augmentation, etc.). The proposed DAUGS analysis approach performed similarly to the established approach on the internal dataset (Dice score for the testing subset of inD: 0.896 ± 0.050 vs. 0.890 ± 0.049; p = n.s.) whereas it significantly outperformed on the external datasets (Dice for exD-1: 0.885 ± 0.040 vs. 0.849 ± 0.065, p < 0.005; Dice for exD-2: 0.811 ± 0.070 vs. 0.728 ± 0.149, p < 0.005). Moreover, the number of image series with "failed" segmentation (defined as having myocardial contours that include bloodpool or are noncontiguous in ≥1 segment) was significantly lower for the proposed vs. the established approach (4.3% vs. 17.1%, p < 0.0005). The proposed DAUGS analysis approach has the potential to improve the robustness of deep learning methods for segmentation of multi-center stress perfusion datasets with variations in the choice of pulse sequence, site location or scanner vendor.

Clinical Trials in Gastroesophageal Cancers: An Analysis of the Global Landscape of Interventional Trials From ClinicalTrials.gov.

To describe the global landscape of clinical research into interventions for gastroesophageal cancers (GECs), with examination of trial characteristics, geographic distribution of trial sites, and factors associated with trial termination. We queried ClinicalTrials.gov to identify all completed or terminated phase III interventional studies investigating GECs (esophageal squamous cell carcinoma [ESCC], esophageal adenocarcinoma [EAC], gastroesophageal junctional [GEJ], and gastric adenocarcinoma). Data on all reported trial characteristics were extracted. Pearson's chi-square and Fisher's exact tests were used to compare differences in completed and terminated trials. Multivariate logistic regression evaluated predictors of termination. A total of 179 trials were identified; of these, 90% were therapeutic. Most included sites in Asia (61%) and Europe (32%); few included sites in Africa (4%). Thirty percent included sites in low- and middle-income countries (LMICs). Most (70%) focused on gastric or GEJ adenocarcinoma, 13% on EAC and ESCC, and 9% on ESCC alone. Sixteen percent (n = 29) of trials terminated prematurely. In multivariate analysis, study site number, location of recruitment sites, and patient population emerged as predictors of termination. Trials recruiting from US-based sites were more likely to terminate (odds ratio [OR], 7.22 [95% CI, 1.59 to 32.69]). Trials conducted exclusively in LMICs were less likely to terminate (OR, 0.04 [95% CI, 0.01 to 0.59] v conducted in high-income countries [HICs] alone). Studies on ESCC were more likely to terminate (OR, 17.74 [95% CI, 1.49 to 210.69]). Although 80% of GECs occur in LMICs, trial activity disproportionately occurs in HICs. Few trials focus on EAC/ESCC despite being highly fatal, highlighting an unmet need. Overall, this study highlights (1) a missed opportunity to recruit patients from high-incidence regions globally; and (2) a pressing need for increasing funding, infrastructure, and support for GEC trials in LMICs.

Integrated approach for seismic wave prediction and structural evaluation of Oya tuff quarry underground spaces: Field observations and numerical modeling

This study evaluates the structural stability of large underground spaces in seismic conditions, represented by the Oya underground stone mining plant. By directly monitoring the seismic response of the underground mining site, significant earthquake activities at the plate boundaries of the Tokyo region and Ibaraki Prefecture offshore area were observed. Additionally, through an in-depth analysis of seismic records from different locations within the underground structure, the dynamic characteristics and motion patterns of the Oya underground stone mining plant were revealed, revealing its movement trajectory during earthquakes. Additionally, this study innovatively applied seismic waves measured at the original site as input parameters and artificially generated seismic waves based on their response spectra. A numerical analysis was performed after ensuring the model's high correlation with the original site was met. The findings demonstrate that the results of both parameter input methods are confirmable and valuable. Under severe seismic conditions, instability was observed in some regions of the underground mining site. The study also discusses the location and damage mechanisms of the mining site's structure under seismic effects, providing valuable insights for the safety assessment of similar large underground spaces and proposing new approaches for selecting input parameters in seismic analysis.

Radiofrequency ablation via catheter and transpapillary access in patients with cholangiocarcinoma (ACTICCA-2 trial) – a multicenter, randomized, controlled, open-label investigator-initiated trial

BackgroundDespite the recent advances in cancer treatment, the therapeutic options for patients with biliary tract cancer are still very limited and the prognosis very poor. More than 50% of newly diagnosed patients with biliary tract cancer are not amenable to curative surgical treatment and thus treated with palliative systemic treatment. Malignant bile duct obstructions in patients with perihilar and/or ductal cholangiocarcinoma (CCA) represents one of the most important challenges in the management of these patients, owning to the risk represented by developing life-threatening cholangitis which, in turn, limits the use of systemic treatment. For this reason, endoscopic stenting and/or bile duct decompression is the mainstay of treatment of these patients. Data on efficacy and safety of adding radiofrequency ablation (RFA) to biliary stenting is not conclusive. The aim of this multicenter, randomized trial is to evaluate the effect of intraductal RFA prior to bile duct stenting in patients with unresectable perihilar or ductal CCA undergoing palliative systemic therapy.Methods/DesignACTICCA-2 is a multicenter, randomized, controlled, open-label, investigator-initiated trial. 120 patients with perihilar or ductal CCA with indication for biliary stenting and systemic therapy will be randomized 1:1 to receive either RFA plus bile duct stenting (interventional arm) or bile duct stenting alone (control arm). Patients will be stratified by trial site and tumor location (perihilar vs. ductal). Both arms receive palliative systemic treatment according to the local standard of care determined by a multidisciplinary tumorboard. The primary endpoint is time to first biliary event, which is determined by an increase of bilirubin to > 5 mg/dl and/or the occurrence of cholangitis leading to premature stent replacement and/or disruption of chemotherapy. Secondary endpoints include overall survival, safety according to NCI CTCAE v5, quality of life assessed by questionnaires (EORTC QLQ-C30 and QLQ-BIL21), clinical event rate at 6 months after RFA and total days of over-night stays in hospital. Follow-up for the primary endpoint will be 6 months, while survival assessment will be continued until end of study (maximum follow-up 30 month). All patients who are randomized and who underwent endoscopic stenting will be used for the primary endpoint analysis which will be conducted using a cause-specific Cox proportional hazards model with a frailty for trial site and fixed effects for the treatment group, tumor location, and stent material.DiscussionACTICCA-2 is a multicenter, randomized, controlled trial to assess efficacy and safety of adding biliary RFA to bile duct stenting in patients with CCA receiving palliative systemic treatment.Trial registrationThe study is registered with ClinicalTrials.gov (NCT06175845) and approved by the local ethics committee in Hamburg, Germany (2024-101232-BO-ff). This manuscript reflects protocol version 1 as of January 9th, 2024.Graphical

Value of high-output pace-mapping of the right phrenic nerve for enabling safe radiofrequency ablation of atrial fibrillation: insights from three-dimensional computed tomography segmentation.

Right phrenic nerve (RPN) injury is a disabling but uncommon complication of atrial fibrillation (AF) radiofrequency ablation. Pace-mapping is widely used to infer RPN's course, for limiting the risk of palsy by avoiding ablation at capture sites. However, information is lacking regarding the distance between the endocardial sites of capture and the actual anatomic RPN location. We aimed at determining the distance between endocardial sites of capture and anatomic CT location of the RPN, depending on the capture threshold. In consecutive patients undergoing AF radiofrequency ablation, we defined the course of the RPN on the electroanatomical map with high-output pacing at up to 50 mA/2 ms, and assessed RPN capture threshold (RPN-t). The true anatomic course of the RPN was delineated and segmented using CT scan, then merged with the electroanatomical map. The distance between pacing sites and the RPN was assessed. In 45 patients, 1033 pacing sites were analysed. Distances from pacing sites to RPN ranged from 7.5 ± 3.0 mm (min 1) when RPN-t was ≤10 mA to 19.2 ± 6.5 mm (min 9.4) in cases of non-capture at 50 mA. A distance to the phrenic nerve > 10 mm was predicted by RPN-t with a ROC curve area of 0.846 [0.821-0.870] (P < 0.001), with Se = 80.8% and Sp = 77.5% if RPN-t > 20 mA, Se = 68.0% and Sp = 91.6% if RPN-t > 30 mA, and Se = 42.4% and Sp = 97.6% if non-capture at 50 mA. These data emphasize the utility of high-output pace-mapping of the RPN. Non-capture at 50 mA/2 ms demonstrated very high specificity for predicting a distance to the RPN > 10 mm, ensuring safe radiofrequency delivery.

Analysis of Tall Building by using Different Dimensions Under Wind Load Effects

Abstract: The expense of land is increasing day by day because of rapid increase in the population whereas vegetation is diminishing, due to diminished vegetation contamination is expanded. In this Research paper, we analyze the various types of the dimensions of the building considering them side ratios too and the effect of windward forces on the building in mainly X and Z direction. This paper is about the study of four-building models as Dimensions (30m*30m), (40m*25m), (55m*20m), (80m*15m) having their horizontal Aspect ratios viz. 1, 1.6, 2.75 &amp; 5.33 at an angle of 0 degrees. The height of the building is 90m. Therefore, the research is proceeding to balance out the structure from an increasingly affordable perspective. To find out the best performance and economical for the lateral wind-force resisting system of different models of 25 storey buildings are modelled in STAAD-PRO, assuming the site location as AGRA (Uttar Pradesh), India. For the different structural systems that are compared for minimum and maximum storey displacement, storey drift. The structural system used is prototype. The axial force, shear force, moment, and reactions at various windward sides are used to compare the best performance of the structure. Above all, wind forces in x- direction shows the adequate displacement and drift values when compared to z- direction but from the economic point of view Model-2 gives the satisfactory result from all the above.

Enhanced anticancer efficacy of TRAIL-conjugated and odanacatib-loaded PLGA nanoparticles in TRAIL resistant cancer

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) demonstrates unique characteristics in anticancer therapies as it selectively induces apoptosis in cancer cells. However, most cancer cells are TRAIL-resistant. Odanacatib (ODN), a cathepsin K inhibitor, is considered a novel sensitizer for cancer treatment. Combination therapy between TRAIL and sensitizers is considered a potent platform that improves TRAIL-based anticancer therapies beyond TRAIL monotherapy. Herein, we developed ODN loaded poly(lactic-co-glycolic) nanoparticles conjugated to GST-TRAIL (TRAIL-ODN-PLGA-NPs) to target and treat TRAIL-resistant cancer.TRAIL-ODN-PLGA-NPs demonstrated a significant increase in cellular uptake via death receptors (DR5 and DR4) on surface of cancer cells. TRAIL-ODN-PLGA-NPs exposure destroyed more TRAIL-resistant cells compared to a single treatment with free drugs. The released ODN decreased the Raptor protein, thereby increasing damage to mitochondria by elevating reactive oxygen species (ROS) generation. Additionally, Bim protein stabilization improved TRAIL-resistant cell sensitization to TRAIL-induced apoptosis. The in vivo biodistribution study revealed that TRAIL-ODN-PLGA-NPs demonstrated high location and retention in tumor sites via the intravenous route. Furthermore, TRAIL-ODN-PLGA-NPs significantly inhibited xenograft tumor models of TRAIL-resistant Caki-1 and TRAIL-sensitive MDA-MB-231 cells.The inhibition was associated with apoptosis activation, Raptor protein stabilizing Bim protein downregulation, Bax accumulation, and mitochondrial ROS generation elevation. Additionally, TRAIL-ODN-PLGA-NPs affected the tumor microenvironment by increasing tumor necrosis factor-α and reducing interleukin-6.In conclusion, we evealed that our formulation demonstrated synergistic effects against TRAIL compared with the combination of free drug in vitro and in vivo models. Therefore, TRAIL-ODN-PLGA-NPs may be a novel candidate for TRAIL-induced apoptosis in cancer treatment.

Identifying managed aquifer recharge and rain water harvesting sites and structures for storing non-conventional water using GIS-based multi-criteria decision analysis approach

In arid climates, conventional water resources are severely limited and stressed in the face of rapid population growth and future climate change. So, it is necessary to find alternative non-conventional water resources for use in drought situations. Additionally, the non-conventional water resources in these areas are not sufficient to meet future water demand. Therefore, non-conventional water resources can be adopted as a strategic reserve to bridge the gap between water supply and demand in case of emergency and drought events. These resources might include rainwater harvesting, treated wastewater, and desalinated seawater. Managed aquifer recharge (MAR) can be applied to store these resources in the hydrogeological system using Geo information System—Multi Criteria Decision Analysis (GIS-MCDA) approach for determining the suitable MAR location for storage. North-west Kingdom of Saudi Arabia area was chosen for this study because it is extremely arid, has high potential for social and economic development, and it has newly constructed non-conventional water infrastructures distributed throughout the area including water desalination plants, Tertiary Sewage Effluent (TSE) waste water plants, and flash-flood storage dams. To identify the suitable MAR site location and structure, different data related to aquifer hydrogeology, surface hydrology, hydrometeorology, and water quality were applied. Then, GIS-MCDA holistic approach was applied with aid of ordered weighting average (OWA) technique. Finally, two maps were created to show the MAR location and structure type. Potential map indicates that ~ 18.85% of the area is suitable for MAR installations. About 0.17% of the total area exhibited very high potential, where infiltration ponds can be applied, 1.86% had high potential for construction of check dams with diversion channels, and 16.82% had moderate potential for installation of recharge wells. Additionally, 56 MAR structures were proposed and a map showing their locations has been created. Thus, results indicated that the study area is promising for MAR installation. These maps could aid the decision makers to propose a sustainable development plan for the future water resources of the area.

3D modeling of anterior 2/3rds glossectomy reconstruction: A volume based donor site evaluation

ObjectiveAnterior 2/3rds glossectomy results in significant patient morbidity due to speech and swallowing impairment. Microvascular free flap reconstruction compensates for large volume defects. Flap volume is based on the adipose content of the donor site and varies by patient body mass index (BMI) and donor site location. We sought to correlate flap thickness at different donor sites with patient BMI to determine optimal donor site selection. MethodsPatients with CT scans of the oral cavity, thorax and lower extremity were identified and included. The volumes of the anterior 2/3rds of the tongue were measured and recorded using computed tomography-generated modeling. Pre-muscular tissue thicknesses at anterolateral thigh (ALT), deep inferior epigastric artery (DIEP), latissimus dorsi, and parascapular donor sites were measured. The donor site adequency was defined as reconstructing the tongue volume within 10% of the ideal volume required and stratified based on patient BMI. ResultsIn 144 patients, the average anterior 2/3rds glossectomy defect was 100.3 cm3. Glossectomy defect size was highly correlated with BMI (p < 0.001). The DIEP flap had the largest volume (155.4 cm3), followed by latissimus (105.6 cm3), parascapula (97.8 cm3), and ALT (60.5 cm3). For patients with BMI ≤ 30, the DIEP flap best reconstructed native tongue volume (up to 113 % of native tongue volume). In patients with BMI > 30.1, native tongue volumes were approximated by the latissimus flap (89–92 % of native tongue) and parascapular flap (85–95 % of native tongue volume). In BMI > 30.1 the DIEP flap provided excess tissue bulk (129–135 % of native tongue volume). ConclusionThe DIEP flap more closely approximates the volume needed to reconstruct anterior two-thirds tongue defects for BMIs ≤ 30. The subscapular system flaps provided the best volume match for BMIs > 30 and the DIEP flap provided excess tissue bulk which could be adjusted in the reconstruction process.

State-dependent effects of responsive neurostimulation depend on seizure localization.

Brain-responsive neurostimulation is firmly ensconced among treatment options for drug-resistant focal epilepsy, but over a quarter of patients treated with the RNS System do not experience meaningful seizure reduction. Initial titration of RNS therapy is typically similar for all patients, raising the possibility that treatment response might be enhanced by consideration of patient-specific variables. Indeed, small, single-center studies have yielded preliminary evidence that RNS System effectiveness depends on the brain state during which stimulation is applied. The generalizability of these findings remains unclear, however, and it is unknown whether state-dependent effects of responsive neurostimulation are also stratified by location of the seizure onset zone where stimulation is delivered. We aimed to determine whether state-dependent effects of the RNS System are evident in the large, diverse, multi-center cohort of RNS System clinical trial participants and to test whether these effects differ between mesiotemporal and neocortical epilepsies. Eighty-one of 256 patients who were treated with the RNS System across 31 centers during clinical trials met criteria for inclusion in this retrospective study. Risk states were defined in relation to phases of daily and multi-day cycles of interictal epileptiform activity that are thought to determine seizure likelihood. We found that the probabilities of risk state transitions depended on the stimulation parameter being changed, the starting seizure risk state, and the stimulated brain region. Changes in two commonly adjusted stimulation parameters, charge density and stimulation frequency, produced opposite effects on risk state transitions depending on seizure localization. Greater variance in acute risk state transitions was explained by state-dependent responsive neurostimulation for bipolar stimulation for neocortical epilepsies and for monopolar stimulation for mesiotemporal epilepsies. Variability in effectiveness of RNS System therapy across individuals may relate, at least partly, to the fact that current treatment paradigms do not account fully for fluctuations in brain states or locations of simulation sites. State-dependence of electrical brain stimulation may inform development of next-generation closed-loop devices that can detect changes in brain state and deliver adaptive, localization-specific patterns of stimulation to maximize therapeutic effects.

Real-Time Measurement of a Weak Interaction of a Transcription Factor Motif with a Protein Hub at Single-Molecule Precision.

Transcription factors often interact with other protein cofactors, regulating gene expression. Direct detection of these brief events using existing technologies remains challenging due to their transient nature. In addition, intrinsically disordered domains, intranuclear location, and lack of cofactor-dependent active sites of transcription factors further complicate the quantitative analysis of these critical processes. Here, we create a genetically encoded label-free sensor to identify the interaction between a motif of the MYC transcription factor, a primary cancer driver, and WDR5, a chromatin-associated protein hub. Using an engineered nanopore equipped with this motif, WDR5 is probed through reversible captures and releases in a one-by-one and time-resolved fashion. Our single-molecule kinetic measurements indicate a weak-affinity interaction arising from a relatively slow complex association and a fast dissociation of WDR5 from the tethered motif. Further, we validate this subtle interaction by determinations in an ensemble using single nanodisc-wrapped nanopores immobilized on a biolayer interferometry sensor. This study also provides the proof-of-concept for a sensor that reveals unique recognition signatures of different protein binding sites. Our foundational work may be further developed to produce sensing elements for analytical proteomics and cancer nanomedicine.

Changing with the times: From agricultural potential to spatially explicit reconstructions of past land use

Past land-use reconstructions are a key tool for studying long-term human ecodynamics and addressing pressing questions about the origins and evolutionary dynamics of the Anthropocene. In particular, agricultural landcover reconstructions are vital for understanding long-term human-environment dynamics. Most past agricultural land-use models, however, rely heavily on modelling assumptions, make limited use of known archaeological site locations to constrain or inform their estimates and tend to be limited to general estimates of percentages of plant types within catchments around pollen trapping lakes. The lack of information outside catchment areas and low spatial resolution even within catchments constrain the utility of these models. To address this problem, we propose a new approach that combines archaeological predictive modelling with pollen-based agricultural landcover reconstructions to produce more accurate, spatially explicit past landcover estimates. Here, we present the results of a case study deploying the new approach to produce improved past landcover maps for a region in the Western Taurus Mountains, southwestern Turkey. The study area surrounds Sagalassos, an antique urban centre with a regional settlement history encompassing nine millennia. We produced five archaeological predictive models for the study region using the ‘Locally Adaptive Models of Archaeological Potential’ (LAMAP) method spanning the Hellenistic through Late Ottoman period. We then combined those predictive surfaces with ‘Regional Estimates of VEgetation Abundance from Large Sites’ (REVEALS) pollen landcover reconstructions for the same periods based on pollen from sediment cores extracted from three catchments within the study area. Lastly, we compared the resulting hybrid landcover models to the archaeological record using data not used to make the predictions. We found that the hybrid landcover model aligned very well with the known extents of agricultural land-use from the study area. These results indicate that the proposed approach is a viable way to combine pollen-based landcover models with archaeological data and produce more accurate, empirically-based landcover reconstructions reflecting real human activity in the past.

Use of proxy observations to evaluate the accuracy of precipitation spatial gridding

AbstractA WRF‐based high‐resolution reanalysis of the Irish climate (1981–2010) is used to create proxy daily precipitation observations at the locations of climatological sites used for precipitation monitoring; the data are statistically representative of the real precipitation climate both for mean (over monthly, seasonal and annual periods) and extreme values. The proxy observations are spatially interpolated to the original WRF grid using a typical gridding package and compared against the original data to assess gridding errors. The errors are more complex than the estimates provided by the gridding software; systematic biases are evident which by the inclusion of strategically placed additional observing sites are shown to be greatly reduced. There is also evidence of systematic differences in trend analyses of extreme precipitation over the period. The method provides independent estimates of the errors that arise from actual gridding applications. It also facilitates the testing of the optimality of a network by highlighting possible inadequacies in an existing station layout and suggesting new observing site locations to fill gaps. Uncertainties regarding the errors in real precipitation observations, and possible spurious impacts linked to temporal changes in the real observing network, are avoided by this method.

Developing a novel ultraselective and ultrasensitive label-free direct spectrofluorimetric nanobiosensor for direct highly fast field detection of explosive triacetone triperoxide

BackgroundDirect detection of the notorious explosive triacetone triperoxide (TATP) is very difficult because it lacks facile ionization and UV absorbance or fluorescence. Besides, the current indirect methods are time-consuming and need a pre-step for TATP cleavage to hydrogen peroxide. Moreover, they commonly show significant false-positive results in the presence of some camouflage which limits their field applications. Herein, for the first time, a novel label-free field-applicable spectrofluorimetric nanobiosensor was developed for direct TATP detection using a novel activated-protein protected gold nanocluster (ABSA-AuNCs; QY = 28.3 %) synthesized by a combined protein-assisted-ultrasonication procedure. ResultsThe ABSA-AuNCs revealed a fluorescence spectrum centered at 330.0 nm which was significantly quenched by TATP (binding constant = 154.06 M-1; ΔG = −12.5 kJ mol−1; E(%) = 88.5 %). This phenomenon was used as a basis for direct TATP quantification, providing a working range of 0.01–40.0 mg L−1 and a detection limit of 6.7 μg L−1 which is the lowest LOD provided for TATP detection up to now. A %RSD of 0.9 % and 1.56 % was obtained for repeatability and inter-day reproducibility, respectively. The selectivity was checked against a variety of camouflages, revealing ultra-selectivity. Several synthetic samples prepared by several camouflages and real samples (clay soil and real water media) were analyzed, revealing quantitative recoveries of TATP. SignificanceDuring the production of the notorious explosive TATP, it can be discharged into water and soil. This novel method eliminated the false-positive results of traditional methods and is applicable for direct quantitative detection of camouflaged TATP and its residues in real soil and water samples in a highly short response time (2 min). The camouflaged TATP analysis is important for tracking the terrorist attacks in field conditions and analysis of soil and water can provide a first indication of the location of the production site.