Estimating the environmental impacts of global lithium-ion battery supply chain: A temporal, geographical, and technological perspective.

A sustainable low-carbon transition via electric vehicles will require a comprehensive understanding of lithium-ion batteries' global supply chain environmental impacts. Here, we analyze the cradle-to-gate energy use and greenhouse gas emissions of current and future nickel-manganese-cobalt and lithium-iron-phosphate battery technologies. We consider existing battery supply chains and future electricity grid decarbonization prospects for countries involved in material mining and battery production. Currently, around two-thirds of the total global emissions associated with battery production are highly concentrated in three countries as follows: China (45%), Indonesia (13%), and Australia (9%). On a unit basis, projected electricity grid decarbonization could reduce emissions of future battery production by up to 38% by 2050. An aggressive electric vehicle uptake scenario could result in cumulative emissions of 8.1 GtCO2eq by 2050 due to the manufacturing of nickel-based chemistries. However, a switch to lithium iron phosphate-based chemistry could enable emission savings of about 1.5 GtCO2eq. Secondary materials, via recycling, can help reduce primary supply requirements and alleviate the environmental burdens associated with the extraction and processing of materials from primary sources, where direct recycling offers the lowest impacts, followed by hydrometallurgical and pyrometallurgical, reducing greenhouse gas emissions by 61, 51, and 17%, respectively. This study can inform global and regional clean energy strategies to boost technology innovations, decarbonize the electricity grid, and optimize the global supply chain toward a net-zero future.

Exclusive Human Milk Diet for Extremely Premature Infants: A Novel Fortification Strategy That Enhances the Bioactive Properties of Fresh, Frozen, and Pasteurized Milk Specimens.

Background: Human milk (HM) fortification has been recommended for the nutritional optimization of very low-birthweight infants. This study analyzed the bioactive components of HM and evaluated fortification choices that could accentuate or attenuate the concentration of such components, with special reference to human milk-derived fortifier (HMDF) offered to extremely premature infants as an exclusive human milk diet. Materials and Methods: An observational feasibility study analyzed the biochemical and immunochemical characteristics of mothers' own milk (MOM), both fresh and frozen, and pasteurized banked donor human milk (DHM), each supplemented with either HMDF or cow's milk-derived fortifier (CMDF). Gestation-specific specimens were analyzed for macronutrients, pH, total solids, antioxidant activity (AA), α-lactalbumin, lactoferrin, lysozyme, and α- and ß-caseins. Data were analyzed for variance applying general linear model and Tukey's test for pairwise comparison. Results: DHM exhibited significantly lower (p < 0.05) lactoferrin and α-lactalbumin concentrations than fresh and frozen MOM. HMDF reinstated lactoferrin and α-lactalbumin and exhibited higher protein, fat, and total solids (p < 0.05) in comparison to unfortified and CMDF-supplemented specimens. HMDF had the highest (p < 0.05) AA, suggesting the potential capability of HMDF to enhance oxidative scavenging. Conclusion: DHM, compared with MOM, has reduced bioactive properties, and CMDF conferred the least additional bioactive components. Reinstatement and further enhancement of bioactivity, which has been attenuated through pasteurization of DHM, is demonstrated through HMDF supplementation. Freshly expressed MOM fortified with HMDF and given early, enterally, and exclusively (3E) appears an optimal nutritional choice for extremely premature infants.

Analysing behavioural outcome effectiveness in a musical theatre-based HIV/AIDS intervention among South African farm workers.

In 2005, an applied theatre community outreach programme was launched to address low levels of HIV/AIDS awareness among farm workers in the Cape Winelands of South Africa. In cooperation with HIV testing organizations, the Lucky, the Hero mini-musical promoted regular HIV testing, condom use and acceptance of people living with HIV until being retired in 2017. Applying principles of the health belief model to interview data collected in 2015 from former Lucky, the Hero participants, this paper examines the effectiveness of the theatre production to achieve the behavioural outcomes of (i) encouraging regular HIV testing and ongoing awareness of HIV serostatus, and (ii) reducing AIDS-related social stigma. The findings suggest that the interventions were successful in persuading participants to know their HIV status immediately following the shows, as well as potentially contributing to a reduction of community-based external social stigma. However, the interventions were unable to maintain engagement with these behavioural outcomes in the years following the performances, resulting in low adherence to regular HIV testing and inconsistent condom use. Additionally, ongoing social and structural barriers to regular HIV testing and the potential for self-imposed HIV-related stigma were highlighted during the discussions. While applied theatre can be an effective avenue for HIV awareness and prevention, the paper demonstrates the importance of creating and maintaining strong community networks to support continued engagement with health-related behavioural outcomes.

New Discrete Formulation for Reduced Population Balance Equation: An Illustration to Crystallization.

In this paper, we focus on providing a discrete formulation for a reduced aggregation population balance equation. The new formulation is simpler, easier to code, and adaptable to any type of grid. The presented method is extended to address a mixed-suspension mixed-product removal (MSMPR) system where aggregation and nucleation are the primary mechanisms that affect particle characteristics (or distributions). The performance of the proposed formulation is checked and verified against the cell average technique using both gelling and non gelling kernels. The testing is carried out on two benchmarking applications, namely batch and MSMPR systems. The new technique is shown to be computationally less expensive (approximately 40%) and predict numerical results with higher precision even on a coarser grid. Even with a revised grid, the new approach tends to outperform the cell average technique while requiring less computational effort. Thus the new approach can be easily adapted to model the crystallization process arising in pharmaceutical sciences and chemical engineering.

Hydrogen-Induced Conversion of SnS2 into SnS or Sn: A Route to Create SnS2 /SnS Heterostructures.

The family of van der Waals (vdW) materials is large and diverse with applications ranging from electronics and optoelectronics to catalysis and chemical storage. However, despite intensive research, there remains significant knowledge-gaps pertaining to their properties and interactions. One such gap is the interaction between these materials and hydrogen, a potentially vital future energy vector and ubiquitous processing gas in the semiconductor industry. This work reports on the interaction of hydrogen with the vdW semiconductor SnS2 , where molecular hydrogen (H2 ) and H-ions induce a controlled chemical conversion into semiconducting-SnS or to ß-Sn. This hydrogen-driven reaction is facilitated by the different oxidation states of Sn and is successfully applied to form SnS2 /SnS heterostructures with uniform layers, atomically flat interfaces and well-aligned crystallographic axes. This approach is scalable and offers a route for engineering materials at the nanoscale for semiconductor technologies based on the earth-abundant elements Sn and S, a promising result for a wide range of potential applications.

Hydroxychloroquine Does Not Function as a Direct Zinc Ionophore.

Drug-mediated correction of abnormal biological zinc homeostasis could provide new routes to treating neurodegeneration, cancer, and viral infections. Designing therapeutics to facilitate zinc transport intracellularly is hampered by inadequate concentrations of endogenous zinc, which is often protein-bound in vivo. We found strong evidence that hydroxychloroquine, a drug used to treat malaria and employed as a potential treatment for COVID-19, does not bind and transport zinc across biological membranes through ionophoric mechanisms, contrary to recent claims. In vitro complexation studies and liposomal transport assays are correlated with cellular zinc assays in A549 lung epithelial cells to confirm the indirect mechanism of hydroxychloroquine-mediated elevation in intracellular zinc without ionophorism. Molecular simulations show hydroxychloroquine-triggered helix perturbation in zinc-finger protein without zinc chelation, a potential alternative non-ionophoric mechanism.

Stabilizing vaccines via drying: Quality by design considerations.

Pandemics and epidemics are continually challenging human beings' health and imposing major stresses on the societies particularly over the last few decades, when their frequency has increased significantly. Protecting humans from multiple diseases is best achieved through vaccination. However, vaccines thermal instability has always been a hurdle in their widespread application, especially in less developed countries. Furthermore, insufficient vaccine processing capacity is also a major challenge for global vaccination programs. Continuous drying of vaccine formulations is one of the potential solutions to these challenges. This review highlights the challenges on implementing the continuous drying techniques for drying vaccines. The conventional drying methods, emerging technologies and their adaptation by biopharmaceutical industry are investigated considering the patented technologies for drying of vaccines. Moreover, the current progress in applying Quality by Design (QbD) in each of the drying techniques considering the critical quality attributes (CQAs), critical process parameters (CPPs) are comprehensively reviewed. An expert advice is presented on the required actions to be taken within the biopharmaceutical industry to move towards continuous stabilization of vaccines in the realm of QbD.

A molecularly enhanced proof of concept for targeting cocrystals at molecular scale in continuous pharmaceuticals cocrystallization.

It is impossible to optimize a process for a target drug product with the desired profile without a proper understanding of the interplay among the material attributes, the process parameters, and the attributes of the drug product. There is a particular need to bridge the micro- and mesoscale events that occur during this process. Here, we propose а molecular engineering methodology for the continuous cocrystallization process, based on Raman spectra measured experimentally with a probe and from quantum mechanical calculations. Using molecular dynamics simulations, the theoretical Raman spectra were calculated from first principles for local mixture structures under an external shear force at various temperatures. A proof of concept is developed to build the process design space from the computed data. We show that the determined process design space provides valuable insight for optimizing the cocrystallization process at the nanoscale, where experimental measurements are difficult and/or inapplicable. The results suggest that our method may be used to target cocrystallization processes at the molecular scale for improved pharmaceutical synthesis.

Formation of Ciprofloxacin-Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes-An Investigation into Critical Process Parameters.

The mechanochemical synthesis of cocrystals has been introduced as a promising approach of formulating poorly water-soluble active pharmaceutical ingredients (APIs). In this study, hot-melt extrusion (HME) as a continuous process and grinding and ball milling as batch processes were employed to explore the feasibility of cocrystallization. Ciprofloxacin (CIP) and isonicotinic acid (INCA) were selected as the model API and coformer. CIP-INCA cocrystal was produced in all techniques. It was revealed that higher cocrystal content could be achieved at longer durations of grinding and ball milling. However, milling for more than 10 min led to increased co-amorphous content instead of cocrystal. A design of experiment (DoE) approach was used for deciphering the complex correlation of screw configuration, screw speed, and temperature as HME process parameters and their respective effect on final relative cocrystal yield. Statistical analysis showed that screw configuration, temperature, and their interaction were the most critical factors affecting cocrystallization. Interestingly, screw speed had minimal impact on the relative cocrystallization yield. Cocrystallization led to increased dissolution rate of CIP in phosphate buffer up to 2.5-fold. Overall, this study shed a light on the potential of mechanochemical synthesis techniques with special focus on HME as a continuous process for producing cocrystals.

Emotive Media as a Counterbalance to AIDS Messaging Fatigue in South Africa: Responses to an HIV/AIDS Awareness Music Video.

South Africa recorded and estimated 230,000 new infections in 2020, and low levels of AIDS risk awareness remain prevalent among the nation's youth. While public health awareness initiatives continue to be necessary, the large quantity of AIDS-related content that has permeated the media landscape since the start of the epidemic has resulted in increasing indifference to health messaging. Drawing from the concept of referent emotional responses, this article analyzes the reception of "Sing," an HIV/AIDS awareness music video characterized by emotive visual representations of AIDS. The data highlight ongoing fatigue towards HIV/AIDS messaging and the potential of highly emotive media to engage target audiences in a climate of indifference to AIDS awareness. The article recommends that future awareness and prevention campaigns consider the role of emotive content in effective AIDS-related health promotion in South Africa.

Pulsing bodies and embodying pulse: musical effervescence in a South African HIV/AIDS community outreach program.

Early in South Africa's HIV/AIDS crisis, entertainment education emerged as a powerful vehicle for communicating health and social messaging to combat the epidemic. Applied theatre now accounts for the majority of arts-based HIV interventions in sub-Saharan Africa, and continues a history of theatre for social change in South Africa in particular. While much has been written about the dramaturgical and communication theories that support such interventions, the role of music, a formidable tool in the applied theatre intervention arsenal, has received considerably less attention within applied arts intervention scholarship. This paper draws from Durkheim's collective effervescence to propose a theoretical approach to music within the creation and maintenance of effervescent assemblies that is being employed by HIV/AIDS interventions to encourage participation in HIV testing. The theoretical model of musical effervescence is situated within ethnographic fieldwork conducted while accompanying an applied HIV/AIDS theatre company on a national tour of South Africa.

Investigating Structural Property Relationships to Enable Repurposing of Pharmaceuticals as Zinc Ionophores.

The importance of zinc in biology has gained greater recognition in recent years due to its essential contributions to the function of many endogenous enzymes. Disruption of zinc homeostasis may be useful in treating pathological conditions, such as Alzheimer's, and for antiviral purposes. Despite the growth of knowledge and increased interest in zinc, little is known about the structure and function of zinc ionophores. In this study we analyse the Cambridge Structural Database and solution complexation studies found in the literature to identify key functional groups which may confer zinc ionophorism. Pharmaceuticals, nutraceuticals and amino acids with these functionalities were selected to enable us to explore the translatability of ionophoric activity from in vitro assays to cellular systems. We find that although certain species may complex to zinc in the solid and solution states, and may carry ions across simple membrane systems, this does not necessarily translate into ionophoric activity. We propose that the CSD can help refine key functionalities but that ionophoric activity must be confirmed in cellular systems.

Wood-Derived Hydrogels as a Platform for Drug-Release Systems.

Wood (cellulose and lignin)-based hydrogels were successfully produced as platforms for drug-release systems. Viscoelastic and cross-linking behaviors of precursor solutions were tuned to produce highly porous hydrogel architectures via freeze-drying. Pore sizes in the range of 100-160 µm were obtained. Varying lignin molecular structure played a key role in tailoring swelling and mechanical performance of these gels with organosolv-type lignin showing optimum properties due to its propensity for intermolecular cross-linking, achieving a compressive modulus around 11 kPa. Paracetamol was selected as a standard drug for release tests and its release rate was improved with the presence of lignin (50% more compared to pure cellulose hydrogels). This was attributed to a reduction in molecular interactions between paracetamol and cellulose. These results highlight the potential for the valorization of lignin as a platform for drug-release systems.

Facile Tailoring of Structures for Controlled Release of Paracetamol from Sustainable Lignin Derived Platforms.

Nowadays, sustainable materials are receiving significant attention due to the fact that they will be crucial for the development of the next generation of products and devices. In the present work, hydrogels have been successfully synthesized using lignin which is non-valorized biopolymer from the paper industry. Hydrogels were prepared via crosslinking with Poly(ethylene) glycol diglycidyl ether (PEGDGE). Different crosslinker ratios were used to determine their influence on the structural and chemical properties of the resulting hydrogels. It has been found that pore size was reduced by increasing crosslinker amount. The greater crosslinking density increased the swelling capacity of the hydrogels due to the presence of more hydrophilic groups in the hydrogel network. Paracetamol release test showed higher drug diffusion for hydrogels produced with a ratio lignin:PEGDGE 1:1. The obtained results demonstrate that the proposed approach is a promising route to utilize lignocellulose waste for producing porous materials for advanced biomedical applications in the pharmacy industry.

In-line Raman spectroscopy and chemometrics for monitoring cocrystallisation using hot melt extrusion.

The application of in-line Raman spectroscopy to monitor the formation of a 1:1 cocrystal of ibuprofen (IBU) as a BCS class II drug and nicotinamide as coformer using hot-melt extrusion (HME) was investigated. The process was monitored over different experimental conditions inserting the Raman probe before the extruder die. Partial least square (PLS) was applied as a robust chemometric technique to build predictive models at different levels of chemometric by dividing the experimental data set into calibration and validation subsets. Powder X-Ray diffraction (PXRD) spectra of a set of standard samples were used as calibration to calculate the cocrystal yield from HME experiments regressed by the PLS models. Examination of the full spectra with standard normal variate (SNV) scatter correction with first derivative provided the best fitting goodness and reliability for prediction. Differential scanning calorimetry (DSC) was used as a complementary technique to confirm the composition of the extrudates. Tracking the cocrystal formation throughout the barrel by inserting two Raman probes simultaneously in two different heating zones revealed highly valuable information for understanding the mechanism of cocrystal formation during the HME process.

Molecular engineering of cocrystallization process in holt melt extrusion based on kinetics of elementary molecular processes.

Continuous co-crystallization in a twin-screw granulator is a promising technology. In order to fundamentally optimize the process flow, it is necessary to investigate the kinetics of molecular interactions within the mixture and the effect of these interactions on co-crystal formation. In this study, the processes governing the co-crystallization of ibuprofen and nicotinamide were considered. Density functional theory calculations employing the Hirshfeld partitioning scheme were used to identify donor-acceptor sites on each molecule. A total of twenty-one different molecular interactions was identified (nine of ibuprofen and nicotinamide (resembling co-crystals), three of ibuprofen and itself (resembling the ibuprofen dimer), and nine of nicotinamide and itself (resembling the nicotinamide dimer)). Each interaction was defined as an artificial reversible reaction and the kinetics were calculated using the transition state theory of chemical reactions, where linear and quadratic synchronous transition methods were utilized to identify transition-state structures; the minimum energy path was determined using the nudged elastic band method. A kinetic Monte Carlo framework was used to study the collective/coupled effect of reactions on the progress of the co-crystallization process. it was found that operating at low temperatures (especially lower or very close to the melting temperature of ibuprofen) for longer residency times creates a safe route for maximizing the presence of ibuprofen and nicotinamide co-crystals. If the proposed route is applied, the purity and properties of the produced co-crystal would be significant, especially its desirable availability within the body.

Understanding solid-state processing of pharmaceutical cocrystals via milling: Role of tablet excipients.

Discovery of novel cocrystal systems and improvement of their physicochemical properties dominates the current literature on cocrystals yet the required end-product formulation is rarely addressed. Drug product manufacturing includes complex API solid state processing steps such as milling, granulation, and tableting. These all require high mechanical stress which can lead to solid-state phase transformations into polymorphs and solvates, or lead to dissociation of cocrystals into their individual components. Here we measured the effect of tablet excipients on solid-state processing of a range of pharmaceutical cocrystal formulations. Our findings were rationalised using Density Functional Theory (DFT) calculations of intermolecular binding energies of cocrystal constituents and co-milling excipients. A 1:1 stoichiometric ratio of API Theophylline (THP) and co-former 4-Aminobenzoic acid (4ABA) was co-milled with five different excipients: hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), lactose, and microcrystalline cellulose (MCC). The experiments were carried out in 10 and 25 ml milling jars at 30 Hz for different milling times. Co-milled samples were characterised for formation of cocrystals and phase transformation using powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). Our data shows that co-milling in the presence of PEG, HMPC or lactose yields purer cocrystals, supported by the calculated stronger excipient interactions for PVP and MCC. We identify a suitably-prepared THP-4ABA pharmaceutical cocrystal formulation that is stable under extended milling conditions.

"Out there it's YOLO": Youth perspectives on a mass media HIV- and gender-based violence campaign in South Africa.

Gender-based violence continues to be a leading determinant of South Africa's HIV/AIDS epidemic. As such, gender socialisation and de-normalisation of gender inequality and violence remain principal objectives for public health organisations. This article discusses youth reception of a mass media HIV/AIDS prevention campaign targeting gender inequality. Applying social cognitive theory to the analysis of focus group data highlights three interrelated challenges to encouraging positive self-efficacy in gender-based violence and HIV prevention: (1) HIV/ AIDS-related media saturation; (2) AIDS messaging fatigue; and (3) challenges reconciling popular youth culture with gender equity messaging. The article recommends public health and social justice organisations consider a flexible approach to the ideological or behavioural congruence of potential celebrity ambassadors and/or media to maximise youth appeal and reduce messaging fatigue.

Image processing for detecting complete two dimensional properties' distribution of granules produced in twin screw granulation.

In this study, an image processing technique is implemented to measure complete two-dimensional particle size and liquid content distribution (2D-distribution) of the granules produced in twin screw granulation (TSG). The effects of liquid binder viscosity and liquid to solid ratio (L/S) on the 2D-distribution, and the residence time distribution were studied. The effect of screw configuration on granule formation at different conditions was also investigated, were the mean residence time distribution (MRTD) in conveying elements decreases with the increase of L/S ratio and viscosity. While in kneading elements the MRTD decreases with the increase of L/S and increases with the increase of viscosity. The mean liquid saturation level of the granule is exponentially related to its size. As well, the increase in binder viscosity and L/S ratio leads to more uneven/bi-model particle size distribution (PSD) in the conveying elements, while kneading elements change the initial bi-model PSDs into more homogenous mono-model like distributions.

Modulation of the powder properties of lamotrigine by crystal forms.

The mechanical properties of powders determine the ease of manufacture and ultimately the quality of the oral solid dosage forms. Although poor mechanical properties of an active pharmaceutical ingredient (API) can be mitigated by using suitable excipients in a formulation, the effectiveness of that approach is limited for high dose drugs or multidrug tablets. In this context, improving the mechanical properties of the APIs through solid form optimisation is a good strategy to address such a challenge. This work explores the powder and tableting properties of various lamotrigine (LAM) solid forms with the aim to facilitate direct compression by overcoming the poor tabletability of LAM. The two drug-drug crystals of LAM with nicotinamide and valproic acid demonstrate superior flowability and tabletability over LAM. The improved powder properties are rationalised by structure analysis using energy framework, scanning electron microscopy, and Heckel analysis.