The ability of dairy cows to discriminate between floors with a smooth epoxy resin surface or with surface-applied bauxite aggregates of mean diameters 0.5 mm, 1.2 mm or 2.5 mm (having coefficients of static friction of 0.35, 0.42, 0.49 and 0.74, respectively) was recorded when they were offered the opportunity to walk down paired floor surfaces to receive a food reward. Following training, one half of the cows were rewarded when they selected the floor with the greater friction and the other half were rewarded when they selected the floor with the least friction. The cows were able to distinguish between the different floor surfaces — even between surfaces with 0.5 mm and 1.2 mm aggregates, which humans found difficult to distinguish. Eight similar cows were then offered a choice of walking down passageways of paired floors with an equal reward at the end of each passageway. There were no consistent preferences for floor type, and when the reward was offered only on the side least favoured by each cow in the initial test, the random pattern of selection was still evident. A final choice test offered the cows the opportunity to traverse passageways of either wet concrete or concrete covered with excreta. All cows avoided the passageway with excreta completely, even when the reward was increased in this passageway and removed from the wet concrete passageway. This avoidance was attributed to the cows’ lack of contact with slurry, as they were at pasture for most of the day, in contrast to the cows used in previous work, which were housed in buildings with passageways covered in excreta and showed little avoidance behaviour of such passageways.

Guidelines for the housing of dairy cows do not address the provision of supplementary lighting in passageways, other than for inspection of the animals. Two experiments were conducted to investigate whether lighting passageways to various intensities influenced the locomotion of dairy cows. The first experiment compared the locomotion of dairy cows in a dark or lighted passageway as they walked back to their accommodation from milking. When the passageway was dark, the cows took shorter but more rapid steps - which probably increased their stability. In the second experiment, cows walked down a cubicle passageway to receive a food reward, with the light intensity in the building varying from 0-250 lux. Step length and stepping rate were recorded, as well as the angles of the cows’ leg joints (which were measured from video recordings). Once again, the cows increased their stepping rate in the dark, and this resulted in an increased walking rate, perhaps because they wished to return more rapidly to other members of their group and found the darkness aversive. In addition, the arcs of travel of the metacarpophalangeal joint and of the fore- and hindfeet angles to the floor were reduced in the dark, probably increasing the cows’ stability, and were greatest at 119 lux. The slowest walking rate was observed at 39 lux. Hence, the optimum illumination for dairy cow locomotion may lie approximately between 39 and 119 lux, as measured by our technique.

We conclude that during locomotion in dark passageways cows have to modify their walking behaviour significantly, so that the provision of at least a low level of lighting is desirable at night.

This Essay explores whether the African Court of Human and People's Rights’ (African Court) Registry and Legal Division have a similar expansive role in the dispute settlement mechanism as the World Trade Organization's (WTO) Secretariat. The African Court is the African Union's regional body for enforcing human rights. This Essay contributes to the scholarship on African international courts by testing the central arguments in Pauwelyn and Pelc's “Who Guards the ‘Guardians of the System’? The Role of the Secretariat in WTO Dispute Settlement”1 through a comparative analysis of the role of the Secretariat within the African Court.2 Despite the growing jurisprudence and influence of Africa's international courts, they continue to be neglected by mainstream scholarship of international courts and tribunals. This is evident in Pauwelyn and Pelc's article, which does not refer to any of Africa's seven international courts and tribunals. For that matter, the article makes no reference to any international tribunal outside Europe or the United States.3 Our analysis illustrates the fact that the influence of the African Court's Registry and Legal Division (Registry) in the process for dispute settlement is not as significant and concerning as that of the WTO Secretariat. As such, the influence of the Registry on the outcome of a case is significantly limited and does not raise any legitimacy crisis like the WTO. We attribute this disparity to the operational and structural disparities between the African Court and the WTO. In the following paragraphs, we examine each of the factors that Pauwelyn and Pelc raise concerning the influence of the WTO staff in WTO panel and Appellate Body proceedings4 in the context of the functions of the African Court Registry.

We prove that certain families of homogenous affine iterated function systems in $\mathbb {R}^{d}$ have the property that the open set condition and the existence of exact overlaps both occur densely in the space of translation parameters. These examples demonstrate that in the theorems of Falconer and Jordan–Pollicott–Simon on the almost sure dimensions of self-affine sets and measures, the set of exceptional translation parameters can be a dense set. The proof combines results from the literature on self-affine tilings of $\mathbb {R}^{d}$ with an adaptation of a classic argument of Erdős on the singularity of certain Bernoulli convolutions. This result encompasses a one-dimensional example due to Kenyon which arises as a special case.

Multisystem inflammatory syndrome in adults (MIS-A) is a hyperinflammatory illness related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The characteristics of patients with this syndrome and the frequency with which it occurs among patients hospitalised after SARS-CoV-2 infection are unclear. Using the Centers for Disease Control and Prevention case definition for MIS-A, we created ICD-10-CM code and laboratory criteria to identify potential MIS-A patients in the Premier Healthcare Database Special COVID-19 Release, a database containing patient-level information on hospital discharges across the United States. Modified MIS-A criteria were applied to hospitalisations with discharge from March to December 2020. The proportion of hospitalisations meeting electronic health record criteria for MIS-A and descriptive statistics for patients in the potential MIS-A cohort were calculated. Of 34 515 SARS-CoV-2-related hospitalisations with complete clinical and laboratory data, 53 met modified criteria for MIS-A (0.15%). The median age was 62 years (IQR 52–74). Most patients met the severe cardiac illness criterion through either myocarditis (66.0%) or new-onset heart failure (35.8%). A total of 79.2% of patients required ICU admission, while 43.4% of patients in the cohort died. MIS-A appears to be a rare but severe outcome of SARS-CoV-2 infection. Additional studies are needed to investigate how this syndrome differs from severe coronavirus disease 2019 (COVID-19) in adults.

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.

The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.

The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

Comparative transcriptomics can be used to translate an understanding of gene regulatory networks from model systems to less studied species. Here, we use RNA-Seq to determine and compare gene expression dynamics through the floral transition in the model species Arabidopsis thaliana and the closely related crop Brassica rapa. We find that different curve registration functions are required for different genes, indicating that there is no single common ‘developmental time’ between Arabidopsis and B. rapa. A detailed comparison between Arabidopsis and B. rapa and between two B. rapa accessions reveals different modes of regulation of the key floral integrator SOC1, and that the floral transition in the B. rapa accessions is triggered by different pathways. Our study adds to the mechanistic understanding of the regulatory network of flowering time in rapid cycling B. rapa and highlights the importance of registration methods for the comparison of developmental gene expression data.

ABSTRACT IMPACT: The pathophysiologic features of a metabolomic endotype that predicts patient outcomes due to sepsis have the potential to direct new therapies that target immune dysregulation and bioenergetic insufficiency. OBJECTIVES/GOALS: Acute respiratory failure (ARF) requiring mechanical ventilation is a frequent complication of sepsis and other disorders. It is associated with high morbidity and mortality. Despite its severity and prevalence, little is known about metabolic and bioenergetic changes that accompanying ARF. METHODS/STUDY POPULATION: In this study, semiquantitative and quantitative ultrahigh performance liquid chromatography mass spectrometry (UHPLC MS) analysis was performed on patient serum collected from the Trial with Acute Respiratory failure patients: evaluation of Global Exercise Therapies (TARGET). Serum from survivors (n=15) and nonsurvivors (n=15) was collected at day 1 and day 3 after admission to the medical intensive care unit as well as at discharge in survivors. Pathway analysis of the biochemical changes was performed to determine whether the disruption in specific metabolic pathways can identify the bioenergetic and metabolomic profile of these patients. RESULTS/ANTICIPATED RESULTS: Significant metabolomic differences were related to biosynthetic intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, and decreased acyl-glycerophosphocholines in nonsurvivors compared to survivors. The metabolites associated with poor outcomes are substrates of enzymatic processes dependent on NAD(P), while the abundance of NAD cofactors rely on the bioavailability of dietary vitamins B1, B2 and B6. Changes in the efficiency of the nicotinamide-derived cofactors’ biosynthetic pathways also associate with an alteration of the glutathione-dependent drug metabolism as characterized by the substantial differences observed in the acetaminophen metabolome. DISCUSSION/SIGNIFICANCE OF FINDINGS: This metabolomic endotype represents a previously unappreciated association between severity of outcomes and micronutrient deficiency, thus pointing to new pharmacologic targets and highlighting the need for nutritional remediation upon hospitalization to improve patient outcomes due to ARF.