Bioinformatic Investigations Into the Genetic Architecture of Renal Disorders

Modern genomic analysis has a significant bioinformatic component due to the high volume of complex data that is involved. During investigations into the genetic components of two renal diseases, we developed two software tools. // Genome-Wide Association Studies (GWAS) datasets may be genotyped on different microarrays and subject to different annotation, leading to a mosaic case-control cohort that has inherent errors, primarily due to strand mismatching. Our software REMEDY seeks to detect and correct strand designation of input datasets, as well as filtering for common sources of noise such as structural and multi-allelic variants. We performed a GWAS on a large cohort of Steroid-sensitive nephrotic syndrome samples; the mosaic input datasets were pre-processed with REMEDY prior to merging and analysis. Our results show that REMEDY significantly reduced noise in GWAS output results. REMEDY outperforms existing software as it has significantly more features available such as auto-strand designation detection, comprehensive variant filtering and high-speed variant matching to dbSNP. // The second tool supported the analysis of a newly characterised rare renal disorder: Polycystic kidney disease with hyperinsulinemic hypoglycemia (HIPKD). Identification of the underlying genetic cause led to the hypothesis that a change in chromatin looping at a specific locus affected the aetiology of the disease. We developed LOOPER, a software suite capable of predicting chromatin loops from ChIP-Seq data to explore the possible conformations of chromatin architecture in the HIPKD genomic region. LOOPER predicted several interesting functional and structural loops that supported our hypothesis. We then extended LOOPER to visualise ChIA-PET and ChIP-Seq data as a force-directed graph to show experimental structural and functional chromatin interactions. Next, we re-analysed the HIPKD region with LOOPER to show experimentally validated chromatin interactions. We first confirmed our original predicted loops and subsequently discovered that the local genomic region has many more chromatin features than first thought

An investigation into the use of haptic modelling during industrial design activity

Physical models continue to form an essential outcome from industrial design practice for both student and professional. Whist the professional may be removed from the “hands-on” model build by employing the services of a modelmaker, students rarely have such resources. Indeed it was (and in many institutions still is) considered an essential part of the education programme for students to develop modelmaking skills and experience the physical interaction with form and material. However, the advent of remote model building technologies via rapid prototyping and computer controlled machining, has given students an alternative, enabling them to become increasingly removed from such interaction. As increasing numbers of industrial design courses utilise remote model build technologies, the emergence of three dimensional (3D) digital modelling via a haptic feedback device may offer a route whereby students can continue to be involved with tactile design modelling. Acknowledging the need to utilise digital design techniques, this paper investigates the capabilities of haptic modelling for use within industrial design practice, with the aim of discussing its suitability for student use. The research is based on an industrial design case study for a communication device that was undertaken by the authors

Combined sterno-clavicular approach as an alternative technique in hybrid exclusion of aortic arch aneurysm

<p>Abstract</p> <p>Background</p> <p>We describe a modified access technique for the proximal (open) part of single stage hybrid exclusion of aneurysm of the aortic arch.</p> <p>Case presentation</p> <p>3 patients had a bifurcated Dacron graft for the innominate and left subclavian arteries and an additional end-to-side anastomosis of the left common carotid artery on the limb to the left subclavian artery. With our modification, access to the left subclavian artery is by left subclavicular incision and creation of an anterior tunnel via the left thoracic outlet from the origin of the left subclavian artery along its anatomical course to the subclavicular plane.</p> <p>Discussion</p> <p>Advantages and disadvantages of this technique in relation to anatomy and pathology.</p

Corrigendum to "Electrodiagnostic assessment of the autonomic nervous system: A consensus statement endorsed by the American Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology" [Clin. Neurophysiol. 132(2) (2021) 666-682].

n/

The FAST-M complex intervention for the detection and management of maternal sepsis in low-resource settings: a multi-site evaluation.

ObjectiveTo evaluate whether the implementation of the FAST-M complex intervention was feasible and improved the recognition and management of maternal sepsis in a low-resource setting.DesignA before and after design.SettingFifteen government healthcare facilities in Malawi.PopulationWomen suspected of having maternal sepsis.MethodsThe FAST-M complex intervention consisted of the following components: i) the FAST-M maternal sepsis treatment bundle and ii) the FAST-M implementation programme. Performance of selected process outcomes were compared between a two month baseline phase and six month intervention phase with compliance used as a proxy measure of feasibility.Main outcome resultCompliance with vital sign recording and use of the FAST-M maternal sepsis bundle.ResultsFollowing implementation of the FAST-M intervention, women were more likely to have a complete set of vital signs taken on admission to the wards (0/163 (0%) vs. 169/252 (67.1%), pConclusionImplementation of the FAST-M complex intervention was feasible and led to the improved recognition and management of suspected maternal sepsis in a low-resource setting such as Malawi

Polarization calibration of the BICEP3 CMB polarimeter at the South Pole

The BICEP3 CMB Polarimeter is a small-aperture refracting telescope located at the South Pole and is specifically designed to search for the possible signature of inflationary gravitational waves in the Cosmic Microwave Background (CMB). The experiment measures polarization on the sky by differencing the signal of co-located, orthogonally polarized antennas coupled to Transition Edge Sensor (TES) detectors. We present precise measurements of the absolute polarization response angles and polarization efficiencies for nearly all of BICEP3's ~800 functioning polarization-sensitive detector pairs from calibration data taken in January 2018. Using a Rotating Polarized Source (RPS), we mapped polarization response for each detector over a full 360 degrees of source rotation and at multiple telescope boresight rotations from which per-pair polarization properties were estimated. In future work, these results will be used to constrain signals predicted by exotic physical models such as Cosmic Birefringence

Alternative Approach for Cerebral Protection during Complex Aortic Arch and Redo Surgery

Total arch replacement remains a very demanding surgical procedure. It can be associated with reasonable long-term outcomes but carries serious perioperative complications. Aortic arch surgery has progressed in recent years to a wider adoption of reproducible and reliable techniques. Conventional open, surgical aortic arch replacement is currently offered to the majority of patients, although hybrid and wholly endovascular techniques are gaining popularity. With regards to open arch replacement, the nuances of surgical technique, the mode of cannulation and the optimal cerebral protection protocols remain a matter of debate. We propose an alternative cannulation approach facilitated by the cooperation between cardiac and vascular surgeons. A three-way arterial cannulation including both carotid arteries and the femoral artery (or ascending aorta) is the key feature of this approach. A case series of complex patients is presented to show both the feasibility and relative safety of a standardised new approach with a 100% technical success rate and a 16% 30-day mortality. The three-way cannulation approach may have a role to play for complex and extensive procedures requiring prolonged cerebral protection. We believe that a shared skill set from cardiac and vascular specialists is essential for the safe management and successful outcomes using this adaptive technique