A revision of the genus Wrangelia (Wrangeliaceae, Ceramiales) in Bermuda resolves six new species including W. ryancraigii from the mesophotic zone.

Four species of the genus Wrangelia are presently known from the western Atlantic Ocean: W. argus, W. bicuspidata, W. penicillata, and W. gordoniae, with the first three historically being reported from Bermuda. Morphological and molecular barcode (COI-5P) and phylogenetic analyses used in this study (SSU, LSU, rbcL) indicated eight species groupings of Wrangelia in Bermuda, excluding two of the historically recognized species, retaining only W. argus while adding seven new species, of which six are formally described. What had been historically reported as W. penicillata from Bermuda was shown to be distinct from Mediterranean Sea specimens (type locality) and was shown to be a mixture of W. hesperia sp. nov. and W. incrassata sp. nov. Along with these two, three other new species (W. laxa sp. nov., W. ryancraigii sp. nov., and W. secundiramea sp. nov.) have complete rhizoidal cortication tightly covering axial cells of indeterminate axes below the apices, distinguishing them from the two local incompletely corticated congeners W. argus and W. abscondita sp. nov., the latter a morphologically cryptic sister species with W. bicuspidata from the Caribbean Sea. Only one of the new species, W. ryancraigii, has thus far been observed in the mesophotic zone off the Bermuda platform, and it is morphologically cryptic with the euphotic zone's W. laxa.

Surface currents shape protist community structure across the Indo-Pacific.

Biogeographic structure in marine protist communities is shaped by a combination of dispersal potential and environmental selection. High-throughput sequencing and global sampling efforts have helped better resolve the composition and functions of these communities in the world's oceans using both molecular and visual methods. However, molecular barcoding data are critically lacking across the Indo-Pacific, a region widely considered the epicenter of marine biodiversity. To fill this gap, we characterized protist communities in four sampling regions across Indonesia that represent the latitudinal, longitudinal, and human population gradients of the region: Lombok, Wakatobi, Misool, and Waigeo. We show high spatial structuring in marine protist communities across Indonesia, and biotic factors appear to play little role in driving this observed structure. Our results appear to be driven by abiotic factors linked to surface current patterns across the Indo-Pacific as a result of: (1) a choke point in circulation at the Indonesian Throughflow leading to low diatom diversity in Lombok, Wakatobi, and Misool; (2) an increase in nutrient availability at the edge of the Halmahera Eddy in Waigeo, leading to an increase in diatom diversity; and/or (3) seasonal variations in protist communities in line with shifts in velocity of the Indonesian Throughflow. Overall, our results highlight the importance of abiotic factors in shaping protist communities on broad geographic scales over biotic, top-down pressures, such as grazing from higher trophic levels.

Comparing first-principles density functionals plus corrections for the lattice dynamics of YBa2Cu3O6.

The enigmatic mechanism underlying unconventional high-temperature superconductivity, especially the role of lattice dynamics, has remained a subject of debate. Theoretical insights have long been hindered due to the lack of an accurate first-principles description of the lattice dynamics of cuprates. Recently, using the r2SCAN meta-generalized gradient approximation (meta-GGA) functional, we have been able to achieve accurate phonon spectra of an insulating cuprate YBa2Cu3O6 and discover significant magnetoelastic coupling in experimentally interesting Cu-O bond stretching optical modes [Ning et al., Phys. Rev. B 107, 045126 (2023)]. We extend this work by comparing Perdew-Burke-Ernzerhof and r2SCAN performances with corrections from the on-site Hubbard U and the D4 van der Waals (vdW) methods, aiming at further understanding on both the materials science side and the density functional side. We demonstrate the importance of vdW and self-interaction corrections for accurate first-principles YBa2Cu3O6 lattice dynamics. Since r2SCAN by itself partially accounts for these effects, the good performance of r2SCAN is now more fully explained. In addition, the performances of the Tao-Mo series of meta-GGAs, which are constructed in a different way from the strongly constrained and appropriately normed (SCAN) meta-GGA and its revised version r2SCAN, are also compared and discussed.

Rates of cortical thinning in Alzheimer's disease signature regions associate with vascular burden but not with ß-amyloid status in cognitively normal adults at age 70.

BACKGROUND: Consistent patterns of reduced cortical thickness have been identified in early Alzheimer's disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain unclear. METHODS: Participants were from the Insight 46 substudy of the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations of baseline cerebral ß-amyloid (Aß) deposition, measured using florbetapir positron emission tomography, and baseline white matter hyperintensity volume (WMHV) on MRI, a marker of cerebral small vessel disease, with subsequent longitudinal changes in AD signature cortical thickness quantified from baseline and repeat MRI (mean [SD] interval 2.4 [0.2] years). RESULTS: In a population-based sample of 337 cognitively normal older white adults (mean [SD] age at baseline 70.5 [0.6] years; 48.1% female), higher global WMHV at baseline related to faster subsequent rates of cortical thinning in both AD signature regions (~0.15%/year faster per 10 mL additional WMHV), whereas baseline Aß status did not. Among Aß positive participants (n=56), there was some evidence that greater global Aß standardised uptake value ratio at baseline related to faster cortical thinning in the AD signature Mayo region, but this did not reach statistical significance (p=0.08). CONCLUSIONS: Cortical thinning within AD signature regions may develop via cerebrovascular pathways. Perhaps reflecting the age of the cohort and relatively low prevalence of Aß-positivity, robust Aß-related differences were not detected. Longitudinal follow-up incorporating additional biomarkers will allow assessment of how these relationships evolve closer to expected dementia onset.

Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease.

BACKGROUND: Monoclonal antibodies that target amyloid-beta (Aß) have the potential to slow cognitive and functional decline in persons with early Alzheimer's disease. Gantenerumab is a subcutaneously administered, fully human, anti-Aß IgG1 monoclonal antibody with highest affinity for aggregated Aß that has been tested for the treatment of Alzheimer's disease. METHODS: We conducted two phase 3 trials (GRADUATE I and II) involving participants 50 to 90 years of age with mild cognitive impairment or mild dementia due to Alzheimer's disease and evidence of amyloid plaques on positron-emission tomography (PET) or cerebrospinal fluid (CSF) testing. Participants were randomly assigned to receive gantenerumab or placebo every 2 weeks. The primary outcome was the change from baseline in the score on the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater cognitive impairment) at week 116. RESULTS: A total of 985 and 980 participants were enrolled in the GRADUATE I and II trials, respectively. The baseline CDR-SB score was 3.7 in the GRADUATE I trial and 3.6 in the GRADUATE II trial. The change from baseline in the CDR-SB score at week 116 was 3.35 with gantenerumab and 3.65 with placebo in the GRADUATE I trial (difference, -0.31; 95% confidence interval [CI], -0.66 to 0.05; P = 0.10) and was 2.82 with gantenerumab and 3.01 with placebo in the GRADUATE II trial (difference, -0.19; 95% CI, -0.55 to 0.17; P = 0.30). At week 116, the difference in the amyloid level on PET between the gantenerumab group and the placebo group was -66.44 and -56.46 centiloids in the GRADUATE I and II trials, respectively, and amyloid-negative status was attained in 28.0% and 26.8% of the participants receiving gantenerumab in the two trials. Across both trials, participants receiving gantenerumab had lower CSF levels of phosphorylated tau 181 and higher levels of Aß42 than those receiving placebo; the accumulation of aggregated tau on PET was similar in the two groups. Amyloid-related imaging abnormalities with edema (ARIA-E) occurred in 24.9% of the participants receiving gantenerumab, and symptomatic ARIA-E occurred in 5.0%. CONCLUSIONS: Among persons with early Alzheimer's disease, the use of gantenerumab led to a lower amyloid plaque burden than placebo at 116 weeks but was not associated with slower clinical decline. (Funded by F. Hoffmann-La Roche; GRADUATE I and II ClinicalTrials.gov numbers, NCT03444870 and NCT03443973, respectively.).

Neuroimaging, clinical and life course correlates of normal-appearing white matter integrity in 70-year-olds.

We investigate associations between normal-appearing white matter microstructural integrity in cognitively normal ∼70-year-olds and concurrently measured brain health and cognition, demographics, genetics and life course cardiovascular health. Participants born in the same week in March 1946 (British 1946 birth cohort) underwent PET-MRI around age 70. Mean standardized normal-appearing white matter integrity metrics (fractional anisotropy, mean diffusivity, neurite density index and orientation dispersion index) were derived from diffusion MRI. Linear regression was used to test associations between normal-appearing white matter metrics and (i) concurrent measures, including whole brain volume, white matter hyperintensity volume, PET amyloid and cognition; (ii) the influence of demographic and genetic predictors, including sex, childhood cognition, education, socio-economic position and genetic risk for Alzheimer's disease (APOE-ɛ4); (iii) systolic and diastolic blood pressure and cardiovascular health (Framingham Heart Study Cardiovascular Risk Score) across adulthood. Sex interactions were tested. Statistical significance included false discovery rate correction (5%). Three hundred and sixty-two participants met inclusion criteria (mean age 70, 49% female). Higher white matter hyperintensity volume was associated with lower fractional anisotropy [b = -0.09 (95% confidence interval: -0.11, -0.06), P < 0.01], neurite density index [b = -0.17 (-0.22, -0.12), P < 0.01] and higher mean diffusivity [b = 0.14 (-0.10, -0.17), P < 0.01]; amyloid (in men) was associated with lower fractional anisotropy [b = -0.04 (-0.08, -0.01), P = 0.03)] and higher mean diffusivity [b = 0.06 (0.01, 0.11), P = 0.02]. Framingham Heart Study Cardiovascular Risk Score in later-life (age 69) was associated with normal-appearing white matter {lower fractional anisotropy [b = -0.06 (-0.09, -0.02) P < 0.01], neurite density index [b = -0.10 (-0.17, -0.03), P < 0.01] and higher mean diffusivity [b = 0.09 (0.04, 0.14), P < 0.01]}. Significant sex interactions (P < 0.05) emerged for midlife cardiovascular health (age 53) and normal-appearing white matter at 70: marginal effect plots demonstrated, in women only, normal-appearing white matter was associated with higher midlife Framingham Heart Study Cardiovascular Risk Score (lower fractional anisotropy and neurite density index), midlife systolic (lower fractional anisotropy, neurite density index and higher mean diffusivity) and diastolic (lower fractional anisotropy and neurite density index) blood pressure and greater blood pressure change between 43 and 53 years (lower fractional anisotropy and neurite density index), independently of white matter hyperintensity volume. In summary, poorer normal-appearing white matter microstructural integrity in ∼70-year-olds was associated with measures of cerebral small vessel disease, amyloid (in males) and later-life cardiovascular health, demonstrating how normal-appearing white matter can provide additional information to overt white matter disease. Our findings further show that greater 'midlife' cardiovascular risk and higher blood pressure were associated with poorer normal-appearing white matter microstructural integrity in females only, suggesting that women's brains may be more susceptible to the effects of midlife blood pressure and cardiovascular health.

Correlation versus hybridization gap in CaMn[Formula: see text]Bi[Formula: see text].

We study the interplay between electronic correlations and hybridization in the low-energy electronic structure of CaMn[Formula: see text]Bi[Formula: see text], a candidate hybridization-gap semiconductor. By employing a DFT+U approach we find both the antiferromagnetic Néel order and band gap in good agreement with the corresponding experimental values. Under hydrostatic pressure, we find a crossover from hybridization gap to charge-transfer insulting physics due to the delicate balance of hybridization and correlations. Increasing the pressure above [Formula: see text] GPa we find a simultaneous pressure-induced volume collapse, plane-to-chain, insulator to metal transition. Finally, we have also analyzed the topology in the antiferromagnetic CaMn[Formula: see text]Bi[Formula: see text] for all pressures studied.

Operationalizing the centiloid scale for [18F]florbetapir PET studies on PET/MRI.

INTRODUCTION: The Centiloid scale aims to harmonize amyloid beta (Aß) positron emission tomography (PET) measures across different analysis methods. As Centiloids were created using PET/computerized tomography (CT) data and are influenced by scanner differences, we investigated the Centiloid transformation with data from Insight 46 acquired with PET/magnetic resonanceimaging (MRI). METHODS: We transformed standardized uptake value ratios (SUVRs) from 432 florbetapir PET/MRI scans processed using whole cerebellum (WC) and white matter (WM) references, with and without partial volume correction. Gaussian-mixture-modelling-derived cutpoints for Aß PET positivity were converted. RESULTS: The Centiloid cutpoint was 14.2 for WC SUVRs. The relationship between WM and WC uptake differed between the calibration and testing datasets, producing implausibly low WM-based Centiloids. Linear adjustment produced a WM-based cutpoint of 18.1. DISCUSSION: Transformation of PET/MRI florbetapir data to Centiloids is valid. However, further understanding of the effects of acquisition or biological factors on the transformation using a WM reference is needed. HIGHLIGHTS: Centiloid conversion of amyloid beta positron emission tomography (PET) data aims to standardize results.Centiloid values can be influenced by differences in acquisition.We converted florbetapir PET/magnetic resonance imaging data from a large birth cohort.Whole cerebellum referenced values could be reliably transformed to Centiloids.White matter referenced values may be less generalizable between datasets.

Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer's disease.

BACKGROUND: Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-ß status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD). METHODS: Following quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638). RESULTS: In the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß = - 0.072, 95%CI = [- 0.12, - 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß = - 0.066, 95% CI = [- 0.11, - 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-ß, and with an AD PRS in our genetic analysis, but none survived multiple testing correction. CONCLUSIONS: Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality.

Asymmetric magnetic proximity interactions in MoSe2/CrBr3 van der Waals heterostructures.

Magnetic proximity interactions between atomically thin semiconductors and two-dimensional magnets provide a means to manipulate spin and valley degrees of freedom in non-magnetic monolayers, without using applied magnetic fields1-3. In such van der Waals heterostructures, magnetic proximity interactions originate in the nanometre-scale coupling between spin-dependent electronic wavefunctions in the two materials, and typically their overall effect is regarded as an effective magnetic field acting on the semiconductor monolayer4-8. Here we demonstrate that magnetic proximity interactions in van der Waals heterostructures can in fact be markedly asymmetric. Valley-resolved reflection spectroscopy of MoSe2/CrBr3 van der Waals structures reveals strikingly different energy shifts in the K and K' valleys of the MoSe2 due to ferromagnetism in the CrBr3 layer. Density functional calculations indicate that valley-asymmetric magnetic proximity interactions depend sensitively on the spin-dependent hybridization of overlapping bands and as such are likely a general feature of hybrid van der Waals structures. These studies suggest routes to control specific spin and valley states in monolayer semiconductors9,10.

Adulthood cognitive trajectories over 26 years and brain health at 70 years of age: findings from the 1946 British Birth Cohort.

Few studies can address how adulthood cognitive trajectories relate to brain health in 70-year-olds. Participants (n = 468, 49% female) from the 1946 British birth cohort underwent 18F-Florbetapir PET/MRI. Cognitive function was measured in childhood (age 8 years) and across adulthood (ages 43, 53, 60-64 and 69 years) and was examined in relation to brain health markers of ß-amyloid (Aß) status, whole brain and hippocampal volume, and white matter hyperintensity volume (WMHV). Taking into account key contributors of adult cognitive decline including childhood cognition, those with greater Aß and WMHV at age 70 years had greater decline in word-list learning memory in the preceding 26 years, particularly after age 60. In contrast, those with smaller whole brain and hippocampal volume at age 70 years had greater decline in processing search speed, subtly manifest from age 50 years. Subtle changes in memory and processing speed spanning 26 years of adulthood were associated with markers of brain health at 70 years of age, consistent with detectable prodromal cognitive effects in early older age.

Rubble fields shape planktonic protist communities in Indonesia at a local scale.

The Coral Triangle encompasses nearly 30% of the world's coral reefs and is widely considered the epicenter of marine biodiversity. Destructive fishing practices and natural disturbances common to this region damage reefs leaving behind fields of coral rubble. While the impacts of disturbances in these ecosystems are well documented on metazoans, we have a poor understanding of their impact on microbial communities at the base of the food web. We use metabarcoding to characterize protist community composition in sites of varying fisheries management schemes and benthic profiles across the island of Lombok, Indonesia. Our study shows that rubble coverage and net primary productivity are the strongest explainers of variation in protist communities across Lombok. More specifically, rubble fields are characterized by increases in small heterotrophic protists, including ciliates and cercozoans. In addition to shifts in heterotrophic protist communities, we also observed increases in diatom relative abundance in rubble fields, which corresponded to sites with higher net primary productivity. These results are the first to characterize protist communities in tropical marine rubble fields and provide insight on environmental factors potentially driving these shifts on a local scale.

Structure, functions, performance and gaps of event-based surveillance (EBS) in Sudan, 2021: a cross-sectional review.

BACKGROUND: Event-based surveillance (EBS) is an essential component of Early Warning Alert and Response (EWAR) as per the International Health Regulations (IHR), 2005. EBS was established in Sudan in 2016 as a complementary system for Indicator-based surveillance (IBS). This review will provide an overview of the current EBS structure, functions and performance in Sudan and identify the gaps and ways forward.  METHODS: The review followed the WHO/EMRO guidelines and tools. Structured discussions, observation and review of records and guidelines were done at national and state levels. Community volunteers were interviewed through phone calls. Directors of Health Emergency and Epidemic Control, surveillance officers and focal persons for EBS at the state level were also interviewed. SPSS software was used to perform descriptive statistical analysis for quantitative data, while qualitative data was analysed manually using thematic analysis, paying particular attention to the health system level allowing for an exploration of how and why experiences differ across levels. Written and verbal consents were obtained from all participants as appropriate. RESULTS: Sudan has a functioning EBS; however, there is an underestimation of its contribution and importance at the national and states levels. The link between the national level and states is ad hoc or is driven by the need for reports. While community event-based surveillance (CEBS) is functioning, EBS from health facilities and from non-health sectors is not currently active. The integration of EBS into overall surveillance was not addressed, and the pathway from detection to action is not clear. The use of electronic databases and platforms is generally limited. Factors that would improve performance include training, presence of a trained focal person at state level, and regular follow-up from the national level. Factors such as staff turnover, income in relation to expenses and not having a high academic qualification (Diploma or MSc) were noticed as inhibiting factors. CONCLUSION: The review recommended revisiting the surveillance structure at national and state levels to put EBS as an essential component and to update guidelines and standard operation procedures SOPs to foster the integration between EBS components and the overall surveillance system. The need for strengthening the link with states, capacity building and re-addressing the training modalities was highlighted.

Diversity and distribution of Symbiodiniaceae detected on coral reefs of Lombok, Indonesia using environmental DNA metabarcoding.

Background: Dinoflagellates of family Symbiodiniaceae are important to coral reef ecosystems because of their contribution to coral health and growth; however, only a few studies have investigated the function and distribution of Symbiodiniaceae in Indonesia. Understanding the distribution of different kinds of Symbiodiniaceae can improve forecasting of future responses of various coral reef systems to climate change. This study aimed to determine the diversity of Symbiodiniaceae around Lombok using environmental DNA (eDNA). Methods: Seawater and sediment samples were collected from 18 locations and filtered to obtain fractions of 0.4-12 and >12 µm. After extraction, molecular barcoding polymerase chain reaction was conducted to amplify the primary V9-SSU 18S rRNA gene, followed by sequencing (Illumina MiSeq). BLAST, Naïve-fit-Bayes, and maximum likelihood routines were used for classification and phylogenetic reconstruction. We compared results across sampling sites, sample types (seawater/sediment), and filter pore sizes (fraction). Results: Phylogenetic analyses resolved the amplicon sequence variants into 16 subclades comprising six Symbiodiniaceae genera (or genera-equivalent clades) as follows: Symbiodinium, Breviolum, Cladocopium, Durusdinium, Foraminifera Clade G, and Halluxium. Comparative analyses showed that the three distinct lineages within Cladocopium, Durusdinium, and Foraminifera Clade G were the most common. Most of the recovered sequences appeared to be distinctive of different sampling locations, supporting the possibility that eDNA may resolve regional and local differences among Symbiodiniaceae genera and species. Conclusions: eDNA surveys offer a rapid proxy for evaluating Symbiodiniaceae species on coral reefs and are a potentially useful approach to revealing diversity and relative ecological dominance of certain Symbiodiniaceae organisms. Moreover, Symbiodiniaceae eDNA analysis shows potential in monitoring the local and regional stability of coral-algal mutualisms.

Life course, genetic, and neuropathological associations with brain age in the 1946 British Birth Cohort: a population-based study.

BACKGROUND: A neuroimaging-based biomarker termed the brain age is thought to reflect variability in the brain's ageing process and predict longevity. Using Insight 46, a unique narrow-age birth cohort, we aimed to examine potential drivers and correlates of brain age. METHODS: Participants, born in a single week in 1946 in mainland Britain, have had 24 prospective waves of data collection to date, including MRI and amyloid PET imaging at approximately 70 years old. Using MRI data from a previously defined selection of this cohort, we derived brain-predicted age from an established machine-learning model (trained on 2001 healthy adults aged 18-90 years); subtracting this from chronological age (at time of assessment) gave the brain-predicted age difference (brain-PAD). We tested associations with data from early life, midlife, and late life, as well as rates of MRI-derived brain atrophy. FINDINGS: Between May 28, 2015, and Jan 10, 2018, 502 individuals were assessed as part of Insight 46. We included 456 participants (225 female), with a mean chronological age of 70·7 years (SD 0·7; range 69·2 to 71·9). The mean brain-predicted age was 67·9 years (8·2, 46·3 to 94·3). Female sex was associated with a 5·4-year (95% CI 4·1 to 6·8) younger brain-PAD than male sex. An increase in brain-PAD was associated with increased cardiovascular risk at age 36 years (ß=2·3 [95% CI 1·5 to 3·0]) and 69 years (ß=2·6 [1·9 to 3·3]); increased cerebrovascular disease burden (1·9 [1·3 to 2·6]); lower cognitive performance (-1·3 [-2·4 to -0·2]); and increased serum neurofilament light concentration (1·2 [0·6 to 1·9]). Higher brain-PAD was associated with future hippocampal atrophy over the subsequent 2 years (0·003 mL/year [0·000 to 0·006] per 5-year increment in brain-PAD). Early-life factors did not relate to brain-PAD. Combining 12 metrics in a hierarchical partitioning model explained 33% of the variance in brain-PAD. INTERPRETATION: Brain-PAD was associated with cardiovascular risk, and imaging and biochemical markers of neurodegeneration. These findings support brain-PAD as an integrative summary metric of brain health, reflecting multiple contributions to pathological brain ageing, and which might have prognostic utility. FUNDING: Alzheimer's Research UK, Medical Research Council Dementia Platforms UK, Selfridges Group Foundation, Wolfson Foundation, Wellcome Trust, Brain Research UK, Alzheimer's Association.

Straight and Divergent Pathways to Cognitive State: Seven Decades of Follow-Up in the British 1946 Birth Cohort.

BACKGROUND: Using the British 1946 birth cohort we previously estimated life course paths to the Addenbrooke's Cognitive Examination (ACE-III). OBJECTIVE: We now compared those whose ACE-III scores were expected, worse and better than predicted from the path model on a range of independent variables including clinical ratings of cognitive impairment and neuroimaging measures. METHODS: Predicted ACE-III scores were categorized into three groups: those with Expected (between -1.5 and 1.5 standard deviation; SD); Worse (&lt; -1.5 SD); and Better (&gt;1.5 SD) scores. Differences in the independent variables were then tested between these three groups. RESULTS: Compared with the Expected group, those in the Worse group showed independent evidence of progressive cognitive impairment: faster memory decline, more self-reported memory difficulties, more functional difficulties, greater likelihood of being independently rated by experienced specialist clinicians as having a progressive cognitive impairment, and a cortical thinning pattern suggestive of preclinical Alzheimer's disease. Those in the Better group showed slower verbal memory decline and absence of independently rated progressive cognitive impairment compared to the Expected group, but no differences in any of the other independent variables including the neuroimaging variables. CONCLUSION: The residual approach shows that life course features can map directly to clinical diagnoses. One future challenge is to translate this into a readily usable algorithm to identify high-risk individuals in preclinical state, when preventive strategies and therapeutic interventions may be most effective.

3D ultrasonic imaging of surface-breaking cracks using a linear array.

Ultrasonic linear arrays have great potential to generate high-quality three-dimensional (3D) images by scanning the array. However, the generated images suffer from low resolution in the elevation plane, limiting the image quality for a reliable 3D Non-Destructive Testing (NDT) inspection. Although several ultrasonic imaging methods have been implemented to inspect different types of defects, there has been limited research to characterise surface-breaking cracks (SBCs) in 3D quantitatively. To improve the characterisation of surface-breaking cracks (SBCs), a 3D hybrid imaging method is proposed by combining the Half Skip Total Focusing Method (HSTFM) and the Synthetic Aperture Focusing Technique (SAFT) using a linear array. This paper proposed the implementation of an array with a reduced element length for full matrix capture (FMC) data acquisition. In conjunction with the hybrid imaging method, a reduced element array enables the utilisation of the information from a broad ultrasonic beam in the elevation direction to achieve improved image resolution. The imaging capability is assessed via a point spread function (PSF) as well as numerical simulations. From the PSF measurements, the image resolution is shown to improve with the smaller element length of the array, which is attributable to the combination of wide beamwidth and hybrid imaging method. Thereafter, experimental validation was performed with arrays of different elevation lengths, where an excellent match with the numerical results was observed. Furthermore, the crack sizing was performed using a 6-dB-drop rule, which assisted in accurately predicting the shape and size of the SBCs and is shown to measure the depth of SBCs with greater confidence. It is shown that a reduced array elevation with the hybrid imaging method and sizing method yields improved image resolution contrary to conventional linear arrays. This approach can offer a significant improvement in manifesting complete comprehension of the spatial defect relationship, enabling NDT engineers to analyse the inspection results quantitatively in 3D for progressive reliability.

Codependence of individuals in the Nephromyces species swarm requires heterospecific bacterial endosymbionts.

Symbiosis is one of the most important evolutionary processes shaping the biodiversity on Earth. Symbiotic associations often bring together organisms from different domains of life, which can provide an unparalleled route to evolutionary innovation.1-4 The phylum Apicomplexa encompasses 6,000 ubiquitous animal parasites; however, species in the recently described apicomplexan family, Nephromycidae, are reportedly non-virulent.5,6 The members of the genus Nephromyces live within a specialized organ of tunicates, called the renal sac, in which they use concentrated uric acid as a primary nitrogen source.7,8 Here, we report genomic and transcriptomic data from the diverse genus Nephromyces, as well as the three bacterial symbionts that live within this species complex. We show that the diversity of Nephromyces is unexpectedly high within each renal sac, with as many as 20 different species inhabiting the renal sacs in wild populations. The many species of Nephromyces can host three different types of bacterial endosymbionts; however, FISH microscopy allowed us to demonstrate that each individual Nephromyces cell hosts only a single bacterial type. Through the reconstruction and analyses of the endosymbiont bacterial genomes, we infer that each bacterial type supplies its host with different metabolites. No individual species of Nephromyces, in combination with its endosymbiont, can produce a complete set of essential amino acids, and culture experiments demonstrate that individual Nephromyces species cannot form a viable infection. Therefore, we hypothesize that Nephromyces spp. depend on co-infection with congeners containing different bacterial symbionts in order to exchange metabolites to meet their needs.