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Residual blood specimens collected at health facilities may be a source of samples for serosurveys of adults, a population often neglected in community-based serosurveys. Anonymized residual blood specimens were collected from individuals 15 – 49 years of age attending two sub-district hospitals in Palghar District, Maharashtra, from November 2018 to March 2019. Specimens also were collected from women 15 – 49 years of age enrolled in a cross-sectional, community-based serosurvey representative at the district level that was conducted 2 – 7 months after the residual specimen collection. Specimens were tested for IgG antibodies to measles and rubella viruses. Measles and rubella seroprevalence estimates using facility-based specimens were 99% and 92%, respectively, with men having significantly lower rubella seropositivity than women. Age-specific measles and rubella seroprevalence estimates were similar between the two specimen sources. Although measles seropositivity was slightly higher among adults attending the facilities, both facility and community measles seroprevalence estimates were 95% or higher. The similarity in measles and rubella seroprevalence estimates between the community-based and facility serosurveys highlights the potential value of residual specimens to approximate community seroprevalence.
Residual blood specimens provide a sample repository that could be analyzed to estimate and track changes in seroprevalence with fewer resources than household-based surveys. We conducted parallel facility and community-based cross-sectional serological surveys in two districts in India, Kanpur Nagar District, Uttar Pradesh, and Palghar District, Maharashtra, before and after a measles-rubella supplemental immunization activity (MR-SIA) from 2018 to 2019. Anonymized residual specimens from children 9 months to younger than 15 years of age were collected from public and private diagnostic laboratories and public hospitals and tested for IgG antibodies to measles and rubella viruses. Significant increases in seroprevalence were observed following the MR SIA using the facility-based specimens. Younger children whose specimens were tested at a public facility in Kanpur Nagar District had significantly lower rubella seroprevalence prior to the SIA compared to those attending a private hospital, but this difference was not observed following the SIA. Similar increases in rubella seroprevalence were observed in facility-based and community-based serosurveys following the MR SIA, but trends in measles seroprevalence were inconsistent between the two specimen sources. Despite challenges with representativeness and limited metadata, residual specimens can be useful in estimating seroprevalence and assessing trends through facility-based sentinel surveillance.
Plane turbulent wall jets are traditionally considered to be composed of a turbulent boundary layer (TBL) topped by a half-free jet. However, certain peculiar features, such as counter-gradient momentum flux occurring below velocity maximum in experiments and numerical simulations, suggest a different structure of turbulence therein. Here, we hypothesize that turbulence in wall jets has two distinct structural modes, wall mode scaling on wall variables and free-jet mode scaling on jet variables. To investigate this hypothesis, experimental data from our wall jet facility are acquired using single hot-wire anemometry and two-dimensional particle image velocimetry at three nozzle Reynolds numbers 10 244, 15 742 and 21 228. Particle image velocimetry measurements with four side-by-side cameras capture the longest field of view studied so far in wall jets. Direct spatial spectra of these fields reveal modal spectral contributions to variances of velocity fluctuations, Reynolds shear stress, shear force, turbulence production, velocity fluctuation triple products and turbulent transport. The free-jet mode has wavelengths scaling on the jet length scale ${z_{T}}$, and contains two dominant submodes with wavelengths $5{z_{T}}$ and $2.5{z_{T}}$. The region of flow above the velocity maximum shows the presence of the outer jet mode whereas the region below it shows robust bimodal behaviour attributed to both wall and inner jet modes. Counter-gradient momentum flux is effected by the outer jet mode intruding into the region below velocity maximum. These findings support the hypothesis of wall and free-jet structural modes, and indicate that the region below velocity maximum could be much complex than a conventional TBL.
The ongoing development of technology and AI facilitates the emergence of service robots in various application fields. Hence, the development of robot-infrastructure product-service systems (PSS) will become increasingly important. Based on the existing literature we propose a new methodological approach for a joint development of robot and infrastructure in the context of a socio-technical system with various stakeholders. We suggest digital models and physical prototypes to synchronize service and product development. The applicability is demonstrated for autonomous waste management robots.
To compare the diagnostic accuracy of angled otoendoscopy with pure tone audiometry in predicting ossicular discontinuity in patients of mucosal chronic otitis media.
Methods
Ninety-four patients were included in this prospective study. A 2.7-mm 30° otoendoscope was used to examine ossicular status preoperatively. Hearing thresholds were recorded by pure tone audiometry. Intraoperative ossicular status was recorded as the gold standard. Otoendoscopic findings were recorded as per the criteria has been devised by the authors of this manuscript.
Results
Otoendoscopy was conclusive in 56 (59.6 per cent) patients, with 100 per cent sensitivity, 95.56 per cent specificity, 84.62 per cent positive predictive value, and 100 per cent negative predictive value in the conclusive group. Overall (in 94 patients), diagnostic test values of otoendoscopy were 73.33 per cent sensitivity, 97.47 per cent specificity, 84.62 per cent positive predictive value, and 95.06 per cent negative predictive value. As per the ROC curve, air–bone gap > 38.12dB had the optimal diagnostic test values, with 73 per cent sensitivity, 72 per cent specificity, 33.3 per cent positive predictive value, and 93.4 per cent negative predictive value.
Conclusion
Angled otoendoscopy has better diagnostic accuracy (93.6 per cent) than pure tone audiometry (72.3 per cent; p < 0.001) for preoperative ossicular discontinuity prediction in patients of mucosal chronic otitis media.
The COVID-19 pandemic may disproportionately affect the mental health of healthcare professionals (HCPs), especially patient-facing HCPs.
Aims
To longitudinally examine mental health in HCPs versus non-HCPs, and patient-facing HCPs versus non-patient-facing HCPs.
Method
Online surveys were distributed to a cohort at three phases (baseline, July to September 2020; phase 2, 6 weeks post-baseline; phase 3, 4 months post-baseline). Each survey contained validated assessments for depression, anxiety, insomnia, burnout and well-being. For each outcome, we conducted mixed-effects logistic regression models (adjusted for a priori confounders) comparing the risk in different groups at each phase.
Results
A total of 1574 HCPs and 147 non-HCPs completed the baseline survey. Although there were generally higher rates of various probable mental health issues among HCPs versus non-HCPs at each phase, there was no significant difference, except that HCPs had 2.5-fold increased risk of burnout at phase 2 (emotional exhaustion: odds ratio 2.50, 95% CI 1.15–5.46, P = 0.021), which increased at phase 3 (emotional exhaustion: odds ratio 3.32, 95% CI 1.40–7.87, P = 0.006; depersonalisation: odds ratio 3.29, 95% CI 1.12–9.71, P = 0.031). At baseline, patient-facing HCPs (versus non-patient-facing HCPs) had a five-fold increased risk of depersonalisation (odds ratio 5.02, 95% CI 1.65–15.26, P = 0.004), with no significant difference in the risk for other outcomes. The difference in depersonalisation reduced over time, but patient-facing HCPs still had a 2.7-fold increased risk of emotional exhaustion (odds ratio 2.74, 95% CI 1.28–5.85, P = 0.009) by phase 3.
Conclusions
The COVID-19 pandemic had a huge impact on the mental health and well-being of both HCPs and non-HCPs, but there is disproportionately higher burnout among HCPs, particularly patient-facing HCPs.
The COVID-19 second wave badly affected India. This study assessed public preparedness and attitude towards a new lockdown in the state of West Bengal (WB) along with perception about the COVID pandemic situation.
Methods:
An anonymous questionnaire was administered to all willing adult attendees of a COVID vaccination centre in Kolkata, capital city of WB. Logistic regression was applied to find the relationship between attitude towards lockdown and other selected independent variables.
Results:
Of the 839 persons analyzed, 72.0% were non-health workers; and 55.4% thought that available vaccines reduce COVID-19 risk. Among them, 54.4% wanted stricter guidelines imposed. For preparedness, 42.6% and 28.8% said they would stock additional food and medicines respectively. On multiple logistic regression, being female, having elderly family members, perceiving the second wave as worse, and favouring stricter restrictions, all had odds of favourable attitude towards the new, proposed lockdown.
Conclusions:
A new lockdown was favoured by the majority. However, a well-planned and phased approach for this is needed in the light of many concerns about the previous lockdown. Mental health issues, financial security, medical help at hand, and ease of travel to workplaces are important issues that need to be addressed in case of future lockdown(s).
A dynamically consistent scaling of mean skin friction in zero-pressure-gradient turbulent boundary layers and fully developed pipe and channel flows, is derived. Theoretical arguments are based on transfer of kinetic energy from mean flow to large eddies of turbulence. A single new velocity scale $M/\nu$ is shown to be dynamically relevant for scaling skin friction in all flows; $M$ is the planar kinematic momentum rate of the shear flow and $\nu$ is fluid kinematic viscosity. An asymptotic $-1/2$ power scaling law (in $M$–$\nu$ scaling) is shown to be universally applicable. It is observed that the semi-empirical finite-$Re$ skin friction model, resulting from the asymptotic scaling law, applies well to individual flows, but fails to describe all flows in a universal fashion. This non-universality could be due to the differences in flow boundary conditions at finite Reynolds numbers and flow geometry, that affect the outer-layer structures in these flows. It is argued that these differences may be simply absorbed by considering differences in the shapes of mean velocity profiles amongst these flows. An empirical correction to $M$–$\nu$ scaling is proposed based on Clauser's shape factor $G$. It is demonstrated that data from all flows in this new, semi-empirical $M$–$\nu$–$G$ scaling collapse remarkably well onto a single universal curve. The corresponding universal finite-$Re$ model in $M$–$\nu$–$G$ scaling is shown to describe this curve to an excellent accuracy. These results underscore the importance of a dynamically consistent approach towards revealing universality of skin friction scaling in wall turbulence.
Data sharing efforts to allow underserved groups and organizations to overcome the concentration of power in our data landscape. A few special organizations, due to their data monopolies and resources, are able to decide which problems to solve and how to solve them. But even though data sharing creates a counterbalancing democratizing force, it must nevertheless be approached cautiously. Underserved organizations and groups must navigate difficult barriers related to technological complexity and legal risk. To examine what those common barriers are, one type of data sharing effort—data trusts—are examined, specifically the reports commenting on that effort. To address these practical issues, data governance technologies have a large role to play in democratizing data trusts safely and in a trustworthy manner. Yet technology is far from a silver bullet. It is dangerous to rely upon it. But technology that is no-code, flexible, and secure can help more responsibly operate data trusts. This type of technology helps innovators put relationships at the center of their efforts.
Differential attainment (DA) amongst Black and Minority Ethnic (BAME) medical students and postgraduate trainees including Psychiatry trainees has been extensively documented in medical education, with non-white medical students being 2.5 times more likely to fail high-stake examinations compared to their White counterparts. The Equality Act 2010 places a responsibility on public bodies such as Royal Colleges to address discrimination in training and assessment. Understanding DA in undergraduate medical education can help understand DA in the postgraduate setting. Consequently, this systematic review aims to detect the processes that enable and impede DA in UK undergraduate medical education.
Method
Seven online databases including PubMed, Scopus, PyschInfo, and ERIC were searched. A formal grey literature search was also conducted. Inclusion criteria comprised studies dated from January 1995 to present and included UK undergraduate medical students. We present the preliminary findings from 13 papers, analysed to create a conceptual framework for a further mixed methods analysis. The studies were critically appraised for methodological quality.
Result
Five key themes emerged from the preliminary analysis of 13 papers. BAME students experienced:
Being ‘divergent’: Not feeling part of the current organisational learning milieu
Lack of social capital: Difficulty in being absorbed into existing ‘networks’ of relationships in a manner that is ‘approachable’ and not ‘intimidating’
Continuum of discrimination: ‘Indirect’ impact of subtle communication processes in the learning environment undermining individual ‘belief’ in own performance
Institutional discriminatory factors: Culture, rules, norms, and behavioural routines of educators that lead to differential outcomes for learners
Lack of external support: Relative lack of interventions tackling DA.
Conclusion
The key finding of this review is that British BAME undergraduate medical students experience discriminatory behaviours early in medical schools that impact on personal, educational, and professional outcomes. These factors may need to be borne in mind by postgraduate training organisations such as the Royal College of Psychiatrists as they commence the challenging task of addressing DA.
ABSTRACT IMPACT: We describe a novel methodology that combines CRISPR/Cas9-induced double stranded DNA breaks with homology dependent repair from an adeno associated virus (AAV) encoded template to generate single-allele edited isogenic cell line models of cancer-associated mutations with high efficiency. OBJECTIVES/GOALS: Conventional approaches to creating isogenic knock-ins, to model disease-associated mutations, are limited by poor efficiency and loss of the mutant allele on extended culture. We present an optimized editing approach combining CRISPR/Cas9 with Adeno-associated virus, using mutant SF3B1 as a prototype. METHODS/STUDY POPULATION: Left and right homology arms for SF3B1 were PCR amplified and cloned into pAAV-SEPT-Acceptor plasmid (containing a chimeric intron, neomycin resistance cassette and polyA tail). The disease-associated K700E mutation was introduced by site-directed mutagenesis. Single guide RNA (sgRNA) complexed with recombinant Cas9 along with the AAV donor were delivered into K562 cells, G418 resistant clones selected, and screened for integration by PCR. Confirmed clones were then transduced with a doxycycline-inducible Cre-recombinase containing lentiviral vector. Inducible expression of Cre-recombinase and expression of the mutant allele were confirmed by Western blot and Sanger sequencing respectively. RESULTS/ANTICIPATED RESULTS: Targeted-integration efficiencies among the Neo-resistant clones, generated by AAV-alone and AAV+CRISPR/Cas9, were 16% and 94%, respectively. Single cell cloning after Cre-mediated excision of loxp was unsuccessful presumably due to toxicity of the K700E mutation. To overcome this limitation, clones were transduced with doxycycline-inducible Cre-recombinase lentiviral vector. Doxycycline induction of Cre-recombinase resulted in reliable excision of the loxp cassette and expression of mutant allele at about 50% variable allele frequency (as determined by Sanger sequencing). The approach was validated in additional cell lines and for introduction of N-terminal FLAG tag for SF3B1. DISCUSSION/SIGNIFICANCE OF FINDINGS: Combining AAV and CRISPR/Cas9 can generate scalable single-dominant allele mutants with high precision and efficiency compared to AAV or CRISPR alone. Together with inducible Cre-recombinase, our approach can generate isogenic models where the mutation confers a growth disadvantage.
Studies in the literature on two-dimensional, fully developed, turbulent wall jets on flat surfaces, have invariably reckoned on either the nozzle initial conditions or the asymptotic conditions far downstream, as scaling parameters for the streamwise variations of length and velocity scales. These choices, however, do not square with the notion of self-similarity, which is essentially a ‘local’ concept. We first demonstrate that the streamwise variations of velocity and length scales in wall jets show remarkable scaling with local parameters, i.e. there appear to be no imposed length and velocity scales. Next, it is shown that the mean velocity profile data suggest the existence of two distinct layers – the wall (inner) layer and the full-free jet (outer) layer. Each of these layers scales on the appropriate length and velocity scales and this scaling is observed to be universal, i.e. independent of the local friction Reynolds number. Analysis shows that the overlap of these universal scalings leads to a Reynolds-number-dependent power-law velocity variation in the overlap layer. It is observed that the mean-velocity overlap layer corresponds well to the momentum-balance mesolayer and there appears to be no evidence for an inertial overlap; only the meso-overlap is observed. Introduction of an intermediate variable absorbs the Reynolds-number dependence of the length scale in the overlap layer and this leads to a universal power-law overlap profile for mean velocity in terms of the intermediate variable.
To compare the microbiological profile, clinical course and outcome of acute diarrhoea in children aged <5 years having severe acute malnutrition (SAM) with those of children having normal nutritional status.
Design:
Cross-sectional comparative study.
Setting:
Tertiary-care hospital catering mainly to the urban poor of East Delhi, India.
Participants:
Children aged <5 years (n 140; seventy with SAM (cases) and seventy with normal anthropometry (controls)) with acute diarrhoea (duration < 14 d). Stool samples were collected for conventional culture, microscopy, acid-fast staining, rotavirus and Cryptosporidium antigen detection, and subtyping of diarrhoeagenic Escherichia coli (DEC). We followed-up these children for persistent diarrhoea and subsequent diarrhoeal episode in the next 3 months.
Results:
Rotavirus was detected in six (9 %) cases and in fifteen (21 %) controls (P = 0·03; OR = 0·34; 95 % CI 0·12, 0·94). DEC was isolated significantly more in cases compared with controls (93 v. 64 %; P < 0·001; OR = 7·25; 95 % CI 2·57, 20·4). Cryptosporidium was detected in seven (10 %) cases and five (7 %) controls. Total duration of diarrhoea and percentage change in weight after resolution of diarrhoea were comparable between cases and controls. At 3-month follow-up, number of subsequent episodes of diarrhoea and persistent diarrhoea were comparable between the two groups.
Conclusions:
Rotavirus was found significantly less frequently, whereas DEC was detected more frequently in children with SAM in comparison to non-malnourished children. To further reduce diarrhoea-related mortality, preventive and therapeutic interventions need to be designed against organisms causing diarrhoea in children with SAM.
(i) To assess diagnostic accuracy of mid-upper arm circumference (MUAC) for screening thinness and severe thinness in Indian adolescent girls aged 10–14 and 15–19 years compared with BMI-for-age Z-score (BAZ) <−2 and <−3 as the gold standard and (ii) to identify appropriate MUAC cut-offs for screening thinness and severe thinness in Indian girls aged 10–14 and 15–19 years.
Design:
Cross-sectional, conducted October 2016–April 2017.
Setting:
Four tribal blocks of two eastern India states, Chhattisgarh and Odisha.
Participants:
Girls (n 4628) aged 10–19 years. Measurements included height, weight and MUAC to calculate BAZ. Standard diagnostic accuracy tests, receiver–operating characteristic curves and Youden index helped arrive at MUAC cut-offs at BAZ < −2 and <−3, as gold standard.
Results:
Mean MUAC and BMI correlation was positive (0·78, P = 0·001 and
r2 = 0·61). Among 10–14 years, MUAC cut-off corresponding to BAZ < −2 and BAZ < −3 was ≤19·4 and ≤18·9 cm. Among 15–19 years, corresponding values were ≤21·6 and ≤20·7 cm. For both BAZ < −2 and BAZ < −3, specificity was higher in 15–19 v. 10–14 years. State-wise variations existed. MUAC cut-offs ranged from 17·7 cm (10 years) to 22·5 cm (19 years) for BAZ < −2, and from 17·0 cm (10 years) to 21·5 cm (19 years) for BAZ < −3. Single-age area under the curve range was 0·82–0·97.
Conclusions:
Study provides a case for use of year-wise and sex-wise context-specific MUAC-cut-offs for screening thinness/severe thinness in adolescents, rather than one MUAC cut-off across 10–19 years, depending on purpose and logistic constraints.
To evaluate the survival outcomes and toxicities experienced by non-metastatic head and neck cancer (HNC) patients receiving modulated radiotherapy (RT).
Materials and methods
A total of 608 HNC patients treated consecutively from March 2010 to December 2014 with common subsites (oral cavity, oropharynx, hypopharynx, larynx and nasopharynx) of HNCs formed the study group. Eligible patients included those treated with radical or postoperative RT between March 2010 and December 2014. More than 90% patients received modulated RT [intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT)] with concurrent chemotherapy as per stage guidelines. Demographic parameters and disease-related factors were analysed. Disease-free survival (DFS) was calculated from end date of RT till last follow-up or last date of disease control. Overall survival (OS) was calculated from date of registration to last follow-up date if alive. The primary endpoint was survival. The statistical analyses were performed using SPSS version 20.0 and Kaplan–Meier method was used for calculation survival.
Results
Among the evaluable patients, the median age was 60 years (range: 16–93) with male preponderance (male:female – 513:95). Majority were squamous cell carcinoma 93·4% (568/608). The subsites treated were oral cavity 36·8% (224). oropharynx 26·4% (161), larynx 19·7% (120), hypopharynx 10% (62) and nasopharynx 6·4% (41). RT intent was radical in 63·5% (386) and postoperative in 36·5% (222), with 59·5% (362) receiving concurrent chemotherapy. At last follow-up, 348 (57·2%) patients were alive, 169 (27·7%) patients had succumbed to disease and 120 (24·6%) patients had recurrent disease. Out of 120 recurrent cases loco-regional recurrence, nodal recurrence and distant metastases were seen in 62 (51·7%), 25 (20·8%), 33 (27·5%), respectively. In the entire study cohort at 2 year OS and DFS was 80 and 79% whereas 3 years OS and DFS was 70 and 75%, respectively.
Conclusions
In our study, 2 years and 3 years OS and DFS rates are found comparable to the international data with acceptable toxicity profile with the use of modulated RT. It seems to be possible because of stringent departmental protocols and good medical physics support. Our data re-validates need and benefit of advanced RT techniques like IG-IMRT and VMAT for both postoperative and radical HNC treatment at the cost of minimal long-term side effects. Future stringent follow-up and quality of life issues are being considered in a prospective manner.
Antioxidant therapies to control oxidative damage have already attracted worldwide attention in recent years. Extensive studies on phytochemicals in cell culture system and animal models have provided a wealth of information on the mechanism by which such nutraceuticals show their beneficial effect. Nutraceuticals include plant-derived factors (phytochemicals) and factors derived from animal sources as well as from microbial sources. The activities of nutraceuticals are broad and include antioxidation, modulation of enzyme activity and modification of natural hormonal activity (agonist or antagonist) to act as a precursor for one or more beneficial molecules. Antioxidants scavenge free radicals that cause cell damage. Antioxidant consumption during radiotherapy and its effects are still controversial. Some studies suggest that antioxidant supplementation during chemotherapy or radiotherapy may be beneficial and some, harmful. Wheat grass is rich in superoxide dismutase, an antioxidant enzyme. Radiotherapy causes tumour cell kill via activation of reactive oxygen species, specifically by the hydroxyl radical and needs the reactive species for effective tumour control. Wheat grass which is rich in free radical scavengers can interfere with reactive oxygen species generated by radiation for tumour cell kill and can be detrimental to the therapy per se.
Purpose
To hypothesise if the antioxidant properties of wheat grass could influence tumour activity, the effects of radiation therapy on tumour cells can be nullified when wheat grass is taken during radiotherapy.
To analyse the preliminary results of CyberKnife stereotactic radiotherapy (SBRT) boost in primary head and neck cancer patients among Indian population.
Methods and materials
A total of nine patients of primary head and neck cancer were treated with CyberKnife SBRT boost after intensity-modulated radiation therapy (IMRT). The median phase 1 IMRT dose was 54 Gy/27 fractions. Histological types included squamous cell carcinoma (n=7) and adenoid cystic carcinoma (n=2). Response was evaluated using positron emission tomography/computed tomography and detailed clinical examination.
Results
As a preliminary analysis with median follow up of 8 months (range: 6–19 months), phase 2 median tumour volume of 16·3 cc and a median dose of 5 Gy per fraction, eight patients had loco-regionally stable disease and one had distant metastasis. With objective assessment five patients had complete response. Treatment was well tolerated with no grade 3 or more acute toxicities directly related to CyberKnife boost.
Conclusion
CyberKnife SBRT boost is an attractive option for primary head and neck cancers especially where disease is in close proximity to critical structures hindering radical dose delivery. Future prospective analysis and optimum assessment of total biological effective dose (BED) in a properly selected case might actually benefit the use of CyberKnife SBRT boost.
Metastases to the parotid region are relatively infrequent and originate primarily from head and neck cancer. Metastases of an infraclavicular origin are uncommon. Moreover, metastasis from the carcinoma of urinary bladder (CUB) to any part of the head and neck, including parotid gland, is rare. Surgery and chemotherapy are usually offered. We report a case of solitary parotid metastasis from CUB, who was successfully treated with stereotactic body radiotherapy (SBRT) using CyberKnife. SBRT is a safe alternative in cases unwilling/unfit for surgery.