Additively manufactured versus conventionally pressed cranioplasty implants: An accuracy comparison

This article compared the accuracy of producing patient-specific cranioplasty implants using four different approaches. Benchmark geometry was designed to represent a cranium and a defect added simulating a craniectomy. An ‘ideal’ contour reconstruction was calculated and compared against reconstructions resulting from the four approaches –‘conventional’, ‘semi-digital’, ‘digital – non-automated’ and ‘digital – semi-automated’. The ‘conventional’ approach relied on hand carving a reconstruction, turning this into a press tool, and pressing titanium sheet. This approach is common in the UK National Health Service. The ‘semi-digital’ approach removed the hand-carving element. Both of the ‘digital’ approaches utilised additive manufacturing to produce the end-use implant. The geometries were designed using a non-specialised computer-aided design software and a semi-automated cranioplasty implant-specific computer-aided design software. It was found that all plates were clinically acceptable and that the digitally designed and additive manufacturing plates were as accurate as the conventional implants. There were no significant differences between the additive manufacturing plates designed using non-specialised computer-aided design software and those designed using the semi-automated tool. The semi-automated software and additive manufacturing production process were capable of producing cranioplasty implants of similar accuracy to multi-purpose software and additive manufacturing, and both were more accurate than handmade implants. The difference was not of clinical significance, demonstrating that the accuracy of additive manufacturing cranioplasty implants meets current best practice

Squirrels in Space: Using Radio Telemetry to Explore the Space Use and Movement of Sciurid Rodents

Biotelemetry is used by researchers to track the interactions of animals with each other and the environment. While advancing technology has led to the development of numerous biotelemetry tools, radio telemetry remains the most common method for tracking small animals. Moreover, telemetry tracking of animal movement is an important skill for entry-level positions in wildlife biology. Thus, hands-on experience using radio telemetry provides students with an advantage as they pursue careers in wildlife biology, as well as an opportunity to build science process skills. We present a lesson in which students use radio telemetry to track animals; collect, analyze and interpret spatial data; and consider its applications to local wildlife management and conservation. Students submit their data to a national database collecting observations from multiple institutions as part of Squirrel-Net (http://squirrel-net.org). The aggregated data allows students to generate and test hypotheses across a broader variety of species and habitats than would be possible at any single institution. The lesson is designed for adaptation to diverse educational contexts, from a single two-hour laboratory period (basic skills acquisition) to a semester-long student-driven research project (open inquiry Course-based Undergraduate Research Experience, or CURE). Although this activity and the national database focus on spatial data for squirrels, which are diurnal, charismatic, easily identified, and present on most college campuses, the same methods and materials can be modified for any animal capable of carrying a radio transmitter and being safely tracked by students

How Many Squirrels Are in the Shrubs? A Lesson Plan for Comparing Methods for Population Estimation

Estimating the population sizes of animals is a key skill for any student interested in ecology, conservation, or management. However, counting animals in natural habitats is difficult, and the many techniques that exist each rely on assumptions that can bias results. Most wildlife courses teach one or two of these methods, but rarely are students given an opportunity to compare approaches and explore how underlying assumptions affect the accuracy of estimates. Here, we describe a hands-on activity in which students estimate the size of a single population of animals using multiple methods: strip censuses, scat counts, and camera traps. They then compare the estimates and evaluate how the assumptions of each model (e.g., random use of habitats and animal behavior) bias the results. Finally, students submit their data to a national database that aggregates observations across multiple institutions as part of Squirrel-Net (http://squirrel-net.org). They can then analyze the national dataset, permitting exploration of these questions across a broader variety of habitats and species than would be possible at any single institution. Extensions of this activity guide students to enumerate the advantages and disadvantages of each method in different contexts and to select the most appropriate method for a given scenario. This activity and the database focus on estimating population sizes of squirrels, which are diurnal, charismatic, easily identified, and present in a wide range of habitats (including many campuses), but the same methods could be broadly used for other terrestrial species, including birds, amphibians, reptiles, or invertebrates

Squirreling from Afar: Adapting Squirrel-Net Modules for Remote Teaching and Learning

The shift from face-to-face instruction to remote teaching and learning has proven to be a challenging endeavor for many reasons, including lack of time, resources, and inspiration. Lab courses, the “hands-on” portion of many curricula, may be especially difficult to adapt to online learning given the common use of specialized equipment, materials, and techniques that require close supervision. Without the time and resources to creatively modify existing activities or create new ones, remote lab courses run the risk of becoming less effective, equitable, and/or engaging. Squirrel-Net has created four field-based activities for biology labs that are easy to implement, highly flexible for different course aims, and readily adaptable to a remote learning environment. In this essay, we briefly summarize the modules and propose several ways that each can be adjusted to accommodate online teaching and learning. By providing authentic learning opportunities through distance delivery we hope to promote widespread student engagement and creative solutions for instructors

Sorry to Eat and Run: A Lesson Plan for Testing Trade-off in Squirrel Behavior Using Giving Up Densities (GUDs)

All animals need to find and compete for food, shelter, and mates in order to survive and reproduce. They also need to avoid being eaten by predators. Optimal foraging theory provides a framework to examine the trade-offs individuals make while foraging for food, taking into account an animal’s body condition, predation pressure, quality of food resources, and food patch availability in the habitat. Here we describe an activity that uses Giving Up Densities (GUDs), which could be used as part of a course-based undergraduate research experience (CURE) or as a stand-alone activity. GUDs provide an experimental approach to quantify the costs and benefits of foraging in a particular patch and is simple to measure in that it is literally the density of food remaining in a patch. However, its interpretation allows students to compare foraging decisions under different environmental conditions, between species, or with different food sources. This activity was designed to study the foraging behavior of squirrels, which are active during the day, forage on seeds, and are found on and around many college campuses, but it can be adapted to nocturnal animals, birds, or other vertebrates. This module is hands-on. Students weigh seeds, sift sand, walk out into the field with bags of sand and trays, and analyze data. The module can be designed at various levels of inquiry to suit the needs of a particular class. Further, students can work individually, in pairs, or in teams. Finally, students and instructors are encouraged to upload their data to a national dataset, which is available to instructors for use in the classroom to broaden the possible hypotheses and analyses students can explore

An Introduction to the Squirrel-Net Teaching Modules

Although course-based undergraduate research experiences (CUREs) are gaining popularity in biology, most are designed for benchwork-based laboratory courses while few focus on field-based skills. Many barriers to implementing field CUREs exist, including the difficulty in designing authentic research that can be accomplished in a limited lab timeframe, permitting and liability issues, and problems gathering sufficient data to meaningfully analyze. Squirrel-Net (http://squirrel-net.org) is a consortium of mammalogists from eight different institutions who have worked to overcome these limitations through four field-based CUREs focused on sciurid rodents (e.g., squirrels, chipmunks, marmots, prairie dogs). Each module is linked to a national dataset, allowing for broader and more complex hypotheses and analyses than would be possible from a single institution. Modules have been field tested at different institutions and are easily implemented and highly flexible for different courses, levels of inquiry, habitats, and focal species. Beyond the basic lesson plan, each module also provides suggestions for adaptation at different levels of inquiry and scaffolding across a course or an entire curriculum. Moreover, our website provides templates to help lower barriers to CURE implementation (e.g., selecting a field site and writing institutional animal care protocols). Here, we introduce Squirrel-Net and give an overview of the four CURE modules. Additionally, we demonstrate how the modules can be used singly or together to provide authentic research experiences to a diversity of undergraduates

Squirreling Around for Science: Observing Sciurid Rodents to Investigate Animal Behavior

Hands-on research experiences are important opportunities for students to learn about the nature of inquiry and gain confidence in solving problems. Here, we present an inquiry-based lesson plan that investigates the foraging behavior of sciurid rodents (squirrels) in local habitats. Squirrels are an ideal study system for student research projects because many species are diurnal, easy to watch, and inhabit a range of habitats including college campuses. In this activity, instructors identify appropriate field sites and focal species, while students generate questions and brainstorm predictions in small groups regarding factors that might influence behavioral trade-offs in sciurids. Students conduct observational surveys of local squirrels in pairs using a standardized protocol and upload their data to a national database as part of the multi-institutional Squirrel-Net (http://squirrel-net.org). Instructors access the nationwide dataset through the Squirrel-Net website and provide students with data for independent analysis. Students across the country observe and record a range of squirrel species, including behaviors and habitat characteristics. The national dataset can be used to answer student questions about why squirrels behave in the way they do and for students to learn about authentic analyses regarding behavior trade-offs. Additionally, the lesson is designed to be modified across a range of inquiry levels, from a single two-hour laboratory activity to a unit- or semester-long student-driven course-based research experience. Our activity highlights the value of using observational data to conduct research, makes use of the Squirrel-Net infrastructure for collaboration, and provides students equitable access to field-based projects with small mammals

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.Peer reviewe

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice