Motivation: A number of available program packages determine the significant enrichments and/or depletions of GO categories among a class of genes of interest. Whereas a correct formulation of the ...problem leads to a single exact null distribution, these GO tools use a large variety of statistical tests whose denominations often do not clarify the underlying P-value computations. Summary: We review the different formulations of the problem and the tests they lead to: the binomial, χ2, equality of two probabilities, Fisher's exact and hypergeometric tests. We clarify the relationships existing between these tests, in particular the equivalence between the hypergeometric test and Fisher's exact test. We recall that the other tests are valid only for large samples, the test of equality of two probabilities and the χ2-test being equivalent. We discuss the appropriateness of one- and two-sided P-values, as well as some discreteness and conservatism issues. Contact:isabelle.rivals@espci.fr Supplementary information: Supplementary data are available at Bioinformatics online.
Chronic pain pathologies, which are due to maladaptive changes in the peripheral and/or central nervous systems, are debilitating diseases that affect 20% of the European adult population. A better ...understanding of the mechanisms underlying this pathogenesis would facilitate the identification of novel therapeutic targets. Functional connectivity (FC) extracted from coherent low-frequency hemodynamic fluctuations among cerebral networks has recently brought light on a powerful approach to study large scale brain networks and their disruptions in neurological/psychiatric disorders. Analysis of FC is classically performed on averaged signals over time, but recently, the analysis of the dynamics of FC has also provided new promising information. Keeping in mind the limitations of animal models of persistent pain but also the powerful tool they represent to improve our understanding of the neurobiological basis of chronic pain pathogenicity, this study aimed at defining the alterations in functional connectivity, in a clinically relevant animal model of sustained inflammatory pain (Adjuvant-induced Arthritis) in rats by using functional ultrasound imaging, a neuroimaging technique with a unique spatiotemporal resolution (100 μm and 2 ms) and sensitivity. Our results show profound alterations of FC in arthritic animals, such as a subpart of the somatomotor (SM) network, occurring several weeks after the beginning of the disease. Also, we demonstrate for the first time that dynamic functional connectivity assessed by ultrasound can provide quantitative and robust information on the dynamic pattern that we define as brain states. While the main state consists of an overall synchrony of hemodynamic fluctuations in the SM network, arthritic animal spend statistically more time in two other states, where the fluctuations of the primary sensory cortex of the inflamed hind paws show asynchrony with the rest of the SM network. Finally, correlating FC changes with pain behavior in individual animals suggest links between FC alterations and either the cognitive or the emotional aspects of pain. Our study introduces fUS as a new translational tool for the enhanced understanding of the dynamic pain connectome and brain plasticity in a major preclinical model of chronic pain.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Alteration of posturo-respiratory coupling (PRC) may precede postural imbalance in patients with chronic respiratory disease. PRC assessment would be appropriate for early detection of ...respiratory-related postural dysfunction. PRC may be evaluated by respiratory emergence (REm), the proportion of postural oscillations attributed to breathing activity; assessed by motion analysis) as measured from the displacement of the center of pressure (CoP) (measured with a force platform). To propose a simplified method of PRC assessment (using motion capture only), we hypothesized that the REm can appropriately be measured derived from single body segment the postural oscillations of a single body segment rather than whole body postural oscillations. An optoelectronic system recorded the breathing pattern and the postural oscillations of six body segments in 50 healthy participants (22 women), 34 years 26; 48. The CoP displacements were assessed using a force platform. One-minute recordings were made in standing position in four conditions by varying vision (eyes opened/closed) and jaw position (rest position/dental contact). The Sway Path and Mean Velocity of the CoP and of the representative point of each body segment were recorded. The REm was measured along the major and the minor axis of the 95% confidence ellipse of the CoP position (REm_MajorAxisCoP; REm_MinorAxisCoP) and of that of each body segment. SwayPathCoP and MVCoP varied widely across the four conditions (par< 0.000001). These changes were related to the visual condition (<inline-formula> <tex-math notation="LaTeX">\text{p} < 0.000001 </tex-math></inline-formula>) while the jaw position had no effect. The REm_MajorAxisCoP and the REm_MinorAxisCoP changed across conditions (<inline-formula> <tex-math notation="LaTeX">\text{p} < 0.05 </tex-math></inline-formula>); this was related to vision while jaw induced changes only for the REm_MinorAxisCoP. The SwayPath, the Mean Velocity and the REm of all body segments were significantly correlated to the CoP, but the highest correlations were observed for the thorax, the pelvis and the shoulder. PRC may be assessed from the postural oscillations of thorax, pelvis and shoulder. This should simplify the evaluation of respiratory-related postural interactions in the clinical environment, by using a single device to simultaneously assess postural oscillations on body segments, and breathing pattern. In addition, this study provides reference data for PRC and its sensory-related modulations on body segments along the postural chain.
•New methods for computerized spiral analysis are proposed, which outperform the usual velocity method.•They provide new insight into tremor amplitude and frequency variations.•They were implemented ...on a computer via a digitized tablet.
Spiral drawing is one of the standard tests used to assess tremor severity for the clinical evaluation of medical treatments. Tremor severity is estimated through visual rating of the drawings by movement disorders experts. Different approaches based on the mathematical signal analysis of the recorded spiral drawings were proposed to replace this rater dependent estimate. The objective of the present study is to propose new numerical methods and to evaluate them in terms of agreement with visual rating and reproducibility.
Series of spiral drawings of patients with essential tremor were visually rated by a board of experts. In addition to the usual velocity analysis, three new numerical methods were tested and compared, namely static and dynamic unraveling, and empirical mode decomposition. The reproducibility of both visual and numerical ratings was estimated, and their agreement was evaluated.
The statistical analysis demonstrated excellent agreement between visual and numerical ratings, and more reproducible results with numerical methods than with visual ratings.
The velocity method and the new numerical methods are in good agreement. Among the latter, static and dynamic unravelling both display a smaller dispersion and are easier for automatic analysis.
The reliable scores obtained through the proposed numerical methods allow considering that their implementation on a digitized tablet, be it connected with a computer or independent, provides an efficient automatic tool for tremor severity assessment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Study objectives
Fluid overload shifting from the legs to the upper airway during sleep promotes obstructive sleep apnea (OSA) and interventions targeting fluid attenuate OSA. Fluid shift has been ...previously measured by bioelectrical impedance, a complex and time-consuming technique not applicable in the daily clinical settings. The aim of this study is to evaluate the presence of clinically detectable fluid overload and shift and its association with OSA.
Methods
Patients undergoing sleep study for suspected OSA were asked to report the presence of 11 signs/symptoms associated to excessive accumulation of fluid in different parts of the body at different times of the day.
Results
Among 392 patients (male: 53%, median interquartile range age: 56 years
1
, body mass index, BMI: 29 kg/m
2
2
) included in the study, 135 (34%) had moderate-to-severe OSA (apnea hypopnea index, AHI ≥ 15). Daytime fluid accumulation and nocturnal fluid shift, clinically detectable by patient-reported “evening sock marks,” “heavy legs during the day,” and “morning stuffed nose,” were prevalent in the entire population (46%, 43%, and 33%, respectively). In multivariate analysis, evening sock marks was an independent correlate of having an AHI ≥ 15, together with male sex, older age, and self-reported snoring and apneas.
Conclusions
Clinically detectable fluid overload and shift are prevalent in patients addressed for suspected OSA, and evening sock marks, a marker for leg swelling, is an independent correlate of moderate-to-severe OSA. This sign might contribute to OSA diagnosis and identification of patients likely to be treated by interventions targeting fluid overload and shift.
Purpose
In healthy humans, postural and respiratory dynamics are intimately linked and a breathing-related postural perturbation is evident in joint kinematics. A cognitive dual-task paradigm that is ...known to induce both postural and ventilatory disturbances can be used to modulate this multijoint posturo-ventilatory (PV) interaction, particularly in the cervical spine, which supports the head. The objective of this study was to assess this modulation.
Methods
With the use of optoelectronic sensors, the breathing profile, articular joint motions of the cervical spine, hip, knees and ankles, and centre of pressure (CoP) displacement were measured in 20 healthy subjects (37 years old 29; 49, 10 females) during natural breathing (NB), a cognitive dual task (COG), and eyes-closed and increased-tidal-volume conditions. The PV interaction in the CoP and joint motions were evaluated by calculating the respiratory emergence (REm).
Results
Only the COG condition induced a decrease in the cervical REm (NB: 17.2% 7.8; 37.2; COG: 4.2% 1.8; 10.0
p
= 0.0020) concurrent with no changes in the cervical motion. The CoP REm (NB: 6.2% 3.8; 10.3; COG: 12.9% 5.8; 20.7
p
= 0.0696) and breathing frequency (NB: 16.6 min-1 13.3; 18.7; COG: 18.6 min-1 16.3; 19.4
p
= 0.0731) tended to increase, while the CoP (
p
= 0.0072) and lower joint motion displacements (
p
< 0.05) increased.
Conclusion
This study shows stable cervical spine motion during a cognitive dual task, as well as increased postural perturbations globally and in other joints. The concurrent reduction in the PV interaction at the cervical spine suggests that this “stabilization strategy” is centrally controlled and is achieved by a reduction in the breathing-related postural perturbations at this level. Whether this strategy is a goal for maintaining balance remains to be studied.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They present also ...learning impairments modeling those encountered in Down syndrome. Previous MRI and histological analyses of a transgenic mice generated using a human YAC construct that contains five genes including DYRK1A reveal that DYRK1A is involved, during development, in the control of brain volume and cell density of specific brain regions. Gene dosage correction induces a rescue of the brain volume alterations. DYRK1A is also involved in the control of synaptic plasticity and memory consolidation. Increased gene dosage results in brain morphogenesis defects, low BDNF levels and mnemonic deficits in these mice. Epigallocatechin gallate (EGCG) — a member of a natural polyphenols family, found in great amount in green tea leaves — is a specific and safe DYRK1A inhibitor. We maintained control and transgenic mice overexpressing DYRK1A on two different polyphenol-based diets, from gestation to adulthood. The major features of the transgenic phenotype were rescued in these mice.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The maintenance of upright balance in healthy humans requires the preservation of a horizontal gaze, best achieved through dynamical adjustments of spinal curvatures and a pelvic tilt that keeps the ...head-to-pelvis alignment close to vertical. It is currently unknown whether the spinal and pelvic compensations of respiratory-related postural perturbations are associated with preservation of the head-to-pelvis vertical alignment. We tested this hypothesis by comparing postural alignment variables at extreme lung volume (total lung capacity, TLC; residual volume, RV) with their reference value at functional residual capacity (FRC). Forty-eight healthy subjects 22 women; median age of 34 (26; 48) years were studied using low dose biplanar X-rays (BPXR; EOS
system). Personalized three-dimensional models of the spine and pelvis were reconstructed at the three lung volumes. Extreme lung volumes were associated with changes of thoracic curvature bringing it outside the normal range. Maximal inspiration reduced thoracic kyphosis T1-T12 angle = 47° (37; 56), -4° variation (-9; 1),
= 0.0007 while maximal expiration induced hyperkyphosis T1-T12 angle = 63° (55; 68); +10° variation (5; 12),
= 9 × 10
. Statistically significant (all
< 0.01) cervical and pelvic compensatory changes occurred C3-C7 angle: +4° (-2; 11) and pelvic tilt +1° (0; 3) during maximal inspiration; C3-C7 angle: -7° (-18; -1) and pelvic tilt +5° (1; 8) during maximal expiration, resulting in preserved head-to-pelvis alignment (no change in the angle between the vertical plane and the line connecting the odontoid process and the midpoint of the line connecting the center of the two femoral heads ODHA). Lung volume related postural perturbations were more marked as a function of age, but age did not affect the head-to-pelvis alignment. These findings should help understand balance alterations in patients with chronic respiratory diseases that modify lung volume and rib cage geometry.
Introduction
Only limited data are available regarding the long-term prognosis of patients with high-grade glioma discharged alive from the intensive care unit. We sought to quantify 1-year mortality ...and evaluate the association between mortality and (1) functional status, and (2) management of anticancer therapy in patients with high-grade glioma discharged alive from the intensive care unit.
Patients and methods
Retrospective observational cohort study of patients with high-grade glioma admitted to two intensive care units between January 2009 and June 2018. Functional status was assessed by the Karnofsky Performance Status. Anticancer therapy after discharge was classified as (1) continued (unchanged), (2) modified (changed or stopped), or (3) initiated (for newly diagnosed disease).
Results
Ninety-one high-grade glioma patients (73% of whom had glioblastoma) were included and 78 (86%) of these patients were discharged alive from the intensive care unit. Anticancer therapy was continued, modified, and initiated in 41%, 42%, and 17% of patients, respectively. Corticosteroid therapy at the time of ICU admission odds ratio (OR) 0.07 and cancer progression (OR 0.09) was independently associated with continuation of anticancer therapy. The mortality rate 1 year after ICU admission was 73%. On multivariate analysis, continuation of anticancer therapy (OR 0.18) and Karnofsky performance status on admission (OR 0.90) were independently associated with lower 1-year mortality.
Conclusion
The presence of high-grade glioma is not sufficient to justify refusal of intensive care unit admission. Performance status and continuation of anticancer therapy are associated with higher survival after intensive care unit discharge.
Previous presentation
Preliminary results were presented at the most recent congress of the French Intensive Care Society, Paris, 2019.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Introduction
To describe the reasons for intensive care unit (ICU) admission and to evaluate the outcomes and prognostic factors of patients with primary central nervous system lymphoma (PCNSL) ...admitted to the ICU.
Patients and methods
Retrospective observational cohort study of 101 PCNSL patients admitted to 3 ICUs over a two-decade period.
Results
Acute respiratory failure, mainly secondary to aspiration pneumonia and
Pneumocystis jirovecii
pneumonia, was the leading reason for ICU admission (33%). Aspiration pneumonia was more common in patients with brainstem tumor (67% vs. 0%,
p
< 0.001), whereas patients with intracranial hypertension were more frequently admitted for coma without seizures (61% vs. 9%,
p
= 0.004). Hospital and 6-month mortality were 47% and 53%, respectively. In multivariate analysis, admission for coma without seizures (OR 7.28), cancer progression (OR 3.47), mechanical ventilation (OR 6.58) and vasopressors (OR 4.07) were associated with higher 6-month mortality. Karnofsky performance status prior to ICU admission was independently associated with lower 6-month mortality (OR 0.96).
Discussion
Six-month survival of PCNSL patients admitted to the ICU appears to be relatively favorable (around 50%) and the presence of PCNSL alone is not a relevant criterion for ICU refusal. Predictive factors of mortality may help clinicians to make optimal triage decisions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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