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Purpose World over, change of base year in the gross domestic product (GDP) is a standard practice of GDP estimation. However, unless a consistent series of GDP is released with respect to the new base for the earlier period, the existence of multiple growth rates creates problems for applied researchers, policymakers and the general public alike. Faced with such a menu of GDP series researchers often try to interpolate a consistent series of GDP. The main purpose of this paper is to analyses the nature of the data generating process of such multiple interpolated series of quarterly growth rates and tries to discern the consistency of such processes. Design/methodology/approach The present paper tries to look into the statistical implications and complications of such interpolated quarterly GDP/growth series in India in terms of three series of GDP, namely, with 1999–2000, 2004–2005 and 2011–2012 as its bases. Findings The analysis reveals that as a result of a change of base year, the nature of the data generating process of the old and new GDP series could undergo changes and experience different breakpoints. While all these conclusions seem to be valid for GDP growth at quarterly intervals, taking the data at annual frequency is less problematic. Practical implications The observation suggests that in most applied work, researchers may not have the luxury of only working with annual data and certain consistency checks will be necessary to check the veracity of the results based on quarterly data with those based on annual data. Second, moving forward it may be useful for the Authorities to make a transition to a chain-based linking method rather than fixed time-period-based bases as is currently done. Originality/value The analysis of Indian GDP in this paper is, perhaps, indicative of the fact that usage of quarterly GDP data is to be handled with caution and it is preferable that any serious empirical analysis uses annual GDP data whenever it is available/feasible. The comparison of GDP growth rates at different frequencies and examining the true nature of the process are quite unique in their contribution towards empirical macroeconomic research.

This paper analyzes the efficacy and skepticism surrounding the economic stimulus package announced by the Indian authorities in response to the Covid-19 pandemic in 2020. While the end of the pand...

Prior research demonstrated the potential for agricultural production systems to contribute to the environmental spread of antibiotic resistance genes (ARGs). However, there is a need for integrated assessment of critical management points for minimizing this potential. Shotgun metagenomic sequencing data were analysed to comprehensively compare total ARG profiles characteristic of amendments (manure or compost) derived from either beef or dairy cattle (with and without dosing antibiotics according to conventional practice), soil (loamy sand or silty clay loam) and vegetable (lettuce or radish) samples collected across studies carried out at laboratory-, microcosm- and greenhouse-scale. Vegetables carried the greatest diversity of ARGs (n = 838) as well as the most ARG-mobile genetic element co-occurrences (n = 945). Radishes grown in manure- or compost-amended soils harboured a higher relative abundance of total (0.91 and 0.91 ARGs/16S rRNA gene) and clinically relevant ARGs than vegetables from other experimental conditions (average: 0.36 ARGs/16S rRNA gene). Lettuce carried the highest relative abundance of pathogen gene markers among the metagenomes examined. Total ARG relative abundances were highest on vegetables grown in loamy sand receiving antibiotic-treated beef amendments. The findings emphasize that additional barriers, such as post-harvest processes, merit further study to minimize potential exposure to consumers. Published version

Antibiotics applied to soil through application of manure are of increasing concern due to their adverse environmental impacts, including their potential contribution to the development of antibiotic resistance in the environment. Two 90-d laboratory incubation studies were conducted to determine the effects of temperature (10 or 21 °C), pH (5, 7, 9), and soil texture (sandy loam, loam) on the persistence of two antibiotics (pirlimycin and cephapirin) applied to soils with dairy manure amendment. Dairy manure from treated and untreated cows was used as the source for this study. However, cephapirin was not detected in manure used for the study. Initial manure pH affected pirlimycin concentration of the manure, and there were differences in initial soil concentration between soil types. In the temperature experiment, pirlimycin concentration was significantly affected by temperature and soil type. In the 10 °C treatments, pirlimycin concentration initially decreased at 7 d but increased to levels similar to 0 d concentrations at 14 d, indicating possible deconjugation of pirlimycin ribonucleotide adducts in the manure applied. Although the loam soil type had a higher pirlimycin concentration in the temperature experiment at 0 d and 14 d, concentrations decreased below the sandy loam soil at 56 d and continued in the 90-d sampling period. Pirlimycin dissipation from dairy manure-amended soils was enhanced by higher temperature and finer soil texture, both of which could affect development of resistance genes if soil microbes are exposed to pirlimycin for longer periods of time.

We describe the use of pancreatic retrograde venous infusion in an orthotopic murine model of pancreatic ductal adenocarcinoma and hypothesize that pancreatic retrograde venous infusion delivery of gemcitabine will increase concentrations of gemcitabine in the tumor and the subsequent tumor response to treatment.Murine pancreatic ductal adenocarcinoma (KPC4580P) was transplanted onto the pancreatic tail of C57BL/6J mice. Groups (n = 15) of mice were assigned to sham laparotomy and 100 mg/kg intraperitoneal infusion of gemcitabine (systemic gemcitabine), pancreatic venous isolation with pancreatic retrograde venous infusion of 100 mg/kg gemcitabine, or pancreatic retrograde venous infusion with saline infusion. Tumor pressures were recorded during pancreatic retrograde venous infusion. Mice were killed at 1 hour or 7 days after infusion.Baseline tumor pressures were 45 ± 8 mm Hg, and pancreatic retrograde venous infusion increased tumor pressures by 29 ± 6 mm Hg (P.01). Pancreatic retrograde venous infusion gemcitabine mice had greater tumor gemcitabine concentrations compared with systemic gemcitabine (127 vs 19 ng/mg; P.01) and lesser tumor volumes compared with both systemic gem and pancreatic retrograde venous infusion with saline (274 vs 857 vs 629 mmPancreatic retrograde venous infusion increased tumor pressures greater than baseline, improved gemcitabine delivery, and increased the treatment response. These findings suggest that pressurized, regional delivery overcomes the increased pressure barrier in pancreatic ductal adenocarcinoma. Additional preclinical studies with cytotoxic and immunotherapeutic agents and clinical trials using pressure-enabled drug delivery with pancreatic retrograde venous infusion devices are underway.

Gastrointestinal stromal tumor (GIST), the most common sarcoma, is characterized by KIT protein overexpression, and tumors are frequently driven by oncogenic KIT mutations. Targeted inhibition of KIT revolutionized GIST therapy and ushered in the era of precision medicine for the treatment of solid malignancies. Here, we present the first use of a KIT-specific DNA aptamer for targeted labeling of GIST. We found that an anti-KIT DNA aptamer bound cells in a KIT-dependent manner and was highly specific for GIST cell labeling in vitro. Functionally, the KIT aptamer bound extracellular KIT in a manner similar to KIT mAb staining, and was trafficked intracellularly in vitro. The KIT aptamer bound dissociated primary human GIST cells in a mutation agnostic manner such that tumors with KIT and PDGFRA mutations were labeled. In addition, the KIT aptamer specifically labeled intact human GIST tissue ex vivo, as well as peritoneal xenografts in mice with high sensitivity. These results represent the first use of an aptamer-based method for targeted detection of GIST in vitro and in vivo.

In the context of the demonetization experiment of November 2016 in the Indian economy, this paper aims at looking into its impact on digital payments. Using the major digital payment modes and fol...

Although the link between the stock market and monetary policy is nebulous in the Indian context, it is perceived to be significant in popular perception. Towards explaining this disconnect, we probe the impact of Indian and US monetary policy announcements on disaggregated sectoral stock indices using the identification through heteroscedasticity approach. Our findings suggest differential impact of monetary policy on stocks across sectors. Illustratively, in terms of monetary policy surprises, the impact on the stocks of banking and financial services as well as the realty sector turns out to be significant. In contrast, sectors like media, metal, pharmaceuticals, information technology or fast moving consumer goods are found to be unresponsive. Interestingly, US unconventional monetary policy (quantitative easing) measures are found to have an impact on fast moving consumer goods and the media sector. These findings are attributed to: (1) dominance of the bank lending channel; (2) predominance of public sector vis-a-vis private banks; (3) significant influence of monetary policy on demand for housing and automobiles; (4) relative ineffectiveness of the asset-price channel of monetary transmission; and (5) sector-specific affects arising out of financial liberalisation.

The binding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein to the Angiotensin-Converting Enzyme 2 (ACE2) receptor expressed on the host cells is a critical initial step for viral infection. This interaction is blocked through competitive inhibition by soluble ACE2 protein. Therefore, developing high-affinity and cost-effective ACE2 peptidomimetic ligands that disrupt this protein-protein interaction is a promising strategy for viral diagnostics and therapy. We employed human and plant defensins, a class of small and highly stable proteins, and engineered the amino acid residues on its conformationally constrained alpha-helices to mimic the critical residues on the ACE2 helix 1 that interacts with the Spike-protein. The engineered proteins were soluble and purified to homogeneity with high yield from a bacterial expression system. The proteins demonstrated exceptional thermostability, high-affinity binding to the Spike protein with dissociation constants in the low nanomolar range, and were used in a diagnostic assay that detected SARS-CoV-2 neutralizing antibodies. This work addresses the challenge of developing helical peptidomimetics by demonstrating that defensins provide promising scaffolds to engineer alpha-helices in a constrained form for designing high-affinity ligands.Broad audience statementThe engineered proteins developed in this study are cost-effective and highly stable reagents for SARS-CoV-2 detection. These features may allow large-scale and cost-effective production of diagnostic tests to assist COVID-19 diagnostic and prevention.

Introduction Antimicrobial resistance (AMR) is a global health issue to humans and livestock (1). To mitigate AMR risks, responsible use of antimicrobials in livestock production systems have been advocated (1). Studies have demonstrated the patterns of antimicrobial use (AMU) in livestock production systems; however, there is limited information on the drivers of AMU. For successful antimicrobial stewardship (AMS), identifying the psychological (knowledge and attitude) and contextual drivers (environmental factors, economic status, and resource accessibility) for intervention is a crucial first step in the agri-food value chain. The theory of planned behaviour (TPB) has been used to understand behaviour influenced by a person’s intention, attitude, and knowledge; therefore, evaluating behaviour allows understanding of drivers that affect and shape the farmers’ intention and decisions (2). Aim To explore and understand the attitude and knowledge of Fijian livestock farmers on AMU and AMR. Methods Face to face one-to-one semi-structured qualitative interviews were conducted between September and November 2019 with Fijian livestock farmers and managers located in the Central and Western divisions of Viti Levu, Fiji. A sample of at least 20 participants from the cattle and poultry production systems was targeted and recruited using purposive and snowball sampling methods. TPB informed the development of the semi-structured interview guide. The interviews were audio-recorded and analysed inductively using Braun and Clarke’s reflexive thematic analysis and deductively using the TPB framework (results reported elsewhere). An interpretative approach underpinned the design and conduct of this study. Results Nineteen livestock farmers and managers took part in interviews. Our analysis generated four themes: 1) Uninformed use of antimicrobials and unaware of AMR, 2) Safeguarding livestock and generating income source as primary motivators for using medicine, 3) Medicine shortage resulting in hoarding and self-prescribing, and 4) Foreign farmers and veterinarians trusted over Fijian veterinarian and para-veterinarian knowledge. Livestock farmers did not differentiate amongst different types of medicine, including antimicrobials. Therefore, antimicrobials were unwittingly used and without an awareness of the risks of AMR. Medicines, including antimicrobials, were used to protect livestock and promote production for food and financial security. Farmers hoarded medicines and self-prescribed them on the farms. Farmers lacked confidence in the advice on livestock management, and medicine use, provided by Fijian veterinarians and para-veterinarians. They sought help online and from foreign farmers and veterinarians. No participant sought advice from pharmacists who are experts in medicine. Conclusion This study uncovered the first documented accounts of Fijian livestock farmers’ attitude and knowledge on AMU and AMR. AMS programmes promoting awareness and rational use of antimicrobials and resistance in Fijian livestock production is recommended. These programmes need to consider the social, economic, and environmental factors driving irrational medicine use by farmers. We acknowledge the views shared by participants may not be representative of all farmers in Fiji; however, we believe all participants provided in-depth insight into the current drivers of AMU. Future studies exploring the attitude and knowledge of Fijian veterinarians, para-veterinarians and pharmacists on AMU and AMR in livestock production can inform the design of AMS programmes that currently do not exist. References (1) WHO. Antimicrobial Resistance Geneva Switzerland: World Health Organization; 2021 [cited 2021 1 September]. Available from: http://www.who.int/en/news-room/fact-sheets/detail/antimicrobial-resistance. (2) Ajzen I. The theory of planned behaviour. Organizational Behaviour and Human Decision Processes. 1991;50(2):179-211.

We present supplementary data for the published article, “Hitting the diagnostic sweet spot: Point-of-care SARS-CoV-2 salivary antigen testing with an off-the-shelf glucometer” [1]. The assay described is designed to be performed at home or in a clinic without expensive instrumentation or professional training. SARS-CoV-2 is detected by an aptamer-based assay that targets the Nucleocapsid (N) or Spike (S) antigens. Binding of the N or S protein to their respective aptamer results in the competitive release of a complementary antisense-invertase enzyme complex. The released enzyme then catalyzes the conversion of sucrose to glucose that is measured by an off-the-shelf glucometer. The data presented here describe the optimization of the assay parameters and their contribution to developing this aptamer-based assay to detect SARS-CoV-2. The assay performance was checked in a standard buffer, contrived samples, and patient samples validated with well-established scientific methods. The resulting dataset can be used to further develop glucometer-based assays for diagnosing other communicable and non-communicable diseases.

This study investigated the effect of seaweed supplementation in dairy cow diets on milk yield, basic composition, and mineral concentrations. Thirty-seven Icelandic cows were split into three diet treatments: control (CON, no seaweed), low seaweed (LSW, 0.75% concentrate dry matter (DM), 13–40 g/cow/day), and high seaweed (HSW, 1.5% concentrate DM, 26–158 g/cow/day). Cows were fed the same basal diet of grass silage and concentrate for a week, and then were introduced to the assigned experimental diets for 6 weeks. The seaweed mix of 91% Ascophyllum nodosum: 9% Laminaria digitata (DM basis), feed, and milk samples were collected weekly. Data were analyzed using a linear mixed effects model, with diet, week, and their interaction as fixed factors, cow ID as random factor, and the pre-treatment week data as a covariate. When compared with CON milk, LSW and HSW milk had, respectively, less Se (−1.4 and −3.1 μg/kg milk) and more I (+744 and +1649 μg/kg milk), while HSW milk also had less Cu (−11.6 μg/kg milk) and more As (+0.17 μg/kg milk) than CON milk. The minimal changes or concentrations in milk for Se, Cu, and As cannot be associated with any effects on consumer nutrition, but care should be taken when I-rich seaweed is fed to cows to avoid excessive animal I supply and milk I concentrations.

An integrated understanding of factors influencing the occurrence, distribution, and fate of antibiotic resistance genes (ARGs) in vegetable production systems is needed to inform the design and development of strategies for mitigating the potential for antibiotic resistance propagation in the food chain. The goal of the present study was to holistically track antibiotic resistance and associated microbiomes at three distinct pre-harvest control points in an agroecosystem in order to identify the potential impacts of key agricultural management strategies. Samples were collected over the course of a single growing season (67 days) from field-scale plots amended with various organic and inorganic amendments at agronomic rates. Dairy-derived manure and compost amendment samples (n = 14), soil samples (n = 27), and lettuce samples (n = 12) were analyzed via shotgun metagenomics to assess multiple pre-harvest factors as hypothetical control points that shape lettuce resistomes. Pre-harvest factors of interest included manure collection during/post antibiotic use, manure composting, and soil amended with organic (stockpiled manure/compost) versus chemical fertilizer. Microbial community resistome and taxonomic compositions were unique from amendment to soil to lettuce surface according to dissimilarity analysis. The highest resistome alpha diversity (i.e., unique ARGs, n = 642) was detected in amendment samples prior to soil application, while the composted manure had the lowest total ARG relative abundance (i.e., 16S rRNA gene-normalized). Regardless of amendment type, soils acted as an apparent ecological buffer, i.e., soil resistome and taxonomic profiles returned to background conditions 67 d-post amendment application. Effects of amendment conditions surprisingly re-emerged in lettuce phyllosphere resistomes, with the highest total ARG relative abundances recovered on the surface of lettuce plants grown in organically-fertilized soils (i.e., compost- and manure-amended soils). Co-occurrence analysis identified 55 unique ARGs found both in the soil amendments and on lettuce surfaces. Among these, arnA and pmrF were the most abundant ARGs co-occurring with mobile genetic elements (MGE). Other prominent ARG-MGE co-occurrences throughout this pre-harvest lettuce production chain included: TetM to transposon (Clostridiodies difficile) in the manure amendment and TriC to plasmid (Ralstonia solanacearum) on the lettuce surfaces. This suggests that, even with imposing manure management and post-amendment wait periods in agricultural systems, ARGs originating from manure can still be found on crop surfaces. This study demonstrates a comprehensive approach to identifying key control points for the propagation of ARGs in vegetable production systems, identifying potential ARG-MGE combinations that could inform future surveillance. The findings suggest that additional pre-harvest and potentially post-harvest interventions may be warranted to minimize risk of propagating antibiotic resistance in the food chain.

Amplified Fragment Length polymorphism (AFLP) was studied involving 48 diverse rice genotypes, comprising of indica, japonica, and Tongil type (indica × japonica) varieties to assess the genetic diversity. Initially 64 primer pair combinations were screened of which 5 were found to be suitable producing clear fragments (35–500 bp). In total 700 amplicons (bands) were produced with an average of 140 bands per primer pair. Maximum (207) from EcoRI AC*/MseI-CAC and minimum (75) amplicons from EcoRI TG*/MseI-CTT primer pairs were observed. Minimum (0.973) and maximum (0.990) PIC values recorded for primer pair EcoRI AC*/MseI-CAC and EcoRI AC*/MseI-CAT, respectively. Pairwise genetic similarity estimates ranged in between 0.6412 and 0.943 with a mean of 0.797. Triguna, an indica high yielding variety (HYV), and a new plant type (NPT) rice, IR 7946-46-1-3-2 having indica x japonica parentage showed minimum genetic similarity coefficient (0.641) with maximum genetic divergence, whereas ADT 41 and Sasyasree, two indica HYVs displayed maximum genetic similarity coefficient—0.953 with lowest genetic distance. All accessions could be clearly identified by using five primer pairs, offers immense scope of AFLP in assessing genetic diversity in rice. The present study also identified prospective varieties for use in selective hybridization and productive progeny selection. Most of the varieties shared distinct clusters based on varietal types, race, parentage and growing area where those are cultivated traditionally albeit with a few exceptions. The dendrogram could demarcate the varieties irrespective of race with unique traits, albeit with exceptions, which warrants further experimentation involving more number of primers in future.

We study the impact of electronic trading in India via two distinct approaches. First, in a more traditional way, we model the data generating process (DGP) of share price index for different tradi...

Microbial communities drive soil ecosystem function but are also susceptible to environmental disturbances. We investigated whether exposure to manure sourced from cattle either administered or not administered antibiotics affected microbially mediated terrestrial ecosystem function. We quantified changes in microbial community composition via amplicon sequencing, and terrestrial elemental cycling via a stable isotope pulse-chase. Exposure to manure from antibiotic-treated cattle caused: (i) changes in microbial community structure; and (ii) alterations in elemental cycling throughout the terrestrial system. This exposure caused changes in fungal : bacterial ratios, as well as changes in bacterial community structure. Additionally, exposure to manure from cattle treated with pirlimycin resulted in an approximate two-fold increase in ecosystem respiration of recently fixed-carbon, and a greater proportion of recently added nitrogen in plant and soil pools compared to the control manure. Manure from antibiotic-treated cattle therefore affects terrestrial ecosystem function via the soil microbiome, causing decreased ecosystem carbon use efficiency, and altered nitrogen cycling.

This article tests for price and volatility linkages between Indian global depositary receipts (GDRs) traded in Luxembourg/London and their underlying shares traded in Mumbai. The relationship is studied between the GDR price and the domestic share price along with the appropriate exchange rates, the foreign stock index and the domestic stock index using the vector autoregression (VAR) and dynamic conditional correlation (DCC) specification of multivariate generalised autoregressive conditional heteroscedasticity (GARCH) models. VAR results indicate a similarity between the two prices of scrips: one trading in Mumbai and the other trading in Luxembourg (London). Further, DCC-GARCH model outcomes point to, by and large, a high-dynamic correlation between Indian GDRs traded in Luxembourg/London and their underlying stocks listed in Mumbai. Thus, the price and volatility linkages between the Indian stock and its European counterpart are invariant with respect to the choice of the foreign stock exchange. Such a similarity in findings, notwithstanding the difference in degree of information disclosure as well as listing requirements at London and Luxembourg, is perhaps indicative of the stock-exchange-invariant nature of law of one price. JEL Classification: G15, C22

External commercial borrowing (ECB) has assumed growing prominence in the Indian economy. This paper analyzes the trends and determinants of ECB flows to India using monthly data for the period 2004M1 to 2015M12. Employing the Johansen cointegration and error correction techniques, our analysis suggests that both domestic factors and global economic conditions have influenced India’s ECB inflows. Regulatory changes in the capital account were found to have the greatest effect on ECB flows among variables considered. While the long-term trend has been toward greater openness, the regulatory authorities have also intervened with an eye to macroeconomic and exchange rate stabilization resulting in sometimes unwitting changes in the composition of capital flows. Other factors found to be significant are the rupee to US dollar exchange rate, the economic growth differential between India and the OECD, the interest rate differential between the domestic lending rate and LIBOR, international credit conditions, and India’s sovereign credit risk rating. Structural break analysis suggests that the global financial crisis of 2008 reduced ECB inflows significantly. Given the impact of changing capital account regulation on the volatility of ECB flows, we recommend simplifying and consolidating India’s regulatory framework without compromising the macro-prudential principles of capital account management.

Now a days the smart device put a huge impact on medical field rapidly. In 20st century everyone concerns about their health to fight with this pandemic. A smart medical ring has been discovered to ensure proper treatment of some health issues. There are so many devices available in the wearable technology market like smart watch, smart mask etc. This device will help to measure the temperature, oxygen level andpulse rate all together. Objective of this project is to combine the features of thermometer and pulse oximeter into a single device with a reducible size compare to other available devices so that anyone can use this device in any place at any time and also can wear the ring in his/her finger. Here two sensors are implemented to measure these three different parameters. The thermometer and the pulse oximeter are most required measuring tools in our daily life to check the common health parameters. That’s why this smart medical ring has been discovered by the researchers to help the common people and medical field.

Antibiotic resistance in urinary tract infections is a major global challenge and improved cost-effective and high throughput antibiotic susceptibility tests (AST) are urgently needed to inform correct antibiotic selection. We evaluated a high throughput microfluidic test strip for AST and minimum inhibitory concentration (MIC) determination in 20 urinary pathogenic E. coli (UPEC) isolates using six commonly prescribed or therapeutically beneficial antibiotics. The microfluidic MIC performs broth microdilution in 1 microliter volume capillaries, 100 X smaller than standard broth microdilution. Each test strip contains 10 parallel capillaries which are dipped into a single well of a 96 well plate, significantly increasing throughput over a microtitre plate. When tested with clinical UPEC isolates at standardised inoculum density, these devices gave 100% essential agreement (+/- 1 doubling dilution of antibiotic) to the gold standard microplate broth microdilution method described by CLSI. Although for some antibiotic/isolate combinations an earlier endpoint readout reduced accuracy, MIC test strips read at a 6h endpoint still gave 69 – 100 % essential agreement depending on the antibiotic. Growth could be detected significantly earlier than 6h, but with a trade-off between speed vs accuracy. These high-throughput, multiplexed test strips could be used to increase throughput and give faster results than microplates while retaining the core broth microdilution methodology of gold standard techniques for AST and MIC determination.

An electrochemical sensor based on a conformation-changing aptamer is reported to detect soluble KIT, a cancer biomarker, in human serum. The sensor was fabricated with a ferrocene-labeled aptamer (Kd < 5 nM) conjugated to a gold electrode. Quantitative KIT detection was achieved using electrochemical impedance spectroscopy (EIS) and square-wave voltammetry (SWV). EIS was used to optimize experimental parameters such as the aptamer-to-spacer ratio, aptamer immobilization time, pH, and KIT incubation time, and the sensor surface was characterized using voltammetry. The assay specificity was demonstrated using interfering species and exhibited high specificity toward the target protein. The aptasensor showed a wide dynamic range, 10 pg/mL-100 ng/mL in buffer, with a 1.15 pg/mL limit of detection. The sensor also has a linear response to KIT spiked in human serum and successfully detected KIT in cancer-cell-conditioned media. The proposed aptasensor has applications as a continuous or intermittent approach for cancer therapy monitoring and diagnostics (theranostics).

Significant barriers to the diagnosis of latent and acute SARS-CoV-2 infection continue to hamper population-based screening efforts required to contain the COVID-19 pandemic in the absence of effective antiviral therapeutics or vaccines. We report an aptamer-based SARS-CoV-2 salivary antigen assay employing only low-cost reagents ($3.20/test) and an off-the-shelf glucometer. The test was engineered around a glucometer as it is quantitative, easy to use, and the most prevalent piece of diagnostic equipment globally making the test highly scalable with an infrastructure that is already in place. Furthermore, many glucometers connect to smartphones providing an opportunity to integrate with contract tracing apps, medical providers, and electronic medical records. In clinical testing, the developed assay detected SARS-CoV-2 infection in patient saliva across a range of viral loads - as benchmarked by RT-qPCR - within one hour, with 100% sensitivity (positive percent agreement) and distinguished infected specimens from off-target antigens in uninfected controls with 100% specificity (negative percent agreement). We propose that this approach can provide an inexpensive, rapid, and accurate diagnostic for distributed screening of SARS-CoV-2 infection at scale.

Background Research is needed to delineate the relative and combined effects of different antibiotic administration and manure management practices in either amplifying or attenuating the potential for antibiotic resistance to spread. Here, we carried out a comprehensive parallel examination of the effects of small-scale (> 55 °C × 3 days) static and turned composting of manures from dairy and beef cattle collected during standard antibiotic administration (cephapirin/pirlimycin or sulfamethazine/chlortetracycline/tylosin, respectively), versus from untreated cattle, on “resistomes” (total antibiotic resistance genes (ARGs) determined via shotgun metagenomic sequencing), bacterial microbiota, and indicator ARGs enumerated via quantitative polymerase chain reaction. To gain insight into the role of the thermophilic phase, compost was also externally heated to > 55 °C × 15 days. Results Progression of composting with time and succession of the corresponding bacterial microbiota was the overarching driver of the resistome composition (ANOSIM; R = 0.424, p = 0.001, respectively) in all composts at the small-scale. Reduction in relative abundance (16S rRNA gene normalized) of total ARGs in finished compost (day 42) versus day 0 was noted across all conditions (ANOSIM; R = 0.728, p = 0.001), except when externally heated. Sul1, intI1, beta-lactam ARGs, and plasmid-associated genes increased in all finished composts as compared with the initial condition. External heating more effectively reduced certain clinically relevant ARGs (blaOXA, blaCARB), fecal coliforms, and resistome risk scores, which take into account putative pathogen annotations. When manure was collected during antibiotic administration, taxonomic composition of the compost was distinct according to nonmetric multidimensional analysis and tet(W) decayed faster in the dairy manure with antibiotic condition and slower in the beef manure with antibiotic condition. Conclusions This comprehensive, integrated study revealed that composting had a dominant effect on corresponding resistome composition, while little difference was noted as a function of collecting manure during antibiotic administration. Reduction in total ARGs, tet(W), and resistome risk suggested that composting reduced some potential for antibiotic resistance to spread, but the increase and persistence of other indicators of antibiotic resistance were concerning. Results indicate that composting guidelines intended for pathogen reduction do not necessarily provide a comprehensive barrier to ARGs or their mobility prior to land application and additional mitigation measures should be considered.

Additional file 1.

CONTEXT\ud Identifying the determinants of phosphorus (P) balance and use efficiency (PUE) is critical to improving the sustainability of dairy farming in countries operating diverse dairy farming systems because each system contributes to eutrophication through different pathways. However, information about P balance and PUE across diverse dairy farming systems is scarce.\ud \ud OBJECTIVE\ud The current study aimed to use a novel approach to determine P balance and PUE, and identify their key determinants across diverse dairy farming systems in GB.\ud \ud METHODS\ud Data from 29 dairy farms representing systems with differing feeding approaches and production levels was collected from farm records or generated by quantifying P concentration in feed, manure, and soil samples. The methodology of the nutrient management tool ‘Planning for Land Application of Nutrients for Efficiency and the environmenT (PLANET) and the principles of ‘Annual Nutrient Cycling Assessment’ (ANCA) were used to calculate farm-gate P balance (FPB) and soil-surface P balance (SPB), respectively. Differences in P balance and PUE between dairy farming systems were investigated using ANOVA. Determinants of P balance and PUE were identified using multiple stepwise linear regressions.\ud \ud RESULTS AND CONCLUSIONS\ud The current study demonstrated a novel approach of calculating FPB and SPB that captures differences in the P concentration of manure and milk between systems.\ud \ud Phosphorus surplus was higher and PUE was lower in housed systems compared to pasture-based systems (except for a Spring-calving system grazing ≥274 days/year) primarily because of greater import of concentrate feed, highlighting the importance of reducing concentrate feed import into housed systems to minimise P import. Farms with greater inclusion rate of home-grown feed (primarily forages) in their herds' diet had higher PUE and lower P surplus. Thus, pasture-based systems could improve PUE by increasing the inclusion rate of home-grown feeds in the herd diet only if they maintain a stocking rate that matches the feed demand of the herd to the availability of home-grown feeds. In conclusion, the assessment of PUE and strategies to improve it should consider system classification beyond strict housed and pasture-based systems.\ud \ud SIGNIFICANCE\ud The current study demonstrated the foundations of an approach to calculate FPB and SPB that could be more robust compared to using standard P coefficients particularly in countries that operate diverse dairy farming systems. With further development, this approach could be adopted and could change the way GB dairy farmers and advisers calculate P balances in diverse systems.

A conformational changing aptamer based electrochemical sensor was developed for the detection of soluble KIT, a cancer biomarker, in human serum. The sensor was fabricated with a ferrocene labeled aptamer (Kd < 5 nM) conjugated to a gold electrode. Quantitative KIT detection was performed using electrochemical impedance spectroscopy (EIS) and square wave voltammetry (SWV). The experimental parameters such as the ratio of aptamer to spacer, aptamer immobilization time, pH, and KIT incubation time were optimized by EIS, and the sensing surface was characterized with voltammetry. The assay specificity was investigated using interfering species showing high specificity towards the target protein. The aptasensor exhibited a wide dynamic range from 10 pg/mL to 100 ng/mL in buffer with a detection limit of 1.15 pg/mL. The sensor also exhibited a linear response with increased KIT concentrations spiked in human serum. The applicability of the sensor was successfully demonstrated using cancer cell conditioned media. The proposed aptasensor can be used in continuous or intermittent approach for cancer therapy monitoring and diagnostics (theranostics).

Minimising phosphorus (P) feeding to dairy cows can reduce feed costs and minimise water pollution without impairing animal performance. This study aimed to determine current P feeding practices and identify the barriers to and motivators for minimising P feeding on dairy farms, using Great Britain (GB) dairy farming as an example of diverse systems. Farmers (n=139) and feed advisers (n=31) were involved simultaneously in independent questionnaire surveys on P feeding in dairy farms. Data on the herd size, milk yield and concentrate fed were analysed using Analysis of Variance (ANOVA) to investigate the effect of farm classification, region, and feed professional advice. Chi-square tests were used to investigate associations between farm characteristics and implemented P feeding and management practices. Most farmers (72%) did not know the P concentration in their lactating cow’s diet and did not commonly adopt precision P feeding practices, indicating that cows might have been offered dietary P in excess of recommended P requirement. Farmers’ tendency to feed P in excess of recommendations increased with herd size, but so did their awareness of P pollution issues and likeliness of testing manure P. However, 68% of farmers did not analyse manure P, indicating that mineral P fertiliser application rates were not adjusted accordingly, highlighting the risk of P being applied beyond crops’ requirement. Almost all farmers (96%) were willing to lower dietary P concentration but the uncertainty of P availability in feed ingredients (30%) and concerns over reduced cow fertility (22%) were primary barriers. The willingness to reduce dietary P concentrations was driven by the prospect of reducing environmental damage (28%) and feed costs (27%) and advice from their feed professionals (25%). Most farmers (70%) relied on a feed professional, and these farmers had a higher tendency to analyse their forage P. However, farmers of pasture-based systems relied less on feed professionals. Both farmers (73%) and feed advisers (68%) were unsatisfied with the amount of training on P management available. Therefore, the training on P management needs to be more available and the influence that feed professionals have over P feeding should be better utilized. Study findings demonstrate the importance of considering type of dairy farming systems when developing precision P feeding strategies and highlight the increasing importance of feed professionals in minimising P feeding.

This paper provides a narrative of Indian monetary policy since the North Atlantic Financial Crisis (NAFC) in the mid‐2008 till the current period. The period 2009–2013 was dominated by the joint monetary and fiscal stimuli of the Indian authorities prompted by the NAFC. These, along with some structural shocks and a hands‐off attitude in forex market intervention, could have had their role in rising inflation and external account instability (leading up to the taper tantrum episode). In such a backdrop, after considerable discussion during 2013–2014, a Monetary Policy Framework Agreement was signed between the Government of India and the Reserve Bank of India on February 20, 2015 that formally adopted flexible inflation targeting (IT) in India. While the IT regime so far has coincided with significant reduction in inflation in India, the atmosphere has been benign. Now that fuel prices have started moving in the north‐east direction, the government has proposed a revised framework for the minimum support price in the Union Budget for 2018–2019 and fiscal slippages have started happening, it remains to be seen whether IT can wither more rough weather in the days to come. Finally, in recent years, Indian monetary policy has been dominated by two significant events: the emergence of significant deterioration of Indian public sector balance sheets, and the demonetization episode in November 2016. Monetary policy in both of these periods wrestled with fashioning an appropriate strategy for managing the impossible trinity.

The objective of the study was to evaluate the effect of inorganic phosphorus (Pi) infusion on P absorption in large intestine, milk production, and phosphorus excretion. Four ruminally and ileally cannulated crossbred cows were used in a 4 × 4 Latin square with 21-d periods. Cows were fed a total mixed ration containing 0.21% P, providing 50% of the cows' P requirement. Cobalt-EDTA was used as marker to measure large intestine digesta flow. On d 13 to 21 of each period, each cow was infused daily with 0, 20.1, 40.2, or 60.3 g of Pi into the abomasum and total collection was conducted on d 18 to 21. Ileal samples were collected every 9 h on d 18 to 21. Feed, digesta, and fecal samples were analyzed for total P and Pi using the molybdovanadate yellow method and blue method, respectively. All data were analyzed using PROC GLIMMIX in SAS 9.3 (SAS Institute Inc., Cary, NC) using contrasts to evaluate linear, quadratic, and cubic effects of Pi infusion dose. Dry matter intake, apparent dry matter digestibility, milk yield, and milk total P were unaffected by Pi infusion. Ileal flow and fecal excretion of total P and Pi increased linearly with increasing infused Pi. In the large intestine, net absorption of TP and Pi was increased linearly with increasing infused Pi. The magnitude of absorption from the large intestine was greater than reflected in current models, raising questions that could be evaluated with longer infusion periods or dietary alteration.

Context: Anatomical and visual outcomes of phacoemulsification and 23-gauge (23G) pars plana vitrectomy (PPV) assisted with perfluorocarbon liquid (PFCL) and 27-gauge twin-chandelier endoillumination for primary rhegmatogenous retinal detachment (RRD). Aims: This study aims to determine the anatomical and visual outcomes of phacoemulsification and 23G PPV for primary RRD assisted with 27-gauge (27G) transconjunctival twin-chandelier endoillumination and bimanual vitreous base shaving under PFCL. Settings and Design: A prospective single tertiary center cohort study of 65 consecutive eyes by a single surgeon between August 2013 and June 2014. Subjects and Methods: The primary outcome measure was the primary retinal reattachment rate. The secondary outcome measure was best-corrected visual acuity (BCVA). All patients were reviewed postoperatively up to 4 months. Statistical Analysis Used: Chi-squared, Student's t-test, and one-way ANOVA test were used in this study. Results: At 4 months, overall retinal reattachment was 83.1% with a single operation and 87.7% with a second surgery. After exclusion of the proliferative vitreoretinopathy (PVR) cases, the primary retinal reattachment rate improved to 93.9% and secondary retinal reattachment rate was 98.0%. The mean BCVA improved from logMAR 1.06–0.83 (P = 0.002). PVR (P = 0.0001), silicone oil tamponade (P = 0.002), macula-off RD (P = 0.12), location of RRD (P = 0.09), and delay of more than 7 days for surgery (P = 0.09) were associated with a higher redetachment rate. The main postoperative complications were small bubbles of PFCL in the posterior segment (18.5%) and subretinal PFCL (3.1%). Conclusions: Chandelier endoillumination and PFCL-assisted 23G PPV with phacoemulsification has reattachment rates and visual outcomes similar to the current standard of RRD repair of different complexities. This surgical technique can be considered an alternative method of repairing RRD, with some advantages.

Advances in patient care often germinate from keen clinical insights and a needs-based approach to innovation. Although there is an important role for incremental improvements to existing solutions, transformational innovation is what truly drives real shifts in clinical outcomes and subsequently patient satisfaction, market access, and economic value. A good example of this is the evolution of the coronary stent market. The best innovation programs are focused on unmet needs rather than solutions, call for a careful articulation of the specific problems to be solved, involve a deep dive within a clinical area, and seek to prioritize research and development investments into areas where the greatest impact can be expected. To enhance its ability to pursue breakthrough innovation, Johnson and Johnson (J&J) has organized itself along priority disease areas, created the global J&J Innovation organization to pursue external technology and know-how, and continues to partner closely with clinical practitioners. The process undertaken at J&J to acquire a microwave ablation technology and enter the interventional oncology space is a recent case study of these innovation principles and organizational focus in action.

In this paper, we propose a multi-objective transhipment problem where the source and destination parameters are chosen as triangular fuzzy numbers. There is an additional entropy objective function in the multi-objective transshipment problem.Using nearest interval approximation and total integral value of the fuzzy number, the problem is transformed into two types of crisp multi-objective problems. Finally, the transformed problems have been solved by fuzzy programming technique (using Bellman and Zadeh's (1970) minimum and additive operator). Numerical examples have been given to illustrate the original problem.

This paper examines the degree of efficiency of Indian ADRs and their underlying stocks trading in NSE/BSE from an adaptive markets hypothesis (AMH) perspective that is theoretically grounded in nonlinear serial dependence. For this purpose, the authors employ the windowed as well as the rolling hinich bicorrelation test procedures on ADRs and the underlying stocks issued by Indian firms such as, and limited to, Dr. Reddy’s Laboratories, HDFC Bank, ICICI Bank, Infosys, Wipro, Tata Motors, and Sterlite Industries. The study’s findings indicate that the degree of market efficiency witnessed at the level of individual scrips (ADRs or underlying domestic stocks) differs considerably from the degree of efficiency of the broader stock market in which such scrips trade. Further, the degree of efficiency witnessed amidst all US and Indian scrips considered for this study was found to be heterogeneous in nature and in-turn warrants a ranking approach. Lastly, the degree of efficiency witnessed in certain (not all) dually-listed Indian scrips was found to be homogenous across trading locations. However, this does not happen to be the case for all other dually-listed scrips considered for this study. The study’s findings bring to light the need for disaggregated, firm level market efficiency studies aimed at examining firm-level market efficiency at different trading locations and in-turn identifying the antecedents behind homogeneity (or lack-thereof) in firm-level market efficiency across multiple trading locations.

Irreversible electroporation (IRE) is a nonthermal ablation technique that is used clinically in selected patients with locally advanced pancreatic cancer, but most patients develop recurrent distant metastatic disease. We hypothesize that IRE can induce an in situ vaccination effect by releasing tumor neoantigens in an inflammatory context. Using an immunocompetent mouse model, we demonstrated that IRE alone produced complete regression of subcutaneous tumors in approximately 20% to 30% of mice. IRE was not effective in immunodeficient mice. Mice with complete response to IRE demonstrated prophylactic immunity and remained tumor free when rechallenged with secondary tumors on the contralateral flank. CD8+ T cells from IRE-responsive mice were reactive against peptides representing model-inherent alloantigens and conferred protection against tumor challenge when adoptively transferred into immunocompromised, tumor-naïve mice. Combining IRE with intratumoral Toll-like receptor-7 (TLR7) agonist (1V270) and systemic anti-programmed death-1 receptor (PD)-1 checkpoint blockade resulted in improved treatment responses. This combination also resulted in elimination of untreated concomitant distant tumors (abscopal effects), an effect not seen with IRE alone. These results suggest that the systemic antitumor immune response triggered by IRE can be enhanced by stimulating the innate immune system with a TLR7 agonist and the adaptive immune system with anti–PD-1 checkpoint blockade simultaneously. Combinatorial approaches such as this may help overcome the immunosuppressive pancreatic cancer microenvironment.

Quantifying antibiotics and antibiotic resistance genes (ARG) in manure exposed to various temperature and pH treatments could guide the development of cost-effective manure handling methods to minimize the spread of antibiotic resistance following land application of manure. This study aimed to investigate the effect of various temperatures and initial pH shocks on the persistence of a cephalosporin antibiotic and ARG in dairy manure slurries. Feces and urine were collected from 5 healthy dairy cows administered with cephapirin (cephalosporin antibiotic) at dry-off via intramammary infusion and were mixed with sterile water to generate manure slurries. In a 28-d incubation study, dairy manure slurries either were continuously exposed to 1 of 3 temperatures (10, 35, and 55°C) or received various initial pH (5, 7, 9, and 12) shocks. Cephapirin was detected in the initial samples and on d 1 following all treatments, but it was undetectable thereafter. This indicates that cephapirin can be rapidly degraded irrespective of temperature and pH treatments. However, degradation was greater on d 1 with the mesophilic (35°C) and thermophilic (55°C) environments compared with the psychrophilic environment (10°C). Increasing pH beyond neutral also accelerated degradation as cephapirin concentrations were lower on d 1 after initial alkaline adjustments (pH 9 and 12) than after neutral and acidic adjustments (pH 7 and 5). No significant effect of temperature or initial pH was observed on abundances of a β-lactam ARG, cfxA, and a tetracycline ARG, tet(W), implying that bacteria that encoded cfxA or tet(W) genes were not sensitive to temperature or pH in dairy manure slurries. However, abundances of a macrolide ARG, mefA, were decreased in the psychrophilic and thermophilic environments and also following exposure to a strong alkaline shock (pH 12). Our results suggest that increasing temperature or pH during storage of dairy manure slurries could be used together with other on-farm practices that are tailored to reduce the transfer of ARG from manure to the environment following land application.