PascalX: a Python library for GWAS gene and pathway enrichment tests.

SUMMARY: 'PascalX' is a Python library providing fast and accurate tools for mapping SNP-wise GWAS summary statistics. Specifically, it allows for scoring genes and annotated gene sets for enrichment signals based on data from, both, single GWAS and pairs of GWAS. The gene scores take into account the correlation pattern between SNPs. They are based on the cumulative density function of a linear combination of χ2 distributed random variables, which can be calculated either approximately or exactly to high precision. Acceleration via multithreading and GPU is supported. The code of PascalX is fully open source and well suited as a base for method development in the GWAS enrichment test context. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/BergmannLab/PascalX and archived under doi://10.5281/zenodo.4429922. A user manual with usage examples is available at https://bergmannlab.github.io/PascalX/.

Editorial for the Special Issue on Flexible Micromanipulators and Micromanipulation.

The field of micromanipulation is rapidly growing and evolving thanks to advancements in microfabrication technologies and the increased demand for precise and accurate manipulation of microscale objects [...].

Direct Kinetostatic Analysis of a Gripper with Curved Flexures.

Micro-electro-mechanical-systems (MEMS) extensively employed planar mechanisms with elastic curved beams. However, using a curved circular beam as a flexure hinge, in most cases, needs a more sophisticated kinetostatic model than the conventional planar flexures. An elastic curved beam generally allows its outer sections to experience full plane mobility with three degrees of freedom, making complex non-linear models necessary to predict their behavior. This paper describes the direct kinetostatic analysis of a planar gripper with an elastic curved beam is described and then solved by calculating the tangent stiffness matrix in closed form. Two simplified models and different contributions to derive their tangent stiffness matrices are considered. Then, the Newton-Raphson iterative method solves the non-linear direct kinetostatic problem. The technique, which appears particularly useful for real-time applications, is finally applied to a case study consisting of a four-bar linkage gripper with elastic curved beam joints that can be used in real-time grasping operations at the microscale.

Dynamic Model of a Conjugate-Surface Flexure Hinge Considering Impacts between Cylinders.

A dynamic model of a Conjugate-Surface Flexure Hinge (CSFH) has been proposed as a component for MEMS/NEMS Technology-based devices with lumped compliance. However, impacts between the conjugate surfaces have not been studied yet and, therefore, this paper attempts to fill this gap by proposing a detailed multibody system (MBS) model that includes not only rigid-body dynamics but also elastic forces, friction, and impacts. Two models based on the Lankarani-Nikravesh constitutive law are first recalled and a new model based on the contact of cylinders is proposed. All three models are complemented by the friction model proposed by Ambrosìo. Then, the non-smooth Moreau time-stepping scheme with Coulomb friction is described. The four models are compared in different scenarios and the results confirm that the proposed model outcomes comply with the most reliable models.

Dynamic assessment of the risk of airborne viral infection.

This paper applies the Rudnick and Milton method through the dynamic evaluation of the probability of airborne contagion, redefining all parameters and variables in discretized form. To adapt the calculation of the risk of contagion to real needs, scenarios are used to define the presence of people, infected subjects, the hourly production of the quanta of infection, and the calculation of the concentration of CO2 produced by exhalation in the air. Three case studies are discussed: a school, an office, a commercial activity. Complex scenarios include environmental sanitization, a variable number of people, and the possibility of simulating work shifts. The dynamic evaluation of the quanta of infection is also estimated, not foreseen by the Rudnick and Milton model, and involves updating the average values of the equivalent fraction of the indoor air with an improvement in the accuracy of the calculation due to the reduction of improper peaks of the stationary variables.

Individual patient data systematic review and meta-analysis of optic nerve sheath diameter ultrasonography for detecting raised intracranial pressure: protocol of the ONSD research group.

BACKGROUND: The purpose of the optic nerve sheath diameter (ONSD) research group project is to establish an individual patient-level database from high quality studies of ONSD ultrasonography for the detection of raised intracranial pressure (ICP), and to perform a systematic review and an individual patient data meta-analysis (IPDMA), which will provide a cutoff value to help physicians making decisions and encourage further research. Previous meta-analyses were able to assess the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP but failed to determine a precise cutoff value. Thus, the ONSD research group was founded to synthesize data from several recent studies on the subject and to provide evidence on the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP. METHODS: This IPDMA will be conducted in different phases. First, we will systematically search for eligible studies. To be eligible, studies must have compared ONSD ultrasonography to invasive intracranial devices, the current reference standard for diagnosing raised ICP. Subsequently, we will assess the quality of studies included based on the QUADAS-2 tool, and then collect and validate individual patient data. The objectives of the primary analyses will be to assess the diagnostic accuracy of ONSD ultrasonography and to determine a precise cutoff value for detecting raised ICP. Secondly, we will construct a logistic regression model to assess whether patient and study characteristics influence diagnostic accuracy. DISCUSSION: We believe that this IPD MA will provide the most reliable basis for the assessment of diagnostic accuracy of ONSD ultrasonography for detecting raised ICP and to provide a cutoff value. We also hope that the creation of the ONSD research group will encourage further study. TRIAL REGISTRATION: PROSPERO registration number: CRD42012003072.

Ocular ultrasound to detect intracranial hypertension in trauma patients.

BACKGROUND: Increases in intracranial pressure (ICP) after head trauma require a rapid recognition to allow for adequate treatments. The aim of this study was to determine whether dilation of the optic nerve sheath, as detected by ocular ultrasound at the bedside, could reliably identify increases in ICP assessed with an intraparenchymal probe in adult head trauma patients. METHODS: Eleven head trauma injured adult patients admitted to the intensive care unit with a Glasgow Coma Scale score ≤8, with cerebral contusion confirmed by computed tomography scan, and that required invasive ICP monitoring, were enrolled in the study. ICP values ≤20 mm Hg were considered as normal. Patients with acute or chronic ocular lesion were excluded. Ten nontrauma intensive care unit patients, with no ICP monitoring, were enrolled as control group. Invasive arterial pressure was monitored, and optic nerve sheath diameter (ONSD) was assessed by ocular ultrasound in all the patients. RESULTS: Head trauma patients without intracranial hypertension had ONSD values, assessed by ultrasound, equivalent to those measured in control patients (5.52 mm ± 0.36 mm vs. 5.51 mm ± 0.32 mm). ONSD, instead, significantly increased to 7.0 mm ± 0.58 mm, when ICP rose in value to >20 mm Hg (p < 0.0001 vs. normal ICP and control). ONSD values were significantly correlated to ICP values (r = 0.74, p < 0.001). CONCLUSIONS: When ICP was higher than 20 mm Hg, the ONSD diameter increased, whereas when the ICP was below 20 mm Hg, the ONSD returned to values equivalent to those assessed in control nontrauma patients. Accordingly, ocular ultrasound may be considered as a good alternative for a rapid indirect evaluation of head trauma patients' ICP.