Lower hepatocellular carcinoma surveillance in metabolic dysfunction-associated steatotic liver disease: Impact on treatment eligibility.

BACKGROUND AND AIM: This study aimed to compare the determinants and impact of hepatocellular carcinoma (HCC) surveillance rates for people with metabolic dysfunction-associated steatotic liver disease (MASLD) versus other chronic liver diseases. METHODS: A dataset of HCC patients from a UK hospital (2007-2022) was analyzed. The Mann-Whitney U-test compared continuous variables. The χ2 and two-tailed Fisher exact tests compared categorical data. Regression modeling analyzed the impact of MASLD on the size and number of HCC nodules and curative treatment. The Cox proportional hazards model assessed the influence of MASLD on overall survival. RESULTS: A total of 176 of 687 (25.6%) HCC patients had MASLD. Fewer people with MASLD HCC were enrolled in HCC surveillance compared to non-MASLD HCC (38 [21.6%] vs 215 [42.1%], P < 0.001). Patients with MASLD HCC were less likely to have been under secondary care (n = 57 [32.4%] vs 259 [50.7%], P < 0.001) and less likely to have cirrhosis (n = 113 [64.2%] vs 417 [81.6%], P < 0.001). MASLD was associated with a 12.3-mm (95% confidence interval [CI] 10.8-14.0 mm) greater tumor diameter compared to people without MASLD (P = 0.002). Patients with MASLD HCC had 0.62 reduced odds (95% CI 0.43-0.91) of receiving curative treatment compared to non-MASLD HCC (P = 0.014). Overall survival was similar for patients with MASLD HCC versus non-MASLD HCC (hazard ratio 1.03, 95% CI 0.85-1.25, P = 0.748). CONCLUSION: Patients with MASLD are less likely to have been enrolled in HCC surveillance due to undiagnosed cirrhosis or presenting with non-cirrhotic HCC. Patients with MASLD HCC present with larger tumors and are less likely to receive curative treatment.

The costs of developing treatments for Alzheimer's disease: A retrospective exploration.

INTRODUCTION: With the exception of the recent accelerated approval of aducanumab, in over 26 years of research and development (R&D) investment in Alzheimer's disease (AD), only five novel drugs-all for symptomatic treatment only-have reached FDA approval. Here, we estimate the costs of AD drug development during this period in the private sector. METHODS: To estimate private R&D funding, we collected information on AD clinical trials (n = 1099; phases 1-4) conducted between January 1, 1995 and June 21, 2021 from various databases. Costs were derived using previously published methodologies and adjusted for inflation. RESULTS: Since 1995, cumulative private expenditures on clinical stage AD R&D were estimated at $42.5 billion, with the greatest costs (57%; $24,065 million) incurred during phase 3; approximately 184,000 participants were registered or are currently enrolled in clinical trials. DISCUSSION: Measures to reduce expenditures while moving toward disease-modifying therapies that alleviate the rising burden of AD require continued investment from industry, government, and academia.

Innovation, growth and the transition to net-zero emissions.

The climate crisis and the global economic impact of the Covid-19 crisis occur against a background of slowing growth and widening inequalities, which together imply an urgent need for a new environmentally sustainable and inclusive approach to growth. Investments in "clean" innovation and its diffusion are key to shaping this, accompanied by investments in complementary assets including sustainable infrastructure, and human, natural and social capital which will not only help achieve net-zero greenhouse gas emissions, but will also improve productivity, living standards and the prospects of individuals. In this article, we draw on the theoretical and empirical evidence on the opportunities, drivers and policies for innovation-led sustainable growth. We highlight the importance of a coordinated set of long-term policies and institutions that can enable and foster private sector investments in clean innovation and assets quickly and at scale. In doing so, we draw inspiration from Chris Freeman's work on the system-wide drivers of innovation, and his early vision of achieving environmental sustainability by reorienting growth.

Transarterial chemo-embolisation of hepatocellular carcinoma: impact of liver function and vascular invasion.

BACKGROUND: Transarterial chemo-embolisation (TACE) is recommended for patients with BCLC intermediate stage hepatocellular carcinoma (stage B), particularly in patients with good underlying liver function and minimal symptoms. The hepatoma arterial embolisation prognostic (HAP) score combines measures of liver function and tumour-related factors to offer a simple prognostic scoring system. The Albumin-Bilirubin (ALBI) grade permits assessment of the impact of liver function on survival. We aimed to investigate these two models and vascular invasion (VI). METHODS: In an international cohort of 3030 patients undergoing TACE, we examined the impact of liver function as assessed by the ALBI score, the HAP score and VI on survival. RESULTS: Classification according to ALBI grade resulted in non-overlapping survival curves in the overall data set and all regional cohorts. The HAP score was also validated. Tumour number, aetiology and VI were identified as additional independent prognostic risk factors not currently included in the HAP score. Survival was particularly poor for patients with VI. CONCLUSIONS: The ALBI grade categorised patients receiving TACE into three clear prognostic groups, thereby emphasising the importance of underlying liver function in the outcome of TACE. The HAP score has been validated internationally and the serious adverse impact of VI is clearly shown.

Economic development, climate and values: making policy.

The two defining challenges of this century are overcoming poverty and managing the risks of climate change. Over the past 10 years, we have learned much about how to tackle them together from ideas on economic development and public policy. My own work in these areas over four decades as an academic and as a policy adviser in universities and international financial institutions has focused on how the investment environment and the empowerment of people can change lives and livelihoods. The application of insights from economic development and public policy to climate change requires rigorous analysis of issues such as discounting, modelling the risks of unmanaged climate change, climate policy targets and estimates of the costs of mitigation. The latest research and results show that the case for avoiding the risks of dangerous climate change through the transition to low-carbon economic development and growth is still stronger than when the Stern Review was published. This is partly because of evidence that some of the impacts of climate change are happening more quickly than originally expected, and because of remarkable advances in technologies, such as solar power. Nevertheless, significant hurdles remain in securing the international cooperation required to avoid dangerous climate change, not least because of disagreements and misunderstandings about key issues, such as ethics and equity.

Disseminated Armillifer Infection in Humans: A Rare Entity.

Armillifer parasites, belonging to the Pentastomida subclass, are commonly known to cause infection in animals, particularly reptiles. Although rare, cases of Armillifer infection in humans have been reported. Most cases are asymptomatic or mildly symptomatic, with severe presentations being uncommon. Symptoms can vary depending on whether the nymph is encysted or actively dying, leading to immune-mediated reactions. Diagnostic imaging findings can be characteristic of Armillifer infection. We present the case of a 61-year-old male from West Africa with a history of snake consumption, who presented with night sweats, fevers, and chills, and imaging consistent with disseminated Armillifer infection.

Towards carbon neutrality and China's 14th Five-Year Plan: Clean energy transition, sustainable urban development, and investment priorities.

China's 14th Five-Year Plan, for the period 2021-25, presents a real opportunity for China to link its long-term climate goals with its short-to medium-term social and economic development plans. China's recent commitment to achieving carbon neutrality by 2060 has set a clear direction for its economy, but requires ratcheting up ambition on its near-term climate policy. Against this background, this paper discusses major action areas for China's 14th Five-Year Plan after COVID-19, especially focusing on three aspects: the energy transition, a new type of sustainable urban development, and investment priorities. China's role in the world is now of a magnitude that makes its actions in the immediate future critical to how the world goes forward. This decade, 2021-2030, is of fundamental importance to human history. If society locks in dirty and high-carbon capital, it raises profound risks of irreversible damage to the world's climate. It is crucial for China to peak its emissions in the 14th Five-Year Plan (by 2025), making the transition earlier and cheaper, enhancing its international competitiveness in growing new markets and setting a strong example for the world. The benefits for China and the world as a whole could be immense.

The Economics of Lockdown.

In this paper, we suggest an approach to analysing policies relating to the COVID-19 pandemic. We discuss the formulation of policy and sketch how the approach can be applied to different specific challenges as policymakers try to make difficult choices for managing the pandemic and protecting the economy and society.

Explicit and implicit memory for music in healthy older adults and patients with mild Alzheimer's disease.

Introduction: Previous studies have found that music paired with lyrics at encoding may improve the memory performance of patients with mild Alzheimer's disease (AD). To further explore memory for different types of musical stimuli, the current study examined both implicit and explicit memory for music with and without lyrics compared to spoken lyrics. Method: In this mixed design, patients with probable mild AD (n = 15) and healthy older adults (n = 13) listened to auditory clips (song, instrumental, or spoken lyrics varied across three sessions) and then had their memory tested. Implicit memory was measured by the mere exposure effect. Explicit recognition memory was measured using a confidence-judgment receiver operating characteristic (ROC) paradigm, which allowed examination of the separate contributions made by familiarity and recollection. Results: A significant implicit memory mere exposure effect was found for both groups in the instrumental and song but not the spoken condition. Both groups had the best explicit memory performance in the spoken condition, followed by song, and then instrumental conditions. Healthy older adults demonstrated more recollection than patients with AD in the song and spoken conditions, but both groups performed similarly in the instrumental condition. Patients with AD demonstrated more familiarity in the instrumental and song conditions than in the spoken condition. Conclusions: The results have implications for memory interventions for patients with mild AD. The implicit memory findings suggest that patients with AD may still show a preference for information familiar to them. The explicit memory results support prior findings that patients with AD rely heavily on familiarity, but also suggest that there may be limitations on the benefits that music can provide to recognition memory performance.

Endoscopic papillary large balloon dilatation with sphincterotomy is safe and effective for biliary stone removal independent of timing and size of sphincterotomy.

AIM: To describe the efficacy and safety of endoscopic papillary large balloon dilatation (EPLBD) in the management of bile duct stones in a Western population. METHODS: Data was collected from the endoscopic retrograde cholangiopancreatography (ERCP) and Radiology electronic database along with a review of case notes over a period of six years from 1st August 2009 to 31st July 2015 and incorporated into Microsoft excel. Statistical analyses were performed using MedCalc for Windows, version 12.5 (MedCalc Software, Ostend, Belgium). Simple statistical applications were applied in order to determine whether significant differences exist in comparison groups. We initially used simple proportions to describe the study populations. Furthermore, we used chi-square test to compare proportions and categorical variables. Non-parametric Mann-Whitney U-test was applied in order to compare continuous variables. All comparisons were deemed to be statistically significant if P values were less than 0.05. RESULTS: EPLBD was performed in 229 patients (46 females) with mean age of 68 ± 14.3 years. 115/229 (50%) patients had failed duct clearance at previous ERCP referred from elsewhere with standard techniques. Duct clearance at the Index* ERCP (1st ERCP at our centre) was 72.5%. Final duct clearance rate was 98%. EPLBD after fresh sphincterotomy was performed in 81 (35.4%). Median balloon size was 13.5 mm (10 - 18). In addition to EPLBD, per-oral cholangioscopy (POC) and electrohydraulic lithotripsy (EHL) was performed in 35 (15%) patients at index* ERCP. 63 (27.5%) required repeat ERCP for stone clearance. 28 (44.5%) required POC and EHL and 11 (17.4%) had repeat EPLBD for complete duct clearance. Larger stone size (12.4 mm vs 17.4 mm, P < 0.000001), multiple stones (2, range (1-13) vs 3, range (1-12), P < 0.006) and dilated common bile duct (CBD) (12.4 mm vs 18.3 mm, P < 0.001) were significant predictors of failed duct clearance at index ERCP. 47 patients (20%) had ampullary or peri-ampullary diverticula. Procedure related adverse events included 2 cases of bleeding and pancreatitis (0.87%) each. CONCLUSION: EPLBD is a safe and effective technique for CBDS removal. There is no difference in outcomes whether it is performed at the time of sphincterotomy or at a later procedure or whether there is a full or limited sphincterotomy.

Music-based memory enhancement in Alzheimer's disease: promise and limitations.

In a previous study (Simmons-Stern, Budson & Ally, 2010), we found that patients with Alzheimer's disease (AD) better recognized visually presented lyrics when the lyrics were also sung rather than spoken at encoding. The present study sought to further investigate the effects of music on memory in patients with AD by making the content of the song lyrics relevant for the daily life of an older adult and by examining how musical encoding alters several different aspects of episodic memory. Patients with AD and healthy older adults studied visually presented novel song lyrics related to instrumental activities of daily living (IADL) that were accompanied by either a sung or a spoken recording. Overall, participants performed better on a memory test of general lyric content for lyrics that were studied sung as compared to spoken. However, on a memory test of specific lyric content, participants performed equally well for sung and spoken lyrics. We interpret these results in terms of a dual-process model of recognition memory such that the general content questions represent a familiarity-based representation that is preferentially sensitive to enhancement via music, while the specific content questions represent a recollection-based representation unaided by musical encoding. Additionally, in a test of basic recognition memory for the audio stimuli, patients with AD demonstrated equal discrimination for sung and spoken stimuli. We propose that the perceptual distinctiveness of musical stimuli enhanced metamemorial awareness in AD patients via a non-selective distinctiveness heuristic, thereby reducing false recognition while at the same time reducing true recognition and eliminating the mnemonic benefit of music. These results are discussed in the context of potential music-based memory enhancement interventions for the care of patients with AD.

Uncertainty in science and its role in climate policy.

Policy-making is usually about risk management. Thus, the handling of uncertainty in science is central to its support of sound policy-making. There is value in scientists engaging in a deep conversation with policy-makers and others, not merely 'delivering' results or analyses and then playing no further role. Communicating the policy relevance of different varieties of uncertainty, including imprecision, ambiguity, intractability and indeterminism, is an important part of this conversation. Uncertainty is handled better when scientists engage with policy-makers. Climate policy aims both to alter future risks (particularly via mitigation) and to take account of and respond to relevant remaining risks (via adaptation) in the complex causal chain that begins and ends with individuals. Policy-making profits from learning how to shift the distribution of risks towards less dangerous impacts, even if the probability of events remains uncertain. Immediate value lies not only in communicating how risks may change with time and how those risks may be changed by action, but also in projecting how our understanding of those risks may improve with time (via science) and how our ability to influence them may advance (via technology and policy design). Guidance on the most urgent places to gather information and realistic estimates of when to expect more informative answers is of immediate value, as are plausible estimates of the risk of delaying action. Risk assessment requires grappling with probability and ambiguity (uncertainty in the Knightian sense) and assessing the ethical, logical, philosophical and economic underpinnings of whether a target of '50 per cent chance of remaining under +2(°)C' is either 'right' or 'safe'. How do we better stimulate advances in the difficult analytical and philosophical questions while maintaining foundational scientific work advancing our understanding of the phenomena? And provide immediate help with decisions that must be made now?

Portal vein cannulation: an uncommon complication of endoscopic retrograde cholangiopancreatography.

Portal vein cannulation is a rare complication of endoscopic retrograde cholangiopancreatography (ERCP). It has been reported that it usually occurs after endoscopic sphincterotomy, whereas in cases without prior sphincterotomy, the presence of portobiliary fistulas has been shown. Here, we present a case in which cannulation of the portal vein occurred despite careful wire-guided cannulation and the absence of sphincterotomy. Although fatal cases of cerebral and pulmonary air and/or bile embolism have been reported in patients with combined portal and hepatic vein trauma after ERCP and sphincterotomy, isolated portal vein cannulation, as in the current case, does not usually result in mortality or serious morbidity. However, awareness of this rare complication is important so that no further intervention is performed.

Familiar smiling faces in Alzheimer's disease: understanding the positivity-related recognition bias.

Recent research has revealed a recognition bias favoring positive faces and other stimuli in older compared to younger adults. However, it is yet unclear whether this bias reflects an age-related preference for positive emotional stimuli, or an affirmatory bias used to compensate for episodic memory deficits. To follow up this point, the present study examined recognition of emotional faces and current mood state in patients with mild Alzheimer disease (AD) and healthy controls. Expecting lower overall memory performance, more negative and less positive mood in AD patients, the critical question was whether the positivity-related recognition bias would be increased compared to cognitively unimpaired controls. Eighteen AD patients and 18 healthy controls studied happy, neutral, and angry faces, which in a subsequent recognition task were intermixed with 50% distracter faces. As expected, the patient group showed reduced memory performance, along with a less positive and more negative mood. The recognition bias for positive faces persisted. This pattern supports the view that the positivity-induced recognition bias represents a compensatory, gist-based memory process that is applied when item-based recognition fails.

Music as a memory enhancer in patients with Alzheimer's disease.

Musical mnemonics have a long and diverse history of popular use. In addition, music processing in general is often considered spared by the neurodegenerative effects of Alzheimer's disease (AD). Research examining these two phenomena is limited, and no work to our knowledge has explored the effectiveness of musical mnemonics in AD. The present study sought to investigate the effect of music at encoding on the subsequent recognition of associated verbal information. Lyrics of unfamiliar children's songs were presented bimodally at encoding, and visual stimuli were accompanied by either a sung or a spoken recording. Patients with AD demonstrated better recognition accuracy for the sung lyrics than the spoken lyrics, while healthy older adults showed no significant difference between the two conditions. We propose two possible explanations for these findings: first, that the brain areas subserving music processing may be preferentially spared by AD, allowing a more holistic encoding that facilitates recognition, and second, that music heightens arousal in patients with AD, allowing better attention and improved memory.