The Characteristics of Compound Heterozygosity for Hemoglobin G-Makassar with Hb E in Malaysia.

Background: Human hemoglobin of G-Makassar and hemoglobin E (Hb E) are hemoglobin variants that affect Beta (ß) globin. Hb G-Makassar is a very rare variant while Hb E is estimated to affect at least one million people worldwide. Both Hb G-Makassar and Hb E can be inherited in the heterozygous, homozygous or compound heterozygous state. This case series describes the characteristics of four individuals with compound heterozygosity for Hb G-Makassar/Hb E cases in Malaysia. To the best of our knowledge, these are the only four individuals with this genotype reported in the literature. Case Series: We present four cases of compound heterozygosity for Hb G-Makassar/Hb E identified from October 2014 to January 2021. All the cases were incidental findings whereby the screening Hb analysis showed the presence of peaks in both Hb S and Hb E zones on capillary electrophoresis (CE) and cation-exchange high-performance liquid chromatography (HPLC). Molecular analysis confirmed the findings of compound heterozygous Hb G-Makassar/Hb E. Two cases had a history of anemia secondary to unrelated conditions that resolved with treatment of the underlying cause. The other two cases were asymptomatic individuals who were detected through Malaysia's National Thalassemia Screening program. On the last follow-up, all the individuals were well, non-transfusion dependent, and had no reported history of chronic anemia, bleeding, hemolysis or thromboembolism complications. Conclusion: The cases reported here highlight the possibilities for rare compound heterozygous states in multi-ethnicity populations such as Malaysia. Compound heterozygous Hb G-Makassar/Hb E individuals are clinically silent with laboratory values suggesting microcytic and hypochromic red blood cells. Further local epidemiology or population studies with genotyping tests are required for a better understanding of the diversity of its clinical phenotype.

In situ self-assembly of molybdenum carbide and iron carbide heterostructures on N-doped carbon for an efficient oxygen reduction reaction.

Identifying highly stable, cost-effective, platinum-free, and efficient electrocatalysts for the oxygen reduction reaction (ORR) remains a formidable challenge. The ORR is important for advancing fuel cell and zinc-air battery (ZAB) technologies towards cost-efficiency and environmental sustainability. This work presents the utilization of economically viable materials through a straightforward synthesis process, exhibiting the development of efficient Mo2C/Fe3C-NC catalysts ingeniously derived from phosphomolybdic acid (PMA) and iron phthalocyanine (FePc). The results demonstrate that the optimized Mo2C/Fe3C-NC3 catalysts exhibit remarkable electrochemical performance, evidenced by an impressive onset potential of ∼1.0 V versus RHE, a half-wave potential of 0.89 V, and a superior current density of about 6.2 mA cm-2. As for their performance in ZABs, the optimized catalysts reach a peak power density of 142 mW cm-2 at a current density of 200 mA cm-2. This synergy, coupled with the uniform distribution of Mo2C and Fe3C nanoparticles, greatly enhances the active catalytic sites and promotes electrolyte diffusion. Our approach diverges from traditional methods by employing an in situ self-assembled heterostructure of Mo2C/Fe3C on nitrogen-doped carbon tubes, avoiding the conventional high-temperature hydrogen gas reduction process. Beyond serving as feasible alternatives to commercially available Pt/C catalysts, these materials hold promise for large-scale production owing to their affordability and the simplicity of the synthesis technique. Such a breakthrough paves the way towards the realization of sustainable energy technologies and lays the groundwork for further exploration into amplifying the scalability and efficiency of ORR catalysts.

Metabolite profiling and in-silico studies show multiple effects of insecticidal actinobacterium on Spodoptera littoralis.

The polyphagous pest, Spodoptera littoralis (Boisduval), poses a significant global economic threat by gregariously feeding on over a hundred plant species, causing substantial agricultural losses. Addressing this challenge requires ongoing research to identify environmentally safe control agents. This study aimed to elucidate the insecticidal activity of the metabolite (ES2) from a promising endophytic actinobacterium strain, Streptomyces sp. ES2 EMCC2291. We assessed the activity of ES2 against the eggs and fourth-instar larvae of S. littoralis through spectrophotometric measurements of total soluble protein, α- and ß-esterases, polyphenol oxidase (PPO), and catalase enzyme (CAT). The assessments were compared to commercial Biosad® 22.8% SC. Untargeted metabolomics using LC-QTOF-MS/MS identified 83 metabolic compounds as chemical constituents of ES2. The median lethal concentration (LC50) of ES2 (165 mg/mL) for treated Spodoptera littoralis eggs showed significant differences in polyphenol oxidase and catalase enzymatic activities, while the LC50 of ES2 (695 mg/mL) for treated S. littoralis fourth instar larvae showed lower significance in α- and ß-esterase activities. Molecular docking of ES2 identified seven potent biocidal compounds, showing strong affinity to PPO and catalase CAT proteins in S. littoralis eggs while displaying limited binding to alpha and beta esterase proteins in the larvae. The results contribute to the understanding of ES2 as a promising alternative biopesticide, providing insights for future research and innovative applications in sustainable pest management strategies.

A Case Report of Traumatic Ulcerative Granuloma With Stromal Eosinophilia (TUGSE): Clinical and Histopathological Diagnostic Challenges.

Traumatic ulcerative granuloma with stromal eosinophilia is a reactive, self-limiting ulcer within the oral cavity; however, clinically, it mimics a malignant ulcer. Here, we report the case of a 13-year-old boy who presented with a painful solitary indurated ulcer at the lower lip for a week. Histopathological examination revealed an ulcerated lesion with significant infiltration of eosinophils, small lymphocytes, and large lymphoid cells. Further immunohistochemistry showed the inflammatory cells were CD3-positive T cells and CD68-positive, with a minority of the cell population showing CD30 positivity. CD1a-positive dendritic cells were also observed. We discuss the clinical and histopathological differential diagnoses of Langerhans cell histiocytosis and CD30-positive T-cell lymphoproliferative disorders and how to correlate them in formulating the final diagnosis.

Clinical and haematological characteristics of 38 individuals with Hb G-Makassar in Malaysia.

Haemoglobin (Hb) G-Makassar is a rare Hb variant. It presents a diagnostic challenge as it imitates sickle Hb (Hb S) in standard electrophoresis and high-performance liquid chromatography assays requiring DNA analysis to confirm diagnosis. Both have point mutations in codon 6, exon 1 in the ß-globin (HBB) gene with different pathogenicities. This study describes the clinical phenotype, haematology and genotype of Hb G-Makassar. Clinical and laboratory data of 38 cases of Hb G-Makassar over 8 years were analysed. Hb G-Makassar was confirmed by a direct sequencing of HBB gene and co-inheritance of α-thalassaemia determined through multiplex gap-PCR and multiplex Amplification Refractory Mutation System polymerase chain reaction. All cases were Malays, predominantly from Terengganu (n = 20, 52.6%). There were 14 (36.8%) males and 24 (63.2%) females with median age of 25 years. Majority (n = 33, 86.8%) had features of thalassaemia trait with mean ± SD for Hb, mean cell volume (MCV) and mean cell haemoglobin (MCH) as 13.21 g/dL ± 1.69, 73.06 ± 4.48 fL and 24.71 ± 1.82 pg, respectively. None had evidence of haemolysis or thromboembolic complications. Six genotypes were identified; ßG-Makassar/ß,αα/αα (n = 19, 50.0%), ßG-Makassar/ßE,αα/αα (n = 4, 10.5%), ßG-Makassar/ßNewYork,αα/αα (n = 1, 2.6%), ßG-Makassar/ß,αα/-α (n = 11, 28.9%), ßG-Makassar/ß,αα/αAdanaα (n = 2, 5.3%) and ßG-Makassar/ß,αα/-SEA (n = 1, 2.6%). The ßG-Makassar/ß,αα/αα showed that features of thalassaemia trait with mean ± SD for Hb, MCV and MCH were 13.74 g/dL ± 2.40, 76.18 ± 6.02 fL and 25.79 ± 2.41 pg, respectively. This is the largest study reporting a significant number of Hb G-Makassar in Malaysia. Although the mutation is similar to Hb S, the phenotype is benign.

Stabilizing a zinc anode via a tunable covalent organic framework-based solid electrolyte interphase.

Zinc (Zn) is an excellent material for use as an anode for rechargeable batteries in water-based electrolytes. Nevertheless, the high activity of water leads to Zn corrosion and hydrogen evolution, along with the formation of dendrites on the Zn surface during repeated charge-discharge (CD) cycles. To protect the Zn anode and limit parasitic side reactions, an artificial solid electrolyte interphase (ASEI) protective layer is an effective strategy. Herein, an ASEI made of a covalent organic framework (COFs: HqTp and BpTp) was fabricated on the surface of a Zn anode via Schiff base reactions of aldehyde and amine linkers. It is seen that COFs can regulate the Zn-ion flux, resulting in dendritic-free Zn. COFs can also mitigate the formation of an irreversible passive layer and the hydrogen evolution reaction (HER). Zn plating/stripping tests using a symmetrical cell suggest that HqTpCOF@Zn shows superior stability and greater coulombic efficiency (CE) compared to bare Zn. The full cell having COFs@Zn also displays much improved cyclability. As a result, the COF proves to be a promising ASEI material to enhance the stability of the Zn anode in aqueous media.

A retroperitoneal cystic lymphangioma involving the spleen and pancreas: a case report.

Retroperitoneal cystic lymphangioma (CL) is a rare condition and accounts for 1% of all CL. It can be congenital in children associated with genetic disorders or acquired in adults with chronic diseases. Case presentation: In the present case, the girl complained of abdominal pain and dysuria. Clinical examinations showed a palpitated mass in her left pelvis; a radiology exam revealed a cystic mass infiltrating the spleen and pancreatic tail, reaching the pelvis. The mass, including the spleen and pancreatic tail, among the cystic compound was removed. The final diagnosis of benign CL was done based on a histopathology exam. A one-year follow-up showed no signs of recurrence. Clinical discussion: CL is usually asymptomatic. The retroperitoneal location of the mass delayed the diagnosis and allowed the mass to grow to a large size and compress nearby structures. The typical presentation of CL is usually a substantial, multichambers cystic mass. However, it could be easily misdiagnosed with other cystic tumors of the pancreas. Age-based differential diagnosis should be taken into consideration in children as abdominal mass can originate from gastrointestinal or genitourinary systems. Conclusion: The imaging features of CL are insufficient, and the final diagnosis depends on the histopathology exam. Furthermore, CL can mimic pancreatic cysts in its presentation and cite; therefore, it must be included in the diagnosing strategy whenever a retroperitoneal cyst is being investigated, as imaging features can be misleading. Surgical treatment of CL should be associated with long-term ultrasound follow-up to identify and manage recurrence early.

Unsteady natural convection flow of blood Casson nanofluid (Au) in a cylinder: nano-cryosurgery applications.

Nano-cryosurgery is one of the effective ways to treat cancerous cells with minimum harm to healthy adjacent cells. Clinical experimental research consumes time and cost. Thus, developing a mathematical simulation model is useful for time and cost-saving, especially in designing the experiment. Investigating the Casson nanofluid's unsteady flow in an artery with the convective effect is the goal of the current investigation. The nanofluid is considered to flow in the blood arteries. Therefore, the slip velocity effect is concerned. Blood is a base fluid with gold (Au) nanoparticles dispersed in the base fluid. The resultant governing equations are solved by utilising the Laplace transform regarding the time and the finite Hankel transform regarding the radial coordinate. The resulting analytical answers for velocity and temperature are then displayed and visually described. It is found that the temperature enhancement occurred by arising nanoparticles volume fraction and time parameter. The blood velocity increases as the slip velocity, time parameter, thermal Grashof number, and nanoparticles volume fraction increase. Whereas the velocity decreases with the Casson parameter. Thus, by adding Au nanoparticles, the tissue thermal conductivity enhanced which has the consequence of freezing the tissue in nano-cryosurgery treatment significantly.

Limitations of using 16S rRNA microbiome sequencing to predict oral squamous cell carcinoma.

A new era of next-generation sequencing has changed our perception of the oral microbiome in health and disease, and with this there is a growing understanding that the oral microbiome is a contributing factor to oral squamous cell carcinoma (OSCC), a malignancy of the oral cavity. This study aimed to analyse the trends and relevant literature based on the 16S rRNA oral microbiome in head and neck cancer using next-generation sequencing technologies, and to conduct a meta-analysis of the studies with OSCC cases and healthy controls. A literature search using the databases Web of Science and PubMed was conducted in a scoping-like review to collect information based on the study design, and plots were generated using RStudio. We selected case-control studies using 16S rRNA oral microbiome sequencing analysis in OSCC cases versus healthy controls for re-analysis. Statistical analyses were conducted using R. Out of 916 original articles, we filtered and selected 58 studies for review, and 11 studies for meta-analysis. Differences between sampling type, DNA extraction methods, next-generation sequencing technology and region of the 16S rRNA were identified. No significant differences in the α- and ß-diversity between health and oral squamous cell carcinoma were observed (p < 0.05). Random Forest classification marginally improved predictability of four studies (training set) when split 80/20. We found an increase in Selenomonas, Leptotrichia and Prevotella species to be indicative of disease. A number of technological advances have been accomplished to study oral microbial dysbiosis in oral squamous cell carcinoma. There is a clear need for standardization of study design and methodology to ensure 16S rRNA outputs are comparable across the discipline in the hope of identifying 'biomarker' organisms for designing screening or diagnostic tools.

Potentials of additional copper filtration on radiation dose and image quality for adults underwent digital chest X-ray imaging in Dubai Health Authority - UAE.

OBJECTIVE: To explore the potentials of adding copper (Cu) filter on image quality and patient dose of adult patients underwent chest X-ray examination METHODS: Patients were divided into four groups. Group 1, patients were exposed with no added Cu filter (standard or control), group 2 a 0.1 mm Cu filter was added, group 3 acquired with 0.2 mm Cu filter and group 4 performed with 0.3 mm Cu filter. Exposure index (EI), entrance surface dose (ESD) and dose area product (DAP) were recorded from the modality and retrospectively analyzed. The visual grading analysis score (VGAS) was used to evaluate image quality. Mann-Whitney T-Test and one-way ordinary ANOVA Test were used to evaluate statistical differences including gender-based findings. RESULTS: EI, ESD and DAP data for a total of 784 patients (422 male and 362 female) that underwent indirect digital chest radiography exam were collected. Image quality was maintained when adding 0.1 mm Cu filter achieved with ∼19% DAP reduction. Female showed a significant DAP reduction comparing to male registered in the same group. CONCLUSIONS: Reducing dose when using indirect digital chest radiography is possible with no trade-off on image quality. No loss of image quality was reported, images were broadly comparable. IMPLICATIONS FOR PRACTICE: This study highlights the importance of utilizing the additional copper filter in digital chest radiography.

Recursive zonotopic set-membership approach for system-level prognostics with application to linear parameter-varying systems.

A robust recursive zonotopic set-membership approach for remaining useful life forecasting with application to linear parameter-varying systems is proposed in this paper. The proposed approach addresses systems with degraded components formulated as a system-level prognostics problem. Thus, the critical degraded components of the system are augmented to the states resulting a nonlinear system that is reformulated as a linear parameter-varying model. Hence, joint estimation of states and parameters is adopted in a zonotopic set-membership scheme with an optimal linear matrix inequality-based tuning and assuming unknown-but-bounded noises and uncertainties. As a result, a recursive zonotopic set-membership approach is proposed for remaining useful life forecasting based on the prediction of the failure precursors of degraded systems. Finally, this approach is tested on a DC-DC converter case study with unknown degradation behaviors, and the obtained results show the estimation and the forecasting accuracy of this methodology.

Single-Anastomosis Sleeve Jejunal Bypass as a Treatment for Morbid Obesity: A Systematic Review and Meta-Analysis.

Single-anastomosis sleeve jejunal (SASJ) bypass is a bariatric surgery technique with promising results. However, evidence of its efficacy and safety is still lacking. This study aimed to summarize the evidence regarding the efficacy and safety of SASJ bypass surgery in the treatment of morbid obesity. The literature was searched for English-language studies published from inception till November 26, 2023, on MEDLINE/PubMed, Cochrane Library, Web of Science, ProQuest, Scopus, SCINAPSE, and Google Scholar. The search terms included "morbid obesity," "bariatric surgery," and "single anastomosis sleeve jejunal bypass." Extracted data included the body mass index (BMI) before and after surgery, percent total weight loss (%TWL), percent excess weight loss (%EWL), and improvement in preoperative comorbidities. Pooling of the data was done using random effects or fixed-effect models based on the presence of significant heterogeneity. Nine studies were included in this systematic review and meta-analysis. The change in BMI from baseline at 12 months after SASJ bypass was significant (standardized mean difference (SMD) = -3.576, 95% confidence interval (CI) = -5.423, -1.730; I² = 99.23%). At 12 months after surgery, the pooled %TWL was 42.526 (95% CI = 37.948, 47.105; I² = 97.15%), and the pooled %EWL was 75.258 (95% CI = 67.061, 83.456; I² = 99.26%). The pooled incidence of postoperative improvement in diabetes mellitus was 91% (95% CI = 79.6%, 98%, I² = 82%). The overall rate of complications was 9.9% (95% CI = 2.5%, 21.6%; I² = 92.64%). Regarding the short- and mid-term outcomes, SASJ bypass is a safe and effective procedure for weight loss in patients with morbid obesity, with an acceptable rate of complications. The procedure is also associated with a marked improvement in obesity-related comorbidities.

Compressed composite carbon felt as a negative electrode for a zinc-iron flow battery.

Flow batteries possess several attractive features including long cycle life, flexible design, ease of scaling up, and high safety. They are considered an excellent choice for large-scale energy storage. Carbon felt (CF) electrodes are commonly used as porous electrodes in flow batteries. In vanadium flow batteries, both active materials and discharge products are in a liquid phase, thus leaving no trace on the electrode surface. However, zinc-based flow batteries involve zinc deposition/dissolution, structure and configuration of the electrode significantly determine stability and performance of the battery. Herein, fabrication of a compressed composite using CF with polyvinylidene fluoride (PVDF) is investigated in a Zn-Fe flow battery (ZFB). Graphene (G) is successfully introduced in order to improve its electrochemical activity towards zinc reactions on the negative side of the ZFB. A compressed composite CF electrode offers more uniform electric field and lower nucleation overpotential (NOP) of zinc than a pristine CF, resulting in higher zinc plating/stripping efficiency. Batteries with modified electrodes are seen to provide lower overpotential. Particularly, the G-PVDF-CF electrode demonstrates maximum discharge capacity of 39.6 mAh cm-2 with coulombic efficiency and energy efficiency over 96% and 61%, respectively. Finally, results lead to increased efficiency and cycling stability for flow batteries.

Burden and Risk Factors of Melioidosis in Southeast Asia: A Scoping Review.

This scoping review aims to provide a comprehensive overview of human melioidosis in Southeast Asia as well as to highlight knowledge gaps in the prevalence and risk factors of this life-threatening disease using available evidence-based data for better diagnosis and treatment. Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) was used as the guideline for this review. The literature search was conducted on 23 March 2022 through two electronic databases (PubMed and Scopus) using lists of keywords referring to the Medical Subject Headings (MeSH) thesaurus. A total of 38 articles related to human melioidosis were included from 645 screened articles. These studies were carried out between 1986 and 2019 in six Southeast Asian countries: Thailand, Cambodia, Malaysia, Myanmar, Singapore, and Vietnam. Melioidosis has been reported with a high disease prevalence among high-risk populations. Studies in Thailand (48.0%) and Cambodia (74.4%) revealed disease prevalence in patients with septic arthritis and children with suppurative parotitis, respectively. Other studies in Thailand (63.5%) and Malaysia (54.4% and 65.7%) showed a high seroprevalence of melioidosis among Tsunami survivors and military personnel, respectively. Additionally, this review documented soil and water exposure, diabetes mellitus, chronic renal failure, thalassemia, and children under the age of 15 as the main risk factors for melioidosis. Human melioidosis is currently under-reported in Southeast Asia and its true prevalence is unknown.

Prevalence of Antimicrobial Resistance Genes in Salmonella Typhi: A Systematic Review and Meta-Analysis.

Salmonella enterica serovar Typhi (S. Typhi) that has developed resistance to many antimicrobials poses a serious challenge to public health. Hence, this study aimed to systematically determine the prevalence of antimicrobial resistance (AMR) in S. Typhi isolated from the environment and humans as well as to ascertain the spread of the selected AMR genes in S. Typhi. This systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, and the study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). A total of 2353 studies were retrieved from three databases, of which 42 studies fulfilled the selection criteria. The pooled prevalence of AMR S. Typhi (using a random-effect model) was estimated at 84.8% (95% CI; 77.3−90.2), with high heterogeneity (I2: 95.35%, p-value < 0.001). The high estimated prevalence indicates that control methods should be improved immediately to prevent the spread of AMR among S. Typhi internationally.

Meta-analysis of caries microbiome studies can improve upon disease prediction outcomes.

As one of the most prevalent infective diseases worldwide, it is crucial that we not only know the constituents of the oral microbiome in dental caries but also understand its functionality. Herein, we present a reproducible meta-analysis to effectively report the key components and the associated functional signature of the oral microbiome in dental caries. Publicly available sequencing data were downloaded from online repositories and subjected to a standardized analysis pipeline before analysis. Meta-analyses identified significant differences in alpha and beta diversities of carious microbiomes when compared to healthy ones. Additionally, machine learning and receiver operator characteristic analysis showed an ability to discriminate between healthy and disease microbiomes. We identified from importance values, as derived from random forest analyses, a group of genera, notably containing Selenomonas, Aggregatibacter, Actinomyces and Treponema, which can be predictive of dental caries. Finally, we propose the most appropriate study design for investigating the microbiome of dental caries by synthesizing the studies, which had the most accurate differentiation based on random forest modelling. In conclusion, we have developed a non-biased, reproducible pipeline, which can be applied to microbiome meta-analyses of multiple diseases, but importantly we have derived from our meta-analysis a key group of organisms that can be used to identify individuals at risk of developing dental caries based on oral microbiome inhabitants.

Are smoking restrictions at public venues and psychosocial beliefs associated with intentions to quit smoking among smokers in Malaysia?

The Malaysian government reinforced smoking restrictions at public venues to protect nonsmokers from secondhand smoke (SHS) exposure. This study examined whether smokers' reports about smoking restrictions and psychosocial beliefs were associated with quit intentions among Malaysian smokers. Data from 1047 cigarette smokers (103 females and 944 males) aged 18 and older from the 2020 International Tobacco Control (ITC) Malaysia Wave 1 Survey were analyzed with bivariate and multivariable logistic regression models. Most Malaysian smokers (85.2%) reported having quit intentions. Smoking was completely restricted in 34.8% of the nighttime venues, 85.3% of air-conditioned (AC) food and beverage (F&B) venues (restaurants, food courts, coffee shops), 87.3% of non-AC F&B, and 69.4% of indoor workplaces. Smokers who visited nighttime entertainment venues where smoking was fully restricted were less likely to have quit intentions. There was no significant association found with quit intentions for smokers who visited AC and non-AC F&B venues and indoor workplaces where smoking was fully restricted. All five psychosocial beliefs assessed, age, and education were positively associated with quit intentions. Malaysian smokers are interested in quitting and psychosocial beliefs were positively associated with quit intentions. There is a need for the Malaysian government to implement and reinforce comprehensive smoking restrictions in all public venues and indoor workplaces to protect nonsmokers from SHS exposure and to encourage smokers to think about quitting, which may influence their quit intentions.

Chemical Transformation Induced Core-Shell Ni2P@Fe2P Heterostructures toward Efficient Electrocatalytic Oxygen Evolution.

The oxygen evolution reaction (OER) is a crucial reaction in water splitting, metal-air batteries, and other electrochemical conversion technologies. Rationally designed catalysts with rich active sites and high intrinsic activity have been considered as a hopeful strategy to address the sluggish kinetics for OER. However, constructing such active sites in non-noble catalysts still faces grand challenges. To this end, we fabricate a Ni2P@Fe2P core-shell structure with outperforming performance toward OER via chemical transformation of rationally designed Ni-MOF hybrid nanosheets. Specifically, the Ni-MOF nanosheets and their supported Fe-based nanomaterials were in situ transformed into porous Ni2P@Fe2P core-shell nanosheets composed of Ni2P and Fe2P nanodomains in homogenous dispersion via a phosphorization process. When employed as the OER electrocatalyst, the Ni2P@Fe2P core-shell nanosheets exhibits excellent OER performance, with a low overpotential of 238/247 mV to drive 50/100 mA cm-2, a small Tafel slope of 32.91 mV dec-1, as well as outstanding durability, which could be mainly ascribed to the strong electronic interaction between Ni2P and Fe2P nanodomains stabilizing more Ni and Fe atoms with higher valence. These high-valence metal sites promote the generation of high-active Ni/FeOOH to enhance OER activity.

Automatic system dynamics characterization of a pharmaceutical continuous production line.

Continuous Manufacturing (CM) of drug products is a new approach in the pharmaceutical industry. In the presented paper, a GMP continuous wet granulation line for production of solid oral dosage forms was investigated in order to assess the system dynamics of the line and to define the best control and diversion strategy. The following steps were involved in the continuous process: dosing/feeding, blending, twin-screw wet granulation, fluid-bed drying, sieving and tableting. Two drug products with two different drug substances were compared during this study: one drug substance as model drug compound and one formulation of a currently evaluated commercial drug product. Several step tests in API concentration were performed in order to characterize the process flow and assess the process dynamics. API content was monitored in real time by Process Analytical Technologies (PAT) thanks to three Near Infrared (NIR) probes located along the process and measuring the API content after blender, after dryer and in the tablet press feed frame. The process parameter values were changed during production in order to detect the impact on the quality of the final product. An automatic residence time distribution (RTD) computation method has been developed in order automate the RTD calculation on the basis of process data to further define and monitor the system dynamics with the final aim of out of specification material diversion during the continuous production. The RTD has been seen as a process fingerprint: a change in the RTD values implies a change in the process.