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Predictive biomarkers can identify patients who are more likely to respond to immunotherapy, which can guide treatment decisions. The objective of this study was to assess the potential value of predictive biomarkers in advanced NSCLC patients to guide the development of cost-effective biomarkers in this field.
Methods
A decision analytical model was constructed to compare theoretical new strategies with biomarkers to the current standard of care. The analysis was performed for three different patient groups based on PD-L1 status. Differences in health outcomes (QALYs) and costs were assessed between the current practice and these biomarker strategies.
Results
Omitting immunotherapy in NSCLC patients with a PD-L1 score < 1 percent or between 1 and 49 percent, and a negative biomarker test, could potentially reduce healthcare costs significantly a small loss in QALYs. In these groups, a biomarker test is potentially cost-effective as the incremental cost-effectiveness ratio largely exceeds a willingness-to-accept threshold of €80,000 saved per QALY lost. For patients with a PD-L1 score > 50 percent, a considerable QALY gain can potentially be realized by adding chemotherapy to patients with a negative biomarker test. However, this comes at a significant increase in costs and appears not to be cost-effective.
Conclusions
In general, predictive biomarkers seem to have the potential to increase the cost-effectiveness of treatment with immunotherapy in patients with advanced NSCLC. Optimal positioning of a biomarker depends on the weighing between health impact and costs.
Workplace exclusion – often subtle and difficult to detect – significantly contributes to employee disengagement and turnover, costing US organizations over $1 trillion annually. This study examines how exclusionary behaviors (EBs) influence turnover intentions (TOIs) through disruption of psychological needs, using Rock’s SCARF model (Status, Certainty, Autonomy, Relatedness, Fairness) and self-determination theory. A two-wave survey of full-time US employees (N = 277) assessed EB, SCARF-based need satisfaction, and TOI. Partial least squares structural equation modeling revealed that EB significantly undermines all five SCARF domains, but only fairness and status mediated the EB–TOI link. Certainty, autonomy, and relatedness did not have significant effects. These findings suggest turnover risk intensifies when employees feel unfairly treated or socially devalued, rather than merely disempowered or disconnected. The study advances theoretical integration between SCARF and SDT and offers practical guidance for managers seeking to reduce attrition by fostering inclusive, respectful, and psychologically safe workplace environments.
Everyday understanding takes empathy to be not just emotional mirroring with a specific etiology, but also a form of feeling for, or on behalf of, another. This article proposes an analysis of that for-relation. The analysis begins with the phenomenon of acting on behalf, which is then used as a template for an analysis of generic on behalfness, applicable to both action and emotion. The key to the relation turns out to be an agent’s espousal of a target’s goal, in light of which the agent acquires reasons for acting or feeling.
Women remain underrepresented in National Institutes of Health (NIH) study sections, panels of scientists who review grant applications to inform national research priorities and funding allocations. This longitudinal, retrospective study examined the representation of women on study sections before and during the COVID-19 pandemic. Overall, 16,902 reviewers served on 1,045 study sections across 2019, 2020, and 2021, of which 40.1% (n = 6,786) were women. The likelihood of reviewers being women significantly increased from 2019 to 2021, except among chairpersons. Understanding the representation of scientists influencing NIH grant decisions is important to ensuring scientific discovery that meets the nation’s pluralistic needs.
Decades of systemic oppression in Syria, from the 1963 state of emergency to the 2011–2024 conflict, have caused widespread psychological devastation. Arbitrary imprisonment, torture and sexual violence have been systematically weaponised. Following the fall of the Syrian regime in December 2024, freed political prisoners face severe mental health challenges due to years of inhumane conditions and trauma. This paper emphasises the urgent need for specialised mental health interventions and outlines evidence-based pathways to healing. A coordinated, multi-tiered response, integrating local and international efforts, is essential to prioritise mental health aid, restore dignity and support survivors in rebuilding their futures.
We explore the drawing of an axisymmetric viscoelastic tube subject to inertial and surface tension effects. We adopt the Giesekus constitutive model and derive asymptotic long-wave equations for weakly viscoelastic effects. Intuitively, one might imagine that the elastic stresses should act to prevent hole closure during the drawing process. Surprisingly, our results show that the hole closure at the take-up point is enhanced by elastic effects for most parameter values. However, the opposite is true if the tube has a sufficiently large hole size at the inlet nozzle of the device or if the axial stretching is sufficiently weak. We explain the physical mechanism underlying this phenomenon by examining how the second normal stress difference induced by elastic effects modifies the hole evolution process. We also determine how viscoelasticity affects the stability of the drawing process and show that elastic effects are always destabilising for negligible inertia. On the other hand, our results show that if the inertia is non-zero, elastic effects can be either stabilising or destabilising depending on the parameters.
Russian nation-building policy has often been described as ambiguous, blending a rhetorical commitment to the state’s multinational character together with more exclusionary rhetoric and policies. Drawing from original survey questions on national identity commissioned in December 2022, I find that Russian citizens continue to endorse a multinational vision of the Russian state during wartime. Respondents are simultaneously likely to exclude minorities from being fully considered as “true Rossians” [istinnye rossiiane], while socioeconomic and political factors are meaningfully associated with these patterns. In line with previous scholarship, these findings underscore the blurriness of the russkii/rossiiskii distinction in practice: just as russkii should not always be interpreted as an exclusively ethnic term, rossiiskii should not be seen as a non-ethnic category, either. The findings in the Russian case carry implications for understanding how nation-builders in multiethnic contexts may seek to cater to ethnic majorities while simultaneously signaling commitments to ethnic diversity.
We investigate the motion of weakly negatively buoyant spheres settling in surface gravity waves using laboratory experiments. The trajectories of the settling spheres are tracked over most of the water depth with simultaneous measurements of the background fluid flow. These experiments are conducted in the regime relevant for environmental and geophysical applications where both particle inertia and fluid inertia are important. Using these data, we show that the sphere motion is well described by the kinematic sum of the undisturbed fluid velocity and the particle terminal settling velocity as long as the fluid inertia is not too large. We show how this result can be understood in the context of an ad hoc Maxey–Riley–Gatignol-type equation where the drag on the particle is given by the Schiller–Naumann drag correlation. We also evaluate whether inertial particles experience enhanced settling in waves, finding that measurement uncertainties in the particle terminal settling velocity and the presence of Eulerian-mean flows do not allow the small percentage increase in the settling velocity to be measured. When the fluid inertia becomes large enough, we observe path instabilities caused by particle wake effects in both quiescent and wavy conditions. However, the particle velocity fluctuations associated with the path instabilities are unaffected by the background flow. The minimal influence of the wavy flow on the particle path instabilities is thought to be due to the large-scale separation between the waves and the particle.
Plastic pollution poses a critical and escalating threat to human health across the full life cycle of plastics. Scientific evidence links exposure to plastics and associated pollution to a range of adverse health outcomes. Vulnerable populations, particularly those in informal settlements and low-resource settings, bear disproportionate health burdens. The UN Global Plastics Treaty presents a vital opportunity to embed human health protection at its core. To be effective, the treaty must apply the precautionary principle, recognise and address health impacts across the full plastics life cycle, and phase out the most harmful plastic products and chemicals. The treaty must be adaptable to emerging scientific evidence, and inclusive of equity and human rights to protect present and future generations. Inclusion of a dedicated health article, alongside specific health considerations across a number of key provisions in the treaty text, and consideration of the right to health throughout all aspects of the treaty, will be essential for delivering on the treaty’s objective to protect human health and the environment from plastic pollution.
Updated estimates of 2024 ice thickness, the surface elevation losses in the last years and simulations of mass balance and evolution (using the Instructed Glacier Model) for the three largest Pyrenean glaciers strongly suggest that by 2034 the Pyrenees will be ice-free. If extreme summers like 2022 and 2023 recur, this could happen even earlier. We show that by 2030, 94% (from 0.22 to 0.01 km2) of the ice in Monte Perdido, 91% (from 0.22 to 0.05 km2) of the ice in Ossoue and 79% of the ice in Aneto (from 0.34 to 0.06 km2) will have melted under the RCP4.5 scenario; these numbers are 83%, 72% and 57% under a committed ice loss scenario, meaning that only 0.05, 0.12 and 0.12 km2 of ice will remain, respectively. In 2034, most likely they will have completely disappeared under the three considered scenarios (RCP 4.5, ‘committed ice loss’ and extreme 2022 year in a loop). The loss of these glaciers is a harbinger for what will happen in many other mountain regions.
How can everyday entertainment shape gender politics in authoritarian regimes? Despite autocrats’ heavy control over media, political scientists studying authoritarianism largely neglect television programming. Particularly surprising given their target demographics, cooking shows are absent in political science gender analyses. Drawing from over 600 hours of Turkish cooking show content, I introduce conservative gender edutainment to capture the mechanisms by which TV shows facilitate authoritarian regimes’ gender construction projects. Using quantitative analysis of cooking show content, I first identify two complementary pedagogies — modeling and othering — that respectively teach adherence to, and vilify deviation from, regime-specified behavioral norms. I then use intertextual analysis to extract content that engagingly instructs viewers in the ideal woman in “New Turkey,” the neoconservative vision articulated by Turkey’s ruling (Justice and Development Party) AKP. Findings provide novel insight into vernacular channels of gender construction, while underscoring the added value TV-as-data holds for studies of identity politics in authoritarian contexts.
Over the past 20–30 years, women’s parties have consistently formed across Europe, aiming to improve women’s substantive representation by politicizing gender issues. Despite their potential impact on the policy agenda, empirical knowledge of the full range and scope of issues these parties mobilize is limited. This paper presents a novel mixed-method text analysis of the issue concerns in an original dataset of European women’s parties’ manifestos spanning a 30-year period. I find that parties across contexts share concerns in social justice and social policy. However, two subtypes of women’s party can be differentiated based on issue focus and framing. Essentialist women’s parties predominantly represent women’s material interests, whereas feminist parties additionally tackle structural gender inequality issues, including gender-based violence and human security. These findings provide a foundation for incorporating women’s parties into growing research on party competition over gender issues.
We strengthen two results of Moretó. We prove that the index of the Fitting subgroup is bounded in terms of the degrees of the irreducible monomial Brauer characters of the finite solvable group G and it is also bounded in terms of the average degree of the irreducible Brauer characters of G that lie over a linear character of the Fitting subgroup.
In the second part of this series of papers, we address the same evolution problem that was considered in part 1 (see [16]), namely the nonlocal Fisher-KPP equation in one spatial dimension,
\begin{equation*} u_t = D u_{xx} + u(1-\phi *u), \end{equation*}
where $\phi *u$ is a spatial convolution with the top hat kernel, $\phi (y) \equiv H\left (\frac {1}{4}-y^2\right )$, except that now we modify this to an associated initial-boundary value problem on the finite spatial interval $[0,a]$ rather than the whole real line. Boundary conditions are required at the end points of the interval, and we address the situations when these are of either Dirichlet or Neumann type. This model is a natural extension of the classical Fisher-KPP model, with the introduction of the simplest possible nonlocal effect into the saturation term. Nonlocal reaction-diffusion models arise naturally in a variety of (frequently biological or ecological) contexts, and as such it is of fundamental interest to examine their properties in detail, and to compare and contrast these with the well known properties of the classical Fisher-KPP model.
To determine the feasibility of implementing a facility-based breastfeeding counselling (BFC) mentorship programme and its effect on mentee confidence and client perceptions of BFC.
Setting:
Mbagathi County Referral Hospital in Nairobi, Kenya.
Participants:
Health facility management, health workers (twenty-one mentees and seven mentors), 120 pregnant women in the third trimester who attended an antenatal care (ANC) appointment at Mbagathi Hospital and reported receiving BFC during a visit in the 2 weeks prior and 120 postpartum women in the postnatal care ward who delivered a full-term infant and reported receiving BFC.
Design:
Mixed-methods study incorporating online surveys, client exit interviews, key informant interviews and focus group discussions. The 4-month intervention involved facility-wide orientations, selection and training of mentors, assigning mentees to mentors and implementing mentorship activities.
Results:
The programme successfully maintained 90·5 % mentee retention (19/21) over 4 months. At baseline, mentees demonstrated high knowledge (94 % questions answered correctly), which was maintained at endline (92 %). Mentees showed significant improvement in confidence counselling on breastfeeding and infant feeding (67 % at baseline v. 95 % at endline, P = 0·014). The percentage of ANC clients who felt BFC gave them more knowledge increased from 73 % to 97 % (P < 0·001). Among postnatal care clients, those reporting friendly treatment increased from 89 % to 100 % (P = 0·007), verbal mistreatment declined from 7 % to 0 % (P = 0·044) and those feeling discriminated decreased from 11 % to 2 % (P = 0·03). Key enablers included administrative support, structured mentorship tools and peer learning communities. Implementation barriers included scheduling conflicts, staff shortages and high patient volumes.
Conclusions:
BFC mentorship was feasible in this setting and was associated with improved health worker confidence in BFC. The programme can be successfully implemented with supportive facility leadership, well-matched mentors and mentees and adaptable mentorship approaches.
LGBTQ+ people remain underrepresented in politics, leading scholars to examine a variety of barriers to office. Based on work on women in politics, this paper focuses on one possible barrier: political finance. Is there a political financing gap between straight cisgender and LGBTQ+ candidates? Are there inequalities among LGBTQ+ candidates? If so, what explains them? This article explores these questions by combining a dataset of out LGBTQ+ candidates in the 2015–21 federal elections with political donations data from Elections Canada. When we examine bivariate financing gaps, we find LGBTQ+ candidates receive less money than their straight cisgender counterparts. These gaps are gendered: queer cisgender women, transgender, and nonbinary candidates receive the least money. When we adjust for other variables, we still find LGBTQ+ candidates in the Conservative Party and transgender and nonbinary candidates across parties receive less money. This article contributes to work on gender and identity in campaign finance and LGBTQ+ representation.