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Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Objective: We evaluated whether memory recall following an extended (1 week) delay predicts cognitive and brain structural trajectories in older adults
Clinically normal older adults (52–92 years old) were followed longitudinally for up to 8 years after completing a memory paradigm at baseline [Story Recall Test (SRT)] that assessed delayed recall at 30 min and 1 week. Subsets of the cohort underwent neuroimaging (N = 134, mean age = 75) and neuropsychological testing (N = 178–207, mean ages = 74–76) at annual study visits occurring approximately 15–18 months apart. Mixed-effects regression models evaluated if baseline SRT performance predicted longitudinal changes in gray matter volumes and cognitive composite scores, controlling for demographics.
Worse SRT 1-week recall was associated with more precipitous rates of longitudinal decline in medial temporal lobe volumes (p = .037), episodic memory (p = .003), and executive functioning (p = .011), but not occipital lobe or total gray matter volumes (demonstrating neuroanatomical specificity; p > .58). By contrast, SRT 30-min recall was only associated with longitudinal decline in executive functioning (p = .044).
Memory paradigms that capture longer-term recall may be particularly sensitive to age-related medial temporal lobe changes and neurodegenerative disease trajectories. (JINS, 2020, xx, xx-xx)
In Germany, sheep are the main source of human Q fever epidemics, but data on Coxiella burnetii (C. burnetii) infections and related risk factors in the German sheep population remain scarce. In this cross-sectional study, a standardised interview was conducted across 71 exclusively sheep as well as mixed (sheep and goat) farms to identify animal and herd level risk factors associated with the detection of C. burnetii antibodies or pathogen-specific gene fragments via univariable and multivariable logistic regression analysis. Serum samples and genital swabs from adult males and females of 3367 small ruminants from 71 farms were collected and analysed using ELISA and qPCR, respectively. On animal level, univariable analysis identified young animals (<2 years of age; odds ratio (OR) 0.33; 95% confidence interval (CI) 0.13–0.83) to reduce the risk for seropositivity significantly (p < 0.05). The final multivariable logistic models identified lambing all year-round (OR 3.46/3.65; 95% CI 0.80–15.06/0.41–32.06) and purchases of sheep and goats (OR 13.61/22.99; 95% CI 2.86–64.64/2.21–239.42) as risk factors on herd level for C. burnetii infection detected via ELISA and qPCR, respectively.
To assess availability, variety, price and quality of different food products in a convenience sample of supermarkets in Germany and the USA.
Cross-sectional study using an adapted version of the Bridging the Gap Food Store Observation Form.
Information on availability, quality, price and variety of selected food products in eight German and seven US supermarkets (discount and full service) was obtained and compared by country.
A general tendency for lower prices of fruits and vegetables in Germany was observed, while produce quality and variety did not seem to differ between countries, with the exception of the variety of some vegetables such as tomatoes. Chips and cereals did not differ significantly in variety nor price. In both countries, high energy-dense foods were lower in energy costs than lower energy-dense foods.
The influence of food prices and availability on consumption should be further explored, including the impact of country differences.
We implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of patients undergoing surgical procedures as a means to conserve personal protective equipment (PPE). The rate of asymptomatic coronavirus disease 2019 (COVID-19) was <0.5%, which suggests that early local public health interventions were successful. Although our protocol was resource intensive, it prevented exposures to healthcare team members.
Continuous arterial spin labelling (cASL) is a non-invasive magnetic resonance imaging method increasingly used to study human brain function and perfusion physiology.
In this study, we investigated distinct patterns of cerebral blood flow (CBF) in MDD patients by means of resting state cASL.
11 healthy controls and 11 patients with MDD according to DSM-IV criteria were included. The individual cASL images underwent data preprocessing steps including the generation of perfusion-weighted images, followed by conversion to quantified CBF. An analysis of temporally coherent CBF patterns was performed using a spatial Independent Component Analysis.
Both groups showed distinct blood flow patterns in a medial frontoparietal and lateral temporal component (“default mode” network), a medial temporal and anterior cingulate component (“limbic” network) and bilateral prefrontal and parietal component (“cognitive” network). Within the “limbic” network, MDD patients showed a pattern of increased CBF in the bilateral ventrolateral prefrontal, cingulate, striatal and hippocampal regions. Within the “cognitive” network, MDD patients showed a pattern of increased CBF in left dorsolateral prefrontal and the inferior parietal areas. Decreased perfusion in MDD patients was found in the right precuneus, the right inferior parietal cortex, the left posterior cingulate and the left lateral temporal cortex.
These preliminary data demonstrate the sensitivity of cASL techniques for detecting resting state CBF changes in MDD patients. Thus, cASL studies in MDD could provide valuable information with regard to neurobiologically characterized endophenotypes, while resting state CBF measures could serve as objective predictors of treatment response in future studies.
Depression and obesity are highly prevalent major public health problems that frequently co-occur. Shared aetiological factors have been found between depression and obesity. The role of the fat mass and obesity associated (FTO) gene in body mass index (BMI) and obesity has been confirmed in many independent studies. Recently, we reported the first study implicating FTO in the association between depression and obesity.
We aimed to confirm these findings by investigating the FTO rs9939609 polymorphism in a meta-analysis of 13,701 individuals.
The sample consists of 6,902 depressed cases and 6,799 controls from five studies (Radiant, PsyCoLaus, GSK, MARS and NESDA/NTR). Common inclusion criteria were information available on a lifetime DSM-IV diagnosis of major depressive disorder (MDD), BMI and genotype data. Linear regression models for quantitative traits assuming an additive genetic model were performed to test for association and interaction between rs9939609, BMI and depression. Fixed and random-effects meta-analyses were performed.
Fixed-effects meta-analyses support a significant association between rs9939609 polymorphism and BMI (whole-sample: ß=0.07, p=1.29×10-12, depressive-cases: ß=0.12, p=6.92×10-12). No association was found in controls (ß=0.02, p=0.15). Meta-analyses further support a significant interaction between FTO, BMI and depression (fixed-effects: ß=0.13, p=3.087×10-7; random-effects: ß=0.12, p=0.027), wherein depressed carriers of the risk allele have an additional increase of 2.2% in BMI.
This meta-analysis demonstrates a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. Depression-related alterations in key biological processes may interact with the rs9939609 FTO risk allele to increase obesity risk.
Minor motor and sensory deficits or neurological soft signs (NSS) are frequently found in patients with schizophrenia at any stage of their illness. Numerous structural magnetic resonance imaging (MRI) studies repeatedly revealed accentuated thinning of cortical mantle in schizophrenia. However, whether NSS are related to alterations of cortical thickness has so far remained mostly unexplored.
Whole brain high-resolution MRI at 3 Tesla was used to investigate cortical thickness in twenty five patients with recent-onset schizophrenia. Cortical reconstruction was performed with the Freesurfer image analysis suite. NSS were examined on the Heidelberg Scale after remission of acute symptoms and related to cortical thickness. Age, education, medication and duration of illness were considered as potential confounders.
Higher NSS scores were associated with decreased cortical thickness in multiple areas. Significant correlations were found in somatosensory and primary motor cortex, pre-motor area and temporal lobe. Our results confirm the hypothesis of significant relationship between alterations of cortical thickness and the extent of NSS in schizophrenia.
Our findings provide new insights into the association of NSS with brain morphometric alterations and an involvement of cortical thickness in schizophrenia.
The promises of precision medicine are often heralded in the medical and lay literature, but routine integration of genomics in clinical practice is still limited. While the “last mile” infrastructure to bring genomics to the bedside has been demonstrated in some healthcare settings, a number of challenges remain — both in the receptivity of today's health system and in its technical and educational readiness to respond to this evolution in care. To improve the impact of genomics on health and disease management, we will need to integrate both new knowledge and new care processes into existing workflows. This change will be onerous and time-consuming, but hopefully valuable to the provision of high quality, economically feasible care worldwide.
A prevalence study was conducted on German sheep flocks including goats if they cohabitated with sheep. In addition, a novel approach was applied to identify an infection at the herd-level before lambing season with preputial swabs, suspecting venereal transmission and ensuing colonisation of preputial mucosa with Coxiella (C.) burnetii. Blood samples and genital swabs were collected from breeding males and females after the mating season and were analysed by enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR) respectively. In total, 3367 animals were sampled across 71 flocks. The true herd-level prevalence adjusted for misclassification probabilities of the applied diagnostic tests using the Rogan-Gladen estimator for the prevalence estimate and a formula by Lang and Reiczigel (2014) for the confidence limits, ranged between 31.3% and 33% (95% confidence interval [95% CI] 17.3–45.5) detected by the ELISA and/or qPCR. Overall 26–36.6% (95% CI 13–56.8) were detected by ELISA, 13.9% (95% CI 4.5–23.2) by the qPCR and 7.9–11.2% (95% CI 0.08–22.3) by both tests simultaneously. The range of results is due to data obtained from literature with different specifications for test quality for ELISA. Among eight farms with females shedding C. burnetii, three farms (37.5%) could also be identified by preputial swabs from breeding sires. This indicates less reliability of preputial swabs if used as a single diagnostic tool to detect C. burnetii infection at the herd-level.
Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions – particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost–benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.
Compound-specific radiocarbon (14C) dating often requires working with small samples of < 100 µg carbon (µgC). This makes the radiocarbon dates of biomarker compounds very sensitive to biases caused by extraneous carbon of unknown composition, a procedural blank, which is introduced to the samples during the steps necessary to prepare a sample for radiocarbon analysis by accelerator mass spectrometry (i.e., isolating single compounds from a heterogeneous mixture, combustion, gas purification and graphitization). Reporting accurate radiocarbon dates thus requires a correction for the procedural blank. We present our approach to assess the fraction modern carbon (F14C) and the mass of the procedural blanks introduced during the preparation procedures of lipid biomarkers (i.e. n-alkanoic acids) and lignin phenols. We isolated differently sized aliquots (6–151 µgC) of n-alkanoic acids and lignin phenols obtained from standard materials with known F14C values. Each compound class was extracted from two standard materials (one fossil, one modern) and purified using the same procedures as for natural samples of unknown F14C. There is an inverse linear relationship between the measured F14C values of the processed aliquots and their mass, which suggests constant contamination during processing of individual samples. We use Bayesian methods to fit linear regression lines between F14C and 1/mass for the fossil and modern standards. The intersection points of these lines are used to infer F14Cblank and mblank and their associated uncertainties. We estimate 4.88 ± 0.69 μgC of procedural blank with F14C of 0.714 ± 0.077 for n-alkanoic acids, and 0.90 ± 0.23 μgC of procedural blank with F14C of 0.813 ± 0.155 for lignin phenols. These F14Cblank and mblank can be used to correct AMS results of lipid and lignin samples by isotopic mass balance. This method may serve as a standardized procedure for blank assessment in small-scale radiocarbon analysis.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Objective: White matter (WM) microstructural changes are
increasingly recognized as a mechanism of age-related cognitive differences.
This study examined the associations between patterns of WM microstructure and
cognitive performance on the University of California, San Francisco (UCSF)
Brain Health Assessment (BHA) subtests of memory (Favorites), executive
functions and speed (Match), and visuospatial skills (Line Orientation) within a
sample of older adults. Method: Fractional anisotropy (FA) in WM
tracts and BHA performance were examined in 84 older adults diagnosed as
neurologically healthy (47), with mild cognitive impairment (19), or with
dementia (18). The relationships between FA and subtest performances were
evaluated using regression analyses. We then explored whether regional WM
predicted performance after accounting for variance explained by global FA.
Results: Memory performance was associated with FA of the
fornix and the superior cerebellar peduncle; and executive functions and speed,
with the body of the corpus callosum. The fornix–memory association and
the corpus callosum–executive association remained significant after
accounting for global FA. Neither tract-based nor global FA was associated with
visuospatial performance. Conclusions: Memory and executive
functions are associated with different patterns of WM diffusivity. Findings add
insight into WM alterations underlying age- and disease-related cognitive
Objectives: To adequately monitor the course of cognitive functioning in persons with moderate to severe dementia, relevant cognitive tests for the advanced dementia stages are needed. We examined the ability of a test developed for the advanced dementia stages, the Severe Impairment Battery Short version (SIB-S), to measure cognitive change over time. Second, we examined type of memory impairment measured with the SIB-S in different dementia stages. Methods: Participants were institutionalized persons with moderate to severe dementia (N = 217). The SIB-S was administered at 6-month intervals during a 2-year period. Dementia severity at baseline was classified according to Global Deterioration Scale criteria. We used mixed models to evaluate the course of SIB-S total and domain scores, and whether dementia stage at baseline affected these courses. Results: SIB-S total scores declined significantly over time, and the course of decline differed significantly between dementia stages at baseline. Persons with moderately severe dementia declined faster in mean SIB-S total scores than persons with moderate or severe dementia. Between persons with moderate and moderately severe dementia, there was only a difference in the rate of decline of semantic items, but not episodic and non-semantic items. Conclusions: Although modest floor and slight ceiling effects were noted in severe and milder cases, respectively, the SIB-S proved to be one of few available adequate measures of cognitive change in institutionalized persons with moderate to severe dementia. (JINS, 2019, 25, 204–214)
AFM-based nanoelectrical modes have numerous
applications in fields ranging from semiconductors
to biology. The data produced have traditionally
been in the form of a 2D map, generated in contact
mode, with a single electrical data point per
XY location. Electrical ramps
or spectra would be generated at a few, carefully
selected locations. This article discusses a new
approach to nanoelectrical imaging that creates an
electrical data cube and a correlated nanomechanical
data cube while operating at normal imaging speeds.
This approach avoids contact mode imaging, thus
extending electrical measurements to soft and
fragile samples and improving measurement
consistency. Moreover, this is a general approach
that is applicable to most nanoelectrical modes and
Background: Minimally invasive techniques for graft procurement are the norm in cardiac surgery and yet their use in neurosurgery is only in its infancy. We present the case of a 10-year-old boy presenting with fluctuating right facial and upper extremity weakness who was found to have a giant, partially thrombosed, fusiform aneurysm of the M1 segment of the left MCA. Methods: Endoscopic harvesting of the saphenous vein was performed with a procedure time of 30 minutes. The graft was used as an interposition graft between the common carotid artery and the superior M2 division of the MCA, which was tunneled subcutaneously. Once Doppler ultrasound confirmed good flow through the graft, an aneurysm clip was then secured on the M1, proximal to the saccular component of the fusiform aneurysm and just distal to the anterior temporal branch. Results: Intraoperative 2D and 3D angiogram confirmed a patent extracranial to intracranial bypass with thrombosis of the giant fusiform M1 aneurysm. By 1-month post-operatively, he had returned to school and routine activities. He continues to do well 6 months post-operatively with a minimal and well-healed donor site scar. Conclusions: Endoscopic graft harvesting is an emerging option in the pediatric population undergoing extracranial to intracranial bypass, associated with lower wound complications and improved cosmesis.