Background
This study aimed to develop an efficient and easily calculable risk score that can be used to identify an individual's risk of having been exposed to alcohol prenatally.
Methods
Data for ...this study were collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Phases 2 and 3. Two cohorts (ages 5 to 17 years) completed a comprehensive neurobehavioral battery and a standard dysmorphology exam: a development cohort (DC; n = 325) and a comparative cohort (CC; n = 523). Both cohorts included two groups: those with histories of heavy prenatal alcohol exposure (AE‐DC, n = 121; AE‐CC, n = 177) and a control group that included subjects with minimal or no prenatal alcohol exposure (CON‐DC, n = 204; CON‐CC, n = 346). Behavioral assessments and physical exam data were combined using regression techniques to derive a risk score indicating the likelihood of prenatal alcohol exposure. Subjects were then divided into two subgroups: (1) low risk and (2) high risk. Chi‐square (χ2) determined classification accuracy and ROC curves were produced to assess the predictive accuracy. Correlations between risk scores and intelligence quotient and executive function scores were calculated.
Results
Subjects were accurately classified in the DC (χ2 = 78.61, p < 0.001) and CC (χ2 = 86.63, p < 0.001). The classification model also performed well in the DC (ROC = 0.835 SE = 0.024, p < 0.001) and CC (ROC = 0.786 SE = 0.021, p < 0.001). In the AE‐CC and CON‐CC, there were modest but significant associations between the risk score and executive function (AE‐CC: r = −0.20, p = 0.034; CON‐CC: r = −0.28, p < 0.001) and intelligence quotient (AE‐CC: r = −0.20, p = 0.034; CON‐CC: r = −0.28, p < 0.001).
Conclusion(s)
The risk score significantly distinguished alcohol‐exposed from control subjects and correlated with important cognitive outcomes. It has significant clinical potential and could be easily deployed in clinical settings.
A risk score was created using physical exam and behavioral assessment variables that indicates the likelihood of prenatal alcohol exposure. The score accurately identified alcohol‐exposed from control subjects with and without clinical concerns, and was moderately but significantly related to intellectual and executive functioning. The risk score could be simply deployed in a clinical setting and has significant clinical potential as an early screening tool.
Risk Stratification of In-Hospital Mortality for Coronary Artery Bypass Graft Surgery
Edward L. Hannan, Chuntao Wu, Edward V. Bennett, Russell E. Carlson, Alfred T. Culliford, Jeffrey P. Gold, Robert ...S. D. Higgins, O. Wayne Isom, Craig R. Smith, Robert H. Jones
Risk scores for in-hospital mortality for coronary artery bypass graft surgery have been used to assess patients’ operative risk. However, none has been developed using data from a population-based region in the U.S. in many years. Data from New York’s Cardiac Surgery Reporting System in 2002 were used to develop a risk index with 10 risk factors. The fit of the index was tested by applying it to another year (2003) and testing the correspondence of expected and observed mortality rates for each risk score in the index. The risk index appears to be a valuable tool for predicting patient risk.
The purpose of this research was to develop a risk index for in-hospital mortality for coronary artery bypass graft (CABG) surgery.
Risk indexes for CABG surgery are used to assess patients’ operative risk as well as to profile hospitals and surgeons. None has been developed using data from a population-based region in the U.S. for many years.
Data from New York’s Cardiac Surgery Reporting System in 2002 were used to develop a statistical model that predicts mortality and to create a risk index based on a relatively small number of patient risk factors. The fit of the index was tested by applying it to another year (2003) of New York data and testing the correspondence of expected and observed mortality rates for each risk score in the index.
The risk index contains a total of 10 risk factors (age, female gender, hemodynamic state, ejection fraction, pre-procedural myocardial infarction, chronic obstructive pulmonary disease, calcified ascending aorta, peripheral arterial disease, renal failure, and previous open heart operations). The score possible for each variable ranges from 0 to 5, and total risk scores possible range from 0 to 34. The highest score observed for any patient was 22, and 93% of the patients had scores of 8 or lower. When the risk index was applied to another year of New York data with a considerably lower mortality rate, the C-statistic was 0.782.
The risk index appears to be a valuable tool for predicting patient risk when applied to another year of New York data. It should now be tested against other risk indexes in a variety of geographical regions.
Studies that are the basis of recommended volume thresholds for CABG surgery are outdated and not reflective of recent advances in the field. This study examines both hospital and surgeon ...volume-mortality relations for CABG surgery through the use of a population-based clinical data set.
Data from New York's clinical CABG surgery registry from 1997 to 1999 (total number of procedures, 57 150) were used to examine the individual and combined impact of annual hospital volume and annual surgeon volume on in-hospital mortality rates after adjusting for differences in severity of illness. Significantly lower risk-adjusted mortality rates occurred above all annual hospital volume thresholds between 200 and 800 and above all surgeon volume thresholds between 50 and 200. The number needed to treat (NNT) at higher-volume providers to avoid a death was minimized for a hospital threshold volume of 100 (NNT=50) and a surgeon threshold volume of 50 (NNT=118). The risk-adjusted mortality rate (RAMR) for patients undergoing surgery performed by surgeons with volumes of > or =125 in hospitals with volumes of > or =600 was 1.89%. The RAMR was significantly higher (2.67%) for patients undergoing surgery performed by surgeons with volumes of <125 in hospitals with volumes of <600.
Higher-volume surgeons and hospitals continue to have lower risk-adjusted mortality rates, and patients undergoing surgery performed by higher-volume surgeons in higher-volume hospitals have the lowest mortality rates.
Non-suicidal self-injury (NSSI) appears to be more common among women than men, though the underlying reasons for this remain unclear. In a community sample of young adults (N = 996, aged 18-33) ...assessed during the COVID-19 pandemic, we investigated alternative explanation for the NSSI prevalence gap: are women more likely to experience the feelings which lead to NSSI as a coping strategy, or does this prevalence gap result from differences in how men and women respond to distress?
Cross-sectional mediation and moderation analyses tested how self-reported psychological distress (K10), emotion dysregulation (DERS), and impulsivity (UPPS-P) may contribute to a higher prevalence of NSSI among women.
Women were twice as likely as men to report past-year NSSI (14.47% versus 7.78%, OR = 2.00, 95% CI 1.29, 3.13). Women reported significantly higher psychological distress and significantly lower sensation seeking and positive urgency than men. Psychological distress partially statistically mediated the relationship between gender and past-year NSSI. Gender did not significantly moderate associations between psychological distress, emotion dysregulation, or impulsivity and past-year NSSI. Past-year NSSI prevalence did not significantly decrease with age and we found no significant age by gender interaction.
Greater levels of NSSI in young women are partly explained by their greater levels of psychological distress, but not by differences in how men and women respond to this distress. Given similar levels of psychological distress, emotion dysregulation, and impulsivity, women and men are similarly likely to experience NSSI.
Highlights
Women aged 18-33 were significantly more likely to report past-year NSSI than men
Women's greater psychological distress contributed to their higher NSSI prevalence
Variables investigated here were similarly associated with NSSI in men and women
Whole brain segmentation from structural magnetic resonance imaging (MRI) is a prerequisite for most morphological analyses, but is computationally intense and can therefore delay the availability of ...image markers after scan acquisition. We introduce QuickNAT, a fully convolutional, densely connected neural network that segments a MRI brain scan in 20 s. To enable training of the complex network with millions of learnable parameters using limited annotated data, we propose to first pre-train on auxiliary labels created from existing segmentation software. Subsequently, the pre-trained model is fine-tuned on manual labels to rectify errors in auxiliary labels. With this learning strategy, we are able to use large neuroimaging repositories without manual annotations for training. In an extensive set of evaluations on eight datasets that cover a wide age range, pathology, and different scanners, we demonstrate that QuickNAT achieves superior segmentation accuracy and reliability in comparison to state-of-the-art methods, while being orders of magnitude faster. The speed up facilitates processing of large data repositories and supports translation of imaging biomarkers by making them available within seconds for fast clinical decision making.
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•Introduces a deep learning based whole brain segmentation tool called QuickNAT, processing each 3D MRI T1 brain scans in 20 secs.•The high segmentation accuracy of QuickNAT was evaluated on 5 different benchmark datasets, containing a wide age range, subjects with different pathologies (AD, MCI and CN), and different scanners (1.5T and 3.0T).•QuickNAT can be effectively used for longitudinal studies as it performs well in test-retest and multi-center experiments.
Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. Bile acids (BAs), products of ...cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer's disease (AD).
Serum levels of 15 primary and secondary BAs and their conjugated forms were measured in 1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 with late mild cognitive impairment, and 305 AD cases enrolled in the AD Neuroimaging Initiative. We assessed associations of BA profiles including selected ratios with diagnosis, cognition, and AD-related genetic variants, adjusting for confounders and multiple testing.
In AD compared to cognitively normal older adults, we observed significantly lower serum concentrations of a primary BA (cholic acid CA) and increased levels of the bacterially produced, secondary BA, deoxycholic acid, and its glycine and taurine conjugated forms. An increased ratio of deoxycholic acid:CA, which reflects 7α-dehydroxylation of CA by gut bacteria, strongly associated with cognitive decline, a finding replicated in serum and brain samples in the Rush Religious Orders and Memory and Aging Project. Several genetic variants in immune response–related genes implicated in AD showed associations with BA profiles.
We report for the first time an association between altered BA profile, genetic variants implicated in AD, and cognitive changes in disease using a large multicenter study. These findings warrant further investigation of gut dysbiosis and possible role of gut-liver-brain axis in the pathogenesis of AD.
Inaccurate estimation of average dielectric properties can have a tangible impact on microwave radar-based breast images. Despite this, recent patient imaging studies have used a fixed estimate ...although this is known to vary from patient to patient. Parameter search algorithms are a promising technique for estimating the average dielectric properties from the reconstructed microwave images themselves without additional hardware. In this work, qualities of accurately reconstructed images are identified from point spread functions. As the qualities of accurately reconstructed microwave images are similar to the qualities of focused microscopic and photographic images, this work proposes the use of focal quality metrics for average dielectric property estimation. The robustness of the parameter search is evaluated using experimental dielectrically heterogeneous phantoms on the three-dimensional volumetric image. Based on a very broad initial estimate of the average dielectric properties, this paper shows how these metrics can be used as suitable fitness functions in parameter search algorithms to reconstruct clear and focused microwave radar images.
The genus Clostridium is a large and diverse group within the Bacillota (formerly Firmicutes), whose members can encode useful complex traits such as solvent production, gas-fermentation, and ...lignocellulose breakdown. We describe 270 genome sequences of solventogenic clostridia from a comprehensive industrial strain collection assembled by Professor David Jones that includes 194 C. beijerinckii, 57 C. saccharobutylicum, 4 C. saccharoperbutylacetonicum, 5 C. butyricum, 7 C. acetobutylicum, and 3 C. tetanomorphum genomes. We report methods, analyses and characterization for phylogeny, key attributes, core biosynthetic genes, secondary metabolites, plasmids, prophage/CRISPR diversity, cellulosomes and quorum sensing for the 6 species. The expanded genomic data described here will facilitate engineering of solvent-producing clostridia as well as non-model microorganisms with innately desirable traits. Sequences could be applied in conventional platform biocatalysts such as yeast or Escherichia coli for enhanced chemical production. Recently, gene sequences from this collection were used to engineer Clostridium autoethanogenum, a gas-fermenting autotrophic acetogen, for continuous acetone or isopropanol production, as well as butanol, butanoic acid, hexanol and hexanoic acid production.
Prenatal alcohol exposure (PAE) adversely affects early brain development. Previous studies have shown a wide range of structural and functional abnormalities in children and adolescents with PAE. ...The current study adds to the existing literature specifically on cortical development by examining cortical gyrification in a large sample of children with PAE compared to controls. Relationships between cortical development and intellectual functioning are also examined.
Included were 92 children with PAE and 83 controls ages 9-16 from four sites in the Collaborative Initiative on FASD (CIFASD). All PAE participants had documented heavy PAE. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Cortical gyrification was examined using a semi-automated procedure.
Whole brain group comparisons using Monte Carlo z-simulation for multiple comparisons showed significantly lower cortical gyrification across a large proportion of the cerebral cortex amongst PAE compared to controls. Whole brain comparisons and ROI based analyses showed strong positive correlations between cortical gyrification and IQ (i.e. less developed cortex was associated with lower IQ).
Abnormalities in cortical development were seen across the brain in children with PAE compared to controls. Cortical gyrification and IQ were strongly correlated, suggesting that examining mechanisms by which alcohol disrupts cortical formation may yield clinically relevant insights and potential directions for early intervention.
Metastasis is the leading cause of death for cancer patients. This multi-stage process requires tumour cells to survive in the circulation, extravasate at distant sites, then proliferate; it involves ...contributions from both the tumour cell and tumour microenvironment ('host', which includes stromal cells and the immune system). Studies suggest the early steps of the metastatic process are relatively efficient, with the post-extravasation regulation of tumour growth ('colonization') being critical in determining metastatic outcome. Here we show the results of screening 810 mutant mouse lines using an in vivo assay to identify microenvironmental regulators of metastatic colonization. We identify 23 genes that, when disrupted in mouse, modify the ability of tumour cells to establish metastatic foci, with 19 of these genes not previously demonstrated to play a role in host control of metastasis. The largest reduction in pulmonary metastasis was observed in sphingosine-1-phosphate (S1P) transporter spinster homologue 2 (Spns2)-deficient mice. We demonstrate a novel outcome of S1P-mediated regulation of lymphocyte trafficking, whereby deletion of Spns2, either globally or in a lymphatic endothelial-specific manner, creates a circulating lymphopenia and a higher percentage of effector T cells and natural killer (NK) cells present in the lung. This allows for potent tumour cell killing, and an overall decreased metastatic burden.
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