A wide-field micro-computed tomography detector: micron resolution at half-centimetre scale.

Ideal three-dimensional imaging of complex samples made up of micron-scale structures extending over mm to cm, such as biological tissues, requires both wide field of view and high resolution. For existing optics and detectors used for micro-CT (computed tomography) imaging, sub-micron pixel resolution can only be achieved for fields of view of <2 mm. This article presents a unique detector system with a 6 mm field-of-view image circle and 0.5 µm pixel size that can be used in micro-CT units utilizing both synchrotron and commercial X-ray sources. A resolution-test pattern with linear microstructures and whole adult Daphnia magna were imaged at beamline 8.3.2 of the Berkeley Advanced Light Source. Volumes of 10000 × 10000 × 7096 isotropic 0.5 µm voxels were reconstructed over a 5.0 mm × 3.5 mm field of view. Measurements in the projection domain confirmed a 0.90 µm measured spatial resolution that is largely Nyquist-limited. This unprecedented combination of field of view and resolution dramatically reduces the need for sectional scans and computational stitching for large samples, ultimately offering the means to elucidate changes in tissue and cellular morphology in the context of larger, whole, intact model organisms and specimens. This system is also anticipated to benefit micro-CT imaging in materials science, microelectronics, agricultural science and biomedical engineering.

A global ecological signal of extinction risk in terrestrial vertebrates.

To determine the distribution and causes of extinction threat across functional groups of terrestrial vertebrates, we assembled an ecological trait data set for 18,016 species of terrestrial vertebrates and utilized phylogenetic comparative methods to test which categories of habitat association, mode of locomotion, and feeding mode best predicted extinction risk. We also examined the individual categories of the International Union for Conservation of Nature Red List extinction drivers (e.g., agriculture and logging) threatening each species and determined the greatest threats for each of the four terrestrial vertebrate groups. We then quantified the sum of extinction drivers threatening each species to provide a multistressor perspective on threat. Cave dwelling amphibians (p < 0.01), arboreal quadrupedal mammals (all of which are primates) (p < 0.01), aerial and scavenging birds (p < 0.01), and pedal (i.e., walking) squamates (p < 0.01) were all disproportionately threatened with extinction in comparison with the other assessed ecological traits. Across all threatened vertebrate species in the study, the most common risk factors were agriculture, threatening 4491 species, followed by logging, threatening 3187 species, and then invasive species and disease, threatening 2053 species. Species at higher risk of extinction were simultaneously at risk from a greater number of threat types. If left unabated, the disproportionate loss of species with certain functional traits and increasing anthropogenic pressures are likely to disrupt ecosystem functions globally. A shift in focus from species- to trait-centric conservation practices will allow for protection of at-risk functional diversity from regional to global scales.

Una Señal Ecológica Mundial del Riesgo de Extinción de los Vertebrados Terrestres Resumen Construimos un conjunto de datos de atributos ecológicos de 18,016 especies de vertebrados terrestres y utilizamos métodos de comparación filogenética para analizar cuáles categorías de asociación de hábitat, modo de locomoción y modo de alimentación predicen de mejor manera el riesgo de extinción. Lo anterior lo hicimos para determinar la distribución y las causas de las amenazas de extinción a lo largo de los grupos funcionales de vertebrados terrestres. También examinamos las categorías individuales de los factores de extinción (p. ej.: agricultura, tala de árboles) de la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza que amenazan a cada especie y determinamos las principales amenazas para cada uno de los cuatro grupos de vertebrados terrestres. Después cuantificamos la suma de los factores de extinción que amenazan a cada especie para proporcionar una perspectiva de estresores múltiples sobre la amenaza. Los anfibios cavernícolas (p < 0.01), mamíferos arbóreos cuadrúpedos (todos son primates) (p < 0.01), aves aéreas y carroñeras (p < 0.01) y los escamados caminantes (p < 0.01) tuvieron una amenaza de extinción desproporcionada en comparación con los otros atributos ecológicos analizados. En todas las especies de vertebrados que estudiamos, los factores de riesgo más comunes fueron la agricultura, que amenaza a 4,491 especies, y la deforestación, que amenaza a 3,187 especies; le siguen las especies invasoras y las enfermedades, que juntas amenazan a 2,053 especies. Las especies con el mayor riesgo de extinción también se encontraban simultáneamente en riesgo por un mayor número de tipos de amenazas. Si esto se mantiene constante, la pérdida desproporcionada de especies con ciertos atributos funcionales y la creciente presión antropogénica probablemente alteren las funciones ecosistémicas a nivel mundial. Un cambio en el enfoque de las prácticas de conservación, de estar centradas en la especie a estar centradas en los atributos, permitirá la protección de la diversidad funcional en riesgo desde la escala regional hasta la global.

Statistical estimates of hominin origination and extinction dates: A case study examining the Australopithecus anamensis-afarensis lineage.

Reliable estimates of when hominin taxa originated and went extinct are central to addressing many paleoanthropological questions, including those relating to macroevolutionary patterns. The timing of hominin temporal ranges can be used to test chronological predictions generated from phylogenetic hypotheses. For example, hypotheses of phyletic ancestor-descendant relationships, based on morphological data, predict no temporal range overlap between the two taxa. However, a fossil taxon's observed temporal range is almost certainly underestimated due to the incompleteness of both the fossil record itself and its sampling, and this decreases the likelihood of observing temporal overlap. Here, we focus on a well-known and widely accepted early hominin lineage, Australopithecus anamensis-afarensis, and place 95% confidence intervals (CIs) on its origination and extinction dates. We do so to assess whether its temporal range is consistent with it being a phyletic descendant of Ardipithecus ramidus and/or a direct ancestor to the earliest claimed representative of Homo (i.e., Ledi-Geraru). We find that the last appearance of Ar. ramidus falls within the origination CI of Au. anamensis-afarensis, whereas the claimed first appearance of Homo postdates the extinction CI. These results are consistent with Homo evolving from Au. anamensis-afarensis, but temporal overlap between Ar. ramidus and Au. anamensis-afarensis cannot be rejected at this time. Though additional samples are needed, future research should extend our initial analyses to incorporate the uncertainties surrounding the range endpoints of Ar. ramidus and earliest Homo. Overall, our findings demonstrate the need for quantifying the uncertainty surrounding the appearances and disappearances of hominin taxa in order to better understand the timing of evolutionary events in our clade's history.

Sunscreen and frontal fibrosing alopecia: A review.

Frontal fibrosing alopecia (FFA) is a cicatricial alopecia of unknown etiology. The incidence of FFA appears to be increasing with time, leading to suspicion of a possible environmental trigger. Observational studies have reported a positive correlation between facial sunscreen use and FFA. This finding raises the question of whether sunscreen use plays a role in disease development. In this article, we review the available literature on the association of sunscreen with FFA. There is insufficient evidence to establish a direct causal relationship between sunscreen and FFA. Further studies are required to better characterize the role of sunscreen and the environment in the pathogenesis of this unique disease.

A novel co-processing method to manufacture an API for extended release formulation via formation of agglomerates of active ingredient and hydroxypropyl methylcellulose during crystallization.

A novel process for generating agglomerates of active pharmaceutical ingredient (API) and polymer by swelling the polymer in a water/organic mixture has been developed to address formulation issues resulting from a water sensitive, high drug load API with poor powder properties. Initially, the API is dissolved in water, following which hydroxypropyl methylcellulose (HPMC) is added, resulting in the imbibing of water, along with the dissolved API, into the HPMC matrix. The addition of acetone and isopropyl acetate (anti-solvents) then causes the API to crystallize inside and on the surface of HPMC agglomerates. The process was scaled up to 20 kg scale. The agglomerates of API and HPMC generated by this process are ∼350 µm diameter, robust, and have significantly better flow than the API as measured by Erweka flow testing. These agglomerates exhibit improved bulk density, acceptable chemical stability, and high compressibility. The agglomerates process well through roller compaction and tableting, with no flow or sticking issues. This process is potentially adaptable to other APIs with similar attributes.

Hierarchical complexity and the size limits of life.

Over the past 3.8 billion years, the maximum size of life has increased by approximately 18 orders of magnitude. Much of this increase is associated with two major evolutionary innovations: the evolution of eukaryotes from prokaryotic cells approximately 1.9 billion years ago (Ga), and multicellular life diversifying from unicellular ancestors approximately 0.6 Ga. However, the quantitative relationship between organismal size and structural complexity remains poorly documented. We assessed this relationship using a comprehensive dataset that includes organismal size and level of biological complexity for 11 172 extant genera. We find that the distributions of sizes within complexity levels are unimodal, whereas the aggregate distribution is multimodal. Moreover, both the mean size and the range of size occupied increases with each additional level of complexity. Increases in size range are non-symmetric: the maximum organismal size increases more than the minimum. The majority of the observed increase in organismal size over the history of life on the Earth is accounted for by two discrete jumps in complexity rather than evolutionary trends within levels of complexity. Our results provide quantitative support for an evolutionary expansion away from a minimal size constraint and suggest a fundamental rescaling of the constraints on minimal and maximal size as biological complexity increases.

Estimating times of extinction in the fossil record.

Because the fossil record is incomplete, the last fossil of a taxon is a biased estimate of its true time of extinction. Numerous methods have been developed in the palaeontology literature for estimating the true time of extinction using ages of fossil specimens. These methods, which typically give a confidence interval for estimating the true time of extinction, differ in the assumptions they make and the nature and amount of data they require. We review the literature on such methods and make some recommendations for future directions.

Image-based cell-resolved screening assays in flow.

A parallel microfluidic cytometer (PMC) is based on a one-dimensional (1D) scanning detector, a parallel array of flow channels, and new multiparameter analysis algorithms that operate on low-pixel-count 1D images. In this article, we explore a series of image-based live- and fixed-cell screening assays, including two NF-kB nuclear translocations and T-cell capping. We then develop a new multiparametric linear weighted classifier that achieves a Z' factor sufficient for scaled pharmaceutical discovery with Jurkat cells in suspension. We conclude that the PMC should have the throughput and statistical power to permit a new capability for image-based high-sample-number pharmaceutical screening with suspension samples.

In situ heater design for nanoscale synchrotron-based full-field transmission X-ray microscopy.

The oxidation of nickel powder under a controlled gas and temperature environment was studied using synchrotron-based full-field transmission X-ray microscopy. The use of this technique allowed for the reaction to be imaged in situ at 55 nm resolution. The setup was designed to fit in the limited working distance of the microscope and to provide the gas and temperature environments analogous to solid oxide fuel cell operating conditions. Chemical conversion from nickel to nickel oxide was confirmed using X-ray absorption near-edge structure. Using an unreacted core model, the reaction rate as a function of temperature and activation energy were calculated. This method can be applied to study many other chemical reactions requiring similar environmental conditions.

Angular spectrum simulation of X-ray focusing by Fresnel zone plates.

A computing simulation routine to model any type of circularly symmetric diffractive X-ray element has been implemented. The wavefield transmitted beyond the diffractive structures is numerically computed by the angular spectrum propagation method to an arbitrary propagation distance. Cylindrical symmetry is exploited to reduce the computation and memory requirements while preserving the accuracy of the numerical calculation through a quasi-discrete Hankel transform algorithm, an approach described by Guizar-Sicairos & Gutierrez-Vega [J. Opt. Soc. Am. A, (2004), 21, 53-58]. In particular, the code has been used to investigate the requirements for the stacking of two high-resolution Fresnel zone plates with an outermost zone width of 20 nm.

Nanostructured high-energy cathode materials for advanced lithium batteries.

Nickel-rich layered lithium transition-metal oxides, LiNi(1-x)M(x)O(2) (M = transition metal), have been under intense investigation as high-energy cathode materials for rechargeable lithium batteries because of their high specific capacity and relatively low cost. However, the commercial deployment of nickel-rich oxides has been severely hindered by their intrinsic poor thermal stability at the fully charged state and insufficient cycle life, especially at elevated temperatures. Here, we report a nickel-rich lithium transition-metal oxide with a very high capacity (215 mA h g(-1)), where the nickel concentration decreases linearly whereas the manganese concentration increases linearly from the centre to the outer layer of each particle. Using this nano-functional full-gradient approach, we are able to harness the high energy density of the nickel-rich core and the high thermal stability and long life of the manganese-rich outer layers. Moreover, the micrometre-size secondary particles of this cathode material are composed of aligned needle-like nanosize primary particles, resulting in a high rate capability. The experimental results suggest that this nano-functional full-gradient cathode material is promising for applications that require high energy, long calendar life and excellent abuse tolerance such as electric vehicles.

Ocular radiation exposure in modern urological practice.

PURPOSE: The human eye is a highly radiosensitive portion of the body and repeat radiation exposure can lead to cataract. The minimum fractionated long-term dose to initiate cataract formation is about 2,500 mSv. We determined whether further radiation related precautions are necessary to protect the eyes of the surgeon. MATERIALS AND METHODS: Radiation doses received near the right eye of the operating surgeon were measured with a thermoluminescent dosimeter badge worn near the eye of 6 urologists for a single endourological procedure at an academic center. Procedures included stent insertion, ureteroscopic lithotripsy and percutaneous nephrolithotomy. The mean radiation dose was calculated. Extrapolated doses required to potentiate cataract formation were also calculated. RESULTS: We assessed 28 urological procedures for radiation exposure, of which 13 were ureteroscopy done for calculus disease (range 0.05 to 0.66 mSv) and 7 were ureteral stent insertion (range 0.13 to 0.32 mSv). The mean radiation dose received during these cases was 0.208 mSv. Based on the mean dose and an average of 20 such cases per month, it would take about 50 years to reach the minimum threshold for progressive cataract formation. Eight percutaneous renal operations were performed and the mean dose received was 0.125 mSv (range 0.04 to 0.22). Based on 10 cases per month, this would require more than 160 years of exposure to reach the minimal threshold. CONCLUSIONS: Long-term radiation can lead to cataract formation. However, the accumulated lifetime exposure of the typical urologist may not necessitate further safety precautions, such as lead-lined glasses.

A new perspective on the mechanical evaluation of granular material.

The mechanical strength of granules is an important parameter to be determined prior to any further downstream formulation processing. It is important to have a good gauge on the granule integrity to forecast any foreseeable powder issues associated with the material processability such as segregation, content uniformity, and material flow-ability. In this study, a systematic methodology has been developed to quantify the integrity of these granules subjected to a low frequency acoustic field to arrive at the Granule Integrity (GI) index. This methodology has been compared to existing well-established bulk characterization techniques reported in the literature such as Heckel analysis, Kawakita analysis, and Young's modulus for four different processed samples. Heckel analysis is more amenable to examine the material deformability while Kawakita analysis is better suited to understand the mechanics of granular material. Individual granule strength measurements to determine Young's modulus often show large variations across the bulk sample. The GI index in conjunction with the Kawakita analysis provides us with more mechanistic insight and understanding into the formation of these granules from a processing perspective. This paper shows the benefits of using the GI index as a practical and direct methodology to characterize the GI of bulk samples in an industrial setting.

Two-phase increase in the maximum size of life over 3.5 billion years reflects biological innovation and environmental opportunity.

The maximum size of organisms has increased enormously since the initial appearance of life >3.5 billion years ago (Gya), but the pattern and timing of this size increase is poorly known. Consequently, controls underlying the size spectrum of the global biota have been difficult to evaluate. Our period-level compilation of the largest known fossil organisms demonstrates that maximum size increased by 16 orders of magnitude since life first appeared in the fossil record. The great majority of the increase is accounted for by 2 discrete steps of approximately equal magnitude: the first in the middle of the Paleoproterozoic Era (approximately 1.9 Gya) and the second during the late Neoproterozoic and early Paleozoic eras (0.6-0.45 Gya). Each size step required a major innovation in organismal complexity--first the eukaryotic cell and later eukaryotic multicellularity. These size steps coincide with, or slightly postdate, increases in the concentration of atmospheric oxygen, suggesting latent evolutionary potential was realized soon after environmental limitations were removed.

The evolutionary consequences of oxygenic photosynthesis: a body size perspective.

The high concentration of molecular oxygen in Earth's atmosphere is arguably the most conspicuous and geologically important signature of life. Earth's early atmosphere lacked oxygen; accumulation began after the evolution of oxygenic photosynthesis in cyanobacteria around 3.0-2.5 billion years ago (Gya). Concentrations of oxygen have since varied, first reaching near-modern values ~600 million years ago (Mya). These fluctuations have been hypothesized to constrain many biological patterns, among them the evolution of body size. Here, we review the state of knowledge relating oxygen availability to body size. Laboratory studies increasingly illuminate the mechanisms by which organisms can adapt physiologically to the variation in oxygen availability, but the extent to which these findings can be extrapolated to evolutionary timescales remains poorly understood. Experiments confirm that animal size is limited by experimental hypoxia, but show that plant vegetative growth is enhanced due to reduced photorespiration at lower O(2):CO(2). Field studies of size distributions across extant higher taxa and individual species in the modern provide qualitative support for a correlation between animal and protist size and oxygen availability, but few allow prediction of maximum or mean size from oxygen concentrations in unstudied regions. There is qualitative support for a link between oxygen availability and body size from the fossil record of protists and animals, but there have been few quantitative analyses confirming or refuting this impression. As oxygen transport limits the thickness or volume-to-surface area ratio-rather than mass or volume-predictions of maximum possible size cannot be constructed simply from metabolic rate and oxygen availability. Thus, it remains difficult to confirm that the largest representatives of fossil or living taxa are limited by oxygen transport rather than other factors. Despite the challenges of integrating findings from experiments on model organisms, comparative observations across living species, and fossil specimens spanning millions to billions of years, numerous tractable avenues of research could greatly improve quantitative constraints on the role of oxygen in the macroevolutionary history of organismal size.

Prevalence and determinants of cervical cancer screening in five sub-Saharan African countries: A population-based study.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide, with an estimate of 570,000 new cases and about 311,000 deaths annually. Low-resource countries, including those in sub-Saharan Africa, have the highest-burden with an estimate of 84 % of all cervical cancers. This study examines the prevalence and socio-demographic-economic factors associated with cervical cancer screening in sub-Saharan Africa. METHODS: A weighted population-based cross-sectional study using Demographic and Health Surveys data. We used available data on cervical cancer screening between 2011 and 2018 from the Demographic and Health Surveys for five sub-Saharan African countries (Benin, Ivory Coast, Kenya, Namibia, and Zimbabwe). The study population included women of childbearing age, 21-49 years (n = 28,976). We fit a multivariable Poisson regression model to identify independent factors associated with cervical cancer screening. RESULTS: The overall weighted prevalence of cervical cancer screening was 19.0 % (95 % CI: 18.5 %-19.5 %) ranging from 0.7 % in Benin to 45.9 % in Namibia. Independent determinants of cervical cancer screening were: older age (40-49 years) adjusted prevalence ratio (aPR) = 1.77 (95 % CI: 1.64, 1.90) compared with younger age (21-29 years), secondary/higher education (aPR = 1.51, 95 CI: 1.28-1.79) compared with no education, health insurance (aPR = 1.53, 95 % CI: 1.44-1.61) compared with no insurance, and highest socioeconomic status (aPR = 1.39, 95 % CI: 1.26-1.52) compared with lowest. CONCLUSION: The prevalence of cervical cancer screening is substantially low in sub-Saharan Africa countries and shows a high degree of between-country variation. Interventions aimed at increasing the uptake of cervical cancer screening in sub-Saharan Africa are critically needed.

The use of barbiturate coma as salvage therapy in a postoperative Jehovah's Witness patient with life-threatening anemia.

Management of the patient who refuses blood products based on religious grounds poses ethical and clinical challenges, especially when the degree of anemia becomes life-threatening. In this report, we present the case of a 52-year-old Jehovah's Witness with sickle cell disease in whom he and his family refused blood products for the treatment of severe anemia associated with profound and progressive acidosis, acute oliguric renal failure, and hemodynamic instability. Attempts carried out during the first 3 hospital days to stabilize the patient using standard therapies to support oxygen delivery as well as the use of sedation, pain control, temperature control, neuromuscular blockade, and mechanical ventilation to reduce oxygen demand were not successful. Thus, because oxygen consumption by the brain represents approximately 20 per cent of the body's oxygen needs, and pentobarbital's primary action is as a central nervous system depressant, the induction of pentobarbital coma was instituted to reduce cerebral oxygen consumption. The institution of pentobarbital on hospital Day 3 was sufficient to acutely stabilize the patient's deteriorating metabolic state and ultimately was associated with survival. Thus, we conclude that there is a potential role for barbiturate coma in Jehovah's Witness patients who refuse blood transfusions and dying of anemia when other modalities of support are not sufficient.