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Identifying predictors of patient outcomes evaluated over time may require modeling interactions among variables while addressing within-subject correlation. Generalized linear mixed models (GLMMs) and generalized estimating equations (GEEs) address within-subject correlation, but identifying interactions can be difficult if not hypothesized a priori. We evaluate the performance of several variable selection approaches for clustered binary outcomes to provide guidance for choosing between the methods.
We conducted simulations comparing stepwise selection, penalized GLMM, boosted GLMM, and boosted GEE for variable selection considering main effects and two-way interactions in data with repeatedly measured binary outcomes and evaluate a two-stage approach to reduce bias and error in parameter estimates. We compared these approaches in real data applications: hypothermia during surgery and treatment response in lupus nephritis.
Penalized and boosted approaches recovered correct predictors and interactions more frequently than stepwise selection. Penalized GLMM recovered correct predictors more often than boosting, but included many spurious predictors. Boosted GLMM yielded parsimonious models and identified correct predictors well at large sample and effect sizes, but required excessive computation time. Boosted GEE was computationally efficient and selected relatively parsimonious models, offering a compromise between computation and parsimony. The two-stage approach reduced the bias and error in regression parameters in all approaches.
Penalized and boosted approaches are effective for variable selection in data with clustered binary outcomes. The two-stage approach reduces bias and error and should be applied regardless of method. We provide guidance for choosing the most appropriate method in real applications.
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.
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.
Surface waves called meniscus waves often appear in systems that are close to the capillary length scale. Since the meniscus shape determines the form of the meniscus waves, the resulting streaming circulation has features distinct from those caused by other capillary–gravity waves recently reported in the literature. In the present study, we produce symmetric and antisymmetric meniscus shapes by controlling boundary wettability and excite meniscus waves by oscillating the meniscus vertically. The symmetric and antisymmetric configurations produce different surface capillary–gravity wave modes and streaming flow structures. The root-mean-square speed of the streaming circulation increases with the second power of the forcing amplitude in both configurations. The flow symmetry of streaming circulation is retained under the symmetric meniscus, while it is lost under the antisymmetric meniscus. The streaming circulation pattern beneath the meniscus observed in our experiments is qualitatively explained using the method introduced by Nicolás & Vega (Fluid Dyn. Res., vol. 32 (4), 2003, pp. 119–139) and Gordillo & Mujica (J. Fluid Mech., vol. 754, 2014, pp. 590–604).
This study aimed to assess whether increasing operative experience results in better surgical outcomes in endoscopic middle-ear surgery.
A retrospective single-institution cohort study was performed. Patients underwent endoscopic tympanoplasty between May 2013 and April 2019 performed by the senior surgeon or a trainee surgeon under direct supervision from the senior surgeon. Following data collection, statistical analysis compared success rates between early (learning curve) surgical procedures and later (experienced) tympanoplasties.
In total, 157 patients (86 male, 71 female), with a mean age of 41.6 years, were included. The patients were followed up for an average of 43.2 weeks. The overall primary closure rate was 90.0 per cent.
This study demonstrates an early learning curve for endoscopic ear surgery that improves with surgical experience. Adoption of the endoscopic technique did not impair the success rates of tympanoplasty.
Previous functional neuroimaging studies in schizophrenia have suggested abnormal patterns of functional connectivity during the resting state. However, little is known about the relationship between specific symptom dimensions and resting-state network (RSN) connectivity.
Using fMRI, this study investigated the relationship between multiple RSN and auditory verbal hallucinations (AVH) in patients with schizophrenia.
Resting state data were acquired from 10 patients with treatment resistant AVH and 14 healthy controls. The data were analyzed using a spatial group independent component analysis, and random effects t-tests were used to compare spatial components between groups (p < 0.001).
16 RSN were identified, from which four networks were selected for further analyses. Within three RSN patients showed increased connectivity of right lateral prefrontal areas and bilateral superior temporal regions as well as decreased connectivity of the anterior cingulate cortex. Correlations were found between measures of AVH severity and functional connectivity of the left anterior cingulate, left superior temporal gyrus and the right lateral prefrontal cortex.
These findings indicate that functional changes of multiple RSN associated with language processing, attention and executive control could underlie persistent AVH in patients with schizophrenia. The relationship between AVH severity and functional connectivity measures suggests that distinct cortical loci of dysfunction could contribute to the phenomenological diversity of AVH.
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.
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.
We present the analysis of global sympagic primary production (PP) from 300 years of pre-industrial and historical simulations of the E3SMv1.1-BGC model. The model includes a novel, eight-element sea ice biogeochemical component, MPAS-Seaice zbgc, which is resolved in three spatial dimensions and uses a vertical transport scheme based on internal brine dynamics. Modeled ice algal chlorophyll-a concentrations and column-integrated values are broadly consistent with observations, though chl-a profile fractions indicate that upper ice communities of the Southern Ocean are underestimated. Simulations of polar integrated sea ice PP support the lower bound in published estimates for both polar regions with mean Arctic values of 7.5 and 15.5 TgC/a in the Southern Ocean. However, comparisons of the polar climate state with observations, using a maximal bound for ice algal growth rates, suggest that the Arctic lower bound is a significant underestimation driven by biases in ocean surface nitrate, and that correction of these biases supports as much as 60.7 TgC/a of net Arctic PP. Simulated Southern Ocean sympagic PP is predominantly light-limited, and regional patterns, particularly in the coastal high production band, are found to be negatively correlated with snow thickness.
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.
Psychotropic prescription rates continue to increase in the United States (USA). Few studies have investigated whether social-structural factors may play a role in psychotropic medication use independent of mental illness. Food insecurity is prevalent among people living with HIV in the USA and has been associated with poor mental health. We investigated whether food insecurity was associated with psychotropic medication use independent of the symptoms of depression and anxiety among women living with HIV in the USA.
We used cross-sectional data from the Women's Interagency HIV Study (WIHS), a nationwide cohort study. Food security (FS) was the primary explanatory variable, measured using the Household Food Security Survey Module. First, we used multivariable linear regressions to test whether FS was associated with symptoms of depression (Center for Epidemiologic Studies Depression [CESD] score), generalised anxiety disorder (GAD-7 score) and mental health-related quality of life (MOS-HIV Mental Health Summary score; MHS). Next, we examined associations of FS with the use of any psychotropic medications, including antidepressants, sedatives and antipsychotics, using multivariable logistic regressions adjusting for age, race/ethnicity, income, education and alcohol and substance use. In separate models, we additionally adjusted for symptoms of depression (CESD score) and anxiety (GAD-7 score).
Of the 905 women in the sample, two-thirds were African-American. Lower FS (i.e. worse food insecurity) was associated with greater symptoms of depression and anxiety in a dose–response relationship. For the psychotropic medication outcomes, marginal and low FS were associated with 2.06 (p < 0.001; 95% confidence interval [CI] = 1.36–3.13) and 1.99 (p < 0.01; 95% CI = 1.26–3.15) times higher odds of any psychotropic medication use, respectively, before adjusting for depression and anxiety. The association of very low FS with any psychotropic medication use was not statistically significant. A similar pattern was found for antidepressant and sedative use. After additionally adjusting for CESD and GAD-7 scores, marginal FS remained associated with 1.93 (p < 0.05; 95% CI = 1.16–3.19) times higher odds of any psychotropic medication use. Very low FS, conversely, was significantly associated with lower odds of antidepressant use (adjusted odds ratio = 0.42; p < 0.05; 95% CI = 0.19–0.96).
Marginal FS was associated with higher odds of using psychotropic medications independent of depression and anxiety, while very low FS was associated with lower odds. These complex findings may indicate that people experiencing very low FS face barriers to accessing mental health services, while those experiencing marginal FS who do access services are more likely to be prescribed psychotropic medications for distress arising from social and structural factors.
The population dynamics of shrimp Pleoticus muelleri was used as a model to verify if the trend of continuous reproduction periodicity, shorter body size and longevity, and early sexual maturity found in tropical regions is corroborated in upwelling regions. Shrimps were sampled in a region under the influence of upwelling (northern coast of Rio de Janeiro State, Brazil). Characteristics of bottom water were registered, and shrimps were measured (carapace length – CL) and classified by sex and gonadal development stages. Reproduction was seasonal, from September to December, and favoured by water mass intrusions of low temperatures and high chlorophyll concentrations. The greatest number of reproductive females preceded periods with the highest chlorophyll concentrations in the water column (cross-correlation; P < 0.05, lag (month) = −3, r = 0.50), suggesting greater developmental success of larval stage due to increase of food availability. Von Bertalanffy growth models resulted in asymptotic carapace length estimates of CL∞ = 40.21 mm and CL∞ = 36.78 mm for females and males, respectively. The reproductive and growth characteristics of the P. muelleri population studied herein were similar to that of populations from higher latitudes, demonstrating that the latitudinal pattern rule cannot be applied in regions influenced by an upwelling phenomenon.
Pulmonary hypertension is a complex and progressive condition that is either idiopathic or heritable, or associated with one or multiple health conditions, with or without congenital or acquired cardiovascular disease. Recent developments have tremendously increased the armamentarium of diagnostic and therapeutic approaches in children and young adults with pulmonary hypertension that is still associated with a high morbidity and mortality. These modalities include non-invasive imaging, pharmacotherapy, interventional and surgical procedures, and supportive measures. The optimal, tailored diagnostic and therapeutic strategies for pulmonary hypertension in the young are rapidly evolving but still face enormous challenges: Healthcare providers need to take the patient’s age, development, disease state, and family concerns into account when initiating advanced diagnostics and treatment. Therefore, there is a need for guidance on core and advanced medical training in paediatric pulmonary hypertension. The Association for European Paediatric and Congenital Cardiology working group “pulmonary hypertension, heart failure and transplantation” has produced this document as an expert consensus statement; however, all recommendations must be considered and applied in the context of the local and national infrastructure and legal regulations.
Cognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial.
In a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS).
MDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance.
Our findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.
Objectives: This study aimed to evaluate the influence of lower limb loss (LL) on mental workload by assessing neurocognitive measures in individuals with unilateral transtibial (TT) versus those with transfemoral (TF) LL while dual-task walking under varying cognitive demand. Methods: Electroencephalography (EEG) was recorded as participants performed a task of varying cognitive demand while being seated or walking (i.e., varying physical demand). Results: The findings revealed both groups of participants (TT LL vs. TF LL) exhibited a similar EEG theta synchrony response as either the cognitive or the physical demand increased. Also, while individuals with TT LL maintained similar performance on the cognitive task during seated and walking conditions, those with TF LL exhibited performance decrements (slower response times) on the cognitive task during the walking in comparison to the seated conditions. Furthermore, those with TF LL neither exhibited regional differences in EEG low-alpha power while walking, nor EEG high-alpha desynchrony as a function of cognitive task difficulty while walking. This lack of alpha modulation coincided with no elevation of theta/alpha ratio power as a function of cognitive task difficulty in the TF LL group. Conclusions: This work suggests that both groups share some common but also different neurocognitive features during dual-task walking. Although all participants were able to recruit neural mechanisms critical for the maintenance of cognitive-motor performance under elevated cognitive or physical demands, the observed differences indicate that walking with a prosthesis, while concurrently performing a cognitive task, imposes additional cognitive demand in individuals with more proximal levels of amputation.
We present the second data release (DR2) of the SkyMapper Southern Survey, a hemispheric survey carried out with the SkyMapper Telescope at Siding Spring Observatory in Australia, using six optical filters: u, v, g, r, i, z. DR2 is the first release to go beyond the
) limit of the Shallow Survey released in the first data release (DR1), and includes portions of the sky at full survey depth that reach
mag in g and r filters. The DR2 photometry has a precision as measured by internal reproducibility of 1% in u and v, and 0.7% in griz. More than 21 000
have data in some filters (at either Shallow or Main Survey depth) and over 7 000
have deep Main Survey coverage in all six filters. Finally, about 18 000
have Main Survey data in i and z filters, albeit not yet at full depth. The release contains over 120 000 images, as well as catalogues with over 500 million unique astrophysical objects and nearly 5 billion individual detections. It also contains cross-matches with a range of external catalogues such as Gaia DR2, Pan-STARRS1 DR1, GALEX GUVcat, 2MASS, and AllWISE, as well as spectroscopic surveys such as 2MRS, GALAH, 6dFGS, and 2dFLenS.