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Colorectal cancer molecular profiling: Opportunities for early detection
No full textColorectal cancer (CRC) is one of the most common and deadliest cancers worldwide, and incidence rates are rising. However, early detection and intervention can improve the survival rates and quality of life of affected patients. Current screening tests used to streamline patients into colonoscopy either lack test adherence or sensitivity for detecting premalignant and early-stage CRC, reducing the advantages of screening measures. Cost-effective and minimally invasive diagnostic tests which can detect immune system and metabolic changes are key to lower the incidence of CRC advanced stages. We herein discuss the statistics, risk factors and unique genetic characteristics of CRC, focussing on the importance of understanding non tumour-derived information in premalignant states for developing comprehensive techniques to achieve earlier diagnosis of CRC. Moreover, the advantages and limitations of current UK and USA screening programmes and emerging detection tools are discussed, along with prospective diagnostics such as genomics, proteomics and spectroscopy
Efficacy and safety of pharmacological therapies for functional constipation in children: a systematic review and meta-analysis
No full textBackground
There has been a substantial increase in studies on functional constipation in children as new therapies are deployed. We aimed to provide an up-to-date, methodologically robust systematic review and meta-analysis on the efficacy and safety of pharmacological therapies for functional constipation in children.
Methods
In this systematic review and meta-analysis, we searched PubMed, Medline, Embase, and the Cochrane library from inception to Feb 5, 2025. We included randomised controlled trials that involved children aged 0 years to younger than 18 years with functional constipation treated with pharmacological interventions compared with placebo, no treatment, or other interventions and with at least a 2-week follow-up period. Studies were excluded if there was no definition of functional constipation, children with organic causes for constipation or previous bowel surgery were included, children with faecal incontinence without the presence of constipation were included, or the aim of treatment was faecal disimpaction rather than maintenance therapy. Pairs of authors independently extracted summary data from published reports and critiqued studies. We assessed risk of bias with the Cochrane tool. Meta-analyses estimated risk ratios (RRs) or mean differences, and 95% CIs. Certainty of evidence was established with GRADE. Our main outcomes were treatment success (as defined by study authors), defecation frequency, and withdrawals due to adverse events. This study was registered on PROSPERO (CRD42022368719).
Findings
Our search identified 4595 articles, of which 59 randomised controlled trials were included, representing 7045 participants with functional constipation. Interventions included polyethylene glycol (n=36 studies), lactulose (n=18), magnesium oxide or magnesium hydroxide (n=7), picosulfate (n=1), liquid paraffin (n=4), prucalopride (n=1), lubiprostone (n=2), linaclotide (n=3), plecanatide (n=1), enemas (n=2), and domperidone (n=1). Meta-analyses for treatment success showed that polyethylene glycol was probably more effective than placebo (RR 1·74 [95% CI 1·25–2·41], moderate certainty of evidence) and may be more effective than lactulose (1·35 [1·11–1·64], low certainty of evidence). There might be no difference in treatment success for linaclotide compared with placebo (1·21 [0·69–2·13], low certainty of evidence), but linaclotide probably leads to higher defecation frequency per week (mean difference 1·10 [95% CI 0·40–1·80], moderate certainty of evidence). There is low to moderate certainty evidence that prucalopride is not more effective than placebo (RR 1·68 [95% CI 0·77 to 3·68]).
Interpretation
Polyethylene glycol is probably more effective than placebo and key comparator therapies and should be considered the standard of first-line care. Future studies should consider polyethylene glycol as an index therapy, and clearly describe methods, patient characteristics, and previous therapeutics.
Funding
None
A Comparison of Cardiovascular Benefits of Dapagliflozin and Empagliflozin in Type 2 Diabetes: A Systematic Review and Meta-analysis
No full textPurpose
Dapagliflozin and Empagliflozin, two widely used sodium-glucose cotransporter 2 (SGLT2) inhibitors, are integral in managing Type 2 Diabetes Mellitus (T2DM) and have shown potential benefits in improving various clinical outcomes. This meta-analysis compares the efficacy and safety of Dapagliflozin versus Empagliflozin in T2DM patients by assessing key cardiovascular outcomes.
Methods
A comprehensive search was conducted across PubMed, EMBASE, and Cochrane databases up to February 2025. Observational studies comparing Dapagliflozin and Empagliflozin in patients with T2DM were included. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for each outcome, and significance was considered when the p-value was less than 0.05. Random-effects models were used when I2 exceeded 50%, indicating substantial heterogeneity, while fixed-effects models were applied when heterogeneity was low (I2 ≤ 50%).
Results
A total of 8 studies were included in this meta-analysis, with a combined patient population of 428,940 individuals, 164,224 treated with Dapagliflozin and 264,716 treated with Empagliflozin. Dapagliflozin and Empagliflozin showed no significant differences in all-cause mortality (RR 1.10, 95% CI 0.84–1.44, p = 0.49), cardiovascular mortality (RR 0.89, 95% CI 0.65–1.23, p = 0.49), myocardial infarction (RR 0.99, 95% CI 0.82–1.20, p = 0.94), ischemic stroke (RR 1.12, 95% CI 0.96–1.30, p = 0.15), major adverse cardiovascular events (RR 1.11, 95% CI 0.94–1.30, p = 0.22), or heart failure (RR 1.10, 95% CI 0.91–1.32, p = 0.33), but Dapagliflozin was associated with a significantly lower risk of hospitalization for heart failure (RR 0.91, 95% CI 0.84–0.99, p = 0.02).
Conclusion
Dapagliflozin and Empagliflozin showed similar efficacy in managing Type 2 Diabetes outcomes, with no significant differences in mortality, cardiovascular events, or stroke. Dapagliflozin was associated with lower hospitalization rates for heart failure. Further studies are needed to evaluate long-term effects and individual patient responses
THE EVOLUTION AND MITIGATION OF RANSOMWARE: TECHNIQUES, TACTICS AND RESPONSE STRATEGIES
No full textRansomware is still one of the most current and dangerous types of malware on the internet. Ransomware is detrimental in its impact towards both personal and corporate entities, while its consequences are often financially and operationally disastrous. This paper focuses on analysing the ransomware threat capabilities and trends during the last ten years and how cybercriminals have updated their approaches to the threat. The research explores the evolution of ransomware, such as the ransomware-as-a-service (raas), second-stage extortion schemes, sophisticated encryption, and obfuscation techniques. Further, the study measures present-day mitigation measures like endpoint protection, employee training, and incident response systems and defines unmet needs in the present defensive measures. While the paper evaluates cases where organisations have successfully enacted response strategies, organization must ensure proactivity, backed-up presence and effective cybersecurity policies. In addition, the study expects future developments in ransomware attacks to involve artificial intelligence tools to enhance the strategies and attacks towards the key areas of interest, such as the healthcare and energy sectors. The study highlights the necessity for effective legal measures to counter the work of ransomware actors who operate internationally and offers improvements to the policy and defence measures
Spatio-temporal modeling of climate change impacts on farming using GNN-LSTM with attention and ensemble learning
No full textClimate change poses a great danger to agriculture today, which in turn affects crop yields, quality, and food security; thus, efforts to create simulation tools that would help in the assessment of these effects are paramount. This work proposes a model of Graph Neural Networks (GNN) and Long Short-Term Memory with attention (LSTMatt) networks. The GNN learns the spatial configuration and interconnection between climate and agricultural data, and the LSTMatt learns the temporal patterns. The model is a combination of outputs from LSTMatt and GNN by Random Forest-based bagging, which thereby improves accuracy and robustness of predictions. This integrated approach provides a more holistic view to ensure a solution to some of the challenges affecting the policymakers, farmers, urban rooftop planners, and smart city developers to make better decisions on suitable options for practices in agriculture to mitigate the effects of climate change
Exploring the concept of ‘service user engagement' in specialist domestic abuse services, and how its use impacts service users and service delivery.
No full textWhen victims/survivors of domestic abuse access support from specialist domestic abuse services – and others – this is labelled ‘service user engagement’, a term also frequently used in the domestic abuse literature on specialist services, with the meaning and application often taken for granted. This study represents the first qualitative exploration of the concept of service user engagement within specialist domestic abuse services, which draws on workers’ perspectives on service user engagement, and on service users’ perspectives on interactions with services. It was funded by, and took place within the parameters of, the UCLan evaluation of the SafeLives/Women’s Aid Federation England ‘Roadmap for System Change’ Project. The study was completed using interpretive qualitative methodology in the form of semi-structured interviews with 15 service users and 16 workers across four specialist domestic abuse services in England. Interviews were analysed following a process of reflexive thematic analysis informed by the study’s theoretical frameworks of feminism and social constructionism. The study demonstrates that exploring the concept of engagement is important: it directly impacts whether service users receive a service, and potentially denies service users specialist support that they cannot access elsewhere due to other services’, family and friends’ lack of understanding of domestic abuse. Service user engagement was presented by workers as a multi-faceted, complex concept; yet in practice – and in the academic literature – it has been reduced to a binary: ‘engaged/not engaged’. The ecological model developed through this study demonstrates how workers conceptualise service user engagement, and the impact this has on service users. The model shows how specialist services are shaped by commissioning and national policy to deliver generic services that focus on the engagement of individual service users, without accounting for wider structural and intersectional inequalities that impact service users and their engagement. Neo-liberal narratives of personal responsibility and the need for public services to avoid ‘service user dependency’ have influenced how workers implement the feminist ethos of empowerment. Service users feel empowered through the non-judgemental, empathetic, and understanding approach taken by workers, and by the actions workers take on service users’ behalf due to their
greater power to enact change. Service users’ lack of power, and lack of support elsewhere, can create a dependency on the specialist service despite workers’ attempts to avoid this. But within ‘engagement’, workers require evidence that service users are being empowered through taking responsibility for actions, and often don’t recognise the ways in which service users lack power compared with themselves and other services. This study has implications for the use of ‘service user engagement’ within the commissioning and delivery of specialist domestic abuse services, and academic research on such services, by highlighting the multifaceted nature of the concept of engagement and the need to understand how it is experienced by service users
TCT-302 High-Risk Plaques in Proximal and Distal Segments Relative to Graft Anastomoses and Non-Grafted Segments
No full textDerivative Actions and LLPs: The Need for Reform
No full textThis article examines the means by which a derivative action can be brought on behalf of a limited liability partnership (LLP) through an analysis of the recent judicial decisions that pave the way for further reforms to extend the statutory regime under the Companies Act 2006 to include LLPs
Prevention of sexual violence and domestic abuse through a university bystander intervention programme: learning from a UK feasibility study
Get PDFIn response to evidence documenting the scale and impact of sexual violence (SV) and domestic abuse (DA) in universities, Universities UK (2016) recommend implementation of a UK based bystander programme, The Intervention Initiative (TII), as a key prevention strategy. However, a recent UK review (Gaffney et al, 2023) concluded that no studies have addressed implementation issues for university-based bystander programmes. Our study explored what is required for implementation of the TII in a UK university, rather than intervention effectiveness. The intervention was delivered to undergraduate students across three school cohorts: medicine, social work and sports coaching.
The study draws on pre- and post-intervention surveys to explore SV and DA knowledge, attitudes, and bystander skills. Focus groups or individual interviews with students (n=11) and staff facilitators (n=10) explored experiences of implementation, delivery and participation. Students reported positive changes across several areas and some evidence of immediate impact on behaviours, suggesting potential for wider implementation across university contexts. Barriers included professionalisation of the application of the bystander intervention, resistance to an underpinning gendered evidence base and a lack of diversity and relatability in programme materials
Examining the role of bullying victimisation in predicting psychopathology among in-school Nigerian adolescents
Get PDFPurpose: This paper reports on a cross-sectional study undertaken to examine the role of bullying victimisation in predicting psychopathology, encompassing post-traumatic stress disorder (PTSD), risk of developing prodromal psychosis, and emotional and behavioural problems, among in-school Nigerian adolescents.
Methodology: Three hundred and fifty-one junior secondary students (n = 173 males, 178 females; age range: 9-17 years) were recruited from five randomly selected public secondary schools in Nigeria. Students completed a variety of self-report measures, including a socio-demographic questionnaire, the Prodromal Questionnaire – brief version, the Strengths and Difficulties Questionnaire (SDQ), and the Multidimensional Peer Victimisation Scale. They were also interviewed using the PTSD module of the Mini International Neuropsychiatric Interview-Kid Version.
Findings: Although bullying victimisation was not found to predict the presence of PTSD, it predicted the risk of developing prodromal psychosis. All SDQ subscales also held significant positive associations with bullying victimisation. This indicates that higher levels of victimisation are associated with increased behavioural and emotional difficulties among adolescents.
Value: The study contributes to the evidence demonstrating a need for improved understanding regarding the role of exposure to bullying victimisation in predicting various forms of psychopathology. Furthermore, there is specifically a need for research with this focus in developing countries in sub-Saharan Africa and the Nigerian education system