Vitamin D insufficiency in the first 6 months of infancy and challenge-proven IgE-mediated food allergy at 1 year of age: a case-cohort study.

BACKGROUND: Ecological evidence suggests vitamin D insufficiency (VDI) due to lower ambient ultraviolet radiation (UVR) exposure may be a risk factor for IgE-mediated food allergy. However, there are no studies relating directly measured VDI during early infancy to subsequent challenge-proven food allergy. OBJECTIVE: To prospectively investigate the association between VDI during infancy and challenge-proven food allergy at 1 year. METHODS: In a birth cohort (n = 1074), we used a case-cohort design to compare 25-hydroxyvitamin D3 (25(OH)D3 ) levels among infants with food allergy vs a random subcohort (n = 274). The primary exposures were VDI (25(OH)D3 <50 nM) at birth and 6 months of age. Ambient UVR and time in the sun were combined to estimate UVR exposure dose. IgE-mediated food allergy status at 1 year was determined by formal challenge. Binomial regression was used to examine associations between VDI, UVR exposure dose and food allergy and investigate potential confounding. RESULTS: Within the random subcohort, VDI was present in 45% (105/233) of newborns and 24% (55/227) of infants at 6 months. Food allergy prevalence at 1 year was 7.7% (61/786), and 6.5% (53/808) were egg-allergic. There was no evidence of an association between VDI at either birth (aRR 1.25, 95% CI 0.70-2.22) or 6 months (aRR 0.93, 95% CI 0.41-2.14) and food allergy at 1 year. CONCLUSIONS: There was no evidence that VDI during the first 6 months of infancy is a risk factor for food allergy at 1 year of age. These findings primarily relate to egg allergy, and larger studies are required.

A coarse-grained model for assisting the investigation of structure and dynamics of large nucleic acids by ion mobility spectrometry-mass spectrometry.

Ion Mobility Spectrometry-Mass Spectrometry (IMS-MS) is a rapidly emerging tool for the investigation of nucleic acid structure and dynamics. IMS-MS determinations can provide valuable information regarding alternative topologies, folding intermediates, and conformational heterogeneities, which are not readily accessible to other analytical techniques. The leading strategies for data interpretation rely on computational and experimental approaches to correctly assign experimental observations to putative structures. A very effective strategy involves the application of molecular dynamics (MD) simulations to predict the structure of the analyte molecule, calculate its collision cross section (CCS), and then compare this computational value with the corresponding experimental data. While this approach works well for small nucleic acid species, analyzing larger nucleic acids of biological interest is hampered by the computational cost associated with capturing their extensive structure and dynamics in all-atom detail. In this report, we describe the implementation of a coarse graining (CG) approach to reduce the cost of the computational methods employed in the data interpretation workflow. Our framework employs a five-bead model to accurately represent each nucleotide in the nucleic acid structure. The beads are appropriately parameterized to enable the direct calculation of CCS values from CG models, thus affording the ability to pursue the analysis of larger, highly dynamic constructs. The validity of this approach was successfully confirmed by the excellent correlation between the CCS values obtained in parallel by all-atom and CG workflows.

Active safety monitoring of measles-mumps-rubella vaccine in the National Immunisation Programme of Sri Lanka

Objectives: This study was designed to report incidence and characteristics of selected adverse events following immunisation which have consistent causal association (AEFIc) with Measles-Mumps-Rubella (MMR) vaccination given at the age of one year in the National Immunisation Programme of Sri Lanka. Methods: The data presented here were obtained from a cohort event monitoring study. It was carried out in the Jaffna Regional Directorate of Health Services area from November 2012 to December 2014. A representative sample of 3002 infants who received MMR immunisation were actively followed up for adverse events (AE) using over the phone interviews, self-reporting, and home or hospital visits up to 45 days. All AEs were reviewed by two investigators independently in two step-wise processes to detect the AEFIc. Seven AEFIc were detected using standard case definitions and onset time limit criteria. They were subjected to further analysis to describe the incidence rates and characteristics. Results: Of the 2398 (80%) infants who completed follow up of 45 days, 1321 infants experienced 2621 AEFI. Of them 209 were classified as AEFIc. Incidence of AEFIc was 87/ 1000 immunisation. They were mainly nonserious and resolved completely. There were no fatal or life threatening AEFIs. Incidence per 1000 immunisations; allergic reactions 0.83, injection site reactions 4.58, fever100.4° F or lasting more than  3 days 9.59, macular papular rash 2.92, parotitis 2.92 and generalised convulsions 1.25. Conclusions: The MMR vaccine used in NIP of Sri Lanka had low incidence of AEFIc and were mainly non-serious in nature.

Safety of live attenuated Japanese encephalitis vaccine given at the age of 9 months in National Immunisation Programme of Sri Lanka.

OBJECTIVES: This study was designed to describe the safety profile of the single dose live attenuated Japanese encephalitis vaccine (LJEV) SA-14-14-2 given at the age of 9 months in the National Immunisation programme of Sri Lanka. METHODS: cohort event monitoring (CEM) was conducted in the Jaffna district during November 2012 to January 2015. A representative sample of 3041 infants who received the LJEV at the age of 9 months was followed up actively over telephone interviews on days 1, 3, 14, 30 and 45 for adverse events (AE). Parents were encouraged to self-report in between these interviews. When an AE is notified, further clinical information was obtained through in-depth interviews and home/hospital visits to determine as an adverse event following immunisation (AEFI). Investigators independently reviewed each AEFI for consistent causal association with LJEV according to WHO causality assessment. RESULTS: Of the 2878 (94%) infants who completed the follow up of 14 days, 911 (32%) experienced 1423 AEFIs. Of them, 376 (26%) were identified as AEFI with consistent causal association to LJEV (AEFIc). Irritability (53/ 1000 doses administered) and fever ≥100.4° F (46/1000 doses administered) accounted for 41% and 35% of AEFIcrespectively. Majority of AEFI (940) were identified as inconsistent as there were alternate causes. Nineteen AEFIc in 14 infants were classified as serious since they led to hospitalisation. Of the 2392 (79%) infants who completed 45 days follow up, 1022 experienced 1804 AEFI during 15-45 days. Only 20 were identified as AEFIc. There were no reported fatal or life threatening AEs. CONCLUSIONS: LJEV administered to infants at 9 months was devoid of any significant safety concerns as most of the AEFIs were non-serious and resolved completely. CEM is a useful method for AEFI surveillance.

Medicines use in hospitalised children: current status and outcome after an intervention.

INTRODUCTION: Challenges in rational use of medicines (RUM) in children are different from that of adults. In Sri Lanka, data on RUM in children are limited. OBJECTIVE: To assess the current status and to investigate effectiveness of an intervention in improving RUM in children. METHODS: Non-randomised controlled before and after study design was employed. Study settings were one paediatric unit in two Teaching Hospitals one for intervention (IU) and the other as a control (CU) unit. After assessing the current status in both units, a combined intervention (one-time training and distribution of a paediatric formulary) was offered to IU and medicine use was re-assessed in both units three months and one year after intervention. Fourteen indicators (7 WHO and 7 developed by investigators) were employed in the assessment. Any improvement was analysed using percentage changes, Chi-square or t tests as appropriate. RESULTS: A total of 1134 charts, 735 (3197 medicines) in IU and 399 (1539 medicines) in CU were subjected to analysis. At base level, of the 14 indicators, 9 were assessed satisfactory in both units. Four could not be assessed without knowing the clinical setting. The remaining indicator, reason for prescribing was recorded for 48% and 76% of medicines respectively in IU and CU. After intervention, only three indicators, medicines that had the reason for prescription recorded in the patient records, children treated without regular medicines, and children received the recommended doses of paracetamol, showed favourable changes in three months and one year. Percentage of medicines written in abbreviation showed an undesirable increase in IU (6.9, 16.2, 29.6) which was higher than what was observed in CU (3.2, 13.5, 18.4). CONCLUSIONS: Passive interventions appear to be ineffective in improving RUM in children. In addition, general medicine use indicators seem to be insensitive to capture the true challenges in paediatric pharmacotherapy.

Resistance and utilisation pattern of antibacterial agents in outpatient settings in two Teaching Hospitals in Colombo.

OBJECTIVES: Antibacterial resistance (ABR) is a public threat. Sri Lanka is a country with limited surveillance of ABR in the community. The WHO methodology was adapted to identify ABR in outpatient settings (nonhospitalised patients) and its link to consumption of antibiotics. METHODS: It was a cross-sectional descriptive community based study to collect ABR data from Out Patient Department (OPD) of two leading Teaching Hospitals in Colombo district. The indicator organism Escherichia coli (E. coli) was obtained from the urine specimens of patients who were suspected to have urinary tract infections. Antibiotic susceptibility testing was performed for commonly used oral antibiotics using disc diffusion method. The antibiotic consumption aggregate data were collected from the OPD pharmacies of the said hospitals and expressed as Defined Daily Doses (DDD) per 1000 inhabitants per 1000 day. RESULTS: Of the 2183 urine samples, pathogenic E. coli was isolated in 9.3% (204), and 8% (n=16) of them were Extended Spectrum Beta Lactamase (ESBL) producers. E.coli was most resistant to ampicillin (85%), followed by nalidixic acid (58.5%), trimethoprim/sulphamethoxazole (47.1%), ciprofloxacin (46.2%), norfloxacin (43.7%) amoxicillin /clavulanic acid (36.3%) and nitrofurantoin (15%). Multi-drug resistance was seen in 44%. Amoxicillin was the most frequently consumed antibacterial agent (2.65 DDD per 1000 inhabitants per day). CONCLUSIONS: There is an alarmingly high antibiotic resistance in the non-hospitalised patients indicating high prevalence of E. coli resistance in the community.

A phase II study of retifanlimab, a humanized anti-PD-1 monoclonal antibody, in patients with solid tumors (POD1UM-203).

BACKGROUND: POD1UM-203, an open-label, multicenter, phase II study, evaluated retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in patients with selected solid tumors where immune checkpoint inhibitor therapies have previously shown efficacy. PATIENTS AND METHODS: Eligible patients (≥18 years) had measurable disease and included unresectable or metastatic melanoma, treatment-naive metastatic non-small-cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression (tumor proportion score ≥50%), cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (UC) with PD-L1 expression (combined positive score ≥10%), or treatment-naive locally advanced/metastatic clear-cell renal cell carcinoma (RCC). Retifanlimab 500 mg was administered intravenously every 4 weeks as a 30-min infusion. The primary endpoint was investigator-assessed overall response rate. RESULTS: Overall, 121 patients (35 melanoma, 23 NSCLC, 29 UC, 34 RCC) were enrolled and treated. The overall response rate [95% confidence interval (CI)] was 40.0% (23.9-57.9) in the melanoma cohort, 34.8% (16.4-57.3) in the NSCLC cohort, 37.9% (20.7-57.7) in the UC cohort, and 23.5% (10.7-41.2) in the RCC cohort. Median duration of response was 11.5 months (95% CI 2.2-not reached) in the UC cohort, and was not reached in the other cohorts. Retifanlimab safety was consistent with previous experience for PD-(L)1 inhibitors. CONCLUSIONS: Retifanlimab demonstrated durable antitumor activity in patients with melanoma, NSCLC, UC, or RCC. The efficacy and safety of retifanlimab were as expected for a PD-(L)1 inhibitor. These data support further study of retifanlimab in solid tumors.

Expiratory airflow at 7-8 years of age in children born extremely low birthweight from 14 years before to 14 years after the introduction of exogenous surfactant.

Background: It is unclear if expiratory airflow in survivors born extremely low birth weight (ELBW; 500-999 g) has improved after the introduction of exogenous surfactant into clinical practice in 1991. The primary aim of this study was to describe the changes in airflow at 7-8 years of age of survivors born ELBW in five discrete cohorts from 14 years before to 14 years after the introduction of exogenous surfactant into clinical practice. Methods: The cohorts comprised consecutive survivors born ELBW in 1977-82 and 1985-87 at the Royal Women's Hospital, Melbourne, and in 1991-92, 1997 and 2005 in the state of Victoria, Australia. Survival rates to 2-years of age for infants born ELBW in the state of Victoria rose from approximately 1-in-4 to 3-in-4 over the time of this study. Expiratory airflow measurements at 7-8 years included the forced expired volume in 1 s (FEV1), converted to z-scores for age, height, sex, and race. Findings: There were 596 ELBW participants with expiratory flow data, 280 (47%) of whom had bronchopulmonary dysplasia (BPD). Overall, there was little change in zFEV1 over the 28-year period (mean change per year; 0.003, 95% CI -0.010, 0.015, P = 0.67). There was, however, evidence of an interaction between BPD and year; zFEV1 in those who had BPD fell over time (mean change per year -0.019, 95% CI -0.037, -0.009, P = 0.035), whereas zFEV1 improved in those who did not have BPD (mean change per year 0.021, 95% CI 0.006, 0.037, P = 0.007). Interpretation: Contrary to recent evidence, expiratory airflow of children born ELBW has not improved with the introduction of surfactant, and may be deteriorating in those who had BPD. Funding: National Health and Medical Research Council (Australia); Victorian Government's Operational Infrastructure Support Program.

The association between gut microbiome and growth in infants with cystic fibrosis.

BACKGROUND: In cystic fibrosis (CF), pathophysiologic changes in the gastrointestinal tract lead to malnutrition and altered gut microbiome. Microbiome alterations have been linked to linear growth, gut inflammation and respiratory manifestations. Elucidating these gut microbiome alterations may provide insight into future nutritional management in CF. METHODS: Infants were followed for 12-months at four sites in the United States (US-CF) and Australia (AUS-CF). 16S rRNA gene sequencing was performed on longitudinal stool samples. Associations between microbial abundance and age, antibiotic prophylaxis, malnutrition, and breast feeding were evaluated using generalized linear mixed models. Taxonomic and predictive functional features were compared between groups. RESULTS: Infants with CF (N = 78) were enrolled as part of a larger study. AUS-CF infants had higher mean weight-for-age z-scores than US-CF infants (p = 0.02). A subset of participants (CF N = 40, non-CF disease controls N = 10) provided stool samples for microbiome analysis. AUS-CF infants had lower stool alpha diversity compared to US-CF infants (p < 0.001). AUS-CF infants had higher relative abundance of stool Proteobacteria compared to US-CF infants which was associated with antibiotic prophylaxis (p < 0.001). Malnutrition (weight-for-age <10th percentile) was associated with depleted Lactococcus (p < 0.001). Antibiotic prophylaxis (p = 0.002) and malnutrition (p = 0.012) were linked with predicted decreased activity of metabolic pathways responsible for short chain fatty acid processing. CONCLUSIONS: In infants with CF, gut microbiome composition and diversity differed between the two continents. Gut microbial diversity was not linked to growth. The relationship between malnutrition and antibiotic prophylaxis with reduced SCFA fermentation could have implications for gut health and function and warrants additional investigation.

Bioinformatics meets parasitology.

The advent and integration of high-throughput '-omics' technologies (e.g. genomics, transcriptomics, proteomics, metabolomics, glycomics and lipidomics) are revolutionizing the way biology is done, allowing the systems biology of organisms to be explored. These technologies are now providing unique opportunities for global, molecular investigations of parasites. For example, studies of a transcriptome (all transcripts in an organism, tissue or cell) have become instrumental in providing insights into aspects of gene expression, regulation and function in a parasite, which is a major step to understanding its biology. The purpose of this article was to review recent applications of next-generation sequencing technologies and bioinformatic tools to large-scale investigations of the transcriptomes of parasitic nematodes of socio-economic significance (particularly key species of the order Strongylida) and to indicate the prospects and implications of these explorations for developing novel methods of parasite intervention.

Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects.

Leptin, the gene product of the obese gene, may play an important role in regulating body weight by signalling the size of the adipose tissue mass. Plasma leptin was found to be highly correlated with body mass index (BMI) in rodents and in 87 lean and obese humans. In humans, there was variability in plasma leptin at each BMI suggesting that there are differences in its secretion rate from fat. Weight loss due to food restriction was associated with a decrease in plasma leptin in samples from mice and obese humans.

A national survey of availability of key essential medicines for children in Sri Lanka.

OBJECTIVES: To investigate the availability of key essential medicines for children in Sri Lanka. METHODS: This national survey assessed the availability of 25 key essential medicines for children using the WHO/Health Action International medicine price methodology. Data were collected from a representative sample of 40 public hospitals (Outpatients Department pharmacies), 40 private and 8 'Rajya Osusala' (ROS) pharmacies. The hospitals and pharmacies were selected from 8 provinces using a multistage clustered approach to represent different levels of public hospitals. Descriptive statistics were used for analysis. RESULTS: The mean per cent availability of the basket of survey medicines was 52% in pubic hospitals when compared to 80% in private, and 88% in ROS pharmacies. teaching/general hospitals had better availability (mean per cent availability 62%) than district hospitals (54%), peripheral units (49%) and central dispensaries (45%). Availability of anti-infectives, anti-asthma medicines and oral liquid preparations of carbamazepine, iron, paracetamol, domperidone and ibuprofen was found to be less in public hospitals than private and ROS pharmacies. Availability in public hospitals similar to that of private and ROS pharmacies was only for paracetamol tablet, oral rehydration salt, vitamin C and chlorphenamine syrup. CONCLUSIONS: Key essential medicines for children were less available in public hospitals than in private and ROS pharmacies. This deprives children from access to effective and safe medicines more in the public hospitals than in the private sector or ROS.

Bioinformatic analysis of abundant, gender-enriched transcripts of adult Ascaris suum (Nematoda) using a semi-automated workflow platform.

Expressed sequence tag (EST) data representing transcripts with a high level of differential hybridization in suppressive-subtractive hybridization (SSH)-based microarray analysis between adult female and male Ascaris suum were subjected to detailed bioinformatic analysis. A total of 361 ESTs clustered into 209 sequences, of which 52 and 157 represented transcripts that were enriched in female and male A. suum, respectively. Thirty (57.7%) of the 'female' subset of 52 sequences had orthologues/homologues in other parasitic nematodes and/or Caenorhabditis elegans, 13 (25%) exclusively in other parasitic nematodes and nine (17.3%) had no match in any other organism for which sequence data are currently available; the C. elegans orthologues encoded molecules involved in reproduction as well as embryonic and gamete development, such as vitellogenins and chitin-binding proteins. Of the 'male' subset of 157 sequences, 73 (46.5%) had orthologues/homologues in other parasitic nematodes and/or C. elegans, 57 (37.5%) in other parasitic nematodes only, and 22 (14.5%) had no significant similarity match in any other organism; the C. elegans orthologues encoded predominantly major sperm proteins (MSPs), kinases and phosphatases, actins, myosins and an Ancylostoma secreted protein-like molecule. The findings of the present study should support further genomic investigations of A. suum.

Management of acute paracetamol poisoning in a tertiary care hospital.

OBJECTIVES: To compare the management of acute paracetamol poisoning with the best evidence available, and to determine the effect of plasma paracetamol level estimation on the management. DESIGN: Descriptive study with an intervention. SETTING: Medical wards of the National Hospital of Sri Lanka, Colombo. PATIENTS: Patients admitted with a history of acute paracetamol poisoning. INTERVENTION: Measurement of plasma paracetamol. METHODS: Data were obtained from the patients, medical staff and medical records. Plasma paracetamol was estimated between 4-24 hours of paracetamol ingestion. The current management practices were compared with the best evidence on acute paracetamol poisoning management. RESULTS: 157 patients were included. The mean ingested dose of paracetamol was 333 mg/kg body weight. Majority of the patients (84%) were transfers. Induced emesis and activated charcoal were given to 91% of patients. N-acetylcysteine was given to 66, methionine to 55, and both to 2. Aclinically important delay in the administration of antidotes was noted; 68% of patients received antidotes after 8 hours of the acute ingestion. Only 31 (26%) had paracetamol levels above the Rumack-Matthew normogram. 74 patients received an antidote despite having a plasma paracetamol level below the toxic level according to the normogram. INTERPRETATION: Management of acute paracetamol poisoning could be improved by following best available evidence and adapting cheaper methods for plasma paracetamol estimation.

The association between higher maternal pre-pregnancy body mass index and increased birth weight, adiposity and inflammation in the newborn.

BACKGROUND: Excess adiposity and adiposity-related inflammation are known risk factors for cardiovascular disease in adults; however, little is known regarding the determinants of adiposity-related inflammation at birth. OBJECTIVES: The aim of this study was to investigate the association between maternal pre-pregnancy BMI and newborn adiposity and inflammation. METHODS: Paired maternal (28-week gestation) and infant (umbilical cord) blood samples were collected from a population-derived birth cohort (Barwon Infant Study, n = 1074). Data on maternal comorbidities and infant birth anthropomorphic measures were compiled, and infant aortic intima-media thickness was measured by trans-abdominal ultrasound. In a selected subgroup of term infants (n = 161), matched maternal and cord lipids, high-sensitivity C-reactive protein (hsCRP) and maternal soluble CD14 were measured. Analysis was completed by using pairwise correlation and linear regression. Because of their non-normal distribution, pathology blood measures were log transformed prior to analysis. RESULTS: Maternal pre-pregnancy BMI was positively associated with increased birth weight (mean difference 17.8 g per kg m-2 , 95% CI 6.6 to 28.9; p = 0.002), newborn mean skin-fold thickness (mean difference 0.1 mm per kg m-2 , 95% CI 0.0 to 0.1; p < 0.001) and cord blood hsCRP (mean difference of 4.2% increase in hsCRP per kg m-2 increase in pre-pregnancy BMI, 95% CI 0.6 to 7.7%, p = 0.02), but not cord blood soluble CD14. Inclusion of maternal hsCRP as a covariate attenuated the associations between pre-pregnancy BMI and both newborn skin-fold thickness and cord blood hsCRP. CONCLUSION: Higher maternal pre-pregnancy BMI is associated with increased newborn adiposity and inflammation. These associations may be partially mediated by maternal inflammation during pregnancy.

Hepatic Hilar Lymph Node Reactivity at Kasai Portoenterostomy for Biliary Atresia: Correlations With Age, Outcome, and Histology of Proximal Biliary Remnant.

We hypothesized that if infection is the proximate cause of congenital biliary atresia, an appropriate response to antigen would occur in lymph nodes contiguous with the biliary remnant. We compared the number of follicular germinal centers (GC) in 79 surgically excised hilar lymph nodes (LN) and 27 incidentally discovered cystic duct LNs in 84 subjects at the time of hepatic portoenterostomy (HPE) for biliary atresia (BA) to autopsy controls from the pancreaticobiliary region of non-septic infants >3 months old at death. All 27 control LN lacked GC, a sign in infants of a primary response to antigenic stimulation. GC were found in 53% of 106 LN in 56 of 84 subjects. Visible surgically excised LN contiguous with the most proximal biliary remnants had 1 or more well-formed reactive GC in only 26/51 subjects. Presence of GC and number of GC/LN was unrelated to age at onset of jaundice or to active fibroplasia in the biliary remnant but was related to older age at HPE. Absent GC in visible and incidentally removed cystic duct LNs predicted survival with the native liver at 2 and 3 years after HPE, P = .03, but significance was lost at longer intervals. The uncommon inflammatory lesions occasionally found in remnants could be secondary either to bile-induced injury or secondary infection established as obstruction evolves. The absence of consistent evidence of antigenic stimulation in LN contiguous with the biliary remnant supports existence of at least 1 major alternative to infection in the etiology of biliary atresia.

A symmetrical indexing scheme for decagonal quasicrystals analogous to Miller-Bravais indexing of hexagonal crystals.

The problems of redundancy and superfluous indices in indexing the planes and axes in a decagonal quasicrystal are considered, using a scheme of five coplanar vectors in the quasiperiodic plane and one perpendicular vector. Of all the indexing schemes in use, this scheme offers the maximum advantage. An analogy is drawn to the hexagonal system using Miller-Bravais indices. Based on this, a symmetry-based indexing system for decagonal phases is devised that follows a simplified approximate zone law analogous to the exact zone law for the hexagonal case. The indices based on this scheme will be designated as ;Frank indices'. High-symmetry electron diffraction zone-axis patterns as well as powder X-ray diffraction patterns are indexed using Frank indices and compared with those of other indexing schemes.

Generalized approach to Ewald sums.

We derive Ewald sum formulas for potential energy and force for a system of point charges interacting with an arbitrary, long-range central potential. The system is made neutral by a uniform background of opposite charge interacting with the same potential. These formulas can be readily used in computer numerical simulations of model physical systems. In particular, expressions for the potential energy and the force have been obtained in both two and three dimensions for Coulomb and other power-law potentials, Yukawa systems, and for an electronic bilayer. We discuss numerical results and their accuracy for various systems and, based on our analysis, suggest values to be used for the parameters that appear in the Ewald sums.

Quantitative assessment of breast density from digitized mammograms into Tabar's patterns.

We describe a semi-automated technique for the quantitative assessment of breast density from digitized mammograms in comparison with patterns suggested by Tabar. It was developed using the MATLAB-based graphical user interface applications. It is based on an interactive thresholding method, after a short automated method that shows the fibroglandular tissue area, breast area and breast density each time new thresholds are placed on the image. The breast density is taken as a percentage of the fibroglandular tissue to the breast tissue areas. It was tested in four different ways, namely by examining: (i) correlation of the quantitative assessment results with subjective classification, (ii) classification performance using the quantitative assessment technique, (iii) interobserver agreement and (iv) intraobserver agreement. The results of the quantitative assessment correlated well (r2 = 0.92) with the subjective Tabar patterns classified by the radiologist (correctly classified 83% of digitized mammograms). The average kappa coefficient for the agreement between the readers was 0.63. This indicated moderate agreement between the three observers in classifying breast density using the quantitative assessment technique. The kappa coefficient of 0.75 for intraobserver agreement reflected good agreement between two sets of readings. The technique may be useful as a supplement to the radiologist's assessment in classifying mammograms into Tabar's pattern associated with breast cancer risk.

Estimation of iodine in salt fortified with iodine & iron.

BACKGROUND & OBJECTIVE: The National Institute of Nutrition (NIN), Hyderabad has developed double fortified salt (DFS) containing both iodine and iron to control the twin problems of iodine deficiency disorders (IDD) and iron deficiency anaemia (IDA). When the iodine content of DFS was estimated by the conventional iodometric titration using sulphuric acid (H(2)SO(4)), problems such as wide variation between duplicate analysis and under/overestimations of iodine content were encountered, which led to inconsistent results. This study was undertaken to develop a modified method for the estimation of iodine in DFS so as to get reliable iodine content of DFS. METHODS: A modified method was developed using orthophosphoric acid (H(3)PO(4)) and the sensitivity of the method was confirmed by estimating the iodine content of potassium iodate (KIO(3)) standard at different concentrations of iodine (0 to 100 ppm). The iodine content of DFS and iodized salt (IS) from local market and factory was estimated by the modified method as well as the conventional iodometric titration and the results were compared. RESULTS: The pH of DFS was acidic. The time gap between the additions of acid and potassium iodide (KI) played a crucial role in getting the actual iodine content of DFS. The H(2)SO(4) and ferrous sulphate (FeSO(4)) interfered with the estimation of iodine in DFS resulting in underestimation or overestimation of iodine. Modified method (H(3)PO(4)) produced consistent and reliable iodine content of DFS. Both H(2)SO(4) and H(3)PO(4) gave same results when tested with KIO(3) standard, Reference salt and IS (both experimental and purchased from local market). Actually 0.50 ml of 1 per cent KI was sufficient to estimate the iodine content of DFS or IS. INTERPRETATION & CONCLUSION: The results of the present study showed that the conventional method using H(2)SO(4) was not suitable for the estimation of iodine in DFS. The modified method using H(2)PO(4) was ideally suited for the estimation of iodine in DFS. Also, iron from DFS did not interfere during estimation of iodine by this method. As both the conventional and the modified methods gave the same results for the iodine content of IS, it is practically prudent to use the modified method (H(2)PO(4)) for both DFS and IS instead of following one method (H(3)PO(4)) for DFS and another (H(2)SO(4)) for IS. The quantity of KI is also reduced and the order of additions of reagents is changed in the modified procedure.