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Novel drugs approved by the EMA, the FDA and the MHRA in 2025: a year in review
Get PDFIn the 2025 novel drug mini-review, one can take a full measure of the ingenuity that underlies current drug design and development, despite the year's smaller harvest (46 novel drugs) compared to 2024 (53) and 2023 (70). 54% of the novel drugs are first-in-class (FIC). The emphasis on proteins/antibodies is maintained (25% novel drugs in 2025), an industry trend that does not seem to abate. Fewer than half of the novel medicines address major or common disorders. Among the FIC drugs, it is worth mentioning the Nav1.8 channel inhibitor suzetrigine, the first non-opioid approved to palliate acute pain; the first positive allosteric modulator of transient receptor potential melastatin 8 (TRPM8), acoltremon, that increases basal tear production in dry eye disease, a globally common disorder; lerodalcibep, a ‘third generation’ adnectin inhibitor of the protease Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) to treat elevated LDL-c; and zoliflodacin and gepotidacin, both innovatively targeting bacterial topoisomerases to treat uncomplicated urinary tract infections. Most of the approved medicines target unmet medical need areas and/or orphan indications (the latter alone accounting for 41% of the 2025 novel drugs) by applying imaginative approaches. These approaches include: the combination of two FIC drugs, the RAF/MEK clamp avutometinib paired with the FAK/Pyk2 inhibitor defactinib, to block more efficiently the RAS–RAF–MEK–ERK/FAK oncogenic pathway in low-grade serous ovarian cancer; fitusiran, the first RNAi therapy for haemophilia, targeting for the first time the production of the natural anticoagulant anti-thrombin in the liver; and brensocatib, which attenuates the activation of downstream neutrophil proteases by inhibiting the protease DPP1, thereby preventing lung tissue destruction in bronchiectasis. The landscape of novel drugs approved in 2025 reveals that pharmaceutical innovation continues to advance through FIC mechanisms, sophisticated therapeutic approaches and a strong focus on unmet medical need
The principle of good faith in the performance of commercial contracts in England and Wales
Get PDFThis thesis explores the necessity of a principle of good faith in the performance of commercial
contracts in England and Wales and suggests that commercial law would benefit from explicitly
recognising such a concept. While the law can provide protection for certain cases of unfair
conduct, such protection is insufficient, particularly where the parties have unequal bargaining
power. Small or inexperienced businesses may find themselves legally obliged to perform
agreements with implications they did not fully understand at the time of contracting. This may
not always be due to their inexperience or oversight but can also result from a change in
circumstances. The main criticism for introducing good faith into contract performance
remains the uncertainty in contract enforcement. For too long the debate has been restricted to
theoretical and judicial confines. The self-imposed rules of the market’s institutions clearly
indicate that such fears are misplaced. In particular, Australia provides a concrete example
showcasing the usefulness of the concept in franchising contracts. Indeed, this thesis argues
that the current judicial stance is significantly delaying the recognition of good faith in
contractual performance, not only by failing to provide an overarching standard of good faith
in commercial contract performance but also by fixating on a traditional antagonistic view of
contractual parties detached from contextual influences in contractual dealings. Legislation is
needed to resolve the conundrum faced by the judiciary in what is perceived to be a colossal
task, and recent legislative endeavours have failed to fully bridge the gap in regulating
opportunistic conduct between businesses where consumer or competition laws are not
triggered. This thesis proposes a pragmatic way forward with a statutory good faith standard
for commercial contracts, with full awareness that this would inevitably necessitate a rehaul of
the entire commercial contract law landscape
The discursive construction of national and tribal identities in Saudi Arabia: a discourse-historical approach
No full textIn Saudi Arabia, modern statehood coexists with longstanding tribal affiliations. Both
national and tribal identities function as prominent discursive constructs through which
members of Saudi tribal communities articulate their sense of belonging. This thesis draws
mainly on Discourse-Historical Approach (DHA) as the overarching framework, while also
employing tools from Corpus Linguistics (CL) and Multimodal Critical Discourse Studies
(MCDS), to examine the discursive construction of Saudi national and tribal identities in the
context of contemporary national reforms and nation-rebuilding efforts driven by the Saudi
Vision 2030 policies. It investigates the construction and recontextualisation of discourses on
national identity from top-down and bottom-up perspectives, identifying intertextual and
interdiscursive relations between discourses produced at the institutional and grassroot levels.
It also explores bottom-up discursive constructions of tribal identities to understand how Saudi
individuals with tribal affiliations position their national and tribal belongings relative to one
another.
Given the pivotal role of education in nation-building (Wodak et al., 2009; Billig, 1997),
this study focuses on the field of education. Top-down discourses were explored through
analysing corpora of multimodal texts drawn from Social Studies textbooks published in 2022
by the Saudi Ministry of Education for third-grade intermediate students in mainstream
education. Bottom-up perspectives on national identity were accessed through interviews with
Saudi teachers and learners who were engaging with the analysed multimodal texts at the time
of the interviews. As all interviewees identified as members of tribal communities, their
accounts also provide insight into bottom-up constructions of tribal identity.
The findings support existing DHA research on national identity. Top-down discourses
employ classical macro-strategies of positive self-presentation and construction of sameness to
promote unity, pride, political continuity, and shared religion, culture, and history. Bottom-up
discourses show alignment with some top-down linguistic and argumentative patterns and, at
the same time, introduce additional positionings to the top-down model of national belonging.
In particular, interview accounts more explicitly construe Saudi society as united yet internally
diverse, i.e., ethnically, culturally, tribally, and linguistically. Their accounts represent broader
and more diverse understandings of the Saudi nation.
The findings also show that tribal identity is discursively constructed through references
to genealogical continuity and the concept of aṣabiyyah, defined in this thesis through Al
Ghathami’s (2009) reinterpretation of Ibn Khaldūn’s (1377) aṣabiyyah as lineage-based social cohesion and collective solidarity within the national community rather than as hostility towards
or harm to others. Interviewees’ accounts on tribal identities foreground lineage-based forms of
solidarity and kinship-oriented belonging as salient identity resources. Most importantly, tribal
identity is not positioned as oppositional to national identity; rather, it is often articulated as
complementary. As tribal and national identities are discursively constructed, participants often
employ discursive strategies that legitimise tribal belonging, align it with national unity, and
position tribal histories within wider narratives of the nation. A dual sense of belonging
emerges, in which loyalty to tribal members coexists with loyalty to fellow nationals.
Interestingly, some aspects of tribal culture were found to extend to the national level; for
example, the principle of reciprocal obligation is rearticulated as participants, in practical terms,
discursively defended the Saudi nation’s reputation and international image while constructing
rulers and government officials as providers of care and protection, an arrangement analogous
to the sheikh-tribe relationship in pre-nation Arabian tribal structures.
This study examines how collective identities are discursively constructed and negotiated
through institutionally situated and socially influenced practices that navigate the dynamics
between unity and diversity alongside tradition and modernity. It offers insight into the ongoing
constructions of prominent social identities in Saudi Arabia within a rapidly transforming
sociopolitical context that is led by Vision 2030’s objectives for national reforms and social
cohesion. Additionally, this study proposes a methodological approach to recontextualisation
in which DHA is extended through incorporating tools from CL and MCDS to systematically
examine how discourse is selectively reproduced, reconstructed, appropriated, omitted,
reshaped, or contested across contexts and modes of communication
Journal ratings changes: implications for author diversity and research characteristics
No full textConcerns have been raised in the business and management literature regarding the role of journal rating lists. Rather than simply reflecting journal performance, these lists may influence the nature of scholarly work produced and published. This study investigates the impact of upgrades and downgrades and inclusions and removals, respectively, to two widely used journal rating sources -- the Academic Journal Guide and the Financial Times List -- on author and paper characteristics. We analyse a large sample of articles, spanning all sub-fields in business and management, published over a 12-year period. Our analysis indicates that female authors publish significantly more in journals that experience downgrades or removal from these lists compared to journals that maintain or improve their ratings. We also observe that authors affiliated with African universities are less represented in journals that have newly entered or been upgraded on these lists. However, our findings do not show a significant effect of journal list recompositions on the most commonly employed research methods. We observe that list entry and rating upgrades are associated with significantly improved article readability. Overall, our results contribute to the ongoing discussion regarding the effects of journal lists on publication outcomes, particularly for groups that are already underrepresented in academic publishing
Vocabulary in listening and speaking
No full textThis chapter explores the critical role of vocabulary in second language (L2) learning, emphasizing its influence on listening and speaking proficiency. It examines how vocabulary knowledge supports comprehension and production, highlighting the interplay between receptive and productive skills. Drawing on theoretical models and empirical evidence, the chapter discusses vocabulary acquisition through listening and speaking, including the impact of factors such as lexical coverage, individual differences, and technology-enhanced tasks. By synthesizing current research, it offers insights into vocabulary’s centrality in L2 learning and suggests implications for future research
Learning enhanced ensemble filters
No full textThe filtering distribution in hidden Markov models evolves according to the law of a mean-field model in state–observation space. The ensemble Kalman filter (EnKF) approximates this mean-field model with an ensemble of interacting particles, employing a Gaussian ansatz for the joint distribution of the state and observation at each observation time. These methods are robust, but the Gaussian ansatz limits accuracy. Here this shortcoming is addressed by using machine learning to map the joint predicted state and observation to the updated state estimate. The derivation of methods from a mean field formulation of the true filtering distribution suggests a single parametrization of the algorithm that can be deployed at different ensemble sizes. And we use a mean field formulation of the ensemble Kalman filter as an inductive bias for our architecture.
To develop this perspective, in which the mean-field limit of the algorithm and finite interacting ensemble particle approximations share a common set of parameters, a novel form of neural operator is introduced, taking probability distributions as input: a measure neural mapping (MNM). A MNM is used to design a novel approach to filtering, the MNM-enhanced ensemble filter (MNMEF), which is defined in both the mean-field limit and for interacting ensemble particle approximations. The ensemble approach uses empirical measures as input to the MNM and is implemented using the set transformer, which is invariant to ensemble permutation and allows for different ensemble sizes. In practice fine-tuning of a small number of parameters, for specific ensemble sizes, further enhances the accuracy of the scheme. The promise of the approach is demonstrated by its superior root-mean-square-error performance relative to leading methods in filtering the Lorenz ‘96 and Kuramoto-Sivashinsky models
SharP: Soft and hard prompt-guided augmentation with LLM for low resource fake news detection
No full textFake news detection under low resource conditions is challenged by the scarcity of labeled data and the difficulty of capturing subtle deceptive patterns. Existing data augmentation methods, such as synonym substitution, generative adversarial networks, and large language model (LLM)-based generation, often produce fluent but overly generic content, lacking the task-specific relevance needed for accurate detection. To address this, we propose SharP, a boundary-aware text generation framework guided by soft and hard prompts, which leverages LLMs as tools adapted to produce task-specific synthetic samples. SharP employs a dual prompt mechanism: hard prompts provide structured
guidance and factual constraints, while soft prompts introduce learned semantic patterns from the data. These two types of prompts are combined to guide the generation process, enabling the model to produce samples that closely align with the characteristics of news. To further enhance detection performance, we incorporate a boundary-aware
strategy that steers generation toward areas where the classifier is less confident, helping to clarify subtle distinctions between real and fake content. In addition, we adopt a dual
objective optimization that balances semantic alignment with the source data and classifier feedback. This encourages the generation of samples that are both domain-consistent
and helpful for refining decision boundaries, ultimately improving model robustness and generalization in low resource fake news detection
An exploratory study of the use of positive writing diaries for autistic females
Get PDFThis thesis explores the use of positive writing as a tool for the management of difficulties
and behaviours associated with autism and the improvement in life satisfaction of the autistic
community within educational settings. This intervention study focuses on adult autistic
females as they are often overlooked in research. A small group of women (13) either
diagnosed with autism, or who self-identify as autistic participated in the study. The study
involved keeping a positive retrospective diary for a period of four weeks, whilst looking for
positive experiences to include in the diary, and answering questionnaire questions about it
and its effects before and afterwards. Thematic Analysis was carried out on diary entries and
questionnaire responses in order to identify themes and sub-themes across participants. All
participants were either school or university students, or professionals working in education.
The pre-diary questionnaires identified many struggles associated with autism, such a strict
routines, social difficulties, and high levels of anxiety. Some of these, such as masking, may
have been particularly associated with females. Post-diary questionnaires commonly
revealed improvement in sense of life satisfaction and well-being associated with the diary
task. It was commonly reported that the positive diary led to an increased focus on happy
events and less negative thinking. The post-diary questionnaires also frequently showed a
marked decrease in anxiety following the diary procedure. Reasons for this and possible
mechanisms are explored. Participants demonstrated enjoyment of the diary task and most
said that they would continue to keep using a positive diary after the study had finished. The
findings of the study contribute new knowledge to understanding and coping with autistic
behaviours and difficulties in educational settings for both workers and students, especially in
helping autistic females to manage anxiety and maximise their potential within education.
This has implications for practice in terms of the way in which autistic students are assisted
and treated by staff, and the way in which autistic academic staff are accommodated. The
findings also have implications for practice beyond education in terms of helping autistic
adults to manage difficulties and anxiety, foster self-awareness and coping skills, and live
more positively. All forms of health practitioners could introduce and recommend positive
diary writing techniques as part of broader well-being interventions. Positive diary writing is
a practical, low cost self-help strategy that can be personalised and used in multiple settings
The role of neglected and underutilized species (NUS) in Sustainable Development Goals (SDGs): the case of sea buckthorn value chain in rural China
Get PDFNeglected and underutilized species (NUS) can play a crucial role in food and nutrition security, agricultural diversity and resilience, poverty reduction, and income generation. Given the importance of NUS in achieving sustainable development goals (SDGs) without notable trade-offs, this study conducts in-depth interviews with sea buckthorn value chain stakeholders in three counties in Gansu Province, China, to understand key drivers for creating new NUS value chains, the strengths, weaknesses, opportunities, and threats (SWOT) of each type of value chain stakeholders, and the role of NUS for sustainable development. The findings show that four drivers, namely infrastructure (e.g., rural roads for logistics, information and communication technology facilities for e-commerce), investment (e.g., agricultural loans/subsidies), scientific and technological (e.g., advanced processing equipment, research on breeding and strategic plantation), and market drivers (e.g., offline and online e-commerce platforms) have better integrated internal natural and human capital and external financial, physical, and social capital into NUS value chains. The study proposes a novel conceptual framework for the adoption of the NUS value chain, highlighting the significant potential of NUS in achieving a balance between the economic, social, and ecological objectives of the SDGs at a regional level through responsible and strategic plantation, production, processing, marketing, and consumption of NUS
Inhibition of low-density lipoprotein oxidation by cysteamine, cystamine, cysteine and cystine at lysosomal pH and pH 7.4
Get PDFLDL can be oxidised in the lysosomes of macrophages. Cysteamine, a thiol antioxidant
that accumulates in lysosomes, inhibits the oxidation of LDL by iron at lysosomal pH
(pH 4.5) and protects against atherosclerosis in mice. We have investigated the effects of
cysteamine and its related thiol cysteine and their disulfides on LDL oxidation by iron or
copper at both pH 4.5 and 7.4. The oxidation of LDL by ferrous iron (5 μM) at pH 4.5 was
delayed 12.9-fold by 100 μM cysteamine and 5.6-fold by 100 μM cysteine. Cystamine and
cystine (the disulfide oxidation products of cyteamine and cysteine, respectively) did not
inhibit LDL oxidation by ferrous iron at pH 4.5. LDL oxidation by 5 μM copper at pH 4.5
was delayed about 2-fold by 100 μM of the thiols cysteamine and cysteine, but there was
little effect of the disulfides cystamine and cystine. Cysteamine and cystine did not inhibit
the oxidation of LDL by ferrous iron at pH 7.4 in a MOPS buffer and even accelerated
LDL oxidation later in the incubation. Cysteine initially inhibited the oxidation of LDL
by ferrous iron at pH 7.4, but increased it later. LDL oxidation by copper at pH 7.4 was
delayed 7.8-fold by 100 μM cysteamine. Cysteine delayed LDL oxidation by copper at
pH 7.4 to a similar extent as cysteamine but, unlike cysteamine, continued to decrease the
rate of oxidation even after the period of total inhibition had ended. Cystamine had no
effect on LDL oxidation by copper at pH 7.4, but cystine partially inhibited LDL oxidation.
The effects of thiols and disulfides on LDL oxidation, therefore, depend not only on the
metal ion catalysing the oxidation but also on the pH of the environment