Thermodynamic Properties of Block Copolymer Electrolytes Containing Imidazolium and Lithium Salts

We report on the thermal properties, phase behavior, and thermodynamics of a series of polystyrene-block-poly(ethylene oxide) copolymers (SEO) mixed with the ionic species Li[N(SO_(2)CF_3)_2] (LiTFSI), imidazolium TFSI (ImTFSI), and an equimolar mixture of LiTFSI and ImTFSI (Mix). Differential scanning calorimetric scans reveal similar thermal behavior of SEO/LiTFSI and SEO/ImTFSI at the same salt concentrations. Phase behavior and thermodynamics were determined using a combination of small-angle X-ray scattering and birefringence. The thermodynamics of our mixtures can be mapped on to the theory of neat block copolymer phase behavior provided the Flory−Huggins interaction parameter, χ, between the blocks is replaced by an effective χ (χ_(eff)) that increases linearly with salt concentration. The phase behavior and the value of m, the slope of the χ_(eff) versus salt concentration data, were similar for SEO/LiTFSI, SEO/ImTFSI, and SEO/Mix blends. The theory developed by Wang [ J. Phys. Chem. B. 2008, 41, 16205] provides a basis for understanding the fundamental underpinnings of the measured value of m. We compare our experimental results with the predictions of this theory with no adjustable parameters

Phase Behavior of a Block Copolymer/Salt Mixture through the Order-to-Disorder Transition

Mixtures of block copolymers and lithium salts are promising candidates for lithium battery electrolytes. Structural changes that occur during the order-to-disorder transition (ODT) in a diblock copolymer/salt mixture were characterized by small-angle X-ray scattering (SAXS). In salt-free block copolymers, the ODT is sharp, and the domain size of the ordered phase decreases with increasing temperature. In contrast, the ODT of the diblock copolymer/salt mixture examined here occurs gradually over an 11 °C temperature window, and the domain size of the ordered phase is a nonmonotonic function of temperature. We present an approach to estimate the fraction of the ordered phase in the 11 °C window where ordered and disordered phases coexist. The domain spacing of the ordered phase increases with increasing temperature in the coexistence window. Both findings are consistent with the selective partitioning of salt into the ordered domains, as predicted by Nakamura et al. ( ACS Macro Lett. 2013, 2, 478−481)

Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers

We assessed the safety, tolerability and efficacy of the immunomodulatory drug, CC-5013 (REVIMID(TM)), in the treatment of patients with metastatic malignant melanoma and other advanced cancers. A total of 20 heavily pretreated patients received a dose-escalating regimen of oral CC-5013. Maximal tolerated dose, toxicity and clinical responses were evaluated and analysis of peripheral T-cell surface markers and serum for cytokines and proangiogenic factors were performed. CC-5013 was well tolerated. In all, 87% of adverse effects were classified as grade 1 or grade 2 according to Common Toxicity Criteria and there were no serious adverse events attributable to CC-5013 treatment. Six patients failed to complete the study, three because of disease progression, two withdrew consent and one was entered inappropriately and withdrawn from the study. The remaining 14 patients completed treatment without dose reduction, with one patient achieving partial remission. Evidence of T-cell activation was indicated by significantly increased serum levels of sIL-2 receptor, granulocyte- macrophage colony-stimulating factor, interleukin-12 (IL-12), tumour necrosis factor-alpha and IL-8 in nine patients from whom serum was available. However, levels of proangiogenic factors vascular endothelial growth factor and basic foetal growth factor were not consistently affected, This study demonstrates the safety, tolerability and suggests the clinical activity of CC-5013 in the treatment of refractory malignant melanoma. Furthermore, this is the first report demonstrating T-cell stimulatory activity of this class of compound in patients with advanced cancer

Restricting Microbial Exposure in Early Life Negates the Immune Benefits Associated with Gut Colonization in Environments of High Microbial Diversity

Background: Acquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity. Methodology/Principal Findings: Piglets were born in indoor or outdoor rearing units, allowing natural colonization in the immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolatorreared animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals. This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in indoor-reared animals. Conclusions/Significance: Environmental factors, in particular microbial exposure, influence expression of a large number of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune homeostasis

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Thermodynamics of block copolymers with and without salt.

Ion-containing block copolymers are of interest for applications such as electrolytes in rechargeable lithium batteries. The addition of salt to these materials is necessary to make them conductive; however, even small amounts of salt can have significant effects on the phase behavior of these materials and consequently on their ion-transport and mechanical properties. As a result, the effect of salt addition on block copolymer thermodynamics has been the subject of significant interest over the past decade. This feature article describes a comprehensive study of the thermodynamics of block copolymer/salt mixtures over a wide range of molecular weights, compositions, salt concentrations, and temperatures. The Flory-Huggins interaction parameter was determined by fitting small-angle X-ray scattering data of disordered systems to predictions based on the random phase approximation. Experiments on neat block copolymers revealed that the Flory-Huggins parameter is a strong function of chain length. Experiments on block copolymer/salt mixtures revealed a highly nonlinear dependence of the Flory-Huggins parameter on salt concentration. These findings are a significant departure from previous results and indicate the need for improved theories for describing thermodynamic interactions in neat and salt-containing block copolymers

Thermodynamics of block copolymers with and without salt.

Ion-containing block copolymers are of interest for applications such as electrolytes in rechargeable lithium batteries. The addition of salt to these materials is necessary to make them conductive; however, even small amounts of salt can have significant effects on the phase behavior of these materials and consequently on their ion-transport and mechanical properties. As a result, the effect of salt addition on block copolymer thermodynamics has been the subject of significant interest over the past decade. This feature article describes a comprehensive study of the thermodynamics of block copolymer/salt mixtures over a wide range of molecular weights, compositions, salt concentrations, and temperatures. The Flory-Huggins interaction parameter was determined by fitting small-angle X-ray scattering data of disordered systems to predictions based on the random phase approximation. Experiments on neat block copolymers revealed that the Flory-Huggins parameter is a strong function of chain length. Experiments on block copolymer/salt mixtures revealed a highly nonlinear dependence of the Flory-Huggins parameter on salt concentration. These findings are a significant departure from previous results and indicate the need for improved theories for describing thermodynamic interactions in neat and salt-containing block copolymers

Effect of Lithium Polysulfides on the Morphology of Block Copolymer Electrolytes

Lithium polysulfides (Li₂S_<i>x</i>, 1 ≤ <i>x</i> ≤ 8) are produced during the discharge of lithium–sulfur batteries. Lithium–sulfur batteries are of interest due to their high energy density. The morphology of mixtures of polystyrene-<i>b</i>-poly(ethylene oxide) (SEO) copolymers and lithium polysulfides were studied using a combination of X-ray diffraction, small-angle X-ray scattering, differential scanning calorimetry, and ultraviolet–visible spectroscopy. This study is motivated by the possibility of using block copolymers as electrolytes in lithium–sulfur cells. The phase behavior of SEO/Li₂S_<i>x</i> mixtures were found to differ fundamentally from mixtures of SEO and other lithium salts. The morphology of certain SEO/Li₂S_<i>x</i> mixtures obtained below the melting temperature of the poly(ethylene oxide) block has not been previously observed in block copolymer/salt mixtures

Thermodynamics of Block Copolymers with and without Salt

Ion-containing block copolymers are of interest for applications such as electrolytes in rechargeable lithium batteries. The addition of salt to these materials is necessary to make them conductive; however, even small amounts of salt can have significant effects on the phase behavior of these materials and consequently on their ion-transport and mechanical properties. As a result, the effect of salt addition on block copolymer thermodynamics has been the subject of significant interest over the past decade. This feature article describes a comprehensive study of the thermodynamics of block copolymer/salt mixtures over a wide range of molecular weights, compositions, salt concentrations, and temperatures. The Flory–Huggins interaction parameter was determined by fitting small-angle X-ray scattering data of disordered systems to predictions based on the random phase approximation. Experiments on neat block copolymers revealed that the Flory–Huggins parameter is a strong function of chain length. Experiments on block copolymer/salt mixtures revealed a highly nonlinear dependence of the Flory–Huggins parameter on salt concentration. These findings are a significant departure from previous results and indicate the need for improved theories for describing thermodynamic interactions in neat and salt-containing block copolymers