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Despite the availability of GNSS on consumer devices enabled personal navigation for most of the World population in most of the outdoor conditions, the problem of precise pedestrian positioning is still quite challenging when indoors or, more in general, in GNSS-challenging working conditions. Furthermore, the covid-19 pandemic also raised of pedestrian tracking, in any environment, but in particular indoors, where GNSS typically does not ensure sufficient accuracy for checking people distance. Motivated by the mentioned needs, this paper investigates the potential of UWB and LiDAR for pedestrian positioning and tracking. The two methods are compared in an outdoor case study, nevertheless, both are usable indoors as well. The obtained results show that the positioning performance of the LiDAR-based approach overcomes the UWB one, when the pedestrians are not obstructed by other objects in the LiDAR view. Nevertheless, the presence of obstructions causes gaps in the LiDAR-based tracking: instead, the combination of LiDAR and UWB can be used in order to reduce outages in the LiDAR-based solution, whereas the latter, when available, usually improves the UWB-based results.

The development and availability on consumer devices of the global navigation satellite systems (GNSS) have dramatically changed the everyday-life of most of the human population, enabling real time navigation on almost any smart device produced in the last years. However, such strong dependence on the availability of the GNSS limits the further spread of location based services to the areas where GNSS is not available or reliable. Motivated by these considerations, several research groups recently considered the problem of developing alternative positioning systems able to compensate the unavailability of GNSS in certain areas. Similarly, this paper also investigates the performance of certain alternative methods, which aim at partially substitute GNSS. In particular, the positioning performance of an affordable Ultra Wide-Band system is compared with that of a vision approach, based on the use of visual information acquired by an Unmanned Aerial Vehicle (UAV) flying over the area of interest. In accordance with the results obtained in our dataset, the drone-based vision system usually allow to obtain better positioning results when the pedestrians are visible in the drone video frames (median 2D positioning error less than 25 cm). Nevertheless, the combination of such strategies shall also be investigated in order to obtain a more robust positioning system.

The increasing demand for reliable indoor navigation systems is leading the research community to investigate various approaches to obtain effective solutions usable with mobile devices. Among the recently proposed strategies, Ultra-Wide Band (UWB) positioning systems are worth to be mentioned because of their good performance in a wide range of operating conditions. However, such performance can be significantly degraded by large UWB range errors; mostly, due to non-line-of-sight (NLOS) measurements. This paper considers the integration of UWB with vision to support navigation and mapping applications. In particular, this work compares positioning results obtained with a simultaneous localization and mapping (SLAM) algorithm, exploiting a standard and a Time-of-Flight (ToF) camera, with those obtained with UWB, and then with the integration of UWB and vision. For the latter, a deep learning-based recognition approach was developed to detect UWB devices in camera frames. Such information is both introduced in the navigation algorithm and used to detect NLOS UWB measurements. The integration of this information allowed a 20% positioning error reduction in this case study.

Alloy 718 is a nickel-based superalloy that is widely used as a structural material for high-temperature applications. One concern that arises when Alloy 718 is manufactured using powder bed fusion (PBF) is that residual stresses appear due to the high thermal gradients. These residual stresses can be detrimental as they can degrade mechanical properties and distort components. In this work, residual stresses in PBF built Alloy 718, using both electron and laser energy sources, were measured by neutron diffraction. The effects of process parameters and thermal post-treatments were studied. The results show that thermal post-treatments effectively reduce the residual stresses present in the material. Moreover, the material built with laser based PBF showed a higher residual stress compared to the material built with electron-beam based PBF. The scanning strategy with the lower amount of residual stresses in case of laser based PBF was the chessboard strategy compared to the bi-directional raster strategy. In addition, the influence of measured and calculated lattice spacing (d0) on the evaluated residual stresses was investigated.

A Correction to this paper has been published: https://doi.org/10.1038/s41389-021-00305-2

Networks of small, low cost Unmanned Aerial Systems (UASs) have the potential to improve responsiveness and situational awareness across an increasing number of applications including defense, surveillance, mapping, search and rescue, disaster management, mineral exploration, assisted guidance and navigation etc. These ad hoc UAS networks typically have the capability to communicate with each other and can share data between the individual UAS nodes. Thus these networks can operate as robust and efficient information acquisition platforms. For any of the applications involving UASs, a primary requirement is the localization i.e. determining the position and orientation of the UAS. The performance requirements of localization can vary with individual applications, for example: mapping applications need much higher localization accuracy as compared to the applications involving only surveillance. The sharing of appropriate data between UASs can prove to be advantageous when compared to a single UAS, in terms of improving the positioning accuracy and reliability particularly in partially or completely GNSS denied environments. This research aims to integrate low cost positioning sensors and cooperative localization technique for a network of UASs. Our hypothesis is that it is possible to achieve high accurate, real-time localization of each of the nodes in the network even with cheaper sensors if the nodes of the network share information among themselves. This hypothesis is validated using simulations and the results are analyzed both for centralized and distributed estimation architectures. At first, the results are studied for a two node network which is then expanded for a network containing more number of nodes. Having more nodes in the network allows us to study the properties of the network including the effect of size and shape of the network on accuracy of the nodes.

Tracking of targets from aerial platforms is an important activity in several applications, especially surveillance. Knowled ge of geolocation of these targets adds additional significant and useful information to the application. This paper determines the geolocation of a target being tracked from an aerial platform using the technique of image registration. Current approaches utilize a POS to determine the location of the aerial platform and then use the same for geolocation of the targets using the principle of photogrammetry. The constraints of cost and low-payload restrict the applicability of this approach using UAV platforms. This paper proposes a methodology for determining the geolocation of a target tracked from an aerial platform in a partially GPS devoid environment. The method utilises automatic feature based registration technique of a georeferenced satellite image with an ae rial image which is already stored in UAV's database to retrieve the geolocation of the target. Since it is easier to register subsequent aerial images due to similar viewing parameters, the subsequent overlapping images are registered together sequentially thus resulting in the registration of each of the images with georeferenced satellite image thus leading to geolocation of the target under interest. Using the proposed approach, the target can be tracked in all the frames in which it is visible. The proposed concept is verified experimentally and the results are found satisfactory. Using the proposed method, a user can obtain location of target of interest as well features on ground without requiring any POS on-board the aerial platform. The proposed approach has applications in surveillance for target tracking, target geolocation as well as in disaster management projects like search and rescue operations.

The limitation of conventional laser scanning methods is that the objects being scanned should be static. The need of scanning moving objects has resulted in the development of new methods capable of generating correct 3D geometry of moving objects. Limited literature is available showing development of very few methods capable of catering to the problem of object motion during scanning. All the existing methods utilize their own models or sensors. Any studies on error modelling or analysis of any of the motion correction methods are found to be lacking in literature. In this paper, we develop the error budget and present the analysis of one such ‘motion correction’ method. This method assumes availability of position and orientation information of the moving object which in general can be obtained by installing a POS system on board or by use of some tracking devices. It then uses this information along with laser scanner data to apply correction to laser data, thus resulting in correct geometry despite the object being mobile during scanning. The major application of this method lie in the shipping industry to scan ships either moving or parked in the sea and to scan other objects like hot air balloons or aerostats. It is to be noted that the other methods of "motion correction" explained in literature can not be applied to scan the objects mentioned here making the chosen method quite unique. This paper presents some interesting insights in to the functioning of "motion correction" method as well as a detailed account of the behavior and variation of the error due to different sensor components alone and in combination with each other. The analysis can be used to obtain insights in to optimal utilization of available components for achieving the best results.

Background: There is conflicting evidence regarding the effect of residual transmitral mean pressure gradient (TMPG) after mitral transcatheter edge-to-edge repair (M-TEER). Different TMPG cutoffs have been employed in prior studies with varying results. Objectives: The purpose of this study was to examine the association between residual TMPG and M-TEER outcomes. Methods: Consecutive patients undergoing M-TEER at our institution between 2014 and 2022 were included and divided based on quartiles of predischarge TMPG. Outcomes were assessed using Kaplan-Meier analysis and Cox proportional hazard models. We performed subgroup analyses according to mitral regurgitation (MR) mechanism. The primary outcome was all-cause mortality or heart failure hospitalization. Results: We included 283 patients (age 76.7 ± 10.8 years, 42.8% women, 78.4% Caucasian, and baseline TMPG 2.4 ± 1.3 mm Hg). Higher baseline TMPG was a predictor of increased TMPG after M-TEER (coefficient 0.60 [95% CI: 0.40-0.70]; P

Monolithic glass shells can be constructed in limited sizes. Segmented shells allow coverage of larger spans. Three shell systems - spherical dome, cylindrical roof and hyperbolic paraboloid were segmented using four different curved glass segment shapes – square, diamond (or pie for dome), hexagon and hexalock. Three joint materials were analysed- glass (resulting in a monolithic glass shell), silicone (soft adhesive) and epoxy (hard adhesive). A Reissner-Mindlin finite element was used in ANSYS to discretize the modelled geometry. The boundary conditions were setup keeping in mind the favourable membrane behaviour of shell structures. It was found out that glass segment shape and joint stiffness has an influence on the shell behaviour. Optimal shapes show similar behaviour in comparison to monolithic glass shell. Others show a significant increase in the deflection and bending moment values which is unwanted. The in-plane membrane forces remain unaffected and thus are found to be independent of glass segment shape and joint stiffness.

Background Coronary microvascular function and hemodynamics may play a role in coronary circulation and myocardial remodeling in patients with aortic stenosis (AS). We aimed to evaluate the relationship between myocardial blood flow and myocardial function in patients with AS, no AS, and aortic valve sclerosis. Methods and Results We included consecutive patients who had resting transthoracic echocardiography and clinically indicated positron emission tomography myocardial perfusion imaging to capture their left ventricular ejection fraction, global longitudinal strain (GLS), and myocardial flow reserve (MFR). The primary outcome was major adverse cardiovascular event (all‐cause mortality, myocardial infarction, or late revascularization). There were 2778 patients (208 with aortic sclerosis, 39 with prosthetic aortic valve, 2406 with no AS, and 54, 49, and 22 with mild, moderate, and severe AS, respectively). Increasing AS severity was associated with impaired MFR (P

Background Pulmonary hypertension (PH) and secondary mitral regurgitation (MR) are associated with adverse outcomes after mitral transcatheter edge‐to‐edge repair. We aim to study the prognostic value of invasively measured right ventricular afterload in patients undergoing mitral transcatheter edge‐to‐edge repair. Methods and Results We identified patients who underwent right heart catheterization ≤1 month before transcatheter edge‐to‐edge repair. The end points were all‐cause mortality and a composite of mortality and heart failure hospitalization at 2 years. Using the receiver operating characteristic curve–derived threshold of 0.6 for pulmonary effective arterial elastance ([Ea], pulmonary artery systolic pressure/stroke volume), patients were stratified into 3 profiles based on PH severity (low elastance [HE]: Ea

Background Prior studies investigating the impact of residual mitral regurgitation (MR), tricuspid regurgitation (TR), and elevated predischarge transmitral mean pressure gradient (TMPG) on outcomes after mitral transcatheter edge‐to‐edge repair (TEER) have assessed each parameter in isolation. We sought to examine the prognostic value of combining predischarge MR, TR, and TMPG to study long‐term outcomes after TEER. Methods and Results We reviewed the records of 291 patients who underwent successful mitral TEER at our institution between March 2014 and June 2022. Using well‐established outcomes‐related cutoffs for predischarge MR (≥moderate), TR (≥moderate), and TMPG (≥5 mm Hg), 3 echo profiles were developed based on the number of risk factors present (optimal: 0 risk factors, mixed: 1 risk factor, poor: ≥2 risk factors). Discrimination of the profiles for predicting the primary composite end point of all‐cause mortality and heart failure hospitalization at 2 years was examined using Cox regression. Overall, mean age was 76.7±10.6 years, 43.3% were women, and 53% had primary MR. Two‐year event‐free survival was 61%. Predischarge TR≥moderate, MR≥moderate, and TMPG≥5 mm Hg were risk factors associated with the primary end point. Compared with the optimal profile, there was an incremental risk in 2‐year event‐rate with each worsening profile (optimal as reference; mixed profile: hazard ratio (HR), 2.87 [95% CI, 1.71–5.17], P

Objective: The study was undertaken to evaluate maternal and Perinatal outcomes following transcervical intrapartum amnioin- fusion in women with meconium stained amniotic fluid. Methods: A randomized control study was conducted on 200 women with moderate to thick meconium stained amniotic fluid during labor. Group A (study group) of 100 cases received amnio- infusion. Group B (control group) of 100 cases received standard obstetric care. Fetal heart rate monitoring was done using cardioto- cography. Results: 66% of women were in the age group of 21-25 years. Av- erage cervical dilatation at detection of meconium and detection of meconium to delivery interval was similar in both groups. In the study group, 68% women had normal vaginal delivery as com- pared to 49% in the control group (p

Background: National Tobacco Control Programme was launched in India in year 2007-08. It was realized that community health workers can play an important role of agents for positive change to bring down the tobacco morbidity and mortality in the country. Keeping this in view, a health worker guide was developed by the Government of India, Ministry of Health and Family Welfare (GOI) in collaboration with The Union South-East Asia (The Union) in the year 2010. The guide provides the information needed by the most basic level of health workers to effectively address the problem of tobacco use in the community. A modular training was conducted in two jurisdictions in India (namely, Chandigarh and Hamirpur (Himachal Pradesh)) to assess the usefulness of the guide as training material for community health workers in undertaking tobacco control activities at community and village levels.Materials and Methods: A total of 271 participants were trained, which included 133 from Chandigarh and 138 from Hamirpur. The pre and post-training assessment of knowledge of health worker was done.Results: There was marked increase in post-test scores as compared to the pretest scores. The health workers scoring more than 60% increased from 40% in the pretest to over 80% in the post-test. Only three workers had a post-test score of less than 30% against 54 workers in the pretest.Conclusion: The understanding on tobacco control had increased significantly after the training in each group. It is strongly recommended that such training should be replicated to all community health workers across all the states in India. [ABSTRACT FROM AUTHOR]

Background The occurrence of an extrarenal Wilms tumor in the lumbosacral region is an extremely uncommon condition. Case report We report a case of Wilms tumor in the lumbosacral region that was associated with diastematomyelia and occult spina bifida. An 18-month-old girl presented with a swelling over the lower back with a tuft of hair on it, which she had had since birth. Imaging of the spine revealed spina bifida, bony diastematomyelia, and tethered cord. Excision of the bony spur and detethering of the cord was done. After a year, she had recurrence of swelling at the same site, weakness of both lower limbs, and incontinence of bladder and bowel. Excision of the mass and bony spur and detethering of the spinal cord were done. Histopathological examination showed features of a Wilms tumor. [ABSTRACT FROM AUTHOR]

The Regional Antarctic ice and Global Ocean (RAnGO) model has been developed to study the interaction between the world ocean and the Antarctic ice sheet. The coupled model is based on a global implementation of the Finite Element Sea-ice Ocean Model (FESOM) with a mesh refinement in the Southern Ocean, particularly in its marginal seas and in the sub-ice-shelf cavities. The cryosphere is represented by a regional setup of the ice flow model RIMBAY comprising the Filchner–Ronne Ice Shelf and the grounded ice in its catchment area up to the ice divides. At the base of the RIMBAY ice shelf, melt rates from FESOM's ice-shelf component are supplied. RIMBAY returns ice thickness and the position of the grounding line. The ocean model uses a pre-computed mesh to allow for an easy adjustment of the model domain to a varying cavity geometry. RAnGO simulations with a 20th-century climate forcing yield realistic basal melt rates and a quasi-stable grounding line position close to the presently observed state. In a centennial-scale warm-water-inflow scenario, the model suggests a substantial thinning of the ice shelf and a local retreat of the grounding line. The potentially negative feedback from ice-shelf thinning through a rising in situ freezing temperature is more than outweighed by the increasing water column thickness in the deepest parts of the cavity. Compared to a control simulation with fixed ice-shelf geometry, the coupled model thus yields a slightly stronger increase in ice-shelf basal melt rates.

Glaciers and ice caps exhibit currently the largest cryospheric contributions to sea level rise. Modelling the dynamics and mass balance of the major ice sheets is therefore an important issue to investigate the current state and the future response of the cryosphere in response to changing environmental conditions, namely global warming. This requires a powerful, easy-to-use, versatile multi-approximation ice dynamics model. Based on the well-known and established ice sheet model of Pattyn (2003) we develop the modular multi-approximation thermomechanic ice model RIMBAY, in which we improve the original version in several aspects like a shallow ice–shallow shelf coupler and a full 3D-grounding-line migration scheme based on Schoof's (2007) heuristic analytical approach. We summarise the full Stokes equations and several approximations implemented within this model and we describe the different numerical discretisations. The results are cross-validated against previous publications dealing with ice modelling, and some additional artificial set-ups demonstrate the robustness of the different solvers and their internal coupling. RIMBAY is designed for an easy adaption to new scientific issues. Hence, we demonstrate in very different set-ups the applicability and functionality of RIMBAY in Earth system science in general and ice modelling in particular.

There is currently no doubt about the existence of a widespread hydrological network under the Antarctic Ice Sheet, which lubricates the ice base and thus leads to increased ice velocities. Consequently, ice models should incorporate basal hydrology to obtain meaningful results for future ice dynamics and their contribution to global sea level rise. Here, we introduce the balanced water layer concept, covering two prominent subglacial hydrological features for ice sheet modeling on a continental scale: the evolution of subglacial lakes and balance water fluxes. We couple it to the thermomechanical ice-flow model RIMBAY and apply it to a synthetic model domain. In our experiments we demonstrate the dynamic generation of subglacial lakes and their impact on the velocity field of the overlaying ice sheet, resulting in a negative ice mass balance. Furthermore, we introduce an elementary parametrization of the water flux–basal sliding coupling and reveal the predominance of the ice loss through the resulting ice streams against the stabilizing influence of less hydrologically active areas. We point out that established balance flux schemes quantify these effects only partially as their ability to store subglacial water is lacking.

Background The clinical significance of mitral annular calcification (MAC) in patients undergoing mitral transcatheter edge‐to‐edge repair is not well understood. There is limited evidence regarding the feasibility, durability of repair, and the prognostic value of MAC in this population. We sought to examine the prognostic value of MAC, its severity, and its impact on procedural success and durability of mitral transcatheter edge‐to‐edge repair. Methods and Results We reviewed the records of 280 patients with moderate–severe or severe mitral regurgitation who underwent mitral transcatheter edge‐to‐edge repair with MitraClip from March 2014 to March 2022. The primary end point was cumulative survival at 1 year. Independent factors associated with the primary end point were identified using multivariable Cox regression. Among 280 patients included in the final analysis, 249 had none/mild MAC, and 31 had moderate/severe MAC. Median follow‐up was 23.1 months (interquartile range: 11.1–40.4). Procedural success was comparable in the MAC and non‐MAC groups (92.6% versus 91.4%, P=0.79) with similar rates of residual mitral regurgitation ≤2 at 1 year (86.7% versus 93.2%, P=0.55). Moderate/severe MAC was associated with less improvement in New York Heart Association III/IV at 30 days when compared with none/mild MAC (45.8% versus 14.3%, P=0.001). The moderate/severe MAC group had lower cumulative 1‐year survival (56.8% versus 80.0%, hazard ratio [HR], 1.98 [95% CI, 1.27–3.10], P=0.002). Moderate/severe MAC and Society of Thoracic Surgeons predicted risk of mortality for mitral valve repair were independently associated with the primary end point (HR, 2.20 [1.10–4.41], P=0.02; and HR, 1.014 [1.006–1.078], P=0.02, respectively). Conclusions Mitral TEER is a safe and feasible intervention in selected patients with significant MAC and associated with similar mitral regurgitation reduction at 1 year compared with patients with none/mild MAC. Patients with moderate/severe MAC had a high 1‐year mortality and less improvement in their symptoms after TEER.

A 59-year-old male patient with history of rheumatic heart disease with 3 previous surgical aortic valve replacements with the last one being homograft followed by transcatheter aortic valve implantation in failed homograft presented with severe aortic regurgitation and cardiogenic shock requiring urgent TAV-in-TAV-in homograft. (Level of Difficulty: Advanced.)

Transesophageal echocardiography is the main imaging modality for localizing and quantifying prosthetic aortic regurgitation. We describe a case of bioprosthetic aortic paravalvular leak (PVL) where transesophageal echocardiography was inadequate; aortic root angiography and computed tomography fusion were critical in diagnosing and guiding closure. Multimodality imaging can be pivotal in localizing PVL and guiding transcatheter PVL closure. (Level of Difficulty: Intermediate.)

Background: We have previously established the recommended phase II dose (RPTD) of ixabepilone as 40 mg/m2 administered over 1 h repeated every 3 weeks with neuropathy as a cumulative dose-limiting toxicity. We expanded the cohort at the RPTD to include detailed assessment of nerve damage in these patients. We report our findings on vibration perception threshold (VPT) and neuropathy. Patients and methods: Forty-four patients were treated with a median (range) of three (1–14) cycles of ixabepilone. The VPT (5-min duration) and nerve conduction test (NCT, 10-min duration) were carried out in the office, before ixabepilone dosing, and every two cycles thereafter. Results: Neuropathy (grade 1 and grades 2–3) was observed in 17 (38.6%) and 11 (25%) patients, respectively. The mean increase in VPT as a function of grade 0–1 versus grades 2–3 neuropathy was 0.235 ± 0.03 versus 0.869 ± 0.09 (P = 0.049) vibration units. The F-wave frequency and distal motor latency, as assessed using the NCT, did not correlate with clinical neurotoxicity. Conclusion: The change in VPT is observed early and likely reflects early vibration perception change. Mean change in VPT correlates with the severity of clinical neuropathy. Whether VPT change predicts onset of severe neuropathy warrants prospective testing and validation. [ABSTRACT FROM AUTHOR]

Gonocytes are primitive germ cells that reside in neonatal testis and are believed to be progenitor-type stem cells that differentiate into spermatogonial stem cells. Because of their self-renewal ability, gonocytes may be one of the targets for cryopreservation of genetic resources in domestic animals and in endangered species. However, there are only a few reports regarding the preservation of gonocytes and spermatogonial stem cells isolated from the testis. In this experiment, porcine gonocytes were used as a model for preservation of genetic resources. Porcine testes were collected at 2–6 days after birth. They were divided into the 5 experimental groups for storage: (1) DMEM/F12 medium, (2) DMEM/F12 + 15 mm HEPES, (3) PBS, (4) PBS + 15 mm HEPES, and (5) Liquid-Free, and stored at 4C for 24 h. The testes were minced by scissors and digested with 2-step enzyme treatments. The gonocytes were isolated by Percoll density gradients and recovered from the fraction between 50 and 60%. The viability of cells was assessed using trypan blue dye exclusion. To determine optimum cryopreservation conditions for gonocytes, 10% DMSO, 10% glycerol, and 0.07 mm sucrose were used as cryoprotectants. The isolated gonocytes were suspended in DMEM/F12 + 10% FBS containing cryoprotectant at 4C, kept at –80C overnight, and finally immersed in liquid nitrogen. After freezing and thawing of gonocytes, cells were examined for viability and then cultured in DMEM/F12 + 10% FBS in 5% CO2, 95% air at 37C in humidified atmosphere. Identification of gonocytes was performed using a specific marker of gonocytes, a lectin Dolichos biflorus agglutinin (DBA; Goel et al. 2007 Biol. Reprod. 77, 127–137). The gonocytes were recovered from testes at the purity level of around 70%. Cell viability in average after storage of testes at 4C was significantly higher in DMEM/F12 + HEPES (95.3%) and PBS + HEPES (89.8%) than in DMEM/F12 (73.9%), PBS (79.7%), and Liquid-Free (72.2%) (P < 0.05; ANOVA). The addition of HEPES in storage medium seemed to be effective for improving cell viability. The use of 10% DMSO and 0.07 mm sucrose as cryoprotectants supported high cell viability (74.4%) of gonocytes after freezing and thawing. The addition of glycerol had an adverse effect on cell viability after freezing (18.3%). When cells were cultured, gonocytes started to form colonies after 3 days and continued to proliferate for at least 7 days in culture. These colonies showed DBA affinity and maintained their nature as gonocytes. The viability of gonocytes can be maintained in the testis at 4C for at least 24 h and after freezing and thawing. The stored gonocytes successfully proliferated in culture for at least 7 days. In conclusion, these results may provide useful information for short-term storage of primitive germ cells and preservation of genetic resources in domestic animals and in endangered species. It may also have implications for assisted reproductive technology in humans. [ABSTRACT FROM AUTHOR]

Background: ING-1 is a high-affinity, human engineered™ monoclonal antibody that recognizes a 40 kilodalton epithelial cell adhesion molecule (EpCAM) glycoprotein that is expressed in high levels on most adenocarcinomas and is an attractive target for immunotherapy. Methods: ING-1 was administered subcutaneously weekly at doses between 0.1 and 2 mg/kg/week. Pharmacokinetic samples were drawn during weeks 1 and 6. Results: Fourteen patients with advanced refractory cancer received a median of 6 (range 1–9) doses of ING-1. At 1 mg/kg, a 62-year-old man with colon cancer developed reversible grade 3 pancreatitis after the third dose. His plasma ING-1 levels were similar to the other two patients dosed at 1 mg/kg. Two patients dosed at 0.6 mg/kg experienced stable disease at 6 weeks. Peak drug levels increased with dose and time, suggesting drug accumulation with repeated dosing. Low human anti-human antibody response was noted in three of the 13 patients assessed and was directed towards the variable region of ING-1. Conclusions: Weekly ING-1 administered subcutaneously was well tolerated at 0.6 mg/kg/week and further experience at this dose is warranted to demonstrate safety. The risk of pancreatitis and the marginal anti-tumor effect may preclude further monotherapy studies; however, combination studies with chemotherapy are warranted. [ABSTRACT FROM AUTHOR]

Livestock transgenesis is primarily directed towards improving productive traits or for biomedical research. Transgenic pig is of immense interest because it could provide tissues and organs for xenotransplantation to humans. Conventional methods like pronuclear microinjection of zygote and, more recently, somatic cell nuclear transfer (SCNT) have been used for generating genetically modified pigs. These methods are, however, inefficient and have numerous shortcomings. Male germline stem cells have enormous potential, because they could serve as an alternative approach to generate genetically modified pigs, in which the homologous recombination technique could be applied. However, this could not be achieved due to lack of knowledge of culture conditions and markers that can distinguish germ cells from somatic cells, enabling their isolation and identification in culture. Lectin dolichos biflourus agglutinin (DBA), which has specific affinity for ?-d-N-acetyl-galactosamine, reacts with the large round primordial germ cells of the pig genital ridge (Takagi et al. 1997 Mol. Reprod. Dev. 46, 567–580). Immunohistochemical analysis of testicular samples from different age groups revealed that DBA binds to primitive germ cells in neonatal pig testis like gonocytes and pre-spermatogonia. Variable DBA affinity among germ cells and its progressive loss with age suggested that DBA bound strongly to gonocytes, weakly to undifferentiated spermatogonia, and not at all to spermatogonia. The presence of alkaline phosphatase activity in germ cells from neonatal pig testis further confirmed the existence of primitive germ cells. Gonocytes from neonatal pig testis were isolated using 2-step enzymatic digestion and discontinuous Percoll density gradient. Approximately 70% gonocytes were present in the fraction 5 (50–60% gradient) that were identified by their DBA affinity. Isolated cells were cultured in DMEM/F12 supplemented with 10 g mL-1 of insulin, 10 g mL-1 of apo-transferrin, 100 U mL-1 of penicillin, 50 g mL-1 of streptomycin, 40 g mL-1 of gentamycin sulphate, 1 mM pyruvate, 1 non-essential amino acid solution, and 10% fetal bovine serum at 37C in 5% CO2 in air in a humidified atmosphere. Initially, gonocytes grew as adherent cells that formed foci of flat colonies. These colonies grew in size during the culture period, and DBA-positive cells were observed. Flat colonies transformed to ES-like colonies by 6–7 days of culture, which were still positive for DBA binding. Proliferation of germ cells was evaluated by double immunostaining with DBA and anti-bromodeoxyuridine (BrdU) antibody following BrdU incorporation, suggesting that 53–55% DBA-positive cells were in S phase after 7 days of culture. In conclusion, lectin DBA is a marker for porcine primitive germ cells in neonatal pig testis including gonocytes that could be used for their identification during isolation and in culture. Isolated gonocytes could proliferate in vitro without specific growth factor supplementation. [ABSTRACT FROM AUTHOR]

Background: Elevated cardiac troponin (cTn) levels in patients with COVID-19 has been associated with worse outcomes. Guidelines on best practices of those patients remain uncertain. Methods: We included patients with COVID-19 and cTn above the assay-specific upper limit of normal (ULN) enrolled in the American Heart Association's COVID-19 registry between March 2020–January 2021. Site-level variability in invasive coronary angiography, LVEF assessment, ICU utilization, and inpatient mortality were determined by calculating adjusted median odds ratio (MOR) using hierarchical logistic regression models. Temporal trends were assessed with Cochran-Armitage trend test. Results: Among 32,636 patients, we included 6234 (19.4 %) with cTn above ULN (age 68.7 ± 16.0 years, 56.5 % male, 51.5 % Caucasian), of whom 1365 (21.6 %) had ≥5-fold elevations. Across 55 sites, the median rate of invasive coronary angiography was 0.1 % with adjusted MOR 1.5(1.0,2.3), median LVEF assessment was 25.5 %, MOR 3.0(2.2,3.9), ICU utilization was 41.7 %, MOR 2.2(1.8,2.6), and mortality was 20.9 %, MOR 1.7(1.5,2.0). Over time, we noted a significant increase in invasive coronary angiography (p-trend = 0.001), and LVEF assessment (p-trend

Translational research should examine racism and bias and improve health equity. We designed and implemented a course for the Master of Science in Clinical Investigation program of the Northwestern University Clinical and Translational Sciences Institute. We describe curriculum development, content, outcomes, and revisions involving 36 students in 2 years of “Anti-Racist Strategies for Clinical and Translational Science.” Ninety-six percent of students reported they would recommend the course. Many reported changes in research approaches based on course content. A course designed to teach anti-racist research design is feasible and has a positive short-term impact on learners.

Transcatheter mitral valve repair using the MitraClip (Abbott Vascular, Santa Clara, CA) is a reasonable option for the treatment of patients with severe symptomatic degenerative mitral regurgitation (MR) who are at prohibitive surgical risk. The occurrence of recurrent severe MR after initial successful MitraClip repair is uncommon. Data are sparse on the management of recurrent severe MR after initial successful repair using the MitraClip. We describe a successful case of redo MitraClip repair for late recurrent severe MR secondary to progressive degenerative mitral valve disease after a successful initial MitraClip procedure and review the literature. Résumé: La réparation transcathéter de la valve mitrale au moyen d’un dispositif MitraClip (Abbott Vascular, Santa Clara, CA) constitue une bonne option pour le traitement de l’insuffisance mitrale (IM) dégénérative symptomatique grave lorsque la chirurgie représente un risque prohibitif pour le patient. Il est rare qu’une IM grave récurrente survienne après l’implantation réussie d’un dispositif MitraClip. On dispose de très peu de données sur la prise en charge de l’IM grave récurrente après une première réparation au moyen d’un dispositif MitraClip. Nous présentons le cas d’une seconde réparation au moyen d’un dispositif MitraClip pour remédier à une IM grave récurrente tardive secondaire à une atteinte dégénérative évolutive de la valve mitrale survenue après une première intervention efficace au moyen d’un dispositif MitraClip, et nous passons en revue les publications portant sur cette question.

This case demonstrates the feasibility and procedural success of a novel supra-annular transcatheter mitral valve, the AltaValve via transapical approach in a patient with severe symptomatic mitral regurgitation who was a prohibitive surgical risk candidate. (Level of Difficulty: Advanced.)

Background Data are limited about young adults' characteristics and outcomes undergoing coronary artery bypass grafting (CABG). Methods and Results We used the National Inpatient Sample database to identify adults aged 18 to 45 years who underwent CABG between 2004 and 2018. The data were weighted to generate national estimates of the entire US hospitalized population. We identified 110 463 CABG cases, equivalent to 62.2 per 1 000 000 person‐years; 27.1% were women, and 70.2% were White adults. Overall, annual CABG volume per 1 000 000 significantly decreased from 87.3 in 2004 to 45.7 in 2018. The prevalence of obesity, diabetes mellitus, hypertension, drug abuse, and chronic medical conditions increased over time. Overall, inpatient mortality was 1.76%; ST‐segment–elevation myocardial infarction, non–ST‐segment–elevation myocardial infarction, heart failure, peripheral vascular disease, renal failure, and valvular surgery were associated with higher inpatient mortality. Women had higher inpatient mortality than men (2.29% versus 1.57%), and Black patients had higher deaths than White patients (2.86% versus 1.58%). Inpatient mortality remained stable overall, according to sex, race, or clinical indication of CABG. However, the mean length of stay (8.4 days in 2004 to 9.5 days in 2018) and inflation‐adjusted cost of care ($40 522.8 in 2004 to $52 434.2 in 2018) significantly increased during the study period. Conclusions Despite the increased burden of cardiometabolic risk factors, the inpatient mortality in young adults undergoing CABG remained stable during the last 15 years. However, CABG volumes have decreased, but length of stay and inflation‐adjusted costs have increased over time.

Aortic stenosis (AS) is a common valvular heart disease in the aging population that is characterized by a variable period of asymptomatic phase before development of symptoms and severe AS. Mortality and morbidity is substantial even after aortic valve replacement, in part related to persistent left ventricular hypertrophy, diastolic dysfunction, and heart failure. Renin‐angiotensin system (RAS) blockade therapy is associated with modulation of adverse left ventricular remodeling, reduction in myocardial hypertrophy, and fibrosis, resulting in clinical improvements in patients with congestive heart failure There are emerging data to suggest benefit of RAS blockade in patients with AS before and after AVR with regard to potentially slower progression of aortic valve calcification, left ventricular mass and survival benefit in favor of RAS blockade group before AVR, and also survival benefit in patients after AVR. We review the available data to understand the role of RAS blockade before AVR and in patients undergoing surgical AVR and transcatheter AVR. There are significant survival advantages of RAS inhibition in patients with AS undergoing surgical AVR or transcatheter AVR. On the basis of existing literature, adequately powered randomized trials are needed to evaluate the role of RAS inhibition in patients with AS.

No crop contributes more to human flesh than the wheat that gives us our daily bread. A range of products can be processed from its flour, like bread, pasta, biscuits, chapatti etc, out of which bread is the most successful one. The end use quality of bread is mainly dependent on the quality and quantity of wheat seed storage proteins. There is a continuously increasing demand for good bread products both by the consumers and baking industry. To meet the growing demand of high quality nutritious bread with long shelf life a range of biotechnical and nanotechnical formulas have been employed to bring a new shape to food for the upcoming generation. Proteomics and transformation led to improved end product by modifying the wheat seed storage proteins for improved end products. Nanotechnology is an upcoming technology which is proving to be helpful in packaging and nutritional enhancement. Here, in this article, we have listed and focused on the techniques that would be helpful in enhancing bread quality and its nutritional status in future.

Abstract Aneurysmal bone cyst (ABC) is an expansile, osteolytic lesion. The association of ABC with pregnancy is a very rare entity. We are reporting a unique case of spinal ABC, presenting as pathological fracture, paraplegia, and abdominal mass in the 28th week of pregnancy. A brief review of the literature is discussed. Dyshomeostasis of bone calcium, hormonal, and mechanical stress can aggravate the severity of ABC during pregnancy. A multidisciplinary approach is required to manage such cases, depending on the fetal gestational age and maternal neurological features.

Experiment was conducted to analyse maize (Zea mays L.) hybrids for antioxidant enzymes and non-enzyme compound at two leaf stages, under normal irrigation (IRR) and water deficit stress (WDS) condition. WDS was induced by withholding irrigation water for three days in seven-day old seedlings grown in pots. The hybrids exhibited wide variability in their antioxidant pools combined with activities of enzymes involved in defence against oxidative stress. The results showed that antioxidant activity was higher in tolerant hybrids than the susceptible hybrids. Superoxide dismutase activity was higher in susceptible hybrids under IRR, whereas it decreased significantly under WDS. On the other hand, peroxidase activity was increased almost two folds in all the tolerant hybrids. Under WDS, glutathione reductase activity increased in all the hybrids except VIVEKHYD-9, whereas the increase was highest, i.e.37.4% in tolerant than the susceptible hybrids. Catalase activity increased 56% in tolerant hybrid, whereas a decrease of about 30% was recorded in susceptible under WDS. Also, ascorbate peroxidase activity increased in tolerant hybrids and decreased in susceptible hybrids under WDS. In response to WDS, glutathione content (GSH) decreased 11% in tolerant while increased 55% in susceptible hybrids. Increase in GSH content was highest (100%) in HQPM-7 followed by NK-6240 (56%). In general, ascorbic acid content increased under WDS in both tolerant and susceptible hybrids, however the increase was higher in tolerant (80%) than susceptible (45%). Among the hybrids, highest increase was recorded in PRAKASH (99%) and lowest in VIVEKHYD-9 (29%), thus PRAKASH seems to be drought tolerant while VIVEKHYD-9 is drought susceptible. Thus status of antioxidant enzymes in maize hybrids could be evaluated with the drought tolerance during different stages of development and growth and could be used in developing climate resilient maize hybrids.

Arachnoid cysts are cerebrospinal fluid collections in the spine that can present with neurological symptoms or be discovered accidentally. Intradural location of such cysts especially in the lumbosacral region is relatively rare. The association of such cysts with other congenital anomalies such as tethered cord lends evidence to the developmental origin of arachnoid cysts. We report a case of lumbosacral arachnoid cyst with tethered cord in a 6-year-old male child and discuss the etiopathogenesis and management options.

Background: We previously demonstrated that peak microtubule bundle formation (MBF) in peripheral blood mononuclear cells (PBMCs) occurs at the end of drug infusion and correlates with drug pharmacokinetics (PK). In the current study, a new expanded evaluation of drug target effect was undertaken.Patients and methods: Patients with advanced solid malignancies were treated with ixabepilone 40 mg/m2 administered as a 1-h i.v. infusion every 3 weeks. Blood, plasma, and tumor tissue sampling was carried out to characterize pharmacodynamics and PK.Results: Forty-seven patients were treated with 141 cycles of ixabepilone. In both PBMCs (n = 27) and tumor cells (n = 9), peak MBF occurred at the end of infusion; however, at 24–72 h after drug infusion, the number of cells with MBF was significantly greater in tumor cells, relative to PBMCs. A Hill model (EC50 = 109.65 ng/ml; r2 = 0.94) was fitted, which demonstrated a relationship between percentage of PBMCs with MBF and plasma ixabepilone concentration. The percentage of PBMCs with MBF at the end of infusion also correlated with severity of neutropenia (P = 0.050).Conclusions: Plasma ixabepilone concentration and severity of neutropenia correlate with the level of MBF in PBMCs. Therefore, this technically straightforward assay should be considered as a complement to the clinical development of novel microtubule-binding agents. [ABSTRACT FROM AUTHOR]