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ObjectivesThis study aimed to investigate short-interval intracortical inhibition (SICI) and muscle function in the Triceps surae of runners with mid-portion Achilles tendinopathy (AT).MethodsRunners with (n=11) and without (n=13) AT were recruited. Plantar flexor isometric peak torque and rate of torque development (RTD) were measured using an isokinetic dynamometer. Triceps surae endurance was measured as single leg heel raise (SLHR) to failure test. SICI was assessed using paired-pulse transcranial magnetic stimulation during a sustained contraction at 10% of plantar flexor isometric peak torque.ResultsTriceps surae SICI was 14.3% (95%CI: -2.1 to 26.4) higher in AT than control group (57.9%, 95%CI: 36.2, to 79.6; and 43.6% 95%CI:16.2 to 71.1; p=0.032) irrespective of the tested muscle. AT performed 16 (95%CI: 7.9 to 23.3, pPerspectiveOur data suggest greater intracortical inhibition for the Triceps surae muscles for the AT group accompanied by reduced SLHR endurance, without deficits in isometric peak torque or RTD. The increased SICI observed in the AT group could be negatively influencing Triceps surae endurance; thus, rehabilitation aiming to reduce intracortical inhibition should be considered to improve patient outcomes. Furthermore, SLHR is a useful clinical tool to assess plantar flexor function in AT patients.

In traditional semantic segmentation, knowing about all existing classes is essential to yield effective results with the majority of existing approaches. However, these methods trained in a Closed Set of classes fail when new classes are found in the test phase, not being able to recognize that an unseen class has been fed. This means that they are not suitable for Open Set scenarios, which are very common in real-world computer vision and remote sensing applications. In this paper, we discuss the limitations of Closed Set segmentation and propose two fully convolutional approaches to effectively address Open Set semantic segmentation: OpenFCN and OpenPCS. OpenFCN is based on the well-known OpenMax algorithm, configuring a new application of this approach in segmentation settings. OpenPCS is a fully novel approach based on feature-space from DNN activations that serve as features for computing PCA and multi-variate gaussian likelihood in a lower dimensional space. In addition to OpenPCS and aiming to reduce the RAM memory requirements of the methodology, we also propose a slight variation of the method (OpenIPCS) that uses an iteractive version of PCA able to be trained in small batches. Experiments were conducted on the well-known ISPRS Vaihingen/Potsdam and the 2018 IEEE GRSS Data Fusion Challenge datasets. OpenFCN showed little-to-no improvement when compared to the simpler and much more time efficient SoftMax thresholding, while being some orders of magnitude slower. OpenPCS achieved promising results in almost all experiments by overcoming both OpenFCN and SoftMax thresholding. OpenPCS is also a reasonable compromise between the runtime performances of the extremely fast SoftMax thresholding and the extremely slow OpenFCN, being able to run close to real-time. Experiments also indicate that OpenPCS is effective, robust and suitable for Open Set segmentation, being able to improve the recognition of unknown class pixels without reducing the accuracy on the known class pixels. We also tested the scenario of hiding multiple known classes to simulate multimodal unknowns, resulting in an even larger gap between OpenPCS/OpenIPCS and both SoftMax thresholding and OpenFCN, implying that gaussian modeling is more robust to settings with greater openness.

Shape memory alloy (SMA) actuators can provide significant advantages for small-scale robotics given their robustness, energy density, and low voltage actuation. However, NiTi thin films typically found in SMA microactuators do not often provide useful forces and displacements for microrobotic applications. This work presents a fabrication process in which NiTi thin film actuators are integrated with two-photon polymerization (TPP) 3D printing to scale these actuators up for use in mesoscale systems. Individual unimorph actuators are characterized with respect to uniformity across many actuators so that actuators can be arrayed together for even larger forces or combined toward the operation of complex mechanisms. The resulting actuators are fast to prototype, reliable and stable (up to 5000 cycles), and can utilize complex geometries that are otherwise challenging to achieve with conventional MEMS microfabrication techniques. A 2D positioner is demonstrated by combining six individually controlled actuators with conventional mm-scale fabrication techniques (3D stereolithography printing, wire bonding and PCB assembly). The actuators are controlled by a commercial microcontroller and powered using a standard Lithium polymer battery. [2020-0208]

Cabozantinib is an oral multikinase inhibitor whose targets include vascular endothelial growth factor receptors, MET, and the TAM family of kinases (TYRO3, AXL, MER). Cabozantinib is approved for patients with advanced hepatocellular carcinoma who have been previously treated with sorafenib, based on improved overall survival and progression-free survival relative to placebo in the phase III CELESTIAL study. During CELESTIAL, the most common adverse events (AEs) experienced by patients receiving cabozantinib included palmar-plantar erythrodysesthesia, fatigue, gastrointestinal-related events, and hypertension. These AEs can significantly impact treatment tolerability and patient quality of life. However, AEs can be effectively managed with supportive care and dose modifications. During CELESTIAL, more than half of the patients receiving cabozantinib required a dose reduction, while the rate of treatment discontinuation due to AEs was low. Here, we review the safety profile of cabozantinib and provide guidance on the prevention and management of the more common AEs, based on current evidence from the literature as well as our clinical experience. We consider the specific challenges faced by clinicians in treating this patient population and discuss factors that may affect exposure and tolerability to cabozantinib. Electronic supplementary material The online version of this article (10.1007/s11523-020-00736-8) contains supplementary material, which is available to authorized users.

The fabrication and integration of microactuators with 3D micromechanisms are necessary to develop microrobots with higher capability and complexity. In this work, a two-step fabrication method combining 3D printing with two-photon polymerization (TPP) and aluminum sputtering is demonstrated. Actuators using two different transduction mechanisms (thermal and electrostatic) were fabricated in this process, and a thermal actuator was printed with a mechanism in three-dimensional space without additional assembly steps. This work also provides parameterized characterizations which can be used as design guidelines for building actuators and mechanisms. A design approach to electrically isolate the actuators from the substrate is introduced so that the device can be functional after two fabrication steps without patterning the metal layer. Metal coverage on the sidewalls of trenches are characterized, which provides a design space for deciding electrode gaps and heights in electrostatic actuators. Using these guidelines, 500 $\mu \text{m}$ long thermal actuators showed a maximum displacement of 18.0 $\mu \text{m}$ at 8.31mW and reliably actuated up to 8,500 cycles. An interdigitated electrostatic comb-drive actuator was also successfully demonstrated, displacing 12.7 $\mu \text{m}$ when 160V was applied. Finally, a 3D actuated mechanism was designed by incorporating a thermal actuator with 3D compliant mechanisms to flap 250 $\mu \text{m}$ long wings. Flapping motion was successfully demonstrated. [2020-0010]

Liquid chromatography coupled to high-resolution mass spectrometry (HRMS) enables data independent acquisition (DIA) and untargeted screening. However, to avoid the handling of the resulting large dataset, most laboratories in that field still use targeted screening methods, which offer good sensitivity and specificity but are limited to known compounds. The promising field of machine learning offers new possibilities such as artificial neural networks that can be trained to classify large amounts of data. In this proof of concept study, we exemplify such a machine learning approach for raw HRMS-DIA data files. We evaluated a machine learning model using training, validation, and test sets of solvent and whole blood samples containing drugs (of abuse) common in forensic toxicology. For that purpose, different platforms were used. With a feedforward neural network model architecture, a category prediction (blank sample vs. drug containing sample) was aimed for. With the applied machine learning approaches, the sensitivity and specificity, of the validation and test set, for the prediction of sample classes were in a suitable range for an actual use in a (routine) laboratory (e.g. workplace drug testing). In conclusion, this proof of concept study clearly demonstrated the huge potential of machine learning in the analysis of HRMS-DIA data.

Network Functions Virtualization (NFV) has received considerable attention in the past few years, both from industry and academia, due to its potential for reducing capital and operational expenditures, thus enabling faster innovation in networks. NFV proposes decoupling network functions from fixed hardware platforms and implementing them as virtual machines on off-the-shelf servers. Although potentially able to provide the mentioned benefits, software-based implementations of compute-intensive network functions still struggle to perform at the desired speed, especially when requiring line-rate processing for ever-faster communication links. To address this, hardware acceleration can be used to improve the throughput and latency of virtualized network functions (VNFs). In order to provide the advantages foreseen for NFV, however, such accelerators cannot be fixed and application-specific hardware, since they need to cope with new VNFs as well as fluctuations in demand. In this context, Field-Programmable Gate Arrays (FPGAs) are particularly suitable, since they are able to provide high-performance implementations of network functions and they are completely reprogrammable, thereby being able to implement different VNFs even after deployment. There have been many recent efforts to enable the use of FPGAs in the NFV context, including efficient implementations of network functions on FPGAs, platforms to manage the integration and coexistence of multiple VNFs on an FPGA, and high-level synthesis tools especially tailored to ease the programming of VNFs for FPGAs. In this work we survey previous work covering these aspects, and discuss the main open research challenges that must be addressed before FPGA adoption in NFV infrastructures becomes effectively seamless and efficient.

BACKGROUND Cytologic analysis of vitreous fluid is an important component in diagnosis of vitreitis. No standard reporting guidelines exist for these specimens. This study chronicles our 24 years experience and proposes a tentative diagnostic model. METHODS Retrospective cytology reports review and database study. Clinical indications, cytologic patterns, ancillary studies performed, and diagnoses were recorded. RESULTS 176 samples from 160 patients were included and main cytologic patterns are reflected in Table 1. Most fluids were negative for malignancy (88%) and patterns IIB (53%) and IIA (19%) were dominant. The non-diagnostic rate was 7%; atypical and suspicious categories represented

Key Points Ponatinib therapy heightens arterial thrombosis and platelet reactivity. Concurrent pioglitazone treatment reverses heightened thrombosis risk and platelet reactivity induced by ponatinib.

BACKGROUND The prevalence of hypertension among black African patients is high, and these patients usually need two or more medications for blood-pressure control. However, the most effective two-drug combination that is currently available for blood-pressure control in these patients has not been established. METHODS In this randomized, single-blind, three-group trial conducted in six countries in sub-Saharan Africa, we randomly assigned 728 black patients with uncontrolled hypertension (≥140/90 mm Hg while the patient was not being treated or was taking only one antihypertensive drug) to receive a daily regimen of 5 mg of amlodipine plus 12.5 mg of hydrochlorothiazide, 5 mg of amlodipine plus 4 mg of perindopril, or 4 mg of perindopril plus 12.5 mg of hydrochlorothiazide for 2 months. Doses were then doubled (10 and 25 mg, 10 and 8 mg, and 8 and 25 mg, respectively) for an additional 4 months. The primary end point was the change in the 24-hour ambulatory systolic blood pressure between baseline and 6 months. RESULTS The mean age of the patients was 51 years, and 63% were women. Among the 621 patients who underwent 24-hour blood-pressure monitoring at baseline and at 6 months, those receiving amlodipine plus hydrochlorothiazide and those receiving amlodipine plus perindopril had a lower 24-hour ambulatory systolic blood pressure than those receiving perindopril plus hydrochlorothiazide (between-group difference in the change from baseline, −3.14 mm Hg; 95% confidence interval [CI], −5.90 to −0.38; P=0.03; and −3.00 mm Hg; 95% CI, −5.8 to −0.20; P=0.04, respectively). The difference between the group receiving amlodipine plus hydrochlorothiazide and the group receiving amlodipine plus perindopril was −0.14 mm Hg (95% CI, −2.90 to 2.61; P=0.92). Similar differential effects on office and ambulatory diastolic blood pressures, along with blood-pressure control and response rates, were apparent among the three groups. CONCLUSIONS These findings suggest that in black patients in sub-Saharan Africa, amlodipine plus either hydrochlorothiazide or perindopril was more effective than perindopril plus hydrochlorothiazide at lowering blood pressure at 6 months. (Funded by GlaxoSmithKline Africa Noncommunicable Disease Open Lab; CREOLE ClinicalTrials.gov number, NCT02742467. opens in new tab.)

Combining electrical and magnetic materials in the same part has been a challenge in 3D printing due to difficulties co-printing complex materials in many additive manufacturing processes. Past 3D printed inductors and other similar magnetic devices have therefore either lacked the magnetic materials necessary for improved performance, or required sintering at high temperatures for extended periods, beyond the capability of most 3D printable polymers. In this work, we demonstrate a room temperature process for incorporating conductive and magnetic materials into the same 3D printed device. A multi-stage fabrication process based on 3D printing followed by fill with magnetic and conductive fluids is proposed. Multi-layer microfluidic channels for magnetic passives are first printed in a stereolithography process. The microfluidic systems are then filled with room temperature liquid metal, a gallium alloy liquid at room temperature, and ferrofluid to create inductors, transformers and wireless power coils. Through the addition of ferrofluid as a magnetic material, increases in inductance density by nearly a factor of three were demonstrated, in addition to coupling improvements for transformer and wireless power coils compared to the devices before magnetic fill.

As part of a longitudinal household transmission study of pets living with persons with COVID-19 in Texas, two pets were confirmed to be infected with the SARS-CoV-2 B.1.1.7 variant of concern (VOC). The pets were a dog and a cat from the same household, sampled two days after their owner tested positive for COVID-19. The oral, nasal, and fur swabs for both pets tested positive for SARS-CoV-2 by qRT-PCR and consensus whole genome sequences from the dog and cat were 100 % identical and matched the B.1.1.7 VOC. Virus was isolated from the cat’s nasal swab. One month after initial detection of infection, the pets were re-tested twice at which time only the fur swabs (both pets) and oral swab (dog only) remained positive, and neutralizing antibodies for SARS-CoV-2 were present in both animals. Sneezing by both pets was noted by the owner in the weeks between initial and follow-up testing. This study documents the first detection of B.1.1.7. in companion animals in the United States, and the first genome recovery and isolation of B.1.1.7 variant of concern globally in any animal.

The world faces two seemingly unrelated challenges—a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.

Objectives Urine sample manipulation including substitution, dilution, and chemical adulteration is a continuing challenge for workplace drug testing, abstinence control, and doping control laboratories. The simultaneous detection of sample manipulation and prohibited drugs within one single analytical measurement would be highly advantageous. Machine learning algorithms are able to learn from existing datasets and predict outcomes of new data, which are unknown to the model. Methods Authentic human urine samples were treated with pyridinium chlorochromate, potassium nitrite, hydrogen peroxide, iodine, sodium hypochlorite, and water as control. In total, 702 samples, measured with liquid chromatography coupled to quadrupole time-of-flight mass spectrometry, were used. After retention time alignment within Progenesis QI, an artificial neural network was trained with 500 samples, each featuring 33,448 values. The feature importance was analyzed with the local interpretable model-agnostic explanations approach. Results Following 10-fold cross-validation, the mean sensitivity, specificity, positive predictive value, and negative predictive value was 88.9, 92.0, 91.9, and 89.2%, respectively. A diverse test set (n=202) containing treated and untreated urine samples could be correctly classified with an accuracy of 95.4%. In addition, 14 important features and four potential biomarkers were extracted. Conclusions With interpretable retention time aligned liquid chromatography high-resolution mass spectrometry data, a reliable machine learning model could be established that rapidly uncovers chemical urine manipulation. The incorporation of our model into routine clinical or forensic analysis allows simultaneous LC-MS analysis and sample integrity testing in one run, thus revolutionizing this field of drug testing.

Current and emerging systems for high-throughput applications, such as machine learning, cloud computing, and real-time video encoding demand real-time processing computations, heavily constrained by latency and power requirements. To deal with the increasing computational complexity, designers may resort to approximate accelerators for error-resilient compute-intensive kernels to meet such requirements with acceptable deviation from the exact implementation. However, since time-to-market is crucial when dealing with evolving applications, technologies, and standards, hand-crafting approximate accelerators may impose prohibitive development time and cost overheads. In this scenario, approximate High-Level Synthesis (HLS) methodologies have been proposed to deal with the complexity of exploring approximation techniques. Nevertheless, current tools are not suitable for exploring throughput optimizations, being instead constrained to perform specific improvements on area, power, and performance. In this work, we propose the use of HLS to generate Pareto-optimal accelerators for throughput-constrained applications. Particularly, we present a throughput-oriented approximate HLS methodology that explores both delay and area optimizations to increase the reuse over time and parallelism of such accelerators. Results show that our method is able to improve throughput by up to 80 % with no additional area costs or to sustain the same throughput of the exact design with about 45 % less area while introducing manageable error for most applications. Moreover, our method can attain throughput improvements of up to 18% when compared with recent works focusing only on performance or area optimizations, with no additional costs.

Intermittent systems are ultra-low-power batteryless devices that are increasing in popularity. These systems operate with energy extracted entirely from the environment. Since most environments cannot ensure sufficient and steady power supply conditions, intermittent devices suffer from frequent power outages, where computation is interrupted due to the lack of energy. While numerous works have enabled intermittent computation via many different techniques, there are no versatile and configurable tools that ensure functionality, and rapid development/design space exploration. Therefore, in this paper, we present Firefly, an intermittent open-source framework for developing ultra-low-power devices based on the RISC-V ISA and the Rocket Chip. Firefly enables developers to modify and extend the project to satisfy their preference, i.e., memory technologies, intermittent environment configuration, and hardware modifications. By exploiting the versatility offered by the Firefly framework, we evaluate different memory technologies in an intermittent environment, showing that in many times PCRAM and RRAM will be the best choices to compose the design.

Fowler syndrome is a rare autosomal recessive brain vascular disorder caused by mutation in FLVCR2 in humans. The disease occurs during a critical period of brain vascular development, is characterized by glomeruloid vasculopathy and hydrocephalus, and is almost invariably prenatally fatal. Here, we sought to gain insights into the process of brain vascularization and the pathogenesis of Fowler syndrome by inactivating Flvcr2 in mice. We showed that Flvcr2 was necessary for angiogenic sprouting in the brain, but surprisingly dispensable for maintaining the blood-brain barrier. Endothelial cells lacking Flvcr2 had altered expression of angiogenic factors, failed to adopt tip cell properties, and displayed reduced sprouting, leading to vascular malformations similar to those seen in humans with Fowler syndrome. Brain hypovascularization was associated with hypoxia and tissue infarction, ultimately causing hydrocephalus and death of mutant animals. Strikingly, despite severe vascular anomalies and brain tissue infarction, the blood-brain barrier was maintained in Flvcr2 mutant mice. Our Fowler syndrome model therefore defined the pathobiology of this disease and provided new insights into brain angiogenesis by showing uncoupling of vessel morphogenesis and blood-brain barrier formation.

Due to the extremely rapid growth of the computing and IT technology market, commercial hardware made for the civilian, consumer sector is increasingly (and inevitably) deployed in security-sensitive environments. With the growing threat of hardware Trojans and backdoors, an adversary could perpetrate a full system compromise, or privilege escalation attack, even if the software is presumed to be perfectly secure. We propose a method of field stripping a computer system by empirically proving an equivalence between the trustability of the fielded system on one hand, and its comprehensive set of sources (including those of all toolchains used in its construction) on the other. In the long run, we hope to facilitate comprehensive verification and validation of fielded computer systems from fully self-contained hard-ware+software sources, as a way of mitigating against the lack of control over (and visibility into) the hardware supply chain.

This preprint has since been peer reviewed and published in the American Journal of Epidemiology. It can be found at the following link: https://doi.org/10.1093/aje/kwab196 Background: The COVID-19 pandemic and associated economic crisis has rendered millions of U.S. households unable to pay rent, placing them at risk for eviction. Evictions may accelerate COVID-19 transmission by increasing household crowding and decreasing individuals’ ability to comply with social distancing directives. We leveraged variation in the expiration of eviction moratoriums in U.S. states to test for associations between evictions and COVID-19 incidence and mortality. Methods: The study included 44 U.S. states that instituted eviction moratoriums., followed from March 13th to September 3rd, 2020. We modeled associations using a difference-in-difference approach with an event study specification. Negative binomial regression models of cases and deaths included fixed effects for state and week and controlled for time-varying indicators of testing, stay-at-home orders, school closures, and mask mandates. We then used model predictions to estimate cumulative cases and deaths associated with expiring eviction moratoriums. Findings: Twenty-seven states lifted eviction moratoriums during the study period. COVID-19 incidence in states that lifted their moratoriums was 1.6 (95% CI 1.0,2.3) times the incidence of states that maintained their moratoriums at 10 weeks post-lifting and grew to a ratio of 2.1 (CI 1.1,3.9) at ≥16 weeks. Mortality in states that lifted their moratoriums was 1.6 (CI 1.2,2.3) times the mortality of states that maintained their moratoriums at 7 weeks post-lifting and grew to a ratio of 5.4 (CI 3.1,9.3) at ≥16 weeks. These results translate to an estimated 433,700 excess cases (CI 365200,502200) and 10,700 excess deaths (CI 8900,12500) nationally. Interpretation: Lifting eviction moratoriums was associated with increased COVID-19 incidence and mortality, supporting the public health rationale for use of eviction moratoriums to prevent the spread of COVID-19.

This work demonstrates the first sputtered thin-film nickel-titanium (NiTi) shape-memory alloy (SMA) actuators combined with direct 3D printing of polymeric structures. Resulting actuators are fast to prototype, reliable and stable (up to 5000 cycles), and can utilize complex geometries challenging to achieve with conventional MEMS microfabrication. The actuator design uses 3D printed polymer as the passive layer in unimorph actuators, adding significant versatility to the actuator design. An actuator designed for high force-displacement was fabricated with a $15\ \ \mu \mathrm{m}$ thick polymer layer and characterized by applying currents up to 18 ma (7.3 mW, producing ∼156°C) resulting in a maximum displacement of $3.3\ \mu \mathrm{m}$ and ∼0.9 mN blocking force. Dynamic operation with falling/rising times of 20.1 ms/9.8 ms and 33.5 Hz maximum operation frequency was also demonstrated.

The primary aim of osteoanabolic therapies is to strategically increase bone mass in skeletal regions likely to experience high strains. In the young healthy skeleton, this is primarily achieved by bone's adaptation to loading. This adaptation appears to fail with age, resulting in osteoporosis and fractures. We previously demonstrated that prior and concurrent disuse enhances bone gain following loading in old female mice. Here, we applied site specificity micro-computed tomography analysis to map regional differences in bone anabolic responses to axial loading of the tibia between young (19-week-old) and aged (19-month-old), male and female mice. Loading increased bone mass specifically in the proximal tibia in both sexes and ages. Young female mice gained more cortical bone than young males in specific regions of the tibia. However, these site-specific sex differences were lost with age such that bone gain following loading was not significantly different between old males and females. To test whether disuse enhances functional adaption in old male mice as it does in females, old males were subjected to sciatic neurectomy or sham surgery, and loading was initiated four days after surgery. Disuse augmented tibial cortical bone gain in response to loading in old males, but only in regions which were load-responsive in the young. Prior and concurrent disuse also increased loading-induced trabecular thickening in the proximal tibia of old males. Understanding how diminished background loading rejuvenates the osteogenic loading response in the old may improve osteogenic exercise regimes and lead to novel osteoanabolic therapies., Highlights • Sex differences in cortical tissue area of young and old mice are not site-specific. • The loading response in young, but not old, mice is sex- and site-specific. • The cortical loading response is site-specifically enhanced by disuse in old mice of both sexes. • The trabecular loading response can be rescued by disuse in old male, but not female, mice.

Citizen-collected arthropod vectors are useful for epidemiological studies of vector–borne disease, especially since the vectors encountered by the public are the subset of vectors in nature that have a disproportionate impact on health. Programs integrating educational efforts with collecting efforts may be particularly effective for public health initiatives, resulting in an empowered public with knowledge of vector–borne disease prevention. Citizen science programs have been successfully implemented for the collection of unprecedented sample sets of mosquitos, ticks, and triatomines. Cyber infrastructure employed in digital epidemiology — including websites, email, mobile phone apps, and social media platforms — has facilitated vector citizen science initiatives to assess disease risk over vast spatial and temporal scales, advancing research to mitigate vector–borne disease risk.

Origami manufacturing, the use of folding to create 3-D shapes using 2-D fabrication tools and techniques, is a promising avenue for creating low cost parts. In this letter, we demonstrate the hands-free cutting and folding of 3-D inductor geometries from blank metal foil using only a 2-D laser cutter. Laser forming, localized laser heating to create thermal stresses to deform a workpiece, is used to fold traces out of plane without manual handling. The laser forming of thin copper foil is first characterized, followed by cutting and folding of two 3-D inductors: a three-turn planar coil with folded overpass and a twelve-turn toroid. The planar coil was found to have inductance 199 nH and peak quality factor of 99.7 at 54.7 MHz, while the toroid had inductance 159 nH with peak quality factor 64.9 at 86.7 MHz. With laser cutters, one of the most widely available machine tools, this technology allows custom, high performance electrical passives to be rapidly fabricated without specialized equipment.

Direct-write laser grayscale lithography has been used to facilitate a single-step patterning technique for multilayer lead zirconate titanate (PZT) thin films. A 2.55- $\mu \text{m}$ -thick photoresist was patterned with a direct-write laser. The intensity of the laser was varied to create both tiered and sloped structures that are subsequently transferred into multilayer PZT(52/48) stacks using a single Ar ion-mill etch. Traditional processing requires a separate photolithography step and an ion mill etch for each layer of the substrate, which can be costly and time consuming. The novel process allows access to buried electrode layers in the multilayer stack in a single photolithography step. The grayscale process was demonstrated on three 150-mm diameter Si substrates configured with a 0.5- $\mu \text{m}$ -thick SiO2 elastic layer, a base electrode of Pt/TiO2, and a stack of four PZT(52/48) thin films of either 0.25- $\mu \text{m}$ thickness per layer or 0.50- $\mu \text{m}$ thickness per layer, and using either Pt or IrO2 electrodes above and below each layer. Stacked capacitor structures were patterned and results will be reported on the ferroelectric and electromechanical properties using various wiring configurations and compared to comparable single layer PZT configurations.

Expanding upon the findings of the 2017 General Accounting Office Review identifying the failure of FERC to develop methodologies to determine the efficacy of RTO electric capacity markets, this article explains in detail why it is likely that capacity markets structured only for the sale of bare megawatts to load-serving utilities through an auction capacity are as lacking as Fitbits are in providing a rounded picture of their users’ health. As currently constituted, capacity markets can never capture all relevant attributes that determine the types of generating resources constructed nor fully reconcile federal and state policies that concurrently affect development of generation.

Fused filament fabrication (FFF) 3D printers have been largely limited to thermoplastics in the past but with new composite materials available on the market there are new possibilities for what these machines can produce. Using a conductive composite filament, electronic components can be manufactured but due to the filament’s relatively poor electrical properties, the resulting traces are typically highly resistive. Selective electroplating on these parts is one approach to incorporate materials with high conductivity onto 3D-printed structures. In this paper, non-conductive and conductive filaments printed in the same part are used to enable selective electroplating directly on regions defined by the conductive filament to create metallic parts through 3D printing. This technique is demonstrated for the creation of multiple distinct conductive segments and to electroplate the same part with multiple metals to, for instance, allow a magnetic metal such as nickel and a highly conductive one such as copper to be incorporated in the same part. Following the characterization of the process, a representative 3D printed electrical device, a selectively electroplated solenoid inductor with low frequency inductance and resistance of 191 nH and 18.7 mΩ respectively was manufactured using this technique. This is a five order of magnitude reduction in resistance over the original value of 3 kΩ for the inductor before electroplating.

Queimadas são uma ameaça a conservação dos ecossistemas em especial em Unidades de Conservação, territórios de grande valor considerando seus atributos físicos e bióticos, podendo resultar em impactos significativos e duradouros tanto do ponto de vista ecológico, como social e econômico. O objetivo deste trabalho foi realizar um mapeamento de áreas susceptíveis a risco de incêndio na APA Sul RMBH com uso de técnicas de geoprocessamento. Foi utilizada a análise multicritérios pelo modelo de Análise Hierárquica de Processos (AHP) considerando dados secundários referentes às características fisiográficas e socioeconômicas da área de estudo. O mapa resultante, com as áreas de maior risco a ocorrência de incêndios, indicou predominância de risco médio ao longo da APA Sul, sendo que as áreas de alto risco concentraram-se em locais com as menores cotas altimétricas do recorte, declividades mais planas, em locais de pastagem e mosaicos de agricultura, regimes de precipitação e temperatura intermediários, enquanto que as áreas menos propícias a incêndios localizaram-se em locais de afloramento rochoso, elevada altimetria, declividade montanhosa a escarpada e afastadas das principais localidades e rodo-ferrovias. Acredita-se que o uso de geotecnologias para esse fim possa subsidiar no planejamento e gestão desta importante unidade de conservação.

Trastuzumab and trastuzumab emtansine (T-DM1) targeted therapies are the main choice for the treatment of HER2-overexpressing breast cancer patients. However, de novo or acquired resistance is still the major obstacle in clinical practice. It has been shown that several pathways, including HER2, can lead to HIF-α stabilization in breast cancer cells. Thus, the purpose of our study was to analyse the effect of hypoxia in acquired resistance to anti-HER2 therapies. We used HER2-overexpressing BT-474 and non-overexpressing MCF-7 human breast cancer cell lines. As an acute hypoxia model, we added CoCl2 (100 µM) to cell culture medium. The hypoxic status of the cells was evaluated by a Western blot analysis, showing a peak of HIF-1α expression after 6 hours of CoCl2 exposure. This result correlated with VEGF induction, as measured by RT-qPCR (p Citation Format: Virginia Judith Wolos, Ivana Jaqueline Tapia, Marianela Abrigo, Ezequiel Lacunza, Elisa Dora Bal de Kier Joffé, Gabriel León Fiszman. Hypoxic microenvironment promotes resistance to targeted therapies in HER2-overexpressing breast cancer involving epithelial-to-mesenchymal transition features [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1078.

Scrubbing has been a traditional way of improving the reliability of SRAM-based FPGAs, which are largely used by the industry but are very sensitive to Single Event Upsets (SEU). This vulnerability mainly resides in the configuration memory, which is very large. The conventional approach to SEU mitigation is to use some form of redundancy with a periodic scrubbing of the configuration memory, thus removing accumulated SEUs. In this paper, we propose a novel approach to scrub FPGAs in real-time systems, by using diagnostic information based on the primary outputs of the circuits, in the form of a coarse-grained DMR, and a specialized scrubbing mechanism to avoid missing real-time deadlines. An alternative diagnostic scheme is also investigated for benchmark circuits that presented subpar repair performance due to large clock cycle overheads.

Preventive intervention effects on adolescent alcohol misuse may differ based on genotypes in gene-by-intervention (G x I) interactions, and these G x I interactions may vary as a function of age. The current study uses a novel statistical method, time-varying effect modeling (TVEM), to test an age-varying interaction between a single nucleotide polymorphism in the GABRA2 gene (rs279845) and a preventive intervention in predicting alcohol misuse in a longitudinal study of adolescents (ages 11-20). The preventive intervention was PROSPER, a community-based system for delivery of family and school programs selected from a menu of evidence-based interventions. TVEM results revealed a significant age-varying GABRA2 x intervention interaction from ages 12 to 18, with the peak effect size seen around age 13 (IRR = 0.50). The intervention significantly reduced alcohol misuse for adolescents with the GABRA2 TT genotype from ages 12.5 to 17 but did not reduce alcohol use for adolescents with the GABRA2 A allele at any age. Differences in intervention effects by GABRA2 genotype were most pronounced from ages 13 to 16-a period when drinking is associated with increased risk for alcohol use disorder. Our findings provide additional evidence that intervention effects on adolescent alcohol misuse may differ by genotype, and provide novel evidence that the interaction between GABRA2 and intervention effects on alcohol use may vary with age. Implications for interventions targeting adolescent alcohol misuse are discussed.

Prostacyclin-associated leg pain is a potentially debilitating adverse effect of prostacyclin therapy for patients with pulmonary arterial hypertension (PAH). However, to our knowledge, this entity has not been systematically studied.To characterize the clinical features and metabolic risk factors for prostacyclin-associated leg pain.At one academic medical center, we assembled and analyzed a case series of patients with PAH and prostacyclin-associated leg pain.Over a period of 2 years, we identified 11 patients with PAH and prostacyclin-associated leg pain who agreed to participate in this study. Subjects underwent a standardized clinical evaluation, electrodiagnostic assessment, and serologic screen for metabolic causes of peripheral neuropathy. All 11 patients were female; their mean (SD) age was 50 (±9) years; their median (interquartile range) PAH duration was 56 (20-96) months; and their prostacyclin therapy duration was a median (interquartile range) of 20 (14-36) months. All patients reported leg pain beginning soon after prostacyclin initiation and varying with dose. All described a neuropathic pain in a symmetric, distal, stocking distribution. Neurologic examination revealed a sensory, small-fiber, predominantly peripheral neuropathy in seven (78%) patients. Results of autonomic reflex testing and thermoregulatory sweat testing were abnormal in 82% and 90% of patients, respectively, suggesting small-fiber neuropathy. Serologic evaluation identified a new, previously unrecognized contributor to neuropathy in eight (73%) patients, including vitamin BChronic prostacyclin-associated leg pain is associated with a small-fiber neuropathy. Treatable metabolic contributors (vitamin B

In the last decade, deep learning has revolutionized various components of the conventional robot autonomy stack including aspects of perception, navigation and manipulation. There have been numerous advances in perfecting individual tasks such as scene understanding, visual localization, end-to-end navigation and grasping, which has given us a critical understanding on how to create individual architectures for a specific task. This now brings us to the question, as to whether this disjoint learning of models for robotic tasks, effective in the real-world and whether it is scalable? And more generally, is training task specific models on task specific datasets beneficial to architecting robot intelligence as a whole? In this paper, we argue that multimodel learning or joint multi-task learning is an effective strategy for enabling robots to excel across multiple domains. We describe how multimodel learning can facilitate generalization to unseen scenarios by utilizing domain-specific cues from auxiliary tasks and discuss some of the current mechanisms that can be employed to design multimodel frameworks for robot autonomy.

High-performance superscalar processors have been developed to satisfy the growing demand for processing modern applications. However, as the transistor size shrinks, the increase in vulnerability to soft errors poses a great challenge, since these effects have been proven to also affect ground-level safety-critical applications. Considering that vulnerability strategies may span across different layers of the system stack, we propose a mixed SW/HW-based design-time methodology aiming to achieve the best tradeoff between vulnerability and area/energy for superscalar processors. By injecting over 10 million faults in 12 significant micro-architectural structures to different versions of the complex BOOM OoO superscalar processor modeled with RTL accuracy, we show that SW-based protection techniques always reach an upper bound that may not be satisfactory. Then, we propose to insert extra low-level HW-based DMR protection at strategic micro-architectural points by reducing this task to the Knapsack Problem. In one of the evaluated cases, we optimally find the best structures to be protected with 55% area overhead to achieve a 95% vulnerability improvement for a quad-issue processor.

The identification of bridges in major infrastructure works is crucial to provide information about the status of these constructions and support possible decision-making processes. Typically, this identification is performed by human agents that must detect the bridges into large-scale datasets, analyzing image by image, a time-consuming task. In this paper, we propose a novel tool to perform bridge detection and identification in large-scale remote sensing datasets. This tool implements a deep learning-based algorithm, the Faster R-CNN (Regions with CNN features), a technique that is the current state-of-the-art for many object detection and identification applications. Since deep training usually requires a lot of data, we also created a bridge image dataset, composed of remote sensing images from around the globe. The proposed tool was encapsulated into an ArcGIS plugin in order to facilitate its use by non-programmer users.

Low-Density Parity-Check (LDPC) codes have been used in many communication standards due to their capacity-approaching performance with feasible decoding architectures. Field-Programmable Gate Arrays (FPGAs) have been shown to be appropriate for the implementation of LDPC decoders, due to their ability to exploit the fine-grained parallelism found in such codes, as well as due to their reconfigurability, which allows to easily adapt the decoder to different codes. The susceptibility of FPGAs to faults affecting their configuration memories, however, demands specific fault tolerance strategies when these devices are used in harsh environments, such as aerospace applications, or even in ground-level critical systems. Thus, in this work we present a characterization of the behavior of LDPC decoders when subject to configuration errors and show that a single error can substantially degrade decoding performance, differently from what is observed in application-specific circuits. Based on this characterization, we propose a cost-effective fault tolerance scheme able to cope with faults in the FPGA fabric. Identifying the most critical components allowed reducing performance degradation by 89 % while only covering 55 % of their area.

IntroductionHIV-exposed uninfected (HEU) children have higher morbidity and mortality compared with HIV unexposed uninfected children. Despite the fact that malnutrition contributes to about half of all infant deaths below 5 years of age in low-income and middle-income countries and that growth impairment has been reported in the HEU population, the spectrum of growth disorders associated with HIV and antiretroviral therapy (ART) exposure during the in utero and perinatal periods is yet to comprehensively summarised among the global HEU population. This protocol for a systematic review and meta-analysis aims to critically synthesise data concerning the prevalence of underweight, stunting and wasting at different ages in the global HEU population.Methods and analysisMedline, EMBASE, Cochrane Library, TOXLINE, WHO Global Index Medicus and the Web of Science will be searched for relevant articles published between 1 January 1989 and 1 December 2017 without language restriction. In addition, conference abstracts and reference lists of eligible papers and relevant review articles will be screened. Authors will screen and select studies, extract data, assess the risk of bias as well as studies individually for heterogeneity. Study-specific estimates will be pooled through a random-effects meta-analysis model for studies that are clinically homogeneous while funnel plots and Egger’s test will be used to detect publication bias. Results will be presented by ART availability period, country income levels and mode of breastfeeding.Ethics and disseminationEthical approval will not be required for this study because it will be based on published data. The final report of this study will be published in a peer-reviewed journal and presented at scientific conferences. This review will summarise the evidence and quantify the problem of growth impairment in HEU infants and so shed more light on our understanding of the higher morbidity and mortality in this growing population.PROSPERO registration numberCRD42018091762.

77 Background: MSS mCRC rarely responds to pembrolizumab monotherapy, but capecitabine and bevacizumab may induce immune-stimulatory effects. This study evaluates the safety, tolerability and preliminary efficacy of pembrolizumab in combination with capecitabine and bevacizumab in MSS mCRC. We present results at the planned interim analysis. Methods: Design:single-arm, open-label, single-site phase 2 trial with a safety lead-in to confirm the recommended phase 2 dose (RP2D) for capecitabine and expansion cohorts. Per the Simon’s 2-stage design, ≤1 response in 29 patients (pts) requires trial suspension. Key eligibility criteria: MSS mCRC with stable disease (SD) or progressive disease (PD) on prior fluoropyrimidine-based therapy. Treatment: RP2D PO capecitabine on days 1-14 plus 200 mg IV pembrolizumab and 7.5 mg/kg IV bevacizumab on day 1 in 21-day cycles. Pts are followed for toxicity and radiographic response. Results: From 04/2018-09/2020, 29 pts were enrolled, of whom 15 (52%) were female; 21 (72%) white; and median age was 55 years (range 36-77 years). Prior therapies: 2 (7%) pts had SD and 27 (93%) pts had PD on fluoropyrimidine-containing regimens; 24 (83%) pts had prior exposure to bevacizumab. The RP2D for capecitabine was 1000 mg/m2 PO BID, with no dose limiting toxicities observed. Complete toxicity data are available for 25 off-treatment pts. The most common related adverse events (AEs) were palmar-plantar erythrodysesthesia (PPE) (64%) and fatigue (68%). Grade ≥3 related AEs occurred in 9 (36%) pts, including immune-related AEs of Grade 3 dyspnea, hypophosphatemia, and pancreatitis in 1 pt each. Treatment related AEs leading to dose interruptions, reductions, or delays occurred in 15 (60%) pts, most commonly PPE in 13 (52%) pts. No pt had a related AE leading to treatment discontinuation or death. Disposition: of 29 pts enrolled, 24 were removed for PD and 1 was removed for an unrelated AE. Best response by RECIST 1.1 in 23 evaluable pts: partial response (PR) in 2 (9%); SD in 14 (61%); PD in 7 (30%). Median time on treatment was 6 months (range 2-26 months). Conclusions: Combination of pembrolizumab with capecitabine and bevacizumab was found to be tolerable with an expected toxicity profile in MSS mCRC pts. With 2 responses, the study met interim analysis criteria to continue accrual. Tissue and blood-based immune correlatives are planned. Clinical trial information: NCT03396926.

Background: Despite the use of saliva with enzyme immunoassay (EIA) methods validated for use with blood to measure interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), there has been limited validation of saliva as a matrix for EIA of IL-6 and TNF-α. Objectives: The study aims were to (a) validate one vendor’s commercially available EIAs for detecting IL-6 and TNF-α in saliva as an alternative matrix to blood and (b) test the long-term stability of EIA detection of IL-6 and TNF-α after 12-month storage of saliva and plasma. Methods: Spike and recovery and linearity experiments were performed. Concentrations of IL-6 and TNF-α in saliva and plasma from 20 healthy adult volunteers (6 men and 14 women) were correlated; the assays were repeated 12 months later. Results: Spike and recovery and linearity performance was adequate for salivary IL-6: intra-assay percentage coefficient of variation, less than or equal to 8.4%; sensitivity, 0.11 pg/ml; mean recoveries, 81% in spiked saliva and 110% in spiked controls; and linearity, r = .995. The association between IL-6 in saliva and plasma was moderate and significant (p = .04). Spike and recovery and linearity performance was inadequate for TNF-α: intra-assay coefficient of variation, 10.8%; sensitivity, 2.3 pg/ml; mean recoveries, 44% in spiked saliva and 92% in spiked controls; and linearity, r = .950. The association between TNF-α in saliva and plasma was low and insignificant. Plasma and saliva IL-6 levels were significantly higher (p < .0001), and plasma and saliva TNF-α levels were significantly lower (p < .0001) after 12-month storage of specimens. Discussion: We concluded that (a) saliva can be used to assess IL-6, but not TNF-α, with an EIA validated for use with blood and (b) 12-month storage of plasma and saliva significantly changes the assay results. Validation of other EIAs would expand assay options for investigators.

Background: Occipital neuromodulation is a promising treatment modality for refractory headache, but lead migration remains a frequent surgical complication. Objectives: The primary objective was to identify surgical techniques that may minimize adverse events, particularly lead migration. We hypothesized that a surgical technique employing 2-point anchoring of stimulator leads designed to provide a tension-relief loop and the use of ultrasound for lead placement would decrease the complication rate. Study Design and Setting: A retrospective analysis was performed through electronic medical record chart review in a tertiary referral center. Methods: Institutional Review Board (IRB) approval was obtained. Eighteen patients had a trial and subsequent permanent occipital nerve stimulator (ONS) implantation between 2004 and 2011 and were included. Adverse events were recorded and efficacy outcome variables analyzed for significance. Results: The cohort was a median (IQR) 45 (37 – 58) in age and 9 (50%) were women. Tension-relief loops placed via a 2-point anchoring technique and ultrasound use for occipital lead placement were evident in 16 (89%) and 13 (72%), respectively. There was one (6%) clinically insignificant lead position change, not definitively a lead migration, which could have been an artifact of fluoroscope positioning. Adverse events included one (6%) battery malfunction, one (6%) lead malfunction, and 2 (12%) post-implantation infections. Following ONS, there were significant reductions in numeric rating scale (NRS) pain scores from a median (IQR) of 9.5 (8.25 – 10) to 2.5 (1 – 4.75) (P < 0.0001), headache days per week from 7 (7 – 7) to 1.5 (0.375 – 1.75) (P = 0.0005), and the number of daily headache medication from 3 (2.25 – 4) to 2.5 (2 – 3.75) (P = 0.0112). Limitations: Limitations include retrospective study design, investigator bias, and nonstandardized intervals of headache burden assessment. Conclusions: In ONS, utilization of a 2-point anchoring technique with a tension-relief loop may significantly minimize the risk of lead migration, based on the absence of definitive lead migration in our series. Ultrasound use may improve the anatomic accuracy of lead placement with the possibility of improved efficacy. ONS was associated with significantly decreased headache pain, frequency, and medication use. Key words: Occipital neuromodulation, occipital nerve stimulation, surgical technique, lead migration, tension-relief loop

This article introduces Live-Out Register Fencing (LoRF), a soft error correction mechanism that uses the novel Spill Register File as a container of checkpointing data. LoRF’s Spill Register File holds the values shared among basic blocks in the program, and, coupled with a new compilation strategy, LoRF allows for error correction in the same basic block where the error was detected. In LoRF, error correction is triggered by a hardware interrupt that restores the registers of a basic block from the Spill Register File. After these registers are restored, the basic block where the error was detected can just be re-executed, thus reducing the costs of error recovery. LoRF’s error correction policy eliminates the need for expensive architectural support for checkpointing and rollback, reducing the performance overhead of online soft error correction. LoRF relies on both a modified processor architecture and a corresponding compiler. The architecture was implemented in synthesizable VHDL, whereas the compiler was developed as an extension of the LLVM framework. Fault injection experiments support an error correction coverage of 99.35% and a mean performance overhead of 1.33 for the entire life cycle of an error from its occurrence to its elimination from the system.