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Neospora caninum is an obligate intracellular parasite that causes abortion in ruminants. Different strains produce differences in the severity of disease outcomes. These differences may cause physiological or pathological changes in cells, modifying the intercellular interactions and intracellular transport pathways that could be evidenced by identifying the terminal sugars. This study aimed to characterize the oligosaccharide pattern in the bovine placenta and uterus after infection with tachyzoites of three different strains of N. caninum (Nc-1, Nc-6 Argentina and Nc Spain-7) during early gestation. Fourteen heifers were inoculated intravenously on day 70 of gestation with 2 108 N. caninum tachyzoites and samples of placentae and uteri were analysed by histology and lectin histochemistry. In the infected groups, severe placentitis was associated with changes in lectin binding in the vascular endothelium by Lens culinaris agglutinin (LCA), Pisum sativum agglutinin (PSA) and Ricinus communis I (RCA-I) lectins, in the epithelial cells of the endometrial glands by RCA-I, Dolichos biflorus agglutinin (DBA), succinylated wheat germ agglutinin, peanut agglutinin (PNA), concanavalin-A (CON-A), LCA, PSA and Phaseolus vulgaris erythroagglutinin (PHA-e), and in the trophoblast layer by PNA, CON-A, LCA, PSA, PHA-e, soybean agglutinin, RCA-I, DBA and Bandieraea simplicifolia agglutinin (BSA-I). The results suggest that N. caninum causes changes in the glycosylation pattern in the maternofetal interface tissues and might cause abortions in early gestation due to changes in the cellular structure of the placenta., Depto. de Sanidad Animal, Fac. de Veterinaria, TRUE, pub

The IUPAC Subcommittee on Polymer Education has been pursuing the development of a compact syllabus covering the essential topics required for a tertiary education in polymer science, with numerical and short answer exercises addressing each topic. The primary goal of the document is to provide a framework for a complete course made freely available worldwide so that any educator can implement a professionally-curated course in polymer science for their students without needing expensive textbooks or reliable internet access. An important secondary goal is to popularize the use of approved IUPAC terminology in polymer science by using it consistently throughout the document and providing references to IUPAC source documents. Professor Melissa Chin Han Chan was an active and enthusiastic participant in the project who played a significant role in its design and implementation. The late Professor Richard ‘Dick’ Jones also had a keen interest in the project and had a great influence on its direction and structure. This brief note is dedicated to these two illustrious polymer scientists.

The IUPAC Subcommittee on Polymer Education has been pursuing the development of a compact syllabus covering the essential topics required for a tertiary education in polymer science, with numerical and short answer exercises addressing each topic. The primary goal of the document is to provide a framework for a complete course made freely available worldwide so that any educator can implement a professionally-curated course in polymer science for their students without needing expensive textbooks or reliable internet access. An important secondary goal is to popularize the use of approved IUPAC terminology in polymer science by using it consistently throughout the document and providing references to IUPAC source documents. Professor Melissa Chin Han Chan was an active and enthusiastic participant in the project who played a significant role in its design and implementation. The late Professor Richard ‘Dick’ Jones also had a keen interest in the project and had a great influence on its direction and structure. This brief note is dedicated to these two illustrious polymer scientists.

Upon T-cell activation, the levels of the secondary messenger diacylglycerol (DAG) at the plasma membrane need to be controlled to ensure appropriate T-cell receptor signaling and T-cell functions. Extended-Synaptotagmins (E-Syts) are a family of inter-organelle lipid transport proteins that bridge the endoplasmic reticulum and the plasma membrane. In this study, we identify a novel regulatory mechanism of DAG-mediated signaling for T-cell effector functions based on E-Syt proteins. We demonstrate that E-Syts downmodulate T-cell receptor signaling, T-cell-mediated cytotoxicity, degranulation, and cytokine production by reducing plasma membrane levels of DAG. Mechanistically, E-Syt2 predominantly modulates DAG levels at the plasma membrane in resting-state T cells, while E-Syt1 and E-Syt2 negatively control T-cell receptor signaling upon stimulation. These results reveal a previously underappreciated role of E-Syts in regulating DAG dynamics in T-cell signaling.

We present highly sampled photometry of the supernova (SN) 2023ixf, a Type II SN in M101, beginning 2 days before its first known detection. To gather these data, we enlisted the global Unistellar Network of citizen scientists. These 252 observations from 115 telescopes show the SN's rising brightness associated with shock emergence followed by gradual decay. We measure a peak $M_{V}$ = -18.18 $\pm$ 0.09 mag at 2023-05-25 21:37 UTC in agreement with previously published analyses., Comment: 4 pages, 1 figure

Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m2. Dose adjustment was defined as a reduction in standard dosing ≥20%, based on ideal, reported dosing and actual weights. We included 2 groups of US patients who had received autoHCT between 2008 and 2014. Specifically, we included patients with multiple myeloma (MM, n = 1696) treated with high-dose melphalan and patients with Hodgkin or non-Hodgkin lymphomas (n = 781) who received carmustine, etoposide, cytarabine, and melphalan conditioning. Chemotherapy dose was adjusted in 1324 patients (78%) with MM and 608 patients (78%) with lymphoma. Age, sex, BMI, race, performance score, comorbidity index, and disease features (stage at diagnosis, disease status, and time to transplant) were similar between dose groups. In multivariate analyses for MM, adjusting for melphalan dose and for center effect had no impact on overall survival (P = .894) and treatment-related mortality (TRM) (P = .62), progression (P = .12), and progression-free survival (PFS; P = .178). In multivariate analyses for lymphoma, adjusting chemotherapy doses did not affect survival (P = .176), TRM (P = .802), relapse (P = .633), or PFS (P = .812). No center effect was observed in lymphoma. This study demonstrates that adjusting chemotherapy dose before autoHCT in obese patients with MM and lymphoma does not influence mortality. These results do not support adjusting chemotherapy dose in this population.

Background: Emotional exhaustion is the most important component of burnout syndrome, which is a threat to nurses' psychological well-being. Objectives: The study investigated the impact of job demands - workload, cognitive demands, emotional demands, role conflict - and perceived leader-follower interaction frequency on emotional exhaustion among nurses. Methods: This study was conducted at three hospitals in northern Italy through an anonymous self-report questionnaire administered to 560 nurses. Multiple hierarchical regression was performed. Results: Workload and role conflict were positively related to emotional exhaustion, whereas cognitive demands and perceived leader-follower interaction frequency were negatively related. Emotional demands displayed a non-significant relationship with emotional exhaustion. Further analyses were performed to comment on the unexpected outcome of cognitive demands. A critical role of the perception of “distance” in leader-follower relationships on burnout was found. Conclusions: This study provides novel insights into the relationship between job demands and burnout, and much needed empirical evidence on leader-follower relationships among nurses, pointing to the important role played by leader distance in nurses' well-being at work. Findings highlight the importance of training head nurses in managing their working relationship distance from their followers in order to help them soothing emotional exhaustion.

We demonstrate a chip-scale quantum emitter-metamaterial device that emits highly directional photons. Our device opens the door for quantum imaging of yveak sources by adding photon(s) to manipulate the photon statistics for improved signal-to-noise ratio.

Neonatal hemophagocytic lymphohistiocytosis (HLH) is a medical emergency that can be associated with significant morbidity and mortality. Often these patients present with familial HLH (f-HLH), which is caused by gene mutations interfering with the cytolytic pathway of cytotoxic T-lymphocytes (CTLs) and natural killer cells. Here we describe a male newborn who met the HLH diagnostic criteria, presented with profound cholestasis, and carried a maternally inherited heterozygous mutation in syntaxin-binding protein-2 [STXBP2, c.568C>T (p.Arg190Cys)] in addition to a severe pathogenic variant in glucose 6-phosphate dehydrogenase [G6PD, hemizygous c.1153T>C (Cys385Arg)]. Although mutations in STXBP2 gene are associated with f-HLH type 5, the clinical and biological relevance of the p.Arg190Cys mutation identified in this patient was uncertain. To assess its role in disease pathogenesis, we performed functional assays and biochemical and microscopic studies. We found that p.Arg190Cys mutation did not alter the expression or subcellular localization of STXBP2 or STX11, neither impaired the STXBP2/STX11 interaction. In contrast, forced expression of the mutated protein into normal CTLs strongly inhibited degranulation and reduced the cytolytic activity outcompeting the effect of endogenous wild-type STXBP2. Interestingly, arginine 190 is located in a structurally conserved region of STXBP2 where other f-HLH-5 mutations have been identified. Collectively, data strongly suggest that STXBP2-R190C is a deleterious variant that may act in a dominant-negative manner by probably stabilizing non-productive interactions between STXBP2/STX11 complex and other still unknown factors such as the membrane surface or Munc13-4 protein and thus impairing the release of cytolytic granules. In addition to the contribution of STXBP2-R190C to f-HLH, the accompanied G6PD mutation may have compounded the clinical symptoms; however, the extent by which G6PD deficiency has contributed to HLH in our

Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m2. Dose adjustment was defined as a reduction in standard dosing ≥ 20%, based on ideal, reported dosing and actual weights. We included 2 groups of US patients who had received autoHCT between 2008 and 2014. Specifically, we included patients with multiple myeloma (MM, n = 1696) treated with high-dose melphalan and patients with Hodgkin or non-Hodgkin lymphomas (n = 781) who received carmustine, etoposide, cytarabine, and melphalan conditioning. Chemotherapy dose was adjusted in 1324 patients (78%) with MM and 608 patients (78%) with lymphoma. Age, sex, BMI, race, performance score, comorbidity index, and disease features (stage at diagnosis, disease status, and time to transplant) were similar between dose groups. In multivariate analyses for MM, adjusting for melphalan dose and for center effect had no impact on overall survival (P = .894) and treatment-related mortality (TRM) (P = .62), progression (P = .12), and progression-free survival (PFS; P = .178). In multivariate analyses for lymphoma, adjusting chemotherapy doses did not affect survival (P = .176), TRM (P = .802), relapse (P = .633), or PFS (P = .812). No center effect was observed in lymphoma. This study demonstrates that adjusting chemotherapy dose before autoHCT in obese patients with MM and lymphoma does not influence mortality. These results do not support adjusting chemotherapy dose in this population.

Dothideomycetes is the most diverse fungal class in Ascomycota and includes species with a wide range of lifestyles. Previous multilocus studies have investigated the taxonomic and evolutionary relationships of these taxa but often failed to resolve early diverging nodes and frequently generated inconsistent placements of some clades. Here, we use a phylogenomic approach to resolve relationships in Dothideomycetes, focusing on two genera of melanized, extremotolerant rock-inhabiting fungi, Lichenothelia and Saxomyces, that have been suggested to be early diverging lineages. We assembled phylogenomic datasets from newly sequenced (4) and previously available genomes (238) of 242 taxa. We explored the influence of tree inference methods, supermatrix vs. coalescent-based species tree, and the impact of varying amounts of genomic data. Overall, our phylogenetic reconstructions provide consistent and well-supported topologies for Dothideomycetes, recovering Lichenothelia and Saxomyces among the earliest diverging lineages in the class. In addition, many of the major lineages within Dothideomycetes are recovered as monophyletic, and the phylogenomic approach implemented strongly supports their relationships. Ancestral character state reconstruction suggest that the rock-inhabiting lifestyle is ancestral within the class.

Patients who undergo hematopoietic stem cell transplantation (HSCT) often experience multiple bacterial infections during the early post-transplant period. In this article, we consider a semiparametric regression model that correlates patient- and transplant-related risk factors with inter-infection gap times. Existing regression methods for recurrent gap times are not directly applicable to study post-transplant infection because the initiating event (transplant) is different than the recurrent events of interest (post-transplant infections); as a result, the time from transplant to the first infection and the time elapsed between consecutive infections have distinct biological meanings and hence follow different distributions. Moreover, risk factors may have different effects on these two types of gap times. We propose a semiparametric estimation procedure to evaluate the covariate effects on time from transplant to thefirst infection and on gap times between consecutive infections simultaneously. The proposed estimator accounts for dependent censoring induced by within-subject correlation among recurrent gap times and length bias in the last censored gap time due to intercept sampling. We study the finite sample properties through simulations and present an application of the proposed method to the post-HSCT bacterial infection data collected at the University of Minnesota.

A primary drawback of solar thermal technologies, especially in a domestic setting, is that collection of thermal energy occurs when solar irradiance is abundant and there is generally little requirement for heating. Thermochemical Energy Storage (TCES) offers a means of storing thermal energy interseasonally with little heat loss. A combination of a Solar Thermal Collector (STC) and TCES system will allow a variety of different heating applications, such as domestic space and hot water heating as well as low temperature industrial process heat applications to be met in a low carbon way. This paper describes and assesses the feasibility of two novel technologies currently under development at Loughborough University; i) an evacuated flat plate STC and ii) composite TCES materials, coupled together into a system designed to store and supply thermal energy on demand throughout the year. Experimental results of composite TCES materials along with predicted performance of STC's are used within a developed model to assess key metrics of conceptual TCES + STC systems feasibility, including; charging time, payback time, cost/kWh, energy savings and CO2 savings. This paper demonstrates the economic, energy and carbon savings potential of conceptual TCES + STC systems suitable for domestic use.

Dothideomycetes is the most diverse fungal class in Ascomycota and includes species with a wide range of lifestyles. Previous multilocus studies have investigated the taxonomic and evolutionary relationships of these taxa but often failed to resolve early diverging nodes and frequently generated inconsistent placements of some clades. Here, we use a phylogenomic approach to resolve relationships in Dothideomycetes, focusing on two genera of melanized, extremotolerant rock-inhabiting fungi, Lichenothelia and Saxomyces, that have been suggested to be early diverging lineages. We assembled phylogenomic datasets from newly sequenced (4) and previously available genomes (238) of 242 taxa. We explored the influence of tree inference methods, supermatrix vs. coalescent-based species tree, and the impact of varying amounts of genomic data. Overall, our phylogenetic reconstructions provide consistent and well-supported topologies for Dothideomycetes, recovering Lichenothelia and Saxomyces among the earliest diverging lineages in the class. In addition, many of the major lineages within Dothideomycetes are recovered as monophyletic, and the phylogenomic approach implemented strongly supports their relationships. Ancestral character state reconstruction suggest that the rock-inhabiting lifestyle is ancestral within the class.

Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients’ skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.

Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients’ skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.

Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients’ skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.

Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients’ skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.

Lord Lothian (Philip Kerr, 1882-1940) was one of the leading exponents of British federalism between the Two World Wars. His federalism was linked to the tradition of Kantian and Hamiltonian thought while simultaneously going beyond this tradition. In the aftermath of the Treaty of Versailles, which saw the Old Continent divided into nation-states as holders of absolute sovereignty, he identified the value of peace in the model of the federal State. This was not, as in the case of the Americans, the pragmatic scheme of constitutionalists imposed upon by their historical circumstances, but the general principle of a State organisation geared towards lasting peace in international relations, first in Europe and then worldwide. At the first signs of crisis within the British Empire, Lothian also consistently advocates the political unity of the English-speaking peoples as the nucleus of a world federation able to institutionalise inter-state conflicts and overcome them through legal means. The anthology contained in this essay includes twenty writings and speeches by Lothian and is divided into two sections. The first traces his original political-ideological path: from his long collaboration with the magazine «The Round Table», which has its roots in his initial South African experience within the «Kindergarten», to his speeches held at Chatham House in London in November 1928 and at the Institut für Auswärtige Politik of Hamburg in October 1929; it also covers the years he spent as Private Secretary to the British Prime Minister, David Lloyd George. The second section focuses on his best-known writings, dating back to the second half of the 1930s – namely Pacifism is not Enough, National Sovereignty and Peace and The Demonic Influence of National Sovereignty – ending with some addresses he delivered as British Ambassador to Washington. In addition there are some significant letters that are part of the extensive correspondence Lothian had with statesmen and federalis

Lord Lothian (Philip Kerr, 1882-1940) was one of the leading exponents of British federalism between the Two World Wars. His federalism was linked to the tradition of Kantian and Hamiltonian thought while simultaneously going beyond this tradition. In the aftermath of the Treaty of Versailles, which saw the Old Continent divided into nation-states as holders of absolute sovereignty, he identified the value of peace in the model of the federal State. This was not, as in the case of the Americans, the pragmatic scheme of constitutionalists imposed upon by their historical circumstances, but the general principle of a State organisation geared towards lasting peace in international relations, first in Europe and then worldwide. At the first signs of crisis within the British Empire, Lothian also consistently advocates the political unity of the English-speaking peoples as the nucleus of a world federation able to institutionalise inter-state conflicts and overcome them through legal means. The anthology contained in this essay includes twenty writings and speeches by Lothian and is divided into two sections. The first traces his original political-ideological path: from his long collaboration with the magazine «The Round Table», which has its roots in his initial South African experience within the «Kindergarten», to his speeches held at Chatham House in London in November 1928 and at the Institut für Auswärtige Politik of Hamburg in October 1929; it also covers the years he spent as Private Secretary to the British Prime Minister, David Lloyd George. The second section focuses on his best-known writings, dating back to the second half of the 1930s – namely Pacifism is not Enough, National Sovereignty and Peace and The Demonic Influence of National Sovereignty – ending with some addresses he delivered as British Ambassador to Washington. In addition there are some significant letters that are part of the extensive correspondence Lothian had with statesmen and federalis

Lord Lothian (Philip Kerr, 1882-1940) was one of the leading exponents of British federalism between the Two World Wars. His federalism was linked to the tradition of Kantian and Hamiltonian thought while simultaneously going beyond this tradition. In the aftermath of the Treaty of Versailles, which saw the Old Continent divided into nation-states as holders of absolute sovereignty, he identified the value of peace in the model of the federal State. This was not, as in the case of the Americans, the pragmatic scheme of constitutionalists imposed upon by their historical circumstances, but the general principle of a State organisation geared towards lasting peace in international relations, first in Europe and then worldwide. At the first signs of crisis within the British Empire, Lothian also consistently advocates the political unity of the English-speaking peoples as the nucleus of a world federation able to institutionalise inter-state conflicts and overcome them through legal means. The anthology contained in this essay includes twenty writings and speeches by Lothian and is divided into two sections. The first traces his original political-ideological path: from his long collaboration with the magazine «The Round Table», which has its roots in his initial South African experience within the «Kindergarten», to his speeches held at Chatham House in London in November 1928 and at the Institut für Auswärtige Politik of Hamburg in October 1929; it also covers the years he spent as Private Secretary to the British Prime Minister, David Lloyd George. The second section focuses on his best-known writings, dating back to the second half of the 1930s – namely Pacifism is not Enough, National Sovereignty and Peace and The Demonic Influence of National Sovereignty – ending with some addresses he delivered as British Ambassador to Washington. In addition there are some significant letters that are part of the extensive correspondence Lothian had with statesmen and federalis

Lord Lothian (Philip Kerr, 1882-1940) was one of the leading exponents of British federalism between the Two World Wars. His federalism was linked to the tradition of Kantian and Hamiltonian thought while simultaneously going beyond this tradition. In the aftermath of the Treaty of Versailles, which saw the Old Continent divided into nation-states as holders of absolute sovereignty, he identified the value of peace in the model of the federal State. This was not, as in the case of the Americans, the pragmatic scheme of constitutionalists imposed upon by their historical circumstances, but the general principle of a State organisation geared towards lasting peace in international relations, first in Europe and then worldwide. At the first signs of crisis within the British Empire, Lothian also consistently advocates the political unity of the English-speaking peoples as the nucleus of a world federation able to institutionalise inter-state conflicts and overcome them through legal means. The anthology contained in this essay includes twenty writings and speeches by Lothian and is divided into two sections. The first traces his original political-ideological path: from his long collaboration with the magazine «The Round Table», which has its roots in his initial South African experience within the «Kindergarten», to his speeches held at Chatham House in London in November 1928 and at the Institut für Auswärtige Politik of Hamburg in October 1929; it also covers the years he spent as Private Secretary to the British Prime Minister, David Lloyd George. The second section focuses on his best-known writings, dating back to the second half of the 1930s – namely Pacifism is not Enough, National Sovereignty and Peace and The Demonic Influence of National Sovereignty – ending with some addresses he delivered as British Ambassador to Washington. In addition there are some significant letters that are part of the extensive correspondence Lothian had with statesmen and federalis

Lord Lothian (Philip Kerr, 1882-1940) was one of the leading exponents of British federalism between the Two World Wars. His federalism was linked to the tradition of Kantian and Hamiltonian thought while simultaneously going beyond this tradition. In the aftermath of the Treaty of Versailles, which saw the Old Continent divided into nation-states as holders of absolute sovereignty, he identified the value of peace in the model of the federal State. This was not, as in the case of the Americans, the pragmatic scheme of constitutionalists imposed upon by their historical circumstances, but the general principle of a State organisation geared towards lasting peace in international relations, first in Europe and then worldwide. At the first signs of crisis within the British Empire, Lothian also consistently advocates the political unity of the English-speaking peoples as the nucleus of a world federation able to institutionalise inter-state conflicts and overcome them through legal means. The anthology contained in this essay includes twenty writings and speeches by Lothian and is divided into two sections. The first traces his original political-ideological path: from his long collaboration with the magazine «The Round Table», which has its roots in his initial South African experience within the «Kindergarten», to his speeches held at Chatham House in London in November 1928 and at the Institut für Auswärtige Politik of Hamburg in October 1929; it also covers the years he spent as Private Secretary to the British Prime Minister, David Lloyd George. The second section focuses on his best-known writings, dating back to the second half of the 1930s – namely Pacifism is not Enough, National Sovereignty and Peace and The Demonic Influence of National Sovereignty – ending with some addresses he delivered as British Ambassador to Washington. In addition there are some significant letters that are part of the extensive correspondence Lothian had with statesmen and federalis

Lord Lothian (Philip Kerr, 1882-1940) was one of the leading exponents of British federalism between the Two World Wars. His federalism was linked to the tradition of Kantian and Hamiltonian thought while simultaneously going beyond this tradition. In the aftermath of the Treaty of Versailles, which saw the Old Continent divided into nation-states as holders of absolute sovereignty, he identified the value of peace in the model of the federal State. This was not, as in the case of the Americans, the pragmatic scheme of constitutionalists imposed upon by their historical circumstances, but the general principle of a State organisation geared towards lasting peace in international relations, first in Europe and then worldwide. At the first signs of crisis within the British Empire, Lothian also consistently advocates the political unity of the English-speaking peoples as the nucleus of a world federation able to institutionalise inter-state conflicts and overcome them through legal means. The anthology contained in this essay includes twenty writings and speeches by Lothian and is divided into two sections. The first traces his original political-ideological path: from his long collaboration with the magazine «The Round Table», which has its roots in his initial South African experience within the «Kindergarten», to his speeches held at Chatham House in London in November 1928 and at the Institut für Auswärtige Politik of Hamburg in October 1929; it also covers the years he spent as Private Secretary to the British Prime Minister, David Lloyd George. The second section focuses on his best-known writings, dating back to the second half of the 1930s – namely Pacifism is not Enough, National Sovereignty and Peace and The Demonic Influence of National Sovereignty – ending with some addresses he delivered as British Ambassador to Washington. In addition there are some significant letters that are part of the extensive correspondence Lothian had with statesmen and federalis

The study investigated two followership behaviors, followers’ active engagement and followers’ independent critical thinking, and their relationship with job satisfaction in a sample of nurses. In addition, the study also considered a number of control variables and classical job demands and job resources—workload and emotional dissonance for job demands, and meaningful work for job resources—which have an impact on well-being at work. A paper- and-pencil questionnaire was administered to 425 nurses in an Italian hospital, and a hierarchical multiple regression was used to test the hypotheses. In addition to the job demands and job resources considered, followers’ active engagement had a significant impact on job satisfaction. Moreover, it showed a significant linear and curvilinear relationship with the outcome variable. Followers’ independent critical thinking has a non significant relationship with job satisfaction, confirming the mixed results obtained in the past for this dimension. These findings bore out the importance of analyzing followers’ behaviors as potential resources that people can use on the job to increase their own well-being. Looking at followers not just as passive recipients but as active and proactive employees can also benefit the organization.

Dry granular flows are very common both in many natural phenomena (flow-like landslides) as well as in industrial processes. To model granular flows in the framework of continuum mechanics, a key issue is the formulation of a suitable constitutive model, capable of capturing the complex rheological behaviour of the granular material in a wide range of strain rates. In this contribution, a physically based model capable of reproducing the behaviour of granular materials in different flow regimes is briefly summarized. Both the stress tensor and the dissipated energy are calculated as the sum of a quasi-static and a collisional contribution: the former one is modelled by employing an elasto-plastic model incorporating the critical state concept, whereas the latter stems from the kinetic theory of granular gases. The constitutive model has been implemented in the MPM research code Anura3D and applied to the simulation of the collapse of a dry granular column. The results show that the model can deal with the phase transition between the solid- and the fluid-like behaviour. The evolution of the state variables, the state of stress and the energy contributions is investigated in details.

Parmi les exilés italiens qui atteignent le Canton du Tessin, après l’action répressive des gouvernements Di Rudini et Pelloux de 1898, figurent Enrico Bignami, Giuseppe Rensi et Arcangelo Ghisleri. Ceux-ci fondent, à Lugano, « Coenobium », la « revue internationale de libres études », qui existera de 1906 à 1919. La naissance de ce périodique coïncide avec la crise du positivisme de la fin du XIXe siècle, le modernisme naissant et un idéal socialiste d’inspiration mazzinienne. Publiée principalement en italien et partiellement en français, « Coenobium » se distingue par la pluralité des thèmes traités : de la science au droit, de l’histoire à la philosophie, de la littérature au spiritualisme, de la pédagogie à la psychologie. Toutefois, avec le premier conflit mondial intervient un changement dans la ligne éditoriale de la revue, alors dirigée par Bignami, qui décide d’en faire un influent instrument de propagande pacifiste grâce à la rubrique « Guerre à la guerre ! ». Le périodique mobilise alors une série de personnalités de premier plan, issues du monde culturel et politique international. Elle publie ainsi les interventions de William Jennings Bryan, Henri La Fontaine, Heinrich Lammasch, Giuseppe Emanuele Modigliani, Giuseppe Motta, Karl Liebknecht, Charles Richet, Romain Rolland, Claudio Treves et Filippo Turati. Leurs textes se retrouvent dans l’anthologie, qui constitue une partie importante de ce livre.

Parmi les exilés italiens qui atteignent le Canton du Tessin, après l’action répressive des gouvernements Di Rudini et Pelloux de 1898, figurent Enrico Bignami, Giuseppe Rensi et Arcangelo Ghisleri. Ceux-ci fondent, à Lugano, « Coenobium », la « revue internationale de libres études », qui existera de 1906 à 1919. La naissance de ce périodique coïncide avec la crise du positivisme de la fin du XIXe siècle, le modernisme naissant et un idéal socialiste d’inspiration mazzinienne. Publiée principalement en italien et partiellement en français, « Coenobium » se distingue par la pluralité des thèmes traités : de la science au droit, de l’histoire à la philosophie, de la littérature au spiritualisme, de la pédagogie à la psychologie. Toutefois, avec le premier conflit mondial intervient un changement dans la ligne éditoriale de la revue, alors dirigée par Bignami, qui décide d’en faire un influent instrument de propagande pacifiste grâce à la rubrique « Guerre à la guerre ! ». Le périodique mobilise alors une série de personnalités de premier plan, issues du monde culturel et politique international. Elle publie ainsi les interventions de William Jennings Bryan, Henri La Fontaine, Heinrich Lammasch, Giuseppe Emanuele Modigliani, Giuseppe Motta, Karl Liebknecht, Charles Richet, Romain Rolland, Claudio Treves et Filippo Turati. Leurs textes se retrouvent dans l’anthologie, qui constitue une partie importante de ce livre.

Parmi les exilés italiens qui atteignent le Canton du Tessin, après l’action répressive des gouvernements Di Rudini et Pelloux de 1898, figurent Enrico Bignami, Giuseppe Rensi et Arcangelo Ghisleri. Ceux-ci fondent, à Lugano, « Coenobium », la « revue internationale de libres études », qui existera de 1906 à 1919. La naissance de ce périodique coïncide avec la crise du positivisme de la fin du XIXe siècle, le modernisme naissant et un idéal socialiste d’inspiration mazzinienne. Publiée principalement en italien et partiellement en français, « Coenobium » se distingue par la pluralité des thèmes traités : de la science au droit, de l’histoire à la philosophie, de la littérature au spiritualisme, de la pédagogie à la psychologie. Toutefois, avec le premier conflit mondial intervient un changement dans la ligne éditoriale de la revue, alors dirigée par Bignami, qui décide d’en faire un influent instrument de propagande pacifiste grâce à la rubrique « Guerre à la guerre ! ». Le périodique mobilise alors une série de personnalités de premier plan, issues du monde culturel et politique international. Elle publie ainsi les interventions de William Jennings Bryan, Henri La Fontaine, Heinrich Lammasch, Giuseppe Emanuele Modigliani, Giuseppe Motta, Karl Liebknecht, Charles Richet, Romain Rolland, Claudio Treves et Filippo Turati. Leurs textes se retrouvent dans l’anthologie, qui constitue une partie importante de ce livre.

Parmi les exilés italiens qui atteignent le Canton du Tessin, après l’action répressive des gouvernements Di Rudini et Pelloux de 1898, figurent Enrico Bignami, Giuseppe Rensi et Arcangelo Ghisleri. Ceux-ci fondent, à Lugano, « Coenobium », la « revue internationale de libres études », qui existera de 1906 à 1919. La naissance de ce périodique coïncide avec la crise du positivisme de la fin du XIXe siècle, le modernisme naissant et un idéal socialiste d’inspiration mazzinienne. Publiée principalement en italien et partiellement en français, « Coenobium » se distingue par la pluralité des thèmes traités : de la science au droit, de l’histoire à la philosophie, de la littérature au spiritualisme, de la pédagogie à la psychologie. Toutefois, avec le premier conflit mondial intervient un changement dans la ligne éditoriale de la revue, alors dirigée par Bignami, qui décide d’en faire un influent instrument de propagande pacifiste grâce à la rubrique « Guerre à la guerre ! ». Le périodique mobilise alors une série de personnalités de premier plan, issues du monde culturel et politique international. Elle publie ainsi les interventions de William Jennings Bryan, Henri La Fontaine, Heinrich Lammasch, Giuseppe Emanuele Modigliani, Giuseppe Motta, Karl Liebknecht, Charles Richet, Romain Rolland, Claudio Treves et Filippo Turati. Leurs textes se retrouvent dans l’anthologie, qui constitue une partie importante de ce livre.

Parmi les exilés italiens qui atteignent le Canton du Tessin, après l’action répressive des gouvernements Di Rudini et Pelloux de 1898, figurent Enrico Bignami, Giuseppe Rensi et Arcangelo Ghisleri. Ceux-ci fondent, à Lugano, « Coenobium », la « revue internationale de libres études », qui existera de 1906 à 1919. La naissance de ce périodique coïncide avec la crise du positivisme de la fin du XIXe siècle, le modernisme naissant et un idéal socialiste d’inspiration mazzinienne. Publiée principalement en italien et partiellement en français, « Coenobium » se distingue par la pluralité des thèmes traités : de la science au droit, de l’histoire à la philosophie, de la littérature au spiritualisme, de la pédagogie à la psychologie. Toutefois, avec le premier conflit mondial intervient un changement dans la ligne éditoriale de la revue, alors dirigée par Bignami, qui décide d’en faire un influent instrument de propagande pacifiste grâce à la rubrique « Guerre à la guerre ! ». Le périodique mobilise alors une série de personnalités de premier plan, issues du monde culturel et politique international. Elle publie ainsi les interventions de William Jennings Bryan, Henri La Fontaine, Heinrich Lammasch, Giuseppe Emanuele Modigliani, Giuseppe Motta, Karl Liebknecht, Charles Richet, Romain Rolland, Claudio Treves et Filippo Turati. Leurs textes se retrouvent dans l’anthologie, qui constitue une partie importante de ce livre.

Parmi les exilés italiens qui atteignent le Canton du Tessin, après l’action répressive des gouvernements Di Rudini et Pelloux de 1898, figurent Enrico Bignami, Giuseppe Rensi et Arcangelo Ghisleri. Ceux-ci fondent, à Lugano, « Coenobium », la « revue internationale de libres études », qui existera de 1906 à 1919. La naissance de ce périodique coïncide avec la crise du positivisme de la fin du XIXe siècle, le modernisme naissant et un idéal socialiste d’inspiration mazzinienne. Publiée principalement en italien et partiellement en français, « Coenobium » se distingue par la pluralité des thèmes traités : de la science au droit, de l’histoire à la philosophie, de la littérature au spiritualisme, de la pédagogie à la psychologie. Toutefois, avec le premier conflit mondial intervient un changement dans la ligne éditoriale de la revue, alors dirigée par Bignami, qui décide d’en faire un influent instrument de propagande pacifiste grâce à la rubrique « Guerre à la guerre ! ». Le périodique mobilise alors une série de personnalités de premier plan, issues du monde culturel et politique international. Elle publie ainsi les interventions de William Jennings Bryan, Henri La Fontaine, Heinrich Lammasch, Giuseppe Emanuele Modigliani, Giuseppe Motta, Karl Liebknecht, Charles Richet, Romain Rolland, Claudio Treves et Filippo Turati. Leurs textes se retrouvent dans l’anthologie, qui constitue une partie importante de ce livre.

Long-baseline interferometry (LBI) is used to reconstruct the image of faint thermal objects. The image quality, for a given exposure time, is in general limited by a low signal-to-noise ratio (SNR). We show theoretically that a significant increase of the SNR, in a LBI, is possible by adding or subtracting photons to the thermal beam. At low photon counts, photon addition-subtraction technology strongly enhances the image quality. We have experimentally realized a nondeterministic physical protocol for photon subtraction. Our theoretical predictions are supported by experimental results.

Probabilistic amplification through photon addition, at the output of an Mach-Zehnder interferometer is discussed for a coherent input state. When a metric of signal to noise ratio is considered, nondeterministic, noiseless amplification of a coherent state shows improvement over a standard coherent state, for the general addition of m photons. The efficiency of realizable implementation of photon addition is also considered and shows how the collected statistics of a post selected state, depend on this efficiency. We also consider the effects of photon loss and inefficient detectors.

Choline acetyltransferase catalyzes the synthesis of acetylcholine at cholinergic nerves. Mutations in human CHAT cause a congenital myasthenic syndrome due to impaired synthesis of ACh; this severe variant of the disease is frequently associated with unexpected episodes of potentially fatal apnea. The severity of this condition varies remarkably, and the molecular factors determining this variability are poorly understood. Furthermore, genotype-phenotype correlations have been difficult to establish in patients with biallelic mutations. We analyzed the protein expression of phosphorylated ChAT of seven CHAT mutations, p.Val136Met, p.Arg207His, p.Arg186Trp, p.Val194Leu, p.Pro211Ala, p.Arg566Cys, and p.Ser694Cys, in HEK-293 cells to phosphorylated ChAT, determined their enzyme kinetics and thermal stability, and examined their structural changes. Three mutations, p.Arg207His, p.Arg186Trp, and p.Arg566Cys, are novel, and p.Val136Met and p.Arg207His are homozygous in three families and associated with severe disease. The characterization of mutants showed a decrease in the overall catalytic efficiency of ChAT; in particular, those located near the active-site tunnel produced the most seriously disruptive phenotypic effects. On the other hand, p.Val136Met, which is located far from both active and substrate-binding sites, produced the most drastic reduction of ChAT expression. Overall, CHAT mutations producing low enzyme expression and severe kinetic effects are associated with the most severe phenotypes.

This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 μg/mL) and paucibacillary (0.662±0.123 μg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDTsupervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software.

This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 μg/mL) and paucibacillary (0.662±0.123 μg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDTsupervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software.

Allogeneic hematopoietic cell transplantation has an established role in the treatment of adults with acute lymphoblastic leukemia whose survival when recipients of grafts from adult unrelated donors approaches that of recipients of grafts from sibling donors. Our aim was to determine the role of mismatched unrelated cord blood grafts in transplantation for 802 adults with acute lymphoblastic leukemia in first or second complete remission. Using Cox regression we compared outcomes after 116 mismatched single or double cord blood transplants, 546 peripheral blood progenitor cell transplants and 140 bone marrow transplants. The characteristics of the recipients and their diseases were similar except cord blood recipients were younger, more likely to be non-Caucasians and more likely to have a low white blood cell count at diagnosis. There were differences in donor-recipient human leukocyte antigen-match depending on the source of the graft. Most adult donor transplants were matched at the allele-level considering human leukocyte antigens-A, -B, -C and -DRB1. In contrast, most cord blood transplants were mismatched and considered antigen-level matching; 57% were mismatched at two loci and 29% at one locus whereas only 29% of adult donor transplants were mismatched at one locus and none at two loci. There were no differences in the 3-year probabilities of survival between recipients of cord blood (44%), matched adult donor (44%) and mismatched adult donor (43%) transplants. Cord blood transplants engrafted slower and were associated with less grade 2-4 acute but similar chronic graft-versus-host disease, relapse, and transplant-related mortality. The survival of cord blood graft recipients was similar to that of recipients of matched or mismatched unrelated adult donor grafts and so cord blood should be considered a valid alternative source of stem cells for adults with acute lymphoblastic leukemia in the absence of a matched unrelated adult donor.