Submicron focusing of high-energy X-rays with silicon saw-tooth refractive lenses - fabrication and aberrations: errata.

Three (3) items of errata are submitted for our recently published paper [Opt. Express28, 36505 (2020)10.1364/OE.405566]. One is a clarifying extension to the Fig. 3 caption. Two are typographical corrections. The scientific results and conclusions are unaffected.

Sub-pixel high-resolution imaging of high-energy x-rays inspired by sub-wavelength optical imaging.

We have developed and demonstrated an image super-resolution method-XR-UNLOC: X-Ray UNsupervised particle LOCalization-for hard x-rays measured with fast-frame-rate detectors that is an adaptation of the principle of photo-activated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM), which enabled biological fluorescence imaging at sub-optical-wavelength scales. We demonstrate the approach on experimental coherent Bragg diffraction data measured with 52 keV x-rays from a nanocrystalline sample. From this sample, we resolve the fine fringe detail of a high-energy x-ray Bragg coherent diffraction pattern to an upsampling factor of 16 of the native pixel pitch of 30 µm of a charge-integrating fastCCD detector. This was accomplished by analysis of individual photon locations in a series of "nearly-dark" instances of the diffraction pattern that each contain only a handful of photons. Central to our approach was the adaptation of the UNLOC photon fitting routine for PALM/STORM to the hard x-ray regime to handle much smaller point spread functions, which required a different statistical test for photon detection and for sub-pixel localization. A comparison to a photon-localization strategy used in the x-ray community ("droplet analysis") showed that XR-UNLOC provides significant improvement in super-resolution. We also developed a metric by which to estimate the limit of reliable upsampling with XR-UNLOC under a given set of experimental conditions in terms of the signal-to-noise ratio of a photon detection event and the size of the point spread function for guiding future x-ray experiments in many disciplines where detector pixelation limits must be overcome.

Focusing with saw-tooth refractive lenses at a high-energy X-ray beamline.

The Advanced Photon Source 1-ID beamline, operating in the 40-140 keV X-ray energy range, has successfully employed continuously tunable saw-tooth refractive lenses to routinely deliver beams focused in both one and two dimensions to experiments for over 15 years. The practical experience of implementing such lenses, made of silicon and aluminium, is presented, including their properties, control, alignment, and diagnostic methods, achieving ∼1 µm focusing (vertically). Ongoing development and prospects towards submicrometre focusing at these high energies are also mentioned.

Submicron focusing of high-energy X-rays with silicon saw-tooth refractive lenses: fabrication and aberrations.

Saw-tooth refractive lenses are extremely well-suited to focus high energy X-rays (>50 keV). These lenses have properties of being continuously tunable (in energy or focal length), effectively parabolic, in-line, and attenuation-free on-axis. Vertical focusing of 60 keV synchrotron X-rays to 690 nm at a focal length f = 1.3 m with silicon saw-tooth lenses at a high-energy undulator radiation beamine is demonstrated, with discussion of relevant fabrication and mounting considerations and of geometrical aberrations unique to these devices. Aberration corrections towards further progress into the diffraction-limited nanofocusing regime are suggested. The versatility of such optics, combined with the attainability of smaller spot sizes at these penetrating photon energies, should continue to enhance material microstructure investigations at increasingly higher spatial resolutions.

Nasopharyngeal teratoma, congenital diaphragmatic hernia and Dandy-Walker malformation - a yet uncharacterized syndrome.

An association of congenital diaphragmatic hernia, dandy walker malformation and nasopharyngeal teratoma is very rare. Here, we report a fourth case with this association where chromosomal microarray and whole exome sequencing (WES) was performed to understand the underlying genetic basis. Findings of few variants especially a novel variation in HIRA provided some insights. An association of congenital diaphragmatic hernia, dandy walker malformation and nasopharyngeal teratoma is very rare. Here, we report a fourth case with this association where chromosomal microarray and whole exome sequencing (WES) was performed to understand the underlying genetic basis. Findings of few variants especially a novel variation in HIRA provided some insights.

Enhancement of lanthanide evaporation by complexation: dysprosium tri-iodide mixed with indium iodide and thulium tri-iodide mixed with thallium iodide.

The vapors in equilibrium with condensates of DyI3, DyI3/InI, TmI3, and TmI3/TlI were observed over the temperature range from 900 K to 1400 K using x-ray induced fluorescence. The total densities of each element (Dy, Tm, In, Tl, and I) in the vapor, summed over all atomic and molecular species, were determined. Dramatic enhancements in the total vapor densities of Dy and Tm were observed in the vapors over DyI3/InI and TmI3/TlI as compared to the vapors over pure DyI3 and pure TmI3, respectively. An enhancement factor exceeding 10 was observed for Dy at T ≈ 1020 K, decreasing to 0 at T ≈ 1250 K. An enhancement factor exceeding 20 was observed for Tm at T ≈ 1040 K, decreasing to 0 at T ≈ 1300 K. Such enhancements are expected from the formation of the vapor-phase hetero-complexes DyInI4 and TmTlI4. Numerical simulations of the thermo-chemical equilibrium suggest the importance of additional complexes in liquid phases. A description of the measurement technique is given. Improvements in the absolute calibration lead to an approximately 40% correction to previously reported preliminary results [J. J. Curry et al., Chem. Phys. Lett. 507, 52 (2011); Appl. Phys. Lett. 100, 083505 (2012)].

Synchrotron Mössbauer spectroscopy using high-speed shutters.

A new method of performing Mössbauer spectroscopy with synchrotron radiation is demonstrated that involves using a high-speed periodic shutter near the focal spot of a microfocused X-ray beam. This fast microshuttering technique operates without a high-resolution monochromator and has the potential to produce much higher signal rates. It also offers orders of magnitude more suppression of unwanted electronic charge scattering. Measurement results are shown that prove the principle of the method and improvements are discussed to deliver a very pure beam of Mössbauer photons (E/ΔE ≃ 10(12)) with previously unavailable spectral brightness. Such a source will allow both Mössbauer spectroscopy in the energy domain with the many advantageous characteristics of synchrotron radiation and new opportunities for measurements using X-rays with ultra-high energy resolution.

Silicon saw-tooth refractive lens for high-energy X-rays made using a diamond saw.

Silicon is a material well suited for refractive lenses operating at high X-ray energies (>50 keV), particularly if implemented in a single-crystal form to minimize small-angle scattering. A single-crystal silicon saw-tooth refractive lens, fabricated by a dicing process using a thin diamond wheel, was tested with 115 keV X-rays, giving an ideal 17 microm line focus width in a long focal length, 2:1 ratio demagnification geometry, with a source-to-focus distance of 58.5 m. The fabrication is simple, using resources typically available at any synchrotron facility's optics shop.

Melting of Bi sublattice in nanosized BiFeO3 Perovskite by resonant X-ray diffraction.

Free-standing BiFeO3 perovskite particles with a size ranging from polycrystalline bulk down to 5 nm have been studied by high-energy resonant (Bi K edge) x-ray diffraction coupled to differential atomic pair distribution function analysis. Nanosized BiFeO3 particles are found to exhibit extra, i.e., beyond the usual thermal, structural disorder that increases progressively with diminishing their size. In particles of size smaller than approximately 18 nm the disorder destroys the structural coherence of the Bi sublattice and disturbs that of the Fe-based sublattice in the perovskite structure, substantially affecting the magnetoelectric properties it carries. The new structural information helps better understand the unusual behavior of perovskites structured at the nanoscale.

Nutritional assessment and counselling of tuberculosis patients at primary care in India: do we measure up?

SETTING: Dakshina Kannada District, coastal South India, under the Revised National Tuberculosis Control Programme (RNTCP). OBJECTIVE: To identify the potential and practices at primary health centres (PHCs) for the assessment of nutritional status of patients with tuberculosis (TB), the basic tools used to measure height and weight and the type of nutritional counselling provided. DESIGN: A cross-sectional study was conducted with physical verification of availability of height and weight measuring equipment. Information was collected on the method used by medical officers for assessing nutritional status in PHCs, action taken in case the patient is undernourished and any formal training in nutritional assessment and counselling. RESULTS: Of 37 PHCs assessed, weighing machines were available in all and stadiometers in 38%. Medical officers were not calculating body mass index for nutritional assessment even when height and weight were being uniformly measured. Nutritional classification was mostly based on the appearance and physique of the patient. Counselling included advice to take milk, eggs and protein powders with efforts to arrange funds from village health, sanitation and nutrition committees. CONCLUSION: There is a need to equip the PHCs and their medical officers with necessary tools and training for nutritional assessment and counselling of patients with tuberculosis.

Cystic fibrosis in India.

Cystic fibrosis (CF) was considered to be non-existent in Indian subcontinent. Reports in last one decade have suggested that cystic fibrosis occurs in India but its precise magnitude is not known. Studies on migrant Indian population in United States and United Kingdom estimate frequency of CF as 1:10,000 to 1:40,000. The clinical features are similar to that reported in Caucasian population. CF in Indian children is usually diagnosed late and in advanced stage. Children are more malnourished and may have clinically evident deficiency of fat soluble vitamins. The frequency of clubbing, colonization with Pseudomonas, and laboratory evidence of pseudo-Bartter syndrome is relatively more at the time of diagnosis. Diagnostic facilities in form of sweat chloride estimation and genetic studies are not available readily. Mutation profile is different. The frequency of common mutation F508del in Indian children is between 19% and 34%. Other mutations are heterogeneous. Management of CF in India is difficult due to less number of trained manpower, limited availability, and high cost of pharmacologic agents. The determinants of early death include: severe malnutrition and colonization with Pseudomonas at the time of diagnosis, more than four episodes of lower respiratory infection per year and age of onset of symptoms before 2 months of age. To conclude, CF does occur in India; however, precise magnitude of problem is not known. There is need to create awareness amongst pediatricians, developing diagnostic facilities, and management protocols based on locally available resources.

Tobacco-related knowledge, attitudes, and practices among urban low socioeconomic women in Mumbai, India.

CONTEXT: Tobacco use is an important health issue globally. It is responsible for a large number of diseases and deaths in India. Female tobacco users have additional health risks. AIMS: The aim was to assess changes in pre and post-intervention tobacco-related knowledge, attitudes, and practices among women from urban low socioeconomic strata, after three rounds of interventions. SUBJECTS AND METHODS: A structured questionnaire was used to interview women living in low socioeconomic housing clusters in Mumbai, regarding their tobacco consumption, attitudes, and practices, by Medical Social Workers. These data were entered into IBM SPSS Statistics, version 20 and analysed. Interventions for tobacco cessation were provided 3 times over a span of 9 months, comprising of health education and counseling. Post-intervention questionnaire was introduced at 12 months. RESULTS: There was statistically significant improvement in the knowledge of women, following the interventions, with particular reference to poor oral hygiene and tobacco use being main cause of oral cancer (P = 0.007), knowledge of ill effects of second hand smoke (P = 0.0001), knowledge about possibility of early detection of oral cancer (P = 0.0001), perception of pictorial and written warnings on tobacco products (P = 0.0001), and availability of help for quitting tobacco (P = 0.024). CONCLUSION: The prevalence of smokeless tobacco use is very high among urban women from lower socioeconomic strata. Therefore, tobacco awareness programs and tobacco cessation services tailor made for this group of women must be planned and implemented.

A population-based screening program for early detection of common cancers among women in India - methodology and interim results.

BACKGROUND: Cancers of the uterine cervix, breast, and oral cavity accounted for 134,420, 115,251, and 24,375 cases, respectively, and were responsible for 52.8% of the total cancers among women in India in 2008. AIM: The major objectives were to create awareness regarding common cancers among women, to detect pre-cancers of the uterine cervix and oral cavity, and early cancers of the breast, uterine cervix, and oral cavity, by conducting screening with simple, low-cost technology, within the community, and to facilitate confirmation of diagnosis among the screen positives and treatment and follow-up among the diagnosed cases. SETTINGS AND METHODS: This is a community-based screening program for early detection of breast, uterine cervix, and oral cancers, being implemented among the socioeconomically disadvantaged women in Mumbai, India. The process involves selection of clusters, household surveys, health education, and screening the eligible women for breast, uterine cervix, and oral cancers, by primary healthcare workers, at a temporarily set-up clinic within the community. The program is planned to cover a 125,000 disadvantaged population in five years. RESULTS: Twenty-one thousand and fifteen people, with 4009 eligible women, have been covered to date. The compliance for screening for breast, cervix, and oral cavity has been 85, 70, and 88% and the screen positivity rates are 3.9, 14.9, and 3.9%, respectively. Twenty-seven oral pre-cancers, 25 cervix pre-cancers, one invasive cancer of the breast, two of the cervix, and one oral cavity cancer have been diagnosed among the screened women and all of them have complied with the treatment. CONCLUSIONS: The program is raising awareness about the common cancers and harms of tobacco among the disadvantaged women population in Mumbai. It is also helping in detecting pre-cancers and cancers among asymptomatic women and is assisting them in receiving treatment.

Accuracy of conventional cytology: results from a multicentre screening study in India.

OBJECTIVE: We conducted a multi-centre cross-sectional study in India to evaluate the accuracy of conventional cytology to detect high-grade squamous intraepithelial lesions (HSIL). SETTING: Cross-sectional studies in Jaipur, Kolkata, Mumbai and Trivandrum, India, during 1999-2003. METHODS: A common protocol and questionnaire were used to test 22,663 women aged 25-65 years with conventional cytology in five cross-sectional studies. Three thresholds were used to define test positivity: atypical squamous cells of uncertain significance (ASCUS), low-grade squamous intra-epithelial lesion (LSIL), or HSIL. All screened women were investigated with colposcopy, and biopsies were taken when necessary. The reference standard for final disease status was histology or negative colposcopy. Data from the studies were pooled to evaluate the test characteristics for the detection of histologically confirmed HSIL. RESULTS: The test positivity rates of cytology were 8.8% at ASCUS, 6.2% at LSIL and 1.8% at HSIL thresholds, and 355 women had histologically confirmed HSIL while 74 had invasive cancer. The pooled sensitivity, specificity, positive and negative predictive values at ASCUS threshold were 64.5%, 92.3%, 11.8% and 99.4% respectively. The corresponding values at LSIL threshold were 58.0%, 94.9%, 15.2% and 99.3%, while at the HSIL threshold they were 45.4%, 99.2%, 46.3% and 99.1%. The sensitivity varied between 37.8-81.3% at ASCUS, 28.9-76.9% at LSIL and 24.4-72.3% at HSIL thresholds. A significantly low sensitivity was observed in women aged 25-39 years (p<0.001). The wide variation in sensitivity across study sites persisted even after age standardisation. CONCLUSION: The sensitivity of cytology varied widely between the study sites. Findings from our study and other reviews indicate that sustained efforts in improving sampling, preparation and reading of cytological specimens and improvements in clinical judgement are essential to achieve concurrently high sensitivity and specificity.

Prenatal diagnosis of Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is one of the most common X-linked genetic disorders seen in children. Mutations in the DMD gene coding for the protein dystrophin causes the severe muscle-wasting disorder leading to death in the second decade of life. In the absence of a cure, prenatal diagnosis (PND) appears to be the best approach to reduce the burden of this disease on the individual family and ultimately on society. There are few published reports worldwide on PND and very few from the developing countries. We report our experience with PND for families with DMD using multiplex polymerase chain reaction (PCR) and microsatellite polymorphic marker analysis. METHODS: From August 1997 to October 1999, PND was offered on request to 23 families with one or two boys affected with DMD. A total of 26 foetuses were screened for DMD. Initially the deletions in the DMD gene in the affected child were identified by multiplex PCR screening for 23 exons in 6 sets. In patients where deletions were not identified, microsatellite repeat analysis was carried out to follow the inheritance of the mutant allele. DNA was extracted from chorionic villus samples obtained by chorionic villus biopsy performed at 10-15 weeks of gestation in 17 families, and at 16-20 weeks in 6 families. RESULTS: Deletions were identified in 20 affected boys. In 2 families, microsatellite repeat analysis was done to identify the mutant allele. Of the 26 foetuses, 5 were found to be affected with DMD and the parents opted for termination of pregnancies. CONCLUSIONS: Multiplex PCR technology and microsatellite repeat analysis can be used effectively for PND of DMD.

Prenatal diagnosis of haemoglobinopathies.

BACKGROUND: Haemoglobinopathies constitute a major health problem in the Indian subcontinent. In the absence of any method for achieving complete cure and treatment being expensive, prenatal diagnosis and selective termination of an affected foetus is a feasible option to decrease the disease load. We report our experience with prenatal diagnosis of haemoglobinopathies over a two-and-a-half year period in 257 pregnancies. METHODS: Amplification refractory mutation system (ARMS) was used to detect beta-thalassaemia, haemoglobin E and sickle cell mutations. RESULTS: Five mutations in the beta-globin gene which are common in the Indian population were detected in 92.3% of mutant chromosomes, whereas 3.1% of chromosomes carried rare mutations followed by 0.8% haemoglobin E and 0.4% sickle cell mutations. Mutations in 3.3% chromosomes were uncharacterized. The prenatal procedure, carried out early in pregnancy, was a chorionic villus sampling in most cases. A confirmed diagnosis based on ARMS-PCR was given in 241 (93.8%) cases. In 10 cases (3.9%) linkage analysis was required to confirm the foetal status, as mutations in both parents were not identified or the chorionic villus sample carried the single identified mutation. Four families with haemoglobin E-beta thalassaemia and one family with sickle cell disease were also included. Of the study population, 91.25% of the couples had a previous child with haemoglobinopathy, whereas 8.75% of the couples came before the birth of the first affected child. CONCLUSION: We conclude that ARMS-PCR is a highly sensitive technique for detecting mutations in the beta-globin gene and its efficacy in the prenatal diagnosis of haemoglobinopathies is proven.

Relationship among particle size distribution, dissolution profile, plasma values, and anthelmintic efficacy of oxfendazole.

Three mean particle sizes of oxfendazole raw material (1.65 micron, lot A; 3.2 micron, 10t B; 12.0 micron, lot C) were prepared and identically formulated as corresponding (A, B, and C) suspensions at 2.26% (W/V) concentration. Studies involving microscopic examination, scanning electron microscope analysis, particle size distribution, and surface area measurement were carried out on raw materials. In vitro dissolution profiles were obtained for the suspensions. A comparative bioavailability study of these 3 suspensions was performed in 12 sheep with each sheep given each formulation in a Latin square crossover study design; oxfendazole was dosed at rate of 5 mg/kg of body weight. Plasma-value measurements were made followed by an analysis of various bioavailability studies. Plasma area values indicated that suspension C (dw = 12.0 micron) was significantly (P less than 0.05) less bioavailable than was suspension A (dw = 1.65 micron); there was no difference between suspension A and suspension B. Significant differences were not seen in biological half-life and maximum plasma concentrations. The term dw refers to that particle diameter (determined by Coulter counting) at which 50% of the oxfendazole mass was in the form of particles having a lesser diameter and 50% was in the form of particles having a greater diameter. In a separate study involving 20 Merino weaner sheep infected with benzimidazole-resistant Haemonchus contortus larvae, oxfendazole's anthelmintic efficacy was demonstrated in the 2.26% suspension dosage form (90% particles less than 10 micron) at a dosing rate of 5 mg/kg. A correlation was found between its anthelmintic activity and plasma area values when compared in individual sheep. Data demonstrated that substantial differences in particle size distribution of oxfendazole could influence its dissolution rate, plasma concentrations, and absorption characteristics, thus indicating that oxfendazole's absorption could be dissolution-rate limited.

Clinical profile and frequency of delta f508 mutation in Indian children with cystic fibrosis.

OBJECTIVE: To document clinical profile of cystic fibrosis (CF) in Indian children and the prevalence of delta F508 mutation in these patients. DESIGN: Observational study. SETTING: Pediatric chest clinic in an urban tertiary care center in north India. PERIOD OF STUDY: July 1995 to June 2002. METHODS: Clinical features of 120 children diagnosed as CF by quantitative pilocarpine iontophoresis were recorded. A polymerase chain reaction based test for identification of delta F 508 mutation was performed on all children. RESULTS: Out of 3500 new cases registered in Pediatric Chest Clinic during this period 120, (3.5%) children were diagnosed as CF. Origin of parents of patients traced from almost all the States of north India. Family history suggestive of CF was present in 41 (34%) and consanguinity in 19 (61%) patients. Common clinical manifestations at the time of presentation included recurrent or persistent pneumonia in 118 (98%), failure to thrive in 108 (90%), malabsorption in 96 (80%), history of meconium ileus in 10 (8%), and rectal prolapse was present in 16 (13%). History of salt craving, salty taste on kissing and skin rashes was present in 5 patients each. 49(41%) patients were severely malnourished. Nasal polyposis was present in 5 (4%) patients. Examination of chest revealed evidence of hyperinflation in 100 (83%), kyphosis 20 (17%), crepitations 110 (92%), wheezing 40 (25%) and bronchial breathing in 20 (17%) patients. Average clinical CF scores were 51 (95%; CI 20-80). 48 (40%) patients had a CF score of LT40. Pseudomonas spp was cultured from respiratory secretions of 51 (42%), Staphylococcus spp in 18 (15%), Klebsiella spp in 8 (7%) and Hemophilus influenzae in 2 (2%) patients. Delta F508 mutation was positive in 45 chromosomes out of 240 tested. Patients originated from Pakistan had more frequency of delta F508 mutations. CONCLUSIONS: Cystic fibrosis does occur in Indian children; clinical features are classical. Diagnosis is often delayed and the disease is advanced in most patients at the time of diagnosis. Frequency of Delta F508 mutation is 19% i.e., less than that seen in Caucasian population. There is need to create awareness about occurrence of CF in Indian children.

An indigenously developed method for sweat collection and estimation of chloride for diagnosis of cystic fibrosis.

An indigenously developed method for sweat collection and titration method for estimation of chloride was validated. The mean difference in estimated chloride value from the known strength of saline in 50 samples was -1.04 +/- 4.13 mEq/L (95% CI: -0.07 to 2.28). The mean difference in the estimated chloride values between two observers when the test was performed on known strengths of saline solution was -2.5 +/- 4.24 mEq/L (95% CI: -3.67 to 1.33). The inter observer variability between two observers when the test was performed on sweat samples obtained from 50 individuals was -1.12 +/- 4.34 mEq/L (95% CI: -2.23 to 0.8 ). Sweat weight of more than 100 mg could be collected in first attempt in 602 of 757 (80%) patient with an average sweat weight of 230 mg. This inexpensive method of sweat collection and chloride estimation has acceptable accuracy and repeatability and can be used in resource poor setting for making a diagnosis of cystic fibrosis.

Comparative evaluation of human papilloma virus-DNA test verses colposcopy as secondary cervical cancer screening test to triage screen positive women on primary screening by visual inspection with 5% acetic acid.

INTRODUCTION: Visual inspection with 5% Acetic acid (VIA) as a low cost screening method has good sensitivity with the limitation of low specificity and low positive predictive values. The present study therefore evaluates the performance of secondary testing by human papillomavirus (HPV) test and Colposcopy in a single-visit screening approach to increase program effectiveness in limited health-care resources settings. MATERIALS AND METHODS: In a cross-sectional cervical cancer screening trial, 3629 women (30-65 years) were screened by primary screening test VIA. VIA test positive women were subsequently tested for the presence of oncogenic HPV types by hybrid capture II and with colposcopy. The reference investigation histopathology was performed for all primary screen positive women. RESULTS: Data for 3613 evaluable women showed 352 (9.7%) women positive on primary screening by VIA. VIA had a sensitivity of 93% (95% confidence interval (CI): 0.76-0.99) and specificity of 91% (95% CI: 0.90-0.92) respectively to detect the cervical intraepithelial neoplasia grade 2+ . HPV DNA and colposcopy as secondary tests to triage VIA positive women had a sensitivity of 61% (95% CI: 0.41-0.78), 43% (95% CI: 0.24-0.63) and specificity of 99% (95% CI: 0.99-1.00), 99% (95% CI: 0.99-0.99) respectively for detecting CIN2+ lesions. CONCLUSION: Two step screening model combining highly sensitive low cost test like VIA for primary screening followed by more specific HPV DNA test as triage test for primary screen positive can be a cost-effective cervical screening strategy in resource constrained settings.