Shrewsbury College

Oligonucleotide-based therapeutics are now widely used in clinical settings. From the late 1980s to the mid-1990s, efforts to improve therapeutic efficacy focused on imparting drug-like properties to oligonucleotides, emphasizing nuclease stability and target sequence affinity. These efforts resulted in the standard gapmer design for RNase H-mediated antisense and the prevalent use of chemical modification such as phosphorothioate and 2'-substituted oligoribonucleotides in oligonucleotide therapeutics. Progress made in the antisense field also enabled the development of splice-modulating oligonucleotide therapeutics and later siRNA therapies. All three modes of action are now widely employed in >25 approved drugs. Since then, we have learned that oligonucleotides and their chemical modifications can interact with pattern recognition receptors as well as various other proteins. This can have both positive and negative effects, such as aiding in oligonucleotide delivery or activating the intracellular innate immune system. My current work aims to optimize the drug-like properties of oligonucleotides by combining the early chemical advances with the more recent insights into off-target protein binding. The present article describes how this resulted in several different cyclic structured oligonucleotide designs, in which 3' and 5' ends are transiently held together via Watson-Crick base pairing. The transient nature of these cyclic structures protects the functional parts of the structure against nucleases during delivery and cell entry while allowing effective release of the oligonucleotide drug into the intracellular environment. These cyclic designs demonstrate significant improvements in potency and specificity over gapmer antisense and are broadly applicable to potentially all types of RNA therapeutics, irrespective of their mechanism of action. © 2026 Wiley Periodicals LLC.

Active rear spoilers represent a significant advancement in the modern automotive industry. Active rear spoilers offering dynamic adjustment of aerodynamic forces to optimise vehicle performance and efficiency. Unlike traditional fixed spoilers, active systems respond to real-time driving conditions. They alter their angle of attack and height to balance the trade-off between downforce and drag. This adaptive capability enhances high-speed stability, cornering grip, braking performance, and overall safety, while also improving energy efficiency—particularly crucial for electric vehicles, where aerodynamic drag directly affects range. This paper examines the aerodynamic principles, control strategies, and structural components of active rear spoilers. It also evaluates their impact on vehicle dynamics, energy consumption, and safety, with case studies from advanced implementations such as the Rimac Nevera and McLaren P1™. The paper highlights current technological achievements, identifies recent research gaps, and outlines future trends in adaptive aerodynamic devices, with a particular focus on rear spoilers.

BackgroundThe adoption of high-quality health apps has been slow, despite the myriad benefits associated with their use. This is partly due to concerns regarding the effectiveness, safety, and data privacy of such apps. Quality assessments with robust and transparent criteria can address these concerns and, thereby, encourage the use of high-quality apps. However, a major challenge for such assessments is reaching a scale at which a substantial proportion of the more than 350,000 available health apps can be evaluated.ObjectiveTo support the scaling of health app quality assessments, this study aimed to examine the preferences and willingness to pay for assessments with different value propositions among potential customers.MethodsWe conducted 2 discrete choice experiments: one with 41 health app developers and another with 46 health system representatives (from health care institutions, authorities, and insurers) from across Europe. Mixed logit models were applied to examine the impact of assessment attributes on participants’ choices as well as to calculate marginal willingness to pay and predicted assessment uptake.ResultsAmong health app developers, the attributes with the largest impact on assessment choices were the associated clinical care uptake (integration into clinical guidelines and reimbursement or procurement) and cost (purchase price). Increased willingness to use assessed apps and app store integration of assessment results had a moderate impact on choices, while required developer time investment and time until assessment results become available made the smallest contribution. Among health system representatives, increased willingness of clinicians and patients to use evaluated apps had the greatest impact on assessment choices, followed by cost. Time until assessment result availability and the percentage of peers recommending the assessment made a moderate contribution, while reassessment frequency had the smallest impact on choices. On average, health app developers were willing to pay an additional €9020 (95% CI €4968-€13,072) if an assessment facilitates guideline integration and procurement or reimbursement (at the time of data collection, €1=US $1.11), while health system representatives were, on average, willing to pay €7037 (95% CI €4267-€9806) more if an assessment results in a large, rather than a small, increase in willingness to use the evaluated app. The predicted uptake of assessments that offer the preferred values for all attributes was 88.6% among app developers and 91.1% among health system representatives.ConclusionsThese findings indicate that, to maximize uptake and willingness to pay among health app developers, it is advisable for assessments to facilitate or enable clinical guideline integration and reimbursement or procurement for high-scoring apps. Assessment scaling thus requires close collaboration with health authorities, health care institutions, and insurers. Furthermore, if health system organizations are targeted as customers, it is essential to provide evidence for the assessment’s impact on patients’ and clinicians’ willingness to use health apps.

Abstract. The Permo-Triassic Sherwood Sandstone Group is an important aquifer with potential for both shallow and deep geothermal energy use in the UK. This study investigates the hydrogeological properties of the shallow buried Sherwood Sandstone Group in Northern Ireland, with a focus on its porosity, using borehole nuclear magnetic resonance (BNMR) and petrophysical models (Archie and Waxman-Smits). BNMR and downhole geophysical logging (resistivity, EC, temperature and natural gamma) were carried out on three boreholes drilled into the lower Sherwood Sandstone Group aquifer at depths of about 100 m on Queen's University Belfast campus. The results showed that the porosity calculated from BNMR and the Waxman-Smits model are comparable, demonstrating the relationship between BNMR and petrophysical-derived porosity. The average porosity of the Sherwood Sandstone Group at this location ranges between 14.9 % and 17.6 %, with maximum values ranging between 33.7 % and 40.4 %. However, the results from the Archie model are significantly larger than those of BNRM, confirming its unsuitability for lithologies containing clays, even in small amounts. This study confirms storage capacities in the lower Sherwood Sandstone Group that make it suitable for ATES systems.

Polycystic Ovary Syndrome (PCOS) is a hormonal disorder that affects approximately 5-10% of women of reproductive age, making it one of the most common endocrine disorders in this population (1).PCOS is characterized by irregular menstrual cycles, elevated androgen levels, insulin resistance, and polycystic ovaries.Currently, there is no cure for PCOS, so treatment focuses on symptom management.Prescription medications like Metformin, which improves insulin sensitivity, and Clomiphene, an ovulation inducer, are commonly used in clinical practice.However, barriers to accessing these drugs can be significant, especially for women in low-resource settings due to high costs and limited availability (1-2).Compared to prescription medications, herbal supplements generally cause fewer and less severe side effects, are more affordable, and are widely available without needing a prescription.This research paper examines the potential of 10 herbal supplements as alternatives to conventional treatments for PCOS: Berberine, Cinnamon, Fenugreek, Shatavari, Chasteberry, Chinese Peony, Red Reishi mushrooms, Ashwagandha, Turmeric, and Spearmint.Herbal treatments are less potent but are easier to access and may be a promising alternative for women in regions where conventional medications are scarce or expensive.Further clinical research on herbal supplements and greater awareness of these alternatives could help address the global challenges of PCOS.

Proximal humerus fractures are prevalent in older adults, particularly women, primarily due to osteoporosis and increased fall risk. These fractures often result from low-energy falls in elderly patients, while in younger individuals, they are more likely to occur with high-energy trauma, which may involve additional injuries to soft tissue and neurovascular structures. Proper anatomical understanding, including key structures and blood supply, is crucial for effective management and to prevent complications.Several classification systems assist in guiding treatment for proximal humerus fractures, including Codman's, Neer's, Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) system, and the Codman-Hertel system, whichhelps predict ischemia risk. Evaluation of proximal humerus fractures begins with Advanced Trauma Life Support (ATLS)protocols, emphasizing a thorough shoulder assessment, particularly focusing on skin integrity in elderly patients. Neurological and vascular examinations are essential due to the common occurrence of nerve injuries, especially involving the axillary nerve. Imaging typically includes multiple standard views, with advanced imaging reserved for complex cases and for assessing associated soft tissue injuries. Treatment options range from conservative management for stable fractures to surgical intervention for more complex cases. Surgical choices include techniques like fixation, nailing, and various arthroplasty options, with some procedures potentially offering advantages for older adults with bone quality or soft tissue challenges. Rehabilitation is a vital component of recovery, with emphasis on early mobility and gradual strengthening to restore function, especially in older patients. Complications following open reduction and internal fixation (ORIF) for proximal humerus fractures can include issues such as non-union, malunion, osteonecrosis, infection, joint stiffness, and fixation failure. In cases where non-union or fixation failure occurs, revision surgery or arthroplasty may be necessary. Joint stiffness may require further intervention if physical therapy is insufficient, while symptomatic osteonecrosis might also need surgical management. Malunion is generally better tolerated in older patients but may require correction in younger individuals. Other surgical options, such as hemiarthroplasty (HA) and reverse shoulder arthroplasty (RSA), share similar risks, including infection, fractures, complications at the tuberosity, stiffness, and instability. RSA may be favored when there are tuberosity or rotator cuff issues. Closed reduction with percutaneous pinning carries a high risk of pin migration and malunion, which can result in deformities, pain, and dysfunction. Proper anatomical knowledge is essential to avoid neurovascular injury and to manage common issues such as pin-site infections effectively.

Introduction: Seizures are a common initial manifestation of cerebral venous thrombosis (CVT). We sought to establish predictive factors for delayed seizures to stratify risk and guide clinical management. Methods: We analyzed data from the Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with CVT from 2015 - 2020. The primary outcome was delayed seizure(s), occurring after 7 days from CVT diagnosis. Patients with outcome data for late seizures and follow-up of at least 7 days from time of diagnosis were included. Univariate analysis was performed using Chi-square, rank-sum, and t-tests. Variables with P-value < 0.2 were included in the backward stepwise regression model with 0.2 as cutoff, based on which we constructed the Delayed Seizure CVT (Delayed Seizures after CVT) score. Results: We identified 599 patients who met inclusion criteria: mean age 44.9(± 16.6) years, 62.9% female. Delayed seizures occurred in 37 (6.1%) patients. Risk factors included intracranial hemorrhage (OR 2.0 95% CI 0.7-5.74 p=0.196), alcohol abuse (OR 3.88 95% CI 1.45-10.38 p=0.007), focal neurologic deficit (OR 2.05 95% CI 0.95-4.44 p=0.067), seizure on presentation (OR 2.88 95% CI 1.32-6.29 p=0.008), hormonal birth control (OR 2.38 95% CI 1.06-5.37 p=0.0036), endovascular therapy (OR 2.86 95% CI 1.16-7.07 p=0.023) and decompressive hemicraniectomy (OR 3.357 95% CI 1.02-10.99 p=0.046), respectively. Based on coefficients of these variables, a 7-item score was created with acceptable performance for seizure prediction (AUC 0.796, 95% CI 0.72 - 0.86) (Table 1). Conclusions: Delayed seizure CVT score is a clinical tool to identify risk of delayed seizure in CVT. Further research is needed to validate these findings in an external cohort.

This essay provides a comprehensive analysis of three major supermarket stocks: Marks & Spencer (M&S), Sainsbury's, and Tesco. The analysis focuses on evaluating the risks, profitability, market ratios, and suitability for different types of investors. M&S exhibits the highest level of risk, while Tesco and Sainsbury's appear to be more stable. M&S is the most profitable stock, followed by Tesco and Sainsbury's. In terms of market ratios, M&S shows potential undervaluation and growth opportunities, Sainsbury's offers a high dividend yield, and both Sainsbury's and Tesco display positive momentum. The preferred stock choices for different types of investors are Sainsbury's for value investors, M&S for growth investors, Tesco for index investors, and Sainsbury's for income investors. These results are used for different investors to analyze and decide which company they will invest to earn more profit in its operation.

An abstract is not available for this content. As you have access to this content, full HTML content is provided on this page. A PDF of this content is also available in through the 'Save PDF' action button.