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OBJECTIVES/GOALS: Assess molecular and cellular mechanisms of allograft loss in kidney biopsies using digital spatial profiling and clinical outcomes data. METHODS/STUDY POPULATION: Patients with chronic allograft dysfunction (CGD), enrolled in the Deterioration of Kidney Allograft Function (DeKAF) study, with or without eventual allograft loss, were included. CGD was defined as a >25% increase in creatinine over 3 months relative to a baseline. Kidney biopsy tissue was assessed by Nanostring GeoMX digital spatial profiling (DSP) after staining with anti-pan-cytokeratin, anti-CD45, anti-CD68, Syto-13, to identify specific cell populations, and Nanostring’s Whole Transcriptome Atlas (WTA), to quantify the distribution of transcripts across the biopsy. Up to 14 regions of interest (ROIs) were selected, with or without glomerulus. CIBERSORT was used to perform cell deconvolution. Clinical and outcomes data were from the DeKAF study and United States Renal Data System. RESULTS/ANTICIPATED RESULTS: Macrophage (M1) cell population abundance was significantly different in ROIs with glomerulus between graft loss and no graft loss. Principle component analysis of differentially expressed genes resulted in transcriptomes in ROIs that cluster together by clinical outcome of graft loss or no graft loss. There were 203 DEGs in ROIs with glomerulus that were different by graft loss or no graft loss. By pathway analysis, these 203 DEGS were enriched in the T-cell activation, integrin signaling and inflammation pathways. DISCUSSION/SIGNIFICANCE: DSP of kidney allograft biopsies allows for the identification and quantification of specific cell types, such as macrophages and molecular transcripts as potential drug targets. This data can be used to understand mechanisms of kidney allograft loss and may lead to improved immune suppression in kidney transplant recipients.
The impact of modern high-precision conformal techniques on rare but highly morbid late complications of head and neck radiotherapy, such as necrosis of the bone, cartilage or soft-tissues, is not well described.
Method
Medical records of head and neck cancer patients treated in prospective clinical trials of definitive high-precision radiotherapy were reviewed retrospectively to identify patients with necrosis.
Results
Twelve of 290 patients (4.1 per cent) developed radiotherapy necrosis at a median interval of 4.5 months. There was no significant difference in baseline demographic (age, gender), disease (primary site, stage) and treatment characteristics (radiotherapy technique, total dose, fractionation) of patients developing radiotherapy necrosis versus those without necrosis. Initial management included antibiotics or anti-inflammatory agents, tissue debridement and tracheostomy as appropriate followed by hyperbaric oxygen therapy and resective surgery for persistent symptoms in selected patients.
Conclusion
Multidisciplinary management is essential for the prevention, early diagnosis and successful treatment of radiotherapy necrosis of bone, cartilage or cervical soft tissues.
In spite of continuous refinements in tympanoplasty techniques, results are variable, and it is not uncommon to see a discharging eardrum even after a good graft uptake. This study aimed to evaluate the efficacy of total annulus excision tympanoplasty in comparison with conventional underlay tympanoplasty.
Method
This was a double blinded, randomised, controlled trial performed at a tertiary care centre. After inclusion and exclusion criteria were met, 56 patients were enrolled and randomised, and 28 patients were allocated to each group (group A (conventional tympanoplasty) and group B (total annulus excision)). Patients and evaluators were blind to the procedure performed.
Results
Patients in group B (total annulus excision) showed better graft uptake and no discharge with better gains in air conduction thresholds (p < 0.05) when compared with group A (conventional tympanoplasty).
Conclusion
In view of the advantages it offers, total annulus excision tympanoplasty may be preferred over the conventional techniques in patients with central perforations.
Non-invasive diagnostic tests (Table 3.1) are undertaken to support the clinical impression of and to quantify the extent of cardiac disease. Repeating the investigations over time allows for monitoring of management protocols and follow-up on disease progression. Information may be supplemented with advanced and invasive investigations (e.g. angiography in suspected coronary artery disease (CAD)).
Introduction: Competence in procedural skills is vital within the emergency department. Challenging procedures such as cricothyroidotomy are difficult to master as they are rare and hard to train for. Additionally, common procedures such as chest tube insertions require practice to become sufficiently competent. Opportunities to hone these skills are essential in residency training. This project aimed to create instructional video modules for specific emergency medicine (EM) procedures and gauge their utility as adjunctive resources for procedural learning in the EM residency curriculum. Methods: Tutorial videos for clamshell thoracotomy, cricothyroidotomy, and chest tube insertion were filmed within a cadaver lab with step-by-step instructions. The footage was edited and overlaid with a pre-prepared audio narration using Camtasia®/Apple® Video Editing software. These videos were embedded within modules that included foundational knowledge relevant to the procedures, including anatomy, physiology and pathophysiology. The modules were peer-edited by licensed EM staff physicians and distributed to EM residents and staff physicians for analysis. Qualitative and quantitative analysis relied upon participants’ answers to questions and a Modified Task Value Scale, respectively. Results: Ten participants were included in the analysis, including EM residents (n = 6) and staff emergency physicians (n = 4). Qualitative feedback suggested that positive aspects of the modules included visuals, content, narration, and review of anatomy. Negative aspects included the lack of indications for procedures, technical details, real patient examples, and a speed up function. Quantitative feedback resulted in scores of 4 and above out of 5 on the Motivated Task Value Scale across all aspects for all the modules. Furthermore, analysis revealed an average score of 3.9 for inclination to access more modules such as these, and a score of 4.4 for overall perception of the modules. Conclusion: Participants found the video modules valuable to their learning, both qualitatively and quantitatively. This study was limited by a small sample size of modules and a low number of participants. Furthermore, a more detailed analysis with further measures, including self-efficacy and self-confidence, would yield more comprehensive conclusions. However, video-based modules provide an effective and easily accessible adjunctive tool to acquire skill and confidence with EM procedures, for medical learners and staff physicians.
Recent work has implicated one type of horizontal strabismus (exotropia) as a risk factor for schizophrenia. This new insight raises questions about a potential common developmental origin of the two diseases. Seasonality of births is well established for schizophrenia. Seasonal factors such as light exposure affect eye growth and can cause vision abnormalities, but little is known about seasonality of births in strabismus. We examined birth seasonality in people with horizontal strabismus in a retrospective study in Washoe County, Nevada, and re-examined similar previously obtained data from Osaka, Japan. We then compared seasonal patterns of births between strabismus, refractive error, schizophrenia and congenital toxoplasmosis. Patients with esotropia had a significant seasonality of births, with a deficit in March, then increasing to an excess in September, while patients with exotropia had a distinctly different pattern, with an excess of births in July, gradually decreasing to a deficit in November. These seasonalities were statistically significant with either χ2 or Kolmogorov–Smirnov-type statistics. The birth seasonality of esotropia resembled that for hyperopia, with an increase in amplitude, while the seasonality for myopia involved a phase-shift. There was no correlation between seasonality of births between strabismus and congenital toxoplasmosis. The pattern of an excess of summer births for people with exotropia was remarkably similar to the well-established birth seasonality of one schizophrenia subtype, the deficit syndrome, but not schizophrenia as a whole. This suggests a testable hypothesis: that exotropia may be a risk factor primarily for the deficit type of schizophrenia.
Soybean is a leading oilseed crop in India, which contains about 40% of protein and 20% of oil. Core collection will accelerate the management and utilization of soybean genetic resources in breeding programmes. In the present study, eight agromorphological traits of 3443 soybean germplasm were analysed for the development of core collection using the principal component score (PCS) strategy and the power core method. The PCS strategy yielded core collection (CC1) of 576 accessions, which accounted for 16.72% of the entire collection (EC). The analysis based on the power core programme resulted in CC2 of 402 accessions, which accounted for 11.67% of the EC. Statistical analysis showed similar trends for the mean and range estimated in both core collections and EC. In addition, the variance, standard deviation and coefficient of variance were in general higher in core collections than in the EC. The correlations observed in the EC in general were preserved in core collections. A total of 311 and 137 unique accessions were found in CC1 and CC2 in addition to 265 accessions that were found to be common in both core collections. These 265 common accessions were the most diverse core sets, which accounted for 7.64% of the EC. We proposed to constitute an integrated core collection (ICC) by integrating both common and unique accessions. The ICC comprised 713 accessions, which accounted for about 20.62% of the EC. Statistical analysis indicated that the ICC captured maximum variation than CC1 and CC2. Therefore, the ICC can be extensively evaluated for a large number of economically important traits for the identification of desirable genotypes and for the development of mini core collection in soybean.
This study aimed to assess the prevalence and profile of ear diseases in children from Delhi, India.
Methods:
A population-based cross-sectional door-to-door survey was carried out in two districts of Delhi, and involved children of all demographic sections of the region. A total of 4626 children aged between 18 days and 15 years underwent examinations including otoscopy, impedance audiometry and hearing screening.
Results:
In all, 14.8 per cent of the study sample was diagnosed with one or more ear morbidities, the most common being cerumen impaction (7.5 per cent) and chronic suppurative otitis media (3.6 per cent). There was clinical evidence of otitis media with effusion in 2 per cent of children, and 0.96 per cent had otitis externa (bacterial and fungal). The point prevalence of acute suppurative otitis media was 0.39 per cent. In all, 0.45 per cent of children were found to have an undiagnosed foreign body within the ear canal.
Conclusion:
The high prevalence of ear disease poses a significant public health problem in Delhi.
Objective: To report the autosomal dominant inheritance of the Jervell and Lange-Nielsen syndrome in a highly inbred family, the initiation of Torsades de Pointes, and the natural history of the syndrome based on a 16-year follow-up of the kindred. Method: A family tree was constructed that included 66 blood relatives from three successive generations. Electrocardiograms were obtained from 59 living members including the proband, four members from a nuclear family, and 54 from the extended family. Evoked response audiometry was recorded for the proband and the nuclear family. All 59 family members were followed up regularly for 16 years. Results: A total of 24 living members were affected – QTc: 480–680 ms. The proband had long QTc, bilateral high-tone sensorineural deafness, recurrent syncope, and Torsades de Pointes. The asymptomatic father had long QTc and unilateral high-tone sensorineural deafness that involved specifically the left ear. One asymptomatic sibling of the proband had long QTc and normal hearing. The mother and another sibling were asymptomatic; QTc and hearing were normal in both. A total of 21 affected members from the extended family had only long QTc, and all were asymptomatic. There were three congenitally deaf first cousins who had recurrent syncope and adrenergic-triggered sudden death. In all, seven of 10 parents had consanguineous marriage to a first cousin. Each affected offspring had at least one affected parent. The severely symptomatic proband who received only β-blocker therapy and the 23 affected members without antiadrenergic therapy, all remained asymptomatic throughout the 16-year follow-up period. Conclusion: Jervell and Lange-Nielsen syndrome was inherited as autosomal dominant in this kindred. The majority of the affected members had a mild phenotype. The severity of auditory and cardiac phenotypes corresponded.
There is a considerable scarcity of reliable population-based data on the prevalence of preventable ear disorders in developing countries. This study was conducted to determine the prevalence of preventable ear disorders in primary school children (aged 5 to 12 years) in northern India.
Method:
A pro forma questionnaire was used to screen 15 718 primary school children in New Delhi for ear disorders. Ear examinations were conducted using otoscopy and impedance audiometry.
Results:
Impacted cerumen was prevalent in 7.93 per cent of schoolchildren, 4.79 per cent suffered from chronic otitis media and 3.06 per cent suffered from otitis media with effusion. Acute otitis media was detected in 0.65 per cent and foreign bodies were found in 0.34 per cent of the children.
Conclusion:
Preventable ear diseases posed a significant health problem among children at primary school level. Regular screening of children during this stage would ensure that their school lives were not affected by hearing impairments or preventable ear disorders. Information gathered in this study will help in effective treatment prioritisation of ear disorders, planning and resource allocation.
The present cross-sectional study was conducted to determine the vitamin D status of pregnant Indian women and their breast-fed infants. Subjects were recruited from the Department of Obstetrics, Armed Forces Clinic and Army Hospital (Research and Referral), Delhi. A total of 541 apparently healthy women with uncomplicated, single, intra-uterine gestation reporting in any trimester were consecutively recruited. Of these 541 women, 299 (first trimester, ninety-seven; second trimester, 125; third trimester, seventy-seven) were recruited in summer (April–October) and 242 (first trimester, fifty-nine, second trimester, ninety-three; third trimester, ninety) were recruited in winter (November–March) to study seasonal variations in vitamin D status. Clinical, dietary, biochemical and hormonal evaluations for the Ca–vitamin D–parathormone axis were performed. A subset of 342 mother–infant pairs was re-evaluated 6 weeks postpartum. Mean serum 25-hydroxyvitamin D (25(OH)D) of pregnant women was 23·2 (sd 12·2) nmol/l. Hypovitaminosis D (25(OH)D < 50 nmol/l) was observed in 96·3 % of the subjects. Serum 25(OH)D levels were significantly lower in winter in the second and third trimesters, while serum intact parathormone (iPTH) and alkaline phosphatase levels were significantly higher in winter in all three trimesters. A significant negative correlation was found between serum 25(OH)D and iPTH in mothers (r − 0·367, P = 0·0001) and infants (r − 0·56, P = 0·0001). A strong positive correlation was observed between 25(OH)D levels of mother–infant pairs (r 0·779, P = 0·0001). A high prevalence of hypovitaminosis D was observed in pregnancy, lactation and infancy with no significant inter-trimester differences in serum 25(OH)D levels.
We have synthesized nickel by means of pulsed laser ablation. A nickel disc was used for ablation with the focused output of fundamental harmonic from Nd:YAG laser. X-ray diffraction result shows that the synthesized nanoparticles are of pure metallic nickel with a face-centred cubic structure and the average particle size is 35 nm. The extended X-ray absorption fine structure (EXAFS) studies of pure nickel foil and the synthesized nanoparticles show similar structures. The position of the main peak is same in these nanoparticles with reference to the nickel foil. The only difference was observed in the reduction of the amplitude. The nearest-neighbour distance is similar as for pure nickel foil. The Debye–Waller factor is also similar. There is no trace of oxide and hydroxide in the EXAFS data, suggesting that the synthesized nanoparticles contain only nickel metal.
Rubella, a mild, vaccine-preventable disease, can manifest as congenital rubella syndrome (CRS), a devastating disease of the fetus. To emphasize the inadequacy of the existing rubella vaccination programme in India, we evaluated epidemiological evidence of rubella virus activity with data available from a tertiary-care centre. The proportion of suspected CRS cases that were laboratory confirmed increased from 4% in 2000 to 11% in 2008. During the same period, 329 clinically suspected postnatal rubella cases were tested of which 65 (20%) were laboratory confirmed. Of women (n=770) of childbearing age, 12·5% were susceptible to rubella.
Phagocytosis prevents the multiplication of Streptococcus suis in blood samples from conventionally reared adult pigs. It is mediated by antibody, probably IgM, present in the serum of adults and specifically directed against the capsular polysaccharide of S. suis. The blood of young pigs reared in a ‘pathogen-free’ environment allows multiplication of encapsulated S. suis. Of 160 piglets conventionally reared, the blood of 92(58%) did not permit multiplication of S. suis. Blood from the remaining 68(42%) allowed multiplication but became bacteriostatic when the animals reached the age of 6 to 8 weeks. Serum from adult pigs confers bacterio static activity on blood from susceptible piglets in vitro and passively protects such piglets against experimental S. suis infection in vivo.
We thank Dr T. J. L. Alexander, formerly of Ontario Veterinary College, and Mr P. C. Trexler of the Royal Veterinary College, London, for providing us with serum from gnotobiotic pigs.
The work described in this report was carried out by one of us (K. K. A.) during the tenure of a Commonwealth Scholarship and was incorporated in a dissertation submitted for the Ph.D. degree of the University of Cambridge.
Field experiments were made under natural rainfall during the winter seasons of 1972–3 and 1973–4 at the Indian Agricultural Research Institute, New Delhi, to study the soil water use by barley varieties as influenced by nitrogen rates, mulching and foliar application of antitranspirants. Both Ratna and Vijaya varieties of barley had similar efficiency of water use.
Total water use was not much different for various treatments but straw mulch and kaolin decreased evapotranspiration at tillering and pre-flowering stages enabling the plants to use more water at critical stages of grain formation. Application of nitrogen, straw mulch and a foliar coating of kaolin increased the efficiency of water use.
To analyse current trends in our population with respect to the presentation, diagnosis and management of tubercular and chronic pyogenic osteomyelitis of the cranio-facial bones.
Design:
Retrospective study.
Setting:
Tertiary healthcare centre.
Patients and methods:
The study population comprised 14 patients with tubercular and chronic pyogenic osteomyelitis who were managed in the otorhinolaryngology department between May 2002 and December 2005.
Results:
Odontogenic infections, sinus infections and aural infections were the most commonly identified aetiological factors. Most of the patients presented with swelling, pain and discharging sinus. The diagnosis was established on the basis of clinical evaluation, radiological investigations and histopathological analysis, with six cases diagnosed with tubercular osteomyelitis and eight cases with chronic pyogenic osteomyelitis. All the patients were initially commenced on oral antibiotics, which were continued for two weeks in all cases with chronic pyogenic osteomyelitis. All the patients with pyogenic osteomyelitis underwent surgical management, with one patient requiring repeated surgical interventions. All the patients with tubercular osteomyelitis received anti-tubercular chemotherapy, with complete cure.
Conclusions:
Osteomyelitis of the cranio-facial bones is an uncommon entity which requires a high index of clinical suspicion along with radiological and histopathological investigations in order to establish the diagnosis. Tubercular osteomyelitis is clinically and radiologically indistinguishable from pyogenic osteomyelitis, and the two conditions can be differentiated only on the basis of histopathological evaluation of involved tissue.