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Under the Universal Health Care Act of the Philippines, all health technologies should undergo health technology assessment. This manuscript details the process of the development of the Philippine guidance document for the use of real-world evidence (RWE) in the clinical evaluation of health technologies.
Methods
This study consisted of two phases. Phase 1 was a comprehensive, systematic review of all available HTA methods guides and literature related to the use of RWE in the clinical evaluation of health technologies. Based on the results of the review, a draft HTA methods guide on the use of RWE was created. Phase 2 was a validation study by expert consultation through key informant interviews (KIIs), and pilot assessment of the methods guide.
Results
Seventy-nine articles and nine guidance papers were included, with pertinent information extracted and organized into sections. The first draft covered definitions of RWE, guidance for RWE utilization, scoping and selecting RWE, critical appraisal, data extraction, and synthesis and analysis of RWE. Changes were made to this draft based on the KIIs and pilot assessment results to produce the final output of the methods guide.
Conclusions
This document describes the process of creating a Philippine guidance document that covers the definition of RWE and the appropriate methods for conducting systematic search, screening, critical appraisal, data extraction, data analysis, and synthesis of RWE.
Severe dilated cardiomyopathy in children may uncommonly be caused by abnormal loading conditions such as mid-aortic pathology and renal artery stenosis. Refractory hypertension and left ventricular dilatation with hypertrophy are important clues to reversible causes. We present a case of dilated cardiomyopathy in a child secondary to mid-aortic syndrome with renal artery stenosis.
We build on a 1990 paper of Bukovský and Copláková-Hartová. First, we remove the hypothesis of ${\mathsf {CH}}$ from one of their minimality results. Then, using a measurable cardinal, we show that there is a $|\aleph _2^V|=\aleph _1$-minimal extension that is not a $|\aleph _3^V|=\aleph _1$-extension, answering the first of their questions.
The goal of this chapter is to explain the normative force of personal projects and the project-dependent reasons they generate. Scheffler argues that it is not wrong to ignore project-dependent reasons. I point to three considerations that aim to show, pace Scheffler, that it is wrong to simply ignore the project-dependent reasons we once acknowledged. First, it is a condition for valuing a particular project that we have reasons to continue to respond to project-dependent reasons, even in cases where the project has been completed, where circumstances have forced us to abandon it, or where we have become less prone to value the project positively. Second, it is the fact of having once attained meaning in our lives by valuing a particular project that explains why we face additional reasons to sustain the project and to continue to respond to the project-dependent reasons we once acknowledged. Third, to the extent that a particular project accounts, in part at least, for our normative identity, and provided that it is valuable to thereby have conditions for having reasons at all, we have a further explanation of why project-dependent reasons carry a particular normative force for us to continue to value that project.
This article examines the politics of restitution within the Black Atlantic through the case of the Restitution Study Group’s legal challenge to the Smithsonian Institution’s return of Benin bronzes to Nigeria. While most scholarship frames restitution as a struggle between Western museums and postcolonial states, this article shifts the lens to intra-Black debates that complicate inherited frameworks of return, foregrounding the unresolved legacies of slavery and the claims of Black American and broader diasporic communities. At the same time, it situates these debates within the larger global landscape in which Western institutions and nation-states continue to define the terms and tempo of restitution. By challenging the assumption that restitution is solely a matter between source nations and former colonial powers, the Restitution Study Group brings attention to how African elites’ historical participation in the transatlantic slave trade and the ongoing marginalization of diaspora communities shape contemporary claims. The article also places these interventions alongside disputes within Nigeria over custodianship between the federal government, Edo State, and the Benin royal court. By tracing these overlapping histories, ethical claims, and political stakes, the article argues that returns of looted artifacts are not simply acts of restitution, but processes of decolonial repair that reconfigure authority, belonging, and historical responsibility across diasporic and national contexts.
Vertically symmetric alternating sign matrices (VSASMs) of order $2n+1$ are known to be equinumerous with lozenge tilings of a hexagon with side lengths $2n+2,2n,2n+2,2n,2n+2,2n$ and a central triangular hole of size $2$ that exhibit a cyclical as well as a vertical symmetry, but finding an explicit bijection proving this belongs to the most difficult problems in bijective combinatorics. Towards constructing such a bijection, we generalize the result by introducing certain natural extensions for both objects along with $n+3$ parameters and show that the multivariate generating functions with respect to these parameters coincide. This is a significant step from a constant number of equidistributed statistics to a linear number of statistics in n. The equinumeracy of VSASMs and the lozenge tilings is then an easy consequence of this result, which is obtained by specializing the generating functions to signed enumerations for both types of objects and then applying certain sign-reversing involutions. Another main result concerns the expansion of the multivariate generating function into symplectic characters as a sum over totally symmetric self-complementary plane partitions, which is in perfect analogy to the situation for ordinary ASMs where the Schur expansion can be written as a sum over totally symmetric plane partitions. This is exciting as it is reminiscent of the well-known Cauchy identity, and the Cauchy identity does have a bijective proof using the Robinson-Schensted-Knuth correspondence, and thus the result raises the question of whether there is a variation of the Robinson–Schensted–Knuth correspondence that does eventually lead to a bijective proof.
Building on the correspondence between finitely axiomatised theories in Łukasiewicz logic and rational polyhedra, we prove that the unification type of the fragment of Łukasiewicz logic with $n\geqslant 2$ variables is nullary. This solves a problem left open by V. Marra and L. Spada [Ann. Pure Appl. Logic 164 (2013), pp. 192–210]. Furthermore, we refine the study of unification with bounds on the number of variables. Our proposal distinguishes the number m of variables allowed in the problem and the number n in the solution. We prove that the unification type of Łukasiewicz logic for all $m,n \geqslant 2$ is nullary.
This Element explores misinformation as a challenge for democracies, using experiments from Germany, Italy, and the UK to assess the role of user-generated corrections on social media. A sample of more than 170,000 observations across a wide range of topics (COVID, climate change, 5G etc.) is used to test whether social corrections help reduce the perceived accuracy of false news and whether miscorrections decrease the credibility of true news. Corrections reduce the perceived accuracy of misinformation, but miscorrections can harm perceptions of true news. The Element also assesses the mechanisms of social corrections, finding evidence for recency effects rather than systematic processing. Additional analyses show the characteristics of individuals who have more difficulties identifying false news. Survey data is included on characteristics of people who write comments often. The conclusion highlights that social corrections can mislead, but also work as remedy. The Element ends with best practices for effective corrections.
Developing therapies for rare diseases is challenging due to limited evidence and high degrees of uncertainty regarding the value of new treatments. Clinical expert judgment can inform modeling assumptions and address areas of uncertainty in reimbursement submissions. As current protocols do not adequately address the challenges faced in rare diseases, this research aimed to generate recommendations for the collection and reporting of clinical expert judgment in rare diseases.
Methods
An international group of industry, payer, and patient experts with a background in rare diseases participated in a roundtable meeting, which aimed to identify practical challenges in and solutions for gathering clinical insights to aid reimbursement decisions for rare disease therapies. Recommendations were cocreated through iterative discussions and group agreement.
Results
Developers should proactively identify uncertainties that expert judgment can address, in parallel with early evidence generation planning. Expert judgment method(s) depend on the uncertainties, with those key to decision-making requiring more robust and time-intensive methods. For highly complex and uncertain topics, methods should facilitate consensus building and expression of diverse views. Given the scarcity of rare disease experts, a high time burden falls on a few experts. Developers should engage diverse stakeholder groups to integrate broader clinical perspectives and reduce reliance on specific individuals while approaching conflicts of interest pragmatically and transparently.
Conclusions
These recommendations create a blueprint for developers of rare disease therapies to conduct high-quality clinical expert judgment studies. Hence, developers can present more robust evidence to inform key areas of uncertainty in reimbursement decisions, where empirical evidence is unavailable.
The temporal contrast requirements for high-power laser pulses have become increasingly stringent with rising irradiance levels. Over the past decade, in addition to discrete pre-pulses, spatiotemporal pulse pedestals have attracted significant attention as a major limiting factor for contrast quality in chirped-pulse amplification systems, primarily caused by imperfections in their stretching and compression optics. In this work, we present the first direct high-resolution single-shot measurement of these contributions in the spatiotemporal domain using an imaging spectrometer in combination with a two-dimensional self-referenced spectral interferometer.
Let $K^r_n$ be the complete $r$-uniform hypergraph on $n$ vertices, that is, the hypergraph whose vertex set is $[n] \, :\! = \{1,2,\ldots ,n\}$ and whose edge set is $\binom {[n]}{r}$. We form $G^r(n,p)$ by retaining each edge of $K^r_n$ independently with probability $p$. An $r$-uniform hypergraph $H\subseteq G$ is $F$-saturated if $H$ does not contain any copy of $F$, but any missing edge of $H$ in $G$ creates a copy of $F$. Furthermore, we say that $H$ is weakly$F$-saturated in $G$ if $H$ does not contain any copy of $F$, but the missing edges of $H$ in $G$ can be added back one-by-one, in some order, such that every edge creates a new copy of $F$. The smallest number of edges in an $F$-saturated hypergraph in $G$ is denoted by ${\textit {sat}}(G,F)$, and in a weakly $F$-saturated hypergraph in $G$ by $\mathop {\mbox{$w$-${sat}$}}\! (G,F)$. In 2017, Korándi and Sudakov initiated the study of saturation in random graphs, showing that for constant $p$, with high probability ${\textit {sat}}(G(n,p),K_s)=(1+o(1))n\log _{\frac {1}{1-p}}n$, and $\mathop {\mbox{$w$-${sat}$}}\! (G(n,p),K_s)=\mathop {\mbox{$w$-${sat}$}}\! (K_n,K_s)$. Generalising their results, in this paper, we solve the saturation problem for random hypergraphs $G^r(n,p)$ for cliques $K_s^r$, for every $2\le r \lt s$ and constant $p$.
The idea of a ‘late colonial state’ has been surprisingly durable. It is also the case that the meaning and significance of decolonisation – indeed our understanding of when it took place and how long it lasted – has been widened and deepened. We no longer tend to think of it as a purely political let alone constitutional event, but as a much broader shift in the relations between the ‘colonial world’ and its (former) masters and as having many more dimensions: economic, cultural, demographic among them. Needless to say, we are no closer to an agreed explanation than we were twenty-five or fifty years ago: the primacy of nationalist resistance, or of metropolitan politics or of geopolitical change still have their adherents even if it was the ricochet effect of all three on each other that offers the most plausible analysis. However, regardless of which account is favoured it seems clear that the nature of the ‘end game’ of the colonial state is the best place in which to search for answers. The late colonial state still has work to do.
Glacier algae are relevant factors in the darkening phenomenon of glaciers, especially at the margins of the ice sheets. This study focuses on glacier algae variation during summer seasons in the 2016–2023 period at Qaanaaq Ice Cap, NW Greenland. Based on ice samples and field spectroscopy measurements, an empirical model is proposed to estimate glacier algae abundance from a reflectance ratio (695/687 or 695/681 nm). By applying this method to Sentinel-2 data at high resolution (10 m), through a phenology approach, algae abundance variation was estimated in relation to glaciological parameters and a marked spatial and temporal heterogeneity was found. High algae concentrations were found in the 2019, 2020 and 2023 summer seasons (∼1 × 106 cells mL−1 on average) especially at low elevations (<800 m a.s.l.). At the scale of an outlet glacier, strong algal blooms were observed with more than one month of continuous positive air temperature and hiatus of snowfalls. The present research represents one of the first estimations of glacier algae phenology for the high latitudes at this high spatial resolution. These results could set the stage for future research focused on understanding the role of glacier algae at the scale of the Greenland Ice Sheet.
Monolingual children tend to assume that a word labels only one object, and this mutual exclusivity supports referent selection and retention of novel words. Bilingual children accept two labels for an object (lexical overlap) for referent selection more than monolingual children, but in these previous studies, information about speakers’ language backgrounds was minimal. We investigated monolingual and bilingual 4-year-old children’s ability to apply mutual exclusivity and lexical overlap flexibly when objects were labelled either by one or two speakers with the same or different language backgrounds. We tested referent selection and retention of word–object mappings. Both language groups performed similarly for mutual exclusivity, were more likely to accept lexical overlap in the two-language than one-language condition, and performance was similar for referent selection and later retention. Monolingual and bilingual children can adapt their word-learning strategies to cope with the demands of different linguistic contexts.
Coastal areas face unprecedented challenges from accelerating sea-level rise, increasing urbanisation and biodiversity loss, necessitating sustainable coastal protection strategies that go beyond traditional engineering approaches: While Nature-based Solutions (NbS) offer ecological benefits, their implementation faces constraints in space, timely readiness and standardisation. Hybrid Nature-based Solutions (HNbS) have emerged as promising alternatives, yet current taxonomic classifications remain ambiguous and insufficient to accommodate emerging technologies. This synthetic review analyses the evolution and current role of NbS in coastal climate change adaptation through a comprehensive juxtaposition of design principles and functional mechanisms of engineered and nature-based coastal defences. The review synthesises knowledge from sustainable climate adaptation and digital fabrication literature to establish precise taxonomic classifications for solutions that integrate engineered and nature-based approaches, namely HNbS. The analysis reveals gaps in the existing HNbS taxonomy, particularly regarding structures enabled by digital fabrication technologies. The three identified, distinct categories of HNbS are: (1) Hybrid Nature-based Strategies, combining engineered and natural elements at planning scales; (2) Hybrid Nature-based Modules, integrating both components within individual structures; and (3) Confluent Hybrid Nature-based Solutions, representing an emerging category where engineering and natural systems converge at material or microorganism scales, offering distinctly engineered infrastructures with natural characteristics. While contemporary hybrid approaches are being implemented, Confluent Hybrid Nature-based Solutions under research, may face a critical timing mismatch due to a gap between lengthy innovation timelines and urgent adaptation needs. Dynamic Adaptive Policy Pathways provide a framework for strategically accommodating these emerging innovations, enabling early-stage solutions and performance demonstration under real-world conditions. The new taxonomic framework outlined in this study prevents imprecise terminology and provides a foundation for robust, low-regret coastal adaptation strategies addressing contemporary and future coastal pressures like climate change impacts and biodiversity conservation requirements.
Gold-silver telluride deposits in central Montana contain > 400 t Au and are spatially and genetically related to major faults in the Great Falls Tectonic Zone (GFTZ) and the Lewis and Clark Line. They are also related to alkaline igneous intrusive rocks, including monzonites, syenites, diorites, tinguaites, dacites, lamprophyres, and trachytes. Deposit styles include bonanza veins, carbonate replacement at igneous-carbonate contacts, breccia pipe-hosted, and structurally controlled igneous-hosted. Ore-related breccias are a common feature. The ore mineralogy is complex, and locally contains native gold/electrum, Au-Ag tellurides (calaverite, sylvanite, krennerite, petzite, empressite, stützite, and hessite), Bi-tellurides (tetradymite, tellurobismuthite), Bi sulphosalts, and rare precious-metal sulphotellurides. Alteration related to ore-stage fluids is localised primarily adjacent to veins and characterised by silicification, fluoritisation, adularia-sericite, and roscoelite±clays. Fluid inclusion studies suggest that gold telluride ores were deposited from low-temperature (130o–270 oC), moderately saline (1–12 equiv. wt % NaCl), locally boiling, CO2-poor, near neutral, relatively oxidising fluids. Oxygen and hydrogen isotope studies support the concept that the deposits formed from a continuum between magmatic and meteoric fluids, whereas sulphur isotope compositions of sulphides suggest a magmatic sulphur source or sulphur that was leached from sulphides in volcaniclastic and clastic sedimentary rocks. Lead isotope compositions are permissive of a crustal source with a contribution from Palaeozoic or Proterozoic sedimentary rocks hosting the alkalic igneous rocks. Porphyry molybdenum and Carlin-like Au-Te deposits are also genetically related to the GFTZ and Lewis and Clark Line and represent end-members that form a continuum with epithermal gold-silver telluride deposits.
The use of cannabis in adolescence and early adulthood, critical phases for brain development, is linked to psychotic-like experiences (PLEs). The underlying mechanisms, however, remain unclear. This research examined the relationship between recreational cannabis use and PLEs, emphasizing the connectivity of the salience network (SN), which plays a role in salience processing and psychosis. To determine whether this relationship reflects shared genetic or environmental contributions, twin modeling was used.
Methods
We included 232 healthy adolescent Turkish twins who underwent diffusion MRI and psychometric assessment. SN connectivity was quantified using graph theory metrics. Linear mixed models were used to examine the associations among cannabis use, SN factors, and PLEs. Mediation analyses assessed whether SN parameters explained the cannabis–PLEs association. Twin models disentangle genetic and environmental contributions to these traits and their covariation.
Results
Cannabis use was significantly associated with higher overall PLE frequency. A specific SN factor predicted both total and positive PLEs. However, SN connectivity did not mediate the cannabis–PLEs relationship. Twin modeling showed that cannabis use and PLEs were mainly influenced by unique environmental factors. No significant phenotypic covariations were found among cannabis use, PLEs, and SN parameters.
Conclusions
Recreational cannabis use during adolescence and young adulthood is associated with heightened PLEs, although this association is not mediated by SN connectivity. The environment plays an important role during adolescence in shaping these traits independently. The findings underscore the need for longitudinal and genetically informed studies to clarify the mental health effects of adolescent cannabis use.
Health technology assessment (HTA) for medical devices (MDs) is essential for adoption decisions, but the sector’s particularities studied here defy regulatory frameworks. In Brazil, the National Policy for Health Technology Management (PNGTS) provides guidelines for HTA, but the reimbursement of MDs in the Brazilian National Health System (SUS) still faces challenges. This study aimed to identify and validate relevant domains and attributes for HTA of MDs in the SUS, considering the perspectives of various stakeholders.
Objectives
To analyze and validate the essential domains and attributes for conducting HTA studies focused on the reimbursement of MDs in the SUS.
Methods
A baseline systematic review was performed, which was followed by two additional stages: a survey with 115 participants and a Delphi panel with 33 experts. Likert scales were used to assess the importance of the domains and attributes, along with open questions to collect suggestions and comments.
Results
The domains “clinical benefits,” “evidence ecosystem,” and “budget impact” were considered fundamental. “Social participation” showed high variability in response, indicating the need for greater engagement and clarity in participation mechanisms. The inclusion of the “public policy” domain emphasizes the importance of aligning government policies with population needs.
Conclusions
This study reinforced the relevance of a multidisciplinary and participatory approach in HTA for MDs, with a focus on clinical outcomes, real-world evidence, and continuous monitoring. Overcoming the identified challenges, such as information gaps and the need for robust methods, is crucial for improving the reimbursement of MDs in the SUS.
Uzelothrips scabrosus Hood is a fungus-feeding thrips rarely encountered in nature that has been recorded in five countries worldwide. This publication aims to report the presence of the species in Oaxaca, Mexico. Larvae and adults of U. scabrosus are known to live in dead branches, where they feed on fungi. Surprisingly, we collected this species from mango flowers. We present the first image of a winged female. Previously recorded in Angola, Australia, Brazil, Singapore, and Indonesia, the present report adds to the global distribution of U. scabrosus and broadens the knowledge of the diversity of thrips in Mexico.