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Supportive robotic solutions take over mundane, but essential tasks from human workforce in biomedical research and development laboratories. The newest technologies in collaborative and mobile robotics enable the utilization in the human-centered and low-structured environment. Their adaptability, however, is hindered by the additional complexity that they introduce. In our paper we aim to entangle the convoluted laboratory robot integration architectures. We begin by hierarchically decomposing the laboratory workflows, and mapping the activity representations to layers and components of the automation control architecture. We elaborate the framework in detail on the example of pick-and-place labware transportation - a crucial supportive step, which we identified as the number one area of interest among experts of the field. Our concept proposal serves as a reference architecture model, the key principles of which were used in reference implementations, and are in line with international standardization efforts.

The Laboratory Automation Plug & Play (LAPP) framework is an over-arching reference architecture concept for the integration of robots in life science laboratories. The plug & play nature lies in the fact that manual configuration is not required, including the teaching of the robots. In this paper a digital twin (DT) based concept is proposed that outlines the types of information that must be provided for each relevant component of the system. In particular, for the devices interfacing with the robot, the robot positions must be defined beforehand in a device-attached coordinate system (CS) by the vendor. This CS must be detectable by the vision system of the robot by means of optical markers placed on the front side of the device. With that, the robot is capable of tending the machine by performing the pick-and-place type transportation of standard sample carriers. This basic use case is the primary scope of the LAPP-DT framework. The hardware scope is limited to simple benchtop and mobile manipulators with parallel grippers at this stage. This paper first provides an overview of relevant literature and state-of-the-art solutions, after which it outlines the framework on the conceptual level, followed by the specification of the relevant DT parameters for the robot, for the devices and for the facility. Finally, appropriate technologies and strategies are identified for the implementation.

Increasing the level of automation in pharmaceutical laboratories and production facilities plays a crucial role in delivering medicine to patients. However, the particular requirements of this field make it challenging to adapt cutting-edge technologies present in other industries. This article provides an overview of relevant approaches and how they can be utilized in the pharmaceutical industry, especially in development laboratories. Recent advancements include the application of flexible mobile manipulators capable of handling complex tasks. However, integrating devices from many different vendors into an end-to-end automation system is complicated due to the diversity of interfaces. Therefore, various approaches for standardization are considered in this article, and a concept is proposed for taking them a step further. This concept enables a mobile manipulator with a vision system to “learn” the pose of each device and - utilizing a barcode - fetch interface information from a universal cloud database. This information includes control and communication protocol definitions and a representation of robot actions needed to operate the device. In order to define the movements in relation to the device, devices have to feature - besides the barcode - a fiducial marker as standard. The concept will be elaborated following appropriate research activities in follow-up papers.

The extracellular matrix is a complex network of proteins and other molecules that are essential for the support, integrity, and structure of cells and tissues within the human body. The genes ZNF469 and PRDM5 each produce extracellular-matrix-related proteins that, when mutated, have been shown to result in the development of brittle cornea syndrome. This dysfunction results from aberrant protein function resulting in extracellular matrix disruption. Our group recently identified and published the first known associations between variants in these genes and aortic/arterial aneurysms and dissection diseases. This paper delineates the proposed effects of mutated ZNF469 and PRDM5 on various essential extracellular matrix components, including various collagens, TGF-B, clusterin, thrombospondin, and HAPLN-1, and reviews our recent reports associating single-nucleotide variants to these genes’ development of aneurysmal and dissection diseases.

Abstract Background Reducing cesarean rates is a public health priority. To help pregnant people select hospitals with lower cesarean rates, numerous organizations publish publically hospital cesarean rate data. Few pregnant people use these data when deciding where to deliver. We sought to determine whether making cesarean rate data more accessible and understandable increases the likelihood of pregnant people selecting low-cesarean rate hospitals. Methods We conducted a 1:1 randomized controlled trial in 2019–2021 among users of a fertility and pregnancy mobile application. Eligible participants were trying to conceive for fewer than five months or were 28–104 days into their pregnancies. Of 189,456 participants approached and enrolled, 120,621 participants met entry criteria and were included in analyses. The intervention group was offered an educational program explaining the importance of hospital cesarean rates and an interactive tool presenting hospital cesarean rates as 1-to-5-star ratings. Control group users were offered an educational program about hospital choice and a hospital choice tool without cesarean rate data. The primary outcome was the star rating of the hospital selected by each patient during pregnancy. Secondary outcomes were the importance of cesarean rates in choosing a hospital and delivery method (post-hoc secondary outcome). Results Of 120,621 participants (mean [SD] age, 27.8 [7.9]), 12,284 (10.2%) reported their choice of hospital during pregnancy, with similar reporting rates in the intervention and control groups. Intervention group participants selected hospitals with higher star ratings (2.52 vs 2.16; difference, 0.37 [95% CI, 0.32 to 0.43] p

ObjectiveTo describe the healthcare provider (HCP) experience of launching a COVID-19 remote patient monitoring (CRPM) program during the global COVID-19 pandemic.MethodsWe conducted qualitative, semi-structured interviews with eight HCPs involved in deploying the CRPM pilot program in the Military Health System (MHS) from June to December 2020. Interviews were audio recorded, transcribed, and analyzed thematically using an inductive approach. We then deductively mapped themes from interviews to the updated Consolidated Framework for Implementation Research (CFIR).ResultsWe identified the following main themes mapped to CFIR domains listed in parentheses: external and internal environments (outer and inner settings), processes around implementation (implementation process domain), the right people (individuals domain), and program characteristics (innovation domain). Participants believed that buy-in from leadership and HCPs was critical for successful program implementation. HCP participants showed qualities of clinical champions and believed in the CRPM program.ConclusionThe MHS deployed a successful remote patient monitoring pilot program during the global COVID-19 pandemic. HCPs found the CRPM program and the technology enabling the program to be acceptable, feasible, and usable. HCP participants exhibited characteristics of clinical champions. Leadership engagement was the most often-cited key factor for successful program implementation.

Thoracic aortic aneurysms and dissections often have inter-related pathologies that are increasingly recognized to have a genetic basis. A patient with a vascular history consisting of a spontaneous aorto-iliac dissection and thoracic aortic aneurysm belonged to a family with a significant self-reported history of aneurysmal disease. Suspecting a genetic component, genetic investigation was undertaken. Three variants of unknown significance were found in the ZNF469 gene, which is responsible for the production of a collagen-related zinc finger protein involved in multiple aspects of the development and regulation of major extracellular matrix components. This is the first report to associate this gene with vasculopathy, and further investigation by our group is underway to understand the role it plays in the development of aneurysmal diseases.

Direct-acting oral anticoagulants (DOACs) are prescribed in the treatment of venous thromboembolism, including pulmonary embolism (PE). Evidence is limited regarding the outcomes and optimal timing of DOACs in patients with intermediate- or high-risk PE treated with thrombolysis. We conducted a retrospective analysis of outcomes among patients with intermediate- and high-risk PE who received thrombolysis, by choice of long-term anticoagulant agent. Outcomes of interest included hospital length of stay (LOS), intensive care unit LOS, bleeding, stroke, readmission, and mortality. Descriptive statistics were used to examine characteristics and outcomes among patients, by anticoagulation group. Patients receiving a DOAC (n = 53) had shorter hospital LOS compared to those in warfarin (n = 39) and enoxaparin (n = 10) groups (mean LOS 3.6, 6.3 and 4.5 days, respectively; P

BackgroundVirtual care (VC) and remote patient monitoring programs were deployed widely during the COVID-19 pandemic. Deployments were heterogeneous and evolved as the pandemic progressed, complicating subsequent attempts to quantify their impact. The unique arrangement of the US Military Health System (MHS) enabled direct comparison between facilities that did and did not implement a standardized VC program. The VC program enrolled patients symptomatic for COVID-19 or at risk for severe disease. Patients’ vital signs were continuously monitored at home with a wearable device (Current Health). A central team monitored vital signs and conducted daily or twice-daily reviews (the nurse-to-patient ratio was 1:30). ObjectiveOur goal was to describe the operational model of a VC program for COVID-19, evaluate its financial impact, and detail its clinical outcomes. MethodsThis was a retrospective difference-in-differences (DiD) evaluation that compared 8 military treatment facilities (MTFs) with and 39 MTFs without a VC program. Tricare Prime beneficiaries diagnosed with COVID-19 (Medicare Severity Diagnosis Related Group 177 or International Classification of Diseases–10 codes U07.1/07.2) who were eligible for care within the MHS and aged 21 years and or older between December 2020 and December 2021 were included. Primary outcomes were length of stay and associated cost savings; secondary outcomes were escalation to physical care from home, 30-day readmissions after VC discharge, adherence to the wearable, and alarms per patient-day. ResultsA total of 1838 patients with COVID-19 were admitted to an MTF with a VC program of 3988 admitted to the MHS. Of these patients, 237 (13%) were enrolled in the VC program. The DiD analysis indicated that centers with the program had a 12% lower length of stay averaged across all COVID-19 patients, saving US $2047 per patient. The total cost of equipping, establishing, and staffing the VC program was estimated at US $3816 per day. Total net savings were estimated at US $2.3 million in the first year of the program across the MHS. The wearables were activated by 231 patients (97.5%) and were monitored through the Current Health platform for a total of 3474 (median 7.9, range 3.2-16.5) days. Wearable adherence was 85% (IQR 63%-94%). Patients triggered a median of 1.6 (IQR 0.7-5.2) vital sign alarms per patient per day; 203 (85.7%) were monitored at home and then directly discharged from VC; 27 (11.4%) were escalated to a physical hospital bed as part of their initial admission. There were no increases in 30-day readmissions or emergency department visits. ConclusionsMonitored patients were adherent to the wearable device and triggered a manageable number of alarms/day for the monitoring–team-to-patient ratio. Despite only enrolling 13% of COVID-19 patients at centers where it was available, the program offered substantial savings averaged across all patients in those centers without adversely affecting clinical outcomes.

Thoracic aortic aneurysms are clinical conditions that are associated with severe clinical endpoints including dissection and rupture, potentially leading to sudden death. Contrary to their abdominal counterparts, thoracic aortic aneurysms are well-recognized to have a genetic basis underlying their development. Among all patients with aneurysmal disease who underwent clinical genetic screening in our program (N = 145), two patients were found to have variants of uncertain significance (VUS) in the PRDM5 gene. This gene is responsible for multiple regulatory functions in extracellular matrix development, and this is the first report, to our knowledge, to associate this gene with aortopathy.

Histoplasmosis is the fungal infection caused by Histoplasma capsulatum fungus. It is commonly found in a few endemic areas in the United States, where there is a large number of birds or bats and can spread through their droppings. Disseminated histoplasmosis is a severe manifestation of the fungal infection which is commonly seen in individuals with underlying immunosuppression. Our case is an unusual case of disseminated histoplasmosis in a 60-year-old, immunocompetent male patient with a history of significant alcohol abuse, which led to end stage liver failure. While the patient showed some signs of improvement initially upon beginning the treatment, he ultimately continued to deteriorate despite treatment due to an overwhelming histoplasmosis infection. This case demonstrates the importance of keeping a high index of suspicion even amongst immunocompetent patients with no obvious exposure to risk factors. It also shows that timely diagnosis with a high index of suspicion is required with an integrated treatment approach.

It is now well established that infection with SARS-CoV-2 resulting in COVID-19 disease includes a severely symptomatic subset of patients in whom an aggressive and/or dysregulated host immune response leads to cytokine storm syndrome (CSS) that may be further complicated by thrombotic events, contributing to the severe morbidity and mortality observed in COVID-19. This review provides a brief overview of cytokine storm in COVID-19, and then presents a mechanistic discussion of how cytokine storm affects integrated pathways in thrombosis involving the endothelium, platelets, the coagulation cascade, eicosanoids, auto-antibody mediated thrombosis, and the fibrinolytic system.

BackgroundDuring the COVID-19 pandemic, individuals with a positive viral test were enrolled in a study, within 48 hours, to remotely monitor their vital signs to characterize disease progression and recovery. A virtual trial design was adopted to reduce risks to participants and the research community in a study titled Risk Stratification and Early Alerting Regarding COVID-19 Hospitalization (RiskSEARCH). The Food and Drug Administration–cleared Current Health platform with a wearable device is a continuous remote patient monitoring technology that supports hospital-at-home care and is used as a data collection tool. Enrolled participants wore the Current Health wearable device continuously for up to 30 days and took a daily symptom survey via a tablet that was provided. A qualitative substudy was conducted in parallel to better understand virtual trial implementation, including barriers and facilitators for participants. ObjectiveThis study aimed to understand the barriers and facilitators of the user experience of interacting with a virtual care platform and research team, while participating in a fully virtual study using qualitative and quantitative data. MethodsSemistructured interviews were conducted to understand participants’ experience of participating in a virtual study during a global pandemic. The schedule included their experience of enrollment and their interactions with equipment and study staff. A total of 3 RiskSEARCH participants were interviewed over telephone, and transcriptions were inductively coded and analyzed using thematic analysis. Themes were mapped onto the Theoretical Domains Framework (TDF) to identify and describe the factors that influenced study adherence. Quantitative metrics, including adherence to wearable and scheduled tasks collected as part of the RiskSEARCH main study, were paired with the interviews to present an overall picture of participation. ResultsAll participants exceeded our definition of a fully adherent participant and reported that participation was feasible and had a low burden. The symptoms progressively resolved during the trial. Inductive thematic analysis identified 13 main themes from the interview data, which were deductively mapped onto 11 of the 14 TDF domains, highlighting barriers and facilitators for each. ConclusionsParticipants in the RiskSEARCH substudy showed high levels of adherence and engagement throughout participation. Although participants experienced some challenges in setting up and maintaining the Current Health kit (eg, charging devices), they reported feeling that the requirements of participation were both reasonable and realistic. We demonstrated that the TDF can be used for inductive thematic analysis. We anticipate expanding this work in future virtual studies and trials to identify barriers and enabling factors for implementation.

BackgroundThe SARS-CoV-2 (COVID-19) pandemic may accelerate the adoption of digital, decentralized clinical trials. Conceptual recommendations for digitalized and remote clinical studies and technology are available to enable digitalization. Fully remote studies may break down some of the participation barriers in traditional trials. However, they add logistical complexity and offer fewer opportunities to intervene following a technical failure or adverse event. ObjectiveOur group designed an end-to-end digitalized clinical study protocol, using the Food and Drug Administration (FDA)–cleared Current Health (CH) remote monitoring platform to collect symptoms and continuous physiological data of individuals recently infected with COVID-19 in the community. The purpose of this work is to provide a detailed example of an end-to-end digitalized protocol implementation based on conceptual recommendations by describing the study setup in detail, evaluating its performance, and identifying points of success and failure. MethodsPrimary recruitment was via social media and word of mouth. Informed consent was obtained during a virtual appointment, and the CH-monitoring kit was shipped directly to the participants. The wearable continuously recorded pulse rate (PR), respiratory rate (RR), oxygen saturation (SpO2), skin temperature, and step count, while a tablet administered symptom surveys. Data were transmitted in real time to the CH cloud-based platform and displayed in the web-based dashboard, with alerts to the study team if the wearable was not charged or worn. The study duration was up to 30 days. The time to recruit, screen, consent, set up equipment, and collect data was quantified, and advertising engagement was tracked with a web analytics service. ResultsOf 13 different study advertisements, 5 (38.5%) were live on social media at any one time. In total, 38 eligibility forms were completed, and 19 (50%) respondents met the eligibility criteria. Of these, 9 (47.4%) were contactable and 8 (88.9%) provided informed consent. Deployment times ranged from 22 to 110 hours, and participants set up the equipment and started transmitting vital signs within 7.6 (IQR 6.3-10) hours of delivery. The mean wearable adherence was 70% (SD 19%), and the mean daily survey adherence was 88% (SD 21%) for the 8 participants. Vital signs were in normal ranges during study participation, and symptoms decreased over time. ConclusionsEvaluation of clinical study implementation is important to capture what works and what might need to be modified. A well-calibrated approach to online advertising and enrollment can remove barriers to recruitment and lower costs but remains the most challenging part of research. Equipment was effectively and promptly shipped to participants and removed the risk of illness transmission associated with in-person encounters during a pandemic. Wearable technology incorporating continuous, clinical-grade monitoring offered an unprecedented level of detail and ecological validity. However, study planning, relationship building, and troubleshooting are more complex in the remote setting. The relevance of a study to potential participants remains key to its success.

The importance of vital sign monitoring to detect deterioration increases during healthcare at home. Continuous monitoring with wearables increases assessment frequency but may create information overload for clinicians. The goal of this work was to demonstrate the impact of vital sign observation frequency and alarm settings on alarms in a real-world dataset. Vital signs were collected from 76 patients admitted to healthcare at home programs using the Current Health (CH) platform; its wearable continuously measured respiratory rate (RR), pulse rate (PR), and oxygen saturation (SpO2). Total alarms, alarm rate, patient rate, and detection time were calculated for three alarm rulesets to detect changes in SpO2, PR, and RR under four vital sign observation frequencies and four window sizes for the alarm algorithms’ median filter. Total alarms ranged from 65 to 3113. The alarm rate and early detection increased with the observation frequency for all alarm rulesets. Median filter windows reduced alarms triggered by normal fluctuations in vital signs without compromising the granularity of time between assessments. Frequent assessments enabled with continuous monitoring support early intervention but need to pair with settings that balance sensitivity, specificity, clinical risk, and provider capacity to respond when a patient is home to minimize clinician burden.

BackgroundThe COVID-19 pandemic has presented obstacles for providers and patients in the maternal health care setting, causing changes to many pregnant women’s birth plans, as well as abrupt changes in hospital labor and delivery policies and procedures. Few data exist on the effects of the COVID-19 pandemic on the maternal health care landscape at the national level in the United States. ObjectiveThe aim of this study is to assess the incidence of key obstetrics outcomes (preterm delivery, Cesarean sections, and home births) and length of hospital stay during the COVID-19 pandemic as compared to the 6 months prior. MethodsWe conducted a retrospective cohort study of women aged 18-44 years in the United States who delivered between October 1, 2019, and September 30, 2020, had singleton deliveries, and completed a birth report in the Ovia Pregnancy mobile app. Women were assigned to the prepandemic cohort if they delivered between October 2019 and March 2020, and the pandemic cohort if they delivered between April and September 2020. Gestational age at delivery, delivery method, delivery facility type, and length of hospital stay were compared. ResultsA total of 304,023 birth reports were collected, with 152,832 (50.26%) in the prepandemic cohort and 151,191 (49.73%) in the pandemic cohort. Compared to the prepandemic cohort, principal findings indicate a 5.67% decrease in preterm delivery rates in the pandemic cohort (P

OBJECTIVES/GOALS: Pancreatic ductal adenocarcinoma (PDAC) is a relatively radioresistant disease, and inhibition of DNA homologous recombination (HR) repair in combination with radiation therapy (RT) is a potentially attractive strategy to overcome radioresistance. We have found that the expression of the HR protein RAD18 is upregulated in PDAC cells. METHODS/STUDY POPULATION: Standard clonogenic assays, γH2aX foci staining, HR-GFP reporter assay, and western blot analysis of DNA damage response proteins were performed in MIA-PaCa2 (MP2) and PANC-1 cells following knockdown of RAD18 in cells via short hairpin RNA (shRNA). Drug targeting of RAD18 was achieved through the use of a USP-7 inhibitor, P5091. Cells with or without stable knockdown of RAD18 were implanted orthotopically in the pancreas of athymic nude mice and treated with sham radiation or radiation to a dose of 20 Gy in 5 daily fractions once tumors reached 100-150 mm3. RESULTS/ANTICIPATED RESULTS: Stable knockdown of RAD18 in MP2 and PANC-1 resulted in decreased radiation clonogenic survival in vitro (dose enhancement factor (DEF)=1.52 and 1.51, respectively), decreased DNA repair after radiation as measured by the increased number of γH2aX nuclear foci assay at 6, 12, and 24 hours (all p

The experience of pregnant and postpartum patients continues to evolve during the COVID-19 pandemic. Limited clinical data and the unknown nature of the virus’ impact and transmission routes have forced constant changes to traditional care delivery. Dependence on telehealth technology such as telephonic and videoconferencing has surged, and patients’ willingness to visit traditional health care facilities has plummeted. We set out to create an ongoing surveillance system to monitor changes to prenatal and obstetric care and the patient experience during the COVID-19 pandemic.

Concussion or mild traumatic brain injury (mTBI) in athletes can cause persistent symptoms, known as post-concussion syndrome (PCS), and repeated injuries may increase the long-term risk for an athlete to develop neurodegenerative diseases such as chronic traumatic encephalopathy (CTE), and Alzheimer’s disease (AD). The Center for Disease Control estimates that up to 3.8 million sport-related mTBI are reported each year in the United States. Despite the magnitude of the phenomenon, there is a current lack of comprehensive prognostic indicators and research has shown that available monitoring tools are moderately sensitive to short-term concussion effects but less sensitive to long-term consequences. The overall aim of this review is to discuss novel, quantitative, and objective measurements that can predict long-term outcomes following repeated sports-related mTBIs. The specific objectives were (1) to provide an overview of the current clinical and biomechanical tools available to health practitioners to ensure recovery after mTBIs, (2) to synthesize potential biological mechanisms in animal models underlying the long-term adverse consequences of mTBIs, (3) to discuss the possible link between repeated mTBI and neurodegenerative diseases, and (4) to discuss the current knowledge about fluid biomarkers for mTBIs with a focus on novel exosomal biomarkers. The conclusions from this review are that current post-concussion clinical tests are not sufficiently sensitive to injury and do not accurately quantify post-concussion alterations associated with repeated mTBIs. In the current review, it is proposed that current practices should be amended to include a repeated symptom inventory, a cognitive assessment of executive function and impulse control, an instrumented assessment of balance, vestibulo-ocular assessments, and an improved panel of blood or exosome biomarkers.

As the number of graduating medical students increases, the number of primary care residency positions is not keeping pace. One solution to this problem is the creation and accreditation of new residencies, although there is little literature describing the perspectives of the residents and educators who found new programs. Seven out of ten resident physicians who served as the inaugural interns in a new residency training program in pediatrics provide their reflection on the distinctive perspective they had from this experience. They have identified consensus themes in topic areas of strengths, challenges, and lessons learned from training in a new program. Themes applying to strengths of participating in a new residency training program were the opportunity to shape the program, individualized learning experience, and enthusiastic faculty. Challenges of a new program included missing upper level residents, diverse faculty expectations, and morale. Themes under lessons learned included resident engagement, expectations and feedback, and wellness. Each theme was then considered in the context of the medical education literature, underscoring the important balance that new program leaders must strike between structure and flexibility. This inaugural resident class has identified key challenges and opportunities to inform education leaders who are planning new GME training programs.

We present a 24-year-old male who developed an infected hematoma that resulted in sciatic nerve injury after he underwent an endoscopic sciatic nerve decompression. He underwent urgent hematoma evacuation and cultures speciated as Salmonella. At 4 months’ follow-up, the patient’s nerve had improved motor and sensory function. This case highlights the importance of obtaining appropriate hemostasis at the end of an endoscopic sciatic nerve decompression.

Objective: Inhalation injury is an independent risk factor for mortality in burn patients. The purpose of this study was to observe the effect of inhaled iloprost on gas exchange in patients with inhalation injury and acute respiratory failure as measured by an improved PaO2/FiO2 ratio. Methods: Patients admitted to the burn intensive care unit from 2013 to 2014 meeting Berlin criteria for acute respiratory distress syndrome (ARDS) with a diagnosis of inhalation injury and who received inhaled iloprost were included. Medical records were reviewed to collect patient demographics, characterize iloprost prescribing practices, and observe changes in oxygenation and hemodynamic status after iloprost administration. Differences were evaluated using a t-test with cluster corrected standard errors. Results: A total of eight patients were included with 157 different PaO2/FiO2 ratios calculated. All patients had moderate or severe ARDS with a baseline PaO2/FiO2 ratio of 131.9 mmHg (IQR 119.3–197.3). Median duration of iloprost therapy was 5 days (IQR ± 7). A statistically significant increase in PaO2/FiO2 ratio was observed after iloprost administration with a mean increase of 9.7 mmHg (95% CI 1.8–17.7, p = 0.023). Inhaled iloprost had no effect on hemodynamic parameters. Conclusions: Inhaled iloprost for inhalation injury and ARDS after burn injury was associated with a small but statistically significant improvement in oxygenation. Keywords: Iloprost, Inhaled prostacyclin, Inhalation injury

Background: To address looming healthcare workforce shortages, the Association of American Medical Colleges (AAMC) has recommended a substantial increase in residency positions. However, new residency programs face unique recruitment challenges. Objective: To identify new program characteristics and recruitment practices that most influence candidate-ranking decisions. Methods: In a post-match survey, applicants who interviewed during the first two recruitment seasons of a new program were asked to rate program characteristics and recruitment techniques regarding the effects they had on ranking decisions, and to describe the most attractive and concerning features. Somers' D directional coefficients were calculated to determine the correlation between applicants' ranking of the program and ranking of survey items. Qualitative responses were analyzed as word clouds. Results: 163/349 surveys were returned (47%). The strongest correlating items included the opportunities to work closely with faculty, to help shape a new program, and to be one of the first graduates. Influential recruitment practices included program communications and website vividness. Concerns included lack of senior residents, fear of unforeseen difficulties, and no evidence of outcomes. Conclusion: New programs have unique features that influence candidates' ranking decisions. Recruitment practices should be designed to identify candidates who embrace the unique opportunities of a new program.

Climate change is expected to lead to increases in drought frequency and severity, with deleterious effects on many ecosystems. Stomatal responses to changing environmental conditions form the backbone of all ecosystem models, but are based on empirical relationships and are not well-tested during drought conditions. Here, we use a dataset of 34 woody plant species spanning global forest biomes to examine the effect of leaf water potential on stomatal conductance and test the predictive accuracy of three major stomatal models and a recently proposed model. We find that current leaf-level empirical models have consistent biases of over-prediction of stomatal conductance during dry conditions, particularly at low soil water potentials. Furthermore, the recently proposed stomatal conductance model yields increases in predictive capability compared to current models, and with particular improvement during drought conditions. Our results reveal that including stomatal sensitivity to declining water potential and consequent impairment of plant water transport will improve predictions during drought conditions and show that many biomes contain a diversity of plant stomatal strategies that range from risky to conservative stomatal regulation during water stress. Such improvements in stomatal simulation are greatly needed to help unravel and predict the response of ecosystems to future climate extremes.

Sagan et al. (1993) used the Galileo space probe data and first principles to find evidence of life on Earth. Here we ask whether Sagan et al. (1993) could also have detected whether life on Earth had three-dimensional structure, based on the Galileo space probe data. We reanalyse the data from this probe to see if structured vegetation could have been detected in regions with abundant photosynthetic pigments through the anisotropy of reflected shortwave radiation. We compare changing brightness of the Amazon forest (a region where Sagan et al. (1993) noted a red edge in the reflectance spectrum, indicative of photosynthesis) as the planet rotates to a common model of reflectance anisotropy and found measured increase of surface reflectance of 0.019 ± 0.003 versus a 0.007 predicted from only anisotropic effects. We hypothesize the difference was due to minor cloud contamination. However, the Galileo dataset had only a small change in phase angle (sun-satellite position) which reduced the observed anisotropy signal and we demonstrate that theoretically if the probe had a variable phase angle between 0-20°, there would have been a much larger predicted change in surface reflectance of 0.1 and under such a scenario three-dimensional vegetation structure on Earth could possibly have been detected. These results suggest that anisotropic effects may be useful to help determine whether exoplanets have three-dimensional vegetation structure in the future, but that further comparisons between empirical and theoretical results are first necessary.

Animals translocate nutrients by consuming nutrients at one point and excreting them or dying at another location. Such lateral fluxes may be an important mechanism of nutrient supply in many ecosystems, but lack quantification and a systematic theoretical framework for their evaluation. This paper presents a mathematical framework for quantifying such fluxes in the context of mammalian herbivores. We develop an expression for lateral diffusion of a nutrient, where the diffusivity is a biologically determined parameter depending on the characteristics of mammals occupying the domain, including size-dependent phenomena such as day range, metabolic demand, food passage time, and population size. Three findings stand out: (a) Scaling law-derived estimates of diffusion parameters are comparable to estimates calculated from estimates of each coefficient gathered from primary literature. (b) The diffusion term due to transport of nutrients in dung is orders of magnitude large than the coefficient representing nutrients in bodymass. (c) The scaling coefficients show that large herbivores make a disproportionate contribution to lateral nutrient transfer. We apply the diffusion equation to a case study of Kruger National Park to estimate the conditions under which mammal-driven nutrient transport is comparable in magnitude to other (abiotic) nutrient fluxes (inputs and losses). Finally, a global analysis of mammalian herbivore transport is presented, using a comprehensive database of contemporary animal distributions. We show that continents vary greatly in terms of the importance of animal-driven nutrient fluxes, and also that perturbations to nutrient cycles are potentially quite large if threatened large herbivores are driven to extinction.