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Acute pain, defined as short-term pain arising from injury or other noxious stimuli, affects patient outcomes, quality of life, and healthcare costs. Safe, effective treatment of acute pain is essential in preventing increased morbidity, mortality, and the transition to chronic pain. In this review, we explore some of the latest therapeutic agents, formulations, combinations, and administration routes of drugs emerging in clinical practice in the USA for the treatment of acute pain. These agents include VX-548 (Suzetrigine), Cebranopadol, AAT-076, Combogesic intravenous (IV), sublingual ketamine, XG004 (naproxen/pregabalin conjugate), and HTX-011 (Zynrelef). We analyze the pharmacodynamics, pharmacokinetics, development status, and clinical implications of these drugs, emphasizing the importance of finding an agent that provides both a strong safety profile and effective relief from acute pain. Our findings show promise but also highlight the need for further large-scale research to allow these drugs to be utilized in a clinical context for patients experiencing acute pain. [ABSTRACT FROM AUTHOR]

Episodic retrieval plays a functional-adaptive role in supporting divergent creative thinking, the ability to creatively combine different pieces of information. However, the same constructive memory process that provides this benefit can also lead to memory errors. Prior behavioral work has shown that there is a positive correlation between the false recognition of lure items in the Deese-Roediger-McDermott paradigm, and divergent creative thinking as assessed on the alternate uses task. Here, we conducted a meta-analysis of functional magnetic resonance imaging studies to test for convergence in the neural substrates associated with these cognitive linkages. Our individual meta-analyses of false recognition-related activity as well as divergent thinking-related neural activity replicated prior meta-analyses. However, there was no significant statistical overlap across the neural regions associated with false recognition and divergent creative thinking. These null findings may reflect the operation of distinct generative retrieval processes engaged during divergent thinking relative to false recognition. [ABSTRACT FROM AUTHOR]

Healthcare breakthroughs are extending the lives of multiple sclerosis (MS) patients and cancer survivors, creating a growing cohort of individuals navigating a dual diagnosis. Determining the relationship between MS and cancer risk remains challenging, with inconclusive findings confounded by age, risk exposures, comorbidities, genetics and the ongoing introduction of new MS disease-modifying therapies (DMTs) across study periods. This research places significant emphasis on cancer survival, with less attention given to the impact on MS outcomes. Our review explores the existing literature on MS, cancer risk and the intersection of DMTs and cancer treatments. We aim to navigate the complexities of managing MS in cancer survivors to optimise outcomes for both conditions. Continuous research and the formulation of treatment guidelines are essential for guiding future care. Collaboration between neuro-immunology and oncology is crucial, with a need to establish databases for retrospective and ultimately prospective analysis of outcomes in these rapidly evolving fields. [ABSTRACT FROM AUTHOR]

With its demonstration of human frailty and finitude, avant-garde literature offers a more rigorous jurisprudence of rights than juridical or legal discourse is capable of offering itself. The paper takes as example the lowering of fault requirements in Canadian criminal law, which weakens common-law protection of the fundamental right to liberty through a fault standard that is "not concerned with what was in the accused's mind, but with what should have been there." Avant-garde literature, in opposition, demonstrates—and cannot help but demonstrate, in a mode unique to its discourse—the real limits of seeing and knowing, as shown through a reading of Claude Ollier's La Mise-en- Scène. [ABSTRACT FROM AUTHOR]

PAX6 is well known as a transcription factor that drives eye development in animals as widely divergent as flies and mammals. In addition to its localization in eyes, PAX6 expression has been reported in the central nervous system, the pancreas, testes, Merkel cells, nasal epithelium, developing cells of the inner ear, and embryonic submandibular salivary gland. Here we show that PAX6 also appears to be present in the mechanosensory neuromasts of the lateral line system in paedomorphic salamanders of the genus Eurycea. Using immunohistochemistry and confocal microscopy to examine a limited number of larvae of two species, listed by the United States of America's federal government as threatened (E. nana) or endangered (E. rathbuni), we found that anti-PAX6 antibody labeled structures that were extranuclear, and labeling was most intense in the apical appendages of the hair cells of the neuromast. This extranuclear localization raises the possibility of an as yet undescribed function for PAX6 as a cytoskeleton-associated protein. [ABSTRACT FROM AUTHOR]

Cystinosis is a rare autosomal recessive disease characterised by an accumulation of cystine in the lysosomes. It is caused by pathogenic variants of the cystinosin gene (CTNS), which interrupts the transport of cystine from the lysosomes into the cytosol. Intra-lysosomal cystine accumulation leads to subsequent cellular dysfunction. Cystinosis has an incidence of 0.5–1/100,000 live births. There are three forms of cystinosis: nephropathic cystinosis, juvenile cystinosis, and ocular cystinosis, with nephropathic cystinosis being the most prevalent disease subtype. Renal impairment is the most common manifestation of disease. Extrarenal manifestations of cystinosis include hypothyroidism, diabetes, and hypogonadism. The current treatment for cystinosis is cysteamine, a cystine-depleting agent. This is not a curative treatment and only aims to slow the progression of disease. A total of 90% of cystinosis patients progress to kidney failure within the first 20 years of life. Kidney transplantation is the only option available to patients once the disease has progressed to this stage. This review highlights the pathogenesis and clinical manifestations of cystinosis, as well as potential future treatment options. [ABSTRACT FROM AUTHOR]

Introduction: The use of prosthetic mesh in laparoscopic repair of large hiatus hernias remains controversial. Clinical and quality of life outcomes from a randomized controlled trial of mesh versus suture repair previously showed few differences at early follow‐up. This study evaluated longer‐term quality of life outcomes from that trial. Methods: A prospective, multicentre, double blind randomized controlled trial assessed three methods of repair for large hiatus hernias: sutures‐only versus absorbable mesh versus non‐absorbable mesh. Quality of life was assessed using the Short‐Form 36 (SF‐36) questionnaire which was completed preoperatively and then at 3, 6, 12 months following surgery and annually thereafter. SF‐36 outcomes were compared across the three repair techniques at longer‐term follow‐up (3–6 years), and to earlier baseline and 12‐month outcomes. Results: 126 patients were randomized; 43—suture‐only, 41—absorbable mesh and 42—non‐absorbable mesh. Questionnaires were completed by 118 patients preoperatively, 115 at 12 months and 98 at longer‐term follow‐up (median 5 years). There were no significant differences between the repair techniques for the subscale and composite scores at longer‐term follow‐up. The mental component score improved significantly after surgery and was sustained across follow‐up for all techniques. The physical component score also improved significantly but was lower at longer‐term follow‐up compared to the 12‐month follow up in both mesh groups. Conclusion: Surgical repair of large hiatus hernias provides sustained long‐term improvement in quality of life. The addition of mesh does not improve quality of life. Trial Registration: This trial is registered with the Australia and New Zealand Clinical Trials Registry ACTRN12605000725662. [ABSTRACT FROM AUTHOR]

Purpose: Intra-Discal Vacuum phenomenon (IDVP) is well-recognised, yet poorly visualised and poorly understood radiological finding in disc degeneration, particularly with regard to its role in spinal alignment. CT analysis of the lumbar spine in an aging population aims to identify patterns associated with IDVP including lumbopelvic morphology and associated spinal diagnoses. Methods: An analysis was performed of an over-60s population sample of 2020 unrelated abdominal CT scans, without acute spinal presentations. Spinal analysis included sagittal lumbopelvic reconstructions to assess for IDVP and pelvic incidence (PI). Subjects with degenerative pathologies, including previous vertebral fractures, auto-fusion, transitional vertebrae, and listhesis, were also selected out and analysed separately. Results: The prevalence of lumbar spine IDVP was 50.3% (955/1898) and increased with age (125 exclusions). This increased in severity towards the lumbosacral junction (L1L2 8.3%, L2L3 10.9%, L3L4 11.5%, L4L5 23.9%, and L5S1 46.3%). A lower PI yielded a higher incidence of IDVP, particularly at L5S1 (p < 0.01). A total of 292 patients had IDVP with additional degenerative pathologies, which were more likely to occur at the level of isthmic spondylolisthesis, adjacent to a previous fracture or suprajacent to a lumbosacral transitional vertebra (p < 0.05). Conclusions: This study identified the prevalence and severity of IDVP in an aging population. Sagittal patterns that influence the pattern of IVDP, such as pelvic incidence and degenerative pathologies, provide novel insights into the function of aging spines. [ABSTRACT FROM AUTHOR]

Epstein–Barr Virus (EBV) exists in a latent state in 90% of the world's population and is linked to numerous cancers, such as Burkitt's Lymphoma, Hodgkin's, and non-Hodgkin's Lymphoma. One EBV latency protein, latency membrane protein 2A (LMP2A), is expressed in multiple latency phenotypes. LMP2A signaling has been extensively studied and one target of LMP2A is the mammalian target of rapamycin (mTOR). Since mTOR has been linked to reprogramming tumor metabolism and increasing levels of hypoxia-inducible factor 1 α (HIF-1α), we hypothesized that LMP2A would increase HIF-1α levels to enhance ATP generation in B lymphoma cell lines. Our data indicate that LMP2A increases ATP generation in multiple Burkitt lymphoma cell lines that were dependent on HIF-1α. Subsequent studies indicate that the addition of the mTOR inhibitor, rapamycin, blocked the LMP2A-dependent increase in HIF-1α. Further studies demonstrate that LMP2A does not increase HIF-1α levels by increasing HIF-1α RNA or STAT3 activation. In contrast, LMP2A and mTOR-dependent increase in HIF-1α required mTOR-dependent phosphorylation of p70 S6 Kinase and 4E-BP1. These findings implicate the importance of LMP2A in promoting B cell lymphoma survival by increasing ATP generation and identifying potential pharmaceutical targets to treat EBV-associated tumors. [ABSTRACT FROM AUTHOR]

Una Stojnić urges the radical view that the meaning of context-sensitive language is not "partially determined by non-linguistic features of utterance situation", as traditionally thought, but rather "is determined entirely by grammar—by rules of language that have largely been missed". The missed rules are ones of discourse coherence. The paper argues against this radical view as it applies to demonstrations, demonstratives, and the indexical 'I'. Stojnić's theories of demon-strations and demonstratives are found to be seriously incomplete, failing to meet the demands on any theory of reference. Furthermore, the paper argues that, so far as Stojnić's theories of these terms go, they are false. This argument appeals to perception-based theories of demonstratives, a part of the tradition that Stojnić strangely overlooks. The paper ends by arguing briefly that though coherence has a place in a theory of understanding, it has no place in a theory of meaning. [ABSTRACT FROM AUTHOR]

A series of experiments were carried out to develop a phytosanitary disinfestation protocol to kill Ceratitis capitata (Weidemann) (Mediterranean fruit fly, Diptera: Tephritidae) in 'Hayward' kiwifruit (Actinidia deliciosa (A. Chev.) C.F. Liang and A.R. Ferguson) and 'Zesy002' kiwifruit (Actinidia chinensis Planch.). Experiments on 4 immature life stages (eggs and 3 larval instars) with treatment durations of between 5 and 18 days showed that third instars were the most tolerant to temperatures around 3 °C, with the lethal time to 99.9968% (probit 9) mortality (LT99.9968) estimated to be 17.3 days (95% confidence interval (CI) 16.4–18.2). Larvae reared and treated in 'Zesy002' were significantly more susceptible to cold treatment than those reared in 'Hayward'. A large-scale trial testing a disinfestation protocol of 3 ± 0.5 °C for 18 days treated over 500,000 third-instar C. capitata with no survivors. These results demonstrate that a cold treatment of 3.5 °C or below for 18 days induces C. capitata mortality in kiwifruit at a rate that exceeds 99.9968% with a degree of confidence greater than 99%. [ABSTRACT FROM AUTHOR]

Experiments have led some philosophers to conclude that the reference determination of natural kind terms is neither simply descriptive nor simply causal‐historical. Various theories have been aired to account for this, including ambiguity, hybrid, and different‐idiolects theories. Devitt and Porter (2021) hypothesized that some terms are covered by one theory, some another, with a place for all the proposed theories. The present paper tests hypotheses that the term 'Rio de Janeiro Myrtle' is simply causal‐historical but the term 'rice' is hybrid. For, whereas the former term is of scientific but little practical interest, the latter is not: rice is a significant part of the human diet. So, we predicted there would be two factors to the reference determination of 'rice': a superficial‐descriptive one and a deep‐causal one. Our experiments confirmed these hypotheses using the methods of elicited production and truth value judgments. We take our results to support the hybrid Theory of 'rice' rather than the ambiguity or different‐idiolects theory. We were not testing 'myrtle' but, surprisingly, our results implied that 'myrtle' was partly descriptive and so like 'rice' but not 'Rio de Janeiro Myrtle'. A follow‐up experiment confirmed these puzzling results. More investigation is needed. [ABSTRACT FROM AUTHOR]

The paper presents a framework for interactive control of multi robots using mixed reality interfaces. The proposed approach can operate with both single and multi-robot systems, including interaction with industrial manipulators, mobile robots, and unmanned aerial vehicles (UAV). The human–robot interface allows both interactive and physical interaction with the robot. Particular attention is paid to a visualisation of the robots' intent during control. The presented framework has Robotic Operation System (ROS) as a core that can be connected to any robot and mixed reality interface. This allows us to make framework scalable and connect several different mixed reality devices and multiple heterogeneous robots. In the implementation part we connected our framework with Microsoft HoloLens, collaborative robot KUKA IIWA, mobile platform Plato, UAV designed on the basis of dji f450. The proposed framework was tested experimentally with real experimental setups mentioned above. The results showed the capabilities of the mixed reality system for interactive control of different robots' type. [ABSTRACT FROM AUTHOR]

Background Textured implants and expanders are associated with an increased risk of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL). As a result, plastic surgeons are utilizing smooth expanders, but many perceive these produce undesirable outcomes including infection, seroma, and lateral displacement. Objectives The aim of this study was to compare clinical outcomes of smooth and textured expanders. Methods Breast reconstruction patients from January 2018 to May 2021 were retrospectively reviewed. Included patients underwent placement of tissue expanders at the time of mastectomy. Primary outcomes included postoperative seroma, infection, malposition, days to final reconstruction, explantation, and the need for capsulorrhaphy. Results In total, 233 patients were reviewed, of whom 167 met both inclusion and exclusion criteria. There was no statistically significant difference in poor outcomes comparing smooth and textured expanders. Days to final reconstruction was lower with smooth expanders per breast (P =.0424). The subpectoral group was associated with an increased likelihood of undergoing capsulorrhaphy (P =.004). Prepectoral placement was associated with more seromas (P =.0176) and infections (P =.0245). Demographic factors included older age as a protective factor for undergoing capsulorrhaphy (odds ratio [OR] = 0.962, P =.038), obesity increased the risk of infection (OR = 5.683, P =.0279) and malposition (OR = 6.208, P =.0222), and radiation was associated with malposition (OR = 3.408, P =.0246). Conclusions There was no significant difference in poor outcomes between smooth and textured expanders. Patient demographics and anatomical plane placement had greater effects on infection, seroma, and the need for capsulorrhaphy compared with tissue expander texturing. Level of Evidence: 3 [ABSTRACT FROM AUTHOR]

The reliable, deterministic production of trustworthy high-quality single photons is a critical component of discrete variable, optical quantum technology. For single-photon based fully error-corrected quantum computing systems, it is estimated that photon sources will be required to produce a reliable stream of photons at rates exceeding 1 GHz (Vigliar et al., 2021). Photon multiplexing, where low probability sources are combined with switching networks to route successful production events to an output, are a potential solution but requires extremely fast single-photon switching with ultra-low-loss rates. In this paper, we examine the specific properties of the switching elements and present a new design that exploits the general one-way properties of common switching elements such as thermal pads. By introducing multiple switches to a basic, temporal multiplexing device, we can use slow switching elements in a multiplexed source being pumped at much faster rates. We model this design under multiple error channels and show that anticipated performance is now limited by the intrinsic loss rate of the optical waveguides within integrated photonic chipsets. While the developed design does not achieve the necessary 1 GHz photon rate, we demonstrate design elements that could become useful when underlying technology improves. [ABSTRACT FROM AUTHOR]

Rainfall intensity in the United Kingdom is projected to increase under climate change with significant implications for rainfall‐driven (combined pluvial and fluvial) flooding. In the UK, the current recommended best practice for estimating changes in pluvial flood hazard under climate change involves applying a simple percentage uplift to spatially uniform catchment rainfall, despite the known importance of the spatial and temporal characteristics of rainfall in the generation of pluvial floods. The UKCP Local Convective Permitting Model (CPM) has for the first time provided the capacity to assess changes in flood hazard using hourly, 2.2 km CPM precipitation data that varies in space and time. Here, we use an event set of ∼13,500 precipitation events across the three UKCP Local epochs (1981–2000, 2021–2040, and 2061–2080) to simulate rainfall‐driven flooding using the LISFLOOD‐FP hydrodynamic model at 20 m resolution over a 750 km2 area of Bristol and Bath, UK. We find that both the event set and uplift approaches indicate an increase in flood hazard under near‐term (2021–2040) and future (2061–2080) climate change. However, the event set produces markedly higher estimates of flood hazard when compared to the uplift approach, ranging from 19% to 49% higher depending on the return period. This suggests including the full spatiotemporal rainfall variability and its future change in rainfall‐driven flood modeling is critical for future flood risk assessment. Plain Language Summary: Climate change is making rainfall more extreme. However, the detailed change in the space and time characteristics of rainfall are not well known and not represented in flood risk assessment. Instead, standard practice uses spatially uniform rainfall derived from historical records and increases them by a fixed percentage uplift to account for the impact of climate change. These uplifts are generated from climate model simulations that are analyzed to determine average rainfall changes. Failure to account for the changing space‐time characteristics of rainfall means that this standard approach likely mis‐estimates future changes in flooding. To test this hypothesis, we use high space and time resolution predictions of future rainfall patterns considering climate change to drive a detailed flood inundation model over the Bristol and Bath urban region in south‐west UK. Flood hazard is projected to increase in future, with increases greater when using full space‐time rainfall data rather than the standard uplift approach. This has important implications for how we estimate changes in flooding from changing rainfall with global warming. Key Points: We produce flood hazard estimates using spatiotemporal rainfall data from new convection permitting climate projections (UKCP Local)We find the UKCP Local rainfall data gives higher estimates of flood hazard compared to standard climate change uplift approachesRepresenting full spatiotemporal rainfall and its future change is crucial for future flood risk assessment [ABSTRACT FROM AUTHOR]

In the last two decades, there has been a global movement towards pedagogies that create more inclusive school environments in order to meet the needs of diverse learners. One such approach is Universal Design for Learning (UDL), which foregrounds the design of flexible and accessible learning experiences for all, regardless of learner characteristics. Technology is a key enabler in this. To date, much of the research on UDL has focused on its impact in higher education, with less evidence available on the use of UDL within second‐level education. This systematic literature review of n = 15 empirical studies selected from a wide‐ranging search that returned an initial result of n = 1253 explores how the affordances of digital technology have been harnessed for UDL enactment at second level. The findings show that, to date, empirical research at second level has focused mostly on the easy wins within the UDL principle of Representation, where educators offer choice about how learners access content. However, there is a clear gap in UDL research on the use of technologies to support the Engagement and Action & Expression principles of UDL, supporting student self‐regulation and self‐assessment, and on technology‐mediated communication and collaboration. The paper highlights the potential for future cross‐pollination of research in educational technology with UDL. Practitioner NotesWhat is already known about this topicUniversal Design for Learning has been extensively researched in higher education and special education contexts but much less so at K‐12, in particular at second level.Technology offers many affordances that can provide choice and variation in the learning process, which can be harnessed in a UDL approach.The transformative potential of technology in educational contexts was not fully realised pre‐COVID.The COVID pandemic saw an acceleration in technology adoption for learning, but it remains to be seen whether technology is being deployed to complement or transform existing practices.What this paper addsThis paper clearly identifies which affordances of technology are commonly deployed in UDL implementations, particularly noting the provision of choice through multi‐media options for Representation and expression.There is a clear gap in UDL research on the use of technologies to support self‐regulation and self‐assessment, (eg, peer, teacher and automated feedback tools) and on technology‐mediated communication and collaboration.The UDL literature does not address the potential negative impacts of technology within the learning context or the short‐lived nature of positive impacts (novelty effect).Implications for practice and/or policyWhile technology affords great opportunities for choice and Engagement, the design of the learning experience must take priority, availing of technology as needed.There are great opportunities for cross‐pollination of research at the forefront of educational technology and universal design to address any gaps in technology use in UDL implementations. [ABSTRACT FROM AUTHOR]

The goal of the study was to identify and characterize RNA virus variants containing mutations spread over genomic distances >5 kb. As proof of concept, high-quality viral RNA of the Dengue 2 component of Takeda's tetravalent dengue vaccine candidate (TDV-2) was used to develop a reverse transcription–polymerase chain reaction protocol to amplify a ∼5.3 kb cDNA segment that contains the three genetic determinants of TDV-2 attenuation. Unique molecular identifiers were incorporated into each viral cDNA molecule for PacBio library preparation to improve the quantitative precision of the observed variants at the attenuation loci. Following assay optimization, PacBio long-read sequencing was validated with multiple clone-derived TDV-2 revertant variants and four complex revertant mixtures containing various compositions of TDV-2 and revertant viruses. PacBio sequencing analysis correctly identified and quantified variant composition in all tested samples, demonstrating that TDV-2 revertants could be identified and characterized and supporting the use of this method in the differentiation and quantification of complex variants of other RNA viruses. Long-read sequencing can identify complex RNA virus variants containing multiple mutations on a single-genome molecule, which is useful for in-depth genetic stability and revertant detection of live-attenuated viral vaccines, as well as research in virus evolution to reveal mechanisms of immune evasion and host cell adaption. [ABSTRACT FROM AUTHOR]

Time-resolved radioluminescence (TRRL) properties of the Cu(I) cluster Cu4I62− upon pulsed X-ray, β-ray or α-particle excitation are described. The longer (>2 μs) TRRL component displays exponential decay comparable to pulsed UV excitation; however, temporal behaviour at shorter times indicates that high local excited state density provides an alternative decay channel. [ABSTRACT FROM AUTHOR]

Background: Supracondylar humerus fractures (SCHFs) represent the most common pediatric elbow fracture, constituting approximately 12–17% of all pediatric fractures. The vast majority of operative supracondylar humerus fractures are treated with closed reduction and percutaneous pinning (CRPP); however, the estimated rate of SCHFs requiring open reduction is approximately 12.7%. Aim: This study aims to analyze the likelihood of open reduction in pediatric extension-type SCHFs and to reaffirm the traditional teaching of reduction techniques described by Smith and Rang. Methods: A single-surgeon retrospective analysis of 56 operative pediatric SCH cases (51 extension-type, 6 flexion-type) who underwent either CRPP or open reduction over a 16-year period was performed. All cases were performed using the aforementioned reduction technique. The Modified Gartland's classification was utilized in the analysis of extension-type SCHF radiographs. Results: Gartland IIA fractures constituted 38% of SCHFs, 9% of Gartland IIB, 43% of Gartland III, and 7% of flexion-type. The rate of open reduction in SCHFs was 1.8% (1 out of 56 cases), performed in a flexion-type injury. All extension-type fractures were successfully managed with either CRPP or manipulation and casting alone. Of the cases requiring CRPP, 45% were divergent lateral wires, and 55% were crossed wires. Conclusions: In our series, a 1.8% rate of open reduction was indicated in flexion-type SCH fractures. All 52 cases of extension-type SCHFs were successfully managed with closed reduction with or without percutaneous pinning. Successful closed reduction using the concept of intact periosteal hinge to aid and maintain reduction is crucial. [ABSTRACT FROM AUTHOR]

The proportion of older adults and frail adults in Canada is expected to rise significantly in upcoming years. Currently, a considerable number of older adults do not actively participate in developing their own care plans; prior research has indicated several benefits of patient engagement in this process. Thus, we conducted a mixed methods study that examined the prevalence of rehabilitation goals and identified these for 305 community dwelling older adults referred to a frailty intervention clinic utilizing Comprehensive Geriatric Assessment (CGA) between 2014 and 2018. Top patient concerns included mobility (84%), services, systems, and policies (51%), sensory functions and pain (50%), and self-care or domestic life (47%). The most common referrals or recommendations for patients included further follow-up with a physician or specialist (36%), referral to an onsite falls prevention clinic (31%), and medication modifications (31%). Based upon these findings, we recommend greater utilization of CGA within a team-based approach to improve patient care by allowing for greater collaboration and shared decision-making by healthcare providers. Moreover, CGA can be an effective tool to meet the complex and unique health-care needs of frail patients while incorporating patient goals. This is vitally important considering the predicted growth in the population of frail and/or older patients, as well as the current challenges and shortfalls in meeting the health-care needs of this population. [ABSTRACT FROM AUTHOR]

In this Tutorial, we introduce basic conceptual elements to understand and build a gate-based superconducting quantum computing system. [ABSTRACT FROM AUTHOR]

Congenital neutropenia, defined by absolute neutrophil count (ANC) <2.5x109/L in infants, includes a variety of genotypic alterations that manifest with chronic immunodeficiency and, as a result, presents in infancy with recurrent infections. The gene that encodes neutrophil elastase, ELANE, has pathological variants yielding two distinct phenotypes: severe congenital neutropenia (SCN) and cyclic neutropenia (CyN). While SCN exhibits persistent pathologic ANC values, CyN exhibits pathologic ANC values in a patterned fashion which can recur in 21-day intervals. Here, we describe a patient with a novel heterozygous ELANE deletion (c.224+(4_19)del16) presenting with clinical features consistent with CyN and a response to first-line therapy of granulocyte colonystimulating factor. [ABSTRACT FROM AUTHOR]

The installation of solar facilities is increasing rapidly in the Mojave Desert USA, with the largest facility in North America (3227 ha) currently being built 30 km north of Las Vegas, NV. At the state level, Nevada (USA) has developed an energy plan to diversify its energy portfolio by 2030 with green energy representing 50% of the energy produced. Although solar is considered a clean energy, it does require significant amounts of land and as such may have negative consequences at the habitat and ecosystem levels. A multi-year study was conducted to assess the impact a photovoltaic facility in the Mojave Desert had on the growth and physiological response of two native shrubs (Ambrosia dumosa and Larrea tridentata) growing inside and outside the facility. These species were selected because they were the dominant species at the site and are representative of desert scrub communities throughout the Mojave Desert. At the time of construction, native plants and washes were left intact inside the solar facility. The solar panel arrays were separated at either 8 m or 10 m. Plants were selected for monitoring on the basis of location: at the panel drip line, below the panels, or midway between panel rows. Abiotic factors, including PAR, reference evapotranspiration, precipitation, soil water in storage, and infiltration, were monitored bi-monthly. The growth and physiological status of the plants were assessed by monitoring leaf water potential, chlorophyll index, canopy temperatures, non-structural carbohydrates in the roots and stems, leaf tissue ion concentrations, stem elongation, and seed production. Plants at the bottom edges of the panels received more precipitation due to runoff from the panels, which led to increased soil moisture in the long spacing but not the short spacing. The lower soil water in storage in the short spacing was related to greater growth and higher soil water extraction. Although the area under the panels provided shade in the summer and warmer temperatures in the winter, the incoming PAR was reduced by as much as 85%, causing plants growing under the panels to be spindly with lower canopy volume (L. tridentata, p = 0.03) and seed yield (A. dumosa, p = 0.05). Ambrosia plants remained green in color year-round (not going into winter dormancy) inside the facility and had elevated levels of starch in their roots and stems compared with plants growing at the outside control sites (p < 0.001). Larrea growing outside the facility had lower xylem water potentials compared with those inside the facility (p < 0.001), lower chlorophyll index (p < 0.001, Ambrosia as well), and lower stem elongation (p < 0.001), supporting the conclusion that both Larrea and Ambrosia performed better inside the facility. Shifts in δ13 C suggested greater water-use efficiency at the locations with the least amount of soil water in storage. Our results support the installation of solar facilities that minimize the impact on native plants and wash connectivity (ecovoltaics), which should translate into a reduced negative impact at the habitat and ecosystem levels. Basedon our results, energy companies that embrace ecovoltaic systems that take an engineering and biological approach should provide acceptable environments for desert fauna. However, corridors (buffers) will need to be maintained between solar facilities, and fences will need to have openings that allow for the continuous flow of animals and resources. [ABSTRACT FROM AUTHOR]

Concerns with cultural variation and epistemic perspectives have played major roles in experimental semantics. They dominate Li's book (2023). Li's own experimental work provides two promising explanations of the cultural variation: Chinese, but not Americans, tend to agree with a character's false statement because they think it is not her fault that she is wrong or because they are socially conforming. So, the notice argues, the cultural variation is a red herring to the theory of reference. Li preferred explanation is that Chinese and Americans take different epistemic perspectives. The notice argues that this is misguided and another red herring. [ABSTRACT FROM AUTHOR]

Background: The natural history of Kaplan fiber (KF) injuries after acute primary anterior cruciate ligament (ACL) reconstruction (ACLR) remains unknown. Purpose/Hypothesis: The purpose of this study was to evaluate the temporal change in the magnetic resonance imaging (MRI) appearance of the KF complex after acute primary ACLR. It was hypothesized that KF injuries would resolve with time. Study Design: Case series; Level of evidence, 4. Methods: A retrospective MRI analysis was conducted on 89 patients with ACL-injured knees to assess the change in the radiological appearance of KFs after primary ACLR. Patients who had undergone index MRI and ACLR within 90 days of the injury and further MRI at 9 months after surgery were included. Diagnostic criteria to identify radiological evidence of a KF injury and its subsequent resolution were applied, including the presence of high signal intensity on fluid-sensitive sequences, which is indicative of a pathological process radiologically. The proximity of KFs to the femoral cortical suspensory device (CSD) was noted on MRI scans and quantified in millimeters. Results: A KF injury was identified in 30.3% (27/89) of patients, with isolated high signal intensity observed in an additional 18.0% (16/89). At 9 months, MRI evidence of the reconstitution of the KF complex was found in 51.9% (14/27) of patients, with persistent discontinuity in the remaining patients (13/27). All patients (16/16) with isolated high signal intensity had complete resolution on repeat MRI scans. KF thickening was observed in 26.1% (12/46) of patients with previously healthy KFs and in 25.0% (4/16) with isolated high signal intensity. The CSD was positioned in close proximity (≤6 mm) to the center of the KF attachment in 61.8% (55/89) of patients, and this was associated with increased rates of KF thickening. Conclusion: The KF injury resolved radiologically in over half of the patients at 9 months after acute primary ACLR. High signal intensity in the region of the KFs on index MRI scans resolved in all cases, with evidence of residual KF thickening in only one-quarter of cases on repeat MRI scans, equivalent to the rate in those with healthy KFs. As such, it is not advisable to use high signal intensity on preoperative MRI scans as the sole criterion for the diagnosis of a KF injury. The position of the CSD after ACLR was intimately related to the KF attachment in the majority of patients, which was associated with KF thickening on postoperative MRI scans. [ABSTRACT FROM AUTHOR]

Constructive episodic retrieval processes play an adaptive role in supporting divergent thinking (i.e., creatively combining diverse bits of information) and means-end problem solving (i.e., generating steps to solve a social problem). However, the constructive nature of episodic memory that supports these adaptive functions also leads to memory error. In three experiments we aimed to identify a direct link between divergent thinking and means-end problem solving – as assessed in the Alternative Uses Task (AUT) and Means-End Problem Solving (MEPS) task – with the generation of false memories in the Deese-Roediger-McDermott paradigm. In Experiment 1, we replicated prior findings where false memory was positively correlated with performance on the AUT, and also showed for the first time that increased performance in the MEPS task is associated with increased false recall. In Experiment 2, we demonstrated that the link between false recall and performance on the MEPS task did not extend to other forms of problem solving, as assessed with the Everyday Descriptions Task (EDT). In Experiment 3, we showed that when the EDT was preceded by the MEPS task in an attempt to influence participants to engage in a similar episodic-problem solving strategy, performance in both tasks was correlated with false memory. These findings provide evidence for a direct link between the adaptive benefits of constructive episodic processes, in the form of enhanced divergent creative thinking and problem solving, and costs, in the form of increased memory error. [ABSTRACT FROM AUTHOR]

We compared the quality of clinician-authored and student-authored multiple choice questions (MCQs) using a formative, mock examination of clinical knowledge for medical students. Multiple choice questions are a popular format used in medical programs of assessment. A challenge for educators is creating high-quality items efficiently. For expediency's sake, a standard practice is for faculties to repeat items in examinations from year to year. This study aims to compare the quality of student-authored with clinician-authored items as a potential source of new items to include in faculty item banks. We invited Year IV and V medical students at the University of Adelaide to participate in a mock examination. The participants first completed an online instructional module on strategies for answering and writing MCQs, then submitted one original MCQ each for potential inclusion in the mock examination. Two 180-item mock examinations, one for each year level, were constructed. Each consisted of 90 student-authored items and 90 clinician-authored items. Participants were blinded to the author of each item. Each item was analyzed for item difficulty and discrimination, number of item-writing flaws (IWFs) and non-functioning distractors (NFDs), and cognitive skill level (using a modified version of Bloom's taxonomy). Eighty-nine and 91 students completed the Year IV and V examinations, respectively. Student-authored items, compared with clinician-authored items, tended to be written at both a lower cognitive skill and difficulty level. They contained a significantly higher rate of IWFs (2–3.5 times) and NFDs (1.18 times). However, they were equally or better discriminating items than clinician-authored items. Students can author MCQ items with comparable discrimination to clinician-authored items, despite being inferior in other parameters. Student-authored items may be considered a potential source of material for faculty item banks; however, several barriers exist to their use in a summative setting. The overall quality of items remains suboptimal, regardless of author. This highlights the need for ongoing faculty training in item writing. [ABSTRACT FROM AUTHOR]

Flooding is one of the most common natural hazards, causing disastrous impacts worldwide. Stress-testing the global human-Earth system to understand the sensitivity of floodplains and population exposure to a range of plausible conditions is one strategy to identify where future changes to flooding or exposure might be most critical. This study presents a global analysis of the sensitivity of inundated areas and population exposure to varying flood event magnitudes globally for 1.2 million river reaches. Here we show that topography and drainage areas correlate with flood sensitivities as well as with societal behaviour. We find clear settlement patterns in which floodplains most sensitive to frequent, low magnitude events, reveal evenly distributed exposure across hazard zones, suggesting that people have adapted to this risk. In contrast, floodplains most sensitive to extreme magnitude events have a tendency for populations to be most densely settled in these rarely flooded zones, being in significant danger from potentially increasing hazard magnitudes given climate change.This study presents a global analysis of the sensitivity of inundated areas and population exposure to varying flood event magnitudes globally for 1.2 million river reaches. The authors show that topography and drainage areas correlate with flood sensitivities as well as with societal behavior. [ABSTRACT FROM AUTHOR]

The c-Jun N-terminal kinases (JNKs) are a family of proteins that, once activated by stress stimuli, can alter neuronal functions and survival. The JNK cascade plays a crucial role in the post-synaptic neuronal compartment by altering its structural organization and leading, at worst, to an overall impairment of neuronal communication. Increasing evidence suggests that synaptic impairment is the first neurodegenerative event in Alzheimer's disease (AD). To better elucidate this mechanism, we longitudinally studied 5xFAD mice at three selected time points representative of human AD symptom progression. We tested the mice cognitive performance by using the radial arm water maze (RAWM) in parallel with biochemical evaluations of post-synaptic enriched protein fraction and total cortical parenchyma. We found that 5xFAD mice presented a strong JNK activation at 3.5 months of age in the post-synaptic enriched protein fraction. This JNK activation correlates with a structural alteration of the post-synaptic density area and with memory impairment at this early stage of the disease that progressively declines to cause cell death. These findings pave the way for future studies on JNK as a key player in early neurodegeneration and as an important therapeutic target for the development of new compounds able to tackle synaptic impairment in the early phase of AD pathology. [ABSTRACT FROM AUTHOR]

Background: The subgenus Syrrhophus (genus Eleutherodactylus) contains >40 species of small, direct-developing frogs that occur at low to moderate elevations from Texas through Mexico and into Guatemala and Belize, with two species in western Cuba. Morphological conservatism and phenotypic convergence have made species delimitation challenging and resulted in a complicated taxonomic history. Since 2015, molecular systematic work has uncovered eleven new species from western Mexico and one from eastern Mexico, but current taxonomy still underestimates species level diversity and there is confusion surrounding the validity and boundary of several species. Methods: We used phylogenetic analysis of 16S ribosomal RNA (rRNA) sequences, multivariate statistical analysis of morphological data, and bioacoustic analysis of male advertisement calls to discover two additional unnamed species of Eleutherodactylus from Central and Western Mexico. We describe those species here. Results: Eleutherodactylus (Syrrhophus) humboldti sp. nov. is described from the Quaternary Valle de Bravo volcanic field of the Eje Neovolcánico in Central Mexico. This species is sister to E. maurus and is 3% divergent in 16S. Eleutherodactylus (Syrrhophus) jamesdixoni sp. nov. is described from the Sierra Madre Occidental of western Mexico. This species is sister to E. nitidus and is 3% divergent. We provide color photographs, advertisement call recordings, and molecular diagnoses of these new species and their sister species to aid future workers. [ABSTRACT FROM AUTHOR]

The renin-angiotensin-aldosterone system (RAAS), traditionally associated with blood pressure and fluid regulation, also plays a role in tumorigenesis. Renin-angiotensin-aldosterone system inhibitors (RAASI), including angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs), have been shown to improve outcomes in various malignant neoplasms. In metastatic urothelial cancer, the use of RAASI have been associated with higher rates of tumor regression in patients receiving immunotherapy (IO) with PD1/L1 inhibitors. This is thought to be due to RAASI-induced downregulation of TGF-beta, for which increased expression is a known mechanism of PD1/L1 inhibitor resistance. We hypothesized that concurrent RAASI in patients with mRCC receiving IO is associated with increased tumor regression. We conducted a retrospective analysis of patients with mRCC receiving IO as a first- or second-line therapy from 2016-2023 at the University of Virginia. A logistic regression model was used to evaluate the impact of concurrent RAASI on tumor regression. The primary endpoint was any regression of tumor on imaging. Data were available for 128 patients with mRCC who received IO as a first- (n = 91, 71.0%) or second- (n = 37, 28.9%) line treatment. Patients who received RAASI during IO were more likely to have tumor regression compared to patients who were not on concurrent RAASI (OR 3.84 [95% CI 1.81-8.47, P =<.001). This held true regardless if patients received IO as a first-line (OR 2.83 [95% CI 1.2-6.94], P =.0173) or second-line (OR 9.5 [95% CI 1.89-73.1], P =.005) treatment. Our hypothesis generating study suggests that in our mRCC population, concurrent use of RAASI in patients receiving IO was associated with a significantly increased likelihood of tumor regression. These findings highlight the potential therapeutic advantage of RAASI in combination with IO for mRCC patients. Further exploration of this association is warranted in prospective studies to improve treatment outcomes for this patient population. Renin-angiotensin-aldosterone system inhibitors (RAASI) have been shown to improve outcomes in various malignancies. In this retrospective, single-center study, we found that concurrent use of RAASI in patients with mRCC receiving IO is associated with a significantly increased likelihood of tumor regression. Our findings suggest the potential therapeutic advantage of RAASI in combination with IO for mRCC patients. [ABSTRACT FROM AUTHOR]

Background: Anterior cruciate ligament (ACL) rupture is an increasingly common injury in the young population. Unfortunately, reinjury rates in this population following ACL reconstruction (ACLR) are also very high. As such, lateral extra-articular procedures have been proposed to augment ACLR and shown to reduce reinjury rates. Most techniques use a strip of iliotibial band (ITB) fixed proximally on the distal femur in close proximity to the lateral femoral epicondyle, which in the skeletally immature patient may be closely associated with the distal femoral physis. In addition, there is also a risk of convergence with the femoral tunnel for the ACLR. The modified Ellison technique avoids both of these risks given it is a distally based tenodesis with its fixation point on the proximal tibial epiphysis. The purpose of this video is to describe a modified Ellison technique in a skeletally immature patient. Indications: Primary ACLR in skeletally immature patients at high risk of ACL graft rerupture due to their young age, a positive family history of ACL rupture in a first-degree relative, previous contra-lateral ACL rupture, generalized joint hypermobility, high-grade pivot-shift test, and participating in pivoting sports. Technique Description: The modified Ellison technique is a distally based lateral extra-articular procedure. A 1-cm strip of ITB is detached from Gerdy's tubercle, passed beneath the lateral collateral ligament, and reattached back to from where it was removed. The fixation is within the proximal epiphysis of the tibia. Results: In a high-risk adult population, the modified Ellison technique has been shown to have a low ACL graft reinjury rate at 2 years following an ACLR. Biomechanical studies have demonstrated that a modified Ellison technique closely restores native knee kinematics following simulated anterolateral complex injury. Discussion/Conclusion: The modified Ellison technique is a safe and reproducible lateral extra-articular procedure in skeletally immature patients when performed in combination with an ACLR. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. Graphical Abstract This is a visual representation of the abstract. [ABSTRACT FROM AUTHOR]