10 research outputs found
3D Imaging of a Phase Object from a Single Sample Orientation Using an Optical Laser
Ankylography is a new 3D imaging technique, which, under certain
circumstances, enables reconstruction of a 3D object from a single sample
orientation. Here, we provide a matrix rank analysis to explain the principle
of ankylography. We then present an ankylography experiment on a microscale
phase object using an optical laser. Coherent diffraction patterns are acquired
from the phase object using a planar CCD detector and are projected onto a
spherical shell. The 3D structure of the object is directly reconstructed from
the spherical diffraction pattern. This work may potentially open the door to a
new method for 3D imaging of phase objects in the visible light region.
Finally, the extension of ankylography to more complicated and larger objects
is suggested.Comment: 22 pages 5 figure
Coherent diffraction microscopy at SPring-8: instrumentation, data acquisition and data analysis
An instrumentation and data analysis review of coherent diffraction microscopy at SPring-8 is given. This work will be of interest to those who want to apply coherent diffraction imaging to studies of materials science and biological samples
Three-dimensional structure determination from a single view
The ability to determine the structure of matter in three dimensions has
profoundly advanced our understanding of nature. Traditionally, the most widely
used schemes for 3D structure determination of an object are implemented by
acquiring multiple measurements over various sample orientations, as in the
case of crystallography and tomography (1,2), or by scanning a series of thin
sections through the sample, as in confocal microscopy (3). Here we present a
3D imaging modality, termed ankylography (derived from the Greek words ankylos
meaning 'curved' and graphein meaning 'writing'), which enables complete 3D
structure determination from a single exposure using a monochromatic incident
beam. We demonstrate that when the diffraction pattern of a finite object is
sampled at a sufficiently fine scale on the Ewald sphere, the 3D structure of
the object is determined by the 2D spherical pattern. We confirm the
theoretical analysis by performing 3D numerical reconstructions of a sodium
silicate glass structure at 2 Angstrom resolution and a single poliovirus at 2
- 3 nm resolution from 2D spherical diffraction patterns alone. Using
diffraction data from a soft X-ray laser, we demonstrate that ankylography is
experimentally feasible by obtaining a 3D image of a test object from a single
2D diffraction pattern. This approach of obtaining complete 3D structure
information from a single view is anticipated to find broad applications in the
physical and life sciences. As X-ray free electron lasers (X-FEL) and other
coherent X-ray sources are under rapid development worldwide, ankylography
potentially opens a door to determining the 3D structure of a biological
specimen in a single pulse and allowing for time-resolved 3D structure
determination of disordered materials.Comment: 30 page
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20
[1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030
Inference from Incomplete Data in Coherent Diffraction Imaging
Progress in nanotechnology and biotechnology are propelled by our ability to manipulate and resolve the structure of matter on fine scales. As imaging at higher resolution is limited by the probing light source and the numerical aperture, lensless imaging offers an advantage over lensed microscopy. Dispensing with lenses allows one to overcome certain intrinsic aberrations and to bypass fabrication costs, in the optical and the X-ray regimes. The long penetration depth of X-rays renders coherent X-ray diffraction imaging (CXDI) the method of choice for high resolution structure determination with broad applications from materials science to biology; moreover, the same methodology is extensible to electrons, optical photons, or even gamma rays or neutrons. Since coherent diffraction imaging (CDI) bypasses the need for focusing optics, it relies upon computer algorithms to reconstruct the structure of the scattering object. Currently, one of the main obstacles to nanometer resolution of biological imaging is noisy, incomplete data due to radiation damage. With the rapid development of new light source facilities and the advancement in image reconstruction techniques, determining the structure of individual virons or cells at high resolution is becoming more feasible. In particular, the femtosecond pulse of a free electron laser (FEL) is shorter than the coulomb explosion of the specimen, and thus, it is possible to collect diffraction data prior to radiation damage. However, to fully exploit the computational aspect of lensless imaging, prior knowledge about the object should be incorporated into the image reconstruction process and yet so far such methods are generally lacking. In this thesis, we develop tools that incorporate prior knowledge and reduce the amount of necessary data to recover the structure. We begin by a brief overview of lensless imaging and its place in the natural sciences. we then review the process of image formation in coherent X-ray scattering, the corresponding phase problem and the current state of image recovery. The contributions to this field are two fold. We first demonstrate that three dimensional information can be extracted from a two dimensional diffraction pattern collected at a high numerical aperture. Second, we present a framework for image discovery through Bayesian inference, where we introduce four general constraints: symmetry, sparsity and bounded local and total variation. Using simulated noisy, incomplete data, we recover the solution in situations where traditional algorithms fail. We anticipate that these results will encourage the broader application of Bayesian learning into the phase retrieval problem from noisy, incomplete diffraction data and further enhance the possibility of single shot three dimensional structure determination
The Surgical Treatment and Genomic Analysis of a Rare Case of Oligometastatic Renal Cell Carcinoma of the Prostate
Deterpenation of Origanum majorana L. essential oil by reduced pressure steam distillation
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease