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High-grade (grade 3) neuroendocrine neoplasms (G3 NENs) have poor survival outcomes. From a clinical standpoint, G3 NENs are usually grouped regardless of primary site and treated similarly. Little is known regarding the underlying genomics of these rare tumors, especially when compared across different primary sites. We performed whole transcriptome (n = 46), whole exome (n = 40), and gene copy number (n = 43) sequencing on G3 NEN formalin-fixed, paraffin-embedded samples from diverse organs (in total, 17 were lung, 16 were gastroenteropancreatic, and 13 other). G3 NENs despite arising from diverse primary sites did not have gene expression profiles that were easily segregated by organ of origin. Across all G3 NENs, TP53, APC, RB1, and CDKN2A were significantly mutated. The CDK4/6 cell cycling pathway was mutated in 95% of cases, with upregulation of oncogenes within this pathway. G3 NENs had high tumor mutation burden (mean 7.09 mutations/MB), with 20% having >10 mutations/MB. Two somatic copy number alterations were significantly associated with worse prognosis across tissue types: focal deletion 22q13.31 (HR, 7.82; P = 0.034) and arm amplification 19q (HR, 4.82; P = 0.032). This study is among the most diverse genomic study of high-grade neuroendocrine neoplasms. We uncovered genomic features previously unrecognized for this rapidly fatal and rare cancer type that could have potential prognostic and therapeutic implications.

Purpose:Taletrectinib (DS-6051b/AB-106) is an oral, tyrosine kinase inhibitor of ROS1 and NTRK with potent preclinical activity against ROS1 G2032R solvent-front mutation among others. We report the first-in-human U.S. phase I results of taletrectinib.Patients and Methods:Patients ≥18 years old with neuroendocrine tumors, with tumor-induced pain, or tumors harboring ROS1/NTRK rearrangements were eligible. Accelerated titration followed by modified continuous reassessment method and escalation with overdose control was used (50–1,200 mg once daily or 400 mg twice daily). Primary objectives were safety/tolerability, and MTD determination. Secondary objectives were food-effect pharmacokinetics and antitumor activity.Results:A total of 46 patients were enrolled. Steady-state peak concentration (Cmax) and exposure (AUC0-8) increased dose dependently from 50-mg to 800-mg once-daily doses. The ratio of the geometric mean of AUC0-24 between low-fat-diet-fed/fasted state was 123% (90% confidence interval, 104%–149%). Dose-limiting toxicities (grade 3 transaminases increase) occurred in two patients (1,200-mg once-daily dose). MTD was 800 mg once daily. Most common treatment-related adverse events were nausea (47.8%), diarrhea (43.5%), and vomiting (32.6%). Pain score reductions were observed in the 800-mg once-daily dose cohort. Confirmed objective response rate was 33.3% among the six patients with RECIST-evaluable crizotinib-refractory ROS1+ NSCLC. One patient with TPM3-NTRK1 differentiated thyroid cancer achieving a confirmed partial response of 27 months at data cutoff. We identified a cabozantinib-sensitive ROS1 L2086F as an acquired taletrectinib-resistance mutation.Conclusions:Taletrectinib has manageable toxicities at the MTD of 800 mg daily. Preliminary efficacy was observed in patients with crizotinib-refractory ROS1+ NSCLC.

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This paper presents a novel 7 DOF (i.e., orientation, translation, and scale) visual simultaneous localization and mapping (vSLAM) system for mobile robots in outdoor environments. In the front end of this vSLAM system, a fast initialization method is designed for different vSLAM backbones, which upgrades the accuracy of trajectory and reconstruction of vSLAM with an absolute scale computed from depth maps generated by building blocks. In the back end of this vSLAM, we propose a nonlinear optimization mechanism throughout which multimodal data are combined for more robust optimization. The modality of building blocks in optimization can improve the tracking accuracy and the scale estimation. By integrating the pose estimated from visual information and the position received through GPS, the optimization further alleviates the drift. The experimental results prove that the proposed method is extremely suitable for outer AR application for outdoor environments, because our method has superior initialization performance, runs in real time, and achieves real scale, higher accuracy, and robustness.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is considered a preinvasive lesion that may progress to carcinoid tumour [1]. Histologically, it is marked by a proliferation of neuroendocrine cells that is confined to the basement membrane (neuroendocrine cell hyperplasia; NECH), and/or has invaded past the basement membrane (carcinoid tumourlet) [2]. Tumourlets equal to or larger than 5 mm are classified as carcinoid tumours. Per the World Health Organization 2021 criteria, DIPNECH can be pathological (based solely on characteristic histological features) or clinical (diagnosed per characteristic symptoms and imaging findings, e.g. respiratory symptoms, bilateral pulmonary nodules, mosaic attenuation on computed tomography (CT)) [2]. In contrast to some lung diseases or neoplasms that can cause secondary, reactive NECH/tumourlets to form, DIPNECH is marked by such hyperplasia without an identifiable cause., DIPNECH is a rare disease that is often misdiagnosed. In this study, it primarily affected elderly white women who were non-smokers. Lung nodules could slowly progress over years to carcinoid tumours. Average growth rate per nodule was 0.8 mm per year. https://bit.ly/3q1HD1k

Background Many patients with chronic medical conditions search the internet to obtain medical advice and health information to improve their health condition and quality of life. Diabetes is a common chronic disease that disproportionately affects different race and ethnicity groups in the United States. In the existing literature on the popularity of internet health information seeking among persons with a chronic medical condition, there are limited data on US adults living with diabetes. Objective This study aims to examine the factors associated with internet health information seeking among US adults living with diabetes and whether there is a disparity in internet health information seeking stratified by race and ethnicity. Methods We conducted a cross-sectional study using the Health Information National Trends Survey data from 2017 to 2020. We selected our study sample based on respondents’ reports on whether they were told they had diabetes, and our primary outcome was internet health information–seeking behavior. We used 2 multivariable logistic regression models to examine the effects of sociodemographic factors and other covariates on the internet health information–seeking behavior of adults with diabetes. Jackknife replicate weights were used to provide bias-corrected variance estimates. Results Our study sample included 2903 adults who self-reported that they had diabetes. In total, 60.08% (1744/2903) were non-Hispanic White individuals, 46.88% (1336/2850) were men, and 64% (1812/2831) had some college or graduate education. The prevalence of internet health information seeking in this population was 64.49% (1872/2903), and the main factors associated with internet health information seeking included education level (some college vs less than high school: odds ratio [OR] 1.42, 95% CI 1.44-1.88; and college graduate or higher vs less than high school: OR 2.50, 95% CI 1.79-3.50), age (age group ≥65 years vs age group 18-44 years: OR 0.46, 95% CI 0.34-0.63), and household income level (P Conclusions The findings from this study suggest that internet health information seeking is common among US adults living with diabetes. Internet health information could influence the relationship between health care providers and adults living with diabetes and improve their self-management and quality of life.

Most current medical imaging Artificial Intelligence (AI) relies upon transfer learning using convolutional neural networks (CNNs) created using ImageNet, a large database of natural world images, including cats, dogs, and vehicles. Size, diversity, and similarity of the source data determine the success of the transfer learning on the target data. ImageNet is large and diverse, but there is a significant dissimilarity between its natural world images and medical images, leading Cheplygina to pose the question, “Why do we still use images of cats to help Artificial Intelligence interpret CAT scans?”. We present an equally large and diversified database, RadImageNet, consisting of 5 million annotated medical images consisting of CT, MRI, and ultrasound of musculoskeletal, neurologic, oncologic, gastrointestinal, endocrine, and pulmonary pathologies over 450,000 patients. The database is unprecedented in scale and breadth in the medical imaging field, constituting a more appropriate basis for medical imaging transfer learning applications. We found that RadImageNet transfer learning outperformed ImageNet in multiple independent applications, including improvements for bone age prediction from hand and wrist x-rays by 1.75 months (p

Multi-agent unmanned aerial vehicle (UAV) teaming becomes an essential part in science mission, modern warfare surveillance, and disaster rescuing. This paper proposes a decentralized UAV swarm persistent monitoring strategy in realizing continuous sensing coverage and network service. A two-layer (high altitude and low altitude) UAV teaming hierarchical structure is adopted in realizing the accurate object tracking in the area of interest (AOI). By introducing the UAV communication channel model in its path planning, both centralized and decentralized control schemes would be evaluated in the waypoint tracking simulation. The UAV swarm network service and object tracking are measured by metrics of communication link quality and waypoints tracking accuracy. UAV swarm network connectivity are evaluated over different aspects, such as stability and volatility. The comparison of proposed algorithms is presented with simulations. The result shows that the decentralized scheme outperforms the centralized scheme in the mission of persistent surveillance, especially on maintaining the stability of inner UAV swarm network while tracking moving objects.

To deal with data sets from real-time 3D sensors of RGB-D or TOF cameras, this paper presents a method for registration of unstructured point clouds. We firstly derive intrinsic shape context descriptors for 3D data organization. To replace the Fast-Marching method, a vertex-oriented triangle propagation method is applied to calculate the ’angle’ and ’radius’ in descriptor charting, so that the matching accuracy at the twisting and folding area is significantly improved. Then, a 3D cylindrical shape descriptor is proposed for registration of unstructured point clouds. The chosen points are projected into the cylindrical coordinate system to construct the descriptors. The projection parameters are respectively determined by the distances from the chosen points to the reference normal vector, and the distances from the chosen points to the reference tangent plane and the projection angle. Furthermore, Fourier transform is adopted to deal with orientation ambiguity in descriptor matching. Practical experiments demonstrate a satisfactory result in point cloud registration and notable improvement on standard benchmarks.

The Internet of Things (IoT) provides applications and services that would otherwise not be possible. However, the open nature of IoT make it vulnerable to cybersecurity threats. Especially, identity spoofing attacks, where an adversary passively listens to existing radio communications and then mimic the identity of legitimate devices to conduct malicious activities. Existing solutions employ cryptographic signatures to verify the trustworthiness of received information. In prevalent IoT, secret keys for cryptography can potentially be disclosed and disable the verification mechanism. Non-cryptographic device verification is needed to ensure trustworthy IoT. In this paper, we propose an enhanced deep learning framework for IoT device identification using physical layer signals. Specifically, we enable our framework to report unseen IoT devices and introduce the zero-bias layer to deep neural networks to increase robustness and interpretability. We have evaluated the effectiveness of the proposed framework using real data from ADS-B (Automatic Dependent Surveillance-Broadcast), an application of IoT in aviation. The proposed framework has the potential to be applied to accurate identification of IoT devices in a variety of IoT applications and services. Codes and data are available in IEEE Dataport., Accepted for publication by IEEE IoTJ on August, 2020. Data and codes are hosted at: [1] Yongxin Liu, Jian Wang, Houbing Song, Shuteng Niu, Thomas Yang, "A 24-hour signal recording dataset with labels for cybersecurity and IoT", IEEE Dataport, 2020. [Online]. Available: http://dx.doi.org/10.21227/gt9v-kz32. Accessed: Aug. 27, 2020

Purpose: Taletrectinib (DS-6051b/AB-106) is an oral, tyrosine kinase inhibitor of ROS1 and NTRK with potent preclinical activity against ROS1 G2032R solvent-front mutation among others. We report the first-in-human U.S. phase I results of taletrectinib. Patients and Methods: Patients ≥18 years old with neuroendocrine tumors, with tumor-induced pain, or tumors harboring ROS1/NTRK rearrangements were eligible. Accelerated titration followed by modified continuous reassessment method and escalation with overdose control was used (50–1,200 mg once daily or 400 mg twice daily). Primary objectives were safety/tolerability, and MTD determination. Secondary objectives were food-effect pharmacokinetics and antitumor activity. Results: A total of 46 patients were enrolled. Steady-state peak concentration (Cmax) and exposure (AUC0-8) increased dose dependently from 50-mg to 800-mg once-daily doses. The ratio of the geometric mean of AUC0-24 between low-fat-diet-fed/fasted state was 123% (90% confidence interval, 104%–149%). Dose-limiting toxicities (grade 3 transaminases increase) occurred in two patients (1,200-mg once-daily dose). MTD was 800 mg once daily. Most common treatment-related adverse events were nausea (47.8%), diarrhea (43.5%), and vomiting (32.6%). Pain score reductions were observed in the 800-mg once-daily dose cohort. Confirmed objective response rate was 33.3% among the six patients with RECIST-evaluable crizotinib-refractory ROS1+ NSCLC. One patient with TPM3-NTRK1 differentiated thyroid cancer achieving a confirmed partial response of 27 months at data cutoff. We identified a cabozantinib-sensitive ROS1 L2086F as an acquired taletrectinib-resistance mutation. Conclusions: Taletrectinib has manageable toxicities at the MTD of 800 mg daily. Preliminary efficacy was observed in patients with crizotinib-refractory ROS1+ NSCLC.

Purpose Chronic axial low-back pain is a debilitating disorder that impacts all aspects of an afflicted individual’s life. Effective, durable treatments have historically been elusive. Interventional therapies, such as spinal cord stimulation (SCS), have shown limited efficacy at best. Recently, a novel treatment, 10 kHz SCS, has demonstrated superior pain relief compared with traditional SCS in a randomized controlled trial (RCT). In this manuscript, we report on the long-term improvements in quality of life (QoL) outcomes for subjects enrolled in this study. Methods A prospective, multicenter, randomized controlled trial (SENZA-RCT) was conducted. Patients with both chronic back and leg pain were enrolled and randomized (1:1) into 10 kHz SCS or traditional SCS treatment groups. A total of 171 subjects received a permanent SCS device implant. QoL and functionality measures were collected up to 12 months. The device remote control utilization, which is an indication of patient interaction with the device for adjustments, was collected at 24-month post-implantation. Results At 12 months, a higher proportion of 10 kHz SCS subjects had marked improvement of their disability (Oswestry Disability Index) to a “moderate” or “minimal” impact on their daily function versus the control group. The subjects also reported better improvement in the Global Assessment of Functioning, Clinician Global Impression of Change, Pittsburgh Sleep Quality Index, and short-form McGill Pain Questionnaire, compared to traditional SCS subjects. The 10 kHz SCS subjects also reported far higher rates of both driving and sleeping with their device turned on, as well as reduced reliance on their programmers to adjust therapy settings. Conclusions In addition to superior pain relief, 10 kHz SCS provides long-term improvements in quality of life and functionality for subjects with chronic low-back and leg pain. Trial registration: ClinicalTrials.gov (NCT01609972).

BACKGROUND Intractable neck and upper limb pain has historically been challenging to treat with conventional spinal cord stimulation (SCS) being limited by obtaining effective paresthesia coverage. OBJECTIVE To assess the safety and effectiveness of the 10-kHz SCS system, a paresthesia-independent therapy, in the treatment of neck and upper limb pain. METHODS Subjects with chronic, intractable neck and/or upper limb pain of ≥5 cm (on a 0-10 cm visual analog scale [VAS]) were enrolled in 6 US centers following an investigational device exemption from the Food and Drug Administration (FDA) and institutional review board approval. Each subject was implanted with 2 epidural leads spanning C2-C6 vertebral bodies. Subjects with successful trial stimulation were implanted with a Senza® system (Nevro Corp) and included in the evaluation of the primary safety and effectiveness endpoints. RESULTS In the per protocol population, the primary endpoint (≥50% pain relief at 3 mo) was achieved in 86.7% (n = 39/45) subjects. Compared to baseline, subjects reported a significant reduction (P

Summary Delineating molecular and cellular events that precede appendage morphogenesis has been challenging due to the inability to distinguish quantitative molecular differences between cells that lack histological distinction. The hair follicle (HF) dermal condensate (DC) is a cluster of cells critical for HF development and regeneration. Events that presage emergence of this distinctive population are poorly understood. Using unbiased single-cell RNA sequencing and in vivo methods, we infer a sequence of transcriptional states through which DC cells pass that begins prior to HF morphogenesis. Our data indicate that Wnt/β-catenin signaling is required to progress into an intermediate stage that precedes quiescence and differentiation. Further, we provide evidence that quiescent DC cells are recent progeny of selectively proliferating cells present prior to morphogenesis and that are later identified in the peri-DC zone during DC expansion. Together, these findings provide an inferred path of molecular states that lead to DC cell differentiation.

BACKGROUND: Pain relief with spinal cord stimulation (SCS) has focused historically on paresthesias overlapping chronically painful areas. A higher level evidence supports the use of SCS in treating leg pain than supports back pain, as it is difficult to achieve adequate paresthesia coverage, and then pain relief, in the low back region. In comparison, 10-kHz high-frequency (HF10 therapy) SCS therapy does not rely on intraoperative paresthesia mapping and remains paresthesia-free during therapy. OBJECTIVE: To compare long-term results of HF10 therapy and traditional low-frequency SCS. METHODS: A pragmatic randomized, controlled, pivotal trial with 24-month follow-up was conducted across 11 comprehensive pain treatment centers. Subjects had Visual Analog Scale scores of ≥5.0/10.0 cm for both back and leg pain, and were assigned randomly (1:1) to receive HF10 therapy or low-frequency SCS. The primary end point was a responder rate, defined as ≥50% back pain reduction from baseline at 3 months with a secondary end point at 12 months (previously reported). In this article, 24-month secondary results are presented. Non-inferiority was first assessed, and if demonstrated the results were tested for superiority. RESULTS: In the study, 198 subjects were randomized (101 HF10 therapy, 97 traditional SCS). One hundred seventy-one subjects (90 HF10 therapy, 81 traditional SCS) successfully completed a short-term trial and were implanted. Subjects averaged 54.9 ± 12.9 years old, 13.6 ± 11.3 years since diagnosis, 86.6% had back surgery, 88.3% were taking opioid analgesics. At 3 months, 84.5% of implanted HF10 therapy subjects were responders for back pain and 83.1% for leg pain, and 43.8% of traditional SCS subjects were responders for back pain and 55.5% for leg pain (P < .001 for both back and leg pain comparisons, non-inferiority and superiority). At 24 months, more subjects were responders to HF10 therapy than traditional SCS (back pain: 76.5% vs 49.3%; 27.2% difference, 95% CI, 10.1%-41.8%; P < .001 for non-inferiority and superiority; leg pain: 72.9% vs 49.3%; 23.6% difference, 95% CI, 5.9%-38.6%; P < .001 for non-inferiority and P = .003 for superiority). Also at 24 months, back pain decreased to a greater degree with HF10 therapy (66.9% ± 31.8%) than traditional SCS (41.1% ± 36.8%, P < .001 for non-inferiority and superiority). Leg pain also decreased to a greater degree with HF10 therapy (65.1% ± 36.0%) than traditional SCS (46.0% ± 40.4%, P < .001 for non-inferiority and P = .002 for superiority). CONCLUSION: This study demonstrates long-term superiority of HF10 therapy compared with traditional SCS in treating both back and leg pain. The advantages of HF10 therapy are anticipated to impact the management of chronic pain patients substantially. ABBREVIATIONS: IPG, implantable pulse generator MCID, minimal clinically important difference PI, permanent implant ODI, Oswestry Disability Index SCS, spinal cord stimulation VAS, Visual Analog Scale

Multiple-input- antennas are investigated for terrestrial point-to-point wireless link. The lack of rich scatters in a terrestrial wireless channel results in an ill-conditioned channel matrix for a long range link with compact arrays, which can cause a high bit error rate. This paper demonstrates that the channel matrix can be improved by carefully selecting the antenna spacing. Unfortunately, an optimum antenna spacing that guarantees a good channel matrix is too large to implement for most long range terrestrial wireless links. On the other hand, a channel capacity study of an 8 � 8 link reveals that multiple antennas do provide more capacity even with small antenna spacing. Constellation multiplexing is then applied to the compact array conguration to solve the unreliable communication problem. In addition, a multilevel maximum ratio combining technique is introduced to improve detection efficiency.

Background: Current treatments for chronic pain have limited effectiveness and commonly known side effects. Given the prevalence and burden of intractable pain, additional therapeutic approaches are desired. Spinal cord stimulation (SCS) delivered at 10 kHz (as in HF10 therapy) may provide pain relief without the paresthesias typical of traditional low-frequency SCS. The objective of this randomized, parallel-arm, noninferiority study was to compare long-term safety and efficacy of SCS therapies in patients with back and leg pain. Methods: A total of 198 subjects with both back and leg pain were randomized in a 1:1 ratio to a treatment group across 10 comprehensive pain treatment centers. Of these, 171 passed a temporary trial and were implanted with an SCS system. Responders (the primary outcome) were defined as having 50% or greater back pain reduction with no stimulation-related neurological deficit. Results: At 3 months, 84.5% of implanted HF10 therapy subjects were responders for back pain and 83.1% for leg pain, and 43.8% of traditional SCS subjects were responders for back pain and 55.5% for leg pain (P < 0.001 for both back and leg pain comparisons). The relative ratio for responders was 1.9 (95% CI, 1.4 to 2.5) for back pain and 1.5 (95% CI, 1.2 to 1.9) for leg pain. The superiority of HF10 therapy over traditional SCS for leg and back pain was sustained through 12 months (P < 0.001). HF10 therapy subjects did not experience paresthesias. Conclusion: HF10 therapy promises to substantially impact the management of back and leg pain with broad applicability to patients, physicians, and payers.

Spinal cord stimulation (SCS) has been successfully used to treat chronic intractable pain for over 40 years. Successful clinical application of SCS is presumed to be generally dependent on maximizing paresthesia-pain overlap; critical to achieving this is positioning of the stimulation field at the physiologic midline. Recently, the necessity of paresthesia for achieving effective relief in SCS has been challenged by the introduction of 10 kHz paresthesia-free stimulation. In a large, prospective, randomized controlled pivotal trial, HF10 therapy was demonstrated to be statistically and clinically superior to paresthesia-based SCS in the treatment of severe chronic low back and leg pain. HF10 therapy, unlike traditional paresthesia-based SCS, requires no paresthesia to be experienced by the patient, nor does it require paresthesia mapping at any point during lead implant or post-operative programming.To determine if pain relief was related to technical factors of paresthesia, we measured and analyzed the paresthesia responses of patients successfully using HF10 therapy.Prospective, multicenter, non-randomized, non-controlled interventional study.Outpatient pain clinic at 10 centers across the US and Italy.Patients with both back and leg pain already implanted with an HF10 therapy device for up to 24 months were included in this multicenter study. Patients provided pain scores prior to and after using HF10 therapy. Each patient's most efficacious HF10 therapy stimulation program was temporarily modified to a low frequency (LF; 60 Hz), wide pulse width (~470 mus), paresthesia-generating program. On a human body diagram, patients drew the locations of their chronic intractable pain and, with the modified program activated, all regions where they experienced LF paresthesia. Paresthesia and pain drawings were then analyzed to estimate the correlation of pain relief outcomes to overlap of pain by paresthesia, and the mediolateral distribution of paresthesia (as a surrogate of physiologic midline lead positioning).A total of 61 patients participated across 11 centers. Twenty-eight men and 33 women with a mean age of 56 ± 12 years of age participated in the study. The average duration of implantable pulse generator (IPG) implant was 19 ± 9 months. The average predominant pain score, as measured on a 0 - 10 visual analog scale (VAS), prior to HF10 therapy was 7.8 ± 1.3 and at time of testing was 2.5 ± 2.1, yielding an average pain relief of 70 ± 24%. For all patients, the mean paresthesia coverage of pain was 21 ± 28%, with 43% of patients having zero paresthesia coverage of pain. Analysis revealed no correlation between percentage of LF paresthesia overlap of predominant pain and HF10 therapy efficacy (P = 0.56). Exact mediolateral positioning of the stimulation electrodes was not found to be a statistically significant predictor of pain relief outcomes.Non-randomized/non-controlled study design; short-term evaluation; certain technical factors not investigated.Both paresthesia concordance with pain and precise midline positioning of the stimulation contacts appear to be inconsequential technical factors for successful HF10 therapy application. These results suggest that HF10 therapy is not only paresthesia-free, but may be paresthesia-independent.

Coordinated Hair Growth Wnt/β-catenin signaling is a key pathway that plays a conserved role in regulating stem cell function during adult tissue regeneration. Using time-lapse imaging of live mice, Deschene et al. (p. 1353 ) show that genetic activation of β-catenin within hair follicle stem cells generates axes of hair growth by coordinated cell divisions and cell movements, even when the normal niches—the dermal papillae—are laser-ablated. Activated β-catenin enhances Wnt ligand secretion, and these ligands can then activate Wnt signaling in adjacent cells that do not have activated β-catenin, indicating how activated stem cells could influence neighboring cells during normal growth and in cancer.

Bacterial vaginosis is a highly prevalent and poorly understood polymicrobial disorder of the vaginal microbiota, with significant adverse sequelae. Gardnerella vaginalis predominates in bacterial vaginosis. Biofilms of G. vaginalis are present in human infections and are implicated in persistent disease, treatment failure, and transmission. Here we demonstrate that G. vaginalis biofilms contain extracellular DNA, which is essential to their structural integrity. Enzymatic disruption of this DNA specifically inhibits biofilms, acting on both newly forming and established biofilms. DNase liberates bacteria from the biofilm to supernatant fractions and potentiates the activity of metronidazole, an antimicrobial agent used in the treatment of bacterial vaginosis. Using a new murine vaginal colonization model for G. vaginalis, we demonstrate >10-fold inhibition of G. vaginalis colonization by DNase. We conclude that DNase merits investigation as a potential nonantibiotic adjunct to existing bacterial vaginosis therapies in order to decrease the risk of chronic infection, recurrence, and associated morbidities.

Conventional, static analyses have historically been the bedrock and tool of choice for the study of skin cancers. Over the past several years, in vivo imaging of tumors using multiphoton microscopy has emerged as a powerful pre-clinical tool in revealing detailed cellular behaviors from the earliest moments of tumor development to the final steps of metastasis. Multiphoton microscopy allows for deep tissue penetration with relatively minor phototoxicity, rendering it an effective tool for the long-term observation of tumor evolution. This review highlights some of the recent preclinical insights gained using multiphoton microscopy, and suggests future advancements that could enhance its power in revealing the mysteries of skin tumor biology.

A key requirement of lunar rover autonomous navigation is to acquire state information accurately in real-time during its motion and set up a gradual parameter-based nonlinear kinematics model for the rover. In this paper, we propose a dual-extended-Kalman-filter- (dual-EKF-) based real-time celestial navigation (RCN) method. The proposed method considers the rover position and velocity on the lunar surface as the system parameters and establishes a constant velocity (CV) model. In addition, the attitude quaternion is considered as the system state, and the quaternion differential equation is established as the state equation, which incorporates the output of angular rate gyroscope. Therefore, the measurement equation can be established with sun direction vector from the sun sensor and speed observation from the speedometer. The gyro continuous output ensures the algorithm real-time operation. Finally, we use the dual-EKF method to solve the system equations. Simulation results show that the proposed method can acquire the rover position and heading information in real time and greatly improve the navigation accuracy. Our method overcomes the disadvantage of the cumulative error in inertial navigation.

Coupled nonlinear dynamical systems have been widely studied recently. However, the dynamical properties of these systems are difficult to deal with. The local activity of cellular neural network (CNN) has provided a powerful tool for studying the emergence of complex patterns in a homogeneous lattice, which is composed of coupled cells. In this paper, the analytical criteria for the local activity in reaction-diffusion CNN with five state variables and one port are presented, which consists of four theorems, including a serial of inequalities involving CNN parameters. These theorems can be used for calculating the bifurcation diagram to determine or analyze the emergence of complex dynamic patterns, such as chaos. As a case study, a reaction-diffusion CNN of hepatitis B Virus (HBV) mutation-selection model is analyzed and simulated, the bifurcation diagram is calculated. Using the diagram, numerical simulations of this CNN model provide reasonable explanations of complex mutant phenomena during therapy. Therefore, it is demonstrated that the local activity of CNN provides a practical tool for the complex dynamics study of some coupled nonlinear systems.

Efficient co-channel and adjacent channel interference rejection is often one of the most demanding requirements for wireless receivers. Independent Component Analysis (ICA) has been previously applied to realize interference suppression. In particular, the fixed-point FastICA and complex FastICA algorithms can successfully perform blind signal extraction for real and complex valued communication signals in stationary or slow fading environments. Both algorithms exhibit fast convergence speed and impressive accuracy due to their Newton type fixed-point iteration. However, under dynamic channel conditions often encountered in practice, the fixed-point algorithms' performance is significantly degraded. In this contribution, a novel complex block adaptive ICA algorithm and its simplified real version is proposed, that overcome this limitation for the separation of complex valued and real signals with known source distributions. The new methods exploit prior information about the modulation scheme of the communication signals of interest, and achieve improved interference suppression performance in dynamic channel environments. The proposed complex ICA algorithm is called Complex Optimum Block Adaptive ICA (Complex OBA-ICA), and its abridged version for separating real signals is called General Optimum Block Adaptation ICA (GOBA-ICA). The proposed methods are applied to interference rejection in linearly and abruptly flat fading dynamic environments for diversity QPSK and BPSK wireless receivers. Simulation results show that the presented techniques demonstrate better convergence properties and accuracy as compared to the complex FastICA and FastICA algorithms.

The conjugate gradient method is a prominent technique for solving systems of linear equations and unconstrained optimization problems, including adaptive filtering. Since it is an iterative method, it can be particularly applied to solve sparse systems which are too large to be handled by direct methods. The main advantage of the conjugate gradient method is that it employs orthogonal search directions with optimal steps along each direction to arrive at the solution. As a result, it has a much faster convergence speed than the steepest descent method, which often takes steps in the same direction as earlier steps. Furthermore, it has lower computational complexity than Newton’s iteration approach. This unique tradeoff between convergence speed and computational complexity gives the conjugate gradient method desirable properties for application in numerous mathematical optimization problems. In this paper, the conjugate gradient principle is applied to complex adaptive independent component analysis (ICA) for maximization of the kurtosis function, to achieve separation of complex-valued signals. The proposed technique is called the complex block conjugate independent component analysis (CBC-ICA) algorithm. The CBC-ICA derives independent conjugate gradient search directions for the real and imaginary components of the complex coefficients of the adaptive system employed for signal separation. In addition, along each conjugate direction an optimal update is generated separately for the real and imaginary components using the Taylor series approximation. Simulation results confirm that in dynamic flat fading channel conditions, the CBC-ICA demonstrates excellent convergence speed and accuracy, even for large processing block sizes.

Electrical wiring on board aircraft has raised serious weight and safety concerns in the aerospace industry. Wires are antennas. Wires that carry signals, particularly high speed data, can radiate some of the energy of those signals. This can cause interference to radio-based systems on board the aircraft, or, in the case of military aircraft, create a "signature" that can be detected by enemy receivers.

The emergence of wireless and mobile networks has made possible the introduction of electronic commerce to a new application and research subject: mobile commerce. Understanding or constructing a mobile or an electronic commerce system is an arduous task because the system involves a wide variety of disciplines and technologies and the technologies are constantly changing. To facilitate understanding and constructing such a system, this article divides the system into six components: (i) applications, (ii) client computers or devices, (iii) mobile middleware, (iv) wireless networks, (v) wired networks, and (vi) host computers. Elements in these components specifically related to the subject are described in detail and lists of current technologies for component construction are discussed. Another important and complicated issue related to the subject is the mobile or electronic commerce application programming. It includes two types of programming: client-side and server-side programming, which will be introduced too.

Current treatments for chronic pain have limited effectiveness and commonly known side effects. Given the prevalence and burden of intractable pain, additional therapeutic approaches are desired. Spinal cord stimulation (SCS) delivered at 10 kHz (as in HF10 therapy) may provide pain relief without the paresthesias typical of traditional low-frequency SCS. The objective of this randomized, parallel-arm, noninferiority study was to compare long-term safety and efficacy of SCS therapies in patients with back and leg pain.A total of 198 subjects with both back and leg pain were randomized in a 1:1 ratio to a treatment group across 10 comprehensive pain treatment centers. Of these, 171 passed a temporary trial and were implanted with an SCS system. Responders (the primary outcome) were defined as having 50% or greater back pain reduction with no stimulation-related neurological deficit.At 3 months, 84.5% of implanted HF10 therapy subjects were responders for back pain and 83.1% for leg pain, and 43.8% of traditional SCS subjects were responders for back pain and 55.5% for leg pain (P0.001 for both back and leg pain comparisons). The relative ratio for responders was 1.9 (95% CI, 1.4 to 2.5) for back pain and 1.5 (95% CI, 1.2 to 1.9) for leg pain. The superiority of HF10 therapy over traditional SCS for leg and back pain was sustained through 12 months (P0.001). HF10 therapy subjects did not experience paresthesias.HF10 therapy promises to substantially impact the management of back and leg pain with broad applicability to patients, physicians, and payers.

Nano-sized pure α-tricalcium phosphate (α-TCP) fabricated by a novel synthesis approach shows great potential for a faster transformation into calcium-deficient hydroxyapatite (CDHA) than conventionally prepared α-TCP. In this work, amorphous tricalcium phosphate precursors were precipitated and treated with a solvent (water or ethanol), and dried (freeze-dried and oven-dried) before heating at 775 °C. Nanosized α-TCP powders were investigated for their phase composition and crystallinity, particle shape and size, reactivity and cellular biocompatibility. Reaction with water showed faster CDHA formation for freeze-dried powder, at 6 hours, compared to ethanol treated powders, whereas a higher biocompatibility was found for pure α-TCP.

Geoacoustic inversions with a towed horizontal array are of interest for rapidly characterizing sediment properties over changing regions. To be of practical value, inversions must yield consistent and reliable results for consecutive or neighboring data. A method of determining inversion reliability a priori is delineated using an empirical approach and confirmed with inversion results in terms of consistency. Geoacoustic parameter hierarchy and resolvability are empirically analyzed using two different methods: one requires knowledge of the source function and the other does not. Inversion results using the two methods are compared using both synthetic data and experimental data from MAPEX2000. The inversions employ a global optimization technique which navigates the parameter space in directions aligned with valleys of the cost function, increasing inversion algorithm efficiency and disclosing parameter correlations and hierarchy.