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Falls account for 95 percent of hip fractures in older adults. Wearable hip protectors reduce hip fracture risk in long-term care settings, but their use is low among community-dwelling older adults. We conducted interviews to explore how hip protectors are perceived by 27 community-dwelling older adults who visited the Fraser Health Fall Prevention Mobile Clinic in British Columbia. Directed content analysis focused on perceived benefits, design preferences, and cost as a barrier to use of hip protectors. Most participants acknowledged the benefits of hip protectors in reducing the risk of hip fracture, enhancing physical activity, and reducing the fear of falling. However, most participants did not perceive they were at high enough risk to warrant the use of hip protectors. Participants also discussed how willingness to wear depended on design features, including style, pad thickness, appearance, ease of use, fit, comfort, and laundering. Participants also noted the cost, ranging from $60 to $120, as a barrier.
Frailty in older adults with cancer is complex, evolving, and often overlooked in care. This qualitative study explored how frailty is experienced and reported using patient-reported outcome measures (PROMs) and visualized over time through journey maps. Eleven participants (65+) completed the Comprehensive Frailty Assessment Instrument (CFAI) and semi-structured interviews. Individual journey maps combined CFAI scores with personal narratives to track changes in physical, mental, and social aspects of frailty over time. While PROMs showed variability in frailty severity, narratives revealed discrepancies, such as low frailty scores despite significant treatment-related challenges. Fatigue, emotional distress, and isolation were common during treatment, with lasting impacts post-treatment. Findings suggest PROMs alone may not fully capture lived experience. Integrating narrative dialogue provides a more person-centred approach to frailty assessment and care planning.
Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.
Background: Traumatic brain injury (TBI) patients exhibit variable post-injury recovery trajectories. Days at Home (DAH) is a patient-centered measure that captures healthcare transitions and offers a more nuanced understanding of recovery. Here, we use DAH to characterize longterm recovery trajectories for moderate to severe TBI (msTBI) survivors. Methods: This multicenter retrospective cohort study utilized population health data from Ontario to identify adults sustaining isolated msTBI hospitalized between 2009-2021. DAH were calculated in distinct 30-day intervals from index admission to 3 years post-injury; latent class mixed modeling identified unique recovery trajectories and trajectory attributes were quantified. Results: There were 2,510 patients eligible for latent class analysis. Four DAH trajectories were identified: early recovery (69.9%), intermediate recovery (11.4%), late recovery (2.9%), and poor recovery (15.8%). Patients in the poor recovery group were older, more frail, and had lower admission GCS scores, while those in early recovery exhibited lower acute care needs. Intermediate and late recovery groups exhibited protracted transitions home, with near-complete reintegration by 24 months. A prediction model distinguished unfavorable trajectories with good accuracy (C-index=0.824). Conclusions: Despite high initial institutional care requirements, 85% of patients reintegrated into the community within three years of msTBI. These findings shed light on post-injury care requirements for brain-injured patients.
We evaluated quality characteristics of cardiac point-of-care ultrasound performed in our paediatric cardiac ICU. Of 47 included patients, diagnostic imaging was feasible in a high percentage of patients with good image quality. Intensivist interpretations of images were highly specific for dichotomised abnormal findings when compared to interpretation from a cardiologist with expertise in imaging but challenges in accurately assessing depressed ventricular function and the risk of discrepant interpretations exist even amongst frequent users with extensive training and experience. These findings may serve as a template for continued development of cardiac point-of-care ultrasound in a high-impact clinical environment.
We provide an assessment of the Infinity Two fusion pilot plant (FPP) baseline plasma physics design. Infinity Two is a four-field period, aspect ratio $A = 10$, quasi-isodynamic stellarator with improved confinement appealing to a max-$J$ approach, elevated plasma density and high magnetic fields ($ \langle B\rangle = 9$ T). Here $J$ denotes the second adiabatic invariant. At the envisioned operating point ($800$ MW deuterium-tritium (DT) fusion), the configuration has robust magnetic surfaces based on magnetohydrodynamic (MHD) equilibrium calculations and is stable to both local and global MHD instabilities. The configuration has excellent confinement properties with small neoclassical transport and low bootstrap current ($|I_{bootstrap}| \sim 2$ kA). Calculations of collisional alpha-particle confinement in a DT FPP scenario show small energy losses to the first wall (${\lt}1.5 \,\%$) and stable energetic particle/Alfvén eigenmodes at high ion density. Low turbulent transport is produced using a combination of density profile control consistent with pellet fueling and reduced stiffness to turbulent transport via three-dimensional shaping. Transport simulations with the T3D-GX-SFINCS code suite with self-consistent turbulent and neoclassical transport predict that the DT fusion power$P_{{fus}}=800$ MW operating point is attainable with high fusion gain ($Q=40$) at volume-averaged electron densities $n_e\approx 2 \times 10^{20}$ m$^{-3}$, below the Sudo density limit. Additional transport calculations show that an ignited ($Q=\infty$) solution is available at slightly higher density ($2.2 \times 10^{20}$ m$^{-3}$) with $P_{{fus}}=1.5$ GW. The magnetic configuration is defined by a magnetic coil set with sufficient room for an island divertor, shielding and blanket solutions with tritium breeding ratios (TBR) above unity. An optimistic estimate for the gas-cooled solid breeder designed helium-cooled pebble bed is TBR $\sim 1.3$. Infinity Two satisfies the physics requirements of a stellarator fusion pilot plant.
Medicare claims are frequently used to study Clostridioides difficile infection (CDI) epidemiology. However, they lack specimen collection and diagnosis dates to assign location of onset. Algorithms to classify CDI onset location using claims data have been published, but the degree of misclassification is unknown.
Methods:
We linked patients with laboratory-confirmed CDI reported to four Emerging Infections Program (EIP) sites from 2016–2021 to Medicare beneficiaries with fee-for-service Part A/B coverage. We calculated sensitivity of ICD-10-CM codes in claims within ±28 days of EIP specimen collection. CDI was categorized as hospital, long-term care facility, or community-onset using three different Medicare claims-based algorithms based on claim type, ICD-10-CM code position, duration of hospitalization, and ICD-10-CM diagnosis code presence-on-admission indicators. We assessed concordance of EIP case classifications, based on chart review and specimen collection date, with claims case classifications using Cohen’s kappa statistic.
Results:
Of 12,671 CDI cases eligible for linkage, 9,032 (71%) were linked to a single, unique Medicare beneficiary. Compared to EIP, sensitivity of CDI ICD-10-CM codes was 81%; codes were more likely to be present for hospitalized patients (93.0%) than those who were not (56.2%). Concordance between EIP and Medicare claims algorithms ranged from 68% to 75%, depending on the algorithm used (κ = 0.56–0.66).
Conclusion:
ICD-10-CM codes in Medicare claims data had high sensitivity compared to laboratory-confirmed CDI reported to EIP. Claims-based epidemiologic classification algorithms had moderate concordance with EIP classification of onset location. Misclassification of CDI onset location using Medicare algorithms may bias findings of claims-based CDI studies.
The selection, design and optimization of a suitable blanket configuration for an advanced high-field stellarator concept is seen as a key feasibility issue and has been incorporated as a vital and necessary part of the Infinity Two fusion pilot plant physics basis. The focus of this work was to identify a baseline blanket which can be rapidly deployed for Infinity Two while also maintaining flexibility and opportunities for higher performing concepts later in development. Results from this analysis indicate that gas-cooled solid breeder designs such as the helium-cooled pebble bed (HCPB) are the most promising concepts, primarily motivated by the neutronics performance at applicable blanket build depths, and the relatively mature technology basis. The lithium lead (PbLi) family of concepts, particularly the dual-cooled lithium lead, offer a compelling alternative to solid blanket concepts as they have synergistic developmental pathways while simultaneously mitigating much of the technical risk of those designs. Homogenized three-dimensional neutronics analysis of the Infinity Two configuration indicates that the HCPB achieves an adequate tritium breeding ratio (TBR) (1.30 which enables sufficient margin at low engineering fidelity), and near appropriate shielding of the magnets (average fast fluence of 1.3 ${\times}$ 10$^{18}$ n cm$^{-2}$ per full-power year). The thermal analysis indicates that reasonably high thermal efficiencies (greater than 30 %) are readily achievable with the HCPB paired with a simple Rankine cycle using reheat. Finally, the tritium fuel cycle analysis for Infinity Two shows viability, with anticipated operational inventories of less than one kilogram (approximately 675 g) and a required TBR (TBR$_{\textrm {req}}$) of less than 1.05 to maintain fuel self-sufficiency (approximately 1.023 for a driver blanket with no inventory doubling). Although further optimization and engineering design are still required, at the physics basis stage all initial targets have been met for the Infinity Two configuration.
We report the results of experiments designed to test the impact of social status on learning in a coordination game. In the experiment, all subjects observe the play of an agent who either has high status or low status. In one treatment the agent is another player in the game; in the other the agent is a simulated player. Status is assigned within the experiment based on answers to a trivia quiz. The coordination game has two equilibria: one is payoff-dominant but risky, and the other is risk-dominant. The latter is most commonly chosen in experiments where there is no coordination device. We find that a commonly observed agent enhances coordination on the payoff-dominant equilibrium more often when the agent has high status.
Transfers of resources in dictator games vary significantly by the characteristics of recipients. We focus on social norms and demonstrate that variation in the recipient changes both giving and injunctive norms and may offer an explanation for differences in giving. We elicit generosity using dictator games, and social norms using incentivized coordination games, with two different recipient types: an anonymous student and a charitable organization. A within-subjects design ensures that other factors are held constant. Our results show that differences in giving behavior are closely related to differences in social norms of giving across contexts. Controlling for individual differences in beliefs about the norm, subjects do not weight compliance with the norms in the student recipient or charity recipient dictator game differently. These results suggest that the impact of context on giving co-occurs with an impact on social norms.
We report the results of experiments conducted over the internet between two different laboratories. Each subject at one site is matched with a subject at another site in a trust game experiment. We investigate whether subjects believe they are really matched with another person, and suggest a methodology for ensuring that subjects’ beliefs are accurate. Results show that skepticism can lead to misleading results. If subjects do not believe they are matched with a real person, they trust too much: i.e., they trust the experimenter rather than their partner.
The potential for physicians, clinicians, and health professionals to contribute to the advancement of medical therapies through clinical research is significant. Yet, a lack of exposure to, or practical training in, the conduct of clinical research can inhibit health profession trainees from considering research careers, thus perpetuating the already limited influx of new talent. To enhance the sustainability of career pathways into research for all trainees, including those from traditionally underrepresented communities, trainees must experience early exposure to research concepts through robust training and hands-on opportunities. In 2015, the Duke Office of Clinical Research created a Research Immersion elective for Duke’s Master in Biomedical Sciences program, which prepares students for additional health professional training. The course trained students through didactic and practical experiences, with a unique interprofessional mentorship team including both principal investigator and clinical research professional mentors. Following eight cohorts of iterative course optimization, students’ confidence increased in all 24 research competencies assessed. A cross-sectional analysis of post-course outcomes in May 2024 revealed 40.4% of students had continued in research after the program and 60.6% had continued their health professions education. We attributed this success to applied learning and clear expectations and guidelines to support the mentor-student relationship.
The January 6th insurrection and its aftermath of obfuscation and denial were ostensibly racialized events. Under the guise of election fraud, white supremacists, white nationalists, and paramilitary groups attempted to overthrow established democratic procedures to retain a president who stoked racial antagonisms and racial divisions. African Americans, like many American citizens, watched in fear, anxiety, and foreboding as the groups most committed to their repression violently attacked and ransacked the Capitol.
We examine the extent to which the January 6th insurrection and its aftermath of denial and obfuscation influence African Americans’ racial resentment. Our results show how the racialized January 6th events were connected to heightened African American racial resentment. The most compelling result confirms that African Americans’ racial resentment stems from beliefs about justice and fairness.
Akathisia is a common adverse effect associated with use of dopamine receptor blocking agents.1,2 Symptoms of akathisia, in severe cases, may lead to discontinuation of treatment. Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist approved to treat schizophrenia and acute manic, mixed, and depressive episodes of bipolar 1 disorder. Cariprazine is well tolerated in patients across its indications, but is associated with a higher incidence of akathisia compared with placebo.3,4 This pooled post hoc analysis of data from phase 3 clinical trials of adjunctive cariprazine aimed to characterize the incidence, severity, and management of akathisia and other extrapyramidal symptoms (EPS) in adult patients with MDD.
Methods
Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to cariprazine 1.5 mg/d + ADT, cariprazine 3 mg/d + ADT, or placebo + ADT for 6 weeks of double-blind treatment. Post hoc analysis evaluated incidence, severity, and time to resolution of akathisia, restlessness, and other EPS; use of rescue medications; and the rate of discontinuation due to these treatment-emergent adverse events (TEAEs).
Results
A total of 1508 patients (cariprazine + ADT: 1.5 mg/d, n=502, 3 mg/d, n=503; placebo + ADT, n=503) were included in these 2 studies. The incidence of akathisia was greater with cariprazine 3 mg/d + ADT (9.7%) than with cariprazine 1.5 mg/d + ADT (6.4%) and placebo + ADT (2.0%). Most patients treated with cariprazine + ADT (94%) experienced only mild or moderate akathisia. The incidence of restlessness was 3.8% for patients treated with cariprazine 3 mg/d + ADT, 3.6% for cariprazine 1.5 mg/d + ADT, and 1.8% for placebo + ADT. The incidence of EPS excluding akathisia and restlessness was 4.4% for patients treated with cariprazine 3 mg/d + ADT, 4.6% for cariprazine 1.5 mg/d + ADT, and 3.2% for placebo + ADT. For patients treated with cariprazine + ADT and placebo + ADT, respectively, EPS-related study discontinuations were 1.4% and 0.4% due to akathisia, 0.2% and 0.0% due to restlessness, and 0.1% and 0.4% due to EPS excluding akathisia and restlessness. Rescue medications were used to treat EPS-related TEAEs during the double-blind treatment period in 3% of cariprazine-treated patients and 0.4% of placebo-treated patients. The mean time to resolution of akathisia during treatment was slightly shorter in cariprazine-treated patients (15.6 days) versus placebo-treated patients (19.5 days).
Importance
Incidence of akathisia was higher for cariprazine than placebo, with a lower incidence observed for patients treated with cariprazine 1.5 + ADT than with cariprazine 3 mg/d + ADT, suggestive of a dose related effect. Most patients experienced mild or moderate akathisia. Rates of study discontinuation and rescue medication use due to akathisia were low, suggesting that akathisia was tolerated by most patients.
This data was previously presented at the CINP World Congress; Montreal, Canada; May 7-10, 2023.
Anhedonia, a multidimensional domain including the reduced ability to experience pleasure, is a core diagnostic symptom of major depressive disorder (MDD) and a common residual symptom. In patients with MDD, anhedonia has been associated with poor treatment outcomes, suicide and reduced functioning and quality of life. This post-hoc analysis of data from a phase 3 trial (NCT03738215) evaluated the efficacy of adjunctive cariprazine (CAR) treatment on anhedonia symptoms in patients with MDD.
Methods
Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to CAR 1.5 mg/d + ADT, CAR 3 mg/d + ADT, or placebo + ADT for 6 weeks of double-blind treatment. Post hoc analyses evaluated the change from baseline to Week 6 in Montgomery–Åsberg Depression Rating Scale (MADRS) total score, MADRS anhedonia subscale score (items: 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]), and MADRS anhedonia item 8 in the overall modified intent-to-treat (mITT) population and in subgroups of patients with baseline MADRS anhedonia item 8 score of ≥4 or baseline anhedonia subscale score of ≥18. Least square (LS) mean change from baseline to Week 6 was analyzed using a mixed-effects model for repeated measures.
Results
There were 751 patients in the mITT population (CAR + ADT: 1.5 mg/d=250, 3 mg/d=252; placebo + ADT=249). At baseline, 508 (67.6%) patients had MADRS anhedonia item 8 scores ≥4, and 584 (77.8%) had MADRS anhedonia subscale scores ≥18. In the overall mITT population, LS mean change from baseline to Week 6 in anhedonia subscale score was significantly greater for CAR 1.5 mg/d + ADT (-8.4) and CAR 3 mg/d + ADT (-7.9) than for placebo + ADT (-6.8; both P<.05). The LS mean change from baseline in MADRS individual item 8 was also significantly greater for CAR 1.5 mg/d + ADT (-1.7) vs placebo + ADT (-1.3; P=.0085). In both subgroups of patients with baseline anhedonia, CAR 1.5 mg/d + ADT was associated with significantly greater reduction in MADRS total score, MADRS anhedonia subscale score, and MADRS item 8 score compared with placebo + ADT (all P<.05). In the CAR 3 mg/d + ADT group, significantly greater reductions vs placebo + ADT were observed for MADRS total score and MADRS anhedonia subscale score in the subgroup of patients with baseline anhedonia subscale scores ≥18 (both P<.05).
Importance
Adjunctive treatment with CAR was associated with a reduction in symptoms of anhedonia relative to adjunctive placebo in patients with MDD and inadequate response to ADT alone. In subgroups of patients with moderate-to-severe anhedonia at baseline, CAR + ADT demonstrated greater improvements than placebo + ADT in overall depressive symptoms and symptoms of anhedonia. These results suggest that adjunctive CAR treatment may be effective for improving symptoms of anhedonia in patients with MDD who have symptoms of anhedonia.
In the early modern period, both legal and illegal maritime predation was a common occurrence, but the expansion of European maritime empires exacerbated existing and created new problems of piracy across the globe. This collection of original case studies addresses these early modern problems in three sections: first, states' attempts to exercise jurisdiction over seafarers and their actions; second, the multiple predatory marine practices considered 'piracy'; and finally, the many representations made about piracy by states or the seafarers themselves. Across nine chapters covering regions including southeast Asia, the Atlantic archipelago, the North African states, and the Caribbean Sea, the complexities of defining and criminalizing maritime predation is explored, raising questions surrounding subjecthood, interpolity law, and the impacts of colonization on the legal and social construction of ocean, port, and coastal spaces. Seeking the meanings and motivations behind piracy, this book reveals that while European states attempted to fashion piracy into a global and homogenous phenomenon, it was largely a local and often idiosyncratic issue.
This article analyzes how under conditions of crisis certain social actors shift the metasemiotic frames through which minority languages may be approached in order to suit place-branding purposes and to make them more widely accessible for business usage. In the cases we investigate in Shetland and Western Ireland, the new meanings associated with language are connected with how crises are framed and constructed in discourse. We thus examine two types of crises in which certain social actors view language as part of the solution to ward off specific trouble: economic recession (Ireland) and depopulation (Shetland). With the branding potential of these languages then positioned as part of the solutions to “crises,” new indexical alignments exemplify the neoliberal metasemiotic framework through which all elements of social and cultural life may be strategically made marketable—in this case on the intra- and international markets on which people themselves are vied for.
Fifty-three tests designed to measure aspects of creative thinking were administered to 410 air cadets and student officers. The scores were intercorrelated and 16 factors were extracted. Orthogonal rotations resulted in 14 identifiable factors, a doublet, and a residual. Nine previously identified factors were: verbal comprehension, numerical facility, perceptual speed, visualization, general reasoning, word fluency, associational fluency, ideational fluency, and a factor combining Thurstone's closure I and II. Five new factors were identified as originality, redefinition, adaptive flexibility, spontaneous flexibility, and sensitivity to problems.