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Mycetoma is a chronic granulomatous, suppurative and progressive inflammatory disease that usually involves the subcutaneous tissue and bones after traumatic inoculation of the causative organism. In India, actinomycotic mycetoma is prevalent in south India, south-east Rajasthan and Chandigarh, while eumycetoma, which constitutes one third of the total cases, is mainly reported from north India and central Rajasthan. The objective was to determine the epidemiological profile and spectrum of eumycetoma from a tertiary care hospital in Delhi, North India. Thirty cases of eumycetoma were diagnosed by conventional methods of direct microscopy, culture and species-specific sequencing as per standard protocol. The spectrum of fungal pathogens included Exophiala jeanselmei, Madurella mycetomatis, Fusarium solani, Sarocladium kiliense, Acremonium blochii, Aspergillus nidulans, Fusarium incarnatum, Scedosporium apiospermum complex, Curvularia lunata and Medicopsis romeroi. Eumycetoma can be treated with antifungal therapy and needs to be combined with surgery. It has good prognosis if it is timely diagnosed and the correct species identified by culture for targeted therapy of these patients. Black moulds required prolonged therapy. Its low reporting and lack of familiarity may predispose patients to misdiagnosis and consequently delayed treatment. Hence health education and awareness campaign on the national and international level in the mycetoma belt is crucial.
In this paper, longitudinal and lateral-directional aerodynamic characterisation of the Cropped Delta Reflex Wing (CDRW) configuration–based unmanned aerial vehicle is carried out by means of full-scale static wind-tunnel tests followed by full-scale flight testing. A predecided set of longitudinal and lateral/directional manoeuvres is performed to acquire the respective flight data, using a dedicated onboard flight data acquisition system. The compatibility of the acquired dynamics is quantified, in terms of scale factors and biases of the measured variables, using Kinematic consistency check. Maximum likelihood (ML), least squares and newly emerging neural Gauss–Newton (NGN) methods were implemented for a wing-alone delta configuration, mainly to capture the dynamic derivatives for both longitudinal and lateral directional cases. Estimated damping and weak dynamic derivatives, which are in general challenging to capture for a wing alone configuration, are consistent using ML and NGN methods. Validation of the estimated parameters with aerodynamic model is performed by proof-of-match exercise and are presented therein.
A novel flexible radio frequency (RF) sensor is designed to facilitate the accurate testing of various samples used in the biomedical industry at the industrial, scientific and medical (ISM) frequency band. The proposed RF biosensor comprises a liquid channel-loaded interdigitated capacitor, which is integrated on a coplanar waveguide structure. The prototype of the sensor is fabricated on a 0.13 mm thin biodegradable polyethylene terephthalate polyester film to perform the testing of various bio-graded samples by recording the corresponding resonant frequency. It is observed that there is a noticeable change between the measured resonant frequencies of these samples, which primarily occurs due to the difference in their dielectric properties. The designed sensor was used to monitor and investigate the quality of glycerol, which is the most commonly used raw ingredient in the biomedical and food industry. The determination of glucose concentration in base fluids is considered to ease the challenges faced by doctors and biochemists regarding the monitoring of glucose concentration. It is found that the proposed sensor can quantify the glycerol purity up to the minimum specified adulteration level of 2 and 1% corresponding to toxic contaminants diethylene glycol and ethylene glycol, respectively, and the glucose concentration of 0.5 mg/ml.
A single-centre, single-blinded prospective experimental study was conducted to determine the effectiveness of autologous platelet-rich plasma applied to the tonsillar bed post-operatively in reducing post-operative pain and haemorrhage.
Platelet-rich plasma, prepared prior to surgery, was applied with calcium gluconate to one randomly chosen tonsillar fossa. Pain and haemorrhage were analysed, using a visual analogue scale and a pre-defined grading scale respectively, four times on the day of surgery at 2-hourly intervals, and thrice on the following day.
The pain score and haemorrhage grade on the test side were lower than on the control side. These findings were statistically significant.
This pilot study, conducted in India, revealed valid positive results for a promising new technology. The manual preparation of platelet-rich plasma could be automated in the future to allow a larger sample size.
To propose a new classification of inner-ear anomalies that is more clinically oriented and surgically relevant: the SMS (Sawai Man Singh) classification of cochleovestibular malformations.
A retrospective multicentric study was conducted of 436 cochlear implantations carried out in 3 Indian tertiary care institutes. Patients with anomalous anatomy were included and classified, as per the new SMS classification, into cochleovestibular malformation types I, II, III and IV, based on cochlear morphology, modiolus and lamina cribrosa.
There were 19, 23, 8 and 4 patients with cochleovestibular malformation types I, II, III and IV, respectively. Two-year post-operative Meaningful Auditory Integration Scale scores were statistically analysed.
This new classification for inner-ear anomalies is a simpler, more practical, outcome-oriented classification that can be used to better plan the surgery. These merits make it a more uniform classification for recording results.
A cross-sectional study was conducted from 2014 to 2017 in 13 organised pig farms located in eight states of India (Northern, North-Eastern and Southern regions) to identify the risk factors, pathotype and antimicrobial resistance of Escherichia coli associated with pre- and post-weaning piglet diarrhoea. The data collected through questionnaire survey were used to identify the risk factors by univariable analysis, in which weaning status, season, altitude, ventilation in the shed, use of heater/cooler for temperature control in the sheds, feed type, water source, and use of disinfectant, were the potential risk factors. In logistic regression model, weaning and source of water were the significant risk factors. The piglet diarrhoea prevalence was almost similar across the regions. Of the 909 faecal samples collected (North – 310, North-East – 194 and South – 405) for isolation of E. coli, pathotyping and antibiotic screening, 531 E. coli were isolated in MacConkey agar added with cefotaxime, where 345 isolates were extended spectrum β-lactamase (ESBL) producers and were positive for blaCTX-M-1 (n = 147), bla TEM (n = 151), qnrA (n = 98), qnrB (n = 116), qnrS (n = 53), tetA (n = 46), tetB (n = 48) and sul1 (n = 54) genes. Multiple antibiotic resistance (MAR) index revealed that 14 (2.64%) isolates had MAR index of 1. On the virulence screening of E. coli, 174 isolates harboured alone or combination of Stx1, Stx2, eaeA, hlyA genes. The isolates from diarrhoeic and post-weaning samples harboured higher number of virulence genes than non-diarrhoeic and pre-weaning. Alleviating the risk factors might reduce the piglet diarrhoea cases. The presence of multidrug-resistant and ESBL-producing pathogenic E. coli in piglets appears a public health concern.
Grewia tenax locally known as ‘Gangerun’, is an important multipurpose underutilized shrub and potentially threaten species of the Thar Desert of India. Owing to its importance, naturally available germplasm was collected and evaluated for its sustainable utilization in future. Data on individual mother plant, seed characters and soil profile were investigated. Habitat occurrence of G. tenax was found in patches with dominant association of Euphorbia caducifolia across the four districts of western Rajasthan. Individual plant on unprotected area portrayed far lower average height (0.95 m) and canopy area (1.75 m2) than protected area (2.63 m and 13.89 m2) signifying level of browsing pressure on this species in Jaisalmer. Soil samples belonging to Pali region have high organic carbon and low electrical conductivity content than Jaisalmer and Jodhpur. The statistical analysis of seed characters revealed the presence of high coefficient of variation (%) in 100-seed weight (HSW; 27.36) followed by seed length (SL; 8.06) and least in seed breadth (SB; 5.85). The range and mean values of HSW, SL, SB and length:breadth ratio (LBR) were (2.02–7.00 and 3.34 g), (4.36–6.15 and 5.36 mm), (3.73–4.68 and 4.25 mm) and (1.11–1.44 and 1.27), respectively. Significantly positive correlation was observed between SL and LBR (0.73) followed by HSW and SL (0.66). Along with these findings, its economic importance, utilization and conservation are detailed in this paper as to hasten further research on its various aspects for its successful conservation and utilization.
The study primarily aimed to calculate the orientation of the cochlea pre-operatively, using high-resolution computed tomography of the temporal bone, and predict the ease of electrode insertion.
Pre-operatively, high-resolution computed tomography scans were conducted on children scheduled for cochlear implantation, and two angles, α and β, were calculated. The values of α and β were then correlated with intra-operative difficulty in insertion of the electrode array.
Ninety-six children were included in the study. Of the seven patients who had an α angle of less than 50 degrees, the surgeon experienced difficulties in electrode insertion. However, there were four patients with an α angle of more than 50 degrees for whom the surgeon also experienced difficulties in electrode insertion. In all these patients, the β angle was more than 20 degrees.
Calculation of cochlear orientation and its angle with the surgical axis (α and β) can aid the planning of surgery, particularly with regard to the cochleostomy site and preservation of residual hearing.
Rice has the lowest grain protein content (GPC) among cereals. Efforts have been made to improve GPC through the modified bulk-pedigree method of selection. A total of 1780 F8 recombinant lines were derived in the year 2013 from five different cross combinations involving two high-GPC landraces, namely ARC10075 and ARC10063, three high-yielding parents, namely Swarna, Naveen and IR64, and one parent, namely Sharbati, known for superior grain quality with high micronutrient content. Near-infrared spectroscopy was used to facilitate high-throughput selection for GPC. Significant selection differential, response to selection and non-significant differences between the predicted and observed response to selection for GPC and protein yield indicated the effectiveness of this selection process. This resulted in lines with high GPC, protein yield and desirable levels of amylose content. Further, based on high mean and stability for GPC and protein yield over the environments in the wet seasons of 2013, 2014 and the dry season of 2014, 12 elite lines were identified. Higher accumulation of glutelin fraction and non-significant change in prolamin/glutelin ratio in the grain suggested safe guarding of the nutritional value of rice grain protein of most of these identified lines. Since rice is the staple food of millions, the output of breeding for high GPC could have a significant role in alleviating protein malnutrition, especially in the developing world.
Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1β (IL-1β) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-β. This immune polarization was also evidenced by upregulation of nuclear factor-κ light-chain enhancer of activated B cells p50 and regulated expression of suppressor of mother against decapentaplegic protein-4. rLd-iPGAM stimulation also promoted lymphocyte proliferation and boosted the leishmaniacidal activity of macrophages by upregulating reactive oxygen species. It also induced 1·8-fold higher release of nitric oxide (NO) by promoting the transcription of inducible nitric oxide synthase gene. Besides, in silico analysis suggested the presence of major histocompatibility complex class I and II restricted epitopes, which can proficiently trigger CD8+ and CD4+ cells, respectively. This study reports rLd-iPGAM as an effective immunoprophylactic agent, which can be used in future vaccine design.
Bovine calf scours reported to be caused by multiple aetiologies resulting in heavy mortality in unweaned calves and huge economic loss to the dairy farmers. Among these, cryptosporidiosis is an emerging waterborne zoonoses and one of the important causes of neonatal calf diarrhoea. Poor immune response coupled with primary cryptosporidial infections predispose neonatal calves to multiple secondary infections resulting in their deaths. In the present study, faecal samples from 100 diarrhoeic calves randomly picked up out of 17 outbreaks of bovine calf diarrhoea in periurban Ludhiana, Punjab in Northern India were subjected to conventional (microscopy, modified Zeihl–Neelsen (mZN) staining) and immunological and molecular techniques (faecal antigen capture ELISA and PCR) for detection of primary Cryptosporidium parvum infection as well as other frequently reported concurrent pathogens, viz. rotavirus and coronavirus, Salmonella spp., Escherichia coli, Clostridium perfringens and Eimeria spp. The faecal antigen capture ELISA and PCR revealed 35% prevalence of C. parvum in contrast to 25% by mZN staining with a relatively higher prevalence (66·7%) in younger (8–14-day-old) calves. The detection rate of the other enteropathogens associated with C. parvum was 45·71% for C. perfringens followed by Salmonella spp (40·0%), rotavirus (36·0%), coronavirus (16·0%), E. coli (12·0%) and Eimeria spp (4·0%) The sensitivity for detection of C. parvum by ELISA and mZN staining in comparison to PCR was 97·14% and 72·72%, respectively. An important finding of the study was that C. parvum alone was found in only 10% of the diarrhoeic faecal samples, whereas, majority of the samples (90%) showed mixed infections ranging from a combination of two to five agents. This is the first documentary proof of C. parvum and associated pathogens responsible for severe periurban outbreaks of bovine calf diarrhoea culminating in heavy mortality from Northern India.
Background: The surgical risk factors and neuro-imaging characteristics associated with cerebellar mutism (CM) remain unclear and require further investigation. We aimed to examine surgical and MRI findings associated with CM in children following posterior fossa tumor resection. Methods: Using our data registry, we retrospectively collected data from pediatric patients who acquired CM and were matched based on age and pathology type with patients not acquiring CM after posterior fossa surgery. The strength of association between surgical and MRI variables and CM were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results: A total of 22 patients were included. Medulloblastoma was the most common pathology among CM patients (91%). Tumor attachment to the floor of the fourth ventricle (OR, 6; 95% CI, 0.7-276), calcification/hemosiderin deposition (OR 7; 95% CI 0.9-315.5), and post-operative peri-ventricular ischemia on MRI (OR, 5; 95% CI, 0.5-236.5) were found to have the highest association with CM. Conclusions: Our results may suggest that tumor attachment to the floor of the fourth ventricle, pathological calcification, and post-operative ischemia are relatively more prevalent in patients with CM. Collectively, our work calls for a larger multi-institutional study of CM patients to further investigate the determinants and management of CM to potentially minimize its development and predict onset.
Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression.
We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol.
We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47–2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04–1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94–1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81–1.32).
Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.
This research article addresses the effect of fillers on the high-temperature corrosion behavior of AISI 347 weld joints. Multi-pass pulsed current gas tungsten arc welding was carried out on 6.67 mm thick plates of AISI 347 using three different fillers namely ER347, ER2553, and ERNiCrMo-3. The fusion zone microstructures of AISI 347 employing ER2553 and ERNiCrMo-3 exhibited columnar and dendritic grain growth; whereas vermicular delta ferrite was observed at the fusion zone of ER347 welds. Tensile studies showed that the weld employing ERNiCrMo-3 exhibited better tensile strength than the parent metal. High-temperature corrosion studies were carried out on the fusion zones by exposing the coupons to an aggressive, synthetic molten-salt incinerator environment containing 40% Na2SO4–40% K2SO4–10% NaCl–10% KCl at 650 °C for 50 cycles. The studies attested that the fusion zone employing ERNiCrMo-3 exhibited better corrosion resistance than the other two fillers used in the study. Spallation of oxides was witnessed due to the dissolution of Cr2O3 in the ER347 and ER2553 fusion zones. The hot corroded samples were characterized using surface analytical techniques.
Medulloblastoma (MB) is the most common malignant pediatric brain tumour, and is categorized into four molecular subgroups, with Group 3 MB having the worst prognosis due to the highest rate of metastatic dissemination and relapse. In this work, we describe the epigenetic regulator Bmi1 as a novel therapeutic target for treatment of recurrent Group 3 MB. Through comparative profiling of primary and recurrent MB, we show that Bmi1 defines a treatment-refractory cell population that is uniquely targetable by a novel class of small molecule inhibitors. We have optimized an in vivo mouse-adapted therapy model that has the advantage of generating recurrent, human, treatment-refractory MBs. Our preliminary studies showed that although chemoradiotherapy administered to mice engrafted with human MB showed reduction in tumour size, Bmi1 expression was enriched in the post-treatment residual tumour. Furthermore, we found that knockdown of Bmi1 in human recurrent MB cells decreases proliferation and self-renewing capacities of MB cells in vitro as well as both tumour size and extent of spinal leptomeningeal metastases in vivo. Oral administration of a potent Bmi1 inhibitor, PTC 028, resulted in a marked reduction in tumour burden and an increased survival in treatment cohort. Bmi1 inhibitors showed high specificity for MB cells and spared normal human neural stem cells, when treated with doses relevant for MB cells. As Group 3 medulloblastoma is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious agent such as Bmi1 inhibitor could be rapidly transitioned to clinical trials.
Glioblastoma (GBM) is an aggressive brain tumor that is resistant to conventional radiation and cytotoxic chemotherapies. We hypothesize that brain tumor initiating cells (BTICs), a subpopulation of treatment-resistant cells with stem cell properties cause tumor relapse and a subset of neural stem cell genes regulate BTIC self-renewal, driving GBM recurrence. We adapted the existing treatment protocol for adults with primary GBM for in vivo treatment of immunocompromised mice engrafted with GBMs. Post-chemoradiotherapy, the recovered GFP+GBMs were profiled for self-renewal and expression of critical stem cell genes. Using invitro and invivo gain-of-function/loss-of-function experiments, we investigated the regulatory functions of Bmi1 in primary neural stem & progenitor cells (NSPCs) and GBM tumor formation. Finally, global RNA-Seq profiling was performed to understand the consequences of Bmi1 dysregulation on target gene expression. GBM cells showed an increase in Bmi1 levels post-chemoradiotherapy, suggesting the presence of a treatment-refractory BTICs. GFP+cells extracted from treated xenografts had higher self-renewal and BTIC marker expression. Although treated mice responded to therapy, we observed tumor relapse with increased Bmi1 expression. Knockdown of Bmi1 diminished self-renewal and proliferation of GBM cells and delayed tumorigenesis, highlighting a critical role for Bmi1 in tumor maintenance. Conversely, over-expressing Bmi1 in NSPCs failed to initiate tumor formation in vivo. Using high-throughput sequencing data, we generated a map of signaling pathways dysregulated in GBM that may lead to tumor recurrence. Our data confirms the existence of a rare treatment-refractory BTIC population with enhanced self-renewal capacity that escapes therapy and drives tumor relapse.
Medulloblastoma (MB), the most common malignant pediatric brain tumor, is categorized into four molecular subgroups. Given the high rate of metastatic dissemination at diagnosis and recurrence in Group 3 MBs, these patients have the worst clinical outcome with a 5-year survivorship of approximately 50%. By adapting the existing COG (Children’s Oncology Group) Protocol for children with newly diagnosed high-risk MB, for treatment of immuno-deficient mice intracranially engrafted with human MB brain tumour initiating cells we aim to identify and characterize the treatment-refractory cell population in Group 3 MBs. Mice were sacrificed at multiple time points during the course of tumor development and therapy: (i) at engraftment; (ii) post-radiation; (iii) post-radiation and chemotherapy; and (iv) at MB recurrence. MB cell populations recovered separately from brains and spines were comprehensively profiled for gene expression analysis, stem cell and molecular features to generate a global, comparative profile of MB cells through therapy. We report a higher expression of CD133, Sox2 and Bmi1 in addition to increased self-renewal capacity following chemoradiotherapy treatment. The enrichment map constructed from global gene expression analysis showed an increase in pathways regulating self-renewal, DNA repair and chemoresistance post-therapy despite the apparent decrease in tumour size and vascularity. Additionally, from gene expression at MB recurrence, we identified a list of genes that negatively correlate with survival in patients diagnosed with Group 3 MB. A differential genomic profile of the “treatment-responsive” tumors against those that fail therapy may contribute to discovery of novel therapeutic approaches for the most aggressive subgroup of MB.
Brain Metastases (BM) represent a leading cause of cancer mortality. While metastatic lesions contain subclones derived from their primary lesion, their functional characterization has been limited by a paucity of preclinical models accurately recapitulating the stages of metastasis. This work describes the isolation of a unique subset of metastatic stem-like cells from primary human patient samples of BM, termed brain metastasis initiating cells (BMICs). Utilizing these BMICs we have established a novel patient-derived xenograft (PDX) model of BM that recapitulates the entire metastatic cascade, from primary tumor initiation to micro-metastasis and macro-metastasis formation in the brain. We then comprehensively interrogated human BM to identify genetic regulators of BMICs using in vitro and in vivo RNA interference screens, and validated hits using both our novel PDX model as well as primary clinical BM specimens. We identified SPOCK1 and TWIST2 as novel BMIC regulators, where in our model SPOCK1 regulated BMIC self-renewal and tumor initiation, and TWIST2 specifically regulated cell migration from lung to brain. A prospective cohort of primary lung cancer specimens was used to establish that SPOCK1 and TWIST2 were only expressed in patients who ultimately developed BM, thus establishing both clinical and functional utility for these gene products. This work offers the first comprehensive preclinical model of human brain metastasis for further characterization of therapeutic targets, identification of predictive biomarkers, and subsequent prophylactic treatment of patients most likely to develop BM. By blocking this process, metastatic lung cancer would effectively become a localized, more manageable disease.
We present preliminary results of grating observations of YY Mensae and V824 Arae by Chandra and XMM-Newton. Spectral features are presented in the context of the emission measure distributions, the coronal abundances, and plasma electron densities. In particular, we observe a coronal N/C enhancement in YY Men believed to reflect the photospheric composition (CN cycle). Finally, we interpret line broadening in YY Men as Doppler thermal broadening in its very hot corona.
Meditation is believed to have many health benefits apart from enhancing spiritual health. However, there is evidence that meditation may even lead to psychosis or worsen it in some cases. The aim of this paper is to present a case and discuss the role of meditation as a precipitating factor to psychosis. A 27-year-old male presented with psychotic symptoms with a temporal correlation with meditation. He was then successfully treated with antipsychotic medication and is maintaining well. This case report highlights the possibility that intense meditation could precipitate psychosis in vulnerable individuals. However, there are several beneficial effects of meditation in patients with psychosis if practiced with caution.