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The study of dose-response relationships underpins analytical biosciences. Droplet microfluidics platforms can automate the generation of microreactors encapsulating varying concentrations of an assay component, providing datasets across a large chemical space in a single experiment. A classical method consists in varying the flow rate of multiple solutions co-flowing into a single microchannel (producing different volume fractions) before encapsulating the contents into water-in-oil droplets. This process can be automated through controlling the pumping elements but lacks the ability to adapt to unpredictable experimental scenarios, often requiring constant human supervision. In this paper, we introduce an image-based, closed-loop control system for assessing and adjusting volume fractions, thereby generating unsupervised, uniform concentration gradients. We trained a shallow convolutional neural network to assess the position of the laminar flow interface between two co-flowing fluids and used this model to adjust flow rates in real-time. We apply the method to generate alginate microbeads in which HEK293FT cells could grow in three dimensions. The stiffnesses ranged from 50 Pa to close to 1 kPa in Young modulus and were encoded with a fluorescent marker. We trained deep learning models based on the YOLOv4 object detector to efficiently detect both microbeads and multicellular spheroids from high-content screening images. This allowed us to map relationships between hydrogel stiffness and multicellular spheroid growth.

ABSTRACTBackground: Artificial intelligence (AI) enables remote patient monitoring (RPM) which reduces costs by triaging patients to optimize hospitalization and avoid complications. The FDA regulates AI in medical devices and aims to ensure patient safety, effectiveness, and transparent AI solutions.Objectives: Identify and summarize FDA approved RPM devices to provide information for the US medical device industry based on previous approvals and the markets’ needs.Methods: We searched publicly available databases on FDA-approved RPM devices. Selection criteria were established to classify a solution as AI. Technical information was analyzed on pre-identified 16 parameters for the qualified solutions.Results: A total of 47 RPM devices were reviewed, among which 12.8% were classified as a De Novo product and the remaining devices fell under the 510(K) FDA category. The cardiovascular (74%) AI RPM solutions dominated the US market, followed by ECG-based arrhythmia detection algorithms (59.4%), and Hemodynamics and Vital Sign monitoring algorithms (21.9%). The trend observed in the FDA rejected devices was their inability to be classified into clinically relevant categories (Criteria 2 and 3).Conclusion: The market needs more innovative RPM solutions under the De Novo category, as there are very few. The transparency is low on the technical aspect of AI algorithms. The market needs AI algorithms that can effectively classify patients rather than merely improve device functionality.

An alarming rise in antimicrobial resistance worldwide has spurred efforts into the search for alternatives to antibiotic treatments. The use of bacteriophages, bacterial viruses harmless to humans, represents a promising approach with potential to treat bacterial infections (phage therapy). Recent advances in microscopy-based single-cell techniques have allowed researchers to develop new quantitative methodologies for assessing the interactions between bacteria and phages, especially the ability of phages to eradicate bacterial pathogen populations and to modulate growth of both commensal and pathogen populations. Here we combine droplet microfluidics with fluorescence time-lapse microscopy to characterize the growth and lysis dynamics of the bacterium Escherichia coli confined in droplets when challenged with phage. We investigated phages that promote lysis of infected E. coli cells, specifically, a phage species with DNA genome, T7 (Escherichia virus T7) and two phage species with RNA genomes, MS2 (Emesvirus zinderi) and Qβ (Qubevirus durum). Our microfluidic trapping device generated and immobilized picoliter-sized droplets, enabling stable imaging of bacterial growth and lysis in a temperature-controlled setup. Temporal information on bacterial population size was recorded for up to 25 h, allowing us to determine growth rates of bacterial populations and helping us uncover the extent and speed of phage infection. In the long-term, the development of novel microfluidic single-cell and population-level approaches will expedite research towards fundamental understanding of the genetic and molecular basis of rapid phage-induced lysis and eco-evolutionary aspects of bacteria-phage dynamics, and ultimately help identify key factors influencing the success of phage therapy.

Uncrewed aerial systems (UASs) are becoming very popular in the domain of water resource mapping and management (WRMM). Being a cheaper and quicker option capable of providing high temporal and spatial resolution data, UAS has become a much sought-after platform for remote sensing. Still, their application in the field is in its early stage. This paper encompasses basic concepts of UAS, different payloads and sensor technologies available, various methodologies for its application in WRMM, different software available, and challenges associated with them, thus presenting a comprehensive review of multiple applications of UAS in different sub-domains of water resources. From cryosphere, rivers and lakes, and coastal areas to sub-surface water, as well as from water quality to wastewater management, the authors have discussed various applications of uncrewed aerial vehicles. At the end of the paper, the authors have identified the issues posing problems in the wider implementation of UAS in WRMM. Also, the future scope of the UAS in WRMM has been discussed.

This research aimed to apply the geospatial techniques and Analytical Hierarchy Process (AHP) approach to find vulnerable areas in terms of flooding in the Neluwa area, Sri Lanka. The study incorporated nine relevant criteria for the vulnerability classification under three sub-criteria; the built environment, physical environment, and socio-economic environment. Under the built environment, road networks and buildings were chosen as sub-criteria. The Normalized Difference Vegetation Index (NDVI), slope, elevation, water bodies, and stream density were taken as physical criteria. Land use and population density were considered as socio-economic criteria. All the criteria are set correctly in raster data, and their contents were well adduced. The study consisted of the use of different levels of criteria and combinations of different processes. The analytical results reveal that 14.24% and 30.24% of the total area are at a very-high risk and high risk for flooding, respectively. Only 5.17% of the land was classified as a risk-free area. Eastern, central, and western divisions of the study area are highly vulnerable to floods due to their low slopes. Based on the produced maps, the spatial extents and levels of risk were systematically identified. Data obtained through qualitative judgments related to the field were validated based on the approach used. The potential of this approach is effective in assessing the spatial vulnerability of these flood-affected areas. Using such criteria and a model-based approach will be constructive in identifying different flood scenarios and in providing a remunerative guideline for potential anticipatory measures and better land-based planning in the area.

BackgroundLeprosy and cutaneous leishmaniasis (CL) are neglected tropical diseases (NTDs) affecting the skin. Their control is challenging but the integration of skin NTDs control programs is recommended to improve timely detection and treatment. However, little is known about the occurrence of leprosy and CL in the same individuals, and what are the characteristics of such patients. This study aimed to identify and characterize patients diagnosed with both leprosy and CL (i.e., outcome) in the hyperendemic state of Mato Grosso, Brazil. Also, we investigated the demographic risk factors associated with the period between the diagnosis of both diseases.Methodology/principal findingsA retrospective cohort study was conducted with patients diagnosed between 2008 and 2017. From the leprosy (n = 28,204) and CL (n = 24,771) databases of the national reporting system, 414 (0.8%; 414/52,561) patients presenting both diseases were identified through a probabilistic linkage procedure. This observed number was much higher than the number of patients that would be expected by chance alone (n = 22). The spatial distribution of patients presenting the outcome was concentrated in the North and Northeast mesoregions of the state. Through survival analysis, we detected that the probability of a patient developing both diseases increased over time from 0.2% in the first year to 1.0% within seven years. Further, using a Cox model we identified male sex (HR: 2.3; 95% CI: 1.7-2.9) and low schooling level (HR: 1.5; 95% CI: 1.2-1.9) as positively associated with the outcome. Furthermore, the hazard of developing the outcome was higher among individuals aged 40-55 years.Conclusions/significanceLeprosy and CL are affecting the same individuals in the area. Integration of control policies for both diseases will help to efficiently cover such patients. Measures should be focused on timely diagnosis by following-up patients diagnosed with CL, active case detection, and training of health professionals.

The present study intended to assess groundwater storage dynamics (GWS) and identify potential zones using the Multi-Criteria Decision Making (MCDM) method and geospatial technology in the Murshidabad district of West Bengal, India. The study district is located in the Ganga–Padma–Bhagirathi rivers’ floodplain and covers approximately a 5324 km2 area, comprising 26 blocks in five sub-divisions. The study portrayed a quantitative investigation of the pre-monsoon and post-monsoon season’s variability of GWS from 2000 to 2020, taking Landsat TM/Landsat 8 OLI/SRTM satellite data. The geo-spatio-temporal analysis of groundwater storage variability for 20 years was carried out by such remotely sensed data with the geospatial method to portray the dynamics and uncover the potential zones of GWS using various cartographic and statistical techniques. We determined nine parameters for the study, and the analytical hierarchy process (AHP) method was employed for the computation. The present estimation and assessment include the MCDM method, covering assorted parameters and the variations and aspects of GWS in the pre- and post-monsoon seasons from 2000 to 2020. The outcome illustrates that a decline in water storage has taken place in most of the blocks of Murshidabad district on average during the study period, which indicates a water stress provison in the near future. However, the micro (block)-level scenario of the spatiotemporal dynamics of GWS and the potential zonation in the Murshidabad District were investigated to form a location-specific micro-level arrangement for the sustainable management of water.

BackgroundLeprosy is a chronic bacterial infection caused by Mycobacterium leprae, which may lead to physical disability, stigma, and discrimination. The chronicity of the disease and disabilities are the prime contributors to the disease burden of leprosy. The current figures of the disease burden in the 2017 global burden of disease study, however, are considered to be under-estimated. In this study, we aimed to systematically review the literature and perform individual patient data meta-analysis to estimate new disability weights for leprosy, using Health-Related Quality of Life (HRQOL) data.Methodology/principal findingsThe search strategy included all major databases with no restriction on language, setting, study design, or year of publication. Studies on human populations that have been affected by leprosy and recorded the HRQOL with the Short form tool, were included. A consortium was formed with authors who could share the anonymous individual-level data of their study. Mean disability weight estimates, sorted by the grade of leprosy disability as defined by WHO, were estimated for individual participant data and pooled using multivariate random-effects meta-analysis. Eight out of 14 studies from the review were included in the meta-analysis due to the availability of individual-level data (667 individuals). The overall estimated disability weight for grade 2 disability was 0.26 (95%CI: 0.18-0.34). For grade 1 disability the estimated weight was 0.19 (95%CI: 0.13-0.26) and for grade 0 disability it was 0.13 (95%CI: 0.06-0.19). The revised disability weight for grade 2 leprosy disability is four times higher than the published GBD 2017 weights for leprosy and the grade 1 disability weight is nearly twenty times higher.Conclusions/significanceThe global burden of leprosy is grossly underestimated. Revision of the current disability weights and inclusion of disability caused in individuals with grade 0 leprosy disability will contribute towards a more precise estimation of the global burden of leprosy.

BackgroundThe Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence.MethodologyThe individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040.Principal findingsIn all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme.ConclusionsThe LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.

Summary: Background: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. Methods: The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. Findings: Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. Interpretation: Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established. Funding: Novartis Foundation.

Neglected tropical diseases characterized by skin lesions are highly endemic in the state of Mato Grosso, Brazil. We analyzed the spatial distribution of leprosy and Cutaneous Leishmaniasis (CL) and identified the degree of overlap in their distribution. All new cases of leprosy and CL reported between 2008 and 2017 through the national reporting system were included in the study. Scan statistics together with univariate Global and Local Moran’s I were employed to identify clusters and spatial autocorrelation for each disease, with the spatial correlation between leprosy and CL measured by bivariate Global and Local Moran’s I. Finally, we evaluated the demographic characteristics of the patients. The number of leprosy (N = 28,204) and CL (N = 24,771) cases in Mato Grosso and the highly smoothed detection coefficients indicated hyperendemicity and spatial distribution heterogeneity. Scan statistics demonstrated overlap of high-risk clusters for leprosy (RR = 2.0; P

India has the highest burden of leprosy in the world. Following a recent WHO guideline, the Indian National Leprosy Programme is introducing post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) in all high-endemic districts of the country. The aim of this study is to estimate the long-term cost-effectiveness of SDR-PEP in different leprosy disability burden situations. We used a stochastic individual-based model (SIMCOLEP) to simulate the leprosy new case detection rate trend and the impact of implementing contact screening and SDR-PEP from 2016 to 2040 (25 years) in the Union Territory of Dadra Nagar Haveli (DNH) in India. Effects of the intervention were expressed as disability adjusted life years (DALY) averted under three assumption of disability prevention: 1) all grade 1 disability (G1D) cases prevented; 2) G1D cases prevented in PB cases only; 3) no disability prevented. Costs were US$ 2.9 per contact. Costs and effects were discounted at 3%. The incremental cost per DALY averted by SDR-PEP was US$ 210, US$ 447, and US$ 5,673 in the 25th year under assumption 1, 2, and 3, respectively. If prevention of G1D was assumed, the probability of cost-effectiveness was 1.0 at the threshold of US$ 2,000, which is equivalent to the GDP per capita of India. The probability of cost-effectiveness was 0.6, if no disability prevention was assumed. The cost per new leprosy case averted was US$ 2,873. Contact listing, screening and the provision of SDR-PEP is a cost-effective strategy in leprosy control in both the short (5 years) and long term (25 years). The cost-effectiveness depends on the extent to which disability can be prevented. As the intervention becomes increasingly cost-effective in the long term, we recommend a long-term commitment for its implementation.

Studies on the assessment of land degradation, overland flow, soil loss, and nutrient loss have emerged as paramount importance for food security and rural livelihood in the mountains. The present study dealt with similar issues in the Eastern Himalayas, for which the primary data were collected from the field during 2017–18. Quantitative and qualitative methods were used to collect data on soil erosion and information on overland flow, soil loss, and nutrient loss was assessed through field experiments in the watershed of Sikkim, Eastern Himalayas. The first section of the methodology deals with the experimental analysis from different land use categories to quantify soil loss. In the second section, detailed qualitative analyses of farmers’ perceptions of soil erosion indicators were recorded through field surveys, i.e., key informant interviews (KEIs) and focus group discussions (FDGs). The results showed that the highest overland flow was in barren land (8.63%) followed by large cardamom-based agroforestry system (7.02%), and mixed cropping (4.84%), and the lowest overland flow was in terrace cultivation (4.69%). Soil loss was estimated to be the highest for barren land (7.73 Mg/ha/year (megagram/hectare/year)) followed by mixed cropping (4.32 Mg/ha/year), and terrace cultivation (3.75 Mg/ha/year), with the least soil loss estimated to be in cardamom-based agroforestry (3.23 Mg/ha/year). Loss of nitrogen (N) (4.49 kg/ha/year) and phosphorous (P) (2.43 kg/ha/year) were highest in barren land, while potassium (K) loss was highest (4.30 kg/ha/year) in mixed farming. The lowest N loss rate (3.34 kg/ha/year) was in terrace cultivation, the lowest P loss rate (8.19 kg/ha/year) was in mixed farming, and the lowest potassium loss rate (3.28 kg/ha/year) was in cardamom-based agroforestry. Approximately 33% of the farmers acknowledged light or no soil losses, while 17% of the farmers accepted moderate soil erosion. The results of field survey indicated that only 15–19% of the farmers reported high or extreme soil loss in the fields. Farmers in the watershed are practicing multiple measures to control land degradation; however, marginal farmers are still vulnerable and need strong support from the government to safeguard their land.

Abstract Background Indonesia ranking third in the world, regarding leprosy burden. Chemoprophylaxis is effective in reducing risk of developing leprosy among contacts. ‘Blanket approach’ is an operational strategy for leprosy post-exposure prophylaxis in which all members of an isolated community, high endemic for leprosy are screened and given a single dose of rifampicin (SDR) in the absence of signs and symptoms of leprosy. The objective is to assess the operational feasibility of a population-wide ‘blanket’ administration of SDR for leprosy prevention in isolated communities in a remote island. Methods A prospective follow-up study was conducted in the year 2014, 2015 and 2016 in Lingat village of Selaru Island, Indonesia. During the first two visits, screening and SDR were provided, whereas only screening was conducted during the third visit. The demographic and clinical data were used for a descriptive analysis of the project coverage and leprosy epidemiology. Results During the first two visits, 1671 persons (88%) were screened, 1499 (79%) received SDR, and 213 (11%) were excluded based on the exclusion criteria. During the first two visits, 43 (2.6%) cases were diagnosed with leprosy with a rate of 2263 per 100,000 population. The prevalence was highest in the age groups 15–24 and 25–49 years. Total, 14 (33%) cases had MB and 29 (67%) PB leprosy. Two cases (5%) had grade 2 disability. During the third visit, 10 new leprosy cases, with no grade 2 disability, were detected out of 1481 screened persons at the rate of 484 cases per 100,000 population (n = 2065 population in 2016). Among those screened during the third visit, there was a 50% reduction of leprosy among those who had previously received SDR compared to those who had not. Conclusion With adequate planning and some additional investment, it is feasible to implement a blanket approach of chemoprophylaxis in a remote island of Indonesia, although effort needs to be made to cover as many people as possible in the first visit. Contingency plans need to be made to actively follow this village closely in the coming years and continue leprosy elimination efforts until no new cases are found any more.

Aim: The aim of present study was to determine seroprevalence of bluetongue virus (BTV) in Haryana state of India. Materials and Methods: A total of 803 serum samples, 408 of cattle and 395 of buffalo origin, respectively, were collected from different villages of Haryana. Sampling was done randomly to obtain unbiased results. The samples were evaluated by a competitive enzyme-linked immunosorbent assay for the presence of BTV antibodies. Results: Overall seroprevalence of BTV antibody in cattle and buffaloes for all 21 districts of Haryana state was found to be 75.49% and 92.91%, respectively. The prevalence of BTV in different agroclimatic zones ranged between 72-77% and 90-94% for cattle and buffalo, respectively. In buffaloes, the BTV seroprevalence was comparatively higher than in cattle. Conclusion: The study showed that BTV is circulating in cattle and buffalo populations in the Northern part of India.

Background: Peripheral vascular disease of lower limbs is a debilitating condition with a significant proportion of patients having diffuse, long segment atherosclerosis. This study emphasizes the role of surgery in this group of patients. Materials and Methods: Eighty patients (95 legs) met the inclusion criteria for this study and were followed prospectively. Patients with Rutherford Class IV–VI were taken. Operative findings (type of operation, number of patches, total length of patches, etc.) were recorded. Subsequently, in postoperative period, they were evaluated for improvement in clinical (Rutherford) class, appearance of distal pulsations, ulcer healing, primary patency rates, freedom from amputation, and associated complications at 1, 3, 6, 12, 18, and 24 months. Results: Sustained clinical treatment efficacy according to Rutherford was 82% at 12 months and 59% at 24 months. Amputation-free survival rate was 86% at 12 months and 74% at 24 months. Until 24 months, 17 legs were amputated (18%) and 10 (10.5%) target limbs were revascularized through femoral embolectomy. At 2 years, cumulative femoral artery patency was 88%, whereas cumulative popliteal artery patency was 71%. Conclusion: The present series evaluated patients with the most advanced form of critical leg ischemia with a high rate of leg salvage with this procedure. Multiple atherectomy with patch plasty does offers hope to such patients and can become part of armamentarium of a vascular surgeon.

Leprosy is a major public health problem in many low and middle income countries, especially in India, and contributes considerably to the global burden of the disease. Leprosy and poverty are closely associated, and therefore the economic burden of leprosy is a concern. However, evidence on patient's expenditure is scarce. In this study, we estimate the expenditure in primary care (outpatient) by leprosy households in two different public health settings.We performed a cross-sectional study, comparing the Union Territory of Dadra and Nagar Haveli with the Umbergaon block of Valsad, Gujrat, India. A household (HH) survey was conducted between May and October, 2016. We calculated direct and indirect expenditure by zero inflated negative binomial and negative binomial regression. The sampled households were comparable on socioeconomic indicators. The mean direct expenditure was USD 6.5 (95% CI: 2.4-17.9) in Dadra and Nagar Haveli and USD 5.4 (95% CI: 3.8-7.9) per visit in Umbergaon. The mean indirect expenditure was USD 8.7 (95% CI: 7.2-10.6) in Dadra and Nagar Haveli and USD 12.4 (95% CI: 7.0-21.9) in Umbergaon. The age of the leprosy patients and type of health facilities were the major predictors of total expenditure on leprosy primary care. The higher the age, the higher the expenditure at both sites. The private facilities are more expensive than the government facilities at both sites. If the public health system is enhanced, government facilities are the first preference for patients.An enhanced public health system reduces the patient's expenditure and improves the health seeking behaviour. We recommend investing in health system strengthening to reduce the economic burden of leprosy.

Jackstone calculi are urinary tract stones that have a specific appearance resembling toy jacks. They are almost always composed of calcium oxalate dihydrate consist of a dense central core and radiating spicules. They are usually light brown with dark patches and are usually described to occur in the urinary bladder and rarely in the upper urinary tract. Their appearance on plain radiographs and computed tomography in human patients has been described.