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The world is facing an existential threat from yoked horses of the apocalypse, including catastrophic climate change, chemical toxicity, mass extinctions, certain populations overconsuming, unstable governments, migration and pandemics. The biosphere of the planet is becoming less conducive to life, including human life. As we enter the Anthropocene, how should we aim to reverse the damaging effects of our technology and culture in order to enter the Ecocene? What role should education play? This paper argues that leadership for sustainability should be a dominant model throughout education and wider society, rather than being consigned to the periphery, or totally unrecognised. It describes how the values and actions of these leaders relate directly to how our type of civilisation can be repurposed and ultimately redeemed for survival into the distant future. It also argues that progressive approaches have more to offer than traditional ones. The paper is polemical in style, and uses broad-brush contexts to hopefully instigate suitably new discussions on leadership in education.

In this paper, we use an open economy model of the United Kingdom to examine the extent to which monetary policy should respond to movements in sectoral inflation rates. To do this we construct a Generalised Taylor model that takes specific account of the sectoral make up of the consumer price index (CPI), where the sectors are based on the COICOP classification the UK CPI microdata. We calibrate the model for each sector using the UK CPI microdata and model the sectoral shocks that drive sectoral inflation rates as white noise processes, as in the UK data. We find that a policy rule that allows for different responses to inflation in different sectors outperforms a rule which just targets aggregate CPI. However, the gain is small and comes from partially looking through movements in aggregate inflation driven by movements in petrol price inflation, which is volatile and tends not to reflect underlying inflationary pressure.

The yolk sac (YS) represents an evolutionarily-conserved extraembryonic structure that ensures timely delivery of nutritional support and oxygen to the developing embryo. However, the YS remains ill-defined in humans. We therefore assemble a complete single cell 3D map of human YS from 3-8 post conception weeks by integrating multiomic protein and gene expression data. We reveal the YS as a site of primitive and definitive haematopoiesis including a YS-specific accelerated route to macrophage production, a source of nutritional/metabolic support and a regulator of oxygen-carrying capacity. We reconstruct the emergence of primitive haematopoietic stem and progenitor cells from YS hemogenic endothelium and their decline upon stromal support modulation as intraembryonic organs specialise to assume these functions. The YS therefore functions as ‘three organs in one’ revealing a multifaceted relay of vital organismal functions as pregnancy proceeds.One Sentence SummaryHuman yolk sac is a key staging post in a relay of vital organismal functions during human pregnancy.

Although individuals with neurodevelopmental disorders (ND), such as intellectual disability (ID) and autism, are overrepresented in the criminal justice system, most psychiatry training is limited regarding NDs, and forensic psychiatry training tends to focus on psychotic and mood disorders. This article explores the complex interactions between NDs and criminality, including direct etiological explanations and potential mediating variables (e.g., trauma), to address common training gaps. We compare and contrast current laws relevant to assessing NDs in criminal responsibility evaluations. Not guilty by reason of insanity (NGRI) criteria vary by jurisdiction, with some specifying ID as one possible insanity defense prerequisite while most jurisdictions are nonspecific. NDs in the absence of psychosis or mania often involve impaired cognition (e.g., comprehension, reasoning, social cognition) and behavioral dysregulation. This article provides potential scenarios by which those with NDs might be competent to stand trial but qualify for one or more NGRI prongs. Suggestions for assessment methods (including for malingering) are addressed for this unique population.

This paper takes the locally collected price-quotes used to construct the CPI index in the UK for the period 1996-2013 to explore the impact of the crisis on the pricing behavior of firms. We develop a time-series framework which is able to capture the link between macroeconomic variables (inflation and output) and the behavior of prices in terms of the frequency of price change, the dispersion of price levels and the dispersion of price-growth. Whilst these effects are present, they are small and do not have significant effects for monetary policy.

Percy Grainger’s compositions during the early twentieth century represent a unique blend of traditional functional harmony and newer musical techniques. This blending produces a distinct compositional style associated with Grainger, featuring simple forms and textures, melodies inspired by traditional folk songs, extended tertian harmony, and an emphasis on voice leading. Grainger’s works often cross genres and explore various instrumentations and stylistic choices. This paper attempts to further define and explain Grainger’s style by analyzing two of his original works that were arranged for the military band setting, namely Children’s March: Over the Hills and Far Away and Colonial Song. Examining these two works through the lens of harmony, melody, form, texture, and rhythm reveals key aspects of Grainger’s early compositional style. Several stylistic choices were found to recur, including Grainger’s use of counterpoint, voice leading, descending chromaticism, specific patterns of articulations, and tension created by increased note density.

Caffeine has the highest use of any psychoactive substance worldwide and is highly appealing to military personnel who are required to work the long, grueling hours necessary to complete a mission. However, published reports of caffeine intoxication in the medical literature are rare. Individuals undergoing military training experience long work hours in a stressful environment. These conditions can make various caffeine supplements enticing. However, most energy drinks contain multiple serving sizes, and supplements are often packaged in large containers, increasing individuals’ risk of caffeine overconsumption and intoxication. Additionally, young adults in stressful environments are the classic demographic in which the first presentation of a psychiatric illness, such as psychotic disorder, occurs. Interestingly, many of the presenting signs and symptoms, including agitation, restlessness, insomnia, tremors, tachycardia, and psychomotor agitation, are the same in both diagnoses. This stresses the importance of differentiating caffeine intoxication from a psychotic disorder. We present a novel case of an active-duty Service member who presented to the emergency room with symptoms concerning the psychotic disorder. After a more detailed history was acquired, caffeine intoxication became more likely and was ultimately treated. We discuss the overlap in presentation and thus difficulty in differentiating caffeine intoxication from a psychotic disorder.

Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11–12 weeks after conception1,2, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6–7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. The substantial expansion of B lymphocytes in FBM contrasts with fetal liver at the same gestational age. Haematopoietic progenitors from fetal liver, FBM and cord blood exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we show are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B lymphocyte, erythroid and myeloid development owing to a cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21). A single-cell atlas of human fetal bone marrow in healthy fetuses and fetuses with Down syndrome provides insight into developmental haematopoiesis in humans and the transcription and functional differences that occur in Down syndrome.

In this paper we consider the effect of epsilon maximization on firm behavior. In particular we focus on the dynamic behavior of firms with the use of the example of price‐setting: We show how almost-rational firms can be more volatile in their behavior. However, if a lexicographic preference for simplicity is made, then we can explain nominal price rigidity as a result of epsilon optimization. The behavior of the firm—which is consistent with its long‐term survival—is examined. We argue that epsilon-optimization is consistent with survival in any context in which something is optimized: such as sales revenue.

Why should readers of this journal be concerned with Island off the Coast of Asia, a book that mentions rights only twice and then in passing? This question can be answered by asking other question...

Summary Presented here is a steam–assisted–gravity–drainage (SAGD) forecasting technique for oil and water production and steam injection based on linear steam–chamber geometry and an empirical form for the progression of the steam/oil interface with time. The oil forecast model generates full–cycle SAGD production profiles using three empirical inputs (the initial plateau oil rate qo,si, an exponent n, and the rising–phase–chamber angle θ) and volumetric parameters (well length, pay thickness, porosity, half–well spacing, and initial and residual oil saturation). Steam and produced–water forecasts are derived analytically using the resulting steam–chamber geometry and the heat required for the fluids, rock, and overburden. Peak rate is a direct input in this methodology, and as a result only volumetric and some thermodynamic parameters are required, but not fluid or transmissibility inputs, such as viscosity and permeability. This allows for direct use of commercial SAGD production data in the forecasting process. The model predictions are validated at a high level with field data from Devon Canada Corporation's Jackfish SAGD project and numerical simulation.

It is commonly believed that gastrointestinal issues during exercise are exacerbated by hypohydration. This study aimed to determine the effect of exercise-induced hypohydration on gastrointestinal integrity, function, symptoms, and systemic endotoxin and inflammatory profiles. In a randomized crossover design, male endurance runners ( n = 11) performed 2 h of running at 70% of maximum oxygen uptake in 25°C ambient temperature with water provision [euhydration (EuH)] and total water restriction [hypohydration (HypoH)] during running, which accounted for 0.6 ± 0.6% and 3.1 ± 0.7% body mass loss, respectively. Blood and fecal samples were collected before and after exercise. Breath samples (H2 determination) were collected and gastrointestinal symptoms (GIS) recorded before, during, and after exercise. HypoH resulted in a higher, yet insignificant, ∆ preexercise to postexercise plasma cortisol concentration (+286 nmol/l vs. +176 nmol/l; P = 0.098) but significantly higher intestinal fatty acid-binding protein (I-FABP) (+539 pg/ml vs. +371 pg/ml; P = 0.047) concentration compared with EuH. A greater breath H2 response ( P = 0.026) was observed on HypoH (1,188 ppm/3 h, peak +12 ppm) vs. EuH (579 ppm/3 h, peak +6 ppm). Despite greater GIS incidence on HypoH (82%) vs. EuH (64%), GIS severity scores were not significant between trials. Exercise-induced leukocytosis (overall pre- to postexercise: 5.9 × 109/l to 12.1 × 109/l) was similar on both trials. Depressed in vitro neutrophil function was observed during recovery on HypoH (−36%) but not on EUH (+6%). A pre- to postexercise increase ( P < 0.05) was observed for circulating cytokine concentrations but not endotoxin values. Hypohydration during 2 h of running modestly perturbs gastrointestinal integrity and function and increases GIS incidence but does not affect systemic endotoxemia and cytokinemia. NEW & NOTEWORTHY Despite anecdotal beliefs that exercise-induced hypohydration exacerbates perturbations to gastrointestinal status, the present study reports only modest perturbations in gastrointestinal integrity, function, and symptoms compared with euhydration maintenance. Exercise-induced hypohydration does not exacerbate systemic endotoxemia and cytokinemia compared with euhydration maintenance. Programmed water intake to maintain euhydration results in gastrointestinal symptom severity similar to exercise-induced hypohydration. Maintaining euhydration during exertional stress prevents the exercise-associated depression in bacterially stimulated neutrophil function.

Climate change, especially in Africa’s central Sahel region, is occurring in the context of exponential population rise with countries like Chad and Niger still in the “early expanding phase” of demographic growth. While many experts predict a mid-century climate and demographic ‘mega crisis’ for the region; our paper looks at the effect of the rising temperature, through the medium of increased temperature and precipitation variability upon fertility and hence demographic trends as we advance into the 21st century. The paper uses climate data and DHS (Demographic and Health Survey) data from Chad, which has demonstrated significant warming since the late 1960’s. We create a weather shock variable that is defined as a t>2 departure from the post-1960 mean of temperature and precipitation by month, year, and GIS location. We regress the following years’ human fertility outcomes by month and GIS location upon these shocks when occurring in the growing months of June, July, and August. We find that the effect is highly negatively significant with a one-year lag. Then we go on to look for the mechanism behind this significance; the literature suggesting that climate effects fertility through biological or food security related channels. We then regress the male/female sex ratio on the same weather shocks to see if there is a rise in miscarriages among male fetuses due to either the direct effect of heat or as an effect of increased female malnutrition. By running both these models with weather shocks from Chad’s dry season months of December, January, and February, we discern whether the significance is driven by pure temperature or by some sort of food security/household income channel. Though we see some dry season effect, most of the significance is driven by the shocks in the growing season and with the significant effect of these shocks on the sex ratio, we can assume that increased female malnutrition is a key driver of both the rise in miscarriages and the drop-in fertility. We then run these models within each of the three Chadian climate zones: the Sahara, the Sahel, and the Sudan. Seeing that the Sahel zone is the major driver for the significance of our models, we discuss if this can have implications for the wider African Sahel.

Throughout postnatal life, haematopoiesis in the bone marrow (BM) maintains blood and immune cell production. Haematopoiesis first emerges in human BM at 12 post conception weeks while fetal liver (FL) haematopoiesis is still expanding. Yet, almost nothing is known about how fetal BM evolves to meet the highly specialised needs of the fetus and newborn infant. Here, we detail the development of fetal BM including stroma using single cell RNA-sequencing. We find that the full blood and immune cell repertoire is established in fetal BM in a short time window of 6-7 weeks early in the second trimester. Fetal BM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell (DC) subsets emerging for the first time. B-lymphocyte expansion occurs, in contrast with erythroid predominance in FL at the same gestational age. We identify transcriptional and functional differences that underlie tissue-specific identity and cellular diversification in fetal BM and FL. Finally, we reveal selective disruption of B-lymphocyte, erythroid and myeloid development due to cell intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in the fetal BM from constitutional chromosome anomaly Down syndrome during this crucial developmental time window.

Growth hormone administration is approved for use in a number of growth failure conditions in children. Optimal growth outcome requires continuous daily injections over many years, leading to problems of persistence and adherence with therapy. The easypod™ connect ecosystem enables electronic monitoring of injection and dose history, transmitted to a secure cloud database via the internet or cellular networks. Thus, healthcare providers can easily monitor adherence with therapy and be alerted to problems. The growlink™ patient app has been added to the ecosystem to provide solutions that can engage and educate patients and their families/caregivers. growlink™ also allows patients to self-report height and weight, enabling healthcare providers to track growth progression. The patient support program, TuiTek and the easypod™ Augmented Reality (AR) app are being developed within the ecosystem to support telehealth services, increase disease awareness and reduce therapy-related anxiety. easypod™ connect provides objective assessments of adherence, shown to be maintained at a high level over several years, and analyses showed that increased adherence was significantly associated with a better growth outcome. Studies have identified factors that influence persistence and adherence with GH therapy via the easypod™ connect ecosystem. These novel technologies are generating solutions that enable data-driven personalized care for children with growth disorders and optimize long-term clinical outcomes.

Cellular beauty is skin deep Human skin works as barrier, preventing the entry of pathogens, among other functions. Reynolds et al. used single-cell sequencing to generate an atlas of the human skin from both developing and adult sources, identifying differences and similarities across heterogeneous populations of skin cells. In this atlas, gene expression in the two disease states studied—atopic dermatitis and psoriasis—varied from that in a healthy adult, suggesting that a fetal skin signature is expressed in adult inflamed skin. Furthermore, differences in immune cell composition between healthy fetal and adult skin and that of individuals suffering from disease were observed. Science , this issue p. eaba6500

Growth hormone administration is approved for use in a number of growth failure conditions in children. Optimal growth outcome requires continuous daily injections over many years, leading to problems of persistence and adherence with therapy. The easypod™ connect ecosystem enables electronic monitoring of injection and dose history, transmitted to a secure cloud database via the internet or cellular networks. Thus, healthcare providers can easily monitor adherence with therapy and be alerted to problems. The growlink™ patient app has been added to the ecosystem to provide solutions that can engage and educate patients and their families/caregivers. growlink™ also allows patients to self-report height and weight, enabling healthcare providers to track growth progression. The patient support program, TuiTek and the easypod™ Augmented Reality (AR) app are being developed within the ecosystem to support telehealth services, increase disease awareness and reduce therapy-related anxiety. easypod™ connect provides objective assessments of adherence, shown to be maintained at a high level over several years, and analyses showed that increased adherence was significantly associated with a better growth outcome. Studies have identified factors that influence persistence and adherence with GH therapy via the easypod™ connect ecosystem. These novel technologies are generating solutions that enable datadriven personalized care for children with growth disorders and optimize long-term clinical outcomes., Studies in Health Technology and Informatics, 281, ISSN:0926-9630, ISSN:1879-8365, Public Health and Informatics: Proceedings of MIE 2021, ISBN:978-1-64368-184-9, ISBN:978-1-64368-185-6

The frequencies at which prices and wages are adjusted, interpreted as price and wage flexibility, are key elements in workhorse models used for policy analysis. Yet, there is little evidence regarding the relationship between these two sources of nominal rigidities. Using two large and highly disaggregated price and wage microdata sets, this paper provides evidence that the industries changing more frequently wages reset prices more often. Once the frequency of wage adjustments is accounted for, the share of labor costs becomes less relevant in explaining the frequency of price changes, calling for a reinterpretation on previous findings that the labor share is a robust determinant of the frequency of price adjustments. The results in this study have implications for New Keynesian models' microfoundations, as their predictions have proven to be sensitive to the nominal rigidities assumptions.

The human skin confers biophysical and immunological protection through a complex cellular network that is established early in development. We profiled ~500,000 single cells using RNA-sequencing from healthy adult and developing skin, and skin from patients with atopic dermatitis and psoriasis. Our findings reveal a predominance of innate lymphoid cells and macrophages in developing skin in contrast to T cells and migratory dendritic cells in adult skin. We demonstrate dual keratinocyte differentiation trajectories and activated cellular circuits comprising vascular endothelial cells mediating immune cell trafficking, disease-specific clonally expanded IL13/IL22 and IL17A/F-expressing lymphocytes, epidermal IL23-expressing dendritic cells and inflammatory keratinocytes in disease. Our findings provide key insights into the dynamic cellular landscape of human skin in health and disease.One Sentence SummarySingle cell atlas of human skin reveals cell circuits which are quantitatively and qualitatively reconfigured in inflammatory skin disease.

The purpose of the present paper is to investigate forecasted inflation gap persistence using professionals’ survey-based data, differentiating between financial and non-financial sectors professionals. We derive the forecasted inflation gap persistence and using a state dependent model, we estimate the non-linear persistence coefficient of the inflation gap. We distinguish between the pre-Great Moderation, Great Moderation and Great Recession periods. Our main results indicate that whilst the estimates of persistence for GDP inflation largely confirm the results obtained using a linear model, for CPI inflation we find that there is strong evidence for state-dependence and time variation. By and large, the results are consistent with the price stability policy pursued in the Great Moderation period and perceived disinflationary pressures during the Great Recession period