The effect of comorbidities on diagnostic interval for lung cancer in England: a cohort study using electronic health record data.

BackgroundComorbid conditions may delay lung cancer diagnosis by placing demand on general practioners’ time reducing the possibility of prompt cancer investigation (“competing demand conditions”), or by offering a plausible non-cancer explanation for signs/symptoms (“alternative explanation conditions”).MethodPatients in England born before 1955 and diagnosed with incident lung cancer between 1990 and 2019 were identified in the Clinical Practice Research Datalink and linked hospital admission and cancer registry data. Diagnostic interval was defined as time from first presentation in primary care with a relevant sign/symptom to the diagnosis date. 14 comorbidities were classified as ten “competing demand“ and four “alternative explanation” conditions. Associations with diagnostic interval were investigated using multivariable linear regression models.ResultsComplete data were available for 11870 lung cancer patients. In adjusted analyses diagnostic interval was longer for patients with “alternative explanation” conditions, by 31 and 74 days in patients with one and ≥2 conditions respectively versus those with none. Number of “competing demand” conditions did not remain in the final adjusted regression model for diagnostic interval.ConclusionsConditions offering alternative explanations for lung cancer symptoms are associated with increased diagnostic intervals. Clinical guidelines should incorporate the impact of alternative and competing causes upon delayed diagnosis.</p

Genital modifications in prepubescent minors: when may clinicians ethically proceed?

When is it ethically permissible for clinicians to surgically intervene into the genitals of a legal minor? We distinguish between voluntary and nonvoluntary procedures and focus on nonvoluntary procedures, specifically in prepubescent minors ("children"). We do not address procedures in adolescence or adulthood. With respect to children categorized as female at birth who have no apparent differences of sex development (i.e., non-intersex or "endosex" females) there is a near-universal ethical consensus in the Global North. This consensus holds that clinicians may not perform any nonvoluntary genital cutting or surgery, from "cosmetic" labiaplasty to medicalized ritual "pricking" of the vulva, insofar as the procedure is not strictly necessary to protect the child's physical health. All other motivations, including possible psychosocial, cultural, subjective-aesthetic, or prophylactic benefits as judged by doctors or parents, are seen as categorically inappropriate grounds for a clinician to proceed with a nonvoluntary genital procedure in this population. We argue that the main ethical reasons capable of supporting this consensus turn not on empirically contestable benefit-risk calculations, but on a fundamental concern to respect the child's privacy, bodily integrity, developing sexual boundaries, and (future) genital autonomy. We show that these ethical reasons are sound. However, as we argue, they do not only apply to endosex female children, but rather to all children regardless of sex characteristics, including those with intersex traits and endosex males. We conclude, therefore, that as a matter of justice, inclusivity, and gender equality in medical-ethical policy (we do not take a position as to criminal law), clinicians should not be permitted to perform any nonvoluntary genital cutting or surgery in prepubescent minors, irrespective of the latter's sex traits or gender assignment, unless urgently necessary to protect their physical health. By contrast, we suggest that voluntary surgeries in older individuals might, under certain conditions, permissibly be performed for a wider range of reasons, including reasons of self-identity or psychosocial well-being, in keeping with the circumstances, values, and explicit needs and preferences of the persons so concerned. Note: Because our position is tied to clinicians' widely accepted role-specific duties as medical practitioners within regulated healthcare systems, we do not consider genital procedures performed outside of a healthcare context (e.g., for religious reasons) or by persons other than licensed healthcare providers working in their professional capacity.</p

Infrastructure alternatives in an incomplete modernity: a case study on the re-emergence of rainwater harvesting in Mexico City

Modern infrastructure networks make cities work by providing essential services such as water, sanitation and energy. However, across the urban Global South, universal and reliable services remain unachieved. What prevails instead is an ‘incomplete modernity’ expressed in unequal, segregated and often decaying networks. In this context, the present thesis addresses the emergence of rainwater harvesting (RwH) as an alternative infrastructure for household water supply in Mexico City, where the shortcomings of the local network have been catalogued as signs of a longstanding ‘water crisis’. In order to understand how new social and technological configurations are incorporated into contexts of incomplete modernity, data was collected through primary and secondary research (interviews, observations and documentary research) and analysed from a qualitative methodological approach. The results indicate that RwH has become a palliative niche for a dysfunctional socio-technical regime that systematically relegates marginalised populations from accessing adequate water services. The development of innovative RwH systems specifically designed for the needs of these populations has matched with concurrent narratives related to sustainability and social justice, contributing to the momentum of a niche space that is now being supported by the state through new policies and regulations. While these developments will not break the structural power arrangements behind the differential access to water in Mexico City, RwH has proven useful as a decentralised infrastructure that enables underserviced populations to improve their autonomy by reducing the time, effort and stress that implies getting water in conditions of disadvantage. The findings of this case study provide a fine-grained account of a contingent socio-technical change process happening in a Latin American megacity, adding to the emerging literature on urban transitions and transitions in the Global South.</p

The territorial scope of Australia's unfair contract terms provisions

Section 23 of the Australian Consumer Law, which is Schedule 2 of the Competition and Consumer Act 2010 (Cth), invalidates unfair terms in particular types of contract. Section 5(1) of the Act extends the application of the Australian Consumer Law to conduct outside Australia by (among others) corporations carrying on business within Australia. In Carnival plc v Karpik (Ruby Princess), the High Court of Australia held that section 5(1) applies to the unfair contract terms provisions without any further territorial limitation. The Court applied the provisions to a contract made in North America between a Canadian resident and a foreign company which was carrying on business in Australia through other transactions. This article investigates the territorial scope of the unfair contract terms provisions.</p

An ALS-associated mutation dysregulates microglia-derived extracellular microRNAs in a sex-specific manner

Evidence suggests the presence of microglial activation and microRNA (miRNA) dysregulation in amyotrophic lateral sclerosis (ALS), the most common form of adult motor neuron disease. However, few studies have investigated whether the miRNA dysregulation may originate from microglia. Furthermore, TDP-43, involved in miRNA biogenesis, aggregates in tissues of ∼98% of ALS cases. Thus, this study aimed to determine whether expression of the ALS-linked TDP-43M337V mutation in a transgenic mouse model dysregulates microglia-derived miRNAs. RNA sequencing identified several dysregulated miRNAs released by transgenic microglia, and a differential miRNA release by lipopolysaccharide-stimulated microglia, which was more pronounced in cells from female mice. We validated the downregulation of three candidate miRNAs, miR-16-5p, miR-99a-5p, and miR-191-5p by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and identified their predicted targets, which include primarily genes involved in neuronal development and function. These results suggest that altered TDP-43 function leads to changes in the miRNA population released by microglia, which may in turn be a source of the miRNA dysregulation observed in the disease. This has important implications for the role of neuroinflammation in ALS pathology and could provide potential therapeutic targets.</p

Characterisation of an XRCC1-deficient human neuronal cell model and investigating PARP1-specific inhibitors as a therapeutic approach

EMBARGOED - expected end date 20.02.2027</p

The impacts of reforming agricultural policy support on cereal prices: a CGE modeling approach

PurposeThis paper investigates the effects of the total abolition of all forms of agricultural subsidies to producers and border tariffs on the prices of staple cereals.Design/methodology/approachThe authors use the GTAP global economy-wide model and focus on 27 countries and 8 regions. The GTAP database that is used contains information on budgetary transfers to producers and market price support such as domestic price support, tariffs, export subsidies, quotas on exports or imports and other border measures.FindingsThe removal of subsidies is estimated to significantly increase the prices of wheat and other cereal grains in Japan, paddy rice in Malaysia and Indonesia, processed rice in Malaysia and Indonesia and wheat in Brazil and India. When border tariffs are removed, cereal prices are projected to fall in several countries, but the decline is more pronounced for wheat in Kenya and Japan, other cereal grains in South Korea and all staples in Nepal.Research limitations/implicationsThe alternative scenarios on the removal of agricultural subsidies in all agricultural sectors and the elimination of border tariffs are purely speculative as the analysis ignores important political economy considerations of agricultural and food policy reforms.Practical implicationsThe findings from this study point to the importance of implementing additional policy measures to mitigate the possible negative effect of repurposing the support to agriculture and ensure the food security and welfare of those categories of buyers who heavily depend on the price of staple food for their livelihoods.Social implicationsThis study’s findings confirm that the elimination of agricultural subsidies would impact global food security directly by making staple food less affordable to the poorest and indirectly by decreasing the available household budget for other presumably more nutritious food groups. Consequently, it is expected that these price increases could make segments of the world population poorer, particularly the net-food buyers due to a decline in their real income.Originality/valueThe authors assess the impact of removing the subsidies on the economy in a comprehensive way, particularly given the recent policy focus on net zero emissions and Sustainable Development Goals that include healthy foods. The authors also consider the counter effects of tariff reduction on this, which is price-reducing.</p

Challenges and prospects for a united opposition in the 2024 Lok Sabha election in India: an analytical perspective

The 2014 Lok Sabha election in India saw the BJP winning majority of seats with a relatively low national vote share of 31%. The BJP won another majority victory in the next Lok Sabha election in 2019 improving its tally of seats, but its vote share remained well short of majority at about 38%. Since the 2019 election, the party has won many state assembly elections and further strengthened its position as the dominant party at the national level. As we approach the 2024 Lok Sabha election, the Congress, the principal opposition party, and several other parties have initiated a major effort to forge electoral alliances with an objective of defeating the BJP. Using constituency level data, this paper provides an analytical perspective on the prospects and challenges for a united opposition to succeed in their efforts to counter the BJP. It finds that even if the opposition parties can put up a united front, it will not be easy to defeat the BJP in most of the seats the party won in 2014 and 2019. The paper concludes that the opposition parties would need both a high degree of unity and coordination across many states, as well as a significant vote swing against the BJP to have any chance of defeating it in 2024. Thus, it is doubtful whether merely forming an anti-BJP alliance, without a credible alternative narrative and policy agenda, can yield substantial electoral benefits for the opposition.</p

Efficient generation of magnetic-field gradients for microwave trapped ion quantum computing using soft ferromagnetic materials in a cryogenic system

EMBARGOED – expected end date 20.03.2027</p

The “stiff-necked parson” and the “stiff-necked” state: religious freedom and the protection of State power and authority

Constitutions are meant to endure, providing both stability and adaptability. Their public legitimacy depends on the ability of the courts and other interpreters to get this balance right. Why, then, has Canada’s constitution – only four decades old – produced so many surprises?Canada’s Surprising Constitution investigates unexpected interpretations of the Constitution Act, 1982 by the courts. In this illuminating collection of essays, leading scholars reflect on these surprising interpretations, focusing on fundamental freedoms; equality, Aboriginal, and language rights; structural features of the Charter; as well as the courts’ approach to the interpretation of the Constitution.The public legitimacy of the Constitution requires that it be seen as both relevant, as circumstances change, but also true to the values it embodies. The responsibility for getting this balance right lies not only with judges but also with legislatures, executives, scholars, advocates, and public interest organizations. The thoughtful work of this volume is crucial in identifying, accounting for, and – looking ahead – anticipating potential surprises. Its thorough analysis also offers a view of the Constitution in action.This wide-ranging collection will appeal to legal scholars and is essential reading for constituional experts. It will also find an audience amoung academics in political science and Canadian history.</p