Omnidirectional Monolithic Marker for Intra-Operative MR-Based Positional Sensing in Closed MRI.

We present a design of an inductively coupled radio frequency (ICRF) marker for magnetic resonance (MR)-based positional tracking, enabling the robust increase of tracking signal at all scanning orientations in quadrature-excited closed MR imaging (MRI). The marker employs three curved resonant circuits fully covering a cylindrical surface that encloses the signal source. Each resonant circuit is a planar spiral inductor with parallel plate capacitors fabricated monolithically on flexible printed circuit board (FPC) and bent to achieve the curved structure. Size of the constructed marker is Ø3-mm ×5 -mm with quality factor > 22, and its tracking performance was validated with 1.5 T MRI scanner. As result, the marker remains as a high positive contrast spot under 360° rotations in 3 axes. The marker can be accurately localized with a maximum error of 0.56 mm under a displacement of 56 mm from the isocenter, along with an inherent standard deviation of 0.1-mm. Accrediting to the high image contrast, the presented marker enables automatic and real-time tracking in 3D without dependency on its orientation with respect to the MRI scanner receive coil. In combination with its small form-factor, the presented marker would facilitate robust and wireless MR-based tracking for intervention and clinical diagnosis. This method targets applications that can involve rotational changes in all axes (X-Y-Z).

Interactive Multi-Stage Robotic Positioner for Intra-Operative MRI-Guided Stereotactic Neurosurgery.

Magnetic resonance imaging (MRI) demonstrates clear advantages over other imaging modalities in neurosurgery with its ability to delineate critical neurovascular structures and cancerous tissue in high-resolution 3D anatomical roadmaps. However, its application has been limited to interventions performed based on static pre/post-operative imaging, where errors accrue from stereotactic frame setup, image registration, and brain shift. To leverage the powerful intra-operative functions of MRI, e.g., instrument tracking, monitoring of physiological changes and tissue temperature in MRI-guided bilateral stereotactic neurosurgery, a multi-stage robotic positioner is proposed. The system positions cannula/needle instruments using a lightweight (203 g) and compact (Ø97 × 81 mm) skull-mounted structure that fits within most standard imaging head coils. With optimized design in soft robotics, the system operates in two stages: i) manual coarse adjustment performed interactively by the surgeon (workspace of ±30°), ii) automatic fine adjustment with precise (<0.2° orientation error), responsive (1.4 Hz bandwidth), and high-resolution (0.058°) soft robotic positioning. Orientation locking provides sufficient transmission stiffness (4.07 N/mm) for instrument advancement. The system's clinical workflow and accuracy is validated with lab-based (<0.8 mm) and MRI-based testing on skull phantoms (<1.7 mm) and a cadaver subject (<2.2 mm). Custom-made wireless omni-directional tracking markers facilitated robot registration under MRI.

Mendelian Randomization Studies of Lifestyle-Related Risk Factors for Osteoarthritis: A PRISMA Review and Meta-Analysis.

Risk factors for osteoarthritis (OA) often exert effects over protracted time-courses. Mendelian randomization (MR) studies therefore have an advantage over conventional observational studies when studying the causal effect of long-term lifestyle-related risk factors on OA. However, given the heterogeneous design of existing MR studies on OA, the reported causal estimates of these effects remain inconsistent, thus obscuring the true extent of the biological effects of OA lifestyle-risk factors. We conducted a PRISMA systematic review and specifically included MR studies that investigated the causal effect between lifestyle-related risk factors and OA, where causal estimates for various lifestyle factors were pooled for meta-analysis. Quality of studies was assessed according to STROBE-MR guidelines. A total of 1576 studies were evaluated and 23 were included. Overall, the studies included were of high quality and had a low risk of bias. Our meta-analysis demonstrates the positive causal effect of BMI (ORIVW-random effects 1.49 [1.23-1.80]) and negative causal effects of serum calcium (ORIVW-random effects 0.69 [0.57-0.83]) and LDL levels (ORIVW-random effects 0.93 [0.90-0.96]) on OA. Despite the heterogeneous designs and estimates of causal effects provided by various MR studies, our meta-analysis suggests that lifestyle-related risk factors in the form of BMI, serum calcium, and LDL have true biological effects on the development of OA.

Exploring Electrochemical C(sp3)-H Oxidation for the Late-Stage Methylation of Complex Molecules.

The "magic methyl" effect, a dramatic boost in the potency of biologically active compounds from the incorporation of a single methyl group, provides a simple yet powerful strategy employed by medicinal chemists in the drug discovery process. Despite significant advances, methodologies that enable the selective C(sp3)-H methylation of structurally complex medicinal agents remain very limited. In this work, we disclose a modular, efficient, and selective strategy for the α-methylation of protected amines (i.e., amides, carbamates, and sulfonamides) by means of electrochemical oxidation. Mechanistic analysis guided our development of an improved electrochemical protocol on the basis of the classic Shono oxidation reaction, which features broad reaction scope, high functional group compatibility, and operational simplicity. Importantly, this reaction system is amenable to the late-stage functionalization of complex targets containing basic nitrogen groups that are prevalent in medicinally active agents. When combined with organozinc-mediated C-C bond formation, our protocol enabled the direct methylation of a myriad of amine derivatives including those that have previously been explored for the "magic methyl" effect. This synthesis strategy thus circumvents multistep de novo synthesis that is currently necessary to access such compounds and has the potential to accelerate drug discovery efforts.

Twenty-four-channel high-impedance glove array for hand and wrist MRI at 3T.

PURPOSE: To present a novel 3T 24-channel glove array that enables hand and wrist imaging in varying postures. METHODS: The glove array consists of an inner glove holding the electronics and an outer glove protecting the components. The inner glove consists of four main structures: palm, fingers, wrist, and a flap that rolls over on top. Each structure was constructed out of three layers: a layer of electrostatic discharge flame-resistant fabric, a layer of scuba neoprene, and a layer of mesh fabric. Lightweight and flexible high impedance coil (HIC) elements were inserted into dedicated tubes sewn into the fabric. Coil elements were deliberately shortened to minimize the matching interface. Siemens Tim 4G technology was used to connect all 24 HIC elements to the scanner with only one plug. RESULTS: The 24-channel glove array allows large motion of both wrist and hand while maintaining the SNR needed for high-resolution imaging. CONCLUSION: In this work, a purpose-built 3T glove array that embeds 24 HIC elements is demonstrated for both hand and wrist imaging. The 24-channel glove array allows a great range of motion of both the wrist and hand while maintaining a high SNR and providing good theoretical acceleration performance, thus enabling hand and wrist imaging at different postures to extract kinematic information.

Analyzing protest mobilization on Telegram: The case of 2019 Anti-Extradition Bill movement in Hong Kong.

Online messaging app Telegram has increased in popularity in recent years surpassing Twitter and Snapchat by the number of active monthly users in late 2020. The messenger has also been crucial to protest movements in several countries in 2019-2020, including Belarus, Russia and Hong Kong. Yet, to date only few studies examined online activities on Telegram and none have analyzed the platform with regard to the protest mobilization. In the present study, we address the existing gap by examining Telegram-based activities related to the 2019 protests in Hong Kong. With this paper we aim to provide an example of methodological tools that can be used to study protest mobilization and coordination on Telegram. We also contribute to the research on computational text analysis in Cantonese-one of the low-resource Asian languages,-as well as to the scholarship on Hong Kong protests and research on social media-based protest mobilization in general. For that, we rely on the data collected through Telegram's API and a combination of network analysis and computational text analysis. We find that the Telegram-based network was cohesive ensuring efficient spread of protest-related information. Content spread through Telegram predominantly concerned discussions of future actions and protest-related on-site information (i.e., police presence in certain areas). We find that the Telegram network was dominated by different actors each month of the observation suggesting the absence of one single leader. Further, traditional protest leaders-those prominent during the 2014 Umbrella Movement,-such as media and civic organisations were less prominent in the network than local communities. Finally, we observe a cooldown in the level of Telegram activity after the enactment of the harsh National Security Law in July 2020. Further investigation is necessary to assess the persistence of this effect in a long-term perspective.

Soft robotic manipulator for intraoperative MRI-guided transoral laser microsurgery.

Magnetic resonance (MR) imaging (MRI) provides compelling features for the guidance of interventional procedures, including high-contrast soft tissue imaging, detailed visualization of physiological changes, and thermometry. Laser-based tumor ablation stands to benefit greatly from MRI guidance because 3D resection margins alongside thermal distributions can be evaluated in real time to protect critical structures while ensuring adequate resection margins. However, few studies have investigated the use of projection-based lasers like those for transoral laser microsurgery, potentially because dexterous laser steering is required at the ablation site, raising substantial challenges in the confined MRI bore and its strong magnetic field. Here, we propose an MR-safe soft robotic system for MRI-guided transoral laser microsurgery. Owing to its miniature size (Ø12 × 100 mm), inherent compliance, and five degrees of freedom, the soft robot ensures zero electromagnetic interference with MRI and enables safe and dexterous operation within the confined oral and pharyngeal cavities. The laser manipulator is rapidly fabricated with hybrid soft and hard structures and is powered by microvolume (<0.004 milliter) fluid flow to enable laser steering with enhanced stiffness and lowered hysteresis. A learning-based controller accommodates the inherent nonlinear robot actuation, which was validated with laser path-following tests. Submillimeter laser steering accuracy was demonstrated with a mean error < 0.20 mm. MRI compatibility testing demonstrated zero observable image artifacts during robot operation. Ex vivo tissue ablation and a cadaveric head-and-neck trial were carried out under MRI, where we employed MR thermometry to monitor the tissue ablation margin and thermal diffusion intraoperatively.

Real-to-virtual domain transfer-based depth estimation for real-time 3D annotation in transnasal surgery: a study of annotation accuracy and stability.

PURPOSE: Surgical annotation promotes effective communication between medical personnel during surgical procedures. However, existing approaches to 2D annotations are mostly static with respect to a display. In this work, we propose a method to achieve 3D annotations that anchor rigidly and stably to target structures upon camera movement in a transnasal endoscopic surgery setting. METHODS: This is accomplished through intra-operative endoscope tracking and monocular depth estimation. A virtual endoscopic environment is utilized to train a supervised depth estimation network. An adversarial network transfers the style from the real endoscopic view to a synthetic-like view for input into the depth estimation network, wherein framewise depth can be obtained in real time. RESULTS: (1) Accuracy: Framewise depth was predicted from images captured from within a nasal airway phantom and compared with ground truth, achieving a SSIM value of 0.8310 ± 0.0655. (2) Stability: mean absolute error (MAE) between reference and predicted depth of a target point was 1.1330 ± 0.9957 mm. CONCLUSION: Both the accuracy and stability evaluations demonstrated the feasibility and practicality of our proposed method for achieving 3D annotations.

Troubling content: Guiding discussion of death by suicide on social media.

Growing concerns about "online harm" and "duty of care" fuel debate about how best to regulate and moderate "troubling content" on social media. This has become a pressing issue in relation to the potential application of media guidelines to online discussion of death by suicide-discussion which is troubling because it is often transgressive and contested. Drawing on an innovative mixed-method analysis of a large-scale Twitter dataset, this article explores in depth, for the first time, the complexities of applying existing media guidelines on reporting death by suicide to online contexts. By focusing on five highly publicised deaths, it illustrates the limits of this translation but also the significance of empathy (its presence and absence) in online accounts of these deaths. The multi-relational and politicised nature of empathy, and the polarised nature of Twitter debate, suggests that we need to step back from calls for the automatic application of guidelines produced in a pre-digital time to understand more about the sociocultural context of how suicide is discussed on social media. This stepping back matters because social media is now a key part of how lives and deaths are deemed grievable and deserving of our attention.

Induced Disassembly of a Virus-like Particle under Physiological Conditions for Venom Peptide Delivery.

Virus-like particles (VLPs) show considerable promise for the in vivo delivery of therapeutic compounds such as bioactive venom peptides. While loading and targeting protocols have been developed for numerous VLP prototypes, induced disassembly under physiological conditions of neutral pH, moderate temperature, and aqueous medium remain a challenge. Here, we implement and evaluate a general mechanism, based on ring-opening metathesis polymerization (ROMP), for controllable VLP disassembly. This mechanism is independent of cell-specific factors or the manipulation of environmental conditions such as pH and temperature that cannot be readily controlled in vivo. The ROMP substrate norbornene is covalently conjugated to surface-exposed lysine residues of a P22 bacteriophage-derived VLP, and ROMP is induced by treatment with the water-soluble ruthenium catalyst AquaMet. Disruption of the P22 shell and release of a GFP reporter is confirmed via native agarose electrophoresis, TEM, and dynamic light scattering (DLS) analyses. Our ROMP disassembly strategy does not depend on the particular structure or morphology of the P22 nanocontainer and is adaptable to other VLP prototypes for the potential delivery of venom peptides for pharmacological applications.

Interfacing Soft and Hard: A Spring Reinforced Actuator.

Muscular hydrostats have long been a source of inspiration for soft robotic designs. With their inherent compliance, they excel in unpredictable environments and can gently manipulate objects with ease. However, their performance lacks where high force or a fast-dynamic response is needed. In this study, we propose a novel spring reinforced actuator (SRA) that explores the intermediate state between muscular hydrostats and endoskeletal mechanisms. The result is that we dramatically enhance the robot dynamic performance, which is unprecedented in similar kinds of soft robots, while retaining compliant omnidirectional bending. Analytical modeling of the flexible backbone was built and experimentally validated. This is also the first attempt to perform detailed finite element analysis to investigate the strain-stress behavior of the constraining braided bellow tube. The braided interweaving threads are modeled, in which complex thread-to-thread contacts occur. Experimental evaluation of SRAs was performed for actuation force, stiffness, and dynamic response. We showcase the enhanced actuator's performance in several applications such as locomotion and heavy object manipulation.

Scoliosis severity does not impact the risk of scoliosis in family members.

Does scoliosis severity increase scoliosis risk or severity in relatives? In a cohort of 1257 severe idiopathic scoliosis patients, the percentage with at least one affected relative was compared across the categories of patient sex, major curve severity (Cobb angle), and treatment method. In total, 138 (11%) of 1257 patients had at least one affected first-degree relative and 59 (5%) had at least one affected second-degree relative. As expected, males were more likely to have affected first-degree relatives than females (18 vs. 10% with a risk difference of -0.0864) [95% confidence interval (CI): -0.14 to -0.03; P=0.0002]. However, the major curve severity of the patient (<25°, 25°-49°, and ≥50°) did not impact the prevalence of having at least one affected relative (P=0.69). Surgically treated patients had no greater risk than nonsurgically treated patients of having either an affected relative or a surgically treated relative [11 vs. 11% (odds ratio: 0.912; 95% CI: 0.640-1.299, P=0.61), 6 vs. 5% (OR: 0.788; 95% CI: 0.485-1.280, P=0.34), respectively]. Therefore, our data suggest that scoliosis severity does not independently influence the risk of either scoliosis or its severity in family members.

Characterization of cell wall components of wheat straw following hydrothermal pretreatment and fractionation.

Thermophysical pretreatment enhances the enzymatic hydrolysis of lignocellulose. However, its impact on cell wall chemistry is still poorly understood. This paper reports the effects of hydrothermal pretreatment on the degradation and alkali-extractability of wheat straw cell wall polymers. Pretreatment resulted in loss and/or solubilization of arabinoxylans (by 53%), ferulic and diferulic acids which are important cross-linking agents accompanied by concomitant increases in cellulose (up to 43%) and lignin (29%). The remaining water-insoluble hemicelluloses were more readily extractable in alkali and were reduced in molecular weight indicating substantial thermochemical depolymerization. They were also associated with smaller but significant amounts of (cellulose-derived) glucose. The alkali-insoluble residues consisted predominantly of cellulosic glucose and lignin and contained p-coumaric acid. The depolymerization of hemicelluloses, reduction in cinnamic acids and partial degradation of cellulose is likely to contribute significantly to the accessibility of cellulases during subsequent enzymolysis.

When should psychiatrists seek criminal prosecution of assaultive psychiatric inpatients?

This Open Forum commentary reviews the ethical considerations relevant to the question of prosecuting assaultive psychiatric patients, with particular attention to the significance that should be attached to the arguments generated by those considerations. A comprehensive literature search was conducted incorporating the terms "assaultive patients," "ethics," "psychiatric inpatients," and "law." The literature of professional medical ethics was applied to identify relevant domains of ethical argument. Five domains were identified: fiduciary obligations of physicians to assaultive and other patients; obligations to staff members; professional virtues of compassion, self-sacrifice, and self-effacement; retributive justice; and the patient's right to confidentiality. The content of each domain is explained, and guidance is provided on how to assess the relative strengths of ethical argument within each domain. All five domains must be explicitly addressed in order to make ethically disciplined judgments about whether to seek prosecution. A distinctive feature of this ethical analysis is the central importance of the professional virtues.

Photolithographic fabrication of gated self-aligned parallel electron beam emitters with a single-stranded carbon nanotube.

In this paper we report on the development of a photolithographic process to fabricate a gated-emitter array with single-stranded carbon nanotubes (CNTs) self-aligned to the center of the emitter gate using plasma-enhanced chemical vapor deposition (PECVD). Si tips are formed on a silicon wafer by anisotropic etching of Si using SiO(2) as a mask. Deposition of a SiO(2) insulating layer and Cr-W electrode layers creates protrusions above the Si tips. This wafer is polished, and the Cr-W on the tips is removed. Etching of the SiO(2) using hydrofluoric acid is performed to expose the gated Si tip. Incorporation of a novel diffusion process produces single-stranded CNTs by depositing a thin Ni layer on the Si tips and thermally diffusing the Ni layer to yield a catalyst particle for single-stranded CNT growth. The large surface to volume ratio at the apex of the Si tip allows a Ni particle to remain to act as a catalyst to grow a single-stranded CNT for fabricating the CNT based emitter structure. Diffusion of the Ni is carried out in situ during the heating phase of the PECVD CNT growth process at 600 °C. The diameters of the observed CNTs are on the order of 20 nm. The field emission characteristics of the gated field emitters are evaluated. The measured turn-on voltage of the gated emitter is 5 V.

Disability, humanity, and personhood: a survey of moral concepts.

Three of the articles included in this issue of the Journal of Medicine and Philosophy - Ron Amundson and Shari Tresky's "On a Bioethical Challenge to Disability Rights"; Rachel Cooper's "Can It Be a Good Thing to Be Deaf?"; and Mark T. Brown's "The Potential of the Human Embryo" - interact (in various ways) with the concepts of disability, humanity, and personhood and their normative dimensions. As one peruses these articles, it becomes apparent that terms like "disability," "human being," and "person" carry with them great normative significance. There is, however, much disagreement concerning both the definition and the extension of such terms. This is significant because different terms and definitions are associated with different sets of normative requirements. In what follows we reconstruct the argument of each of the articles, and then offer some brief critical analysis intended to stimulate further thought about and discussion of the issues that each raises.