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At the beginning of the war in Ukraine in 2022, Ukrainian forces deployed a handful of Turkish-made Bayraktar TB2 uncrewed aerial vehicles to hit Russian targets. Those precise drone strikes [...]

Mountainous terrain has proven to be the ultimate combat and sustainment equalizer, but the U.S. Army's 10th Mountain Division has been 'flattening' mountainous and alpine terrain for the U.S. military's [...]

Don't Let's Be Beastly to the Germans: The British Occupation of Germany, 1945-49. Head of Zeus, 2023 416 pp. $61.00 ISBN: 978-1800243507 Reviewed by Michael C. Davies As an idea [...]

Continuing our partnership with the Center for Labor and Employment Law at New York University School of Law, the ABA Journal of Labor & Employment Law is pleased to publish [...]

This article details how universities could actively influence both the development and use of artificial intelligence (AI) with an emphasis on social responsibility. The articles explores four university missions—education, research, community collaboration, and public service—that can serve as areas of influence for the social responsibility of AI development and use.

Technology changes rapidly. Within a short time, innovations and advancements present overwhelming benefits for humanity. But there are also downsides, including greater access to tools used for nefarious use by [...]

Introduction It has been fifty years since the National Commission on State Workmen's Compensation Laws released its landmark report concluding that the workers' compensation system in the United States "was [...]

Welcome, readers to the second issue of volume 37. This issue is something of a hybrid, with two main themes. The first theme is a focus on collective bargaining and [...]

This Article examines the nature of the threats that climate change poses and will continue to pose for salmon recovery, as well as possible legal responses to combat these threats. It also considers the future prospects of Pacific salmon in a world that will include significant climate change and other threats to preserving and equitably apportioning the salmon resource, whose environmental sensitivity and expansive life cycle will continue to pose substantial challenges for the foreseeable future. The Article is adapted from Pacific Salmon Law and the Environment: Treaties, Endangered Species, Dam Removal, Climate Change, and Beyond (ELI Press 2022)., I. The Effects of Climate Change on Salmon (1) Among the many threats facing salmon, climate change poses an additional, perhaps existential, risk to salmon and its recovery by exacerbating [...]

Joshua D. Zimmerman, Jozef Pilsudski: Founding Father of Modern Poland (Cambridge: Harvard University Press). 640 pp., $39.95. Eastern Europe occupies an increasingly prominent place in American foreign policy. The United [...]

Introduction Over the past decade, the debate over which businesses should be assigned liability for the denial of employee statutory rights has focused almost exclusively on the doctrine of joint [...]

President Joe Biden's Executive Order No. 14008 of January 2021 called for the Administration to conserve at least 30% of the nation's lands and waters by 2030. (1) To accomplish [...]

Gunpowder. The combustion engine. The airplane. These are just some of the technologies that have forever changed the face of warfare. Now, the world is experiencing another transformation that could [...]

Louisiana surveys waterfowl hunters every 5 years to assess hunter effort, harvest success, demographics, and preferences for proposed regulations and management practices. The 2020 Survey of Louisiana Waterfowl Hunters addressed hunter satisfaction patterns, hunter perceptions on waterfowl migration, associations of field experiences to satisfaction, associations among distribution waves, the efficacy of sample coverage by an email survey, and allowed comparison with hunter satisfaction with surveys in 2005, 2010, and 2015. We distributed a 31‐question survey by email to 73,554 Louisiana waterfowl hunters following the 2019–2020 season. We received 13,483 total responses, of which 8,218 were usable (licensed respondents actively hunting waterfowl during the 2019–2020 season), resulting in a qualified response rate of 12.0%. We compared qualified respondents to the overall population of Harvest Information Program registrants (169,891) and found no significant differences for age class, geographic distribution, and license type. Our results indicated that surveys should be distributed in 3 waves, as the number of days hunted would be overestimated by 7% (mean of 15 days [95% confidence interval = 14.7–15.7] compared to a mean of 14 days [95% confidence interval = 13.7–14.4]) by a single survey. Hunters' satisfaction was independent of which geographic zone they hunted, whether they were members of conservation organizations, or how many waterfowl were seen. Our results also indicated that the probability of greater hunter satisfaction was increased by 98% as the number of waterfowl harvested surpassed 57, by 68% for respondents reporting that their actual harvest exceeded expected harvest by at least one bird, and by 61% for respondents reporting that their actual days hunted exceeded expected days hunted by at least one day. [ABSTRACT FROM AUTHOR]

Optimal perioperative pain management is an essential component of perioperative care for the cardiac surgical patient. This turnkey order set is part of a series created by the Enhanced Recovery After Surgery Cardiac Society, first presented at the Annual Meeting of The American Association for Thoracic Surgery in 2023. Several guidelines and expert consensus documents have been published to provide guidance on pain management and opioid reduction in cardiac surgery. Our objective is to consolidate that guidance into an evidence-based order set that will assist in the implementation of a comprehensive multimodal approach to pain management.

Cell size is tightly controlled in healthy tissues and single-celled organisms, but it remains unclear how cell size influences physiology. Increasing cell size was recently shown to remodel the proteomes of cultured human cells, demonstrating that large and small cells of the same type can be compositionally different. In the present study, we utilize the natural heterogeneity of hepatocyte ploidy and yeast genetics to establish that the ploidy-to-cell size ratio is a highly conserved determinant of proteome composition. In both mammalian and yeast cells, genome dilution by cell growth elicits a starvation-like phenotype, suggesting that growth in large cells is restricted by genome concentration in a manner that mimics a limiting nutrient. Moreover, genome dilution explains some proteomic changes ascribed to yeast aging. Overall, our data indicate that genome concentration drives changes in cell composition independently of external environmental cues.

The management of preoperative medications is an essential component of perioperative care for the cardiac surgical patient. This turnkey order set is part of a series created by the Enhanced Recovery After Surgery Cardiac Society, first presented at the Annual Meeting of The American Association for Thoracic Surgery in 2023. Numerous guidelines and expert consensus documents have been published to provide guidance in preoperative medication management. Our objective is to integrate these documents into an evidence-based order set that will facilitate standardized implementation of best practices for preoperative medication management for nonemergent adult cardiac surgery.

Aroma dramatically impacts the overall flavor profiles and consumer acceptance; therefore, it is necessary to conduct a comprehensive analysis of the aroma characteristics of apples. In this study, the aroma differences among four popular apple varieties (“Ruixue”, “Liangzhi”, “Crystal Fuji,” and “Guifei”) were compared using two extraction methods (headspace-solid phase microextraction, and solvent-assisted flavor evaporation) coupled with gas chromatography–mass spectrometry–olfactometry (GC–MS–O) and two-dimensional gas chromatography-quadrupole mass spectrometry (GC × GC-qMS). A total of 82 odorants were identified via GC–MS–O, and 143 volatiles were identified by GC× GC-qMS. Among them, 41 key aroma-active compounds (butanal, ethyl acetate, 3-methylbutanal, methyl butanoate, 2-methylpropyl acetate, ethyl 2-methylbutanoate, ethyl 3-methylbutanoate, butyl acetate, hexanal, 2-methylbutyl acetate, 1-butanol, 2-methylpropyl butanoate, 3-methylbutyl acetate, (E)-2-hexenal, butyl butanoate, butyl 2-methylbutanoate, hexyl acetate, hexyl butanoate, hexyl, 2-methylbutanoate, 1-octen-3-ol, 3-methylthiopropanol, 1,3-octanediol, linalyl acetate, and so on) with high odor activity values (OAVs) and AI value (odor activity values ≥1 or aroma intensity ≥3) were identified. Partial least-squares-discriminant analysis showed that Ruixue exhibited a high “fruity” note, Guifei and Crystal Fuji had the greatest “wood,” “floral,” and “sweet” notes, while Liangzhi presented a significant “green” note. This study provided flavor chemistry support for the apple quality control and production.

The incorporation of photoresponsive groups into porous materials is attractive as it offers potential advantages in controlling the pore size and selectivity to guest molecules. A combination of computational modeling and experiment resulted in the synthesis of two azobenzene-derived organic cages based on building blocks identified in a computational screen. Both cages incorporate three azobenzene moieties, and are therefore capable of 3-fold isomerization, using either ditopic or tetratopic aldehydes containing diazene functionality. The ditopic aldehyde forms a Tri2Di3cage via a 6-fold imine condensation and the tritopic aldehyde forms a Tet3Di6cage via a 12-fold imine condensation. The relative energies and corresponding intrinsic cavities of each isomeric state were computed, and the photoswitching behavior of both cages was studied by UV–Vis and 1H NMR spectroscopy, including a detailed kinetic analysis of the thermal isomerization for each of the EEZ, EZZand ZZZmetastable isomers of the Tet3Di6cage. Both cages underwent photoisomerization, where a photostationary state of up to 77% of the cis-isomer and overall thermal half-life of 110 h was identified for the Tet3Di6species. Overall, this work demonstrates the potential of computational modeling to inform the design of photoresponsive materials and highlights the contrasting effects on the photoswitching properties of the azobenzene moieties on incorporation into the different cage species.

Trade‐offs among objectives in natural resource management can be exacerbated in altered ecosystems and when there is uncertainty in predicted management outcomes. Multi‐criteria decision analysis and value of information (VOI) are underutilized decision tools that can assist fisheries managers in handling trade‐offs and evaluating the importance of uncertainty. We demonstrate the use of these tools using a case study in the Sacramento River, California, USA, where two imperiled species with different temperature requirements, winter‐run Chinook Salmon Oncorhynchus tshawytschaand Green Sturgeon Acipenser medirostris, spawn and rear in the artificially cold Shasta Dam tailwater. A temperature‐control device installed on Shasta Dam maintains cool water for Chinook Salmon; however, uncertainties exist related to the effects of temperatures on the spawning and rearing of both species. We consider four alternative hypotheses in models of early life‐stage dynamics to evaluate the effects of alternative temperature management strategies on Chinook Salmon and Green Sturgeon management objectives. We used VOI to quantify the increase in management performance that can be expected by resolving hypothesis‐based uncertainties as a function of the weight assigned to species‐specific objectives. We found the decision was hindered by uncertainty; the best performing alternative depends on which hypothesis is true, with warmer or cooler alternative management strategies recommended when weights favor Green Sturgeon or Chinook Salmon objectives, respectively. The value of reducing uncertainty was highest when Green Sturgeon was slightly favored, highlighting the interaction between scientific uncertainty and decision makers' values. Our demonstration features multi‐criteria decision analysis and VOI as transparent, deliberative tools that can assist fisheries managers in confronting value conflicts, prioritizing resolution of uncertainty, and optimally managing aquatic ecosystems.

Itepekimab, a monoclonal antibody against interleukin‐33, has demonstrated clinical utility in previous studies in patients with asthma and chronic obstructive pulmonary disease. An autoinjector (AI) has been developed for administering itepekimab to facilitate further development. This study compared pharmacokinetics of single 300‐mg itepekimab subcutaneous administration via an AI versus a prefilled syringe (PFS). Of 90 healthy volunteers enrolled in this Phase 1, parallel‐design, randomized study and stratified by body weight (50 to <70 kg, ≥70 to <80 kg, ≥80 to 100 kg) and injection site (abdomen, thigh, or arm), 84 completed the study. Systemic exposure of itepekimab was similar for both groups. Point estimates for geometric mean ratios of pharmacokinetic parameters for AI versus PFS groups were 1.01 for maximum serum concentration, 1.06 for area under the serum concentration‐time curve to the last quantifiable concentration, and 1.04 for area under the serum concentration‐time curve extrapolated to infinity. The exposure was similar for both devices in each body weight and injection site subgroup. Overall, systemic exposure of 300‐mg single‐dose itepekimab in healthy participants was comparable when administered subcutaneously via an AI device and PFS, with an acceptable safety profile in both device groups.

Germinal matrix hemorrhage (GMH) is a devastating neurodevelopmental condition affecting preterm infants, but why blood vessels in this brain region are vulnerable to rupture remains unknown. Here we show that microglia in prenatal mouse and human brain interact with nascent vasculature in an age-dependent manner and that ablation of these cells in mice reduces angiogenesis in the ganglionic eminences, which correspond to the human germinal matrix. Consistent with these findings, single-cell transcriptomics and flow cytometry show that distinct subsets of CD45+cells from control preterm infants employ diverse signaling mechanisms to promote vascular network formation. In contrast, CD45+cells from infants with GMH harbor activated neutrophils and monocytes that produce proinflammatory factors, including azurocidin 1, elastase and CXCL16, to disrupt vascular integrity and cause hemorrhage in ganglionic eminences. These results underscore the brain’s innate immune cells in region-specific angiogenesis and how aberrant activation of these immune cells promotes GMH in preterm infants.

Masticatory myositis (MM) is an inflammatory myopathy reported in dogs and is characterized by inflammation of the masticatory muscles (temporalis, masseter, and pterygoid muscles). Immunosuppressive therapy is the current recommended treatment for MM and may involve glucocorticoids, cyclosporine, azathioprine, mycophenolate mofetil, leflunomide, or a combination of these treatments that are slowly tapered to the lowest effective dose. However, side effects from multimodal medical therapy and complications associated with MM relapses have been reported. The purpose of this case series was to report oclacitinib as a treatment alternative to traditional medical management of MM. The intent of this alternative is to manage side effects from glucocorticoid use. Oclacitinib (1mg/kg per os q12h) was used solely for treatment of MM in three dogs. The dogs were followed up to >6 months after oclacitinib administration. An increase in oral range of motion, as determined by gape angle, was noted in all three dogs. However, a corresponding drop in antibody titers (2M fiber) did not occur. All dogs showed improvement in overall clinical management of MM, side effects from glucocorticoids, and clinical signs related to chronic prednisone use. Larger controlled trials with consistent measurements (interincisal distance, gape angle) and 2M fiber antibody titers are indicated to further assess validation of oclacitinib treatment of MM. The clinical outcome of all dogs was considered successful.

Preprocedural oxygenation (pre-emptive oxygenation started during presedation and/or induction) and procedural oxygenation (pre-emptive oxygenation started during any phase of sedation) are easy-to-use strategies with potential to decrease adverse events. Here, we describe practice patterns of preprocedural oxygenation and procedural oxygenation. We hypothesized that patients who received preprocedural oxygenation or procedural oxygenation would have a lower risk of airway/breathing/circulation interventions during sedation compared with patients without procedural oxygenation.

To study the spatial interactions among cancer and non-cancer cells1, we here examined a cohort of 131 tumour sections from 78 cases across 6 cancer types by Visium spatial transcriptomics (ST). This was combined with 48 matched single-nucleus RNA sequencing samples and 22 matched co-detection by indexing (CODEX) samples. To describe tumour structures and habitats, we defined ‘tumour microregions’ as spatially distinct cancer cell clusters separated by stromal components. They varied in size and density among cancer types, with the largest microregions observed in metastatic samples. We further grouped microregions with shared genetic alterations into ‘spatial subclones’. Thirty five tumour sections exhibited subclonal structures. Spatial subclones with distinct copy number variations and mutations displayed differential oncogenic activities. We identified increased metabolic activity at the centre and increased antigen presentation along the leading edges of microregions. We also observed variable T cell infiltrations within microregions and macrophages predominantly residing at tumour boundaries. We reconstructed 3D tumour structures by co-registering 48 serial ST sections from 16 samples, which provided insights into the spatial organization and heterogeneity of tumours. Additionally, using an unsupervised deep-learning algorithm and integrating ST and CODEX data, we identified both immune hot and cold neighbourhoods and enhanced immune exhaustion markers surrounding the 3D subclones. These findings contribute to the understanding of spatial tumour evolution through interactions with the local microenvironment in 2D and 3D space, providing valuable insights into tumour biology.

Ageing impairs the ability of neural stem cells (NSCs) to transition from quiescence to proliferation in the adult mammalian brain. Functional decline of NSCs results in the decreased production of new neurons and defective regeneration following injury during ageing1–4. Several genetic interventions have been found to ameliorate old brain function5–8, but systematic functional testing of genes in old NSCs—and more generally in old cells—has not been done. Here we develop in vitro and in vivo high-throughput CRISPR–Cas9 screening platforms to systematically uncover gene knockouts that boost NSC activation in old mice. Our genome-wide screens in primary cultures of young and old NSCs uncovered more than 300 gene knockouts that specifically restore the activation of old NSCs. The top gene knockouts are involved in cilium organization and glucose import. We also establish a scalable CRISPR–Cas9 screening platform in vivo, which identified 24 gene knockouts that boost NSC activation and the production of new neurons in old brains. Notably, the knockout of Slc2a4, which encodes the GLUT4 glucose transporter, is a top intervention that improves the function of old NSCs. Glucose uptake increases in NSCs during ageing, and transient glucose starvation restores the ability of old NSCs to activate. Thus, an increase in glucose uptake may contribute to the decline in NSC activation with age. Our work provides scalable platforms to systematically identify genetic interventions that boost the function of old NSCs, including in vivo, with important implications for countering regenerative decline during ageing.

IMPORTANCE: Identifying disparities in health outcomes related to modifiable patient factors can improve patient care. OBJECTIVE: To compare likelihood of withdrawal of life-supporting treatment (WLST) and mortality in patients with complete cervical spinal cord injury (SCI) with different types of insurance. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study collected data between 2013 and 2020 from 498 trauma centers participating in the Trauma Quality Improvement Program. Participants included adult patients (older than 16 years) with complete cervical SCI. Data were analyzed from November 1, 2023, through May 18, 2024. EXPOSURE: Uninsured or public insurance compared with private insurance. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were WLST and mortality. The adjusted odds ratio (aOR) of each outcome was estimated using hierarchical logistic regression. Propensity score matching was used as an alternative analysis to compare public and privately insured patients. Process of care outcomes, including the occurrence of a hospital complication and length of stay, were compared between matched patients. RESULTS: The study included 8421 patients with complete cervical SCI treated across 498 trauma centers (mean [SD] age, 49.1 [20.2] years; 6742 male [80.1%]). Among the 3524 patients with private insurance, 503 had WLST (14.3%) and 756 died (21.5%). Among the 3957 patients with public insurance, 906 had WLST (22.2%) and 1209 died (30.6%). Among the 940 uninsured patients, 156 had WLST (16.6%) and 318 died (33.8%). A significant difference was found between uninsured and privately insured patients in the adjusted odds of WLST (aOR, 1.49; 95% CI, 1.11-2.01) and mortality (aOR, 1.98; 95% CI, 1.50-2.60). Similar results were found in subgroup analyses. Matched public compared with private insurance patients were found to have significantly greater odds of hospital complications (odds ratio, 1.27; 95% CI, 1.14-1.42) and longer hospital stay (mean difference 5.90 days; 95% CI, 4.64-7.20), which was redemonstrated on subgroup analyses. CONCLUSIONS AND RELEVANCE: Health insurance type was associated with significant differences in the odds of WLST, mortality, hospital complications, and days in hospital among patients with complete cervical SCI in this study. Future work is needed to incorporate patient perspectives and identify strategies to close the quality gap for the large number of patients without private insurance.

Recombinant adeno-associated virus (rAAV) vector gene delivery systems have demonstrated great promise in clinical trials but continue to face durability and dose-related challenges. Unlike rAAV gene therapy, integrating gene addition approaches can provide curative expression in mitotically active cells and pediatric populations. We explored a novel in vivodelivery approach based on an engineered transposase, Sleeping Beauty(SB100X), delivered as an mRNA within a lipid nanoparticle (LNP), in combination with an rAAV-delivered transposable transgene. This combinatorial approach achieved correction of ornithine transcarbamylase deficiency in the neonatal Spfashmouse model following a single delivery to dividing hepatocytes in the newborn liver. Correction remained stable into adulthood, while a conventional rAAV approach resulted in a return to the disease state. In non-human primates, integration by transposition, mediated by this technology, improved gene expression 10-fold over conventional rAAV-mediated gene transfer while requiring 5-fold less vector. Additionally, integration site analysis confirmed a random profile while specifically targeting TA dinucleotides across the genome. Together, these findings demonstrate that transposable elements can improve rAAV-delivered therapies by lowering the vector dose requirement and associated toxicity while expanding target cell types.

For the past 11 years, a dedicated effort in our research group focused on fundamentally advancing the photophysical properties of cuprous bis-phenanthroline-based metal-to-ligand charge transfer (MLCT) excited states. We rationalized that, by gaining control over the numerous factors limiting the more widespread use of CuIMLCT photosensitizers, they would be readily adopted in numerous light-activated applications given the earth-abundance of copper and the extensive library of 1,10-phenanthrolines developed over the last century. Significant progress has been achieved by recognizing valuable structure–property concepts developed by other researchers in tandem with detailed ultrafast and conventional time-scale investigations, in-silico-inspired molecular designs to predict spectroscopic properties, and applying novel synthetic methodologies. Ultimately, we achieved a plateau in exerting cooperative steric influence to control CuIMLCT excited state decay. This led to combining sterics with π-conjugation and/or inductive electronic effects to further exert control over molecular photophysical properties. The lessons gleaned from our studies of homoleptic complexes were recently extended to heteroleptic bis(phenanthrolines) featuring enhanced visible light absorption properties and long-lived room-temperature photoluminescence. This Accountnavigates the reader through our intellectual journey of decision-making, molecular and experimental design, and data interpretation in parallel with appropriate background information related to the quantitative characterization of molecular photophysics using CuIMLCT chromophores as prototypical examples.

Clinical trials in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) require histologic scoring for assessment of inclusion criteria and endpoints. However, variability in interpretation has impacted clinical trial outcomes. We developed an artificial intelligence-based measurement (AIM) tool for scoring MASH histology (AIM-MASH). AIM-MASH predictions for MASH Clinical Research Network necroinflammation grades and fibrosis stages were reproducible (κ= 1) and aligned with expert pathologist consensus scores (κ= 0.62–0.74). The AIM-MASH versus consensus agreements were comparable to average pathologists for MASH Clinical Research Network scores (82% versus 81%) and fibrosis (97% versus 96%). Continuous scores produced by AIM-MASH for key histological features of MASH correlated with mean pathologist scores and noninvasive biomarkers and strongly predicted progression-free survival in patients with stage 3 (P< 0.0001) and stage 4 (P= 0.03) fibrosis. In a retrospective analysis of the ATLAS trial (NCT03449446), responders receiving study treatment showed a greater continuous change in fibrosis compared with placebo (P= 0.02). Overall, these results suggest that AIM-MASH may assist pathologists in histologic review of MASH clinical trials, reducing inter-rater variability on trial outcomes and offering a more sensitive and reproducible measure of patient responses.

Until recently, surgery had been passed over in the domain of global health, historically being described as “the neglected stepchild of global health.” Knowledge of the existing global disparities in neurosurgical care has led to neurosurgery capacity-building efforts especially in low-income and middle-income countries. While many global collaborative projects are currently undertaken with philanthropic support, sustainability and scalability are not likely without governmental adoption of neurosurgery-inclusive national surgical plans. Momentum grows for the global neurosurgery community to develop a global neurosurgery action plan outlining goals, a guiding framework, an execution plan, and indicators for monitoring and evaluation.

Warehouse CITY is an open data product used to visualize and quantify the cumulative impact of warehouses within Southern California. Community groups, researchers, planners, and local agencies apply this open data product in project approval processes, research, lawsuits, and education. Warehouse CITY estimates the cumulative impacts of warehouse counts, acreage, building footprint, heavy-duty truck trips, diesel particulate matter emissions, oxides of nitrogen emissions, carbon dioxide emissions, and jobs. The Warehouse CITY open data product and dashboard is available as a website and at a GitHub repository.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disorder caused by a mutation in the X-linked CDKL5gene. CDKL5 is a serine/threonine kinase that is critical for axon outgrowth and dendritic morphogenesis as well as synapse formation, maturation, and maintenance. This disorder is characterized by early-onset epilepsy, hypotonia, and failure to reach cognitive and motor developmental milestones. Because the disease is monogenic, delivery of the CDKL5gene to the brain of patients should provide clinical benefit. To this end, we designed a gene therapy vector, adeno-associated virus (AAV)9.Syn.hCDKL5, in which human CDKL5gene expression is driven by the synapsin promoter. In biodistribution studies conducted in mice, intracerebroventricular (i.c.v.) injection resulted in broader, more optimal biodistribution than did intra-cisterna magna (i.c.m.) delivery. AAV9.Syn.hCDKL5 treatment increased phosphorylation of EB2, a bona fide CDKL5 substrate, demonstrating biological activity in vivo. Our data provide proof of concept that i.c.v. delivery of AAV9.Syn.hCDKL5 to neonatal male Cdkl5knockout mice reduces pathology and reduces aberrant behavior. Functional improvements were seen at doses of 3e11 to 5e11 vector genomes/g brain, which resulted in transfection of ≥50% of the neurons. Functional improvements were not seen at lower doses, suggesting a requirement for broad distribution for efficacy.

Graphical abstract:

Margin status in head and neck cancer has important prognostic implications. Currently, resection is based on manual palpation and gross visualization followed by intraoperative specimen or tumor bed–based margin analysis using frozen sections. While generally effective, this protocol has several limitations including margin sampling and close and positive margin re-localization. There is a lack of evidence on the association of use of frozen section analysis with improved survival in head and neck cancer. This article reviews novel technologies in head and neck margin analysis such as 3-dimensional scanning, augmented reality, molecular margins, optical imaging, spectroscopy, and artificial intelligence.

Multimodal artificial intelligence models using digital histopathology slides outperform clinical and pathological variables for prognostic prediction of distant metastasis and prostate cancer–specific mortality, and can be incorporated in clinical practice for personalized risk stratification.

Graphical abstract:

The views and opinions expressed within this article are the authors' own and do not necessarily reflect the views of their employers. CRISIS loves company. Like many of the readers [...]

There I was: tasked with piloting an RQ-4 (call sign: Hawk 17) on a routine ferry flight from Andersen AFB in Guam to Beale AFB in California. These flights usually [...]

'You can't repeat the past,' a character is told in F. Scott Fitzgerald's The Great Gatsby, to which he grandly replies, 'Can't repeat the past? Why of course you can!' [...]

The United States faces a protracted conflict in Ukraine. There is almost no chance of this war ending soon, and it is already having ripple effects across Europe, the Middle [...]

ABSTRACT Since the Republican Senate refused to consider President Obama's nomination of Merrick Garland to the Supreme Court in 2016--coupled with the Trump Administration's success in filling that seat with [...]

Objective. Deficits in vestibular function increase the risk for falls while turning. However, the clinical assessment of turning in patients with vestibular dysfunction is lacking, and evidence is limited that identifies the effectiveness of vestibular physical therapy in improving turning performance. The purpose of this study was to quantify walking and turning performance during the instrumented Timed "Up & Go" (TUG) test using body-worn inertial measurement units (IMUs). Novel instrumented TUG parameters were investigated for ability to distinguish patients with unilateral vestibular deafferentation (UVD) from control groups and discriminate the differences in turning parameters of patients with UVD following vestibular physical therapy. Methods. Thirty-eight individuals were recruited following UVD surgery: 26 age-matched veteran controls with reports of dizziness not from a peripheral vestibular origin, and 12 age-matched healthy controls. Participants were donned with IMUs and given verbal instructions to complete the TUG test as fast as safely possible. The IMU-instrumented and automated assessment of the TUG test provided component-based TUG parameters, including the novel walk:turn ratio. Among the participants with UVD, 19 completed an additional instrumented TUG testing after vestibular physical therapy. Results. The walk:turn time ratio showed that turning performance in patients with UVD before rehabilitation is significantly more impaired than both the individuals with nonperipheral conditions and healthy controls. Vestibular rehabilitation significantly improved turning performance and "normalized" their walk:turn time ratio compared with healthy controls. The duration of the straight walking component in individuals with UVD before vestibular physical therapy, however, was not significantly different compared with that component in people after vestibular physical therapy and in healthy controls. Conclusion. The IMU-instrumented TUG test can be used to distinguish individuals with vestibular deafferentation and to objectively quantify the change in their turning performance after vestibular physical therapy. Impact. The IMU-based instrumented TUG parameters have the potential to quantify the efficacy of vestibular physical therapy and be adopted in the clinic. Keywords: Gait, Inertial Measurement Unit, Rehabilitation, Timed Up and Go, Turn, Vestibular Hypofunction, Introduction Individuals with vestibular hypofunction commonly present with dizziness, balance deficits, and gaze disturbance. (1) Such symptoms can cause changes in movement kinematics and compensatory alterations, with respect to gait [...]