Two-Capacitor Direct Interface Circuit for Resistive Sensor Measurements.

Direct interface circuits (DICs) avoid the need for signal conditioning circuits and analog-to-digital converters (ADCs) to obtain digital measurements of resistive sensors using only a few passive elements. However, such simple hardware can lead to quantization errors when measuring small resistance values as well as high measurement times and uncertainties for high resistances. Different solutions to some of these problems have been presented in the literature over recent years, although the increased uncertainty in measurements at higher resistance values is a problem that has remained unaddressed. This article presents an economical hardware solution that only requires an extra capacitor to reduce this problem. The circuit is implemented with a field-programmable gate array (FPGA) as a programmable digital device. The new proposal significantly reduces the uncertainty in the time measurements. As a result, the high resistance errors decreased by up to 90%. The circuit requires three capacitor discharge cycles, as is needed in a classic DIC. Therefore, the time to estimate resistance increases slightly, between 2.7% and 4.6%.

Development of Novel Micro-dystrophins with Enhanced Functionality.

Gene therapies using adeno-associated viral (AAV) vectors have advanced into clinical trials for several diseases, including Duchenne muscular dystrophy (DMD). A limitation of AAV is the carrying capacity (∼5 kb) available for genes and regulatory cassettes (RCs). These size constraints are problematic for the 2.2-Mb dystrophin gene. We previously designed a variety of miniaturized micro-dystrophins (µDys) that displayed significant, albeit incomplete, function in striated muscles. To develop µDys proteins with improved performance, we explored structural modifications of the dystrophin central rod domain. Eight µDys variants were studied that carried unique combinations of between four and six of the 24 spectrin-like repeats present in the full-length protein, as well as various hinge domains. Expression of µDys was regulated by a strong but compact muscle-restricted RC (CK8e) or by the ubiquitously active cytomegalovirus (CMV) RC. Vectors were evaluated by intramuscular injection and systemic delivery to dystrophic mdx4cv mice, followed by analysis of skeletal muscle pathophysiology. Two µDys designs were identified that led to increased force generation compared with previous µDys while also localizing neuronal nitric oxide synthase to the sarcolemma. An AAV vector expressing the smaller of these (µDys5) from the CK8e RC is currently being evaluated in a DMD clinical trial.

Klotho gene silencing promotes pathology in the mdx mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a lethal muscle disease involving progressive loss of muscle regenerative capacity and increased fibrosis. We tested whether epigenetic silencing of the klotho gene occurs in the mdx mouse model of DMD and whether klotho silencing is an important feature of the disease. Our findings show that klotho undergoes muscle-specific silencing at the acute onset of mdx pathology. Klotho experiences increased methylation of CpG sites in its promoter region, which is associated with gene silencing, and increases in a repressive histone mark, H3K9me2. Expression of a klotho transgene in mdx mice restored their longevity, reduced muscle wasting, improved function and greatly increased the pool of muscle-resident stem cells required for regeneration. Reductions of fibrosis in late, progressive stages of the mdx pathology achieved by transgene expression were paralleled by reduced expression of Wnt target genes (axin-2), transforming growth factor-beta (TGF-ß1) and collagens types 1 and 3, indicating that Klotho inhibition of the profibrotic Wnt/TGFß axis underlies its anti-fibrotic effect in aging, dystrophic muscle. Thus, epigenetic silencing of klotho during muscular dystrophy contributes substantially to lost regenerative capacity and increased fibrosis of dystrophic muscle during late progressive stages of the disease.

Assistive Handlebar Based on Tactile Sensors: Control Inputs and Human Factors.

Tactile sensors can be used to build human-machine interfaces, for instance in isometric joysticks or handlebars. When used as input sensor device for control, questions arise related to the contact with the human, which involve ergonomic aspects. This paper focuses on the example application of driving a powered wheelchair as attendant. Since other proposals use force and torque sensors as control input variables, this paper explores the relationship between these variables and others obtained from the tactile sensor. For this purpose, a handlebar is instrumented with tactile sensors and a 6-axis force torque sensor. Several experiments are carried out with this handlebar mounted on a wheelchair and also fixed to a table. It is seen that it is possible to obtain variables well correlated with those provided by force and torque sensors. However, it is necessary to contemplate the influence of issues such as the gripping force of the human hand on the sensor or the different kinds of grasps due to different physical constitutions of humans and to the inherent random nature of the grasp. Moreover, it is seen that a first step is necessary where the contact with the hands has to stabilize, and its characteristics and settle time are obtained.

High-Accuracy Readout Electronics for Piezoresistive Tactile Sensors.

The typical layout in a piezoresistive tactile sensor arranges individual sensors to form an array with M rows and N columns. While this layout reduces the wiring involved, it does not allow the values of the sensor resistors to be measured individually due to the appearance of crosstalk caused by the nonidealities of the array reading circuits. In this paper, two reading methods that minimize errors resulting from this phenomenon are assessed by designing an electronic system for array reading, and the results are compared to those obtained using the traditional method, obviating the nonidealities of the reading circuit. The different models were compared by testing the system with an array of discrete resistors. The system was later connected to a tactile sensor with 8 × 7 taxels.

Accuracy and Resolution Analysis of a Direct Resistive Sensor Array to FPGA Interface.

Resistive sensor arrays are formed by a large number of individual sensors which are distributed in different ways. This paper proposes a direct connection between an FPGA and a resistive array distributed in M rows and N columns, without the need of analog-to-digital converters to obtain resistance values in the sensor and where the conditioning circuit is reduced to the use of a capacitor in each of the columns of the matrix. The circuit allows parallel measurements of the N resistors which form each of the rows of the array, eliminating the resistive crosstalk which is typical of these circuits. This is achieved by an addressing technique which does not require external elements to the FPGA. Although the typical resistive crosstalk between resistors which are measured simultaneously is eliminated, other elements that have an impact on the measurement of discharge times appear in the proposed architecture and, therefore, affect the uncertainty in resistance value measurements; these elements need to be studied. Finally, the performance of different calibration techniques is assessed experimentally on a discrete resistor array, obtaining for a new model of calibration, a maximum relative error of 0.066% in a range of resistor values which correspond to a tactile sensor.

Improved Circuits with Capacitive Feedback for Readout Resistive Sensor Arrays.

One of the most suitable ways of distributing a resistive sensor array for reading is an array with M rows and N columns. This allows reduced wiring and a certain degree of parallelism in the implementation, although it also introduces crosstalk effects. Several types of circuits can carry out the analogue-digital conversion of this type of sensors. This article focuses on the use of operational amplifiers with capacitive feedback and FPGAs for this task. Specifically, modifications of a previously reported circuit are proposed to reduce the errors due to the non-idealities of the amplifiers and the I/O drivers of the FPGA. Moreover, calibration algorithms are derived from the analysis of the proposed circuitry to reduce the crosstalk error and improve the accuracy. Finally, the performances of the proposals is evaluated experimentally on an array of resistors and for different ranges.

Insights into the Mechanical Behaviour of a Layered Flexible Tactile Sensor.

This paper shows realizations of a piezoresistive tactile sensor with a low cost screen-printing technology. A few samples were fabricated for different materials used as insulator between the conductive layers and as top layer or cover. Both can be used to tune the sensitivity of the sensor. However, a large influence is also observed of the roughness at the contact interface on the sensitivity and linearity of the output, as well as on mismatching between the outputs from different taxels. The roughness at the contact interface is behind the transduction principle of the sensor, but it also limits its performance if the wavelength of the roughness is comparable or even longer than the size of the contacts. The paper shows experimental results that confirm this relationship and discusses its consequences in sensor response related to the materials chosen for the insulator and the cover. Moreover, simulations with FEA tools and with simple models are used to support the discussions and conclusions obtained from the experimental data. This provides insights into the sensor behaviour that are shared by other sensors based on the same principle.

A new model based on adaptation of the external loop to compensate the hysteresis of tactile sensors.

This paper presents a novel method to compensate for hysteresis nonlinearities observed in the response of a tactile sensor. The External Loop Adaptation Method (ELAM) performs a piecewise linear mapping of the experimentally measured external curves of the hysteresis loop to obtain all possible internal cycles. The optimal division of the input interval where the curve is approximated is provided by the error minimization algorithm. This process is carried out off line and provides parameters to compute the split point in real time. A different linear transformation is then performed at the left and right of this point and a more precise fitting is achieved. The models obtained with the ELAM method are compared with those obtained from three other approaches. The results show that the ELAM method achieves a more accurate fitting. Moreover, the involved mathematical operations are simpler and therefore easier to implement in devices such as Field Programmable Gate Array (FPGAs) for real time applications. Furthermore, the method needs to identify fewer parameters and requires no previous selection process of operators or functions. Finally, the method can be applied to other sensors or actuators with complex hysteresis loop shapes.

Smart Capture Modules for Direct Sensor-to-FPGA Interfaces.

Direct sensor-digital device interfaces measure time dependent variables of simple circuits to implement analog-to-digital conversion. Field Programmable Gate Arrays (FPGAs) are devices whose hardware can be reconfigured to work in parallel. They usually do not have analog-to-digital converters, but have many general purpose I/O pins. Therefore, direct sensor-FPGA connection is a good choice in complex systems with many sensors because several capture modules can be implemented to perform parallel analog data acquisition. The possibility to work in parallel and with high frequency clock signals improves the bandwidth compared to sequential devices such as conventional microcontrollers. The price to pay is usually the resolution of measurements. This paper proposes capture modules implemented in an FPGA which are able to perform smart acquisition that filter noise and achieve high precision. A calibration technique is also proposed to improve accuracy. Resolutions of 12 effective number of bits are obtained for the reading of resistors in the range of an example piezoresistive tactile sensor.

Influence of Errors in Tactile Sensors on Some High Level Parameters Used for Manipulation with Robotic Hands.

Tactile sensors suffer from many types of interference and errors like crosstalk, non-linearity, drift or hysteresis, therefore calibration should be carried out to compensate for these deviations. However, this procedure is difficult in sensors mounted on artificial hands for robots or prosthetics for instance, where the sensor usually bends to cover a curved surface. Moreover, the calibration procedure should be repeated often because the correction parameters are easily altered by time and surrounding conditions. Furthermore, this intensive and complex calibration could be less determinant, or at least simpler. This is because manipulation algorithms do not commonly use the whole data set from the tactile image, but only a few parameters such as the moments of the tactile image. These parameters could be changed less by common errors and interferences, or at least their variations could be in the order of those caused by accepted limitations, like reduced spatial resolution. This paper shows results from experiments to support this idea. The experiments are carried out with a high performance commercial sensor as well as with a low-cost error-prone sensor built with a common procedure in robotics.

Mixed-Method Precooling Enhances Self-Paced 20-km Cycling Time-Trial Performance When Apparent Temperature Is >46 °C but May Not Be a Priority in <46 °C.

PURPOSE: Precooling (PreC) may only benefit performance when thermal strain experienced by an individual is sufficiently high. We explored the effect of mixed-method PreC on 20-km cycling time-trial (CTT) performance under 3 different apparent temperatures (AT). METHODS: On separate days, 12 trained or highly trained male cyclists/triathletes completed six 20-km CTTs in 3 different ATs: hot-dry (35 °C AT), moderately hot-humid (40 °C AT), and hot-humid (46 °C AT). All trials were preceded by 30 minutes of mixed-method PreC or no PreC (control [CON]). RESULTS: Faster 2.5-km-split completion times occurred in PreC compared with CON in 46 °C AT (P = .02), but not in 40 °C AT (P = .62) or 35 °C AT (P = .57). PreC did not affect rectal and body temperature during the 20-km CTT. Skin temperature was lower throughout the CTT in PreC compared with CON in 46 °C AT (P = .01), but not in 40 °C AT (P = 1.00) and 35 °C AT (P = 1.00). Heart rate had a greater rate of increase during the CTT for PreC compared with CON in 46 °C AT (P = .01), but not in 40 °C AT (P = .57) and 35 °C AT (P = 1.00). Ratings of perceived exertion (P < .001) and thermal comfort (P = .04) were lower for PreC compared with CON in 46 °C AT only, while thermal sensation was not different between PreC and CON. CONCLUSION: Mixed-method PreC should be applied prior to 20-km CTTs conducted in hot-humid conditions (≥46 °C AT). Alternatively, mixed-method PreC may be a priority in moderately hot-humid (∼40 °C AT) conditions but should not be in hot-dry (∼35 °C AT) conditions for 20-km CTT.

Single Session Intermittent Heat Exposure With More Frequent and Shorter Cooling Breaks Facilitates Greater Training Intensity and Elicits Physiological Responses Comparable to Continuous Heat Exposure.

PURPOSE: To investigate the influence of shorter, more frequent rest breaks with per-cooling as an alternative heat-acclimation session on physiological, perceptual, and self-paced maximal cycling performance, compared with continuous heat exposure. METHODS: Thirteen participants completed 1 continuous and 3 intermittent-heat-exposure (IHE) maximal self-paced cycling protocols in a random order in heat (36 °C, 80% relative humidity): 1 × 60-minute exercise (CON), 3 × 20-minute exercise with 7.5-minute rest between sets (IHE-20), 4 × 15-minute exercise with 5-minute rest between sets (IHE-15), and 6 × 10-minute exercise with 3-minute rest between sets (IHE-10). Mixed-method per-cooling (crushed-ice ingestion and cooling vest) was applied during rest periods of all IHE protocols. RESULTS: Total distance completed was greater in IHE-10, IHE-15, and IHE-20 than in CON (+11%, +9%, and +8%, respectively), with no difference observed between IHE protocols. Total time spent above 38.5 °C core temperature was longer in CON compared with IHE-15 and IHE-20 (+62% and +78%, respectively) but similar to IHE-10 (+5%). Furthermore, a longer time above 38.5 °C core temperature occurred in IHE-10 versus IHE-15 and IHE-20 (+54% and +69%, respectively). Sweat loss did not differ between conditions. CONCLUSION: IHE with per-cooling may be a viable alternative heat-acclimation protocol in situations where training quality takes precedence over thermal stimulus or when both factors hold equal priority.

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011-2012 season in Spain, among population targeted for vaccination.

BACKGROUND: In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011-2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. METHODS: Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed <8 days after symptom onset were included. Cases tested positive for influenza and controls tested negative for any influenza virus. To examine the effect of a late season, analyses were performed according to the phase of the season and according to the time between vaccination and symptoms onset. RESULTS: The overall adjusted influenza VE against A(H3N2) was 45% (95% CI, 0-69). The estimated influenza VE was 52% (95% CI, -3 to 78), 40% (95% CI, -40 to 74) and 22% (95% CI, -135 to 74) at 3.5 months, 3.5-4 months, and >4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. CONCLUSIONS: The 2011-2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season.

Improving the Gleason grading accuracy of transrectal ultrasound-guided biopsy.

BACKGROUND: Transrectal ultrasound (TRUS)-guided prostate biopsy is the technique of choice for the assessment of clinical suspicion of prostate cancer (PC) based on abnormal digital rectal examination (DRE) and/or elevated or rising levels of prostate-specific antigen (PSA). PURPOSE: To identify factors involved in TRUS-guided prostate biopsy, which can be modified by radiologists in order to improve Gleason score (GS) accuracy, and to assess the influence of clinical variables. MATERIAL AND METHODS: We carried out a retrospective review of the records of 185 patients with PC treated surgically at our hospital between 2005 and 2008. Biopsy schemes were classified according to the number of cores (≤7, 8-9, 10-11, 12-15) and the needle length (11, 16, 20 mm). Clinical characteristics - age, family history of PC, DRE, PSA levels, and sonographic data - and prostatectomy GS (pGS) were collected. RESULTS: Non-random concordance between biopsy Gleason score (bGS) and pGS was obtained for 36% of patients (P < 0.001). Under- and over-staging were 30% and 4%, respectively. Concordance was correlated with the core number (45% for ≤7, 54% for 8-9, 85% for 10-11, and 80% for 12-15; P < 0.001), but not with the needle length. The concordance rate showed a seven-fold increase when 10-11 cores were obtained (95% CI, 2-18; P < 0.001) compared to those cases in which the core number obtained was ≤7. Among clinical variables, only PSA correlated with concordance, showing an inverse relationship. CONCLUSION: The Gleason correlation values were not improved when 12 or more cores were collected. These values reached a plateau beyond that number of samples. Therefore, when determining treatment strategies, physicians must consider the biopsy scheme used since it has proven to be a predictor of the accuracy of the PC grading system.

West Nile virus emergence in humans in Extremadura, Spain 2020.

In Spain, the largest human West Nile virus (WNV) outbreak among humans was reported in 2020, constituting the second most important outbreak in Europe that season. Extremadura (southwestern Spain) was one of the affected areas, reporting six human cases. The first autochthonous human case in Spain was reported in Extremadura in 2004, and no other human cases were reported until 2020. In this work, we describe the first WNV human outbreak registered in Extremadura, focusing on the most important clinical aspects, diagnostic results, and control actions which followed. In 2020, from September to October, human WNV infections were diagnosed using a combination of molecular and serological methods (an in-house specific qRT-PCR and a commercial ELISA for anti-WNV IgM and IgG antibodies) and by analysing serum, urine, and/or cerebrospinal fluid samples. Serological positive serum samples were further tested using commercial kits against related flaviviruses Usutu and Tick-borne encephalitis in order to analyse serological reactivity and to confirm the results by neutralisation assays. In total, six cases of WNV infection (five with neuroinvasive disease and one with fever) were identified. Clinical presentation and laboratory findings are described. No viral RNA was detected in any of the analysed samples, but serological cross-reactivity was detected against the other tested flaviviruses. Molecular and serological methods for WNV detection in various samples as well as differential diagnosis are recommended. The largest number of human cases of WNV infection ever registered in Extremadura, Spain, occurred in 2020 in areas where circulation of WNV and other flaviviruses has been previously reported in humans and animals. Therefore, it is necessary to enhance surveillance not only for the early detection and implementation of response measures for WNV but also for other emerging flaviviruses that could be endemic in this area.

Using surveillance data to estimate pandemic vaccine effectiveness against laboratory confirmed influenza A(H1N1)2009 infection: two case-control studies, Spain, season 2009-2010.

BACKGROUND: Physicians of the Spanish Influenza Sentinel Surveillance System report and systematically swab patients attended to their practices for influenza-like illness (ILI). Within the surveillance system, some Spanish regions also participated in an observational study aiming at estimating influenza vaccine effectiveness (cycEVA study). During the season 2009-2010, we estimated pandemic influenza vaccine effectiveness using both the influenza surveillance data and the cycEVA study. METHODS: We conducted two case-control studies using the test-negative design, between weeks 48/2009 and 8/2010 of the pandemic season. The surveillance-based study included all swabbed patients in the sentinel surveillance system. The cycEVA study included swabbed patients from seven Spanish regions. Cases were laboratory-confirmed pandemic influenza A(H1N1)2009. Controls were ILI patients testing negative for any type of influenza. Variables collected in both studies included demographic data, vaccination status, laboratory results, chronic conditions, and pregnancy. Additionally, cycEVA questionnaire collected data on previous influenza vaccination, smoking, functional status, hospitalisations, visits to the general practitioners, and obesity. We used logistic regression to calculate adjusted odds ratios (OR), computing pandemic influenza vaccine effectiveness as (1-OR)*100. RESULTS: We included 331 cases and 995 controls in the surveillance-based study and 85 cases and 351 controls in the cycEVA study. We detected nine (2.7%) and two (2.4%) vaccine failures in the surveillance-based and cycEVA studies, respectively. Adjusting for variables collected in surveillance database and swabbing month, pandemic influenza vaccine effectiveness was 62% (95% confidence interval (CI): -5; 87). The cycEVA vaccine effectiveness was 64% (95%CI: -225; 96) when adjusting for common variables with the surveillance system and 75% (95%CI: -293; 98) adjusting for all variables collected. CONCLUSION: Point estimates of the pandemic influenza vaccine effectiveness suggested a protective effect of the pandemic vaccine against laboratory-confirmed influenza A(H1N1)2009 in the season 2009-2010. Both studies were limited by the low vaccine coverage and the late start of the vaccination campaign. Routine influenza surveillance provides reliable estimates and could be used for influenza vaccine effectiveness studies in future seasons taken into account the surveillance system limitations.

Three realizations and comparison of hardware for piezoresistive tactile sensors.

Tactile sensors are basically arrays of force sensors that are intended to emulate the skin in applications such as assistive robotics. Local electronics are usually implemented to reduce errors and interference caused by long wires. Realizations based on standard microcontrollers, Programmable Systems on Chip (PSoCs) and Field Programmable Gate Arrays (FPGAs) have been proposed by the authors for the case of piezoresistive tactile sensors. The solution employing FPGAs is especially relevant since their performance is closer to that of Application Specific Integrated Circuits (ASICs) than that of the other devices. This paper presents an implementation of such an idea for a specific sensor. For the purpose of comparison, the circuitry based on the other devices is also made for the same sensor. This paper discusses the implementation issues, provides details regarding the design of the hardware based on the three devices and compares them.

A large area tactile sensor patch based on commercial force sensors.

This paper reports the design of a tactile sensor patch to cover large areas of robots and machines that interact with human beings. Many devices have been proposed to meet such a demand. These realizations are mostly custom-built or developed in the lab. The sensor of this paper is implemented with commercial force sensors. This has the benefit of a more foreseeable response of the sensor if its behavior is understood as the aggregation of readings from all the individual force sensors in the array. A few reported large area tactile sensors are also based on commercial sensors. However, the one in this paper is the first of this kind based on the use of polymeric commercial force sensing resistors (FSR) as unit elements of the array or tactels, which results in a robust sensor. The paper discusses design issues related to some necessary modifications of the force sensor, its assembly in an array, and the signal conditioning. The patch has 16 × 9 force sensors mounted on a flexible printed circuit board with a spatial resolution of 18.5 mm. The force range of a tactel is 6 N and its sensitivity is 0.6 V/N. The array is read at a rate of 78 frames per second. Finally, two simple application examples are also carried out with the sensor mounted on the forearm of a rescue robot that communicates with the sensor through a CAN bus.