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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.
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.
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.
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.
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.
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.
Cross-sectional comparative study.
Tertiary-care hospital catering mainly to the urban poor of East Delhi, India.
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.
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.
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.
Giant cell tumor (GCT) of bone is a common benign lesion that causes significant morbidity due to the failure of modern medical and surgical treatment. Surface ultra-structures of giant cells (GCs) may help in distinguishing aggressive tumors from indolent GC lesions. This study aimed to standardize scanning electron microscopic (SEM) imaging of GC from GCT of bone. Fresh GCT collected in Dulbecco's Modified Eagle Medium was washed to remove blood, homogenized, or treated with collagenase to isolate the GCs. Mechanically homogenized and collagenase-digested GCs were imaged on SEM after commonly used drying methodologies such as air-drying, tetramethylsilane (TMS)-drying, freeze-drying, and critical point-drying (CPD) for the optimization of sample processing. The collagenase-treated samples yielded a greater number of isolated GC and showed better surface morphology in comparison to mechanical homogenization. Air-drying was associated with marked cell shrinkage, and freeze-dried samples showed severe cell damage. TMS methodology partially preserved the cell contour and surface structures, although the cell shape was distorted. GC images with optimum surface morphology including membrane folding and microvesicular structures on the surface were observed only in collagenase-treated and critical point-dried samples. Collagenase digestion and critical point/TMS-drying should be performed for optimal SEM imaging of individual GCs.
(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.
Cross-sectional, conducted October 2016–April 2017.
Four tribal blocks of two eastern India states, Chhattisgarh and Odisha.
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.
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.
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.
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.
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.
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.
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.
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.
Constitute hypothesis for origin of supernumerary phantom limb (SPL) after stroke.
Single case description, review of literature and formulation of hypothesis.
A 59-year-old lady was evaluated for complaints of left-sided hemiparesis and extra limbs attached to her left shoulder for the past 7 months. Neuropsychological assessment revealed left hemineglect with SPL, and profile suggested bilateral frontal, right parietotemporal and basal ganglia involvement. Magnetic resonance imaging brain scan showed gliotic cavity secondary to the old haematoma in right putamen with white matter changes in the right frontoparietotemporal lobes.
The conceptual framework of body schema can be used to classify many of the neurological disorders of body representation. Generation of SPL comes under the subtype of pathology of updating among the disorders of body schema. The continuous updating allows the body schema to modulate perceptual processing of objects according to their position in space. Brain areas classified as parts of motor system can, under pathological conditions (haemorrhage), influence body perception. So, when she used to move her arm, the representation of the estimated position was not updated by the motor commands. Sensory and motor information therefore becomes discrepant, and failure to integrate these two sources of information leads to loss of normal coherence, and the perceived shape of the body was altered by adding a SPL to accommodate the discrepancy.
The motivation and distinct approach for this work is the use of intraband transitions within colloidal quantum dots for the detection of mid- (3-5 μm) and/or long-wave (8-14 μm) infrared light. The CdSe colloidal quantum dot/MEH-PPV conducting polymer nanocomposite material is well-suited for this application due to the ∼1.5 eV difference between the corresponding electron affinities. Therefore, CdSe colloidal quantum dots embedded in MEH-PPV should provide electron quantum confinement such that intraband transitions can occur in the conduction band. Further, it is desirable to deposit these nanocomposites on semiconductor substrates to enable charge transfer of photogenerated electron-hole pairs from the substrate to the nanocomposite. In this way, optoelectronic devices analogous to those achieved using Stranski-Krastanow quantum dots grown by epitaxy can be realized. To date, there have been relatively few investigations of colloidal quantum dot nanocomposites deposited on GaAs substrates. However, it is crucial to develop a better understanding of the optical properties of these hybrid material systems if such heterostructures are to be used for optoelectronic devices, such as infrared photodetectors. By depositing the nanocomposites on GaAs substrates featuring different doping characteristics and measuring the corresponding Fourier transform infrared absorbance, the feasibility of these intraband transitions is demonstrated at room temperature.
We have investigated the diffusion characteristics of Cu in nanocrystalline, polycrystalline and single crystal TiN thin films, which are being used as a diffusion barrier for sub-quarter-micron metallization. These films were synthesized on Si (100) substrate by first ablating TiN and then ablating Cu targets using Pulse Laser Deposition technique. The three different microstructures of TiN were achieved by growing the films at different substrate temperatures, where higher temperatures (650 °C) leads to epitaxy. Then a uniform thin layer of Cu was deposited on TiN/Si substrate at room temperature for all the three depositions above. These structures were characterized using X-Ray diffraction technique and high-resolution transmission electron microscopy. Each sample is then annealed at 500 °C for 30min to study the diffusion barrier characteristics as a function of microstructure of TiN. Study of diffusion profile and Cu concentration measurement were performed using Scanning Transmission Electron Microscopy-Z contrast Imaging (0.12nm resolution), Electron Energy Loss Spectroscopy and Secondary Ion Mass Spectroscopy. From the results obtained the effect of microstructure of TiN thin films on the diffusion characteristics of Cu after annealing was analyzed. Four points probe resistivity measurements were made to establish structure property correlations.
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