Markovian language model of the DNA and its information content

S.S. and M.S.B. acknowledge the Engineering and Physical Sciences Research Council (EPSRC), grant ref. EP/I032608/1.Peer reviewedPublisher PD

Bottling the Criminal Contempt Law – A Search for ‘Intention’ in ‘Scandalizing the Court’

The right to speak and express freely is arguably the most contentious fundamental right guaranteed to the citizens by the Indian Constitution. Like all the other rights and privileges in a democracy, freedom of speech is not absolute and is subject to restrictions. One such restriction is the offence of contempt of court. In doing so, courts have been successful in upholding their dignity and majesty but often at the cost of stifling criticism and instilling fear amongst the critics of the institution. There is a sense of anxiety among the citizens as they anticipate an over-disciplined regime and struggle to understand what constitutes criminal contempt and how it works. In this article, the authors have attempted to suggest a development in the existing criminal contempt law by scrutinising the mental element of the publisher or the person making the criticism

Genomic evaluation of multiparametric magnetic resonance imaging-visible and -nonvisible lesions in clinically localised prostate cancer

Background: The prostate cancer (PCa) diagnostic pathway is undergoing a radical change with the introduction of multiparametric magnetic resonance imaging (mpMRI), genomic testing, and different prostate biopsy techniques. It has been proposed that these tests should be used in a sequential manner to optimise risk stratification. Objective: To characterise the genomic, epigenomic, and transcriptomic features of mpMRI-visible and -nonvisible PCa in clinically localised disease. Design, setting, and participants: Multicore analysis of fresh prostate tissue sampled immediately after radical prostatectomy was performed for intermediate- to high-risk PCa. Intervention: Low-pass whole-genome, exome, methylation, and transcriptome profiling of patient tissue cores taken from microscopically benign and cancerous areas in the same prostate. Circulating free and germline DNA was assessed from the blood of five patients. Outcome measurement and statistical analysis: Correlations between preoperative mpMRI and genomic characteristics of tumour and benign prostate samples were assessed. Gene profiles for individual tumour cores were correlated with existing genomic classifiers currently used for prognostication. Results and limitations: A total of 43 prostate cores (22 tumour and 21 benign) were profiled from six whole prostate glands. Of the 22 tumour cores, 16 were tumours visible and six were tumours nonvisible on mpMRI. Intratumour genomic, epigenomic, and transcriptomic heterogeneity was found within mpMRI-visible lesions. This could potentially lead to misclassification of patients using signatures based on copy number or RNA expression. Moreover, three of the six cores obtained from mpMRI-nonvisible tumours harboured one or more genetic alterations commonly observed in metastatic castration-resistant PCa. No circulating free DNA alterations were found. Limitations include the small cohort size and lack of follow-up. Conclusions: Our study supports the continued use of systematic prostate sampling in addition to mpMRI, as avoidance of systematic biopsies in patients with negative mpMRI may mean that clinically significant tumours harbouring genetic alterations commonly seen in metastatic PCa are missed. Furthermore, there is inconsistency in individual genomics when genomic classifiers are applied. Patient summary: Our study shows that tumour heterogeneity within prostate tumours visible on multiparametric magnetic resonance imaging (mpMRI) can lead to misclassification of patients if only one core is used for genomic analysis. In addition, some cancers that were missed by mpMRI had genomic aberrations that are commonly seen in advanced metastatic prostate cancer. Avoiding biopsies in mpMRI-negative cases may mean that such potentially lethal cancers are missed

Do brain networks evolve by maximizing their information flow capacity?

We propose a working hypothesis supported by numerical simulations that brain networks evolve based on the principle of the maximization of their internal information flow capacity. We find that synchronous behavior and capacity of information flow of the evolved networks reproduce well the same behaviors observed in the brain dynamical networks of Caenorhabditis elegans and humans, networks of Hindmarsh-Rose neurons with graphs given by these brain networks. We make a strong case to verify our hypothesis by showing that the neural networks with the closest graph distance to the brain networks of Caenorhabditis elegans and humans are the Hindmarsh-Rose neural networks evolved with coupling strengths that maximize information flow capacity. Surprisingly, we find that global neural synchronization levels decrease during brain evolution, reflecting on an underlying global no Hebbian-like evolution process, which is driven by no Hebbian-like learning behaviors for some of the clusters during evolution, and Hebbian-like learning rules for clusters where neurons increase their synchronization

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Meaning-making of historical episodes by the Punjabi-Sikh youth in Vancouver

This thesis explores the ways in which the youth from the Punjabi-Sikh community in Vancouver, Canada relate to three historical episodes associated with the community, namely, ‘Events of 1984’(The Indian Army’s 1984 attack on the Golden Temple in Amritsar, as well as, the anti-Sikh riots in Delhi, India), ‘Events of 1985’ (The Air India bombings) and the Komagata Maru episode of 1914. Exploring the youth narratives and non-narratives on these violent episodes intrinsically connected with the Sikh diasporic community in Canada, provides for an analysis of the meaning-making processes that the youth engage with to make sense of these episodes. By emphasizing on how the youth remember, what they remember (and what they forget), I draw attention to linkages between these processes of recall and the present day realities of the youth. By juxtaposing the dominant narratives on the episodes with the youth narratives, the research also explores the relationship of these ‘grand’ narratives with the personal narratives of the youth, the space and reception of the contending forms of remembrances of these violent histories, and its effect on present day politics.Arts, Faculty ofGeography, Department ofGraduat

Inulin as a Delivery Vehicle for Targeting Colon-Specific Cancer

Natural polysaccharides, as well as biopolymers, are now days widely developed for targeting colon cancer using various drug delivery systems. Currently, healing conformations are being explored that can efficiently play a multipurpose role. Owing to the capability of extravagance colonic diseases with the least adverse effects, biopolymers for site specific colon delivery have developed an increased curiosity over the past decades. Inulin (INU) was explored for its probable application as an entrapment material concerning its degradation by enzymes in the colonic microflora and its drug release behavior in a sustained and controlled manner. INU is a polysaccharide and it consists of 2 to 1 linkage having an extensive array of beneficial uses such as a carrier for delivery of therapeutic agents as an indicative/investigative utensil or as a dietary fiber with added well-being aids. In the main, limited research, as well as information, is available on the delivery of therapeutic agents using inulin specifically for colon cancer because of its capability to subsist in the stomach’s acidic medium. This exceptional steadiness and robustness properties are exploited in numerous patterns to target drugs securely for the management of colonic cancer, where they effectively act and kills colonic tumor cells easily. In this review article, recent efforts and inulin-based nano-technological approaches for colon cancer targeting are presented and discussed. </jats:sec