36 research outputs found
Quantitative Analysis of Ictal Head Movements in Temporal Lobe Epilepsy
Purpose: To quantitatively evaluate the lateralizing significance of ictal head movements of patients with temporal lobe epilepsy (TLE).
Methods: We investigated EEG-video recorded seizures of patients with TLE, in which the camera position was perpendicular to the head facing the camera in an upright position and bilateral head movement was recorded. Thirty-eight seizures (31 patients) with head movement in both directions were investigated. Ipsilateral and contralateral head movement were defined according to ictal EEG. Head movements were quantified by selecting the movement of the nose in relation to a defined point on the thorax (25/s) in a defined plane facing the camera. The duration of the head version was determined independently of the camera angle. The angle, duration and angular speed of the head movements were computed and inter- and intrasubject analyses were performed (Wilcoxon rank sum).
Results: Ipsilateral movement always preceded contralateral movement. The positive predictive value (PPV) was 100% for movement in both directions. The duration of contralateral head version was significantly longer than ipsilateral head movement (6.4s ± 4.1s vs. 3.9s ± 3.1s, p<0.001). The angular speed of both movements was similar (15.5deg/s ± 12.1 deg/s vs. 17.3 deg/s ± 13.0 deg/s).
Conclusion: The quantitative analysis shows the importance of sequence in the seizure’s evolution and duration, but not angular speed for correct lateralization of versive head movement. This quantitative method shows the high lateralizing value of ictal lateral head movements in TLE
Quantitative Analysis of Ictal Head Movements in Temporal Lobe Epilepsy
Purpose: To quantitatively evaluate the lateralizing significance of ictal head movements of patients with temporal lobe epilepsy (TLE).
Methods: We investigated EEG-video recorded seizures of patients with TLE, in which the camera position was perpendicular to the head facing the camera in an upright position and bilateral head movement was recorded. Thirty-eight seizures (31 patients) with head movement in both directions were investigated. Ipsilateral and contralateral head movement were defined according to ictal EEG. Head movements were quantified by selecting the movement of the nose in relation to a defined point on the thorax (25/s) in a defined plane facing the camera. The duration of the head version was determined independently of the camera angle. The angle, duration and angular speed of the head movements were computed and inter- and intrasubject analyses were performed (Wilcoxon rank sum).
Results: Ipsilateral movement always preceded contralateral movement. The positive predictive value (PPV) was 100% for movement in both directions. The duration of contralateral head version was significantly longer than ipsilateral head movement (6.4s ± 4.1s vs. 3.9s ± 3.1s, p<0.001). The angular speed of both movements was similar (15.5deg/s ± 12.1 deg/s vs. 17.3 deg/s ± 13.0 deg/s).
Conclusion: The quantitative analysis shows the importance of sequence in the seizure’s evolution and duration, but not angular speed for correct lateralization of versive head movement. This quantitative method shows the high lateralizing value of ictal lateral head movements in TLE
Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways
OBJECTIVE
The aim of this study was to evaluate the role of interleukin (IL)-6 pathways in postoperative immune suppression and to assess the reversibility of this phenomenon.
BACKGROUND
The postoperative period is characterized by increased IL-6 production and features of immune suppression. In vitro, IL-6 mediates anti-inflammatory effects through inhibition of interferon gamma (IFN-γ) pathways. The significance of the immunomodulatory effects of IL-6 in the clinical setting of postoperative immune suppression remains unclear.
METHODS
Patients over 45 years old undergoing elective surgery, involving the gastrointestinal tract, were recruited. IL-6 levels were assayed using an enzyme linked immunosorbent assay preoperatively, and at 24 and 48 hours. Peripheral blood mononuclear cells from healthy volunteers were cultured in perioperative serum and CD14Human Leukocyte Antigen-DR (HLA-DR) [monocyte HLA-DR (mHLA-DR)] geometric mean florescent intensity was measured in the presence and absence of IL-6 neutralizing antibody and recombinant IFN-γ.
RESULTS
Of the 108 patients, 41 developed a postoperative infection. The IL-6 levels increased 19-fold from the preoperative sample to 24 hours postoperatively (P < 0.0001). Higher IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with subsequent postoperative infectious complications. mHLA-DR mean florescent intensity fell when healthy peripheral blood mononuclear cells were cultured with postoperative serum compared with preoperative serum (P = 0.008). This decrease was prevented by the presence of IFN-γ in the culture media, but not by the presence of IL-6-neutralizing antibody.
CONCLUSIONS
IL-6 levels increase after a major surgery and are associated with an increased susceptibility to postoperative infections. Serum obtained from postoperative patients induces an immunosuppressive response, reflected in reduced mHLA-DR levels, mediated through IL-6 independent pathways and is reversible with IFN-γ. These data may have therapeutic implications for the prevention of infection in patients undergoing major surgery
Strong signature of natural selection within an FHIT intron implicated in prostate cancer risk
Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, resequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. © 2008 Ding et al
OpenSAFELY: a platform for analysing electronic health records designed for reproducible research
Electronic health records (EHRs) and other administrative health data are increasingly used in research to generate evidence on the effectiveness, safety, and utilisation of medical products and services, and to inform public health guidance and policy. Reproducibility is a fundamental step for research credibility and promotes trust in evidence generated from EHRs. At present, ensuring research using EHRs is reproducible can be challenging for researchers. Research software platforms can provide technical solutions to enhance the reproducibility of research conducted using EHRs. In response to the COVID-19 pandemic, we developed the secure, transparent, analytic open-source software platform OpenSAFELY designed with reproducible research in mind. OpenSAFELY mitigates common barriers to reproducible research by: standardising key workflows around data preparation; removing barriers to code-sharing in secure analysis environments; enforcing public sharing of programming code and codelists; ensuring the same computational environment is used everywhere; integrating new and existing tools that encourage and enable the use of reproducible working practices; and providing an audit trail for all code that is run against the real data to increase transparency. This paper describes OpenSAFELY’s reproducibility-by-design approach in detail
Modulation of the thalamus by microburst vagus nerve stimulation: a feasibility study protocol
Vagus nerve stimulation (VNS) was the first device-based therapy for epilepsy, having launched in 1994 in Europe and 1997 in the United States. Since then, significant advances in the understanding of the mechanism of action of VNS and the central neurocircuitry that VNS modulates have impacted how the therapy is practically implemented. However, there has been little change to VNS stimulation parameters since the late 1990s. Short bursts of high frequency stimulation have been of increasing interest to other neuromodulation targets e.g., the spine, and these high frequency bursts elicit unique effects in the central nervous system, especially when applied to the vagus nerve. In the current study, we describe a protocol design that is aimed to assess the impact of high frequency bursts of stimulation, called “Microburst VNS”, in subjects with refractory focal and generalized epilepsies treated with this novel stimulation pattern in addition to standard anti-seizure medications. This protocol also employed an investigational, fMRI-guided titration protocol that permits personalized dosing of Microburst VNS among the treated population depending on the thalamic blood-oxygen-level-dependent signal. The study was registered on clinicaltrials.gov (NCT03446664). The first subject was enrolled in 2018 and the final results are expected in 2023
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Abstract
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
Regulation of P-glycoprotein expression at the levels of transcription and translation
EThOS - Electronic Theses Online ServiceGBUnited Kingdo
'It can be a lonely job sometimes': The use of collaborative space and social network theory in support of programme leaders
At one University in the East Midlands region of the UK, a core strand of programme leader support centres on the professional space and networks provided by a regular forum which is facilitated by educational developers. Drawing on the concept of distributed leadership the forum was intended as a low-resource, high-impact means of recognising the contribution of programme leaders to the institution and to facilitate the sharing of best practice and professional networking. This chapter explores the reality of implementing that idea, including the challenges and opportunities of fostering this approach to supporting academic programme leaders