Awareness, interest, and preferences of primary care providers in using point-of-care cancer screening technology

Well-developed point-of-care (POC) cancer screening tools have the potential to provide better cancer care to patients in both developed and developing countries. However, new medical technology will not be adopted by medical providers unless it addresses a population’s existing needs and end-users’ preferences. The goals of our study were to assess primary care providers’ level of awareness, interest, and preferences in using POC cancer screening technology in their practice and to provide guidelines to biomedical engineers for future POC technology development. A total of 350 primary care providers completed a one-time self-administered online survey, which took approximately 10 minutes to complete. A $50 Amazon gift card was given as an honorarium for the first 100 respondents to encourage participation. The description of POC cancer screening technology was provided in the beginning of the survey to ensure all participants had a basic understanding of what constitutes POC technology. More than half of the participants (57%) stated that they heard of the term “POC technology” for the first time when they took the survey. However, almost all of the participants (97%) stated they were either “very interested” (68%) or “somewhat interested” (29%) in using POC cancer screening technology in their practice. Demographic characteristics such as the length of being in the practice of medicine, the percentage of patients on Medicaid, and the average number of patients per day were not shown to be associated with the level of interest in using POC. These data show that there is a great interest in POC cancer screening technology utilization among this population of primary care providers and vast room for future investigations to further understand the interest and preferences in using POC cancer technology in practice. Ensuring that the benefits of new technology outweigh the costs will maximize the likelihood it will be used by medical providers and patients

Carbon reductions and health co-benefits from US residential energy efficiency measures

The United States (US) Clean Power Plan established state-specific carbon dioxide (CO2) emissions reduction goals for fossil fuel-fired electricity generating units (EGUs). States may achieve these goals through multiple mechanisms, including measures that can achieve equivalent CO2 reductions such as residential energy efficiency, which will have important co-benefits. Here, we develop state-resolution simulations of the economic, health, and climate benefits of increased residential insulation, considering EGUs and residential combustion. Increasing insulation to International Energy Conservation Code 2012 levels for all single-family homes in the US in 2013 would lead to annual reductions of 80 million tons of CO2 from EGUs, with annual co-benefits including 30 million tons of CO2 from residential combustion and 320 premature deaths associated with criteria pollutant emissions from both EGUs and residential combustion sources. Monetized climate and health co-benefits average $49 per ton of CO2 reduced from EGUs (range across states:$12–$390). State-specific co-benefit estimates can inform development of optimal Clean Power Plan implementation strategies

A prion-like domain in ELF3 functions as a thermosensor in Arabidopsis.

Temperature controls plant growth and development, and climate change has already altered the phenology of wild plants and crops1. However, the mechanisms by which plants sense temperature are not well understood. The evening complex is a major signalling hub and a core component of the plant circadian clock2,3. The evening complex acts as a temperature-responsive transcriptional repressor, providing rhythmicity and temperature responsiveness to growth through unknown mechanisms2,4-6. The evening complex consists of EARLY FLOWERING 3 (ELF3)4,7, a large scaffold protein and key component of temperature sensing; ELF4, a small α-helical protein; and LUX ARRYTHMO (LUX), a DNA-binding protein required to recruit the evening complex to transcriptional targets. ELF3 contains a polyglutamine (polyQ) repeat8-10, embedded within a predicted prion domain (PrD). Here we find that the length of the polyQ repeat correlates with thermal responsiveness. We show that ELF3 proteins in plants from hotter climates, with no detectable PrD, are active at high temperatures, and lack thermal responsiveness. The temperature sensitivity of ELF3 is also modulated by the levels of ELF4, indicating that ELF4 can stabilize the function of ELF3. In both Arabidopsis and a heterologous system, ELF3 fused with green fluorescent protein forms speckles within minutes in response to higher temperatures, in a PrD-dependent manner. A purified fragment encompassing the ELF3 PrD reversibly forms liquid droplets in response to increasing temperatures in vitro, indicating that these properties reflect a direct biophysical response conferred by the PrD. The ability of temperature to rapidly shift ELF3 between active and inactive states via phase transition represents a previously unknown thermosensory mechanism

Using Motor Tempi to Understand Rhythm and Grammatical Skills in Developmental Language Disorder and Typical Language Development

Children with developmental language disorder (DLD) show relative weaknesses on rhythm tasks beyond their characteristic linguistic impairments. The current study compares preferred tempo and the width of an entrainment region for 5- to 7-year-old typically developing (TD) children and children with DLD and considers the associations with rhythm aptitude and expressive grammar skills in the two populations. Preferred tempo was measured with a spontaneous motor tempo task (tapping tempo at a comfortable speed), and the width (range) of an entrainment region was measured by the difference between the upper (slow) and lower (fast) limits of tapping a rhythm normalized by an individual’s spontaneous motor tempo. Data from N = 16 children with DLD and N = 114 TD children showed that whereas entrainment-region width did not differ across the two groups, slowest motor tempo, the determinant of the upper (slow) limit of the entrainment region, was at a faster tempo in children with DLD vs. TD. In other words, the DLD group could not pace their slow tapping as slowly as the TD group. Entrainment-region width was positively associated with rhythm aptitude and receptive grammar even after taking into account potential confounding factors, whereas expressive grammar did not show an association with any of the tapping measures. Preferred tempo was not associated with any study variables after including covariates in the analyses. These results motivate future neuroscientific studies of low-frequency neural oscillatory mechanisms as the potential neural correlates of entrainment-region width and their associations with musical rhythm and spoken language processing in children with typical and atypical language development

Encountering Berlant part one: Concepts otherwise

In Part 1 of ‘Encountering Berlant’, we encounter the promise and provocation of Lauren Berlant's work. In 1000-word contributions, geographers and others stay with what Berlant's thought offers contemporary human geography. They amplify an encounter with their work, demonstrating how a concept, idea, or style disrupts something, opens up a new possibility, or simply invites thinking otherwise. The encounters range across the incredible body of work Berlant left us with, from the ‘national sentimentality’ trilogy through to recent work on negativity. Varying in form and tone, the encounters exemplify and enact the inexhaustible plenitude of Berlant's thought: fantasy, the case, love, impasse, feel tanks, slow death, ellipses, gesture, attrition, intimate public, ambivalence, style. Part 2 of ‘Encountering Berlant’ focuses on Berlant's most influential concept: ‘cruel optimism’. Across these heterogeneous encounters, Berlant's enduring concern with the tensions and possibilities of relationality and how to enact better forms of common life shine through. These enduring concerns and Berlant's commitment to the incoherence and overdetermination of phenomena are summarised in the Introduction, which also explores how Berlant's work has been engaged with in geography. The result is a repository of what an encounter with Berlant's thought makes possible. Short Abstract Part 1 of ‘Encountering Berlant’ explores the promise and provocation of Lauren Berlant's work. Contributors amplify an encounter with Berlant's concepts, tones, and styles, drawing out their implications for understanding relationality and how to invent and live better ways of being in common. The result is a repository of what Berlant's thinking offers geographers

Encountering Berlant part 1: Concepts otherwise

In Part 1 of ‘Encountering Berlant’, we encounter the promise and provocation of Lauren Berlant's work. In 1000-word contributions, geographers and others stay with what Berlant's thought offers contemporary human geography. They amplify an encounter with their work, demonstrating how a concept, idea, or style disrupts something, opens up a new possibility, or simply invites thinking otherwise. The encounters range across the incredible body of work Berlant left us with, from the ‘national sentimentality’ trilogy through to recent work on negativity. Varying in form and tone, the encounters exemplify and enact the inexhaustible plenitude of Berlant's thought: fantasy, the case, love, impasse, feel tanks, slow death, ellipses, gesture, attrition, intimate public, ambivalence, style. Part 2 of ‘Encountering Berlant’ focuses on Berlant's most influential concept: ‘cruel optimism’. Across these heterogeneous encounters, Berlant's enduring concern with the tensions and possibilities of relationality and how to enact better forms of common life shine through. These enduring concerns and Berlant's commitment to the incoherence and overdetermination of phenomena are summarised in the Introduction, which also explores how Berlant's work has been engaged with in geography. The result is a repository of what an encounter with Berlant's thought makes possible

Clinical risk stratification of paediatric renal transplant recipients using C1q and C3d fixing of de novo donor-specific antibodies

Introduction: We have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes. Methods: A total of 75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. The primary event was defined as 50% reduction from baseline estimated glomerular filtration rate and was analysed using the Kaplan–Meier estimator. Results: Of 65 patients tested, 32 (49%) and 23 (35%) tested positive for C1q and C3d fixing, respectively. Of the 32 C1q-positive (c1q+) patients, 13 (41%) did not show concomitant C3d fixing. The mean fluorescence intensity values of the original immunoglobulin G DSA correlated poorly with complement-fixing positivity (C1q: adjusted R2 0.072; C3d: adjusted R2 0.11; p < 0.05). C1q+ antibodies were associated with acute tubulitis [0.75 ± 0.18 (C1q+) vs. 0.25 ± 0.08 (C1q−) episodes per patient (mean ± standard error of the mean; p < 0.05] but not with worse long-term renal allograft dysfunction (median time to primary event 5.9 (C1q+) vs. 6.4 (C1q−) years; hazard ratio (HR) 0.74; 95% confidence ratio (CI) 0.30–1.81; p = 0.58]. C3d-positive (C3d+) antibodies were associated with positive C4d histological staining [47% (C3d+) vs. 20% (C3d−); p = 0.04] and with significantly worse long-term allograft dysfunction [median time to primary event: 5.6 (C3d+) vs. 6.5 (C3d−) years; HR 0.38; 95% CI 0.15–0.97; p = 0.04]. Conclusion: Assessment of C3d fixing as part of prospective HLA monitoring can potentially aid stratification of patients at the highest risk of long-term renal allograft dysfunction

HPV-FRAME: A consensus statement and quality framework for modelled evaluations of HPV-related cancer control.

Intense research activity in HPV modelling over this decade has prompted the development of additional guidelines to those for general modelling. A specific framework is required to address different policy questions and unique complexities of HPV modelling. HPV-FRAME is an initiative to develop a consensus statement and quality-based framework for epidemiologic and economic HPV models. Its development involved an established process. Reporting standards have been structured according to seven domains reflecting distinct policy questions in HPV and cancer prevention and categorised by relevance to a population or evaluation. Population-relevant domains are: 1) HPV vaccination in pre-adolescent and young adolescent individuals; 2) HPV vaccination in older individuals; 3) targeted vaccination in men who have sex with men; 4) considerations for individuals living with HIV and 5) considerations for low- and middle-income countries. Additional considerations applicable to specific evaluations are: 6) cervical screening or integrated cervical screening and HPV vaccination approaches and 7) alternative vaccine types and alternative dosing schedules. HPV-FRAME aims to promote the development of models in accordance with an explicit framework, to better enable target audiences to understand a model's strength and weaknesses in relation to a specific policy question and ultimately improve the model's contribution to informed decision-making

Disability, atrophy and cortical reorganization following spinal cord injury

The impact of traumatic spinal cord injury on structural integrity, cortical reorganization and ensuing disability is variable and may depend on a dynamic interaction between the severity of local damage and the capacity of the brain for plastic reorganization. We investigated trauma-induced anatomical changes in the spinal cord and brain, and explored their relationship to functional changes in sensorimotor cortex. Structural changes were assessed using cross-sectional cord area, voxel-based morphometry and voxel-based cortical thickness of T1-weighted images in 10 subjects with cervical spinal cord injury and 16 controls. Cortical activation in response to right-sided (i) handgrip; and (ii) median and tibial nerve stimulation were assessed using functional magnetic resonance imaging. Regression analyses explored associations between cord area, grey and white matter volume, cortical activations and thickness, and disability. Subjects with spinal cord injury had impaired upper and lower limb function bilaterally, a 30% reduced cord area, smaller white matter volume in the pyramids and left cerebellar peduncle, and smaller grey matter volume and cortical thinning in the leg area of the primary motor and sensory cortex compared with controls. Functional magnetic resonance imaging revealed increased activation in the left primary motor cortex leg area during handgrip and the left primary sensory cortex face area during median nerve stimulation in subjects with spinal cord injury compared with controls, but no increased activation following tibial nerve stimulation. A smaller cervical cord area was associated with impaired upper limb function and increased activations with handgrip and median nerve stimulation, but reduced activations with tibial nerve stimulation. Increased sensory deficits were associated with increased activations in the left primary sensory cortex face area due to median nerve stimulation. In conclusion, spinal cord injury leads to cord atrophy, cortical atrophy of primary motor and sensory cortex, and cortical reorganization of the sensorimotor system. The degree of cortical reorganization is predicted by spinal atrophy and is associated with significant disability

High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival

Numerous cell states are known to comprise the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). However, the developmental stemness and co-occurrence of these cell states remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort of treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) samples (n = 25). We then combined these samples with surgical resection (n = 6) and publicly available samples to increase statistical power (n = 80). Following annotation into 25 distinct cell states, cells were scored for developmental stemness, and a customized version of the Ecotyper tool was used to identify communities of co-occurring cell states in bulk RNA-seq samples (n = 268). We discovered a tumor microenvironmental community comprised of aggressive basal-like malignant cells, tumor-promoting SPP1+ macrophages, and myofibroblastic cancer-associated fibroblasts associated with especially poor prognosis. We also found a developmental stemness continuum with implications for survival that is present in both malignant cells and cancer-associated fibroblasts (CAFs). We further demonstrated that high-dimensional analyses predictive of survival are feasible using standard-of-care, time-of-diagnosis EUS-FNB specimens. In summary, we identified tumor microenvironmental and developmental stemness characteristics from a high-dimensional gene expression analysis of PDAC using human tissue specimens, including time-of-diagnosis EUS-FNB samples. These reveal new connections between tumor microenvironmental composition, CAF and malignant cell stemness, and patient survival that could lead to better upfront risk stratification and more personalized upfront clinical decision-making