Rapid and sensitive point-of-care detection of Leptospira by RPA-CRISPR/Cas12a targeting lipL32

Background One of the key barriers preventing rapid diagnosis of leptospirosis is the lack of available sensitive point-of-care testing. This study aimed to develop and validate a clustered regularly-interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 12a (CRISPR/Cas12a) platform combined with isothermal amplification to detect leptospires from extracted patient DNA samples. Methodology/Principal findings A Recombinase Polymerase Amplification (RPA)-CRISPR/Cas12a-fluorescence assay was designed to detect the lipL32 gene of pathogenic Leptospira spp. The assays demonstrated a limit of detection (LOD) of 100 cells/mL, with no cross-reactivity against several other acute febrile illnesses. The clinical performance of the assay was validated with DNA extracted from 110 clinical specimens and then compared to results from qPCR detection of Leptospira spp. The RPA-CRISPR/Cas12a assay showed 85.2% sensitivity, 100% specificity, and 92.7% accuracy. The sensitivity increased on days 4–6 after the fever onset and decreased after day 7. The specificity was consistent for several days after the onset of fever. The overall performance of the RPA-CRISPR/Cas12a platform was better than the commercial rapid diagnostic test (RDT). We also developed a lateral flow detection assay (LFDA) combined with RPA-CRISPR/Cas12a to make the test more accessible and easier to interpret. The combined LFDA showed a similar LOD of 100 cells/mL and could correctly distinguish between known positive and negative clinical samples in a pilot study. Conclusions/Significance The RPA-CRISPR/Cas12 targeting the lipL32 gene demonstrated acceptable sensitivity and excellent specificity for detection of leptospires. This assay might be an appropriate test for acute leptospirosis screening in limited-resource settings.

System on Chip (SoC) for Invisible Electrocardiography (ECG) Biometrics

Biometric identification systems are a fundamental building block of modern security. However, conventional biometric methods cannot easily cope with their intrinsic security liabilities, as they can be affected by environmental factors, can be easily “fooled” by artificial replicas, among other caveats. This has lead researchers to explore other modalities, in particular based on physiological signals. Electrocardiography (ECG) has seen a growing interest, and many ECG-enabled security identification devices have been proposed in recent years, as electrocardiography signals are, in particular, a very appealing solution for today’s demanding security systems—mainly due to the intrinsic aliveness detection advantages. These Electrocardiography (ECG)-enabled devices often need to meet small size, low throughput, and power constraints (e.g., battery-powered), thus needing to be both resource and energy-efficient. However, to date little attention has been given to the computational performance, in particular targeting the deployment with edge processing in limited resource devices. As such, this work proposes an implementation of an Artificial Intelligence (AI)-enabled ECG-based identification embedded system, composed of a RISC-V based System-on-a-Chip (SoC). A Binary Convolutional Neural Network (BCNN) was implemented in our SoC’s hardware accelerator that, when compared to a software implementation of a conventional, non-binarized, Convolutional Neural Network (CNN) version of our network, achieves a 176,270× speedup, arguably outperforming all the current state-of-the-art CNN-based ECG identification methods.

COVID-19 vaccine trials with children: ethics pointers

As healthcare authorities around the world strive to get as many citizens as possible vaccinated against the SAR-CoV-2 virus, many countries have begun including children in the population groups to be vaccinated. Properly designed clinical trials involving children are important to ensure safety, efficacy, and dosage of therapies in (developing) children. Within the complex health, social, and political scenario of the ongoing pandemic, ethics committees and policy makers in low-income and middle-income settings need to consider additional ethical questions when called on to review phase III COVID-19 vaccine trials involving in children. We set out some of the ethical questions to keep in mind before, during, and after the implementation of phase III COVID-19 vaccine trials in limited resource settings. Specifically, we discuss and offer succinct answers to the following questions: How relevant will the trial vaccine be for the population participating in the trial? Should vaccines that have not been approved for use among adults be approved for use in trials with children? Which children should be involved in COVID-19 vaccine trials? What criteria of informed consent are to be adopted with minors? Placebo versus an existing already approved vaccine? What specific duties of ancillary care should be taken into consideration for COVID-19 vaccines especially in low-income and middle-income countries? The answers we offer are considerations that can serve as ‘things to think about’ when reviewing or implementing COVID-19 trials involving children in low-income settings.

Logistics support planning model in the conditions of limited resources

Introduction/purpose: The paper presents a model of logistics support planning in the conditions of limited logistic resources based on the prioritization of customer requirements and resource allocation. Decisionmakers play a crucial role in the efficient and equitable allocation of resources as they prioritize among different user requirements. Methods: Requirement prioritization techniques that use nominal scale, ordinal scale, and ratio scale, and five methods for converting ranks into weighting coefficients have been applied to determine the degree of significance of user requirements. The Requirements triage method has been used for establishing relative priorities, while the heuristic algorithm determining the Kemeny median was used to consolidate individually ranked requests into a group rank. In order to balance opposing demands of users, consensus measures of group decision making were used. For obtaining an optimal planned solution of logistic support, the methods and techniques of resource allocation were applied. Results: A model for adaptive planning of logistics support in the conditions of limited resource capacities of the logistics system has been developed. Conclusion: The proposed model can be effectively applied in other areas of resource allocation.

Changes in the growth and reproduction of a clonal plant as a result of disruption of mycorrhizal network

In a clonal network, a mother plant is connected with daughter ramets. During network development, new ramets may encounter barriers that disrupt network integrity. As a result, resource allocation within a network is disturbed. In this study, the effect of network integrity disruption on the size of ramets and their sexual reproduction was investigated in mouse-ear hawkweed (Hieracium pilosella). Three types of networks were formed experimentally with unlimited resource allocation, with limited resource allocation between a mother plant and its daughter ramets and with limited resource allocation between all ramets. Networks were either supported by the presence of a mycorrhizal fungus or restricted by its absence. We found that the size of the mother and the effectiveness of sexual reproduction did not differ among network types. The length and dry mass of runners were higher in cases with limited resource exchange between a mother plant and its daughters. In the clonal plant network without any barriers to connection, a higher number of rosettes and lower dry mass of daughters were recorded. The mean number of daughter flowers did not differ among the network types. Mycorrhizal network is one of the most important factors for the sexual reproduction of clonal plants. With a reduced mycorrhizal network, plants invested in clonal growth.

Outcome of Locally Assembled Continous Positive Airway Pressure Device in Neonates with Respiratory Distress in Low Resource Setting

Respiratory distress is the most frequent cause of neonatal admission in neonatal intensive care unit (NICU). Continuous Positive Airway Pressure (CPAP) is an effective mode of treatment in newborn with respiratory distress. CPAP is the application of positive pressure to the airways of spontaneously breathing patient throughout the respiratory cycle. Low cost CPAP can be locally assembled and used in neonates with respiratory distress to reduce the mortality. This is a cross sectional descriptive study conducted in NICU of Nepal Medical College Teaching Hospital from the period of June 2021 to September 2021 to assess the outcome of locally assembled CPAP. A total of 96 newborns with respiratory distress were included in the study. Severity of respiratory distress was assessed by Downes score. Downes score before and after CPAP were recorded. Newborn with Downes score of ≥4 was started with locally assembled CPAP. Outcome was taken as improvement when the respiratory distress was decreased with Downes score<4. And it was taken as a failure when baby required mechanical ventilation. Mean Downes score before starting CPAP was 4.81 and after CPAP was 0.51. Mean CPAP pressure was 4.27cm of water. Outcome of study showed, 80 (83.3%) babies were improved, 7 (7.3%) had failed CPAP who required mechanical ventilation and 1 (1%) baby expired. In conclusion, locally assembled CPAP shown to be equally effective as standard CPAP device and can be used as an effective alternative to mechanical ventilator in developing country with limited resource setting.

Differences in running performance of single- and group-housed mice

Mice are one of several common animal models in neuroscience and mouse behavior is becoming increasingly relevant. Mice are housed either in groups or alone in standard cages during which they show a variety of different behaviors. Moreover, housing conditions might alter the behavior of the mice as do social interactions. When given access to running wheels as an environmental enrichment, mice tend to run long distances preferentially during their dark cycle. However, it is currently not well understood whether and how mice utilize running wheels when single-housed or group-housed. Here we developed a low-cost running wheel data acquisition system to study running in adult C57BL/6 mice at high temporal resolution under different social conditions. As expected, adult C57BL/6 mice prefer to run in stretches during the dark cycle and mostly rest during the light cycle. When single-housed, running bouts occur independent from each other as indicated by an exponential decaying autocorrelation. In contrast, mice run ~50% less when housed in groups of n = 3 and their temporal pattern of running exhibits a power law decay in the autocorrelation indicative of potential social interactions. Our results demonstrate that running wheels are a limited resource for which mice compete for when they are group-housed, thereby reducing their overall running activity.

Ultrasound-Guided Brachytherapy for Cervical Cancer - A Tool for Quality Improvement in Brachytherapy?

Nowadays, brachytherapy is one of the major components to treat inoperable cervical cancer. Brachytherapy yields a higher dose to the target (cervix) while sparing normal tissues. Developments of brachytherapy stepped forward in the previous decade by image-guided brachytherapy (IGBT) turning brachytherapy from point-based planning to volume-based planning and IGBT improves the treatment quality for cervical cancer. Magnetic resonance imaging (MRI) or computed tomography (CT) is utilized in brachytherapy and showed promising results internationally. However, in a limited-resource area, the implementation of IGABT is difficult due to many causes (manpower, equipment, or budgets). To improve the quality in limited resources, ultrasound is introduced. The utilization of ultrasound in brachytherapy practice is to prevent uterine perforation during application. With present data, measurement by ultrasound showed the correlation to MRI measurement in uterine dimensions. With these aspects, there are many researches using ultrasound to improve the quality of treatment in brachytherapy, for example, to guide contouring on CT or to support brachytherapy planning. The use of ultrasound improves the quality of brachytherapy in comparison to conventional planning and supports the improvement in brachytherapy for cervical cancer.