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Deaf spaces are unique indoor environments designed to optimize visual communication and Deaf cultural expression. However, much of the technological research geared towards the deaf involve use of video or wearables for American sign language (ASL) translation, with little consideration for Deaf perspective on privacy and usability of the technology. In contrast to video, RF sensors offer the avenue for ambient ASL recognition while also preserving privacy for Deaf signers. Methods: This paper investigates the RF transmit waveform parameters required for effective measurement of ASL signs and their effect on word-level classification accuracy attained with transfer learning and convolutional autoencoders (CAE). A multi-frequency fusion network is proposed to exploit data from all sensors in an RF sensor network and improve the recognition accuracy of fluent ASL signing. Results: For fluent signers, CAEs yield a 20-sign classification accuracy of %76 at 77 GHz and %73 at 24 GHz, while at X-band (10 Ghz) accuracy drops to 67%. For hearing imitation signers, signs are more separable, resulting in a 96% accuracy with CAEs. Further, fluent ASL recognition accuracy is significantly increased with use of the multi-frequency fusion network, which boosts the 20-sign fluent ASL recognition accuracy to 95%, surpassing conventional feature level fusion by 12%. Implications: Signing involves finer spatiotemporal dynamics than typical hand gestures, and thus requires interrogation with a transmit waveform that has a rapid succession of pulses and high bandwidth. Millimeter wave RF frequencies also yield greater accuracy due to the increased Doppler spread of the radar backscatter. Comparative analysis of articulation dynamics also shows that imitation signing is not representative of fluent signing, and not effective in pre-training networks for fluent ASL classification. Deep neural networks employing multi-frequency fusion capture both shared, as well as sensor-specific features and thus offer significant performance gains in comparison to using a single sensor or feature-level fusion.

The neural circuits that regulate placebo analgesia responsivity are unknown, although engagement of brainstem pain modulatory regions is likely critical. Here we show in 47 participants that differences are present in neural circuit connectivity’s in placebo responders versus non-responders. We distinguish stimulus-independent and stimulus-dependent neural networks that display altered connections between the hypothalamus, anterior cingulate cortex and midbrain periaqueductal gray matter. This dual regulatory system underpins an individual’s ability to mount placebo analgesia.

The chemokine network is comprised of a family of signal proteins that encode messages for cells displaying chemokine G-protein coupled receptors (GPCRs). The diversity of effects on cellular functions, particularly directed migration of different cell types to sites of inflammation, is enabled by different combinations of chemokines activating signal transduction cascades on cells displaying a combination of receptors. These signals can contribute to autoimmune disease or be hijacked in cancer to stimulate cancer progression and metastatic migration. Thus far, three chemokine receptor-targeting drugs have been approved for clinical use: Maraviroc for HIV, Plerixafor for hematopoietic stem cell mobilization, and Mogalizumab for cutaneous T-cell lymphoma. Numerous compounds have been developed to inhibit specific chemokine GPCRs, but the complexity of the chemokine network has precluded more widespread clinical implementation, particularly as anti-neoplastic and anti-metastatic agents. Drugs that block a single signaling axis may be rendered ineffective or cause adverse reactions because each chemokine and receptor often have multiple context-specific functions. The chemokine network is tightly regulated at multiple levels, including by atypical chemokine receptors (ACKRs) that control chemokine gradients independently of G-proteins. ACKRs have numerous functions linked to chemokine immobilization, movement through and within cells, and recruitment of alternate effectors like β-arrestins. Atypical chemokine receptor 1 (ACKR1), previously known as the Duffy antigen receptor for chemokines (DARC), is a key regulator that binds chemokines involved in inflammatory responses and cancer proliferation, angiogenesis, and metastasis. Understanding more about ACKR1 in different diseases and populations may contribute to the development of therapeutic strategies targeting the chemokine network.

Macrophages are a heterogeneous population of innate immune cells that are often divided into two major subsets: classically activated, typically pro-inflammatory (M1) macrophages that mediate host defense, and alternatively activated, tolerance-inducing (M2) macrophages that exert homeostatic and tissue-regenerative functions. Disturbed macrophage function/differentiation results either in inadequate, excessive immune activation or in a failure to induce efficient protective immune responses against pathogens. Loss-of-function variants in protein tyrosine phosphatase non-receptor type 2 (PTPN2) are associated with chronic inflammatory disorders, but the effect of macrophage-intrinsic PTPN2 loss is still poorly understood. Here we report that PTPN2-deficient macrophages fail to acquire an alternatively activated/M2 phenotype. This was the consequence of reduced IL-6 receptor expression and a failure to induce IL-4 receptor in response to IL-6, resulting in an inability to respond to the key M2-inducing cytokine IL-4. Ultimately, failure to adequately respond to IL-6 and IL-4 resulted in increased levels of M1 macrophage marker expression in vitro and exacerbated lung inflammation upon infection with Nippostrongylus brasiliensis in vivo. These results demonstrate that PTPN2 loss interferes with the ability of macrophages to adequately respond to inflammatory stimuli and might explain the increased susceptibility of PTPN2 loss-of-function carriers to developing inflammatory diseases.

Paraconduit hiatal hernia (PCHH) is a known complication of esophagectomy with significant morbidity. PCHH may be more common with the transition to a minimally invasive approach and improved survival. We studied the PCHH occurrence following minimally invasive esophagectomy to determine the incidence, treatment, and associated risk factors.We retrospectively reviewed records of patients who underwent esophagectomy at an academic tertiary care center between 2013-2020. We divided the cohort into those who did and did not develop PCHH, identifying differences in demographics, perioperative characteristics and outcomes. We present video of our laparoscopic repair with mesh.Of 49 patients who underwent esophagectomy, seven (14%) developed PCHH at a median of 186 d (60-350 d) postoperatively. They were younger (57 versus 64 y, P0.01), and in cases of resection for cancer, more likely to develop tumor recurrence (71% versus 23%, P= 0.02). There was a significant difference in 2-y cancer free survival of patients with a PCHH (PCHH 19% versus no hernia 73%, P0.01), but no significant difference in 5-y overall survival (PCHH 36% versus no hernia 68%, P= 0.18). Five of seven PCHH were symptomatic and addressed surgically. Four PCHH repairs recurred at a median of 409 d.PCHH is associated with younger age and tumor recurrence, but not mortality. Safe repair of PCHH can be performed laparoscopically with or without mesh. Further studies, including systematic video review, are needed to address modifiable risk factors and identify optimal techniques for durable repair of post-esophagectomy PCHH.

Pain perception can be powerfully influenced by an individual's expectations and beliefs. Although the cortical circuitry responsible for pain modulation has been thoroughly investigated, the brainstem pathways involved in the modulatory phenomena of placebo analgesia and nocebo hyperalgesia remain to be directly addressed. This study used ultra-high-field 7 tesla functional MRI (fMRI) to accurately resolve differences in brainstem circuitry present during the generation of placebo analgesia and nocebo hyperalgesia in healthy human participants (N= 25, 12 male). Over 2 successive days, through blinded application of altered thermal stimuli, participants were deceptively conditioned to believe that two inert creams labeled lidocaine (placebo) and capsaicin (nocebo) were acting to modulate their pain relative to a third Vaseline (control) cream. In a subsequent test phase, fMRI image sets were collected while participants were given identical noxious stimuli to all three cream sites. Pain intensity ratings were collected and placebo and nocebo responses determined. Brainstem-specific fMRI analysis revealed altered activity in key pain modulatory nuclei, including a disparate recruitment of the periaqueductal gray (PAG)–rostral ventromedial medulla (RVM) pathway when both greater placebo and nocebo effects were observed. Additionally, we found that placebo and nocebo responses differentially activated the parabrachial nucleus but overlapped in engagement of the substantia nigra and locus coeruleus. These data reveal that placebo and nocebo effects are generated through differential engagement of the PAG–RVM pathway, which in concert with other brainstem sites likely influences the experience of pain by modulating activity at the level of the dorsal horn.SIGNIFICANCE STATEMENTUnderstanding endogenous pain modulatory mechanisms would support development of effective clinical treatment strategies for both acute and chronic pain. Specific brainstem nuclei have long been known to play a central role in nociceptive modulation; however, because of the small size and complex organization of the nuclei, previous neuroimaging efforts have been limited in directly identifying how these subcortical networks interact during the development of antinociceptive and pro-nociceptive effects. We used ultra-high-field fMRI to resolve brainstem structures and measure signal change during placebo analgesia and nocebo hyperalgesia. We define overlapping and disparate brainstem circuitry responsible for altering pain perception. These findings extend our understanding of the detailed organization and function of discrete brainstem nuclei involved in pain processing and modulation.

OBJECTIVE To evaluate the efficacy and safety of tin mesoporphyrin (SnMP) in neonates with hyperbilirubinemia (HB) due to hemolysis. STUDY DESIGN This multicenter, placebo-controlled phase 2b study (NCT01887327) randomized newborns (35-42 weeks) with hemolysis started on phototherapy (PT) to placebo (Ctrl), SnMP 3.0 mg/kg, or SnMP 4.5 mg/kg given once IM within 30 min of initiation of PT. RESULTS In all, 91 patients were randomized (Ctrl: n = 30; 3 mg/kg SnMP: n = 30; 4.5 mg/kg SnMP: n = 31). At 48 h TSB significantly increased in Ctrl by 17.5% (95% CI 5.6-30.7; p = 0.004) and significantly decreased by -13% (95% CI -21.7 to -3.2; p = 0.013) in the 3.0 mg/kg and by -10.5% (95% CI -19.4 to -0.6; p = 0.041) in the 4.5 mg/kg group. Decreases in SnMP groups were significant (p

To characterize national outcomes of oocyte thaw (OT) cycles.Retrospective descriptive study.All autologous OT cycles reported to the Society of Assisted Reproductive Technology Clinic Outcome Reporting System from 2012 to 2018.All women undergoing OT cycles in the United States.None.Absolute numbers of oocyte cryopreservation (OC) and OT cycles over time. Among OT cycles, patient and cycle characteristics, the ratio of the total number of oocytes thawed to the number of live births by maternal age at the time of cryopreservation (ATOC), and outcomes including pregnancy, miscarriage, live birth, and good perinatal outcome (GPO) by age ATOC.From 2012 to 2018, 54,675 OC and 6,413 OT cycles were performed; the absolute numbers increased from 2,719 to 13,824 and from 348 to 1,810, respectively. The ratio of the total number of oocytes thawed to the number of live births increased significantly with increasing age ATOC, from 41.4 (age35 years) to 122.4 (age41 years). Among OT cycles resulting in embryo transfer, the live birth rate decreased with increasing age ATOC from 42.8% (age35 years) to 10.8% (age42 years). The live birth rate was higher when calculated per transfer (42.8% in women aged35 years ATOC) rather than per thaw cycle (31.5% in women aged35 years ATOC) because of the number of patients with no transfer. Among 1,124 cycles resulting in pregnancy, the chance of a GPO was highest among women aged35 years ATOC (65.8%) and decreased as age at ATOC increased.Among reported OT cycles, the rates of pregnancy and live birth decreased as age ATOC increased. The number of oocytes thawed to achieve one live birth increased significantly with increasing age ATOC. In addition, among the resulting pregnancies, the rate of GPO decreased as age ATOC increased.

To determine the value of early exome sequencing (eES) relative to the current typical care (TC) in the diagnosis of newborns with suspected severe mitochondrial disorders (MitD). We used a decision tree–Markov hybrid to model neonatal intensive care unit (NICU)–related outcomes and costs, lifetime costs and quality-adjusted life-years among patients with MitD. Probabilities, costs, and utilities were populated using published literature, expert opinion, and the Pediatric Health Information System database. Incremental cost-effectiveness ratios (ICER) and net monetary benefits (NMB) were calculated from lifetime costs and quality-adjusted life-years for singleton and trio eES, and TC. Robustness was assessed using univariate and probabilistic sensitivity analyses (PSA). Scenario analyses were also conducted. Findings indicate trio eES is a cost-minimizing and cost-effective alternative to current TC. Diagnostic probabilities and NICU length-of-stay were the most sensitive model parameters. Base case analysis demonstrates trio eES has the highest incremental NMB, and PSA demonstrates trio eES had the highest likelihood of being cost-effective at a willingness-to-pay (WTP) of $200,000 relative to TC, singleton eES, and no ES. Trio and singleton eES are cost-effective and cost-minimizing alternatives to current TC in diagnosing newborns suspected of having a severe MitD.

Objective To identify opportunities for discontinuing elective and nonemergency surgical cases in a regional surgical practice in response to coronavirus disease 2019 (COVID-19). Patients and Methods COVID-19 began to affect surgical practices across the United States in March 2020. On March 17, 2020, all elective and nonemergency surgical care was deferred to prepare the Mayo Clinic Health System sites in northwestern Wisconsin for an anticipated surge in patients with COVID-19. When the decision was made to reactivate the surgical practice, several major structural and operational changes were made to the regional surgical practice to optimize efficiencies. Results The structural and operational changes implemented during reactivation resulted in improved utilization of surgical resources including improvement in operating room (OR) block utilization, increased available OR time, and increased case volumes. Conclusion Surgical and procedural leaders should consider a limited-time deferral of elective surgical cases to implement widespread OR efficiency strategies. The time selected for deferral of surgical cases should target a period of historically low surgical volume to minimize disruption to patient care and impact on overall OR functions.

This literature review explores prior research involving physiological-based mobile educational systems. Mobile computing is advancing, and implementations of ubiquitous systems for educational purposes are increasing. Another growing field is physiological computing, where the user's states are retrieved and applied as control inputs in applications. The integration of physiological signals such as electroencephalography (EEG), heart rate (ECG/EKG), and eye-tracking (EOG) to mobile learning (m-learning) applications can enhance the learning experiences to provide content tailored to the student's and educator's preferences. This article centers around a selection of core papers that represent the most relevant contributions to the research that falls at the intersection of m-learning and physiological computing. Specifically, this article presents an analysis and discussion of state-of-the-art mobile educational systems that leverage physiological technology.