Combating Terrorism in Bosnia-Herzegovina: Explaining and Assessing Article 201 of the Bosnian Criminal Code

This paper explores the legal measures that have been enacted in Bosnia-Herzegovina (BiH) to counter the threat of terrorism, focusing particularly on the international and domestic political context in which the reform of the Bosnian criminal code was carried out, on the apparent origins of Article 201 of the BiH criminal code in the European Union Framework Decision on Combating Terrorism of June 2002 and on the strengths and weaknesses of this definition in the Bosnian context. The paper argues firstly that the events of 9/11, while certainly of significance, were less salient to the definition of terrorism adopted in the BiH criminal code than the enhanced engagement of the European Union with processes of law reform in BiH in recent years seems to have been. The paper also concludes that despite various shortcomings (which should be addressed) the treatment of terrorism in the BiH criminal code has a number of strengths that make it particularly appropriate in the Bosnian context

Delineating the Interests of Justice: Prosecutorial Discretion and the Rome Statute of the International Criminal Court

Article 53(1) and 53(2) of the Rome Statute allow the prosecutor of the International Criminal Court (ICC) to decline to pursue an investigation or prosecution in the ‘interests of justice’. Some commentators have taken the view that the Office of the Prosecutor of the ICC should not invoke this ground for declining to act in situations where there is a possibility that investigations or prosecutions might impede or interfere with local peace and reconciliation initiatives such as amnesties or truth commissions. According to at least one prominent non-governmental organisation, such decisions are properly the domain of the UN Security Council, rather than of the Office of the Prosecutor. This paper argues, however, that it is neither necessary nor desirable for the ICC prosecutor to defer to the Security Council in such circumstances. The interests of justice would best be served if discretion remains with the prosecutor

Harnessing autophagy to overcome mitogen‐activated protein kinase kinase inhibitor‐induced resistance in metastatic melanoma

Background Patients with malignant melanoma often relapse after treatment with BRAF and/or mitogen‐activated protein kinase kinase (MEK) inhibitors (MEKi) owing to development of drug resistance. Objectives To establish the temporal pattern of CD271 regulation during development of resistance by melanoma to trametinib, and determine the association between development of resistance to trametinib and induction of prosurvival autophagy. Methods Immunohistochemistry for CD271 and p62 was performed on human naevi and primary malignant melanoma tumours. Western blotting was used to analyse expression of CD271, p62 and LC3 in melanoma subpopulations. Flow cytometry and immunofluorescence microscopy was used to evaluate trametinib‐induced cell death and CD271 expression. MTS viability assays and zebrafish xenografts were used to evaluate the effect of CD271 and autophagy modulation on trametinib‐resistant melanoma cell survival and invasion, respectively. Results CD271 and autophagic signalling are increased in stage III primary melanomas vs. benign naevi. In vitro studies demonstrate MEKi of BRAF‐mutant melanoma induced cytotoxic autophagy, followed by the emergence of CD271‐expressing subpopulations. Trametinib‐induced CD271 reduced autophagic flux, leading to activation of prosurvival autophagy and development of MEKi resistance. Treatment of CD271‐expressing melanoma subpopulations with RNA interference and small‐molecule inhibitors to CD271 reduced the development of MEKi resistance, while clinically applicable autophagy modulatory agents – including Δ9‐tetrahydrocannabinol and Vps34 – reduced survival of MEKi‐resistant melanoma cells. Combined MEK/autophagy inhibition also reduced the invasive and metastatic potential of MEKi‐resistant cells in an in vivo zebrafish xenograft. Conclusions These results highlight a novel mechanism of MEKi‐induced drug resistance and suggest that targeting autophagy may be a translatable approach to resensitize drug‐resistant melanoma cells to the cytotoxic effects of MEKi

Cost-effectiveness analysis of endoscopic eradication therapy for treatment of high-grade dysplasia in Barrett's esophagus

AIM: The aim was to evaluate the cost-effectiveness of endoscopic eradication therapy (EET) with combined endoscopic mucosal resection and radiofrequency ablation for the treatment of high-grade dysplasia (HGD) arising in patients with Barrett's esophagus compared with endoscopic surveillance alone in the UK. MATERIALS & METHODS: The cost-effectiveness model consisted of a decision tree and modified Markov model. A lifetime time horizon was adopted with the perspective of the UK healthcare system. RESULTS: The base case analysis estimates that EET for the treatment of HGD is cost-effective at a GB£20,000 cost-effectiveness threshold compared with providing surveillance alone for HGD patients (incremental cost-effectiveness ratio: GB£1272). CONCLUSION: EET is likely to be a cost-effective treatment strategy compared with surveillance alone in patients with HGD arising in Barrett's esophagus in the UK

Role of artificial intelligence in the diagnosis of oesophageal neoplasia: 2020 an endoscopic odyssey

The past decade has seen significant advances in endoscopic imaging and optical enhancements to aid early diagnosis. There is still a treatment gap due to the underdiagnosis of lesions of the oesophagus. Computer aided diagnosis may play an important role in the coming years in providing an adjunct to endoscopists in the early detection and diagnosis of early oesophageal cancers, therefore curative endoscopic therapy can be offered. Research in this area of artificial intelligence is expanding and the future looks promising. In this review article we will review current advances in artificial intelligence in the oesophagus and future directions for development

Multisensor perfusion assessment cohort study: Preliminary evidence toward a standardized assessment of indocyanine green fluorescence in colorectal surgery

Background: Traditional methods of assessing colonic perfusion are based on the surgeon's visual inspection of tissue. Fluorescence angiography provides qualitative information, but there remains disagreement on how the observed signal should be interpreted. It is unclear whether fluorescence correlates with physiological properties of the tissue, such as tissue oxygen saturation. The aim of this study was to correlate fluorescence intensity and colonic tissue oxygen saturation. Methods: Prospective cohort study performed in a single academic tertiary referral center. Patients undergoing colorectal surgery who required an anastomosis underwent dual-modality perfusion assessment of a segment of bowel before transection and creation of the anastomosis, using near-infrared and multispectral imaging. Perfusion was assessed using maximal fluorescence intensity measurement during fluorescence angiography, and its correlation with tissue oxygen saturation was calculated. Results: In total, 18 patients were included. Maximal fluorescence intensity occurred at a mean of 101 seconds after indocyanine green injection. The correlation coefficient was 0.73 (95% confidence interval of 0.65–0.79) with P < .0001, showing a statistically significant strong positive correlation between normalized fluorescence intensity and tissue oxygen saturation. The use of time averaging improved the correlation coefficient to 0.78. Conclusion: Fluorescence intensity is a potential surrogate for tissue oxygenation. This is expected to lead to improved decision making when transecting the bowel and, consequently, a reduction in anastomotic leak rates. A larger, phase II study is needed to confirm this result and form the basis of computational algorithms to infer biological or physiological information from the fluorescence imaging data

Intraoperative colon perfusion assessment using multispectral imaging

In colorectal surgery an anastomosis performed using poorly-perfused, ischaemic bowel segments may result in a leak and consequent morbidity. Traditional measures of perfusion assessment rely on clinical judgement and are mainly subjective, based on tissue appearance, leading to variability between clinicians. This paper describes a multispectral imaging (MSI) laparoscope that can derive quantitative measures of tissue oxygen saturation (SO2). The system uses a xenon surgical light source and fast filter wheel camera to capture eight narrow waveband images across the visible range in approximately 0.3 s. Spectral validation measurements were performed by imaging standardised colour tiles and comparing reflectance with ground truth spectrometer data. Tissue spectra were decomposed into individual contributions from haemoglobin, adipose tissue and scattering, using a previously-developed regression approach. Initial clinical results from seven patients undergoing colorectal surgery are presented and used to characterise measurement stability and reproducibility in vivo. Strategies to improve signal-To-noise ratio and correct for motion are described. Images of healthy bowel tissue (in vivo) indicate that baseline SO2 is approximately 75 } 6%. The SO2 profile along a bowel segment following ligation of the inferior mesenteric artery (IMA) shows a decrease from the proximal to distal end. In the clinical cases shown, imaging results concurred with clinical judgements of the location of well-perfused tissue. Adipose tissue, visibly yellow in the RGB images, is shown to surround the mesentery and cover some of the serosa. SO2 in this tissue is consistently high, with mean value of 90%. These results show that MSI is a potential intraoperative guidance tool for assessment of perfusion. Mapping of SO2 in the colon could be used by surgeons to guide choice of transection points and ensure that well-perfused tissue is used to form an anastomosis. The observation of high mesenteric SO2 agrees with work in the literature and warrants further exploration. Larger studies incorporating with a wider cohort of clinicians will help to provide retrospective evidence of how this imaging technique may be able to reduce inter-operator variability

Copper nanowire embedded hypromellose: An antibacterial nanocomposite film

The present work reports a novel antibacterial nanocomposite film comprising of copper nanowire impregnated biocompatible hypromellose using polyethylene glycol as a plasticiser. Detailed physico-chemical characterization using X-ray diffraction, Fourier transform infrared spectroscopy, UV–Visible spectroscopy and electron microscopy shows uniform dispersion of copper nanowire in the polymer matrix without any apparent oxidation. The film is flexible and shows excellent antibacterial activity against both Gram positive and negative bacteria at 4.8 wt% nanowire loading with MIC values of 400 µg/mL and 500 µg/mL for E. coli and S. aureus respectively. Investigation into the antibacterial mechanism of the nanocomposite indicates multiple pathways including cellular membrane damage caused by released copper ions and reactive oxygen species generation in the microbial cell. Interestingly, the film showed good biocompatibility towards normal human dermal fibroblast at minimum bactericidal concentration (MBC). Compared to the copper nanoparticles reported earlier in vitro studies, this low cytotoxicity of copper nanowires is due to the slow dissolution rate of the film and production of lower amount of ROS producing Cu2+ ions. Thus, the study indicates a strong potential for copper nanowire-based composites films in broader biomedical and clinical applications

Behavioral Impact of the Regulation of the Brain 2-Oxoglutarate Dehydrogenase Complex by Synthetic Phosphonate Analog of 2-Oxoglutarate: Implications into the Role of the Complex in Neurodegenerative Diseases

Decreased activity of the mitochondrial 2-oxoglutarate dehydrogenase complex (OGDHC) in brain accompanies neurodegenerative diseases. To reveal molecular mechanisms of this association, we treated rats with a specific inhibitor of OGDHC, succinyl phosphonate, or exposed them to hypoxic stress. In males treated with succinyl phosphonate and in pregnancy-sensitized females experiencing acute hypobaric hypoxia, we revealed upregulation of brain OGDHC (within 24 hours), with the activity increase presumably representing the compensatory response of brain to the OGDHC inhibition. This up-regulation of brain OGDHC was accompanied by an increase in exploratory activity and a decrease in anxiety of the experimental animals. Remarkably, the hypoxia-induced elevation of brain OGDHC and most of the associated behavioral changes were abrogated by succinyl phosphonate. The antagonistic action of hypoxia and succinyl phosphonate demonstrates potential therapeutic significance of the OGDHC regulation by the phosphonate analogs of 2-oxoglutarate