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Organ transplantation is a modern medical success story. However, since its inception it has been limited by the need for pharmacological immunosuppression. Regulatory cellular therapies offer an attractive solution to these challenges by controlling transplant alloresponses through multiple parallel suppressive mechanisms. A number of cell types have seen an accelerated development into human trials and are now on the threshold of a long-awaited breakthrough in personalized transplant therapeutics. Here we assess recent developments with a focus on the most likely candidates, some of which have already facilitated successful immunosuppression withdrawal in early clinical trials. We propose that this may constitute a promising approach in clinical transplantation but also evaluate outstanding issues in the field, providing cause for cautious optimism.

Zusammenfassung Hintergrund Die Behandlung komplexer abdomineller und thorakoabdomineller Aortenaneurysmen stellt für alle Beteiligten eine Herausforderung dar. Die offene chirurgische Versorgung ist ein Hochrisikoeingriff und ist besonders im Notfall mit erhöhter Morbidität und Mortalität assoziiert. Die endovaskuläre Ausschaltung mithilfe eines patientenspezifischen maßgefertigten Stentgrafts steht aufgrund der erforderlichen Herstellungszeit bei Patienten mit symptomatischen oder rupturierten komplexen Aneurysmen nicht zur Verfügung. In diesen Fällen müssen alternative endovaskuläre Techniken angewendet werden. Ergebnisse Zu den endovaskulären Therapieoptionen komplexer Aneurysmen in dringenden Fällen und Notfällen zählen die „off-the-shelf“ und die „surgeon-modified“ Stentgrafts. Die ersten sind standardisiert hergestellte fenestrierte oder gebranchte Endoprothesen, die aufgrund der anatomischen Gegebenheiten bei etwa 50 – 80% der Patienten eingesetzt werden können. Die „surgeon-modified“ oder „vom Chirurgen modifizierten“ Stentgrafts beschreiben eine Technik, bei der eine kommerzielle Stentprothese unter sterilen Bedingungen und direkt vor der Implantation durch den Operateur bearbeitet wird, damit die benötigten Fenestrierungen, Scallops und Branches geschaffen werden. Die Modifikationsdauer beträgt 60 – 120 min angepasst an die Anatomie des Patienten. Es handelt sich um einen „off-label“-Gebrauch eines kommerziellen Stentgrafts außerhalb der Anweisungen des Herstellers und wenn möglich, sollte eine entsprechende ausführliche Patientenaufklärung als Behandlungsversuch stattfinden. In der Literatur sind ähnliche Ergebnisse bez. Morbidität und Mortalität zwischen „off-the-shelf“ und „surgeon-modified“ Prothesen publiziert. Ein direkter Vergleich dieser Verfahren scheint aus mehreren Gründen (unterschiedliches Prothesendesign, Selektionsbias, unterschiedliche Techniken in der Prothesenmodifikation) jedoch schwierig und anhand der Literatur allein nicht eindeutig durchführbar. Schlussfolgerung Die „surgeon-modified“ sowie die „off-the-shelf“ fenestrierten/gebranchten Stentprothesen werden in der Versorgung von Hochrisikopatienten mit symptomatischen oder gedeckt rupturierten komplexen Aortenaneurysmen angewendet. Die Ergebnisse beider Techniken sind vergleichbar gut, obwohl die langfristige Funktionsdauer der modifizierten Stentprothesen weiter getestet werden sollte.

The aim of this article is to discuss offset versus off-the-shelf options for arms procurement in Lithuania between 2014 and 2022, including the acquisition of the Boxer infantry fighting vehicle. ...

Objectives: In the era of increasing antimicrobial resistance, the need for early identification and prompt treatment of multi-drug-resistant infections is crucial for achieving favorable outcomes in critically ill patients. As traditional microbiological susceptibility testing requires at least 24 hours, automated machine learning (AutoML) techniques could be used as clinical decision support tools to predict antimicrobial resistance and select appropriate empirical antibiotic treatment.Methods: An antimicrobial susceptibility dataset of 11,496 instances from 499 patients admitted to the internal medicine wards of a public hospital in Greece was processed by using Microsoft Azure AutoML to evaluate antibiotic susceptibility predictions using patients’ simple demographic characteristics, as well as previous antibiotic susceptibility testing, without any concomitant clinical data. Furthermore, the balanced dataset was also processed using the same procedure. The datasets contained the attributes of sex, age, sample type, Gram stain, 44 antimicrobial substances, and the antibiotic susceptibility results.Results: The stack ensemble technique achieved the best results in the original and balanced dataset with an area under the curve-weighted metric of 0.822 and 0.850, respectively.Conclusions: Implementation of AutoML for antimicrobial susceptibility data can provide clinicians useful information regarding possible antibiotic resistance and aid them in selecting appropriate empirical antibiotic therapy by taking into consideration the local antimicrobial resistance ecosystem.

Aims The main advantage of 3D-printed, off-the-shelf acetabular implants is the potential to promote enhanced bony fixation due to their controllable porous structure. In this study we investigated the extent of osseointegration in retrieved 3D-printed acetabular implants. Methods We compared two groups, one made via 3D-printing (n = 7) and the other using conventional techniques (n = 7). We collected implant details, type of surgery and removal technique, patient demographics, and clinical history. Bone integration was assessed by macroscopic visual analysis, followed by sectioning to allow undecalcified histology on eight sections (~200 µm) for each implant. The outcome measures considered were area of bone attachment (%), extent of bone ingrowth (%), bone-implant contact (%), and depth of ingrowth (%), and these were quantified using a line-intercept method. Results The two groups were matched for patient sex, age (61 and 63 years), time to revision (30 and 41 months), implant size (54 mm and 52 mm), and porosity (72% and 60%) (p > 0.152). There was no difference in visual bony attachment (p = 0.209). Histological analysis showed greater bone ingrowth in 3D-printed implants (p < 0.001), with mean bone attachment of 63% (SD 28%) and 37% (SD 20%), respectively. This was observed for all the outcome measures. Conclusion This was the first study to investigate osseointegration in retrieved 3D-printed acetabular implants. Greater bone ingrowth was found in 3D-printed implants, suggesting that better osseointegration can be achieved. However, the influence of specific surgeon, implant, and patient factors needs to be considered. Cite this article: Bone Joint Res 2021;10(7):388–400.

Vaccination against tumors using antigen-pulsed dendritic cell (DC) vaccines has greatly evolved over the last decade, with hundreds of active human clinical trials well on the way. The use of an autologous source for DC-based vaccine therapeutics remains the obvious choice in the majority of clinical studies; however, novel evidence suggests that an allogeneic source of DCs can yield success if administered in the right context. One of the challenges facing successful DC vaccination protocols is the generation of large enough numbers of DCs intended for vaccination and standardization of these procedures. In addition, variations in the quality of DC vaccines due to donor-to-donor variation represent an important therapeutic factor. To this day it has not been shown whether DCs from different donors can readily co-exist within the same co-culture for the extended periods required for vaccine manufacture. We demonstrate that generation of allogeneic DC co-cultures, generated from multiple unrelated donors, allows the preservation of their phenotypical and functional properties in vitro for up to 72 hours. Therefore, in the case of an allogeneic vaccination approach, one could ensure large numbers of DCs generated from a primary cell source intended for multiple vaccinations. By generating large amounts of ex vivo manufactured DCs from multiple donors, this would represent the possibility to ensure sufficient amounts of equipotent "off the shelf" product that could e.g. be used for an entire cohort of patients within a study.

Background Revision total hip arthroplasty (THA) has been a challenge for surgeons. The purpose of this study was to explore the short-to mid-term clinical and radiological outcomes of Chinese patients who underwent revision THA using a new off-the-shelf three-dimensional (3D)-printed trabecular titanium (TT) acetabular cup by comparison with a conventional porous coated titanium acetabular cup, to provide a reference for the recommendation of this prostheses. Methods A retrospective analysis of 57 patients (57 hips) who received revision THA was performed from January 2016 to June 2019. A total of 23 patients received 3D-printed cups (observation group) and 34 patients received non-3D-printed cups (control group). Clinical scores including Visual Analogue Scale (VAS), Harris Hip Score (HHS) and Short Form 36 (SF-36), upward movement of the hip center of rotation(HCOR)and limb-length discrepancy (LLD), stabilization and bone ingrowth of cups were compared between two groups. The multivariate linear regression was used to determine the factors potentially influencing the HHS score. Postoperative complications in the two groups were also recorded. Results All 57 patients were routinely followed up. The average follow-up durations in the control and observation groups were 43.57 ± 13.68 (24–65) months and 41.82 ± 11.44 (24–64) months, respectively (p = 0.618). The postoperative clinical scores significantly improved in both groups compared to the preoperative scores (p p = 0.946) or 12 (p = 0.681) months postoperatively, or at the last follow-up (p = 0.885). The HHS score did not significantly differ between the groups at 3 months (p = 0.378) postoperatively but differed at 12 months (p p p = 0.289) postoperatively, but was significantly different at 12 months (p p p = 0.037). Multivariate linear regression analysis showed that different cup types, upward movement of the HCOR, and LLD influenced the HHS score at the last follow-up (p p = 0.005, respectively). None of the patients exhibited severe postoperative complications. Conclusion The new off-the-shelf 3D-printed TT acetabular cup demonstrated encouraging short-to mid-term clinical outcomes in Chinese patients. It can effectively relieve pain, improve hip function, provide satisfactory biological fixation and high survival rate. But further follow up is necessary to assess its long-term outcomes.

Global Navigation Satellite Systems or GNSS is a space technology that has become an essential element nowadays for positioning, navigation & timing (PNT) with wide range of applications in many civilian sectors as well as across military. The reliability, accuracy and availability of GNSS are highly important especially for critical and precise positioning applications. However, the signals from space are weak and it can be easily blocked, disrupted or compromised by several other threats including intentional and unintentional interferences or jamming. GPS jammer is widely available off the shelf with an affordable price and capable of interfering the GPS signal, and many authorities worldwide have raised concerns and a lot of efforts and research have been put in place to reduce and mitigate the threats. In Malaysia, understanding and countering threats to GNSS/GPS based applications will be a new and unfamiliar discipline for public and organizations. This study intended to provide an overview of the GNSS interferences environment in a local study area, in terms of interference type and the number of activity pattern that were detected. A system called Detector V1 has been used in this study. The result showed that significant interference cases happened in the study area and some of the high power interferences may impact GNSS tracking and precision of the positioning output. The role objective of having this done is to create a public awareness regarding the threat of GNSS interferences to the local users. The content also includes the proposed initiative to overcome the issue.

Three-dimensional (3D)-printed titanium cups used in primary total hip arthroplasty (THA) were developed to combine the benefits of a low elastic modulus with a highly porous surface. The aim was to improve local vascularization and bony ingrowth, and at the same time to reduce periprosthetic stress shielding. Additive manufacturing, starting with a titanium alloy powder, allows serial production of devices with large interconnected pores (trabecular titanium), overcoming the drawbacks of tantalum and conventional manufacturing techniques. To date, 3D-printed cups have achieved dependable clinical and radiological outcomes with results not inferior to conventional sockets and with good rates of osseointegration. No mechanical failures and no abnormal ion release and biocompatibility warnings have been reported. In this review, we focused on the manufacturing technique, cup features, clinical outcomes, open questions and future developments of off-the-shelf 3D-printed titanium shells in THA.

A new framework allows intelligence on mainstream end devices without special hardware.

Temcell is a cryopreserved, human bone marrow-derived mesenchymal stem cell (MSC) product approved for the treatment of patients of all ages with acute graft-versus-host disease (GVHD). Initial experience with Temcell in a real-world setting from a cellular therapy registry in Japan is presented. A total of 381 consecutive patients were enrolled since its approval in 2016. The median cell number infused was 2.00 × 106/kg. The most common number of infusions was 8 in 100 patients. Of the 306 evaluable patients, the overall response rate (ORR) on day 28 after the start of MSC therapy was 56%. Of the 151 evaluable patients who received it as second-line therapy following first-line steroid therapy for classic acute GVHD, the ORR was 61%. Liver involvement of GVHD and ≥14 days from first-line steroid therapy to second-line MSC therapy was associated with a lower ORR. Day 28 ORR, patient age, GVHD grade, GVHD organ involvement, and a number of GVHD therapies before MSC therapy were associated with nonrelapse mortality. Overall survival at 6 months in 381 patients was 40%. This study suggests that Temcell is one of the treatment options for steroid-refractory acute GVHD until a new treatment with survival benefit is developed.

Chemosensor arrays are useful analytical methods in supramolecular analytical chemistry, which discriminate molecular information such as species and their concentrations based on pattern recogniti...

In this article, we are interested in through-wall gait-based identification of multiple people who are simultaneously walking in an area, using only the WiFi magnitude measurements of a small number of transceivers. This is a considerably challenging problem as the gait signatures of the walking people are mixed up in the WiFi measurements. In order to solve this problem, we propose a novel multidimensional framework, spanning time, frequency, and space domains, that can separate the signal reflected from each walking person and extract its corresponding gait content, in order to identify multiple people through walls. To the best of our knowledge, this is the first time that WiFi signals can identify multiple people in an area. We extensively validate our proposed system with 92 test experiments conducted in four different areas, where the WiFi transceivers are placed behind walls, and where two or three people (randomly selected from a pool of six test subjects) are walking in the area. Our system achieves an overall average accuracy of 82% in correctly identifying whether a person walking in the test experiment (referred to as a query) is the same as a candidate person, based on 6404 query-candidate test pairs. It is noteworthy that none of the test subjects/areas has been seen in the training phase.

Introduction Urgent or emergency treatment of patients with abdominal aortic aneurysms that are anatomically unsuitable for conventional repair because of short proximal necks, small diameters and access vessel calcification, and high risk for open repair can be performed with commercially available branched or fenestrated aortic endografts or physician modified stent grafts. Report A technique is described for modification and successful implantation of a commercially available standard aortic stent graft with a low profile main body in two patients at high risk for open repair, with small access vessels and requiring uni- or bilateral renal artery fenestration for juxtarenal aneurysm repair. Discussion Based on two case experiences, the use of physician modified off the shelf endografts appears to be a feasible and effective alternative to fenestrated endovascular repair in patients with juxtarenal abdominal aortic aneurysms at high risk for open surgical repair. Studies comparing effectiveness of the different options, including chimney/snorkel technique and debranching, are warranted., Highlights • Retrospective review of two cases from a prospective, single center registry. • Physician-modified technique success was 100%, no related deaths or re-interventions at 12m FU. • Modified-endograft appears feasible to seal juxtarrenal AAA in patients with small access.

Objective Fenestrated endovascular aneurysm repair (FEVAR) is a well established treatment for complex abdominal aortic aneurysms (AAAs). FEVAR with custom made devices (CMDs) has limitations in both the emergency and elective settings due to time consuming manufacture. “Off the shelf” (OTS) fenestrated stent grafts are a potential solution. The primary goal was to evaluate the five year outcome of the COOK Zenith p-Branch OTS device at a single centre. Methods Patients with juxtarenal AAA meeting the inclusion criteria for the COOK Zenith p-Branch device were enrolled in a prospective, non-randomised, non-comparative trial from July 2012 to September 2015. Demographic, anatomical, procedure related, and five year follow up data were collected, analysed, and adjudicated by a core laboratory. The primary aims were to assess intervention free survival and overall survival at five years. Results Twenty-three patients were treated and 21 completed follow up. Mean time to p-Branch implantation after patient presentation was 28 hours (range 0–122 hours) in emergency cases and 67 days (range 20–112 days) in elective cases. Median procedure time was 283 minutes (range 161–475 minutes) and technical success was 91%. Mean follow up was 45 months (standard deviation ± 24.4 months). The most common adverse events were renal injuries. Primary target vessel patency was 96.4% and 94.0% after one and five years respectively. Mean time to first re-intervention was 469 days (range 0–1 567 days). Survival during the follow up period was 76%, with no aneurysm related deaths. Conclusion FEVAR with the COOK Zenith p-Branch device is safe and effective for juxtarenal AAA in a selected patient population, in both elective and emergency settings. Long term outcomes are acceptable although inferior to CMDs. Mid and long term outcomes emphasise the p-Branch as a possible endovascular treatment for juxtarenal aortic pathology where CMD is not an option. Further innovation to address target vessel complications is needed, as these seem more prevalent than after repair with CMDs.

Autism spectrum disorder (ASD) is associated with deficits in the processing of social information and difficulties in social interaction, and individuals with ASD exhibit atypical attention and gaze. Traditionally, gaze studies have relied upon precise and constrained means of monitoring attention using expensive equipment in laboratories. In this work we develop a low-cost off-the-shelf alternative for measuring attention that can be used in natural settings. The head and iris positions of 104 16-31 months children, an age range appropriate for ASD screening and diagnosis, 22 of them diagnosed with ASD, were recorded using the front facing camera in an iPad while they watched on the device screen a movie displaying dynamic stimuli, social stimuli on the left and non-social stimuli on the right. The head and iris position were then automatically analyzed via computer vision algorithms to detect the direction of attention. We validate the proposed framework and computational tool showing that children in the ASD group paid less attention to the movie, showed less attention to the social as compared to the non-social stimuli, and often fixated their attention to one side of the screen. These results are expected from the ASD literature, here obtained with significantly simpler and less expensive attention tracking methods. The proposed method provides a low-cost means of monitoring attention to properly designed stimuli, demonstrating that the integration of stimuli design and automatic response analysis results in the opportunity to use off-the-shelf cameras to assess behavioral biomarkers.

Purpose: To demonstrate an off-the-shelf multibranched (t-Branch) modification to allow intercostal arteries preservation during juxtarenal, pararenal, paravisceral, and extent IV thoracoabdominal aortic aneurysm repair. Technique: The t-Branch is an off-the-shelf device not customized for specific patient anatomy and may be offered for urgent endovascular repair for patients with complex aortic aneurysms. However, a concern when treating patients who do not aneurysms extending above the celiac axis is that the more proximal extension which is required with this device may render patients at high risk for spinal cord injury. We report a novel technique with t-Branch modification performing a 180° fabric back windows at the first 2 sealing stents that allow perfusion to the intercostal arteries. Conclusion: T-Branch-PIA (preserving intercostal arteries) modification limits intercostal arteries coverage while optimizing proximal seal zone in juxtarenal, pararenal, paravisceral, and extent IV thoracoabdominal aneurysms, thereby may decrease the risk of spinal cord injury.

We describe a novel technique in which predictive holes, normally unique to patient-specific plates, may be utilized with off the shelf stock plates. This allows for the numerous benefits of predictive holes in mandibular reconstruction while negating the added cost of a custom milled plate. Three case examples are presented for technique illustration.

Increasingly globalized communication networks in the modern world may influence traditional patterns of linguistic change: in contrast to an orderly sequential pathway of change, more recently a number of “mega trends” have been identified, which accelerate simultaneously in time and space. The rise of obviously within the cohort of adverbs of evidentiality—naturally, evidently, clearly, and of course—may be one such trend. To examine this possibility, we conduct a large-scale sociolinguistic analysis of c12,000 adverbs of evidentiality across over thirty communities in the UK and Canada. The results reveal parallel development across time and space: obviously advances rapidly among individuals born in the 1960s in both countries. The rise of obviously illustrates key attributes that are beginning to emerge from other rapidly innovating features: “off the shelf” changes that (1) are easily borrowed, (2) receptive to global trends, but (3) exhibit parallel patterns as the change progresses.

Background Ultra-high spatial resolution imaging of whole, ex vivo brains provides new opportunities to understand neurological disease. Recent work has demonstrated that 100 μm isotropic resolution can reveal anatomical details that are otherwise difficult to appreciate, but relied on fabrication facilities, fabrication expertise and programming expertise that is not available at clinical imaging sites that lack a dedicated research staff and resources. The purpose of this work is to describe a whole-brain, ultra-high spatial resolution imaging procedure for ex vivo specimens using equipment that can be purchased, assembled and implemented by most clinical sites. We provide enough detail so that other groups can readily reproduce the approach. Methods A container and hardware for holding the brain fixed for long scan times was developed, along with a procedure for removing bubbles, which can cause artifact. Imaging was performed on a standard knee coil on a whole-body 7 T MRI at 170 μm isotropic spatial resolution. Five specimens were examined in Fomblin or formalin to evaluate consistency of image quality. Results High quality images were acquired on all specimens. Anatomical features that are not readily observed at standard resolution, such as subthalamic nuclei, are readily observed. Disease-related features such as microscopic infarcts are also readily observed. Conclusions Ultra-high spatial resolution, whole-brain images can be readily achieved without specialized hardware and software development. The approach is expected to be valuable as a complement to histology and to discover relationships among pathology located at different places throughout the brain.

In this work, 22 off-the-shelf propellers of 15–40 inches in diameter are reverse-engineered using a scanning system and reverse engineering software. Geometric information, including the diameter and pitch of the propeller and its airfoil sections, are extracted, and the chord length and twist angle of the extracted airfoil sections are investigated. All processes for reverse engineering are validated through comparison with design drawing information, product and performance data of the KPROP propeller designed by Korea Aerospace Research Institute. Based on the validated process, a database of 22 commercial propellers from four companies is constructed containing all the reverse-engineered information. The chord length, the maximum length and twist angle with respect to the diameter of the extracted airfoil section are analyzed in comparison with each other depending on the company and propeller size. In addition, the thrust and torque are simulated using computational fluid dynamic methodology, and the predictions are compared with reference data provided by the manufacturers.

BACKGROUND: It is known that the so-called “rocker” outsole helps to reduce the load on the forefoot and toes. Such an outsole is available in ready-made orthopedic shoes of some Russian manufacturers, however, an objective assessment of their impact on the load distribution under the foot during walking has not been carried out.AIMS: To study the pressure distribution inside the off-the-shelf orthopedic shoes“Sursil-Ortho” in comparison with the load inside the shoes used by patients on a daily basis.METHODS: We studied 20 patients (40 feet) with a high risk of diabetic foot syndrome. According to clinical data, a risk regions were determined on the plantar surface of the feet. In-shoe pedography (pedar, novel,Germany) was performed in shoes usually worn by the patients, and in orthopedic shoes“Sursil-Orto”(Moscow). The maximum peak pressure (MPP) was calculated. Criterion of efficiency: MPP in the risk regionRESULTS: There was a significant decrease of the median MPP in the forefoot and in the risk region. The percentage of feet with MPP >200 kPa in the risk region decreased from 58% to 30% (p=0,014), in any area of the forefoot — from 63% to 30% (p=0,04). The increase in MPP under the midfoot and hindfoot did not exceed +14% (ns). Tested footwear was effective in 71% of cases. Predictors of the insufficient effect were: higher initial MPP in the risk region, risk region on the hallux or in the lateral part of the forefoot.CONCLUSIONS: Shoes with a rigid rocker outsole significantly reduce the pressure under the forefoot and under the toes during walking. The degree of load reduction varies: the lateral part of the forefoot and 2-5 toes are most unloaded, and the hallux and medial forefoot are slightly less.

The microfluidic droplet method has excellent promise for preparing hollow particles because it can be versatile in realizing multi-level size distribution and scalable in production. However, the application of this method is still limited due to the complexity of the device preparation process. Here, an off-the-shelf microfluidic device is developed for the fast and straightforward fabrication of highly uniform multiple-holed hollow particles. Most importantly, the structure, size, morphology, and properties of the particles can be easily adjusted by varying the fabrication conditions, including the diameter of the capillaries, the flow rate of the water and oil phases, the start polymerization time, and the composition of the emulsion droplets. Therefore, the developed device provides a powerful platform for the controllable fabrication of multiple-holed hollow particles with exceptionally diverse structures and properties. Furthermore, well-ordered hollow particle arrays were quickly fabricated for three-dimensional (3D) cell culture by a simple molding method. HepG2 3D tumor spheroids with excellent viability and uniformity were efficiently produced using the particle arrays. Thus, the multiple-holed hollow particles will offer a unique opportunity for application in various cell-based research studies.

Immunotherapy, especially immune cell-based therapy, is a strategy for cancer treatment that has over the past decades focused on novel modifications and targets. In recent years, adoptive cell immunotherapy has continuously evolved, with studies of different platforms utilizing different immune effector cells to kill a variety of cancer cells. This review summarizes the various kinds of immune cells which have been used in adoptive cell therapy (ACT), including natural killer cells, cytokine-induced killer cells, T cells, and engineered immune cells. Most reports have shown that ACT can induce tumor regression, both in animal studies and clinical trials. However, the high cost of ACT is the greatest disadvantage of this strategy. Moreover, the efficacy of treatment is variable among patients. To reduce these disadvantages, off-the-shelf immune cells are considered the best solution to reduce the cost while maintaining the efficacy of treatment. In this review, we will discuss the potential of various kinds of immune cells for development as ``off-the-shelf'' immune cells for use in adoptive cell therapy, based on their unique advantages.

Building and programming tiny battery-free energy harvesting embedded computer systems is hard for the average maker because of the lack of tools, hard to comprehend programming models, and frequent power failures. With the high ecologic cost of equipping the next trillion embedded devices with batteries, it is critical to equip the makers, hobbyists, and novice embedded systems programmers with easy-to-use tools supporting battery-free energy harvesting application development. This way, makers can create untethered embedded systems that are not plugged into the wall, the desktop, or even a battery, providing numerous new applications and allowing for a more sustainable vision of ubiquitous computing. In this paper, we present BFree, a system that makes it possible for makers, hobbyists, and novice embedded programmers to develop battery-free applications using Python programming language and widely available hobbyist maker platforms. BFree provides energy harvesting hardware and a power failure resilient version of Python, with durable libraries that enable common coding practice and off the shelf sensors. We develop demonstration applications, benchmark BFree against battery-powered approaches, and evaluate our system in a user study. This work enables makers to engage with a future of ubiquitous computing that is useful, long-term, and environmentally responsible.

Introduction Immune-mediated liver and gastrointestinal diseases are chronic conditions that lack curative treatments. Despite advances in the understanding and treatment of these conditions, they frequently remain refractory to treatment and represent a significant unmet need. Cellular therapies are an emerging option and hold the potential to have a major impact. Data sources A literature review was carried out using Pubmed. Keywords used for search were ‘ATMP’, ‘immune mediated’, ‘autoimmune liver disease’ and ‘immune mediated gastrointestinal conditions’, ‘cell therapy’, ‘MSC’, ‘HSCT’, ‘Regulatory T cells’, ‘GVHD’, ‘Coeliac disease’ ‘IBD’, ‘PSC’, ‘AIH’, ‘PBC’. No new data were generated or analysed in support of this review. Areas of agreement There is substantial evidence from clinical trials to support the use of cell therapies as a treatment for immune-mediated liver and gastrointestinal conditions. Cellular therapy products have the ability to ‘reset’ the dysregulated immune system and this in turn can offer a longer term remission. There are ongoing clinical trials with mesenchymal stromal cells (MSCs) and other cells to evidence their efficacy profile and fill the gaps in current knowledge. Insights gained will inform future trial designs and subsequent therapeutic applications. Areas of controversy There remains some uncertainty around the extrapolation of results from animal studies to clinical trials. Longevity of the therapeutic effects seen after the use of cell therapy needs to be scrutinized further. Heterogeneity in the selection of cells, source, methods of productions and cell administration pose challenges to the interpretation of the data. Growing points MSCs are emerging as a key therapeutic cells in immune-mediated liver and gastrointestinal conditions. Ongoing trials with these cells will provide new insights and a better understanding thus informing future larger scale studies. Areas timely for developing research Larger scale clinical trials to build on the evidence from small studies regarding safety and efficacy of cellular therapy are still needed before cellular therapies can become off the shelf treatments. Alignment of academia and industry to standardize the processes involved in cell selection, manipulation and expansion and subsequent use in clinical trials is an important avenue to explore further.

INTRODUCTION: Introducing a new arthroplasty system into clinical routine is challenging and could have an effect on early results. Since UKA are known to have failure mechanisms related to technical factors, reliable results and easy adoption are ideal. The question remains whether there are differences in objective procedure parameters in the early learning curve of different UKA systems. METHODS: two different UKA implants (Biomet Oxford[BO] followed by Conformis iuni[CI]) were introduced consecutively into clinical routine. We retrospectively analyzed the first 20 cases of each implant for one arthroplasty surgeon regarding operating time, correction of the mechanical axis, learning curve parameters, and revision rate of implants for 1.5 years postoperatively. RESULTS: Operating time (BO:98.3 ± 26.3min, CI:83.85 ± 21.8min (p

Background Mesenchymal stem cells (MSC)-based tissue engineered breast represent the visible future for breast reconstruction after mastectomy. However, autologous MSCs might not be appropriate for the large graft construction due to cell senescence during excessive cell expansion, thus hindering its further off-the-shelf application. The human umbilical cord mesenchymal stem cells (hUCMSCs) have been found to induce low immune response and can be easily stored, making them ideal for off-the-shelf tissue engineering application. Here, we explored the feasibility of using umbilical cord mesenchymal stem cells as tissue-engineered breast seed cells. Methods The allogenic hUCMSCs were injected into transplanted fat tissue with or without breast scaffolds as an alternative for breast tissue engineering in vivo, and its potential mechanism of angiogenesis in vitro was explored. Results Transplantation of hUCMSCs promoted proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) through paracrine mechanism by activating the integrin β1/ERK1/2/HIF-1α/VEGF-A signaling pathway. Histological examination of grafted fat revealed that the group which received hUCMSCs transplantation had more fat tissue [(93.60 ± 2.40) %] and fewer MAC2+CD206− M1 macrophages [(0.50 ± 0.47) cells/field] compared to the control group [fat tissue (45.42 ± 5.96) and macrophage cells/field (5.00 ± 2.23)]. Moreover, the hUCMSCs- labeled with a tracing dye differentiated into adipocytes and vascular endothelial cells in the adipose tissue. When applied to the tissue-engineered breast with a scaffold, the group treated with hUCMSCs had more adipose tissues and CD31+ cells than the control group. Conclusions These results demonstrate that allogeneic hUCMSCs promote the regeneration of adipose tissue and can be used to construct a tissue engineered breast.

In neuroimaging, spatial normalization is an important step that maps an individual's brain onto a template brain permitting downstream statistical analyses. Yet, in infant neuroimaging, there remain several technical challenges that have prevented the establishment of a standardized template for spatial normalization. Thus, many different approaches are used in the literature. To quantify the popularity and variability of these approaches in infant neuroimaging studies, we performed a systematic review of infant magnetic resonance imaging (MRI) studies from 2000 to 2020. Here, we present results from 834 studies meeting inclusion criteria. Studies were classified into (a) processing data in single subject space, (b) using an off the shelf, or "off the shelf," template, (c) creating a study specific template, or (d) using a hybrid of these methods. We found that across the studies in the systematic review, single subject space was the most used (no common space). This was the most used common space for diffusion-weighted imaging and structural MRI studies while functional MRI studies preferred off the shelf atlases. We found a pattern such that more recently published studies are more commonly using off the shelf atlases. When considering special populations, preterm studies most used single subject space while, when no special populations were being analyzed, an off the shelf template was most common. The most used off the shelf templates were the UNC Infant Atlases (24%). Using a systematic review of infant neuroimaging studies, we highlight a lack of an established "standard" template brain in these studies.

Purpose This article aims to present all aspects regarding patient selection, planning, and implantation technique for a new off-the-shelf pre-cannulated multi-inner branch stent graft. The stent graft comes in 4 different versions with proximal diameters of 33 and 38 mm and distal diameters of 26 and 30 mm. The 4 inner branches are located in the middle segment, which has a diameter of 24 mm. Technique With inner branch technology, the field of application for the treatment of thoracoabdominal aortic aneurysms (TAAA) has been further extended. In addition to routine use in elective cases the pre-cannulation of the inner branches predisposes especially for emergencies. Pre-cannulation is intended to reduce the time to cannulation and the radiation dose. All steps of planning, stent-graft deployment, and cannulation of the inner branches are described in detail. Conclusion The E-nside stent graft represents a promising new endovascular therapy in the treatment of acute and elective TAAA. By using inner branch technology, this endograft combines the advantages of fenestrated and branched stent grafts. Indication, planning, and implantation require experience in branched and fenestrated stent graft technology.

Cloud computing, big data, wearables, the internet of things, artificial intelligence, robotics, and virtual reality (VR), when seamlessly combined, will create the healthcare of the future. In the presented study, the authors aim to provide tools and methodologies to efficiently create 3D virtual learning environments (VLEs) to immerse participants in 3600, six degrees of freedom (6DoF) patient examination simulations. Furthermore, the authors will discuss specific methods and features to improve visual realism in VR, such as post-processing effects (ambient occlusion, bloom, depth of field, anti-aliasing), texturing (normal maps, transparent, and reflective materials), and realistic lighting (spotlights and custom lights). The presented VLE creation techniques will be used as a testbed for medical simulation, created using the Unity game engine.

Objective The goal of this study was to select branched endograft designs that could fit most aortic arch anatomies. Such off-the-shelf endografts, once available, would be an endovascular therapeutic option to consider in the acute setting and would shorten the design and manufacturing process. Methods We retrospectively analyzed the endograft plans of all custom-made aortic arch branched endografts implanted between 2013 and early 2018 provided by the Cook Planning Center (EMEA Planning Services; Cook Medical, London, United Kingdom). Available data points of the endograft plans include proximal, intermediate, and distal endograft diameters; number of sealing stents; total length of the endograft; and number of branches. Results There were 286 two-branch endografts analyzed. We divided the endografts in three groups according to their proximal diameters: 34 mm, 36 mm, and 38 mm (group 1); 40 mm and 42 mm (group 2); and 44 mm and 46 mm (group 3). In group 1, 63% of the endografts had one proximal sealing stent, whereas in group 3, 63% had two proximal sealing stents. The distal diameters of the endografts ranged from 26 mm to 46 mm. The mean length was 236 mm (186-256 mm). A shorter standardized length of 211 mm was selected to anticipate distal extensions. According to our analysis, most group 1 patients could have been treated with a 38-mm proximal diameter and 30-mm distal diameter endograft with one sealing stent; most group 2 patients, with a 42-mm proximal diameter and 32-mm distal diameter endograft with both one and two proximal sealing stents; and most group 3 patients, with a 46-mm proximal diameter and 36-mm distal diameter endograft, also with both one and two proximal sealing stents. Conclusions Five standardized off-the-shelf endografts can cover a majority of aortic arch anatomies and offer an option for acute endovascular treatment of aortic arch disease.

The immune barrier to transplantation has widely been recognized as the ultimate hurdle to the translation of stem cell-based therapies. In particular the polymorphic nature of the human leucocyte antigens (HLA) poses an imminent barrier to the successful engraftment of cells from other than autologous sources. To make stem cell therapies available to a larger pool of patients and a commercially viable option several groups have attempted to create hypoimmunogenic “universal” donor stem cells that evaded immune detection. The goal of this commentary is to give a brief overview of the current approaches taken and discuss challenges that need to be addressed to turn such cells into a viable commercial option.

Learning Objectives Upon completion of this activity, participants will be able to:Assess the efficacy of off-the-shelf use of 2-diopter cylinder correction toric intraocular lenses in cataract surgery for patients with preoperative corneal astigmatism of 2.00 D or more, based on a prospective randomised study.Evaluate the safety and patient-reported outcomes of off-the-shelf use of 2-diopter cylinder correction toric intraocular lenses in cataract surgery for patients with preoperative corneal astigmatism of 2.00 D or more, based on a prospective randomised study.Determine the potential suitability of off-the-shelf use of toric intraocular lenses for more widespread adoption by the National Health Service or other large public health programs, and other clinical implications of their efficacy and safety, based on a prospective randomised study. Continuing Medical Education In support of improving patient care, this activity has been planned and implemented by Medscape, LLC and Springer Nature. Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s). Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 75% minimum passing score and complete the evaluation at www.medscape.org/journal/eye; (4) view/print certificate. Credit hours 1.0 Release date: July 30, 2020 Expiration date: July 30, 2021 Post-test link: https://medscape.org/eye/posttest929021 Authors/Editors disclosure information Sobha Sivaprasad, MD, has disclosed the following relevant financial relationships: served as an advisor or consultant for: Allergan, Inc.; Apellis; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Heidelberg Pharma GmbH; Novartis; Oculis; Optos; Oxurion; Roche. Served as a speaker or a member of a speakers bureau for: Allergan, Inc.; Bayer AG; Novartis Pharmaceuticals Corporation; Optos. Received grants for clinical research from: Allergan, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Optos. Nick Stanojcic, BSc, MCOptom, FRCOphth, has disclosed no relevant financial relationships. Harry Roberts, MSc, FRCOphth, has disclosed the following relevant financial relationships: served as an advisor or consultant for: Alcon UK. Vijay Wagh, FRCOphth, has disclosed no relevant financial relationships. Bruno Zuberbuhler, PhD, FRCOphth, has disclosed no relevant financial relationships. David O'Brart, MD (Res), FRCOphth, FRCS, RefCert(RCOphth), has disclosed the following relevant financial relationships: received grants for clinical research from: Alcopn Inc., Rayner Ltd, Avedro Inc. Owns stock, stock options, or bonds from: Sparca Inc. Employed by a commercial interest: Sparca Inc., Background/objectives To compare visual and refractive outcomes of monofocal intraocular lenses (IOLs) with limbal relaxing incisions (LRI) with ‘off-the-shelf’ use of toric IOLs (TIOLs), with a fixed 2-dioptre cylinder (DC) correction, for cataract patients with pre-existing corneal astigmatism in a public-sector setting. Subjects/methods Seventy-seven patients (77 eyes, first treated eye) with visually significant cataract and pre-operative corneal astigmatism ≥2.00 DC were randomised to receive either ‘off-the-shelf’ TIOLs, with a fixed 2.00 DC cylinder correction (39 eyes), or monofocal IOLs (38 eyes) with LRIs. The concept of fixing the cylindrical correction was to minimise costs, allow a full TIOL bank to be available and eliminate the need for individual TIOL ordering. Outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA) and refraction. Astigmatic changes were evaluated using the Alpins vector method. Results Mean UDVA improved from logMAR 0.88 (SD 0.56)[~20/150] pre-operatively to 0.18 (SD 0.19)[~20/30] post-operatively in TIOL group, versus 0.82 (SD 0.55)[~20/130] to 0.27 (SD 0.15)[~20/40] in monofocal/LRI group (P = 0.02; 95% CI: −0.17, −0.01). Mean CDVA improved from logMAR 0.40 (SD 0.26)[~20/50] to 0.01 (SD 0.12)[~20/20] in TIOL group, and 0.41 (SD 0.38)[~20/40] to 0.06 (SD 0.12)[~20/25] in LRI group (P = 0.07; 95% CI: −0.11, 0.01). Average post-operative refractive cylinder in TIOL group was 1.35 DC (SD 0.84 DC) and in LRI group 1.91 DC (SD 1.07 DC) (P = 0.01; 95% CI: −1, −0.12). Mean difference vector magnitude was 1.92 DC (SD 1.08 DC) in LRI group and 1.37 DC (SD 0.84 DC) in TIOL group (P = 0.02; 95% CI: 0.11, 0.99). Conclusions TIOLs with a fixed 2.00 DC correction during cataract surgery may improve UDVA, reduce post-operative cylinder and result in a more reliable astigmatic correction compared with monofocal IOLs with LRIs.

Neoantigen, as an important member of tumor-specific antigens, has attracted a great deal of attention as a target for immunotherapy. Neoantigens are potential targets for personalized vaccines and adoptive cell transfer therapies. However, most of the neoantigen-targeted immunotherapies in the process are customized and costly. So, we are inclined to find shared neoantigens suitable for more patients. With the help of existing neoantigen prediction algorithms, we found that the most frequent shared neoantigens occurred in more than 1% of patients for 17 tumor types and the ten most frequent shared neoantigens covered approximately 50% of pancreatic cancer patients, providing a potential list of targets for off-the-shelf immunotherapy.

Iliotibial band syndrome (ITBS) is a common chronic pathology mediated via excessive Iliotibial band (ITB) strain. The purpose using a three-experiment approach is to provide insight into the differences in strain between different athletic movements, the incidence of ITBS in females, the efficacy of different prophylactic modalities for ITBS and also the kinematic parameters associated with ITB strain. Experiment 1 examined male and female athletes performing run, 45° cut and one-legged hop movements, experiment 2 observed males and females, whilst running in five different orthotic conditions and experiment 3 examined males and females riding a cycle ergometer at 70, 80 and 90 RPM whilst in prophylactic knee brace and no-brace conditions. In each experiment, kinematics were obtained using a motion capture system and ITB strain was measured using a musculoskeletal simulation approach. In experiment 1, ITB strain was greater in the run (male = 3.87% and female = 4.37%; P

Before humans inserted themselves into the aquatic food chain, sharks were at the top maintaining balance and playing a crucial role on this earth. For hundreds of millions of years (even before the dinosaurs!) sharks have been shaping our underwater ecosystem and creating a foundation for life in all parts of the sea. Now with 95% of shark populations decreasing everywhere our health and the planet's health is at major risk. Shark livers contain an oil so hydrating and rich all cosmetic that companies want to get their hands on it. This simple substance, also known as squalene, is found all around the world in the form of cosmetics (lotions, anti-wrinkle creams, sunscreen, foundations) and daily off the shelf supplements. With the serious lack of education about what’s in our cosmetics, it makes it scary to think that almost all of us have been absentmindedly plastering on prehistoric predators on our body in the name of beauty.

Modern cities are densely populated spaces and number of people living in cities is increasing rapidly by years. The air monitoring stations exist in most of the cities to monitor air pollution. However, their number is insufficient having in mind the high cost of stations, as well as annual calibration cost. The potential solution is to use low-cost off-the-shelf sensors to monitor related air quality parameters, but they are not reliable due to the low accuracy, calibration issues, and short life cycle. In this paper, the methodology is proposed for calibration off-the-shelf air quality sensors using statistical algorithms and offset values from the official public measurement stations. The possibilities are analysed to improve the reliability of low-cost sensors by processing the obtained raw data. Special attention is devoted to the detection and elimination of short intervals when the raw results have the extraordinary high value-peaks and to the corresponding interpolation of these data. New algorithm for “peaks” detection and elimination is proposed and evaluated. Common Air Quality Index (CAQI) is calculated and evaluated in comparison with public monitoring station. It is shown that low-cost sensors could be used with high reliability as a complementary network to public monitoring stations.

The current epidemic caused by a novel coronavirus SARS-CoV2 as well as two previously documented pandemic caused by SARS-CoV and MERS-CoV imposes that a spillover of an animal coronavirus to humans is a continuous threat. The zoonotic nature of the infection contributes to the unpredictability of the pandemic. In such situations, the availability of the ‘off the shelf’ vaccines that target the conserved region of the coronavirus might help in preventing the spread of the diseases. Therefore, efforts to generate such vaccines should be considered as a priority. The whole genome of SARS-CoV2 is readily available in the public database one month after the first case was identified. The platform technology known as the “genome to vaccine” approach would provide useful start to identify parts of the virus proteome which can be the candidate for vaccine components. This study used an immunoinformatic approach to identify T cell epitopes from SARS-CoV2 ORF1ab polyprotein in an attempt to design a genome-derived epitope-based universal coronavirus vaccine.