Access to health knowledge for health equality: a multi-phase review focused on disability-health.

BACKGROUND: The existing evidence base indicates increased interest in knowledge translation (KT), or, the dissemination of research to ensure uptake and impact. Given this definition, this study aimed to review existing scholarship on knowledge translation (KT) of health research to people living with disabilities (PLWD), and assess the current state of accessibility of health knowledge for people living with disabilities. METHODS: Given existing heterogeneity in literature as well as a number of varying definitions for both disability and knowledge translation, a reflexive, three-phase approach was utilized to improve methodological soundness. Phase I recognizes that existing review-style studies have been conducted on disability-KT. An existing systematic review on KT specific to the field of rehabilitation and physical medicine was analyzed to assess potential best practices towards inclusivity and accessibility for people living with disability. Phase II used the Center on Knowledge Translation for Disability and Rehabilitation Research (KTDRR) database as an information-source with high-specificity to disability-health KT. Phase III sought to rapidly assess the current landscape of systematic reviews relevant to disability-health KT, with four systematic reviews meeting the inclusion criteria across Cochrane, Psycinfo, CINAHL, PubMed, Web of Science, and EMBASE. RESULTS: The current landscape of disability-health KT is primarily targeted at health professionals who serve PLWD. PLWD are included in KT, mostly as key informants, or as study participants in KT-studies designed as health interventions. Multiple systematic reviews on disability-health KT exist, presenting vastly different foci which prevent assessment of best practices. CONCLUSIONS: KT efforts are abundant and can be seen across health research related to disabilities, generating considerable literature and systematic reviews. With regards to meeting the public health objective of equalizing and enhancing access to health knowledge, future knowledge translation efforts intending to provide PLWD with up-to-date health research can be of significant value.

In Science Journals.

Highlights from the Science family of journals.

Two annual cycles of the Pacific cold tongue under orbital precession.

The Pacific cold tongue annual cycle in sea surface temperature is presumed to be driven by Earth's axial tilt1-5 (tilt effect), and thus its phasing should be fixed relative to the calendar. However, its phase and amplitude change dramatically and consistently under various configurations of orbital precession in several Earth System models. Here, we show that the cold tongue possesses another annual cycle driven by the variation in Earth-Sun distance (distance effect) from orbital eccentricity. As the two cycles possess slightly different periodicities6, their interference results in a complex evolution of the net seasonality over a precession cycle. The amplitude from the distance effect increases linearly with eccentricity and is comparable to the amplitude from the tilt effect for the largest eccentricity values over the last million years (e value approximately 0.05)7. Mechanistically, the distance effect on the cold tongue arises through a seasonal longitudinal shift in the Walker circulation and subsequent annual wind forcing on the tropical Pacific dynamic ocean-atmosphere system. The finding calls for reassessment of current understanding of the Pacific cold tongue annual cycle and re-evaluation of tropical Pacific palaeoclimate records for annual cycle phase changes.

Split westerlies over Europe in the early Little Ice Age.

The Little Ice Age (LIA; ca. 1450-1850 C.E.) is the best documented cold period of the past millennium, characterized by high-frequency volcanism, low solar activity, and high variability of Arctic sea-ice cover. Past studies of LIA Atlantic circulation changes have referenced the North Atlantic Oscillation (NAO), but recent studies have noted that LIA climate patterns appear to possess complexity not captured by an NAO analogue. Here, we present a new precipitation-sensitive stalagmite record from northern Italy that covers the past 800 years. We show that in the early LIA (1470-1610 C.E.), increased atmospheric ridging over northern Europe split the climatological westerlies away from central and northern Europe, possibly caused by concurrent Artic sea-ice reduction. With ongoing ice melting in the northern high latitudes and decreasing solar irradiance in the coming years, the early LIA may potentially serve as an analogue for European hydroclimatic conditions in the coming decades.

Unsupervised learning approaches to characterizing heterogeneous samples using X-ray single-particle imaging.

One of the outstanding analytical problems in X-ray single-particle imaging (SPI) is the classification of structural heterogeneity, which is especially difficult given the low signal-to-noise ratios of individual patterns and the fact that even identical objects can yield patterns that vary greatly when orientation is taken into consideration. Proposed here are two methods which explicitly account for this orientation-induced variation and can robustly determine the structural landscape of a sample ensemble. The first, termed common-line principal component analysis (PCA), provides a rough classification which is essentially parameter free and can be run automatically on any SPI dataset. The second method, utilizing variation auto-encoders (VAEs), can generate 3D structures of the objects at any point in the structural landscape. Both these methods are implemented in combination with the noise-tolerant expand-maximize-compress (EMC) algorithm and its utility is demonstrated by applying it to an experimental dataset from gold nanoparticles with only a few thousand photons per pattern. Both discrete structural classes and continuous deformations are recovered. These developments diverge from previous approaches of extracting reproducible subsets of patterns from a dataset and open up the possibility of moving beyond the study of homogeneous sample sets to addressing open questions on topics such as nanocrystal growth and dynamics, as well as phase transitions which have not been externally triggered.

Reprint of: Inversion of dynamical Bragg intensities to complex structure factors by iterated projections. For Ultramic. 2020. ("Pico" Festschrift, May 2021).

A method for recovering complex structure factors from many simultaneously excited Bragg beam in- tensities is described. The method is applied to simulated transmission electron diffraction data over a wide range of crystal thickness and beam energies. The method is based on iterated projections between structure and scattering matrices, which are related by a matrix unit ary transformation, exponential, which we invert. The algorithm removes multiple-scattering perturbations from diffraction data and might be extended to other fields, including X-ray and neutron diffraction and cryo-electron microscopy. Because coherent multiple scattering involves interference between Bragg beams, the method also solves the phase problem. Unlike dynamical inversion from electron microscope images or ptychography data, the method, which starts with Bragg beam intensities, provides complex structure factors unaffected by focusing errors or resolution limitations imposed by lenses. We provide inversions from simulated data with 441 simultaneously excited Bragg beams over a range of thickness and beam energy. We discuss the retrieval of chirality information from enantiomorphs, the efficient incorporation of symmetry information using the irreducible representation of the group of structure matrices, and the effect of HOLZ lines to provide three-dimensional information.

Global warming-induced Asian hydrological climate transition across the Miocene-Pliocene boundary.

Across the Miocene-Pliocene boundary (MPB; 5.3 million years ago, Ma), late Miocene cooling gave way to the early-to-middle Pliocene Warm Period. This transition, across which atmospheric CO2 concentrations increased to levels similar to present, holds potential for deciphering regional climate responses in Asia-currently home to more than half of the world's population- to global climate change. Here we find that CO2-induced MPB warming both increased summer monsoon moisture transport over East Asia, and enhanced aridification over large parts of Central Asia by increasing evaporation, based on integration of our ~1-2-thousand-year (kyr) resolution summer monsoon records from the Chinese Loess Plateau aeolian red clay with existing terrestrial records, land-sea correlations, and climate model simulations. Our results offer palaeoclimate-based support for 'wet-gets-wetter and dry-gets-drier' projections of future regional hydroclimate responses to sustained anthropogenic forcing. Moreover, our high-resolution monsoon records reveal a dynamic response to eccentricity modulation of solar insolation, with predominant 405-kyr and ~100-kyr periodicities between 8.1 and 3.4 Ma.

Observation of substrate diffusion and ligand binding in enzyme crystals using high-repetition-rate mix-and-inject serial crystallography.

Here, we illustrate what happens inside the catalytic cleft of an enzyme when substrate or ligand binds on single-millisecond timescales. The initial phase of the enzymatic cycle is observed with near-atomic resolution using the most advanced X-ray source currently available: the European XFEL (EuXFEL). The high repetition rate of the EuXFEL combined with our mix-and-inject technology enables the initial phase of ceftriaxone binding to the Mycobacterium tuberculosis ß-lactamase to be followed using time-resolved crystallography in real time. It is shown how a diffusion coefficient in enzyme crystals can be derived directly from the X-ray data, enabling the determination of ligand and enzyme-ligand concentrations at any position in the crystal volume as a function of time. In addition, the structure of the irreversible inhibitor sulbactam bound to the enzyme at a 66 ms time delay after mixing is described. This demonstrates that the EuXFEL can be used as an important tool for biomedically relevant research.

'J'accuse.!': the continuous failure to address radiophobia and placing radiation in perspective.

As far as carcinogens are concerned, radiation is one of the best studied, having been researched for more than 100 years. Yet, radiation remains feared in many contexts as a result of its invisibility, its relationship with cancers and congenital disorders, aided by a variety of heuristics and reinforced by negative imagery. The strong socio-psychological response relating to nuclear energy has made radiation a classical case in the risk literature. This is reflected clearly following the nuclear accidents that have taken place, where the socio-psychological impacts of the clear dissonance between real and perceived health effects due to radiation exposure have caused considerable health detriment, outweighing the actual radiological impacts. Despite considerable efforts to normalise humankind's relationship with radiation, there has been little shift away from the perceived uniqueness of the health risks of radiation. One consistent issue is the failure to place radiation within its proper perspective and context, which has ensured that radiophobia has persisted. The radiation protection community must get better at placing its research within the appropriate perspective and context, something that is far too rarely the case in discussions on radiation matters outside of the scientific community. Each member of the radiation protection community has an ethical, professional and moral obligation to set the record straight, to challenge the misconceptions and factual errors that surround radiation, as well as putting it into the proper perspective and context. Failing to do so, the well-established harms of radiophobia will remain, and the many benefits of nuclear technology risk being withheld.

Early-stage dynamics of chloride ion-pumping rhodopsin revealed by a femtosecond X-ray laser.

Chloride ion-pumping rhodopsin (ClR) in some marine bacteria utilizes light energy to actively transport Cl- into cells. How the ClR initiates the transport is elusive. Here, we show the dynamics of ion transport observed with time-resolved serial femtosecond (fs) crystallography using the Linac Coherent Light Source. X-ray pulses captured structural changes in ClR upon flash illumination with a 550 nm fs-pumping laser. High-resolution structures for five time points (dark to 100 ps after flashing) reveal complex and coordinated dynamics comprising retinal isomerization, water molecule rearrangement, and conformational changes of various residues. Combining data from time-resolved spectroscopy experiments and molecular dynamics simulations, this study reveals that the chloride ion close to the Schiff base undergoes a dissociation-diffusion process upon light-triggered retinal isomerization.

Synchronous RNA conformational changes trigger ordered phase transitions in crystals.

Time-resolved studies of biomacromolecular crystals have been limited to systems involving only minute conformational changes within the same lattice. Ligand-induced changes greater than several angstroms, however, are likely to result in solid-solid phase transitions, which require a detailed understanding of the mechanistic interplay between conformational and lattice transitions. Here we report the synchronous behavior of the adenine riboswitch aptamer RNA in crystal during ligand-triggered isothermal phase transitions. Direct visualization using polarized video microscopy and atomic force microscopy shows that the RNA molecules undergo cooperative rearrangements that maintain lattice order, whose cell parameters change distinctly as a function of time. The bulk lattice order throughout the transition is further supported by time-resolved diffraction data from crystals using an X-ray free electron laser. The synchronous molecular rearrangements in crystal provide the physical basis for studying large conformational changes using time-resolved crystallography and micro/nanocrystals.

Inversion of dynamical Bragg intensities to complex structure factors by iterated projections. For Ultramic. 2020. ("Pico" Festschrift, May 2021).

A method for recovering complex structure factors from many simultaneously excited Bragg beam in- tensities is described. The method is applied to simulated transmission electron diffraction data over a wide range of crystal thickness and beam energies. The method is based on iterated projections between structure and scattering matrices, which are related by a matrix unit ary transformation, exponential, which we invert. The algorithm removes multiple-scattering perturbations from diffraction data and might be extended to other fields, including X-ray and neutron diffraction and cryo-electron microscopy. Because coherent multiple scattering involves interference between Bragg beams, the method also solves the phase problem. Unlike dynamical inversion from electron microscope images or ptychography data, the method, which starts with Bragg beam intensities, provides complex structure factors unaffected by focusing errors or resolution limitations imposed by lenses. We provide inversions from simulated data with 441 simultaneously excited Bragg beams over a range of thickness and beam energy. We discuss the retrieval of chirality information from enantiomorphs, the efficient incorporation of symmetry information using the irreducible representation of the group of structure matrices, and the effect of HOLZ lines to provide three-dimensional information.

Inversion of Many-Beam Bragg Intensities for Phasing by Iterated Projections: Removal of Multiple Scattering Artifacts from Diffraction Data.

An iterated projection algorithm (N-Phaser) is developed that reconstructs a scattering potential from N-beam multiple Bragg scattered intensities. The method may be used to eliminate multiple scattering artifacts from electron diffraction data, solving the phase problem and increasing the thicknesses of samples used in materials science, solid-state chemistry, and small molecule crystallography. For high-energy transmission electron diffraction, we show that the algorithm recovers accurate complex structure factors from a wide range of thicknesses, orientations, and relativistic beam energies, and does not require known thickness or atomic-resolution data if sufficient multiple scattering occurs. Extensions to Cryo-electron microscopy and Micro-electron diffraction are suggested.

3D printing of gas-dynamic virtual nozzles and optical characterization of high-speed microjets.

Gas dynamic virtual nozzles (GDVNs) produce microscopic flow-focused liquid jets and droplets and play an important role at X-ray free-electron laser (XFEL) facilities where they are used to steer a stream of hydrated biomolecules into an X-ray focus during diffraction measurements. Highly stable and reproducible microjet and microdroplets are desired, as are flexible fabrication methods that enable integrated mixing microfluidics, droplet triggering mechanisms, laser illumination, and other customized features. In this study, we develop the use of high-resolution 3D nano-printing for the production of monolithic, asymmetric GDVN designs that are difficult to fabricate by other means. We also develop a dual-pulsed nanosecond image acquisition and analysis platform for the characterization of GDVN performance, including jet speed, length, diameter, and directionality, among others. We show that printed GDVNs can form microjets with very high degree of reproducibility, down to sub-micron diameters, and with water jet speeds beyond 170 m/s.

Enhanced X-ray diffraction of in vivo-grown µNS crystals by viscous jets at XFELs.

µNS is a 70 kDa major nonstructural protein of avian reoviruses, which cause significant economic losses in the poultry industry. They replicate inside viral factories in host cells, and the µNS protein has been suggested to be the minimal viral factor required for factory formation. Thus, determining the structure of µNS is of great importance for understanding its role in viral infection. In the study presented here, a fragment consisting of residues 448-605 of µNS was expressed as an EGFP fusion protein in Sf9 insect cells. EGFP-µNS(448-605) crystallization in Sf9 cells was monitored and verified by several imaging techniques. Cells infected with the EGFP-µNS(448-605) baculovirus formed rod-shaped microcrystals (5-15 µm in length) which were reconstituted in high-viscosity media (LCP and agarose) and investigated by serial femtosecond X-ray diffraction using viscous jets at an X-ray free-electron laser (XFEL). The crystals diffracted to 4.5 Šresolution. A total of 4227 diffraction snapshots were successfully indexed into a hexagonal lattice with unit-cell parameters a = 109.29, b = 110.29, c = 324.97 Å. The final data set was merged and refined to 7.0 Šresolution. Preliminary electron-density maps were obtained. While more diffraction data are required to solve the structure of µNS(448-605), the current experimental strategy, which couples high-viscosity crystal delivery at an XFEL with in cellulo crystallization, paves the way towards structure determination of the µNS protein.

Enriched East Asian oxygen isotope of precipitation indicates reduced summer seasonality in regional climate and westerlies.

Speleothem oxygen isotope records over East Asia reveal apparently large and rapid paleoclimate changes over the last several hundred thousand years. However, what the isotopic variation actually represent in terms of the regional climate and circulation is debated. We present an answer that emerges from an analysis of the interannual variation in amount-weighted annual δ18O of precipitation over East Asia as simulated by an isotope-enabled model constrained by large-scale atmospheric reanalysis fields. 18O-enriched years have reduced summer seasonality both in terms of precipitation isotopes and in the large-scale circulation. Changes occur between June and October, where the δ18O of precipitation (δ18Op) transitions from the isotopically heavier winter to the lighter summer regime. For 18O-enriched years, this transition is less pronounced. Variations in precipitation amount alone are insufficient to explain the amount-weighted annual δ18Op between 18O-enriched and 18O-depleted years. Reduced summer seasonality is also expressed in the low-level monsoonal southerlies and upper-level westerlies; for the latter, the northward migration across the Tibetan Plateau in the summer is less pronounced. Our result thus implicates the westerlies across the plateau as the proximate cause of East Asian paleomonsoon changes, manifested as a modulation of its summer peak.

Precession modulation of the South Pacific westerly wind belt over the past million years.

The southern westerly wind belt (SWW) interacts with the Antarctic Circumpolar Current and strongly impacts the Southern Ocean carbon budget, and Antarctic ice-sheet dynamics across glacial-interglacial cycles. We investigated precipitation-driven sediment input changes to the Southeast Pacific off the southern margin of the Atacama Desert over the past one million years, revealing strong precession (19/23-ka) cycles. Our simulations with 2 ocean-atmosphere general circulation models suggest that observed cyclic rainfall changes are linked to meridional shifts in water vapor transport from the tropical Pacific toward the southern Atacama Desert. These changes reflect a precessional modulation of the split in the austral winter South Pacific jet stream. For precession maxima, we infer significantly enhanced rainfall in the southern Atacama Desert due to a stronger South Pacific split jet with enhanced subtropical/subpolar jets, and a weaker midlatitude jet. Conversely, we derive dry conditions in northern Chile related to reduced subtropical/subpolar jets and an enhanced midlatitude jet for precession minima. The presence of precessional cycles in the Pacific SWW, and lack thereof in other basins, indicate that orbital-scale changes of the SWW were not zonally homogeneous across the Southern Hemisphere, in contrast to the hemispherewide shifts of the SWW suggested for glacial terminations. The strengthening of the jet is unique to the South Pacific realm and might have affected winter-controlled changes in the mixed layer depth, the formation of intermediate water, and the buildup of sea-ice around Antarctica, with implications for the global overturning circulation and the oceanic storage of atmospheric CO2.

High-viscosity injector-based pink-beam serial crystallography of microcrystals at a synchrotron radiation source.

Since the first successful serial crystallography (SX) experiment at a synchrotron radiation source, the popularity of this approach has continued to grow showing that third-generation synchrotrons can be viable alternatives to scarce X-ray free-electron laser sources. Synchrotron radiation flux may be increased ∼100 times by a moderate increase in the bandwidth ('pink beam' conditions) at some cost to data analysis complexity. Here, we report the first high-viscosity injector-based pink-beam SX experiments. The structures of proteinase K (PK) and A2A adenosine receptor (A2AAR) were determined to resolutions of 1.8 and 4.2 Šusing 4 and 24 consecutive 100 ps X-ray pulse exposures, respectively. Strong PK data were processed using existing Laue approaches, while weaker A2AAR data required an alternative data-processing strategy. This demonstration of the feasibility presents new opportunities for time-resolved experiments with microcrystals to study structural changes in real time at pink-beam synchrotron beamlines worldwide.