Phase 1 Study of High-Specific-Activity I-131 MIBG for Metastatic and/or Recurrent Pheochromocytoma or Paraganglioma

Context: No therapies are approved for the treatment of metastatic and/or recurrent pheochromocytoma or paraganglioma (PPGL) in the United States. Objective: To determine the maximum tolerated dose (MTD) of high-specific-activity I-131 meta-iodobenzylguanidine (MIBG) for the treatment of metastatic and/or recurrent PPGL. Design: Phase 1, dose-escalating study to determine the MTD via a standard 3 + 3 design, escalating by 37 MBq/kg starting at 222 MBq/kg. Setting: Three centers. Patients: Twenty-one patients were eligible, received study drug, and were evaluable for MTD, response, and toxicity. Intervention: Open-label use of high-specific-activity I-131 MIBG therapy. Main Outcome Measures: Dose-limiting toxicities, adverse events, radiation absorbed dose estimates, radiographic tumor response, biochemical response, and survival. Results: The MTD was determined to be 296 MBq/kg on the basis of two observed dose-limiting toxicities at the next dose level. The highest mean radiation absorbed dose estimates were in the thyroid and lower large intestinal wall (each 1.2 mGy/MBq). Response was evaluated by total administered activity: four patients (19%), all of whom received \u3e18.5 GBq of study drug, had radiographic tumor responses of partial response by Response Evaluation Criteria in Solid Tumors. Best biochemical responses (complete or partial response) for serum chromogranin A and total metanephrines were observed in 80% and 64% of patients, respectively. Overall survival was 85.7% at 1 year and 61.9% at 2 years after treatment. The majority (84%) of adverse events were considered mild or moderate in severity. Conclusions: These findings support further development of high-specific-activity I-131 MIBG for the treatment of metastatic and/or recurrent PPGL at an MTD of 296 MBq/kg

Dopant clustering, electronic inhomogeneity, and vortex pinning in iron-based superconductors

We use scanning tunneling microscopy to map the surface structure, nanoscale electronic inhomogeneity, and vitreous vortex phase in the hole-doped superconductor Sr0.75K0.25Fe2As2 with Tc=32 K. We find that the low-T cleaved surface is dominated by a half Sr/K termination with 1×2 ordering and ubiquitous superconducting gap, while patches of gapless, unreconstructed As termination appear rarely. The superconducting gap varies by σ/Δ¯=16% on a ∼3 nm length scale, with average 2Δ¯/kBTc=3.6 in the weak-coupling limit. The vortex core size provides a measure of the superconducting coherence length ξ=2.3 nm. We quantify the vortex lattice correlation length at 9 T in comparison to several iron-based superconductors. The comparison leads us to suggest the importance of dopant size mismatch as a cause of dopant clustering, electronic inhomogeneity, and strong vortex pinning.Physic

Designing a suite of measurements to understand the critical zone

Many scientists have begun to refer to the earth surface environment from the upper canopy to the depths of bedrock as the critical zone (CZ). Identification of the CZ as an integral object worthy of study implicitly posits that the study of the whole earth surface will provide benefits that do not arise when studying the individual parts. To study the CZ, however, requires prioritizing among the measurements that can be made – and we do not generally agree on the priorities. Currently, the Susquehanna Shale Hills Critical Zone Observatory (SSHCZO) is expanding from a small original focus area (0.08 km2 , Shale Hills catchment), to a larger watershed (164 km2 , Shavers Creek watershed) and is grappling with the prioritization. This effort is an expansion from a monolithologic first-order forested catchment to a watershed that encompasses several lithologies (shale, sandstone, limestone) and land use types (forest, agriculture). The goal of the project remains the same: to understand water, energy, gas, solute, and sediment (WEGSS) fluxes that are occurring today in the context of the record of those fluxes over geologic time as recorded in soil profiles, the sedimentary record, and landscape morphology. Given the small size of the Shale Hills catchment, the original design incorporated measurement of as many parameters as possible at high temporal and spatial density. In the larger Shavers Creek watershed, however, we must focus the measurements. We describe a strategy of data collection and modeling based on a geomorphological and land use framework that builds on the hillslope as the basic unit. Interpolation and extrapolation beyond specific sites relies on geophysical surveying, remote sensing, geomorphic analysis, the study of natural integrators such as streams, groundwaters or air, and application of a suite of CZ models. We hypothesize that measurements of a few important variables at strategic locations within a geomorphological framework will allow development of predictive models of CZ behavior. In turn, the measurements and models will reveal how the larger watershed will respond to perturbations both now and into the future

Field-testing of a rapid survey method to assess the prevalence and causes of hearing loss in Gao'an, Jiangxi province, China.

BACKGROUND: The Rapid Assessment of Hearing Loss (RAHL) survey protocol aims to measure the prevalence and causes of hearing loss in a low cost and rapid manner, to inform planning of ear and hearing services. This paper reports on the first field-test of the RAHL in Gao'an County, Jiangxi Province, China. This study aimed to 1) To report on the feasibility of RAHL; 2) report on the estimated prevalence and causes of hearing loss in Gao'an. METHODS: A cross-sectional population-based survey was conducted in September-October 2018. Forty-seven clusters in Gao'an County were selected using probability-proportionate-to-size sampling. Within clusters, compact segment sampling was conducted to select 30 people aged 50+. A questionnaire was completed covering sociodemographics, hearing health, and risk factors. Automated pure-tone audiometry was completed for all participants, using smartphone-based audiometry (hearTest), at 0.5, 1, 2, 4 kHz (kHz). All participants had their ears examined by an Ear Nose and Throat (ENT) doctor, using otoscopy, and probable causes of hearing loss assigned. Prevalence estimates were age and sex standardised to the Jiangxi population. Feasibility of a cluster size of 30 was examined by assessing the response rate, and the proportion of clusters completed in 1 day. RESULTS: 1344 of 1421 eligible participants completed the survey (94.6%). 100% of clusters were completed in 1 day. The survey was completed in 4.5 weeks. The prevalence of moderate or greater hearing loss (pure-tone average of 0.5, 1, 2, 4 kHz of > = 41dBHL in the better ear) was 16.3% (95% CI = 14.3, 18.5) and for any level of hearing loss (pure-tone average of > = 26dBHL in the better ear) the prevalence was 53.2% (95% CI = 49.2, 57.1). The majority of hearing loss was due to acquired sensorineural causes (91.7% left; 92.1% right). Overall 54.0% of the population aged 50+ (108,000 people) are in need of diagnostic audiology services, 3.4% were in need of wax removal (7000 people), and 4.8% were in need of surgical services (9500 people). Hearing aid coverage was 0.4%. CONCLUSION: The RAHL survey protocol is feasible, demonstrated through the number of people examined per day, and the high response rate. The survey was completed in a much shorter period than previous all-age surveys in China. Some remaining challenges included assignment of causes of probable sensorineural loss. The data obtained from this survey can be used to scale-up hearing services in Gao'an

Implementation of a standardized protocol to manage elderly patients with low energy pelvic fractures: can service improvement be expected?

Purpose: The incidence of low energy pelvic fractures (FPFs) in the elderly is increasing. Comorbidities, decreased bone-quality, problematic fracture fixation and poor compliance represent some of their specific difficulties. In the absence of uniform management, a standard operating procedure (SOP) was introduced to our unit, aiming to improve the quality of services provided to these patients. Methods: A cohort study was contacted to test the impact of (1) using a specific clinical algorithm and (2) using different antiosteoporotic drugs. Multivariate regression analysis was used to determine prognostic factors. Study endpoints were the time-to-healing, length-of-stay, return to pre-injury mobility, union status, mortality and complications. Results: A total of 132 elderly patients (≥65 years) admitted during the period 2012–2014 with FPFs were enrolled. High-energy fractures, acetabular fractures, associated trauma affecting mobility, pathological pelvic lesions and operated FPFs were used as exclusion criteria. The majority of included patients were females (108/132; 81.8%), and the mean age was 85.8 years (range 67–108). Use of antiosteoporotics was associated with a shorter time of healing (p = 0.036). Patients treated according to the algorithm showed a significant protection against malunion (p < 0.001). Also, adherence to the algorithm allowed more patients to return to their pre-injury mobility status (p = 0.039). Conclusions: The use of antiosteoporotic medication in elderly patients with fragility pelvic fractures was associated with faster healing, whilst the adherence to a structured clinical pathway led to less malunions and non-unions and return to pre-injury mobility state

Real-Time, Real World Learning—Capitalising on Mobile Technology

This chapter explores the adoption of Web 2.0 technologies to promote active learning by students and to both mediate and enhance classroom instruction. Web 2.0 refers to open source, web-enabled applications (apps) that are driven by user-manipulated and user-generated content (Kassens-Noor, 2012). These apps are often rich in user participation, have dynamic content, and harness the collective intelligence of users (Chen, Hwang, & Wang, 2012). As such, these processes create “active, context based, personalised learning experiences” (Kaldoudi, Konstantinidis, & Bamidis, 2010, p. 130) that prioritise learning ahead of teaching. By putting the learner at the centre of the education process educators can provide environments that enhance employability prospects and spark a passion for learning that, hopefully, lasts a lifetime. As such, we critique an active learning approach that makes use of technology such as mobile applications (apps), Twitter, and augmented reality to enhance students’ real world learning. Dunlap and Lowenthal (2009) argue that social media can facilitate active learning as they recreate informal, free-flowing communications that allow students and academics to connect on a more emotional level. Furthermore, their use upskills students in the technical complexities of the digital world and also the specialised discourses that are associated with online participation, suitable for real world learning and working (Fig. 16.1). Three case studies explore the benefits of Web 2.0 processes. The first details the use of Twitter chats to connect students, academics, and industry professionals via online synchronous discussions that offer a number of benefits such as encouraging concise writing from students and maintaining on-going relationships between staff, students, and industry contacts. The second details a location-based mobile app that delivers content to students when they enter a defined geographical boundary linked to an area of a sports precinct. Finally, we explore the use of augmented reality apps to enhance teaching in Human Geography and Urban Studies

Artificial Intelligence for Science in Quantum, Atomistic, and Continuum Systems

Advances in artificial intelligence (AI) are fueling a new paradigm of discoveries in natural sciences. Today, AI has started to advance natural sciences by improving, accelerating, and enabling our understanding of natural phenomena at a wide range of spatial and temporal scales, giving rise to a new area of research known as AI for science (AI4Science). Being an emerging research paradigm, AI4Science is unique in that it is an enormous and highly interdisciplinary area. Thus, a unified and technical treatment of this field is needed yet challenging. This work aims to provide a technically thorough account of a subarea of AI4Science; namely, AI for quantum, atomistic, and continuum systems. These areas aim at understanding the physical world from the subatomic (wavefunctions and electron density), atomic (molecules, proteins, materials, and interactions), to macro (fluids, climate, and subsurface) scales and form an important subarea of AI4Science. A unique advantage of focusing on these areas is that they largely share a common set of challenges, thereby allowing a unified and foundational treatment. A key common challenge is how to capture physics first principles, especially symmetries, in natural systems by deep learning methods. We provide an in-depth yet intuitive account of techniques to achieve equivariance to symmetry transformations. We also discuss other common technical challenges, including explainability, out-of-distribution generalization, knowledge transfer with foundation and large language models, and uncertainty quantification. To facilitate learning and education, we provide categorized lists of resources that we found to be useful. We strive to be thorough and unified and hope this initial effort may trigger more community interests and efforts to further advance AI4Science

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Microelectronics-Based Biosensors Dedicated to the Detection of Neurotransmitters: A Review

Dysregulation of neurotransmitters (NTs) in the human body are related to diseases such as Parkinson's and Alzheimer's. The mechanisms of several neurological disorders, such as epilepsy, have been linked to NTs. Because the number of diagnosed cases is increasing, the diagnosis and treatment of such diseases are important. To detect biomolecules including NTs, microtechnology, micro and nanoelectronics have become popular in the form of the miniaturization of medical and clinical devices. They offer high-performance features in terms of sensitivity, as well as low-background noise. In this paper, we review various devices and circuit techniques used for monitoring NTs in vitro and in vivo and compare various methods described in recent publications