Marginal Response Research Articles

An Imidazoline 2 Receptor Ligand Relaxes Mouse Aorta via Off-Target Mechanisms Resistant to Aging.

Imidazoline receptors (IR) are classified into three receptor subtypes (I1R, I2R, and I3R) and previous studies showed that regulation of I2R signaling has neuroprotective potential. In order to know if I2R has a role in modulating vascular tone in health and disease, we evaluated the putative vasoactive effects of two recently synthesized I2R ligands, diethyl (1RS,3aSR,6aSR)-5-(3-chloro-4-fluorophenyl)-4,6-dioxo-1-phenyl-1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole -1-phosphonate (B06) and diethyl [(1-(3-chloro-4-fluorobenzyl)-5,5-dimethyl-4-phenyl-4,5-dihydro-1H-imidazol-4-yl]phosphonate] (MCR5). Thoracic aortas from Oncins France 1 (3- to 4-months-old) and C57BL/6 (3- to 4- and 16- to 17-months-old mice) were mounted in tissue baths to measure isometric tension. In young mice of both strains, MCR5 induced greater relaxations than either B06 or the high-affinity I2R selective ligand 2-(2-benzofuranyl)-2-imidazoline (2-BFI), which evoked marginal responses. MCR5 relaxations were independent of I2R, as IR ligands did not significantly affect them, involved activation of smooth muscle KATP channels and inhibition of L-type voltage-gated Ca2+ channels, and were only slightly modulated by endothelium-derived nitric oxide (negatively) and prostacyclin (positively). Notably, despite the presence of endothelial dysfunction in old mice, MCR5 relaxations were preserved. In conclusion, the present study provides evidence against a functional contribution of I2R in the modulation of vascular tone in the mouse aorta. Moreover, the I2R ligand MCR5 is an endothelium-independent vasodilator that acts largely via I2R-independent pathways and is resistant to aging. We propose MCR5 as a candidate drug for the management of vascular disease in the elderly.

Population aging and fiscal sustainability: Nonlinear evidence from Europe

This study investigates the effects of population aging on fiscal sustainability for 14 European countries from 1970 to 2014. With a novel nonlinear econometric method, we estimate the dynamic transition of the marginal response of the primary surplus (MRPS) to public debt driven by the demographic shift. We find that the dynamics of the MRPS are highly nonlinear and exhibit opposite patterns between countries with major fiscal crises and those without such crises. The “non-crisis” countries have raised their MRPS to positive values despite population aging, thereby satisfying the conditions sufficient for fiscal solvency. By contrast, the “crisis” countries have let their MRPS decline to negative values and violated the solvency conditions, as the population aged. To account for the contrasting patterns of the MRPS, we estimate the effects of the elderly’s population share on the public expenditures for pension and health care in the cointegration and error-correction models. We find that population aging tends to increase such expenditures, but this effect is much stronger in the crisis countries. This result suggests that their policies for improving fiscal sustainability have been relatively ineffective, which can explain the diminishing MRPS in the crisis countries.

Climate adaptation guidance: New roles for hydroeconomic analysis

Climate water stress internationally challenges the goal of achieving food, energy, and water security. This challenge is elevated by population and income growth. Increased climate water stress levels reduce water supplies in many river basins and elevate competition for water among sectors. Organized information is needed to guide river basin managers and stakeholders who must plan for a changing climate through innovative water allocation policies, trade-off analysis, vulnerability assessment, capacity adaptation, and infrastructure planning. Several hydroeconomic models have been developed and applied assessing water use in different sectors, counties, cultures, and time periods. However, none to date has presented an optimization framework by which historical water use and economic benefit patterns can be replicated while presenting capacity to adapt to future climate water stresses to inform the design of policies not yet been implemented. This paper's unique contribution is to address this gap by designing and presenting results of a hydroeconomic model for which optimized base conditions exactly match observed data water use and economic welfare for several urban and agricultural uses at several locations in a large European river basin for which water use supports a population of more than 3.2 million. We develop a state-of-the arts empirical dynamic hydroeconomic optimization model to discover land and water use patterns that optimize sustained farm and city income under various levels of climate-water stress. Findings using innovative model calibration methods allow for the discovery of efficient water allocation plans as well as providing insight into marginal behavioral responses to climate water stress and water policies. Results identify that water trade policy under climate water stress provides more economically efficient water use patterns, reallocating water from lower valued uses to higher valued uses such as urban water. The Ebro River Basin in Spain is used as an example to investigate water use adaptation patterns under various levels of climate water stress. That basin's issues and challenges can be of relevance to other river basins internationally.

Primary Intraosseous Rhabdomyosarcoma: Rare Subtype Involving Mandible with Unique Translocation

<h3>Introduction</h3> A rare subtype of spindled and epithelioid rhabdomyosarcoma (RMS) with unique gene rearrange- ments (FUS-TFCP2 or EWSR1-TFCP2) was first described in 2018 (J Pathol 245:29–40). These aggressive tumors occur in a wide age range with a female predilection and develop almost exclusively within a variety of bone sites, in par- ticular, the craniofacial bones. Majority of affected individuals died of disease within 15 months. FUS-TFCP2 is the predominant translocation associated with this RMS subtype. This case report describes a rare mandibular sarcoma in a child with a complex, oncologic, medical history. <h3>Clinical Presentation and Pathology Findings</h3> 15-year-old female experienced acute lymphoblastic leukemia at 11 months of age, with oncologic resolution. At age 7, anthracycline-induced cardiomyopathy was diagnosed, ne- cessitating heart transplantation at age 9. Subsequently, EBV-associated diffuse large cell lymphoma involving the retropharynx was diagnosed at age 10, with successful oncologic management. At age 15, a left mandibular en- largement was noted. Fine needle core biopsy identified a spindled and epithelioid sarcoma, diffusely positive for nuclear MyoD1 with rare cytoplasmic desmin and rare nuclear myogenin. ALK and S100 immunostaining were positive in a certain tumor cell population. The diagnosis of spindled and epithelioid RMS was made. Conventional cytogenetics demonstrated a complex hyperdiploid tumor (78XXX with numerous derivative aberrations). Next- generation sequencing identified a FUS-TFCP2 translocation, which appears to be tumor-defining with this primary intrabony RMS subtype. Oncologic sarcoma management was performed with a marginal response to chemother- apy and low-dose radiation therapy. Left mandible resection was performed with negative bone and soft tissue margins (3.5cm tumor size). <h3>Conclusion</h3> Primary intraosseous RMS is a rare and aggressive subtype, which has tumor-defining translocations and expresses MyoD1 to a greater extent than Desmin or Myogenin. Of interest, is the overexpression of ALK, which may provide a target for ALK inhibitors.

Evaluation of the Retinopathy of Prematurity Activity Scale (ROP-ActS) in a randomised controlled trial aiming for prevention of severe ROP: a substudy of the Mega Donna Mega trial

ObjectiveThe current grading of retinopathy of prematurity (ROP) does not sufficiently discriminate disease severity for evaluation of trial interventions. The published ROP Activity Scales (original: ROP-ActS and modified: mROP-ActS), describing...

A lot of convergence, a bit of divergence: Environment and interspecific interactions shape body colour patterns in Lissotriton newts.

Coexistence with related species poses evolutionary challenges to which populations may react in diverse ways. When exposed to similar environments, sympatric populations of two species may adopt similar phenotypic trait values. However, selection may also favour trait divergence as a way to reduce competition for resources or mates. The characteristics of external body parts, such as coloration and external morphology, are involved to varying degrees in intraspecific signalling as well as in the adaptation to the environment and consequently may be diversely affected by interspecific interactions in sympatry. Here, we studied the effect of sympatry on various colour and morphological traits in males and females of two related newt species Lissotriton helveticus and L.vulgaris. Importantly, we did not only estimate how raw trait differences between species respond to sympatry, but also the marginal responses after controlling for environmental variation. We found that dorsal and caudal coloration converged in sympatry, likely reflecting their role in adaptation to local environments, especially concealment from predators. In contrast, aspects of male and female ventral coloration, which harbours sexual signals in both species, diverged in sympatry. This divergence may reduce opportunities for interspecific sexual interactions and the associated loss of energy, suggesting reproductive character displacement (RCD). Our study emphasizes the contrasting patterns of traits involved in different functions and calls for the need to consider this diversity in evolutionary studies.

Circadian activity in different photoperiod (12L: 12 D) and (8L: 16D) in passerine finches

Circadian rhythms are more synchronized in birds than mammals. Circadian clock functions as a timing reference allow organisms fluctuations in their environments and are the basis for the transduction of seasonality from photoperiod. The present study was performed to determine the effect of constant dim and bright light illumination on circadian behavior of baya weaver bird ( Ploceus philippinus), black-headed munia ( Lonchura malaca malaca), and red-headed bunting ( Emberiza bruniceps). It analyzed the data of locomotors activity of these under the effect of different photoperiods (12L: 12D and 8L: 16D) for a period of 30 days. In the captivity, birds were acclimatized for 4 weeks and were subjected to photoperiodic chambers (60×45×35 cm3) providing short-day conditions (8h light: 16h darkness; 8L:16D). Total activity profile was observed for 30 days under 12L: 12D and 8L: 16D photoperiod. Under 12 L: 12D photoperiod, significant response was observed in two of the four birds in daily profile of baya weaver bird and also in black-headed munia but the marginal significant response noticed in one of the four birds under 8L: 16D. The comparison of day and night total activity count in baya weaver bird and black-headed munia showed the maximum activity in weaver bird under 12L: 12D photoperiod.

Optimal Prosumers’ Peer-to-Peer Energy Trading and Scheduling in Distribution Networks

The emergence of prosumers in the distribution networks provides the proactive local management of distributed energy resources (DERs) and distributed energy trading. A bilevel framework of prosumers is proposed, enabling the joint optimization of the internal scheduling and external peer-to-peer (P2P) trading. Interactive benefit is defined as the marginal response cost. On the lower prosumer scheduling level, instead of concurrent scheduling process considering merely internal DERs’ response, interactive benefits of the DERs and the P2P trading are both taken into consideration while solving prosumers’ scheduling problem. Subsequently, a cooperative interaction method using the interactive benefit prioritization principle is proposed for the joint optimization problem in prosumer, considering both internal and external strategies. On the upper P2P trading level, an iterative bilateral negotiation algorithm is proposed, integrated with network charges. The proposed algorithm enables trading peers to reach an agreement, without the intervention of DSO. As a means to attribute the costs incurred by P2P trades to prosumers, the network charges include the congestion and loss costs, and the maintenance and modernization costs. Finally, the proposed method is implemented and benchmarked on a test case using the IEEE 33 bus system. The effectiveness of the method is verified in terms of promoting the consumption of DERs and prosumers’ benefits. Also, it is verified that the appropriate network charges may facilitate both the P2P trades and the secure operation.

Complex shearlets and rotary phase congruence tensor for corner detection

Corner detection algorithms based on multi-scale analysis attract more attention due to their promising performance. However, they only consider amplitude information, neglect phase information and partially utilize multi-scale decomposition coefficients to detect corners. This limits their detection accuracy, repeatability and localization ability. This paper describes a new multi-scale analysis based corner detector. To overcome the problems of bilateral margin responses, edge extension and lack of phase information in traditional shearlets, a novel complex shearlet transform is proposed to better localize distributed discontinuities and especially to extract phase information from geometrical features. Moreover, a new rotary phase congruence tensor is proposed to utilize all amplitude and phase information for corner detection. Its tolerances to noise and ability for corner localization are improved further by screening and normalizing the amplitude information. Experimental results demonstrate that the localization ability and detection accuracy of the proposed method are superior to current detectors, and its repeatability is generally higher than current detectors and recent machine learning based interest point detectors.

High-digestible silages allow low concentrate supply without affecting milk production or methane emissions

In this study, we tested a response function comprising responses in milk to changes in organic matter digestibility of silages and concentrate supply. We studied the effect of changes in silage digestibility and concentrate supply on milk yield, feed intake, body weight, and methane production using 60 Norwegian Red cows. The experiment was a complete randomized block design comprising 3 periods. The pre-experimental period lasted 20 d and all the cows were fed a common silage for ad libitum intake and concentrate according to yield. Next, response period 1 lasted 17 d and the cows were divided into 2 treatments, where a low-digestible silage (LDS) was fed to half of the cows, and the other half were fed a high-digestible silage (HDS). Both groups were fed silage for ad libitum silage intake. Concentrate was optimized according to the yield and type of silage offered. In this period, the effect of silage was evaluated using a mixed model, including the results from pre-experimental period, with parity as a covariate and animal as a random effect. In response period 2, which lasted 20 d, the concentrate level was evaluated by dividing the silage digestibility treatments further into 3 subgroups. Concentrate was increased by 2 kg of dry matter (DM) per day, decreased by 2 kg of DM/d, or remained unchanged. In response period 1, silage treatments were optimized to obtain similar yields and resulted in a lower concentrate offer to HDS treatment. However, the HDS treatment showed a 3.0 kg of DM/d higher total feed intake due to a higher than expected silage intake. This resulted in 3.5 kg higher energy-corrected milk (ECM). Methane emissions were similar between silage treatments, but HDS showed lower methane per kilogram of DM due to its higher intake. The effect of concentrate supply level and interaction with silage digestibility was evaluated using mixed models, including the results for response period 1, with parity as a covariate and animal as a random effect. The reduction in concentrate offer by 2 kg/d in response period 2 was compensated for by increased 1.3 kg of DM/d of silage intake for HDS, resulting in similar intake (22.1 kg of DM/d and 21.7 kg of DM/d without and with concentrate reduction, respectively) and ECM yields (29.4 and 29 kg of ECM without and with concentrate reduction, respectively). However, concentrate offer reduction could not be compensated for by increased silage intake for LDS and resulted in lower milk yields (27.5 kg of ECM). Increased concentrate showed a higher marginal ECM response (kg of ECM per kg of additional concentrate intake) for LDS (1.8 vs. 3.3 kg of ECM for HDS and LDS, respectively). Thus, the drop in milk yields could be compensated for by increased concentrate offers if LDS are fed. Total methane production increased with increased concentrate intake, regardless of silage digestibility. Methane emissions per unit of milk were affected by total DM intake rather than by changes in silage digestibility and concentrate level. The results of this study are based on short-term periods and could show differences if study periods were longer; the results should be interpreted accordingly.

Vegetation phenology in the Argentinean Wet Chaco: Assessing seasonality and precipitation dependence throughNDVI MODIStime series (2000–2018)

AbstractPlant phenology, that is, the timing of plant growth and development, is sensitive to climate and land‐use changes. Despite its importance in the context of global change, little is known about the plant phenology of subtropical regions. In the Argentinean Wet Chaco region, which is currently under high pressure due to land‐use intensification, the phenology patterns of its natural land covers are remarkably understudied. This important aspect of vegetation functioning can be effectively monitored through indices based on satellite imagery, such as the Normalized Difference Vegetation Index (NDVI). Thus, in this work, we used the NDVI from MODIS imagery to analyse plant phenology in the Argentinean Wet Chaco and discuss its implications in the current context of global change. NDVI time series were analysed for the period 2000–2018 for the following plant categories: riparian forest, forest islet, dense and open palm savanna and flooding grassland. Their seasonality and precipitation marginal response (PMR) were also assessed. The riparian forest presented the highest NDVI annual mean values and lowest PMR, followed by the forest islet. The flooding grassland presented the highest seasonality and palm savannas the highest precipitation dependence, with even higher PMR values in drier years. Climate change models predict an increase in precipitation in the region. If this occurs, palm savannas and flooding grasslands could present a more stable phenology. This would imply better conditions for cattle grazing and would, thus, reinforce the current land‐use pressure. On the contrary, this increase in precipitation would not have an impact over the photosynthetic activity of both types of forest, since our results suggest that this parameter is not limited by rainfall. In the current context of climate change and land‐use intensification, the results obtained provide key knowledge for a better use, management and conservation of the environments of the Argentinean Wet Chaco.Abstract in Spanish is available with online material.

Stabilization of the Cart-Inverted-Pendulum System Using State-Feedback Pole-Independent MPC Controllers.

In this paper, a pole-independent, single-input, multi-output explicit linear MPC controller is proposed to stabilize the fourth-order cart–inverted-pendulum system around the desired equilibrium points. To circumvent an obvious stability problem, a generalized prediction model is proposed that yields an MPC controller with four tuning parameters. The first two parameters, namely the horizon time and the relative cart–pendulum weight factor, are automatically adjusted to ensure a priori prescribed system gain margin and fast pendulum response while the remaining two parameters, namely the pendulum and cart velocity weight factors, are maintained as free tuning parameters. The comparison of the proposed method with some optimal control methods in the absence of disturbance input shows an obvious advantage in the average peak efficiency in favor of the proposed SIMO MPC controller at the price of slightly reduced speed efficiency. Additionally, none of the compared controllers can achieve a system gain margin greater than 1.63, while the proposed one can go beyond that limit at the price of additional degradation in the speed efficiency.

Mismatch between soil nutrient deficiencies and fertilizer applications: Implications for yield responses in Ethiopia

AbstractLack of accurate information about soil nutrient deficiencies coupled with limited access to appropriate fertilizers could lead to mismatch between soil nutrient deficiencies (requirements) and fertilizer applications. Such anomalies and mismatches are likely to have important implications for agricultural productivity. In this article we use experimental (spectral soil analysis) data from Ethiopia to examine farmers’ response to soil nutrient deficiencies and its implications for yield responses. We find that farmers’ response to macronutrient (nitrogen and phosphorus) deficiencies is not always consistent with agronomic recommendations. For example, we find that farmers in our sample are applying nitrogen fertilizers to soils lacking phosphorus, potentially due to lack of information on soil nutrient deficiencies or lack of access to appropriate fertilizers in rural markets. On the other hand, farmers respond to perceivably poor‐quality and acidic soils by applying higher amount of nitrogen and phosphorus fertilizers. We further show that such mismatches between fertilizer applications and soil macronutrient deficiencies are potentially yield‐reducing. Those farmers matching their soil nutrient deficiencies (requirements) and fertilizer application are likely to enjoy additional yield gains. Marginal yield response associated with nitrogen (phosphorus) application increases with nitrogen (phosphorus) deficiency in soils. Similarly, we find that farmers’ response to acidic soils is not yield‐enhancing. These findings suggest that such mismatches may explain heterogeneities in marginal returns to chemical fertilizers and the observed low adoption rates of chemical fertilizers in sub‐Saharan Africa.

Mesozoic-Cenozoic multistage tectonic deformation of the Qilian Shan constrained by detrital apatite fission track and zircon U[sbnd]Pb geochronology in the Yumu Shan area

The Qilian Shan on the northeastern edge of the Tibetan Plateau contains structural, sedimentary and tectonothermal records of plateau formation and growth in response to the Indian-Asian continental collision. In this study, we reveal the tectonic deformation evolution of the Qilian Shan by detrital apatite fission track (AFT) thermochronology and provenance analysis of a sedimentary section on the northern flank of the Qilian Shan based on paleocurrent measurements and detrital zircon UPb geochronology. The unannealed detrital AFT peak ages span ~154–10 Ma, and the zircon UPb ages range between ~3260 Ma and ~ 178 Ma. Detrital AFT ages showing that the initial exhumation occurs ca. 154–135 Ma and ca. 105–81 Ma and abundant ages of ca. 61–24 Ma indicate the prominent exhumation of the sedimentary provenance from the Qilian Shan at those times. Zircon UPb analysis suggests that the sediments were generally sourced from the Qilian Shan to the south, with moderate provenance changes at ~10 Ma and 5.1 Ma. These geochronological datasets imply that the Qilian Shan experienced multistage deformation during the Mesozoic-Cenozoic, i.e., late Jurassic-early Cretaceous (153.6–135.2 Ma), late Cretaceous (104.5–80.9 Ma), late Paleocene-Oligocene (61–43.1 Ma;38.2–24.6 Ma), mid-late Miocene (10 ± 4 Ma) and Pliocene (5.1–3.6 Ma). During the Cenozoic, the deformation initiated in the late Paleocene reflects the synchronous far-field response of the northeastern Tibetan Plateau margin to the Indian-Asian plate collision.

The telomere regulatory gene POT1 responds to stress and predicts performance in nature: Implications for telomeres and life history evolution.

Telomeres are emerging as correlates of fitness-related traits and may be important mediators of ecologically relevant variation in life history strategies. Growing evidence suggests that telomere dynamics can be more predictive of performance than length itself, but very little work considers how telomere regulatory mechanisms respond to environmental challenges or influence performance in nature. Here, we combine observational and experimental data sets from free-living tree swallows (Tachycinetabicolor) to assess how performance is predicted by the telomere regulatory gene POT1, which encodes a shelterin protein that sterically blocks telomerase from repairing the telomere. First, we show that lower POT1 gene expression in the blood was associated with higher female quality, that is, earlier breeding and heavier body mass. We next challenged mothers with an immune stressor (lipopolysaccharide injection) that led to "sickness" in mothers and 24h of food restriction in their offspring. While POT1 did not respond to maternal injection, females with lower constitutive POT1 gene expression were better able to maintain feeding rates following treatment. Maternal injection also generated a 1-day stressor for chicks, which responded with lower POT1 gene expression and elongated telomeres. Other putatively stress-responsive mechanisms (i.e., glucocorticoids, antioxidants) showed marginal responses in stress-exposed chicks. Model comparisons indicated that POT1 mRNA abundance was a largely better predictor of performance than telomere dynamics, indicating that telomere regulators may be powerful modulators of variation in life history strategies.

Stereotactic Radiosurgery for Olfactory Groove Meningiomas: An International, Multicenter Study.

Stereotactic radiosurgery (SRS) is increasingly considered for selected olfactory groove meningiomas (OGMs). To investigate the safety and efficacy of SRS for OGMs. From 20 institutions participating in the International Radiosurgery Research Foundation, we pooled patients who underwent SRS for histologically confirmed or radiologically suspected WHO grade I OGMs and were followed for 6 mo or more after the SRS. In total, 278 (median age 57 yr) patients underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) WHO grade I OGMs Median treatment volume was 4.60 cm3 (range: 0.12-27.3 cm3), median prescription dose was 12Gy, and median dose to the olfactory nerve was 11.20Gy. During median post-SRS imaging follow-up of 39 mo (range: 6-240 mo), 43% of patients had partial or marginal response, 54% of patients had stable disease, and 3% of patients experienced progression. During median post-SRS clinical follow-up of 51 mo (range: 6-240 mo), 36 (13%) patients experienced clinical and/or radiological adverse radiation events (AREs). Elevated risk of AREs was associated with larger OGM volume (P=.009) and pre-SRS peritumoral T2/fluid-attenuated inversion-recovery signal abnormalities (P<.001). After the SRS, olfaction remained stable, improved, or deteriorated in 90%, 8%, and 2% of patients, respectively. Complete post-SRS anosmia was predicted by partial/complete anosmia before the SRS (odds ratio [OR]=83.125; 95% CI [24.589-281.01], P<.001) and prior resection of OGM (OR=3.919; 95% CI [1.713-8.970], P=.001). SRS is associated with durable local control of the majority of OGM patients with acceptable safety profile. SRS allows preservation or improvement of olfactory function in the majority of OGM patients.

Using Nonlinear Budget Sets to Estimate Extensive Margin Responses: Method and Evidence from the Earnings Test

We estimate the impact of the Social Security Annual Earnings Test (AET) on older workers’ employment. The AET reduces social security claimants’ current benefits in proportion to their earnings in excess of an exempt amount. Using a regression kink design and Social Security Administration data, we document that the discontinuous change in the benefit reduction rate at the exempt amount causes a corresponding change in the slope of the employment rate, suggesting that the extensive margin of labor supply is more sensitive to this policy than commonly thought. We develop a model and method that allow us to translate the behavioral responses into a lower bound estimate of 0.49 for the extensive margin elasticity, which implies more than a 1 percentage point increase in work in the absence of the AET. (JEL H55, J14, J22, J26, J31)

Transcranial focused ultrasound modulates cortical and thalamic motor activity in awake sheep

Transcranial application of pulsed low-intensity focused ultrasound (FUS) modulates the excitability of region-specific brain areas, and anesthetic confounders on brain activity warrant the evaluation of the technique in awake animals. We examined the neuromodulatory effects of FUS in unanesthetized sheep by developing a custom-fit headgear capable of reproducibly placing an acoustic focus on the unilateral motor cortex (M1) and corresponding thalamic area. The efferent responses to sonication, based on the acoustic parameters previously identified in anesthetized sheep, were measured using electromyography (EMG) from both hind limbs across three experimental conditions: on-target sonication, off-target sonication, and without sonication. Excitatory sonication yielded greater amplitude of EMG signals obtained from the hind limb contralateral to sonication than that from the ipsilateral limb. Spurious appearance of motion-related EMG signals limited the amount of analyzed data (~ 10% selection of acquired data) during excitatory sonication, and the averaged EMG response rates elicited by the M1 and thalamic stimulations were 7.5 ± 1.4% and 6.7 ± 1.5%, respectively. Suppressive sonication, while sheep walked on the treadmill, temporarily reduced the EMG amplitude from the limb contralateral to sonication. No significant change was found in the EMG amplitudes during the off-target sonication. Behavioral observation throughout the study and histological analysis showed no sign of brain tissue damage caused by the acoustic stimulation. Marginal response rates observed during excitatory sonication call for technical refinement to reduce motion artifacts during EMG acquisitions as well as acoustic aberration correction schemes to improve spatial accuracy of sonication. Yet, our results indicate that low-intensity FUS modulated the excitability of regional brain tissues reversibly and safely in awake sheep, supporting its potential in theragnostic applications.

Psychological Responses of Motorcar Drivers to Flashing Amber Lights at Signalised T-Intersections

The accurate and timely decision making of drivers is vital to ensuring public safety and reaching the destination in time. This paper presents a detailed comparison of the expectation of regulatory bodies in implementing flashing amber lights and explores the actual driver responses to flashing amber lights at a signalised T-intersection by taking speed variation as a proxy for their decision making. A survey was conducted at a signalised T-intersection during the operation of flashing amber lights to measure the speed variation. Time-distance and speed gun techniques were used to collect speed data of motor cars. Results reflect those drivers show only a marginal response to flashing amber lights. Therefore, the intention of regulatory bodies that vehicles maintaining lower speed at a T-intersection with flashing amber lights was not satisfactorily fulfilled. The marginal response of drivers to flashing amber lights can be a leading cause of accidents occurring in signalised T-intersections at odd (night) hours.

A Prospective Study to Assess the Toxicity and Response of Preoperative Chemoradiotherapy in Oesophageal or Oesophagogastric Junction Cancer

Background: Carcinoma of the esophagus is an aggressive disease. Neoadjuvant chemoradiotherapy achieves the highest complete pathologic response rates, R0 resection rates, and improves 3-5 years survival rates. Methods: Patients with resectable carcinoma oesophagus were included in this prospective study. 22 patients were enrolled. All eligible patients were given radiation for a total radiation dose of 41.4Gy in 23 fractions of 1.8Gy each with five fraction administered per week. Weekly chemotherapy given with carboplatin (AUC 2mg/mm/mt) and paclitaxel (50mg/m2 of BSA). The patients were monitored weekly during the treatment for toxicities. These patients were evaluated with CECT after four to six weeks, and sent for surgery. Histopathological reports of these patients which included lymph node status, pathological response and resection margins were noted. Results: A total of 22 patients were enrolled. Neutropenia was the most common hematological toxicity and 4.5% had grade 2 neutropenia.There was no Grade 3 or 4 hematological toxicity. Most common GI toxicity seen was esophagitis and anorexia. 1 patient developed grade 3 esophagitis. 22% patients had grade 2 anorexia.17 patients underwent surgery and all of them had negative resected margins, 5 out of these 17 patients had pathological complete response. Conclusion: Preoperative chemoradiotherapy with weekly paclitaxel and carboplatin have good clinical response in terms of negative resection margin and pathological complete response with accepted level of toxicity. Prospective trials in larger series of patients are needed with long follow up.