Search

Studies comparing 5-fluorouracil (5-FU), imiquimod, and photodynamic therapy with aminolevulinic acid (PDT-ALA) have evaluated the efficacy of destroying actinic keratosis (AK). However, this end point may not directly translate to cutaneous squamous cell carcinoma (cSCC) prevention. No study to date has evaluated these field therapies for cSCC prevention in the long term, defined as greater than 1-year posttreatment.Determine the time to surgically treat invasive cSCC development after treatment with 5-FU, imiquimod, or PDT-ALA beginning 1-year posttreatment.Retrospective cohort study using the Optum Clinformatics Data Mart database from 2012 to 2019 RESULTS: The rate of cSCC development in patients treated with 5-FU showed no significant difference compared with imiquimod (0.99; 95% CI, 0.90-1.08). PDT-ALA was worse than 5-FU (1.27; 95% CI, 1.19-1.36) and imiquimod (HR, 1.29; 95% CI, 1.17-1.43). Other known predictors of cSCC were consistent with previous literature.The location of field therapy could not be determined with a claims database.5-FU is not superior to imiquimod beginning 1 year posttreatment, despite previously demonstrated superior AK destruction efficacy, but was superior to PDT-ALA. Conflating AK destruction and cSCC prevention efficacy may not be appropriate. Future prospective studies should aim to use an end point of cSCC development.

Cells secrete numerous bioactive molecules essential for the function of healthy organisms. However, there are no scalable methods to link individual cell secretions to their transcriptional state. By developing and using secretion encoded single-cell sequencing (SEC-seq), which exploits hydrogel nanovials to capture individual cells and their secretions, we simultaneously measured the secretion of vascular endothelial growth factor A (VEGF-A) and the transcriptome for thousands of individual mesenchymal stromal cells (MSCs). We found that VEGF-A secretion is heterogeneous across the cell population and lowly correlated with theVEGFAtranscript level. While there is a modest population-wide increase in VEGF-A secretion by hypoxic induction, highest VEGF-A secretion across normoxic and hypoxic culture conditions occurs in a subpopulation of MSCs characterized by a unique gene expression signature. Taken together, SEC-seq enables the identification of specific genes involved in the control of secretory states, which may be exploited for developing means to modulate cellular secretion for disease treatment.

Early naturalists suggested that predation intensity increases toward the tropics, affecting fundamental ecological and evolutionary processes by latitude, but empirical support is still limited. Several studies have measured consumption rates across latitude at large scales, with variable results. Moreover, how predation affects prey community composition at such geographic scales remains unknown. Using standardized experiments that spanned 115° of latitude, at 36 nearshore sites along both coasts of the Americas, we found that marine predators have both higher consumption rates and consistently stronger impacts on biomass and species composition of marine invertebrate communities in warmer tropical waters, likely owing to fish predators. Our results provide robust support for a temperature-dependent gradient in interaction strength and have potential implications for how marine ecosystems will respond to ocean warming.

We determined which educational and/or psychological interventions were most effective in atopic dermatitis (AD). A systematic review of published studies evaluated the effectiveness of educational and/or psychological interventions in MEDLINE, Embase, SCOPUS, LILACS, Cochrane, China National Knowledge Infrastructure, Taiwan Electronic Periodical Services, and CiNii. Two reviewers conducted title/abstract, full-text review, and data extraction. Twenty-four prospective studies were included, including 20 randomized controlled trials. Educational (4/7 studies) and combined educational and psychological (5/6 studies) interventions reduced AD severity; psychological (10/11 studies) interventions showed the greatest benefit. The most commonly studied psychological intervention was habit reversal training (8/11 studies), which was most frequently incorporated in studies that reduced AD severity (8/10 studies). The most commonly studied educational interventions were education on AD triggers (7/7 studies) and skin care (7/7 studies); they were incorporated in all studies that reduced AD severity. Different psychological and/or educational interventions successfully reduced AD severity, especially habit reversal training.

Hairy cell leukemia (HCL) is a rare hematologic disorder characterized by pancytopenia and splenomegaly for which a single course of cladribine is highly effective in inducing complete remissions. However, there is limited real-world data on outcomes and complications among geriatric patients with HCL treated with cladribine. We conducted a retrospective review of all patients 70 years or older within the Scripps Clinic HCL Database at the time of first treatment with cladribine. Of the 45 patients meeting inclusion criteria, 32 (71%) achieved CR and 4 (9%) achieved PR. Of the 9 remaining patients, 7 achieved normalization of peripheral blood counts after a single course of cladribine (complete hematologic response, CHR) and 2 had no response. The median duration of response for all responders was 119 months. Nine (20%) patients relapsed with a median time to first relapse of 28 months. Ten patients subsequently developed 12 primary malignancies with an excess frequency (observed-to-expected ratio) of 0.85 (95% confidence interval, 0.48-1.49). Median overall survival for the entire cohort was 166 months from time of HCL diagnosis and 119 months from time of first cladribine administration. Forty patient deaths were observed; the standardized mortality ratio (observed-to-expected ratio) was 1.42 (95% confidence interval, 1.03-1.96), representing a statistically significant increase in the risk of death (P = .03). This study supports the high rate of complete and durable responses following a single course of cladribine in geriatric patients.

Staphylococcus aureus infections represent a major public health threat, but previous attempts at developing a universal vaccine have been unsuccessful. We attempted to identify a vaccine that would be protective against both skin/soft tissue and bloodstream infections. We first tested a panel of staphylococcal antigens that are conserved across strains, combined with aluminum hydroxide as an adjuvant, for their ability to induce protective immunity in both skin and bacteremia infection models. Antigens were identified that reduced dermonecrosis during skin infection, and other non-overlapping antigens were identified that showed trends to protection in the bacteremia model. However, individual antigens were not identified that mediated substantial protection in both the skin and bacteremia infection models. We therefore tested a variety of combinations of proteins to seek a single combination that could mediate protection in both models. After iterative testing, a vaccine consisting of 3 antigens, ABC transporter protein (SACOL2451), ABC2 transporter protein (SACOL0695), and α-hemolysin (SACOL1173), was identified as the most effective combination. This combination vaccine provided protection in a skin infection model. However, these antigens were only partially protective in the bacteremia infection model. Even by testing multiple different adjuvants, optimized efficacy in the skin infection model did not translate into efficacy in the bacteremia model. Thus protective vaccines against skin/soft tissue infections may not enable effective protection against bloodstream infections.

Aim: Spermidine/spermine N1-acetyltransferase (SSAT-1) plays a critical role in cell growth, proliferation and death, and is known to be activated in human cancer cells. Amantadine, a US FDA-approved antiviral drug, is a substrate for SSAT-1 and can be used to indirectly measure SSAT-1 activity because of its conversion to acetylamantadine (AA). This study was undertaken to further validate SSAT-1 activity in breast and lung cancer patients. Results: An increase in the urinary concentration of AA in lung and breast cancer patients was observed. The 0–2 h collection time point was determined to be optimal in revealing significant differences in urinary AA concentration between healthy controls and cancer patients. Conclusion: The high urine concentration of AA could be used as a simple and useful test for the detection of breast and lung cancer., Lay abstract This study describes a novel noninvasive urine test for detecting and screening of breast and lung cancer using a safe and approved drug called amantadine. Higher concentration of the acetylated form of amantadine in the urine are detectable in the urine of both breast and lung cancer patients as compared with healthy adult volunteers. This test is simple and may serve as a useful tool for determining the presence of breast and lung cancer.

Aim: SSAT-1 is an enzyme that plays a critical role in cell growth. Amantadine, a FDA-approved antiviral drug, is a substrate for SSAT-1. The utility of amantadine as an agent to demonstrate elevated SSAT-1 activity linked to cancer was conducted. Results: High levels of SSAT-1 expression were measured in tumor human cell lines, and in breast, prostate and lung tumor tissue. An increase in the urinary levels of acetylated amantadine in cancer patients was observed. Conclusion: Increases in SSAT-1 contents in tumor tissue could be of value in targeting cancers with high SSAT-1 expression for confirmation/quantification. The high levels of acetylated amantadine could be used as a simple and useful screening test for the presence of cancer., Lay abstract In response to cancer, cells tend to overproduce specific enzymes as a self-defense mechanism. By using a safe and reliable method to capture and measure the excess enzyme spermidine/spermine N1-acetyltransferase-1, the presence of cancer can be established. This study describes a novel approach of detecting and screening cancer noninvasively in the urine of cancer patients using a safe and approved drug called amantadine that acts as a smart-tracking agent. Higher levels of the acetylated form of amantadine are detectable in the urine of cancer patients, which may serve as a detection tool. In addition, increases in the amount of spermidine/spermine N1-acetyltransferase-1 in tumor tissue may provide a tool for determining the presence of cancer during pathology assessment.

As with other genitourinary malignancies, a variety of paraneoplastic syndromes have been revealed to occur in patients with prostate cancer. Stauffer's Syndrome is a well-described clinical syndrome which manifests via intrahepatic cholestasis in patients with renal cell carcinoma. Less common is intrahepatic cholestasis occurring in association with prostate cancer. The current case report discusses a 67-year-old man presenting with liver failure secondary to intrahepatic cholestasis co-existing with metastatic prostate adenocarcinoma. The patient's liver failure completely resolved with androgen-deprivation therapy suggesting an association between these two entities. The case report evaluates existing literature on this uncommon syndrome including the clinical presentation, natural history, and potential pathophysiology.

Objectives.Although laser lithotripsy is now the preferred treatment option for urolithiasis due to shorter operation time and a better stone-free rate, the optimal laser settings for URS (ureteroscopic lithotripsy) for less operation time remain unclear. The aim of this study was to look for quantitative responses of calculus ablation and retropulsion by performing operator-independent experiments to determine the best fit versus the pulse energy, pulse width, and the number of pulses.Methods.A lab-built Ho:YAG laser was used as the laser pulse source, with a pulse energy from 0.2 J up to 3.0 J and a pulse width of 150 μs up to 1000 μs. The retropulsion was monitored using a high-speed camera, and the laser-induced craters were evaluated with a 3-D digital microscope. The best fit to the experimental data is done by a design of experiment software.Results.The numerical formulas for the response surfaces of ablation speed and retropulsion amplitude are generated.Conclusions.The longer the pulse, the less the ablation or retropulsion, while the longer pulse makes the ablation decrease faster than the retropulsion. The best quadratic fit of the response surface for the volume of ablation varied nonlinearly with pulse duration and pulse number.

Efficiency is one of the key performance factors for the multiphase voltage regulators (VRs), especially for the workstation and server applications. To further improve the efficiency, a new topology by having different phase inductances in multiphase VRs is proposed in this paper. However, the phase interleaving, current sharing, and dynamic phase shedding (DPS) functions would become more challenging in this proposed topology. In order to overcome those challenges, a programmable current sharing ratio scheme is considered to improve the phase interleaving and current sharing of the proposed topology. In addition, a fast phase adding logic is also presented to improve the load transient response speed. All of these efforts aim at realizing fast transient response and high efficiency simultaneously for a multiphase VR. The simulation and experimental results show the effectiveness of the proposed topology and the control scheme.

When treating ureteral calculi, retropulsion can be reduced by using a longer pulse width without compromising fragmentation efficiency (from the studies by David S. Finley et al. and Hyun Wook Kang et al.). In this study, a lab build Ho:YAG laser was used as the laser pulse source, with pulse energy from 0.2J up to 3.0 J, and electrical pump pulse width from 150 us up to 1000 us. The fiber used in the investigation is a 365 μm core diameter fiber, SureFlexTM, Model S-LLF365. Plaster of Paris calculus phantoms were ablated at different energy levels (0.2, 0.5, 1, 2, 3J) and with different number of pulses (1, 3, 10) using different electrical pump pulse width (333, 667, 1000 μs). The dynamics of the recoil action of a calculus phantom was monitored using a high-speed camera with frame rate up to 1 million frame per second (Photron Fastcam SA5); and the laser-induced craters were evaluated with a 3-D digital microscope (Keyence VHX-900F). A design of experiment software (DesignExpert-10, Minneapolis, MN, USA) is used in this study for the best fit of surface response on volume of dusting and retropulsion amplitude. The numerical formulas for the response surfaces of dusting speed and retropulsion amplitude are generated. More detailed investigation on the optimal conditions for dusting of other kinds of stone samples and the fiber size effect will be conducted as a future study.

These days, constant on-time current mode (COTCM) control schemes are widely used in the industry VR controllers for its light load efficiency and higher BW design with simpler compensation requirement. In COTCM control, external ramp is required to be added for jittering reduction to improve the noise performance of the controller. But unfortunately, with the increment of external ramp value, although the jittering in the system gets better, transient performance becomes worse. For this reasons, from transient point of view, it is very challenging to use large external ramp in the system to improve the noise performance. In this paper, a novel method is proposed to modify the external ramp at the transient instant to improve the transient response by increasing the slope of the ramp, and thus allows the control to use the large external ramp for noise performance improvement and enjoys the fast transient response at the same time.

In this paper, a novel approach to determine the small signal model of an LLC resonant converter is presented. The proposed model uses analysis techniques from communications theory to determine the control-to-output transfer function required for the design of a digital compensation network. The model considers the effects of higher order harmonics and sideband frequencies generated by the variable switching frequency control method, as well as the effects of the LLC resonant tank and the output voltage rectifier. Experimental data from a prototype LLC resonant converter was obtained to verify the analytical results, and revealed that the proposed model is an accurate representation of the prototype converter dynamics. Simulation results demonstrated that a digital compensator design based on the proposed model was able to achieve output voltage regulation.

This paper presents adaptive ripple-based constant on-time control architecture for buck converter ICs with wide duty ratio applications. An internal ramp compensation with emulating inductor current ripple is implemented to solve the ripple oscillation instability issue when using low-ESR output capacitors in buck converters. Therefore, no external compensation is required to simplify the system applications and to achieve universal applications. However, in order to guarantee the stability margin and the jitter performance for wide duty-ratio applications with different switching frequencies, a large internal ramp is normally applied, but it may not be optimal for different applications. Besides, in order to avoid the voltage droop caused by the internal ramp compensation, a high-pass filter is usually utilized to cancel the DC offset. However, the DC cancellation network may cause phase margin issues when applying too large internal ramp. Hence, the internal ramp must be carefully designed to guarantee the stability margin while maintaining fast load transients and adequate phase margin for wide duty-ratio applications. In this paper, an adaptive ripple tuning algorithm is proposed to fine tune the internal ramp compensation automatically based on the duty ratios, output voltage, and the switching frequency. The small-signal model is derived to provide the design guide, and the simulation and experimental results are given to verify the effectiveness of the proposed adaptive ripple-based control.

Maritime observation systems currently are insufficient in spatial distribution, sensor type availability, interoperability, cost, and deployment utility to adequately support coastal marine and estuarine decision-makers and event responders. The goal of the Autonomous Sensor Network (ASN) project is twofold. First is to develop the rapidly deployable Noblis Autonomous Marine Sensor System (NAMSS) to demonstrate that more affordable and capable small sensor systems can be developed to significantly augment the currently expensive and limited number of systems in use. Second is to integrate NAMSS (and other existing operational sensor systems, both satellite and in situ) with emerging capabilities in the Noblis Sensor Service Oriented Architecture (SOA) along with geospatial analysis and visualization services to demonstrate the value of this enhanced capability. The ASN will be an automated observation, detection, alert, tasking, deployment, and product delivery system designed to allow domain users to react quickly and efficiently to a variety of emergent incidents, as well as improve the efficacy of longer-term monitoring, in estuarine and coastal marine waters. Noblis originated this project through internal corporate research and is working with partners in the Chesapeake Bay Observing System (CBOS) to build upon the initial work of the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center on the NASA Earth Observing (EO)-1 Sensor Web. The ASN will expand current EO-1 Sensor Web capabilities and extend them into the logistically and operationally challenging coastal marine and estuarine environment of the Chesapeake Bay, U.S. national marine sanctuaries, and other vitally important marine ecosystems. The ASN is intended to be a demonstration of the benefit of a rapid prototyping approach to exemplify the potential of CBOS and the Integrated Ocean Observing System (IOOS). While initial efforts focus on a few select marine environments, this project is adaptable and scalable to national use for IOOS.

Broadband satellite based IP network congestion control is becoming a serious issue towards commitment of service level agreements (SLAs) to honor the guaranteed quality of service (QoS). In satellite communication systems, the channel performance might be severely degraded due to the dynamic weather conditions leading to network congestion. The inherent large bandwidth-delay product of satellite channels impede the existing numerous congestion control schemes to be applied to satellite networks. In this paper, a new congestion index is defined to indicate the degree of the network congestion as a function of queue and weather characteristics. A novel intelligent packet dropping mechanism is designed based on fuzzy logic. Simulation results and analyses show that the newly developed congestion control method is effective and efficient for broadband satellite-based IP networks.

Rain and snow can have a distorting effect on Ku and Ka bands signal fidelity resulting in excessive digital transmission errors. This loss of signal attenuation is commonly referred to as rain fade. Rain fade impacts the Quality of Service in wireless and satellite networks. A decision support system is therefore necessary for service providers to accurately predict rain fade and establish mitigation planning by adaptively selecting appropriate power level, coding and modulation schemes. This paper establishes an important component of the decision support system by adaptively computing rainfall rate and rain attenuation at any location on earth using ITU-R models combined with bi-linear interpolation and frequency extrapolation. We also introduce a novel method for accurately determining rain attenuation as a function of frequency based on proceeding results from prediction weather database, since rain attenuation is considered a dominant impairment for wireless signals [1]–[6]. Finally, a three dimensional relationship is proposed for rain attenuation with both frequency and probability to provide decision support system with an accurate view of satellite’s parameters. The derived parameter values, being fed through neural networks and fuzzy systems to improve estimate Signal to Noise Ratio, will enable the decision support system to maintain Quality of Service and Service Level Agreements by adaptively adjusting satellite signal power, modulation, coding, and data rate at unpredictable weather conditions.