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There is growing concern about the proliferation of radical groups and violent content on social media platforms such as YouTube. These platforms present unique capacities to promote radicalised content, as they allow the flourishing of digital creators who amass large audiences and communicate their ideas in a compelling video format. Notwithstanding, consumer research has not yet provided a conceptualisation of such antagonistic online consumer gatherings in the ephemeral social media context. We investigate this phenomenon by combining netnographic sensibility with digital methods to explore the case of pro-gun YouTubers in Brazil. We propose the notion of online consumer counterpublics, which are online consumer collectives socio-technically shaped and promoted by social media influencers and their audiences on social media platforms based on strong oppositional discourses, ideas, affectivities, and values associated with a consumption topic, and who develop a compelling counter-hegemonic social identity. [ABSTRACT FROM AUTHOR]

The skin is the largest organ in the body and the only one to come into contact with solar UV radiation (UVR). UVA (320-400 nm) is a significant contributor to UV-related skin damage. The UVA spectrum makes up over 95% of solar-UV energy reaching the earth's surface causing the majority of the visible signs of skin photoaging. Many consumer products also emit UVA, including nail dryers. There have been sporadic reports suggesting that these units may be contributing to skin cancer incidence. This notion was recently bolstered by a finding that nail dryer-irradiated mammalian skin cells develop a mutational signature consistent with UVA exposure. This report was surprising considering the comparatively low level of UVA to which the skin is exposed during nail treatments. In this research, we investigated how UVA-emitting devices caused cytotoxic/genotoxic impact after only low levels of UVA exposure. Our data showed that levels of UVA in the unit are highly variable and location dependent. We confirm previous reports that using prolonged exposure protocols could induce significant levels of DNA damage. It was also determined that UV-induced DNA damage only partially correlated with the level of UVA fluency. On investigation, we found that the unit had a rapid increase in internal temperature when in use. Exposing human cells to these elevated temperatures acted synergistically with UVA to magnify the cytotoxic and genotoxic impact of UV irradiation. [ABSTRACT FROM AUTHOR]

This is a single arm, open label perioperative trial to assess the feasibility, pharmacokinetics and pharmacodynamics of treatment with safusidenib following biopsy, and prior to surgical resection in patients with IDH1 mutated glioma who have not received radiation therapy or chemotherapy. Fifteen participants will receive treatment in two parts. First, biopsy followed by one cycle (28 days) of safusidenib, an orally available, small molecular inhibitor of mutated IDH1, then maximal safe resection of the tumor (Part A). Second, after recovery from surgery, safusidenib until disease progression or unacceptable toxicity (Part B). This research will enable objective measurement of biological activity of safusidenib in patients with IDH1 mutated glioma. Anti-tumor activity will be assessed by progression free survival and time to next intervention. Clinical Trial Registration:NCT05577416 (ClinicalTrials.gov) Plain Language Summary Adult low-grade gliomas (aLGG) are primary brain cancers, defined by mutations in IDH1 or IDH2. When the IDH gene becomes abnormal (mutated), production of a metabolite that causes cancer cells to grow is increased. These tumors grow slowly but invade the normal functioning brain, making them nearly impossible to cure. The current standard of care treatment includes surgery, followed by radiation therapy and chemotherapy, the timing of which depends on the risk of cancer regrowth. Some patients may be suitable for monitoring with MRI scans alone, however recurrences will inevitably occur. Recently developed targeted mutant IDH inhibitors for aLGG patients may be beneficial both at diagnosis and recurrence. Notably, early treatment prior to radiation therapy and chemotherapy delays growth of aLGG and the need for subsequent radiation therapy and chemotherapy. Nevertheless, most patients will eventually suffer further tumor growth and the optimal timing and sequencing of these therapies remains an area of active research. This research investigates the mutant IDH1 inhibitor safusidenib. The researchers are conducting an innovative clinical trial where patients with aLGG, who have not received radiation therapy or chemotherapy, are treated with safusidenib following a biopsy and prior to surgical removal of their tumor. In this study they investigate whether this trial design is safe and feasible, and how safusidenib works; with the goal to better understand the optimal use of IDH inhibitors for patients with aLGG. Article highlights Introduction Background & rationale Adult low-grade gliomas (aLGGs) are defined by IDH1/2 mutations which lead to accumulation of 2-HG, an oncometabolite affecting tumorigenesis. 2-HG inhibits α-KG-dependent enzymes, affecting epigenetic regulation, collagen synthesis and cell signaling, hindering progenitor cell differentiation and promoting cancer. In addition, 2-HG promotes angiogenesis, an immunosuppressive tumor microenvironment and oxidative damage. aLGGs grow slowly, diffusely infiltrating the brain and are difficult to cure. Emergence of targeted mutant IDH inhibitors has shifted focus toward identifying prognostic markers and future combination studies. Current treatment of aLGG Treatment includes maximal safe surgical resection, radiation therapy and sequential chemotherapy. Early, extensive surgery improves overall survival. Active surveillance with MRI is suitable for some patients to delay side effects. Mutant IDH inhibitors for glioma Multiple mutant IDH inhibitors have shown promise in glioma. Vorasidenib (IDH1/2 inhibitor) improved progression-free survival in the INDIGO Phase III trial. Safusidenib (DS-1001b, AB-218) is an orally available small molecule inhibitor of mutant IDH1 with demonstrated brain penetration and clinical activity in Phase I trials. Perioperative trials There have been few therapeutic advances in glioma due to challenges in measuring drug penetration and pharmacodynamic (PD) evaluation. Perioperative trials, including biopsy to obtain pre-treatment tissue, are feasible and offer a means to examine the direct effects of new drugs. These studies allow evaluation of drug pharmacokinetics (PK) and PD outcomes. Objectives Hypothesis: Treatment with safusidenib following biopsy and prior to resection in newly diagnosed IDH1 mutated glioma is feasible. Estimate: >60% of screened patients completing planned investigations and procedures. Primary objective: Assess feasibility and acceptability of a perioperative study in IDH1 mutated aLGG patients. Secondary end points: Determine safusidenib toxicity, safety of two-stage surgery and biological activity by changes in 2-HG levels. Methods Participants, interventions, & outcomes Key inclusion: Adults ≥18 years with aLGG diagnosis not requiring urgent resection. Key exclusion: prior chemotherapy/radiation, cerebellar/brainstem tumors. Procedures: Open biopsy, oral safusidenib, second-stage resection, continued safusidenib post-resection. Data collection: tumor tissue, CSF and blood samples processed per protocols. PK/PD relationships: Evaluated by blood, tumor and CSF samples. Biological activity: Assessed by changes in 2-HG levels and IDH1 ctDNA. Data collection, management, & analysis Tumor tissue, CSF and blood samples collected for research. Safusidenib PK will be investigated to evaluate PK/PD relationships. Translational end points include paired whole-genome transcriptome profiling, single nuclei RNA sequencing, bulk metabolomics and DNA methylation. Spatial transcriptomics using in situ digital sequencing and spatial metabolomics on sections pre- and post-safusidenib treatment. Descriptive statistics for demographics, safety, PK, PD, efficacy and biomarker data by dose and time. Monitoring Toxicity: Monitored by adverse events, clinical tests and vital signs. Safety of surgery: 30-day morbidity and mortality recorded post-biopsy and resection. Radiological response: Determined by MRI changes and LGG-RANO criteria. Progression-free survival and time to treatment failure: Calculated from biopsy date. Conclusion Perioperative studies in aLGG offer a unique opportunity to study drug effects and are feasible, ethical and acceptable to patients. [ABSTRACT FROM AUTHOR]

Many societies have aging populations. Getting older people to exercise can help them achieve a higher quality of life. Fitness tracking and social support can buttress that goal. This study tested the effects of fitness tracking and spousal influence on the physical activity of older adults. In a 2 (blinded vs. feedback) × 2 (individual vs. dyad) between-group experiment, 240 participants received a fitness tracker with a visible or blinded display. They participated in the three-month experiment either individually or with their spouses. Participants who received feedback met daily step counts of 7500 and 10,000 more frequently than those without feedback. Interestingly, those who participated with their spouses had lower mean and median step counts and met daily step counts of 10,000 and 15,000 less frequently than those who participated by themselves. The results show that real-time personalized feedback can motivate physical activity among older adults, while engrained routines among older couples may impede behavior change. Whereas individuals can adjust their personal routines to achieve a physical activity goal, such adjustment is more complex when it involves the quotidian routines of dyadic partners. [ABSTRACT FROM AUTHOR]

The 2022 American Society of Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) updated the indications for Metabolic and Bariatric Surgery (MBS), replacing the previous guidelines established by the NIH over 30 years ago. The evidence supporting these updated guidelines has been strengthened to assist metabolic and bariatric surgeons, nutritionists, and other members of multidisciplinary teams, as well as patients. This study aims to assess the level of evidence and the strength of recommendations compared to the previously published criteria. [ABSTRACT FROM AUTHOR]

Background: Comprehensive studies on priority areas for improving geriatric surgery outcomes, inclusive of geriatric‐pertinent data, are limited. Methods: The ACS NSQIP geriatric database (2014–2018) was used to abstract older adults (≥65 years) undergoing inpatient general surgery procedures. Thirty‐day complication, functional decline, and mortality rates were analyzed, with a focus on two geriatric‐pertinent complications: delirium and new/worsening pressure ulcers. Results: There were 9062 patients; 41.9% were ≥75 years. Mean age was 73.9 years. The majority of patients were female (54.0%), White (77.7%), and had independent functional status before surgery (94.0%). Overall 30‐day complication, functional decline, and mortality rates were 33.6%, 34.5%, and 3.5%, respectively; failure to the rescue rate was 9.7%. Including geriatric‐pertinent complications increased the overall complication rate by 20.4%. Delirium emerged as the leading complication (11.9%), followed by bleeding (11.1%), and wound‐related complications (10.1%); these three accounted for 53.7% of complications. Delirium and pressure ulcers were associated with a >50% rate of postoperative functional decline (52.0% and 71.4%, respectively); pressure ulcers were also notable for a 25.5% failure to the rescue rate. Both were also among complications most likely to occur following the 3 most common procedures (colorectal surgery, pancreatic resections, and exploratory laparotomy), which overall accounted for approximately 79.6% of complications, 73.4% of patients experiencing functional decline, and 82.3% of mortality. Conclusions: Delirium is the leading complication among older adults undergoing inpatient surgery. Overall, a small number of complications and procedure groups account for most surgical morbidity and mortality among older adults and thus constitute priority areas for outcomes improvement. [ABSTRACT FROM AUTHOR]

The production, social, and ecological requirements for maintaining the quality of inland waters necessitated establishing a network of hydrochemical observation posts. The variability in the monitored indicators required implementing regular chemical and analytical studies. Conventional rigid statistical methods in analytical chemistry often fail to address the specifics of studying fuzzy experimental data, such as series of impurity concentration values in a river flow over space and time. In this context, alternative soft computing tools, particularly those based on neuro fuzzy hybrid algorithmic structures related to the ANFIS architecture, are more suitable. An analysis of chemicoanalytical data arrays for copper and zinc in the Volga River, considering water flow at various distances from the shore and depths, revealed a complex oscillatory behavior in the concentrations of both substances. This analysis concluded that the neuro-fuzzy processing scheme of the monitoring results enables a more in-depth study of the poorly understood processes of hydrochemical dynamics in systems far from thermodynamic equilibria, such as natural watercourses. [ABSTRACT FROM AUTHOR]

Immunosuppression after solid organ transplantation is associated with an increased risk of keratinocyte carcinoma (KC). Despite its established morbidity, KC risk in liver transplant (LT) recipients is understudied, including the contribution of immunosuppression regimen and latitude. A retrospective cohort of 9,966 adult first LT alone recipients alive with their native allograft at 1-year post-LT without prior KC between 2007 and 2016 were identified using linked data from the Organ Procurement and Transplantation Network and Medicare administrative claims. The primary exposures were immunosuppression regimen and latitude of residence. The primary outcome was incident, de novo KC occurring at least 1-year after LT. Adjusted Cox regression analysis stratified by transplant center was used in all analyses. The cohort was 63.4% male, 70.2% White and with median age 61 years (interquartile range, IQR, 54–66) at transplant. Calcineurin inhibitor (CNI) with anti-metabolite combination was independently associated with incident KC when measured as intention-to-treat (adjusted hazard ratio (aHR) 1.21 vs. CNI monotherapy, 95% CI 1.02–1.43, p = 0.026), in a time-updating as-treated analysis (aHR 1.61, 95% CI 1.34–1.93; p < 0.001) and when measured as cumulative exposure (aHR 1.13 per 6-month increase, 95% CI: 1.02–1.33; p = 0.027). More southern latitude of residence was also independently associated with incident KC with an aHR of 1.26 per 5°N decrease towards the Equator (95% CI: 1.08–1.47, p = 0.003). We demonstrate independent effects of CNI with antiM immunosuppression regimen and latitude of residence on the risk of post-LT KC, which will better inform screening practices and immunosuppression management. [ABSTRACT FROM AUTHOR]

Background: Positive surgical margin rates remain high in head and neck cancer surgery. Relocation is challenging given the complex, three‐dimensional (3D) anatomy. Methods: Prospective, multi‐institutional study to determine accuracy of head and neck surgeons and pathologists relocating margins on virtual 3D specimen models using written descriptions from pathology reports. Using 3D models of 10 head and neck surgical specimens, each participant relocated 20 mucosal margins (10 perpendicular, 10 shave). Results: A total of 32 participants, 23 surgeons and 9 pathologists, marked 640 margins. Of the 320 marked perpendicular margins, 49.7% were greater than 1 centimeter from the true margin with a mean relocation error of 10.2 mm. Marked shave margins overlapped with the true margin a mean 54% of the time, with no overlap in 44 of 320 (13.8%) shave margins. Conclusions: Surgical margin relocation is imprecise and challenging even for experienced surgeons and pathologists. New communication technologies are needed. [ABSTRACT FROM AUTHOR]

Background Silicone implants are by far the most widely used implant globally for breast augmentation. Despite technological advancements, complications persist, with silicone lymphadenopathy (siliconoma) being a noteworthy concern. This phenomenon has been inadequately addressed in the existing literature. Objectives The aim of this study was to characterize axillary siliconomas and identify potential risk factors to help reduce their occurrence. Methods The authors conducted a retrospective observational cross-sectional study spanning between 2011 and 2021 at the Shamir Assaf Harofeh Medical Center, Israel. Preoperative ultrasound examination was conducted, categorizing patients into those with siliconomas and those without. Results A total of 614 women (1209 breasts) met the inclusion criteria. The incidence of siliconomas was 13.6% (165 breasts). In univariate analysis, older age (47 years vs 43 years, P <.001), older implant age (12.2 years vs 11 years, P =.026), ruptured implants (59.4% vs 17.7%, P <.001), subpectoral placement (P =.019), severe capsular contracture, and the use of Mentor implants (Irvine, CA; P =.007) and Poly Implant Prothèse implants (PIP; La Seyne-sur-Mer, France; P =.001) correlated significantly with the presence of siliconomas. In a multivariate analysis, implant rupture (odds ratio [OR] = 6.342), and implant manufacturer—Mentor (OR = 3.047) and PIP (OR = 3.475)—were identified as independent risk factors associated with a higher incidence of siliconomas. Severe capsular contracture was also associated with a higher incidence of siliconomas (OR = 1.65). Conclusions Surgeons should inform candidates about the potential risk of silicone migration. Patients with ruptured implants, significant capsular contracture, and Mentor and PIP implants face an increased risk for developing siliconomas. Closer monitoring for the detection of siliconomas in the axilla for these patients is advisable, and potential prophylactic replacement or removal of implants may be warranted to mitigate siliconoma risk. Level of Evidence: 3 [ABSTRACT FROM AUTHOR]

Mono-n-hexyl phthalate (MnHexP) is a primary metabolite of di-n-hexyl phthalate (DnHexP) and other mixed side-chain phthalates that was recently detected in urine samples from adults and children in Germany. DnHexP is classified as toxic for reproduction category 1B in Annex VI of Regulation (EC) 1272/2008 and listed in Annex XIV of the European chemical legislation REACH; thereby, its use requires an authorisation. Health-based guidance values for DnHexP are lacking and a full-scale risk assessment has not been carried out under REACH. The detection of MnHexP in urine samples raises questions about the sources of exposure and concerns of consumer safety. Here, we propose the calculation of a provisional oral tolerable daily intake value (TDI) of 63 µg/kg body weight/day for DnHexP and compare it to intake levels corresponding to levels of MnHexP found in urine. The resulting mean intake levels correspond to less than 0.2% of the TDI, and maximum levels to less than 5%. The TDI was derived by means of an approximate probabilistic analysis using the credible interval from benchmark dose modelling of published ex vivo data on reduced foetal testosterone production in rats. Thus, for the dose associated to a 20% reduction in testosterone production, a lower and upper credible interval of 14.9 and 30.0 mg/kg bw/day, respectively, was used. This is considered a conservative approach, since apical developmental endpoints (e.g. changed anogenital distance) were only observed at higher doses. In addition, we modelled various scenarios of the exposure to the precursor substance DnHexP from different consumer products, taking measured contamination levels into account, and estimated systemic exposure doses. Of the modelled scenarios including the application of sunscreen (as a lotion or pump spray), the use of lip balm, and the wearing of plastic sandals, and considering conservative assumptions, the use of DnHexP-contaminated sunscreen was highlighted as a major contributing factor. A hypothetical calculation using conservative assumptions for the latter resulted in a margin of safety in relation to the lower credible interval of 3267 and 1007 for adults and young children, respectively. Most importantly, it was found that only a fraction of the TDI is reached in all studied exposure scenarios. Thus, with regard to the reported DnHexP exposure, a health risk can be considered very unlikely. [ABSTRACT FROM AUTHOR]

While grandfamily support groups are the most widely used interventions for grandfamilies, we are still beginning to understand what GRG groups provide, what outcomes they achieve and how are they sustained overtime. This study shares the results of administering the GrOW Support Group Scale to 240 grandfamily support group participants in California, Connecticut, and Florida. This is the first study to include more than one state to explore a convenience sample of support groups for grandparents raising grandchildren and include a way to measure outcomes using the GrOW Support Group Scale (GSGS). A descriptive analysis of this large sample of caregivers assessed on key concepts such as self-efficacy, stress, protective factors, group engagement, and family resources and supports showed areas in need of future study. Results of a crisis checklist from the GSGS showed that the three most urgent grandfamilies needs include: financial trouble, emotional difficulties, and custody issues. Reliability estimates for the GRGS Supplements were good and ranged from.71 to.96. GRG Support Groups can use the GSGS to help existing groups articulate membership growth and outcomes. Future studies can utilize GSGS to promote support group efficacy for grandfamily caregivers. [ABSTRACT FROM AUTHOR]

Prize law was a legal regime that played a crucial role in maritime trade and warfare in the European imperial world before the twentieth century, governing both the capture and disposition of enemy property seized by belligerents at sea during wartime. Prize law outlined the rules by which captures were to take place and how captured property was to be handled, adjudicated, and (if "condemned" or deemed a valid capture), disposed of. All European maritime powers had prize regimes during the early modern era, which collectively adjudicated the fates of tens of thousands of vessels worth the equivalent of hundreds of millions of today's dollars. This article examines the procedural law of prize in the long eighteenth century: the rules that governed how legal actors in the prize regime brought cases before tribunals and the tribunals' rules for adjudicating them. It shows that the law of prize was an interpolity legal regime, generated within the ambiguous legal spaces that existed between the jurisdictional boundaries of individual states and empires. The article focuses on three important areas of procedural law for evidence of the interpolity character of the prize regime. It looks first at the distinctive role played by mariners in prize procedures. Captains of privateers and other capturing vessels functioned as quasi-officers of the court, responsible for assembling the documentary record that prize tribunals used to adjudicate captures and bringing the cases before the courts. Imperial prize regulations gave almost no guidance on the rules that they were to follow. The proper procedures were defined by mariners and merchants themselves, as unwritten rules articulated at sea. Second, we turn to how the prize tribunals managed language diversity and translation. I show that, a few exceptions aside, prize tribunals did not acknowledge linguistic difference among litigants. Instead, the tribunals relied on silent and often unacknowledged translation processes, which embedded in their proceedings a fiction that all of the actors before them communicated in a common language. Last, the article shows that prize tribunals applied foreign law in their proceedings, in ways that were not formally authorized by imperial law. By focusing on the neglected procedural law of prize, this article offers a different view of the prize regime than the one that has been painted by many studies of substantive law of prize in the long eighteenth century, in at least two ways. One is that studying the procedural law of prize casts into sharp relief the bottom-up character of prize law. Far from being dictated by sovereigns or from imperial centers, much about the prize regime was created informally by lower-level legal actors. Second, a focus on procedural law reveals important continuities in prize law across space and time. Substantive prize law during the period saw extensive debates about the nature of neutral rights, among other issues, with different empires articulating radically different doctrines. The procedural law of prize, true to its interpolity origins, remained remarkably constant across empires and over time. [ABSTRACT FROM AUTHOR]

Background/Aims: In people with opioid use disorder (OUD), buprenorphine is a vital treatment to decrease opioid use and overdose. The US Food and Drug Administration's prescribing information for buprenorphine advises dosing up to 24 mg/day; however, doses of buprenorphine up to 32 mg have been shown to be safe and effective. We compared outcomes associated increased dosing from 24 to 32 mg/day. Design: Prospective cohort investigation. Setting: Low‐barrier buprenorphine clinic in Washington, District of Columbia, USA. Participants: Participants in the ANCHOR study (people with hepatitis C virus (HCV), OUD, and active opioid misuse who were treated for HCV and offered buprenorphine) who received buprenorphine at doses of 24 and/or 32 mg/day. 72 participants were included in the analysis: 24 (33%) patients stabilized on 24 mg, and 48 (67%) patients stabilized on 32 mg. Patients were predominantly male (78%), Black (96%), unstably housed (57%), and used opioids by injection (93%). Measurements: Patient‐reported drug use, use frequency, triggers for use, and urine drug screens were collected at each visit. For analysis, the cohort was divided into individuals stabilized on 24 mg (24 mg cohort) or 32 mg (32 mg cohort). Drug use outcomes were assessed between cohorts at 24 mg dosing and at respective maximum dosing. Within the 32 mg cohort, outcomes were compared at 24 mg versus 32 mg dosing. Findings Within the 32 mg cohort, increased dosing from 24 to 32 mg was associated with a decline in opioid use (68.5% [5.2%] at 24 mg vs 59.5% [5.6%] at 32 mg; P = 0.02), frequency of use per week (1.58 [0.19] at 24 mg vs. 1.15 [0.16] at 32 mg; P = 0.0002) and physiologic triggers for use (38.2% [6.0%] at 24 mg vs 7.0% [1.9%] at 32 mg; P < 0.0001). At the end of the study period, there were significantly more patients retained in the 32 mg cohort (78.7%) compared with the 24 mg cohort (50.0%, P = 0.02). Conclusion: Higher buprenorphine dosing (32 mg/day) appears to improve outcomes in people with opioid use disorder, even in the absence of abstinence. [ABSTRACT FROM AUTHOR]

Cell surface scavenger receptors contribute to homoeostasis and the response to pathogens and products associated with damage by binding to common molecular features on a wide range of targets. Apoptosis inhibitor of macrophage (AIM/CD5L) is a soluble protein belonging to the scavenger receptor cysteine-rich (SRCR) superfamily that contributes to prevention of a wide range of diseases associated with infection, inflammation, and cancer. AIM forms complexes with IgM pentamers which helps maintain high-levels of circulating AIM in serum for subsequent activation on release from the complex. The structural basis for AIM recognition of IgM as well as other binding targets is unknown. Here we apply cryogenic electron microscopy imaging (cryo-EM) to show how interfaces on both of AIM's C-terminal SRCR domains interact with the Fcμ constant region and J chain components of the IgM core. Both SRCR interfaces are also shown to contribute interactions important for AIM binding to damage-associated molecular patterns (DAMPs). Here the authors use cryo-EM imaging to show how the AIM protein (apoptosis inhibitor of macrophage/CD5L) uses tandem scavenger receptor cysteine-rich domains to bind immunoglobulin M (IgM) using interactions also used to bind damage-associated molecular patterns (DAMPs). [ABSTRACT FROM AUTHOR]

DNA damage is a primary trigger for cellular senescence, which in turn causes organismal aging and is a promising target of anti-aging therapies. Most DNA damage occurs when DNA is fragile during DNA replication in S phase, but senescent cells maintain DNA damage long-after DNA replication has stopped. How senescent cells induce DNA damage and why senescent cells fail to repair damaged DNA remain open questions. Here, we combine reversible expression of the senescence-inducing CDK4/6 inhibitory protein p16INK4 (p16) with live single-cell analysis and show that sustained mTORC1 signaling triggers senescence in non-proliferating cells by increasing transcriptional DNA damage and inflammation signaling that persists after p16 is degraded. Strikingly, we show that activation of E2F transcriptional program, which is regulated by CDK4/6 activity and promotes expression of DNA repair proteins, repairs transcriptionally damaged DNA without requiring DNA replication. Together, our study suggests that senescence can be maintained by ongoing mTORC1-induced transcriptional DNA damage that cannot be sufficiently repaired without induction of protective E2F target genes. Persistent DNA damage is a hallmark of senescence. Here, the authors show that senescent cells accumulate DNA damage due to transcriptional stress and are unable to repair DNA damage due to the absence of cell-cycle regulated DNA repair programs. [ABSTRACT FROM AUTHOR]

Background: Variants of the gene triggering receptor expressed on myeloid cells-2 (TREM2) increase the risk of Alzheimer's disease (AD) and other neurodegenerative disorders. Signaling by TREM2, an innate immune receptor expressed by microglia, is thought to enhance phagocytosis of amyloid beta (Aβ) and other damaged proteins, promote microglial proliferation, migration, and survival, and regulate inflammatory signaling. Thus, TREM2 activation has potential to alter the progression of AD. AL002 is an investigational, engineered, humanized monoclonal immunoglobulin G1 (IgG1) antibody designed to target TREM2. In AD mouse models, an AL002 murine variant has been previously shown to induce microglial proliferation and reduce filamentous Aβ plaques and neurite dystrophy. Methods: Preclinical studies assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of AL002 in cynomolgus monkeys. INVOKE-1 (NCT03635047) was a first-in-human phase 1, randomized, placebo-controlled, double-blind study assessing the safety, tolerability, PK, and PD of AL002 administered as single ascending doses (SAD) in healthy volunteers. Results: In cynomolgus monkeys, weekly intravenous injections of AL002 for 4 weeks were well tolerated, dose-dependently decreased soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF) and total TREM2 in hippocampus and frontal cortex, and increased biomarkers of TREM2 signaling in CSF and brain. In the phase 1 study of 64 healthy volunteers, a single intravenous infusion of AL002 demonstrated brain target engagement based on a dose-dependent reduction of sTREM2 in CSF and parallel increases in biomarkers of TREM2 signaling and microglia recruitment. Single-dose AL002 showed central nervous system penetrance and was well tolerated, with no treatment-related serious adverse events over 12 weeks. Conclusions: These findings support the continued clinical development of AL002 for AD and other neurodegenerative diseases in which TREM2 activation may be beneficial. AL002 is currently being tested in a phase 2, randomized, double-blind, placebo-controlled study in early AD. Trial registration: Clinicaltrials.gov, NCT03635047. Registered on August 15, 2018, https://www.clinicaltrials.gov/study/NCT03635047. [ABSTRACT FROM AUTHOR]

The mental health impacts of climate change are increasingly documented; however, less research has investigated the relationship between climate change-related psychological distress and engagement with the issue. The results from two national probability samples of U.S. adults show that 16% report at least one feature of climate change psychological distress and that certain groups have higher levels of distress than others (e.g., Hispanic/Latinos, lower income adults, younger adults). Importantly, people experiencing distress are more likely to engage in collective action on climate change or express a willingness to do so, even when controlling for several correlates of environmental behavior (e.g., political ideology, collective efficacy beliefs). These findings highlight that many Americans are experiencing psychological distress from climate change, and those who do are more involved in collective climate action. People experiencing such distress may benefit from resources to support mental health and engagement with climate change. [ABSTRACT FROM AUTHOR]

Background: For decades, Israel's economic policy has favored either outsourcing or privatization of public services, including healthcare, generating an ongoing and prolonged debate of this approach. In 1997 school health services (SHS) for elementary and middle school pupils was outsourced to a sub-contractor firm, reducing budget, but also standards, for nurses and physicians. Consequently, the service has dwindled and was focused more and more on vaccinations. Between 2007 and 2012, under full private contractor delivery, SHS quality diminished substantially, leading to a significant decline in vaccination coverage in the Southern District. In 2012, a decision was made to return SHS to state control. Methods: This study analyzes the delivery parameters of SHS between the period when the service was operated by a private contractor from 2011to 2/2012, and the subsequent provision of the service directly by Ministry of Health (MoH) between 3/2012 and 2013. We compared the rates of vaccination coverage, screening tests and health education programs. Results: A statistically significant increase in SHS delivery for vaccinations and screening was observed in the Southern District of MoH after the transfer of service from contractor. The increase was variable in different population subgroups, and especially notable in the Bedouin schools of the District, where the MMRV vaccination rose from 19.3% to 96.8%. However, a substantial and significant reduction in health education activities was also noted, overall from 24.9% to 5.0%. Conclusions: The findings suggest that substantial benefits can be derived from direct provision of SHS by MoH and its regional offices, especially in the areas of reduced accessibility and lower socio-economic status. The case study of SHS in the Southern District of Israel can serve as an important example highlighting the impacts of privatization vs nationalization, with potential implications in other fields. These insights should be integral to future discussions of healthcare service provision. [ABSTRACT FROM AUTHOR]

Hypercalcemia can result from either hyperparathyroidism or non-parathyroid conditions. When hypercalcemia is accompanied by undetectable parathyroid hormone (PTH) levels, hyperparathyroidism is rarely considered the diagnosis. Herein, we report the case of a 65-year-old Caucasian woman referred to our hospital for further evaluation of hypercalcemia. Her symptoms included fatigue and brain fog, with undetectable PTH levels. A comprehensive workup, including a series of laboratory and imaging tests, excluded common non-parathyroid causes such as malignancy and familial hypocalciuric hypercalcemia. Ultrasound identified a likely enlarged parathyroid gland, which was further confirmed by a sestamibi scan. After 2 weeks of cinacalcet treatment, the patient's calcium levels decreased, indicating the parathyroid gland as the likely source of hypercalcemia. Parathyroidectomy was subsequently performed, revealing a 1927 mg adenoma. Postoperatively, the patient's calcium levels normalized, PTH levels became detectable within the normal range, and her symptoms resolved, with a marked improvement in energy. This case demonstrates that primary hyperparathyroidism can present with hypercalcemia and undetectable PTH. A genetic mutation in the PTH gene within the adenoma may explain the undetectable PTH levels preoperatively. Plain Language Summary: This case report discusses a 65-year-old woman who was found to have high calcium levels in her blood, a condition known as hypercalcemia. Typically, hypercalcemia can result from either a condition where the parathyroid glands produce too much parathyroid hormone (PTH) or from other non-parathyroid-related issues like cancer. However, when hypercalcemia occurs with undetectable levels of PTH, it is unusual for hyperparathyroidism to be the cause. In this patient's case, she experienced symptoms like fatigue and brain fog, but her initial tests showed undetectable PTH levels. Further tests ruled out other common causes of high calcium, such as cancer or a genetic condition called familial hypocalciuric hypercalcemia. An ultrasound and a special scan called a sestamibi scan revealed an enlarged parathyroid gland, suggesting the presence of a parathyroid adenoma, a non-cancerous tumor. To confirm this, the doctors gave the patient a medication called cinacalcet, which is known to lower calcium levels if the parathyroid glands are involved. After two weeks of treatment, her calcium levels dropped, indicating that the parathyroid gland was indeed the source of the problem. The patient underwent surgery to remove the adenoma, which weighed nearly two grams. Following the surgery, her calcium levels returned to normal, and her PTH levels became detectable again within the normal range. Her symptoms, including fatigue, improved significantly, and she reported feeling more energetic. This case is unusual because it demonstrates that primary hyperparathyroidism can still be the cause of hypercalcemia even when PTH levels are initially undetectable. The doctors suspect that a genetic mutation in the adenoma might explain why PTH levels were undetectable before surgery. This case emphasizes the importance of thorough clinical evaluation, even when initial test results are not typical. [ABSTRACT FROM AUTHOR]

Background Atrioventricular block is common with adult congenital heart disease and pacemaker implantation is challenging. Atrioventricular synchronous pacing is important for better haemodynamics. This case reports the implantation of a dual-chamber leadless pacemaker in a patient with univentricular heart physiology and contributes to the literature regarding the management option in complex adult congenital heart disease patients with conduction abnormalities. Case summary A 25-year-old male with double inlet left ventricular, transposition of great arteries, hypoplastic aortic arch receive multiple surgeries including the Glenn shunt at the age of 1. He presented with 2:1 and 3:1 heart block at the age of 13 with a transvenous dual-chamber pacemaker implanted by pacing the superior vena cava stump and puncturing the Glenn shunt for the ventricular lead. A decade later, lead malfunctioned and the patient progressed to complete heart block. A subcutaneous implantable cardioverter defibrillator was implanted when he was 23 for monomorphic ventricular tachycardia. Given the anticipated challenges with transvenous lead extraction and epicardial pacemaker implantation, we implanted the novel dual-chamber leadless pacemakers which resulted in satisfactory atrioventricular synchronous pacing performance immediately post-op and 2 weeks after the procedure. Discussion We present a case of a novel dual-chamber leadless pacemaker implantation to maintain atrioventricular synchrony in the patient with complete heart block and univentricular physiology. This case illustrates an additional pacing option in complex adult congenital heart to maintain atrioventricular synchrony. [ABSTRACT FROM AUTHOR]

Piezoelectric ultrasound transducers are constrained by size, bandwidth, and angular response, limiting their ability to fully characterize the acoustic properties of objects. In this study, we introduce a novel modular all-optical platform for ultrasound generation and detection to overcome these limitations, demonstrating wideband operation (>50 MHz), omnidirectional response, and high signal fidelity. Ultrasound generation is performed via the optoacoustic effect by illuminating an optically absorbing coating with spatially modulated pulsed light, and ultrasound detection is carried out using a silicon-photonic acoustic detector. By illuminating patterns that span a basis and scanning the detector, the full transmission matrix is measured, consisting of the acoustic waveforms for all the transmitter–receiver pairs in the measurement geometry. Our method is experimentally demonstrated in transmission mode for beam steering, beam focusing, and imaging, achieving excellent agreement with the theory. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: Many patients develop bladder symptoms after radical hysterectomy. This study compared urinary outcomes following radical hysterectomy based on trial of void (TOV) timing (pre-discharge TOV versus post-discharge TOV). Methods: A retrospective non-inferiority study of patients at two academic tertiary referral centers who underwent radical hysterectomy between January 2010 and January 2020 was carried out. Patients were stratified according to timing of postoperative TOV: either pre-discharge or post-discharge from the hospital. Short-term urinary outcomes (including passing TOV, representation with retention) and long-term de novo urinary dysfunction (defined as irritative voiding symptoms, urgency, frequency, nocturia, stress or urgency incontinence, neurogenic bladder, and/or urinary retention) were extracted from the medical record. We hypothesized that the proportion of patients who failed pre-discharge TOV would be within a 15% non-inferiority margin of post-discharge TOV. Results: A total of 198 patients underwent radical hysterectomy for cervical (118 out of 198; 59.6%), uterine (36 out of 198; 18.2%), and ovarian (29 out of 198; 14.6%) cancer. One hundred and nineteen patients (119 out of 198, 60.1%) underwent pre-discharge TOV, of whom 14 out of 119 (11.8%) failed. Of the post-discharge TOV patients (79 out of 198, 39.9%), 5 out of 79 (6.3%) failed. The proportion of patients who failed a pre-discharge TOV was within the non-inferiority margin (5.4% difference, p = 0.23). A greater proportion of patients in the post-discharge TOV group developed long-term de novo urinary dysfunction (27.2% difference, p = 0.005). Median time to diagnosis of de novo urinary dysfunction was 0.5 years (range 0–9) in the pre-discharge TOV group versus 1.0 year (range 0–6) in the post-discharge TOV group (p > 0.05). Conclusions: In this study, pre-discharge TOV had non-inferior short-term outcomes and improved long-term outcomes. [ABSTRACT FROM AUTHOR]

This study investigated community empowerment as a means of addressing food insecurity amongst underserved neighborhoods by increasing available and affordable food choices through Clementine Collective stands in Staten Island, New York (Richmond County), one of the 5 Boroughs of New York City. Given the growing complexity of food insecurity, inclusive and equitable action must be taken that incorporates the voices, perspectives and needs of those most impacted. Through methods of community engagement and empowerment, the Clementine Collective collaborates with local community residents to introduce sustainable solutions that address food insecurity. A survey (N = 132) was administered to customers of a Clementine Collective stand, located in Staten Island, that assessed customers' food habits and attitudes towards their food environment and solutions. The stand was placed in a local meat market grocery store. Descriptive statistics suggested that residents recognized gaps in their food environment and were empowered to advocate for solutions. Engaging residents from their food environment to advocate for local solutions, such as at community bodegas, or small grocery stores, may be an effective method of addressing food insecurity. [ABSTRACT FROM AUTHOR]

The bacterium Zymomonas mobilis is investigated as a model organism for the cultivation and separation of ethanol as a product by in situ extraction in continuous flow microreactors. The considered microreactor is the Coiled Flow Inverter (CFI), which consists of a capillary coiled onto a support structure. Like other microreactors, the CFI benefits from a high surface-to-volume ratio, which enhances mass and heat transfer. Compared to many other microreactors, the CFI offers the advantage of operating without internal structures, which are often used to ensure good mixing. The simplicity of the design makes the CFI particularly suitable for biochemical applications as cells do not get stuck or damaged by internal structures. Despite this simplicity, good mixing is achieved through flow vortices caused by Taylor and Dean vortices. The reaction system consists of two phases, in which the aqueous phase carries the bacterium and an oleyl alcohol phase is used to extract the ethanol produced. Key parameters for evaluation are bacteria growth and the amount of ethanol produced by the microorganism. The results show the suitability of the CFI for microbial production of valuable compounds. A maximum ethanol concentration of 1.26 g L−1 was achieved for the experiment in the CFI. Overall, the cultivation in the CFI led to faster growth of Z. mobilis, resulting in 25% higher ethanol production than in conducted batch experiments. [ABSTRACT FROM AUTHOR]

Multiple breath washout (MBW) has successfully assessed the silent lung zone particularly in cystic fibrosis lung disease, however, it is limited to the communicating lung only. There are a number of different pulmonary function methods that can assess what is commonly referred to as trapped air, with varying approaches and sensitivity. Twenty-five people with cystic fibrosis (pwCF) underwent MBW, spirometry, body plethysmography, and spirometry-controlled computed tomography (spiro-CT) on the same day. PwCF also performed extensions to MBW that evaluate air trapping, including our novel extension (MBWShX), which reveals the extent of underventilated lung units (UVLU). In addition, we used two previously established 5-breath methods that provide a volume of trapped gas (VTG). We used trapped air % from spiro-CT as the gold standard for comparison. UVLU derived from MBWShX showed the best agreement with trapped air %, both in terms of correlation (RS 0.89, P < 0.0001) and sensitivity (79%). Bland–Altman analysis demonstrated a significant underestimation of the VTG by both 5-breath methods (−249 mL [95% CI −10,796; 580 mL] and −203 mL [95% CI −997; 591 mL], respectively). Parameters from both spirometry and body plethysmography were suboptimal at assessing this pathophysiology. The parameters from MBWShX demonstrated the best relationship with spiro-CT and had the best sensitivity compared with the other pulmonary function methods assessed in this study. MBWShX shows promise to assess and monitor this critical pathophysiological feature, which has been shown to be a driver of lung disease progression in pwCF. NEW & NOTEWORTHY: We consider the term "trapped air" either in the use of imaging or pulmonary function testing, something of a misnomer that can lead to an inaccurate assessment of an important physiological feature. Instead, we propose the term underventilated lung units (UVLU). Of the many pulmonary function methods we used in this study, we found that the use of multiple breath washout with short extension (MBWShX) to be the best nonimaging method. [ABSTRACT FROM AUTHOR]

Background: Surgical treatments of refractory gastroparesis include pyloromyotomy and gastric electrical stimulator (GES). It is unclear if patients may benefit from a combined approach with concomitant GES and pyloromyotomy. Methods: Retrospective cohort analysis of all patients with refractory gastroparesis treated with GES implantation with and without concomitant pyloromyotomy at Cleveland Clinic Florida from January 2003 to January 2023. Primary endpoint was efficacy (clinical response duration and success rate) and secondary endpoints included safety (postoperative morbidity) and length of stay. Success rate was defined as the absence of one of the following reinterventions during follow-up: Roux-en-Y gastric bypass (RYGB), pyloromyotomy, GES removal. Results: During a period of 20 years, 134 patients were treated with GES implantation. Three patients with history of previous surgical pyloromyotomy or RYGB were excluded from the analysis. Median follow-up was 31 months (IQR 10, 72). Forty patients (30.5%) had GES with pyloromyotomy, whereas 91 (69.5%) did not have pyloromyotomy. Most of the patients had idiopathic (n = 68, 51.9%) or diabetic (n = 58, 43.3%) gastroparesis. Except for preoperative use of opioids (47.5 vs 14.3%; p < 0.001), patient's characteristics were similar in both groups. There were no significant differences between the two groups in terms of overall postoperative complications (17.5% vs 14.3%; p = 0.610), major postoperative complications (0% vs 2.2%; p = 1), and length of stay (2(IQR 1, 2) vs 2(IQR 1, 3) days; p = 0.068). At 5 years, success rate was higher in patients with than without pyloromyotomy however not statistically significant (82% versus 62%, p = 0.066). Especially patients with diabetic gastroparesis seemed to benefit from pyloromyotomy during GES (100% versus 67%, p = 0.053). In an adjusted Cox regression, GES implantation without pyloromyotomy was associated with a 2.66 times higher risk of treatment failure compared to GES implantation with pyloromyotomy (HR 2.66, 95% CI 1.03–6.94, p = 0.044). Conclusion: Pyloromyotomy during GES implantation for gastroparesis seems to be associated with a longer clinical response with similar postoperative morbidity and length of hospital stay than GES without pyloromyotomy. Patient with diabetic gastroparesis might benefit from a combination of GES implantation and pyloromyotomy. [ABSTRACT FROM AUTHOR]

Ge‐rich Ge–Sb–Te alloy is a good candidate for future automotive applications due to its high crystallization temperature, which allows good data retention at elevated temperatures. Crystallization in this material is governed by elemental segregation which is key to thermal stability and device performance. In this work, elemental (Ge, Sb, Te) segregation is studied in situ during thermal annealing of Ge‐rich Ge–Sb–Te thin films using X‐ray fluorescence microscopy at ID16B beamline of ESRF with a beam size of 50 nm. Spatially resolved maps of Ge, Te, and Sb fluorescence yield are monitored and statistically analyzed as a function of temperature/time. In all investigated samples Sb appears to segregate much less than Te and Ge, indicating a lower mobility of this element. In situ, fluorescence mapping of samples doped with different amounts of carbon by ion implantation shows that carbon delays Ge and Te segregation to higher temperatures. Comparison with crystallization kinetics monitored by X‐ray diffraction shows a good correlation between the occurrence of spatially resolved chemical inhomogeneities and the appearance of crystallized phases. [ABSTRACT FROM AUTHOR]

Background: Physicians are experiencing an increasing burden of messaging within the electronic health record (EHR) inbox. Studies have called for the implementation of tools and resources to mitigate this burden, but few studies have evaluated how these interventions impact time spent on inbox activities. Objective: Explore the association between existing EHR efficiency tools and clinical resources on primary care physician (PCP) inbox time. Design: Retrospective, cross-sectional study of inbox time among PCPs in network clinics affiliated with an academic health system. Participants: One hundred fifteen community-based PCPs. Main Measures: Inbox time, in hours, normalized to eight physician scheduled hours (IB-Time8). Key Results: Following adjustment for physician sex as well as panel size, age, and morbidity, we observed no significant differences in inbox time for physicians with and without message triage, custom inbox QuickActions, encounter specialists, and message pools. Moreover, IB-Time8 increased by 0.01 inbox hours per eight scheduled hours for each additional staff member resource in a physician's practice (p = 0.03). Conclusions: Physician inbox time was not associated with existing EHR efficiency tools evaluated in this study. Yet, there may be a slight increase in inbox time among physicians in practices with larger teams. [ABSTRACT FROM AUTHOR]

Background and Objective: Recently, a consensus process specified a core outcome set (COS) of domains to be assessed in each comparative effectiveness research and clinical practice related to acute postoperative pain. Physical function (PF) was one of these domains. The aim of this review was to investigate which patient‐reported outcome measures (PROMs) are used to assess PF after total knee arthroplasty (TKA) in clinical trials and if they fulfil basic requirements for a COS of PROMs based on their psychometric properties. Methods: A systematic review of randomized controlled trials and observational studies based on a search in MEDLINE, EMBASE and CENTRAL was undertaken. PROMs and performance measures were extracted and investigated, including evaluation of psychometric properties of PROMs based on COSMIN recommendations. Results: From initially 2896 identified records, 479 studies were included in the qualitative synthesis. Only 87 of these trials (18%) assessed PF using PROMs, whereas especially performance outcome measures were used in 470 studies (98%). Application of the 'COSMIN Risk‐of‐Bias‐Box 1' to 13 of the 14 identified PROMs resulted in insufficient content validity of the included PROMs regarding the target population based on the inauguration or development articles. Conclusion: Our data indicate that a patient‐centred postoperative assessment of PF in pain‐related clinical trials early after TKA is not common, even though patient‐reported assessment is widely recommended. In addition, none of the applied PROMs shows content validity based on their inauguration or development articles for the assessment of postoperative pain‐related PF after TKA. Significance: A systematic search for patient‐reported outcome measures assessing postoperative, pain‐related physical function after total knee arthroplasty in clinical trials and assessment of their content validity revealed none that fulfilled requirements based on COSMIN recommendations. [ABSTRACT FROM AUTHOR]

Objective: Intravenous (IV) push (IVP) is an alternative administration method for levetiracetam, but evidence evaluating it compared to IV piggyback (IVPB) for loading doses in acutely seizing patients is limited, particularly in patients with status epilepticus (SE). This study aimed to compare the efficiency and safety of IVP versus IVPB levetiracetam loading doses. Methods: This was a single‐center sequential retrospective study conducted in adult (≥18 years) patients who received an IV levetiracetam loading dose (>2000 mg or ≥20 mg/kg) for acute or suspected seizure. The primary outcome was time to administration, compared between doses given as IVP versus IVPB. Secondary outcomes included rates of adverse events (AEs), rescue benzodiazepine or antiseizure medication administration, intubation, and intensive care unit (ICU) admission between groups. Results: A total of 246 patients were included; 116 received IVP and 130 received IVPB loading doses. Median age was 56 years; most patients were male (62%) and White (60%) and had witnessed seizures (67%). Doses were administered for SE in 32 (27.5%) and 46 (35.4%) patients in the IVP and IVPB arms, respectively. Median time to administration was shorter in the IVP group (12 vs. 38 min, p <.001). Bradycardia (1.7% vs. 2.3%, p =.99), hypotension (7.8% vs. 12%, p =.30), sedation (6% vs. 12.3%, p =.09), intubation (10% vs. 8%, p =.37), ICU admission (32% vs. 39%, p =.31), and rescue medication administration (8.6% vs. 14.6% p =.10) were similar between groups. In SE patients, IVP was associated with shorter time to administration (12 vs. 44 min, p =.003) and lower odds of ICU admission after adjustment for age, dose, Status Epilepticus Severity Score, and seizure history (adjusted odds ratio =.23, 95% confidence interval =.06–.81). Significance: IVP reduced time to levetiracetam administration versus IVPB and was not associated with more AEs. Rescue agent use, intubation, and ICU admission were similar between arms, but IVP may reduce ICU admissions in SE patients. Prospective studies should assess the effectiveness of IVP versus IVPB. [ABSTRACT FROM AUTHOR]

The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, and Speech. It was developed as a potentially clinically meaningful measure of spinocerebellar ataxia (SCA) progression for clinical trial use. Here, we evaluated content validity of the f-SARA. Qualitative interviews were conducted among individuals with SCA1 (n = 1) and SCA3 (n = 6) and healthcare professionals (HCPs) with SCA expertise (USA, n = 5; Europe, n = 3). Interviews evaluated symptoms and signs of SCA and relevance of f-SARA concepts for SCA. HCP cognitive debriefing was conducted. Interviews were recorded, transcribed, coded, and analyzed by ATLAS.TI software. Individuals with SCA1 and 3 reported 85 symptoms, signs, and impacts of SCA. All indicated difficulties with walking, stance, balance, speech, fatigue, emotions, and work. All individuals with SCA1 and 3 considered Gait, Stance, and Speech relevant f-SARA concepts; 3 considered Sitting relevant (42.9%). All HCPs considered Gait and Speech relevant; 5 (62.5%) indicated Stance was relevant. Sitting was considered a late-stage disease indicator. Most HCPs suggested inclusion of appendicular items would enhance clinical relevance. Cognitive debriefing supported clarity and comprehension of f-SARA. Maintaining current abilities on f-SARA items for 1 year was considered meaningful for most individuals with SCA1 and 3. All HCPs considered meaningful changes as stability in f-SARA score over 1–2 years, 1–2-point change in total f-SARA score, and deviation from natural history. These results support content validity of f-SARA for assessing SCA disease progression in clinical trials. [ABSTRACT FROM AUTHOR]

This article explores Jacques Derrida's writings on money, language, and justice. Derrida emphasizes the interconnectedness of these concepts and cautions against isolating money as a separate subject of study. The text also discusses the relationship between money and authenticity, as well as the role of the law in guaranteeing belief in money. It raises questions about the ethical and social implications of money and the choices individuals and societies make in relation to it. Additionally, the article explores the concepts of gift, solidarity, and justice, and suggests that Derrida's work can help address the challenges of contemporary capitalism and promote a more just society. [Extracted from the article]

In this paper I explore how the limitations of sociological and economic approaches to the gift can be exposed not only through deconstructive analysis, such as Jacques Derrida pursues in Given Time, vols. I & II, but also through the philological resources and biological conceptuality of 'metabolism'. By bridging Derrida's textual conception of survival with neurobiological and phenomenological approaches to life, I argue that what 'gift' names is nothing distinctly human but, rather, a possibility at the origin of any economization of differences, be they 'textual' or 'biological' in nature. [ABSTRACT FROM AUTHOR]

The Second Amendment is on a jurisprudential march. An individual right to "keep and bear arms" for purposes unrelated to militia or military service was not recognized until the Supreme Court's 2008 decision, applying what it took to be the original meaning of the "right to keep and bear arms" found in the Second Amendment, in District of Columbia v. Heller. Subsequently, the Court, in New York State Rifle & Pistol Ass'n v. Bruen, invalidated a statule requiring a permit to carry concealable firearms on a showing of particularized need. Most recently, in United States v. Rahimi, the Court seemingly changed course, upholding a statute prohibiting the possession of firearms by those under domestic violence orders of protection. There is a great deal to criticize in the Court's treatment of the original meaning of the Second Amendment in the line of cases beginning with Heller and culminating in Rahimi. That is the focus of Part I. Part I observes that by the time of Bruen, the Court had taken to ignoring the Second Amendment's preamble altogether; a position difficult to reconcile with the view taken of preambles in both the framing era and Heller itself. The Court had also managed to both acknowledge and then ignore the demonstrable ambiguity in the meaning of the Second Amendment right to "bear arms." In Rahimi, the Court ignored its prior account of the original meaning of the Second Amendment's text altogether. We are left with an incoherent originalism, which the Court elevates framing-era regulatory practice and its contemporary analogs over its own account of the original meaning of the Second Amendment's text, albeit without claiming any justification for doing so, or even admitting what it is doing. Part 1 is a relatively conventional example of the type of legal scholarship that dissects Supreme Court opinions. Part II takes a less familiar turn by focusing on the lawyering of those who defended the laws at issue in these cases. After undertaking to show that the Supreme Court's decisions should not be regarded as autonomous, but instead as reflecting to a considerable extent the arguments pressed on it, Part II demonstrates that the Court's errors mirror serious litigating errors by the attorneys defending the laws at issue in these cases. These flawed litigating strategies reflect, Part II shows, an incomplete grasp of the conceptual underpinnings of originalism as a method of constitutional interpretation. Lawyers defending statutes or other legal regimes without clear framing-era antecedents must develop a more sophisticated understanding of originalist constitutional interpretation. Part III offers a guide for avoiding the kind of errors reflected in the thus-far unavailing efforts to defend challenged firearms regulation from Second Amendment attack, in both Second Amendment litigation and other areas of constitutional law. [ABSTRACT FROM AUTHOR]

Essential oils (EOs) have antimicrobial properties, but their low solubility in water and strong flavor pose challenges for direct incorporation into food, as they can negatively impact organoleptic properties. To overcome these issues, strategies such as oil-in-water (O/W) nanoemulsions have been developed to improve EO dispersion and protection while enhancing antimicrobial efficacy. The objective of this study was to create sodium alginate-pink pepper essential oil (PPEO) nanoemulsions using microfluidization. Various formulations were assessed for physicochemical, physical, and antimicrobial properties to evaluate their potential in food applications. The microfluidized emulsions and nanoemulsions had droplet sizes ranging from 160 to 443 nm, polydispersity index (PdI) ranging from 0.273 to 0.638, and zeta potential (ζ) ranging from −45.2 to 66.3 mV. The nanoemulsions exhibited Newtonian behavior and remarkable stability after 20 days of storage. Antimicrobial testing revealed effectiveness against Staphylococcus aureus and Listeria monocytogenes, with minimum inhibitory concentrations (MIC) of 200 µg/mL for both microorganisms and minimum bactericidal concentrations (MBC) of 800 µg/mL and 400 µg/mL, respectively, proving that encapsulation of PPEO in nanoemulsions significantly increased its antibacterial activity. These results present the possibility of using PPEO nanoemulsions as a more effective natural alternative to synthetic preservatives in food systems. [ABSTRACT FROM AUTHOR]

The term institutional betrayal (Smith and Freyd, 2014) builds on the conceptual framework of betrayal trauma theory (see Freyd, 1996) to describe the ways that institutions (e.g., universities, workplaces) fail to take appropriate steps to prevent and/or respond appropriately to interpersonal trauma. A nascent literature has begun to describe individual costs associated with institutional betrayal throughout the United States (U.S.), with implications for public policy and institutional practice. A scoping review was conducted to quantify existing study characteristics and key findings to guide research and practice going forward. Multiple academic databases were searched for keywords (i.e., "institutional betrayal" and "organizational betrayal"). Thirty-seven articles met inclusion criteria (i.e., peer-reviewed empirical studies of institutional betrayal) and were included in analyses. Results identified research approaches, populations and settings, and predictor and outcome variables frequently studied in relation to institutional betrayal. This scoping review describes a strong foundation of published studies and provides recommendations for future research, including longitudinal research with diverse individuals across diverse institutional settings. The growing evidence for action has broad implications for research-informed policy and institutional practice. [ABSTRACT FROM AUTHOR]

Objective: To provide healthcare professionals guidance on youth at risk for prolonged recovery and post‐traumatic headache (PTH), and on pharmacologic and non‐pharmacologic management of PTH due to concussion and mild traumatic brain injury. Background: Headache is the most common persistent post‐concussive symptom affecting 8% of youth for >3 months after concussion. Over the past decade, many studies have explored the treatment of PTH in youth, but there are no established guidelines. Methods: This white paper is based on a synthesis of an updated systematic review of the literature on treatment of PTH and a narrative review of the literature on risk factors for prolonged recovery and health disparities. Results were interpreted by a group of expert providers in PTH in children and adolescents through collaboration of the PTH and pediatric special interest groups of the American Headache Society. Results: Factors that consistently were associated with prolonged recovery from concussion and persistent PTH included female sex, a high number of acute symptoms, and adolescent age. Social determinants of health also likely play an important role in PTH and deserve consideration in the clinical and research settings. A total of 33 studies met the criteria for inclusion in the systematic review of PTH treatment in youth, although most were retrospective and of fair‐to‐poor quality. Treatment strategies included acute and preventive pharmacologic management, procedures, neuro‐modulatory devices, physical therapy, physical activity, and behavioral health support. A collaborative care approach that includes a thoughtful combination of these management strategies is likely most effective. Conclusions: This white paper provides a roadmap for tailoring the treatment of PTH based on factors influencing prolonged headache, the timing of therapies, and therapies with the most evidence for treating PTH in youth. We also highlight research needed for developing more definitive guidelines on PTH management in youth. Plain Language Summary: Post‐traumatic headache (PTH) following concussion is a common and potentially disabling condition impacting youth, yet there are no standards for treatment. This article reviews current evidence and identifies knowledge gaps to guide future research. Based on the limited available evidence and expert opinion, we offer a roadmap for the treatment of PTH in children. [ABSTRACT FROM AUTHOR]