Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25–26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs. Prominent themes surfaced, including competing research priorities and incentives, inadequate representation of patient population in clinical trials, opportunities to better leverage existing technology and infrastructure in trial design, and a need for heightened transparency and accountability in research practices. The group determined that together these elements contribute to an inefficient and costly clinical research enterprise, amplifying disparities in population health and sustaining gaps in evidence that impede advancements in equitable healthcare delivery and outcomes. The goal of addressing the identified challenges is to ultimately make clinical trials faster, more inclusive, and more efficient across diverse communities and settings.

Pectin is composed of a group of complex polysaccharides that are naturally found in various plants and are associated with a range of beneficial health effects. Health outcomes from dietary pectin can vary depending on botanical origin, dietary dose and structure of pectin. The objective of this scoping review is to build a comprehensive overview of the current evidence available on intervention studies conducted in humans and to better understand the possible knowledge gaps in terms of structure–function relationships across the different health-related effects. PubMed and Embase databases were searched using PRISMA-ScR guidelines, yielding 141 references (from the initial 3704), representing 134 intervention studies performed between 1961 and 2022 that met inclusion criteria. Studies were divided into six categories, which included gut health, glycaemic response and appetite, fat metabolism, bioavailability of micronutrients, immune response and other topics. Review of these human intervention studies identified a variety of cohort characteristics and populations (life stage, health status, country), sources/types of pectin (i.e. citrus, sugarbeet, apple, other and non-defined), intervention timeframes (from one single intake to 168 d) and doses (0.1–50 g/d) that were tested for health outcomes in people. Gut health, post-prandial glucose regulation and maintenance of blood cholesterol represented the largest categories of studied outcomes. Further research to strengthen the structure–function relationships for pectin with health properties and associated outcomes is warranted and will benefit from a more precise description of physico-chemical characteristics and molecular compositions, such as degree of esterification, weight, degree of branching, viscosity, gel formation and solubility.

Background: Frailty and sarcopenia predict worse surgical outcomes among spinal degenerative and deformity-related populations; this association is less clear in the context of spinal oncology. Here, we identified frailty and sarcopenia tools applied in spinal oncology and appraised their clinimetric properties. Methods: A systematic review was conducted from January 1st, 2000, until June 2022. Study characteristics, frailty tools, measures of sarcopenia, component domains, individual items, cut-off values, and measurement techniques were collected. Clinimetric assessment was performed according to Consensus-based Standards for Health Measurement Instruments. Results: Twenty-two studies were included (42,514 patients). The three most employed frailty tools were the Metastatic Spine tumor Frailty Index (MSTFI), Modified Frailty Index-11 (mFI-11), and the mFI-5. The three most common sarcopenia measures were the L3-Total Psoas Area (TPA)/Vertebral Body Area (VBA), L3-TPA/Height2, and L3-Spinal Muscle Index (L3-Cross-Sectional Muscle Area/Height2). Frailty and sarcopenia measures lacked content and construct validity. Positive predictive validity was observed in select studies employing the HFRS, mFI-5, MSTFI, and L3-TPA/VBA. All frailty tools had floor or ceiling effects. Conclusions: Existing tools for evaluating frailty and sarcopenia in surgical spine oncology have poor clinimetric properties. Here, we provide a pragmatic approach to utilizing existing frailty and sarcopenia tools, until more clinimetrically robust instruments are developed.

Tight focusing with very small f-numbers is necessary to achieve the highest at-focus irradiances. However, tight focusing imposes strong demands on precise target positioning in-focus to achieve the highest on-target irradiance. We describe several near-infrared, visible, ultraviolet and soft and hard X-ray diagnostics employed in a ∼1022 W/cm2 laser–plasma experiment. We used nearly 10 J total energy femtosecond laser pulses focused into an approximately 1.3-μm focal spot on 5–20 μm thick stainless-steel targets. We discuss the applicability of these diagnostics to determine the best in-focus target position with approximately 5 μm accuracy (i.e., around half of the short Rayleigh length) and show that several diagnostics (in particular, 3$\omega$ reflection and on-axis hard X-rays) can ensure this accuracy. We demonstrated target positioning within several micrometers from the focus, ensuring over 80% of the ideal peak laser intensity on-target. Our approach is relatively fast (it requires 10–20 laser shots) and does not rely on the coincidence of low-power and high-power focal planes.

Mercury ion removal from waste-waters has been the subject of extensive research. The aim of the present investigation was to report the incorporation of the n-alkylamine molecules onto a bentonite surface and the capacities of these new chelating moieties on this modified bentonite surface for mercury removal from water. Bentonite collected from the Amazon region, Brazil, was used in an intercalation process with polar n-alkylamine molecules of general formula H3C(CH2)n-NH2 (n = 1 to 4) in 1,2-dichloroethane. The natural and modified bentonite samples were characterized by elemental analysis, Xray diffraction, helium picnometry, mercury porosimetry, and 29Si, 27Al, and 13C nuclear magnetic resonance spectroscopy. Because of the increasing size of the molecules attached to the pendant chains, the metal-adsorption capability of the final chelating materials was measured in each case. The adsorption of Hg(II) on natural and modified bentonites was determined under different conditions. The effects of concentration of Hg(II), contact time, and pH were investigated; batch and dynamic adsorption experiments of Hg(II) were conducted on bentonite samples under various conditions. The ability of these materials to remove Hg(II) from aqueous solution was assessed by means of a series of adsorption isotherms at room temperature and pH 4.0. In order to evaluate the bentonite samples as adsorbents in a dynamic system, a glass column was filled with clay samples (1.0 g each) and fed with 1.8 × 10−4 mol dm−3 Hg(II) at pH 4.0. The energetic effects caused by adsorption of metal cations were determined by means of calorimetric titrations. Thermodynamics indicated the existence of favorable conditions for such Hg(II)-nitrogen interactions.

We evaluated diagnostic test and antibiotic utilization among 252 patients from 11 US hospitals who were evaluated for coronavirus disease 2019 (COVID-19) pneumonia during the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) omicron variant pandemic wave. In our cohort, antibiotic use remained high (62%) among SARS-CoV-2–positive patients and even higher among those who underwent procalcitonin testing (68%).

Intravesical Bacillus Calmette-Guérin (BCG) is a standard therapy for non–muscle-invasive bladder cancer used in urology clinics and inpatient settings. We present a review of infection risks to patients receiving intravesical BCG, healthcare personnel who prepare and administer BCG, and other patients treated in facilities where BCG is prepared and administered. Knowledge of these risks and relevant regulations informs appropriate infection prevention measures.

Spatially resolved transcriptomics (SRT) is a growing field that links gene expression to anatomical context. SRT approaches that use next-generation sequencing (NGS) combine RNA sequencing with histological or fluorescent imaging to generate spatial maps of gene expression in intact tissue sections. These technologies directly couple gene expression measurements with high-resolution histological or immunofluorescent images that contain rich morphological information about the tissue under study. While broad access to NGS-based spatial transcriptomic technology is now commercially available through the Visium platform from the vendor 10× Genomics, computational tools for extracting image-derived metrics for integration with gene expression data remain limited. We developed VistoSeg as a MATLAB pipeline to process, analyze and interactively visualize the high-resolution images generated in the Visium platform. VistoSeg outputs can be easily integrated with accompanying transcriptomic data to facilitate downstream analyses in common programing languages including R and Python. VistoSeg provides user-friendly tools for integrating image-derived metrics from histological and immunofluorescent images with spatially resolved gene expression data. Integration of this data enhances the ability to understand the transcriptional landscape within tissue architecture. VistoSeg is freely available at http://research.libd.org/VistoSeg/.

Addressing many social challenges requires both structural and behavioral change. The binary of an i- and s-frame obscures how behavioral science can help foster bottom-up collective action. Adopting a community-frame perspective moves toward a more integrative view of how social change emerges, and how it might be promoted by policymakers and publics in service of addressing challenges like climate change.

Background: Frailty is increasingly recognized for an association with adverse events, mortality, and hospital discharge disposition among surgical patients. The purpose of this study was to describe how spinal surgeons conceptualize, define, and assess frailty in the context of spinal metastatic disease (SMD). Methods: We conducted an international, cross-sectional, 33-question survey of the AO Spine community. The survey was developed using a modified Delphi technique and was designed to elucidate preoperative surrogate markers of frailty in the context of SMD. Responses were ranked using weighted averages. Consensus was defined as ≥ 70% agreement among respondents. Results: Results were analyzed for 312 respondents (86% completion rate). Study participants represented 71 countries. Most respondents informally assess frailty in patients with SMD by forming a general perception based on clinical condition and patient history. Consensus was attained regarding the association between 14 clinical variables and frailty. Severe comorbidities, systemic disease burden, and poor performance status were most associated with frailty; severe comorbidities included high-risk cardio-pulmonary disease, renal failure, liver failure, and malnutrition. Conclusions: Surgeons recognized frailty is important but commonly evaluate it based on general clinical impression rather than using existing frailty tools. We identified preoperative surrogate markers of frailty perceived as most relevant in this population.

Diagnosing the evolution of laser-generated high energy density (HED) systems is fundamental to develop a correct understanding of the behavior of matter under extreme conditions. Talbot–Lau interferometry constitutes a promising tool, since it permits simultaneous single-shot X-ray radiography and phase-contrast imaging of dense plasmas. We present the results of an experiment at OMEGA EP that aims to probe the ablation front of a laser-irradiated foil using a Talbot–Lau X-ray interferometer. A polystyrene (CH) foil was irradiated by a laser of 133 J, 1 ns and probed with 8 keV laser-produced backlighter radiation from Cu foils driven by a short-pulse laser (153 J, 11 ps). The ablation front interferograms were processed in combination with a set of reference images obtained ex situ using phase-stepping. We managed to obtain attenuation and phase-shift images of a laser-irradiated foil for electron densities above ${10}^{22}\;{\mathrm{cm}}^{-3}$. These results showcase the capabilities of Talbot–Lau X-ray diagnostic methods to diagnose HED laser-generated plasmas through high-resolution imaging.

Viruses are the most numerically abundant biological entities on Earth. As ubiquitous replicators of molecular information and agents of community change, viruses have potent effects on the life on Earth, and may play a critical role in human spaceflight, for life-detection missions to other planetary bodies and planetary protection. However, major knowledge gaps constrain our understanding of the Earth's virosphere: (1) the role viruses play in biogeochemical cycles, (2) the origin(s) of viruses and (3) the involvement of viruses in the evolution, distribution and persistence of life. As viruses are the only replicators that span all known types of nucleic acids, an expanded experimental and theoretical toolbox built for Earth's viruses will be pivotal for detecting and understanding life on Earth and beyond. Only by filling in these knowledge and technical gaps we will obtain an inclusive assessment of how to distinguish and detect life on other planetary surfaces. Meanwhile, space exploration requires life-support systems for the needs of humans, plants and their microbial inhabitants. Viral effects on microbes and plants are essential for Earth's biosphere and human health, but virus–host interactions in spaceflight are poorly understood. Viral relationships with their hosts respond to environmental changes in complex ways which are difficult to predict by extrapolating from Earth-based proxies. These relationships should be studied in space to fully understand how spaceflight will modulate viral impacts on human health and life-support systems, including microbiomes. In this review, we address key questions that must be examined to incorporate viruses into Earth system models, life-support systems and life detection. Tackling these questions will benefit our efforts to develop planetary protection protocols and further our understanding of viruses in astrobiology.