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Gut microbiota (GM) affects muscle homeostasis, and growing evidence indicates dysbiosis of GM may be a contributing factor in the pathogenesis of dystrophies. Furthermore, GM metabolites can interact with DNA methylation. Facioscapulohumeral muscular dystrophy (FSHD) is the second common dystrophy with hypomethylation of DR1 and 5P regions of D4Z4 repeat on 4qter.
Objective:
Considering alteration of GM may be a contributing factor, we investigated (i) GM alterations and (ii) the correlation of microbial-derived free fatty acids (FFAs) with methylation of DR1 and 5P regions in FSHD.
Methods:
Twenty-eight FSHD patients and 28 gender-age-matched controls were included. GM characterisation was performed through 16S-rRNA sequencing. Methylation levels of DR1 and 5P regions were assessed by bisulphite sequencing. Faecal and circulating FFAs including short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs) and long-chain fatty acids (LCFAs) were analysed with gas chromatography-mass spectrometry.
Results:
Altered GM was observed in patients, along with distinct profiles of faecal and circulating SCFAs, MCFAs and LCFAs. DR1 and 5P regions exhibited significant hypomethylation in FSHD compared to control. Hypomethylation correlated with faecal and circulating FFAs in patients, while no correlation was identified in healthy controls. The severely affected patients exhibited a notable increase in the prevalence of Pasteurellaceae, while the FFA profile was similar among mild and severely affected patients. This is the first study revealing that FSHD patients showed compositional and functional GM dysbiosis. A strong association between proximal D4Z4 hypomethylation with microbial-derived SCFAs was identified.
Conclusion:
These findings suggest that GM modulation with its metabolites could be a promising strategy for interventions in FSHD management.
Eclipta [Eclipta prostrata (L.) L.] is an important tropical weed that has recently emerged as a problematic weed in dry direct-seeded rice (Oryza sativa L.) (DSR) fields in China. Understanding its seed germination biology and ecology is crucial for developing integrated weed management strategies in the DSR system. Laboratory experiments were conducted to investigate seed germination of E. prostrata seeds under varying environmental conditions. Germination was greatest under alternating temperature regimes of 25/15 to 40/30 C, whereas it wa-s significantly reduced at 20/10 C and completely inhibited at 15/5 C. Germination was also fully suppressed under continuous darkness, indicating strong light dependency. Eclipta prostrata seeds tolerated a broad range of pH values (4 to 10) with germination rates consistently greater than 95%. However, germination declined sharply under osmotic potentials, falling below 2% at −0.6 MPa, and being completely inhibited at −0.7 MPa. Seeds also showed moderate salt tolerance, with 50% inhibition at 150 mM NaCl and no germination at 300 mM NaCl. Exposure to radiant heat (>90 C for 5 min) prevented germination, suggesting residue burning may be an effective control measure. Seedling emergence was highest (100%) on the soil surface but declined steeply with increasing burial depth, with no emergence observed beyond 0.5 cm. Similarly, surface application of wheat (Triticum aestivum L.) straw residue (2 to 6 Mg ha−1) significantly reduced seedling emergence and biomass. These findings provide essential insights into E. prostrata germination ecology and offer practical implications for its integrated management in DSR systems.
We present a philosophically motivated framework for modelling moral agency. In addition to choosing strategies, agents in this framework choose among an appropriate exogenous set of moralities that depends on the context of the game. Further, agents can use mixed strategies to choose their degree of morality. We present two models to demonstrate the framework. In the first model, agents choose between empathy and selfishness while playing prisoner’s dilemma. In the second, agents choose between Kantian universalizing and selfishness while playing a public goods game. For both models, the degree of morality gets determined endogenously rather than assigned parametrically.
To compare the association of participation in Supplemental Nutrition Assistance Program (SNAP) alone v. in combination with Head Start (HS), Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) or both on household dietary environment (HDE) indicators: food security, nutrition security, healthfulness choice, dietary choice, perceived food store availability, utilisation barriers and healthy food access barriers in families with young children.
Design:
This study, part of SNAP-Ed Nebraska’s Needs and Assets Assessment ‘Healthy People, Healthy State’, utilised a cross-sectional design. HDE indicator means were compared across the federal assistance program (FAP) participation groups using multivariate ANCOVA, controlling for significant demographics, with Benjamini–Hochberg-adjusted P values compared with α = 0·05.
Setting:
Nebraska’s low-income households.
Participants:
Households (n 821) with at least one child aged 2–6 years participating in SNAP-only (n 257), SNAP + HS (n 349), SNAP + WIC (n 132) and SNAP + WIC + HS (n 83).
Results:
Compared with other groups, SNAP + HS reported comparatively higher levels of household food security, whereas SNAP + HS + WIC reported lower levels (P < 0·01). SNAP + HS also showed higher levels of nutrition security, dietary choices, perceived availability of healthy foods in stores, fewer healthy food access and utilisation barriers (P < 0·05).
Conclusions:
The findings support recent joint policy changes by Administration for Children and Families and Food and Nutrition Service, facilitating SNAP households’ access to HS. HS performance standards for nutrition and family engagement can serve as a model for creating healthy HDE. Future research should employ quasi-experimental or longitudinal designs to establish causal relationships between FAP participation and HDE outcomes.
Over 1% of the world’s population have been forcibly displaced. Asylum seekers and refugees (ASR) are at higher risk of serious mental illnesses. Despite a high need for care, little is known about the attitudes, knowledge and competencies of psychiatrists who may treat ASR subjects.
Aims
The study aimed to identify perceived gaps in psychiatric training that could help guide medical education and policymaking related to treating ASR mental health.
Method
We conducted the first national survey of UK-based psychiatrists to assess attitudes, knowledge and competencies around treating ASR subjects. The online survey was sent to all psychiatrists (N = 18 182) and registered trainees (N = 4700) on the Royal College of Psychiatrists databases in 2022. We used exploratory and confirmatory factor analyses to identify the optimal factor structure underlying the questionnaire. Variations in scores on extracted latent constructs by sociodemographic and clinical variables were explored using linear regression.
Results
Data from 609 psychiatrists (77%) and trainees (22%) were included in the final analysis. We identified four latent constructs concerning perceived knowledge, positive attitudes, negative attitudes and perceived distress. Only 42% of respondents felt they had sufficient knowledge to work competently with ASR subjects, and 34.7% found the work emotionally distressing. Greater knowledge predicted both more positive (β = 0.26, 95% CI: 0.20–0.33) and more negative (β = 0.17, 95% CI: 0.09–0.26) attitudes, and was associated with less self-reported distress among psychiatrists (β = –0.34, 95% CI: –0.43 to –0.21). Female psychiatrists reported more distress related to treating ASR subjects (β = 0.29, 95% CI: 0.14–0.44).
Conclusions
Less than half of psychiatrists in this survey believed they possessed adequate knowledge to treat ASR subjects, and some found working with such individuals distressing. Our results suggest that these issues could be mitigated by improving knowledge related to treating ASR subjects.
Finding the right balance between education and entertainment in science communication has always been a challenge. This essay argues that this balance has often been framed in terms of the correct proportion and use of animation and live-action footage in popular-science media. Clarifying the assumptions behind a century of concerns about animation and science, this historical case study examines the advisory board’s complaints about animation in the Bell System Science Series, which aired in the United States between 1956 and 1964. AT&T interrupted the series mid-stream by switching the creative team from Frank Capra and his production company to Owen Crump at Warner Bros. Studio. Capra’s use of animation in the series featured prominently in this decision. The historical record – as well as Capra’s and Crump’s different aesthetic choices about animation – tells us much about the board’s objections and how they were resolved in production. This essay examines the differences between the two parts of the series to uncover a course correction steered primarily by the scientific advisory board, which reveals a sometimes-fraught relationship between live-action footage and animation in science education that persists even today.
Nursing homes residents have a high prevalence of multidrug-resistant organism (MDRO) colonization. Recent trials demonstrated that decolonizing residents reduces infection. However, decolonization’s impact on environmental MDRO contamination is not well understood.
Methods:
We performed a 9-month pilot (3-month baseline, 3-month phase-in and 3-month intervention) in 3 nursing homes implementing routine chlorhexidine bathing/showering and nasal iodophor. We repeatedly tested for colonization via skin and nasal swabs for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum beta-lactamase producers (ESBLs), and carbapenem-resistant Enterobacterales (CRE). We also swabbed high-touch surfaces in rooms of MDRO carriers for MDRO fomite contamination.
Results:
Decolonization decreased the odds of MDRO colonization in nursing home residents by 55% (OR 0.45, P < 0.001, raw reduction from 46% (411/900) to intervention: 29% (262/900); colonization with MRSA, VRE, and ESBL all significantly decreased (P < 0.001). Among residents who remained colonized with any MDRO, 288/330 (87%) of high-touch bedroom objects were colonized with ≥1 MDRO. In a multivariable analysis, MDRO fomite contamination in rooms of MDRO carriers was associated with antibiotic use (OR = 1.54 [95% CI: 1.19–1.98], wound presence (OR = 1.34 (95% CI: 1.02–1.77), and specific fomites such as bedside table/bedrails (OR = 12.7 (95% CI: 9.37–17.25), but not the intervention period (OR = 1.02 [0.81–1.27]).
Conclusion:
Routine chlorhexidine bathing and nasal iodophor significantly reduced MDRO body colonization among nursing home residents. However, in rooms of residents who remained MDRO carriers, environmental contamination was unchanged during the decolonization intervention. Efforts to ensure fomite surface clearance in rooms of MDRO carriers may be key to reducing environmental MDRO spread.
Cannabis use is elevated in youth with depression and attention-deficit/hyperactivity disorder (ADHD), but drivers of this increase remain underexplored. The self-medication hypothesis suggests cannabis is used by patients for mood regulation, a common difficulty in ADHD and depression. This study aimed to examine associations between mood instability and cannabis use in a large, representative clinical cohort of adolescents diagnosed with ADHD and/or depression.
Methods
Natural language processing (NLP) approaches were utilised to identify references to mood instability and cannabis use in the electronic health records of adolescents (aged 11–18 years) with primary diagnoses of ADHD (n = 7,985) or depression (n = 5,738). Logistic regression was used to examine mood instability as the main exposure for cannabis use in models stratified by ADHD and depression.
Results
Mood instability was associated with a 25% higher probability of cannabis use in adolescents with ADHD compared to those with depression. Following adjustment for available sociodemographic and clinical covariates, mood instability was associated with increased cannabis use in both ADHD (aOR: 1.61 [95% CI: 1.41–1.84]) and depression (aOR: 1.38 [95% CI: 1.21–1.57]) groups.
Conclusions
This was the first study to explore the differential impact of mood instability on adolescent cannabis use across distinct diagnostic profiles. NLP analysis proved an efficient tool for examining large populations of adolescents accessing psychiatric services and provided preliminary evidence of a link between mood instability and cannabis use in ADHD and depression. Longitudinal studies using direct measures or tailored NLP techniques can further establish the directionality of these associations.
Power outages can lead to food-borne and water-borne illness risks for consumers if proper protective measures are not taken at home. The purpose of this study was to understand the behaviors of Canadians related to food and water safety preparedness at home during power outages and floods.
Methods
A qualitative descriptive study was conducted, consisting of 6 virtual focus groups, each with 8 people, in July 2023. Participants were selected from geographically dispersed locations in Ontario, Canada that had experienced power outages due to weather events. Thematic analysis was conducted to generate key themes.
Results
Four themes were generated related to participants’ food and water safety preparedness: 1) trusted information sources and lived experiences; 2) support and resources; 3) factors beyond one’s control; and 4) differences in psychosocial determinants.
Conclusions
Effective risk communication targeting misconceptions, incentivization programs, and community resilience planning may help prevent or reduce enteric illness risks during such emergencies.
The Deerni copper deposit is one of the largest in Qinghai province, China, with proven copper reserves of 0.556 Mt. To explore new copper orebodies, we conducted a geological study at western Deerni focusing on hydrothermal alterations and ore-controlling structures. Field investigation shows that the deposit is hosted mainly within the central segment of the Deerni ophiolite. Additional hosts include Lower-Permian slate, limestone, gabbro and volcanic rock, as well as the contact zone between granite and slate. Such observations indicate that the Deerni copper deposit is not only associated with the ophiolite, but its formation is also controlled by faults. Alterations including serpentinization, carbonatization, silicification and malachite, and magnetite mineralization occurred along fractures within the wall rocks and surrounding strata. This means the alteration post-dated structural activity that affected the Lower Permian strata in the region. The Deerni copper deposit is controlled by the NW-striking faults. This is evidenced by (1) slate fragments and breccias within the orebodies, (2) saw-toothed boundaries between the orebodies and host rocks, (3) copper ore veinlets and (4) striations and step patterns on the orebody surface and hanging-wall-hosted quartz veins. Mineralization controlled by NW-trending faults suggests a major orebody (‘No. 2’) likely extends to either northwest or southeast. Field investigations along with geophysical and geochemical data, thus predicted the presence of concealed copper orebodies in western Deerni. Subsequent drilling projects have verified this prediction and revealed three concealed orebodies with widths of 7.15–13.87 m and Cu grade of 1.00–11.34 wt.%, adding 10,000 tonnes to the copper reserves.
Current scholarship conceives of courts as victims or targets of populist authoritarians. But can empowered courts facilitate democratic backsliding? This article develops a new framework for understanding the approaches judiciaries take when tackling political corruption and argues that when judges attempt to replace ‘corrupted’ elected branches as the primary representative institution, their actions and rhetoric can enable populist authoritarians to seize power, raising the risk of democratic backsliding. I combine jurisprudence, newspaper archives and interviews to trace the process through which Pakistan’s Supreme Court, committed to playing a representation-replacement role, enabled the military-backed populist Pakistan Tehreek-e-Insaaf to come to power in 2018, and use its powers to reverse Pakistan’s democratic transition. I also probe the political impact of anti-corruption jurisprudence in more established democracies. In doing so, I introduce a typology for understanding approaches courts take when combating corruption, and highlight the threat to democracy that can emerge from judiciaries.
Can we quantify over absolutely every set? Absolutists typically affirm, while relativists typically deny, the possibility of unrestricted quantification (in set theory). In the first part of this article, I develop a novel and intermediate philosophical position in the absolutism versus relativism debate in set theory. In a nutshell, the idea is that problematic sentences related to paradoxes cannot be interpreted with unrestricted quantifier domains, while prima facie absolutist sentences (e.g., “no set is contained in the empty set”) are unproblematic in this respect and can be interpreted over a domain containing all sets. In the second part of the paper, I develop a semantic theory that can implement the intermediate position. The resulting framework allows us to distinguish between inherently absolutist and inherently relativist sentences of the language of set theory.
With formal international organizations (IOs) facing gridlock and informal IOs proliferating, cooperation in the twenty-first century looks different than it did in previous eras. Global governance institutions today also face additional challenges, including a fragmented information environment where publics are increasingly vulnerable to misinformation and disinformation. What do these trends portend for international politics? One way to answer this question is to return to a core ingredient of a well-functioning IO—information provision—and ask how such changes affect efficiency. Viewed through this lens, we see decline in some arenas and adaptation in others. Formal IOs are struggling to retain relevance as their weak policy responses and ambiguous rules create space for competing signals. The proliferation of informal institutions, on the other hand, may represent global governance evolution, as these technocratic bodies are often well-insulated from many political challenges. Yet even if global governance retains functionality, the legitimacy implications of such trends are troubling. IO legitimacy depends in part on process, and from this standpoint, the informational gains of informal governance must be weighed against losses of accountability and transparency. Ultimately, evaluating the normative implications of these trends requires making judgments about the preferred legitimizing principles for global governance.
We investigate a Leslie-type prey–predator system with an Allee effect to understand the dynamics of populations under stress. First, we determine stability conditions and conduct a Hopf bifurcation analysis using the Allee constant as a bifurcation parameter. At low densities, we observe that a weak Allee effect induces a supercritical Hopf bifurcation, while a strong effect leads to a subcritical one. Notably, a stability switch occurs, and the system exhibits multiple Hopf bifurcations as the Allee effect varies. Subsequently, we perform a sensitivity analysis to assess the robustness of the model to parameter variations. Additionally, together with the numerical examples, the FAST (Fourier amplitude sensitivity test) approach is employed to examine the sensitivity of the prey–predator system to all parameter values. This approach identifies the most influential factors among the input parameters on the output variable and evaluates the impact of single-parameter changes on the dynamics of the system. The combination of detailed bifurcation and sensitivity analysis bridges the gap between theoretical ecology and practical applications. Furthermore, the results underscore the importance of the Allee effect in maintaining the delicate balance between prey and predator populations and emphasize the necessity of considering complex ecological interactions to accurately model and understand these systems.
With fintech investment apps providing convenience and round-the-clock access to financial markets on the go, investors are becoming more active in managing their financial lives through smartphones and other mobile devices. However, fintech investing’s role in the financialization of everyday life remains unclear. Combining insights from Foucauldian governmentality and Science and Technology Studies (STS), this article positions fintech brokerage apps as both neoliberal tools in governing investor conduct and as agencements in reconfiguring financial subjectivities. Based on a survey and interviews with lay investors in Singapore, the findings reveal that fintech investors use app-based brokerages as a tool to invest conveniently and at low cost. However, users themselves may resist the financial subjectivities promoted by fintech investing, driven by skepticism towards gamified and other algorithmic app features. They are also motivated by feelings of uncertainty towards fledgling fintech startups and difficulties in their interactions with the app user interface. To mitigate uncertainty, investors adopt various tactics to protect their portfolios.
Evaluation supports the translation of knowledge into practice by systematically assessing what works, for whom, and under what conditions. It generates evidence to guide improvements, inform decision-making, and identify how programs, research studies, or interventions should be scaled. Within a Clinical and Translational Science Award (CTSA) hub, evaluation is typically focused on internal evaluation and administrative functions. However, expanding evaluation to also support efforts based outside of a CTSA hub (i.e., to the larger institution and community), akin to other CTSA cores and services, can support overarching translational goals. This paper outlines the process and benefits of institutionalizing a partnership between clinical and translational science and social science to provide expertise, resulting in evaluation as a translational resource. Herein, we describe developing the Duke Office of Evaluation and Applied Research Partnership, an organizational unit that, by bridging a university’s CTSA hub and interdisciplinary social science institute, expanded the scope and capacity of evaluation to advance clinical and translational science. We outline the specific activities supported by this initiative, facilitators involved in its establishment, and barriers to implementation and success. This model and lessons learned can inform broader opportunities to leverage multidisciplinary evaluation expertise to support clinical and translational science.
This essay reveals the institutional dynamics of hard times in the issue area of human rights. I show that the human rights regime has developed innovative-yet-informal institutions like individuals-based coalitions for the international protection and progressive development of human rights. Yet, as these informal institutions function very much based on, first, the interpersonal relations among their members, and, second, legal instruments that require no further consent by states, the advocacy success of liberal human rights defenders has, in turn, provided a playbook for advocates and governments from the illiberal end of the ideology spectrum. In addition, new human rights advocates in the form of certain private law firms have entered the UN through their pro bono work. They promise valuable resources for a crisis-ridden system but often represent corporate clients with conflicts of interest. Given the imminent risk of ideological capture and illiberal interests in human rights paralyzing the system, I reemphasize the need for regulating access to the human rights global governance institutions.
Physiologic changes in the peripartum period put women with CHD at increased risk for morbidity. This study examines factors associated with peripartum complications and length of stay compared to patients without CHD.
Methods:
This single-institution retrospective case-control study included women with CHD (2000–2017) and a control population without CHD. A review of clinical and echocardiographic data was used to assign baseline characteristics, disease severity, and adverse outcomes. Primary outcomes were composite variables of cardiac and obstetric adverse events, along with peripartum length of stay. The relationship between maternal CHD, baseline characteristics, and peripartum adverse events was evaluated by multivariable regression.
Results:
The cohort and control groups included 162 deliveries among 113 women and 321 deliveries among 321 women, respectively. Cardiac complications, including arrhythmia, heart failure, pulmonary oedema, and thromboembolic events, occurred in 8.6% of the cohort (RR 2.52, 95% CI 1.17–5.42), with the most common event being arrhythmia. Obstetric events, such as caesarean delivery, assisted vaginal delivery, preterm birth, and pre-eclampsia, occurred in 67.9% versus 56.1% in the control group (RR 1.21, 95% CI 1.05–1.40). In multivariable models, increasing age was associated with increased composite cardiac events. Length of stay was longer in the cohort group (p < 0.001) and significantly associated with modified World Health Organization classification (p = 0.016).
Conclusions:
Women with CHD experience increased cardiac and obstetric morbidity compared to controls during peripartum admission. Those with CHD have longer hospital stays around delivery, which is associated with disease severity.
When Johann Wolfgang von Goethe coined the term ‘world literature’ (Weltliteratur) in 1831, he made it clear that this epoch had begun in his time and, like every epoch, would come to an end. This article is about the end of that epoch and the future of comparative literature in an era after the end of world literature. It is easy to see that we are now living in the era of world literatures. In a world in which, at first sight, literature counts for less and less, it must emphasize its unique selling point: it is the only form of human discourse that has actively expanded the realm of knowledge over several millennia. Only comparative literature, which draws on the most diverse literatures of the world, is able to bring this uniqueness into focus and highlight its social relevance.