Broiler chickens are the most numerous terrestrial farmed animals on earth. These birds can suffer a range of pathologies which result in lameness, and one technique for assessing the impact of lameness on the individual bird, and on the flock has been gait scoring. This paper describes a study where the results of the same training programme for validated gait scoring are compared for groups of assessors in Thailand, Brazil and New Zealand. A uniform course of training carried out in the classroom, through video assessment and through on-farm training was carried out in the countries named; a total of 95 persons being trained overall. A measure of agreement with the reference scale for the assessors' numerical responses was carried out using a Cohen's Kappa test, and the results indicated significant differences in the ‘origin position’ ie the view taken by the assessors of the impact of lameness on the bird before training had taken place, but a high degree of consistency in the response to training. The study demonstrated that gait scoring can be learned by assessors from different geographical and social backgrounds, and that the ‘rate of learning’ – the improvement in performance in relation to a standard, was similar between the countries studied. The ‘origin’ and ‘final’ position of the assessors pre- and post-training, from the different countries in relation to the reference standard is discussed.

Animal and human data demonstrate independent relationships between fetal growth, hypothalamic-pituitary-adrenal axis function (HPA-A) and adult cardiometabolic outcomes. While the association between fetal growth and adult cardiometabolic outcomes is well-established, the role of the HPA-A in these relationships is unclear. This study aims to determine whether HPA-A function mediates or moderates this relationship. Approximately 2900 pregnant women were recruited between 1989-1991 in the Raine Study. Detailed anthropometric data was collected at birth (per cent optimal birthweight [POBW]). The Trier Social Stress Test was administered to the offspring (Generation 2; Gen2) at 18 years; HPA-A responses were determined (reactive responders [RR], anticipatory responders [AR] and non-responders [NR]). Cardiometabolic parameters (BMI, systolic BP [sBP] and LDL cholesterol) were measured at 20 years. Regression modelling demonstrated linear associations between POBW and BMI and sBP; quadratic associations were observed for LDL cholesterol. For every 10% increase in POBW, there was a 0.54 unit increase in BMI (standard error [SE] 0.15) and a 0.65 unit decrease in sBP (SE 0.34). The interaction between participant’s fetal growth and HPA-A phenotype was strongest for sBP in young adulthood. Interactions for BMI and LDL-C were non-significant. Decomposition of the total effect revealed no causal evidence of mediation or moderation.

Psychiatrists often order investigations such as blood tests, neuroimaging and electroencephalograms for their patients. Rationales include ruling out ‘organic’ causes of psychiatric presentations, providing baseline parameters before starting psychotropic medications, and screening for general cardiometabolic health. Hospital protocols often recommend an extensive panel of blood tests on admission to a psychiatric ward. In this Against the Stream article, we argue that many of these investigations are at best useless and at worst harmful: the yield of positive findings that change clinical management is extremely low; special investigations are a poor substitute for a targeted history and examination; and incidental findings may cause anxiety and further unwarranted investigation. Cognitive and cultural reasons why over-investigation continues are discussed. We conclude by encouraging a more targeted approach guided by a thorough bedside clinical assessment.

Knotweed (Fallopia spp.) is an herbaceous perennial from East Asia that was brought to Europe and North America and, despite control efforts, subsequently spread aggressively on both continents. Data are available on knotweed’s modes of sexual and asexual spread, historical spread, preferred habitat, and ploidy levels. Incomplete information is available on knotweed’s current global geographic distribution and genetic diversity. The chemical composition of knotweed leaves and rhizomes has been partially discovered as related to its ability to inhibit growth and germination of neighboring plant communities via phytochemicals. There is still critical information missing. There are currently no studies detailing knotweed male and female fertility. Specifically, information on pollen viability would be important for further understanding sexual reproduction as a vector of spread in knotweed. This information would help managers determine the potential magnitude of knotweed sexual reproduction and the continued spread of diverse hybrid swarms. The potential range of knotweed and its ability to spread into diverse habitats makes studies on knotweed seed and rhizome cold tolerance of utmost importance, yet to date no such studies have been conducted. There is also a lack of genetic information available on knotweed in the upper Midwest. Detailed genetic information, such as ploidy levels and levels of genetic diversity, would answer many questions about knotweed in Minnesota, including understanding its means of spread, what species are present in what densities, and current levels of hybridization. This literature review summarizes current literature on knotweed to better understand its invasiveness and to highlight necessary future research that would benefit and inform knotweed management in the upper Midwest.

OBJECTIVES/GOALS: Irreproducible and incompletely reported research lead to misallocated resources, wasted effort in pursing inappropriate avenues of investigation, and loss of public trust. To address this challenge, we employed a Team Science approach to create a multi-modal program to support Rigor, Reproducibility, and Reporting in Translational Science. METHODS/STUDY POPULATION: We conducted literature searches to reveal sources of irreproducibility and recommended corrective actions, invited leaders in the field to give lectures on opportunities to support reproducible science, and worked with the Rockefeller team science leadership group to instill an overarching rigor approach, infused into all training efforts. This multifaceted program was labeled R3 (R-cubed) for Enhancing Scientific Rigor, Reproducibility, and Reporting. RESULTS/ANTICIPATED RESULTS: Didactic Courses:

• Introduction to Biostatistics and Critical Thinking – focus on pitfalls in inferential statistics, consequences of poor research, and errors in published research.

• Scientific Writing – teaches methods and procedures in writing to ensure reproducibility. Lecture Series

• Established nine lectures on topics related to R3, including Data Management, Statistical Methods, Genomic Analyses, Data Repositories, Data Sharing, Pharmacy Formulation, and e-lab notebooks. Website

• Creating a comprehensive website as repository for research, methods, programs, updates, and improvements related to R3. KL2 Clinical Scholars Seminars and Navigation

• Scholars participate in seminars and tutorials to discuss opportunities to improve R3 across the research life-course.

DISCUSSION/SIGNIFICANCE OF IMPACT: Striving for research reproducibility takes focused energy, discipline, and vigilance, but the effort is worthwhile as rigorous and reproducible science is the prerequisite for successful translation of great discoveries into improved health. CONFLICT OF INTEREST DESCRIPTION: none

The need for hollow microneedle arrays is important for both drug delivery and wearable sensor applications; however, their fabrication poses many challenges. Hollow metal microneedle arrays residing on a flexible metal foil substrate were created by combining additive manufacturing, micromolding, and electroplating approaches in a process we refer to as electromolding. A solid microneedle with inward facing ledge was fabricated with a two photon polymerization (2PP) system utilizing laser direct write (LDW) and then molded with polydimethylsiloxane. These molds were then coated with a seed layer of Ti/Au and subsequently electroplated with pulsed deposition to create hollow microneedles. An inward facing ledge provided a physical blocking platform to restrict deposition of the metal seed layer for creation of the microneedle bore. Various ledge sizes were tested and showed that the resulting seed layer void could be controlled via the ledge length. Mechanical properties of the PDMS mold was adjusted via the precursor ratio to create a more ductile mold that eliminated tip damage to the microneedles upon removal from the molds. Master structures were capable of being molded numerous times and molds were able to be reused. SEM/EDX analysis showed that trace amounts of the PDMS mold were transferred to the metal microneedle upon removal. The microneedle substrate showed a degree of flexibility that withstood over 100 cycles of bending from side to side without damaging. Microneedles were tested for their fracture strength and were capable of puncturing porcine skin and injecting a dye.

Subglacial hydrology plays a key role in many glaciological processes, including ice dynamics via the modulation of basal sliding. Owing to the lack of an overarching theory, however, a variety of model approximations exist to represent the subglacial drainage system. The Subglacial Hydrology Model Intercomparison Project (SHMIP) provides a set of synthetic experiments to compare existing and future models. We present the results from 13 participating models with a focus on effective pressure and discharge. For many applications (e.g. steady states and annual variations, low input scenarios) a simple model, such as an inefficient-system-only model, a flowline or lumped model, or a porous-layer model provides results comparable to those of more complex models. However, when studying short term (e.g. diurnal) variations of the water pressure, the use of a two-dimensional model incorporating physical representations of both efficient and inefficient drainage systems yields results that are significantly different from those of simpler models and should be preferentially applied. The results also emphasise the role of water storage in the response of water pressure to transient recharge. Finally, we find that the localisation of moulins has a limited impact except in regions of sparse moulin density.

Outbreaks of Old World cutaneous leishmaniasis (CL) have significantly increased due to the conflicts in the Middle East, with most of the cases occurring in resource-limited areas such as refugee settlements. The standard methods of diagnosis include microscopy and parasite culture, which have several limitations. To address the growing need for a CL diagnostic that can be field applicable, we have identified five candidate neoglycoproteins (NGPs): Galα (NGP3B), Galα(1,3)Galα (NGP17B), Galα(1,3)Galβ (NGP9B), Galα(1,6)[Galα(1,2)]Galβ (NGP11B), and Galα(1,3)Galβ(1,4)Glcβ (NGP1B) that are differentially recognized in sera from individuals with Leishmania major infection as compared with sera from heterologous controls. These candidates contain terminal, non-reducing α-galactopyranosyl (α-Gal) residues, which are known potent immunogens to humans. Logistic regression models found that NGP3B retained the best diagnostic potential (area under the curve from receiver-operating characteristic curve = 0.8). Our data add to the growing body of work demonstrating the exploitability of the human anti-α-Gal response in CL diagnosis.

We present and analyze three powerful long-term historical trends in the electrification of energy by free-fuel sources. These trends point toward a future in which energy is affordable, abundant, and efficiently deployed; with major economic, geo-political, and environmental benefits to humanity.

We present and analyze three powerful long-term historical trends in energy, particularly electrical energy, as well as the opportunities and challenges associated with these trends. The first trend is from a world containing a diversity of energy currencies to one whose predominant currency is electricity, driven by electricity’s transportability, exchangeability, and steadily decreasing cost. The second trend is from electricity generated from a diversity of sources to electricity generated predominantly by free-fuel sources, driven by their steadily decreasing cost and long-term abundance. These trends necessitate a just-emerging third trend: from a grid in which electricity is transported unidirectionally, traded at near-static prices, and consumed under direct human control; to a grid in which electricity is transported bidirectionally, traded at dynamic prices, and consumed under human-tailored artificial agential control. These trends point toward a future in which energy is not costly, scarce, or inefficiently deployed but instead is affordable, abundant, and efficiently deployed; with major economic, geo-political, and environmental benefits to humanity.

We present a series of experiments on novel, line-tied plasma geometries as a study of the generation of chaos and turbulence in line-tied systems. Plasma production and the injection scale for magnetic energy is provided by spatially discrete plasma guns that inject both plasma and current. The guns represent a technique for controlling the injection scale of magnetic energy. A two-dimensional (2-D) array of magnetic probes provides spatially resolved time histories of the magnetic fluctuations at a single cross-section of the experimental cylinder, allowing simultaneous spatial measurements of chaotic and turbulent behaviour. The first experiment shows chaotic fluctuations and self-organization in a hollow-current line-tied screw pinch. These dynamics is modulated primarily by the applied magnetic field and weakly by the plasma current and safety factor. The second experiment analyses the interactions of multiple line-tied flux ropes. The flux ropes all exhibit chaotic behaviour, and under certain conditions develop an inverse cascade to larger scales and a turbulent inertial range with magnetic energy ($E$) related to perpendicular wave number ($k_{\bot }$) as $E\propto k_{\bot }^{-2.5\pm 0.5}$.

Vertebrate microfossil bonebeds (VMBs)—localized concentrations of small resilient vertebrate hard parts—are commonly studied to recover otherwise rarely found small-bodied taxa, and to document relative taxonomic abundance and species richness in ancient vertebrate communities. Analyses of taphonomic comparability among VMBs have often found significant differences in size and shape distributions, and thus considered them to be non-isotaphonomic. Such outcomes of “strict” statistical tests of isotaphonomy suggest discouraging limits on the potential for broad, comparative paleoecological reconstruction using VMBs. Yet it is not surprising that sensitive statistical tests highlight variations among VMB sites, especially given the general lack of clarity with regard to the definition of “strict” isotaphonomic comparability. We rigorously sampled and compared six VMB localities representing two distinct paleoenvironments (channel and pond/lake) of the Upper Cretaceous Judith River Formation to evaluate biases related to sampling strategies and depositional context. Few defining distinctions in bioclast size and shape are evident in surface collections, and most site-to-site comparisons of sieved collections are indistinguishable (p≤0.003). These results provide a strong case for taphonomic equivalence among the majority of Judith River VMBs, and bode well for future studies of paleoecology, particularly in relation to investigations of faunal membership and community structure in Late Cretaceous wetland ecosystems. The taphonomic comparability of pond/lake and channel-hosted VMBs in the Judith River Formation is also consistent with a formative model that contends that channel-hosted VMBs were reworked from pre-existing pond/lake assemblages, and thus share taphonomic history.