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ObjectiveTo optimise dementia prevention strategies, we must understand the complex relationships between lifestyle behaviours, frailty and genetics.MethodsWe explored relationships between frailty index, healthy lifestyle and polygenic risk scores (all assessed at study entry) and incident all-cause dementia as recorded on hospital admission records and death register data.ResultsThe analytical sample had a mean age of 64.1 years at baseline (SD=2.9) and 53% were women. Incident dementia was detected in 1762 participants (median follow-up time=8.0 years). High frailty was associated with increased dementia risk independently of genetic risk (HR 3.68, 95% CI 3.11 to 4.35). Frailty mediated 44% of the relationship between healthy lifestyle behaviours and dementia risk (indirect effect HR 0.95, 95% CI 0.95 to 0.96). Participants at high genetic risk and with high frailty had 5.8 times greater risk of incident dementia compared with those at low genetic risk and with low frailty (HR 5.81, 95% CI 4.01 to 8.42). Higher genetic risk was most influential in those with low frailty (HR 1.31, 95% CI 1.22 to 1.40) but not influential in those with high frailty (HR 1.09, 95% CI 0.92 to 1.28).ConclusionFrailty is strongly associated with dementia risk and affects the risk attributable to genetic factors. Frailty should be considered an important modifiable risk factor for dementia and a target for dementia prevention strategies, even among people at high genetic risk.

Solution-processed organic photovoltaic cells (OPVs) hold great promise to enable roll-to-roll printing of environmentally friendly, mechanically flexible and cost-effective photovoltaic devices. Nevertheless, many high-performing systems show best power conversion efficiencies (PCEs) with a thin active layer (thickness is ~100 nm) that is difficult to translate to roll-to-roll processing with high reproducibility. Here we report a new molecular donor, benzodithiophene terthiophene rhodanine (BTR), which exhibits good processability, nematic liquid crystalline behaviour and excellent optoelectronic properties. A maximum PCE of 9.3% is achieved under AM 1.5G solar irradiation, with fill factor reaching 77%, rarely achieved in solution-processed OPVs. Particularly promising is the fact that BTR-based devices with active layer thicknesses up to 400 nm can still afford high fill factor of ~70% and high PCE of ~8%. Together, the results suggest, with better device architectures for longer device lifetime, BTR is an ideal candidate for mass production of OPVs. There is a trade-off between increasing thickness of active layers in organic photovoltaic cells to be compatible with modern printing techniques and decreasing it to improve the device performance. Sun et al. report a nematic liquid crystalline molecular electron donor material used in thick layers.

BackgroundThe past two decades have witnessed a surge in the use of lumbar facet blocks and radiofrequency ablation (RFA) to treat low back pain (LBP), yet nearly all aspects of the procedures remain controversial.MethodsAfter approval by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, letters were sent to a dozen pain societies, as well as representatives from the US Departments of Veterans Affairs and Defense. A steering committee was convened to select preliminary questions, which were revised by the full committee. Questions were assigned to 4–5 person modules, who worked with the Subcommittee Lead and Committee Chair on preliminary versions, which were sent to the full committee. We used a modified Delphi method, whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chair, who incorporated the comments and sent out revised versions until consensus was reached.Results17 questions were selected for guideline development, with 100% consensus achieved by committee members on all topics. All societies except for one approved every recommendation, with one society dissenting on two questions (number of blocks and cut-off for a positive block before RFA), but approving the document. Specific questions that were addressed included the value of history and physical examination in selecting patients for blocks, the value of imaging in patient selection, whether conservative treatment should be used before injections, whether imaging is necessary for block performance, the diagnostic and prognostic value of medial branch blocks (MBB) and intra-articular (IA) injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for a prognostic block, how many blocks should be performed before RFA, how electrodes should be oriented, the evidence for larger lesions, whether stimulation should be used before RFA, ways to mitigate complications, if different standards should be applied to clinical practice and clinical trials and the evidence for repeating RFA (see table 12 for summary).ConclusionsLumbar medial branch RFA may provide benefit to well-selected individuals, with MBB being more predictive than IA injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of more false-negatives. Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.

Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.

We evaluated the performance of the MinION DNA sequencer in-flight on the International Space Station (ISS), and benchmarked its performance off-Earth against the MinION, Illumina MiSeq, and PacBio RS II sequencing platforms in terrestrial laboratories. Samples contained equimolar mixtures of genomic DNA from lambda bacteriophage, Escherichia coli (strain K12, MG1655) and Mus musculus (female BALB/c mouse). Nine sequencing runs were performed aboard the ISS over a 6-month period, yielding a total of 276,882 reads with no apparent decrease in performance over time. From sequence data collected aboard the ISS, we constructed directed assemblies of the ~4.6 Mb E. coli genome, ~48.5 kb lambda genome, and a representative M. musculus sequence (the ~16.3 kb mitochondrial genome), at 100%, 100%, and 96.7% consensus pairwise identity, respectively; de novo assembly of the E. coli genome from raw reads yielded a single contig comprising 99.9% of the genome at 98.6% consensus pairwise identity. Simulated real-time analyses of in-flight sequence data using an automated bioinformatic pipeline and laptop-based genomic assembly demonstrated the feasibility of sequencing analysis and microbial identification aboard the ISS. These findings illustrate the potential for sequencing applications including disease diagnosis, environmental monitoring, and elucidating the molecular basis for how organisms respond to spaceflight.

The 2016 moment magnitude (Mw) 7.8 Kaikoura earthquake was one of the largest ever to hit New Zealand. Hamling et al. show with a new slip model that it was an incredibly complex event. Unlike most earthquakes, multiple faults ruptured to generate the ground shaking. A remarkable 12 faults ruptured overall, with the rupture jumping between faults located up to 15 km away from each other. The earthquake should motivate rethinking of certain seismic hazard models, which do not presently allow for this unusual complex rupture pattern. Science, this issue p. eaam7194 On 14 November 2016 (local time), northeastern South Island of New Zealand was struck by a major moment magnitude (Mw) 7.8 earthquake. The Kaikoura earthquake was the most powerful experienced in the region in more than 150 years. The whole of New Zealand reported shaking, with widespread damage across much of northern South Island and in the capital city, Wellington. The earthquake straddled two distinct seismotectonic domains, breaking multiple faults in the contractional North Canterbury fault zone and the dominantly strike-slip Marlborough fault system. Earthquakes are conceptually thought to occur along a single fault. Although this is often the case, the need to account for multiple segment ruptures challenges seismic hazard assessments and potential maximum earthquake magnitudes. Field observations from many past earthquakes and numerical models suggest that a rupture will halt if it has to step over a distance as small as 5 km to continue on a different fault. The Kaikoura earthquake's complexity defies many conventional assumptions about the degree to which earthquake ruptures are controlled by fault segmentation and provides additional motivation to rethink these issues in seismic hazard models. Field observations, in conjunction with interferometric synthetic aperture radar (InSAR), Global Positioning System (GPS), and seismology data, reveal the Kaikoura earthquake to be one of the most complex earthquakes ever recorded with modern instrumental techniques. The rupture propagated northward for more than 170 km along both mapped and unmapped faults before continuing offshore at the island's northeastern extent. A tsunami of up to 3 m in height was detected at Kaikoura and at three other tide gauges along the east coast of both the North and South Islands. Geodetic and geological field observations reveal surface ruptures along at least 12 major crustal faults and extensive uplift along much of the coastline. Surface displacements measured by GPS and satellite radar data show horizontal offsets of ~6 m. In addition, a fault-bounded block (the Papatea block) was uplifted by up to 8 m and translated south by 4 to 5 m. Modeling suggests that some of the faults slipped by more than 20 m, at depths of 10 to 15 km, with surface slip of ~10 m consistent with field observations of offset roads and fences. Although we can explain most of the deformation by crustal faulting alone, global moment tensors show a larger thrust component, indicating that the earthquake also involved some slip along the southern end of the Hikurangi subduction interface, which lies ~20 km beneath Kaikoura. Including this as a fault source in the inversion suggests that up to 4 m of predominantly reverse slip may have occurred on the subduction zone beneath the crustal faults, contributing ~10 to 30% of the total moment. Although the unusual multifault rupture observed in the Kaikoura earthquake may be partly related to the geometrically complex nature of the faults in this region, this event emphasizes the importance of reevaluating how rupture scenarios are defined for seismic hazard models in plate boundary zones worldwide. (A and B ) Photos showing the coastal uplift of 2 to 3 m associated with the Papatea block [labeled in (C)]. The inset in (A) shows an aerial view of New Zealand. Red lines denote the location of known active faults. The black box indicates the Marlborough fault system. (C ) Three-dimensional displacement field derived from satellite radar data. The vectors represent the horizontal displacements, and the colored background shows the vertical displacements. On 14 November 2016, northeastern South Island of New Zealand was struck by a major moment magnitude (Mw) 7.8 earthquake. Field observations, in conjunction with interferometric synthetic aperture radar, Global Positioning System, and seismology data, reveal this to be one of the most complex earthquakes ever recorded. The rupture propagated northward for more than 170 kilometers along both mapped and unmapped faults before continuing offshore at the island's northeastern extent. Geodetic and field observations reveal surface ruptures along at least 12 major faults, including possible slip along the southern Hikurangi subduction interface; extensive uplift along much of the coastline; and widespread anelastic deformation, including the ~8-meter uplift of a fault-bounded block. This complex earthquake defies many conventional assumptions about the degree to which earthquake ruptures are controlled by fault segmentation and should motivate reevaluation of these issues in seismic hazard models.

An analysis of present-day global depth distributions of reef-building corals and underlying environmental drivers contradicts a commonly held belief that ocean warming will promote tropical coral expansion into temperate latitudes. Using a global data set of a major group of reef corals, we found that corals were confined to shallower depths at higher latitudes (up to 0.6 meters of predicted shallowing per additional degree of latitude). Latitudinal attenuation of the most important driver of this phenomenon—the dose of photosynthetically available radiation over winter—would severely constrain latitudinal coral range extension in response to ocean warming. Latitudinal gradients in species richness for the group also suggest that higher winter irradiance at depth in low latitudes allowed a deep-water fauna that was not viable at higher latitudes.

We evaluated eye lenses as potential recorders of stable isotope histories in fish because they consist of metabolically inert optical proteins that are deposited in successive, concentric circles (laminae) much like otolith circuli and tree rings. We conducted four different tests on lenses from red snapper, red grouper, gag, and white grunt. The first test was a low-resolution screening of multiple individuals (4-5 radial groups of laminae per lens, all species except white grunt). Along the radial axis, all individuals exhibited substantial isotopic variability. Red snapper individuals separated into two groups based on δ15N and gag separated into two groups based on δ13C. Two gag with the greatest variation were chosen for high-resolution temporal analysis using individual laminae from their second eye lenses. The first-order patterns from the high-resolution analysis generally mimicked patterns from the low-resolution screening of grouped laminae, yet the high-resolution plots revealed early-life details that were not apparent in the low-resolution screenings. For the third test, left- versus right-eye variation was compared using high-resolution methods. White grunt left- and right-eye radial isotopic patterns were almost identical for both δ13C and δ15N, suggesting the variations observed among individual fish were not artifacts. The final test evaluated intra-laminar variation; multiple samples were analyzed from different parts of the same lamina. Seven laminae from three individuals of two species were analyzed in this manner; variations among laminae were found to be much higher than variations within laminae. However, nominal intra-laminar variations were comparable to nominal differences between left and right lenses, suggesting intra-laminar variation established measurement precision. Eye lens isotopes appear to be useful for reconstructing the isotopic histories of individual fish; these histories can be compared with spatially-derived isoscapes to reconstruct individual histories for site fidelity, movement and trophic position.

Deepwater formation in the North Atlantic by open-ocean convection is an essential component of the overturning circulation of the Atlantic Ocean, which helps regulate global climate. We use water-column radiocarbon reconstructions to examine changes in northeast Atlantic convection since the Last Glacial Maximum. During cold intervals, we infer a reduction in open-ocean convection and an associated incursion of an extremely radiocarbon (¹⁴C)-depleted water mass, interpreted to be Antarctic Intermediate Water. Comparing the timing of deep convection changes in the northeast and northwest Atlantic, we suggest that, despite a strong control on Greenland temperature by northeast Atlantic convection, reduced open-ocean convection in both the northwest and northeast Atlantic is necessary to account for contemporaneous perturbations in atmospheric circulation.

Abstract Rationale Although the number of intensive care unit (ICU) beds in the United States is increasing, it is unknown whether this trend is consistent across all regions. Objectives We sought to better characterize regional variation in ICU bed changes over time and identify regional characteristics associated with these changes. Methods We used data from the Centers for Medicare and Medicaid Services and the U.S. Census to summarize the numbers of hospitals, hospital beds, ICU beds, and ICU occupancy at the level of Dartmouth Atlas hospital referral region from 2000 to 2009. We categorized regions into quartiles of bed change over the study interval and examined the relationship between change categories, regional characteristics, and population characteristics over time. Measurements and Main Results From 2000 to 2009 the national number of ICU beds increased 15%, from 67,579 to 77,809, mirroring population. However, there was substantial regional variation in absolute changes (median, +16 ICU beds; interquartile range, −3 to +51) and population-adjusted changes (median, +0.9 ICU beds per 100,000; interquartile range, −3.8 to +5.9), with 25.0% of regions accounting for 74.8% of overall growth. At baseline, regions with increasing numbers of ICU beds had larger populations, lower ICU beds per 100,000 capita, higher average ICU occupancy, and greater market competition as measured by the Herfindahl-Hirschman Index (P < 0.001 for all comparisons). Conclusions National trends in ICU bed growth are not uniformly reflected at the regional level, with most growth occurring in a small number of highly populated regions.