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The current COVID-19 pandemic contributed by the SARS-CoV-2 has put in place an urgent need for new and promising antiviral therapeutics. The viral RNA-dependent RNA polymerase (RdRp) enzyme plays a vital role in viral replication for all RNA viruses, including SARS-CoV-2, thereby making it a prime and promising candidate for novel antiviral targeting. Interestingly, the human telomerase reverse transcriptase (hTERT), a common catalytic subunit of the telomerase enzyme in many cancers, has also been identified with structural and functional similarities to the viral RdRp. Therefore, it becomes essential to evaluate and consider anticancer drugs that target hTERT towards antiviral RdRp activity, and vice versa. For instance, Floxuridine, an hTERT inhibitor, and VX-222, a hepatitis C virus RdRp inhibitor, are now gaining recognition as a potential antiviral against SARS-CoV-2 and anti-hTERT for cancer, simultaneously. While limited studies on hTERT inhibitors for use as viral RdRp, and anti-RdRp inhibitors as hTERT inhibitors are available, in this review, we aim at bringing to light this close structural and functional relationship between both these enzymes. We punctuate this idea with specific examples on how potential anticancer inhibitors can effectively be brought to use as inhibitors against the SARS-CoV-2 virus, a relatively new pathogen, compared to the very well-studied field of cancer research.
This study is on the absolute age dating of a multicultural site of Erenda, East Medinipur district, in coastal West Bengal, India. Charcoal samples were collected and measured using the accelerator mass spectrometry (AMS) facility at the Inter-University Accelerator Centre, New Delhi, India. These samples were collected from secured stratigraphic context of two excavated trenches. A careful collection of samples from two trenches provided us with the first calendar dates, 950 BCE and 1979 BCE, of protohistoric sites in coastal West Bengal. These calibrated calendar dates not only have wider significance in terms of archaeology but also methodological implications to understand the relevance of application of AMS from the dynamic coastal landscape in the humid tropics during the late Holocene period.
Accelerator mass spectrometry (AMS) activities at the Inter-University Accelerator Centre (IUAC) in New Delhi, India, started with its 15UD Pelletron accelerator and cosmogenic radionuclide (CRN) measurements of 10Be and 26Al. Realizing the demand of a radiocarbon (14C) AMS facility in India, a 500kV Pelletron accelerator based AMS system was installed in 2015. This facility was designated with the lab code IUACD for 14C measurements. 14C dates measured in 2015 and 2016 were published in the first radiocarbon date list (see text for details). The present list is the second 14C date list and consists of dates measured from January to December 2017.
Experimental studies are conducted on a rotationally oscillating cylinder with an attached flexible filament at a Reynolds number of 150. Parametric studies are carried out to investigate the effect of cylinder forcing parameters and filament stiffness on the resultant wake structure. The diagnostics are flow visualization using the laser-induced fluorescence technique, frequency measurement using a hot film, and characterization of the velocity and vorticity field using planar particle image velocimetry. The streamwise force and power are estimated through control volume analysis, using a modified formulation, which considers the streamwise and transverse velocity fluctuations in the wake. These terms become important in a flow field where asymmetric wakes are observed. An attached filament significantly modifies the flow past a rotationally oscillating cylinder from a Bénard–Kármán vortex street to a reverse Bénard–Kármán vortex street, albeit over a certain range of Strouhal number, $St_{A} \sim 0.25\text {--}0.5$, encountered in nature in flapping flight/fish locomotion and in the flow past pitching airfoils. The transition from a Kármán vortex street to a reverse Kármán vortex street precedes the drag-to-thrust transition. The mechanism of unsteady thrust generation is discussed. Maximum thrust is generated at the instants when vortices are shed in the wake from the filament tip. At $St_{A} > 0.4$, a deflected wake associated with the shedding of an asymmetric vortex street is observed. Filament flexibility delays the formation of an asymmetric wake. Wake symmetry is governed by the time instant at which a vortex pair is shed in the wake from the filament tip.
Smallflower umbrella sedge is one of the most problematic weeds in direct-seeded rice in India. Bispyribac-sodium (acetolactate synthase [ALS]-inhibiting herbicide) is commonly used in rice, but growers have recently reported lack of smallflower umbrella sedge control with this herbicide. An extensive survey was carried out in two rice-growing states, Chhattisgarh and Kerala, where 53 putative bispyribac-sodium-resistant (BR) biotypes were collected. Studies were conducted to confirm resistance to bispyribac-sodium and to test the efficacy of the newly developed synthetic auxin herbicide florpyrauxifen-benzyl on putative BR biotypes. A whole-plant bioassay revealed that bispyribac-sodium is no longer effective. Of 53 putative BR biotypes, 17 biotypes survived the recommended label rate of 25 g ai ha−1. The effective bispyribac-sodium rate required to control 50% of the plants in most of the BR biotypes (ED50) ranged from 19 to 96 g ha−1, whereas it was 10 g ha−1 in a susceptible biotype. In two highly resistant biotypes, the ED50 was beyond the maximum tested rate, 200 g ha−1. This suggests 2- to >20-fold resistance in BR biotypes. An ALS enzyme activity assay suggests an altered target site as mechanism of resistance to bispyribac-sodium. This study confirms the first case of evolved resistance to bispyribac-sodium in smallflower umbrella sedge in India. However, the newly developed synthetic auxin florpyrauxifen-benzyl effectively controlled all BR biotypes at the field use rate of 31.25 g ai ha−1.
For any odd prime p, we construct an infinite family of imaginary quadratic fields whose class numbers are divisible by p. We give a corollary that settles Iizuka’s conjecture for the case n=1 and p>2.
Fundamental knowledge about the processes that control the functioning of the biophysical workings of ecosystems has expanded exponentially since the late 1960s. Scientists, then, had only primitive knowledge about C, N, P, S, and H2O cycles; plant, animal, and soil microbial interactions and dynamics; and land, atmosphere, and water interactions. With the advent of systems ecology paradigm (SEP) and the explosion of technologies supporting field and laboratory research, scientists throughout the world were able to assemble the knowledge base known today as ecosystem science. This chapter describes, through the eyes of scientists associated with the Natural Resource Ecology Laboratory (NREL) at Colorado State University (CSU), the evolution of the SEP in discovering how biophysical systems at small scales (ecological sites, landscapes) function as systems. The NREL and CSU are epicenters of the development of ecosystem science. Later, that knowledge, including humans as components of ecosystems, has been applied to small regions, regions, and the globe. Many research results that have formed the foundation for ecosystem science and management of natural resources, terrestrial environments, and its waters are described in this chapter. Throughout are direct and implicit references to the vital collaborations with the global network of ecosystem scientists.
Background: Healthcare-associated infections (HAIs) are a major global threat to patient safety. Systematic surveillance is crucial for understanding HAI rates and antimicrobial resistance trends and to guide infection prevention and control (IPC) activities based on local epidemiology. In India, no standardized national HAI surveillance system was in place before 2017. Methods: Public and private hospitals from across 21 states in India were recruited to participate in an HAI surveillance network. Baseline assessments followed by trainings ensured that basic microbiology and IPC implementation capacity existed at all sites. Standardized surveillance protocols for central-line–associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) were modified from the NHSN for the Indian context. IPC nurses were trained to implement surveillance protocols. Data were reported through a locally developed web portal. Standardized external data quality checks were performed to assure data quality. Results: Between May 2017 and April 2019, 109 ICUs from 37 hospitals (29 public and 8 private) enrolled in the network, of which 33 were teaching hospitals with >500 beds. The network recorded 679,109 patient days, 212,081 central-line days, and 387,092 urinary catheter days. Overall, 4,301 bloodstream infection (BSI) events and 1,402 urinary tract infection (UTI) events were reported. The network CLABSI rate was 9.4 per 1,000 central-line days and the CAUTI rate was 3.4 per 1,000 catheter days. The central-line utilization ratio was 0.31 and the urinary catheter utilization ratio was 0.57. Moreover, 3,542 (73%) of 4,742 pathogens reported from BSIs and 868 (53%) of 1,644 pathogens reported from UTIs were gram negative. Also, 1,680 (26.3%) of all 6,386 pathogens reported were Enterobacteriaceae. Of 1,486 Enterobacteriaceae with complete antibiotic susceptibility testing data reported, 832 (57%) were carbapenem resistant. Of 951 Enterobacteriaceae subjected to colistin broth microdilution testing, 62 (7%) were colistin resistant. The surveillance platform identified 2 separate hospital-level HAI outbreaks; one caused by colistin-resistant K. pneumoniae and another due to Burkholderia cepacia. Phased expansion of surveillance to additional hospitals continues. Conclusions: HAI surveillance was successfully implemented across a national network of diverse hospitals using modified NHSN protocols. Surveillance data are being used to understand HAI burden and trends at the facility and national levels, to inform public policy, and to direct efforts to implement effective hospital IPC activities. This network approach to HAI surveillance may provide lessons to other countries or contexts with limited surveillance capacity.
The purpose of the present study was to assess the accuracy of radiotherapy (RT) structure volume generated by the Monaco treatment planning system (TPS) for three different computed tomography (CT) slice thicknesses. Further, this study addressed the important issue of ‘different volumes of the same RT structure shown at different places’ in the Monaco TPS. Also, the practical impact of this difference in structure volumes has been studied for brain or head and neck patients.
Materials and Methods:
Objects of known volumes were scanned with different CT slice thicknesses and contoured as an RT structure in Monaco TPS and two different volumes provided by the TPS for each RT structure were noted and compared with the real volumes of these objects. In addition, correlation was also assessed between TPS provided volumes and real volumes of these objects. The study was further extended to obtain correlation of volumes in cases of organs that exist in pairs (e.g., eye) in the human body.
Results:
Monaco TPS overestimates structure volumes except for objects with sharp corners. Although, volumes shown at different places of the same structure have nearly a linear correlation, volumes under structure table are more accurate than those shown under dose–volume histogram (DVH) statistics (total volume) table. Difference in magnitude between these two volumes has no correlation if this difference is analysed for paired organs.
Findings:
This study confirmed that Monaco TPS provides ‘different value at different places’ of the volume of a given contoured structure. It is recommended that this issue should be reviewed and resolved by the supplier.
The optimal management of symptomatic tetralogy of Fallot in neonates and younger infants with unfavourable anatomy is unclear and is further constrained by resource limitations in low and middle income countries.
Methods:
Retrospective medical record review of infants with tetralogy of Fallot undergoing corrective or palliative procedures between January 2016 and June 2019.
Results:
The study included 120 infants; of whom 83 underwent primary complete repair, four underwent surgical palliation, and 33 underwent catheter-based palliation, including balloon pulmonary valvuloplasty (n = 18), right ventricular outflow tract stenting (n = 14), and stenting of the patent arterial duct (n = 1). Infants undergoing catheter-based procedures were younger in age (median 32 days; inter-quartile range (IQR) 7–144 versus 210 days; IQR 158–250), with lower baseline saturation (65 ± 12% versus 87 ± 7%) and had smaller pulmonary artery z-scores compared to the complete repair cohort. Follow-up was available for 31/33 (94%) infants (median 7 months [IQR 4–11]) who underwent trans-catheter palliation; 12 underwent complete repair, 10 are well, awaiting repair, eight required further palliation (catheter: 6; surgical: 2), and one died post-discharge from non-cardiac causes.
Conclusion:
Catheter-based palliation is a safe and effective alternative in infants with tetralogy of Fallot who are at high risk for primary surgical repair.
A new facility for radiocarbon dating by accelerator mass spectrometry (AMS) was established in early 2015 at the Inter-University Accelerator Centre in New Delhi, India. The facility uses a 500 kV National Electrostatic Corporation (NEC) Pelletron accelerator for AMS measurements on graphite produced using the automated graphitization equipment (AGE) interfaced with an elemental analyzer and the carbonate handling system (CHS). A precision of better than 1‰ in the ratio of 14C/12C for the modern carbon sample and the background level of 1 × 10–15 from dead carbon sample has been achieved. This is the first dedicated accelerator of India only for AMS activities. This AMS system has the capabilities to perform 10Be and 26Al measurements as well.
Comparison of the integral dose (ID) delivered to organs at risk (OAR), non-target body and target body by using different techniques of craniospinal irradiation (CSI).
Materials and methods:
Ten CSI patients (medulloblastoma) already planned and treated either with linear accelerator three-dimensional conformal radiation therapy (Linac-3DCRT) technique or with linear accelerator RapidArc (Linac-RapidArc) technique by Novalis-Tx Linac machine have been analysed. Retrospectively, these patients are again planned on Radixact-X9 Linac with Helical, Direct-3DCRT and Direct-intensity-modulated radiation therapy (Direct-IMRT) techniques. The dose prescription to planning target volume brain (PTV-Brain) and PTV-Spine is 36 Gy in 20 fractions and is kept the same for all techniques. The target body, non-target body, OARs and total body dose are compared.
Results:
ID is lowest in the RapidArc plan for every patient in comparison to Helical and Direct-IMRT. The ID for Body-PTV was found slightly higher in the RapidArc plan in comparison to 3DCRT plans. But there is better normal tissue sparing for most of the OARs in RapidArc plans if it compares with 3DCRT plans.
Findings:
RapidArc is a better alternative for the treatment of CSI. It provides better target coverage and better OARs sparing from any other treatment techniques.
Early weight trends after cardiac surgery in infants from low- and middle-income countries where the majority are undernourished have not been defined. We studied the early post-operative weight trends to identify specific factors associated with early weight loss and poor weight gain after discharge following congenital heart surgery in consecutive infants undergoing cardiac surgery at a referral hospital in Southern India.
Methods:
This was a prospective observational study. Weights of the babies were recorded at different time points during the hospital stay and at 1-month post-discharge. A comprehensive database of pre-operative, operative, and post-operative variables was created and entered into a multivariate logistic regression analysis model to identify factors associated with excessive early weight loss after cardiac surgery, and poor weight gain following hospital discharge.
Results:
The study enrolled 192 infants (mean age 110.7 ± 99.9 days; weight z scores − 2.5 ± 1.5). There was a small but significant (p < 0.001) decline in weight in the hospital following surgery (1.6% decline (interquartile range −5.3 to +1.7)); however, there was substantial growth following discharge (26.7% increase (interquartile range 15.3–41.8)). The variables associated with post-operative weight loss were cumulative nil-per-oral duration and cardiopulmonary bypass time, while weight gain following discharge was only associated with age.
Conclusion:
Weight loss is almost universal early after congenital heart surgery and is associated with complex surgery and cumulative nil-per-oral duration. After discharge, weight gain is almost universal and not associated with any of the perioperative variables.
Experiments were carried out with air as the test gas to obtain the surface convective heating rate and surface pressure distribution on blunt and sharp cone models flying at hypersonic speeds. Tests were performed in a hypersonic shock tunnel at two different angles of attack: ${0}^\circ$ and ${5}^\circ$ with angles of rotation $\phi = {0}^\circ, {90}^\circ$, and ${180}^\circ$. The experiments were conducted at a stagnation enthalpy of 1.4MJ/kg, flow Mach number of 6.56 and free stream Reynolds number based on the model length of $9.1 \times {10}^{5}$. The effective test time of the shock tunnel is 3ms. The results obtained for cone model with a bluntness ratio of 0.2 were compared with sharp cone models for $\alpha ={0}^\circ$. The measured stagnation heat transfer value matched well with the theoretical value predicted by the Fay and Riddell correlation and with the CFD results.
Cerebral malaria (CM) is the severe neurological complication causing acute non-traumatic encephalopathy in tropical countries. The mechanisms underlying the fatal cerebral complications are still not fully understood. Glutamate, a major excitatory neurotransmitter in the central nervous system of the mammalian brain, plays a key role in the development of neuronal cells, motor function, synaptic plasticity, learning and memory processes under normal physiological conditions. The subtypes of ionotropic glutamate receptor are N-methyl-D-aspartate receptors (NMDARs) which are involved in cellular mechanisms of learning and memory, synaptic plasticity and also mediate excitotoxic neuronal injury. In the present study, we found that glutamate level in synaptosomes, as well as expression of NMDAR, was elevated during the extreme condition of CM in C57BL6 mice. Arteether at 50 mg kg−1 × 1, 25 mg kg−1 × 2, days decreased the NMDAR expression and increased the overall survival of the experimental CM mice.
This study was undertaken with an aim of exploring community knowledge and treatment practices related to malaria and their determinants in high- and low-transmission areas of central India. A community-based cross-sectional study was carried out between August 2015 and January 2016 in two high- and two low-malaria-endemic districts of central India. A total of 1470 respondents were interviewed using a pre-tested structured interview schedule. Respondents residing in high-transmission areas with higher literacy levels, and of higher socioeconomic status, were found to practise more modern preventive measures than those living in low-transmission areas with low literacy levels and who were economically poor. Level of literacy, socioeconomic status and area (district) of residence were found to be the main factors affecting people’s knowledge of malaria aetiology and clinical features, and prevention and treatment practices, in this community in central India.
Invasive populations of Dalmation toadflax [Linaria dalmatica (L.) Mill.] and yellow toadflax (Linaria vulgaris Mill.) are widespread throughout the Intermountain West, where gene flow between these nonnative species is producing vigorous and fertile hybrids. These hybrid toadflax populations are less responsive to herbicides than either parent species, and biocontrol agents routinely released on L. dalmatica and L. vulgaris often fail to establish on hybrid hosts. Early detection of hybrid Linaria populations is therefore essential for effective management, but resources are limited for scouting large expanses of range and wildland. We used species distribution modeling to identify environmentally suitable areas for these invasive Linaria taxa in Montana, Wyoming, and Colorado. Areas suitable for hybrid Linaria establishment were estimated using two different modeling approaches: first, based on known hybrid occurrence and associated environmental conditions, and second, based on zones environmentally suitable for co-occurrence of the parent species. This also allowed comparison of different model outputs, especially relevant when modeling emerging invasives, such as novel hybrids, with minimal occurrence data. Combining the two model outputs identified areas at greatest risk of hybrid Linaria invasion, including parts of north-central Montana, where model estimates indicate the hybrid may spread without prior co-invasion of the parents. Potential hybrid hot spots were also identified in western Montana; northwestern, northeastern, and southeastern Wyoming; and the Western Slope and Front Range of Colorado. Despite relatively few confirmed occurrences of hybrid populations to date, our results indicate that extensive spread of hybrid populations is possible within the studied area. Model-based maps of potential Linaria distributions will allow area weed managers to direct limited resources more effectively for locating and controlling these invaders.
An important step towards developing a successful integrated pest management (IPM) programme for the control of banana pseudostem weevil, Odoiporus longicollis (Olivier), a serious pest of banana in India, is the study of the population structure of the pest. In the present study, the genetic variation among 30 individual weevils of O.longicollis collected from six different locations was assessed by analysing the primary nucleotide sequences of the rDNA ITS1 and ITS2 regions. AMOVA, Mantel test, and the maximum likelihood trees of the haplotypes failed to reveal any phylogeographic structuring, which was confirmed by haplotype analysis and genetic differentiation estimates. The results indicate that the locations are not differentiated, i.e. there is gene flow between the locations. The star-shaped networks revealed a signature of demographic expansion that was confirmed by the different demographic tests. These results provide important information, which is essential for the development of suitable strategies for the control of this banana pest, as well as management of its resistance to insecticides.
Interrupted aortic arch is a rare congenital anomaly in newborns and infants and is commonly associated with other cardiovascular anomalies. Here, we report an unusual case of type A interrupted cervical aortic arch associated with long segment coarctation of the descending thoracic aorta. Patent ductus arteriosus reconstituted the descending thoracic aorta. Proximal segments of the left common carotid and left subclavian arteries were atretic. Echocardiography-gated multidetector CT angiography not only identified the type of aortic arch interruption in the neonate but also delineated the exact anatomical details.
We could find a new 5 year periodicity in the occurrences of peaks in sunspot activity and inferred deviations of annual Indian monsoon rainfall variations from the normal during the Maunder minimum (MM) period. This result is explained in terms of solar dynamo functioning in a different mode from normal during the MM where quadrupole field (first harmonic, 5-5.5 years) dominate over dipole field (fundamental, 11 years) causing extreme north south asymmetry in sunspot activity.