3D printing of drug-loaded gyroid lattices using selective laser sintering

Three-dimensional printing (3DP) is gaining momentum in the field of pharmaceuticals, offering innovative opportunities for medicine manufacture. Selective laser sintering (SLS) is a novel, high resolution and single-step printing technology that we have recently introduced to the pharmaceutical sciences. The aim of this work was to use SLS 3DP to fabricate printlets (3D printed tablets) with cylindrical, gyroid lattice and bi-layer structures having customisable release characteristics. Paracetamol-loaded constructs from four different pharmaceutical grade polymers including polyethylene oxide, Eudragit (L100-55 and RL) and ethyl cellulose, were created using SLS 3DP. The novel gyroid lattice structure was able to modulate the drug release from all four polymers. This work is the first to demonstrate the feasibility of using SLS to achieve customised drug release properties of several polymers, in a swift, cost-effective manner, avoiding the need to alter the formulation composition. By creating these constructs, it is therefore possible to modify drug release, which in practice, could enable the tailoring of drug performance to the patient simply by changing the 3D design

An Airboat For Rural Riverine Transportation and Mangrove Marine Environment Applications

The present works describe the design and initial performance study of a prototype airboat for riverine transportation, including mangrove habitat applications, with particular reference to Sarawak, East Malaysia. Many local rural riverine transportation and marine habitat studies are limited due to tide-line dependent and the limitation of conventional blade type marine engine. The use of airboat could ply at the local everglades areas and shallow waters; however the conventional airboat having flat bottom hall may at times not suitable in the narrow mangrove habitat which generally has extended roots. In the present study, our boat was custom designed with Shallow-Vee hall shape, employing a 2-stroke engine. Experimental results have shown that the new airboat built has good performance and balancing capability. Subsequent simulation study employing PROLINE software suggest that 2 passengers as the optimum number for the airboat overall performance (optimum performance and stability), coherent with the experimental trials. Compared with conventional air boats, the new boat design is likely to have two added advantages: (1) relative cheap cost and affordable in development, and (2) shallow-Vee shape design is more suitable then the wider flat bottom shape type due to narrow mangrove habitat, where the shallow mangrove trees generally having roots in the water and extended roots on the water surface

Characterization of mesenchymal stem cells in pre-B acute lymphoblastic leukemia

Components of the bone marrow microenvironment (BMM) have been shown to mediate the way in which leukemia develops, progresses and responds to treatment. Increasing evidence shows that leukemic cells hijack the BMM, altering its functioning and establishing leukemia-supportive interactions with stromal and immune cells. While previous work has highlighted functional defects in the mesenchymal stem cell (MSC) population from the BMM of acute leukemias, thorough characterization and molecular profiling of MSCs in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, has not been conducted. Here, we investigated the cellular and transcriptome profiles of MSCs isolated from the BMM of an immunocompetent BCR-ABL1+ model of B-ALL. Leukemia-associated MSCs exhibited reduced self-renewal capacity in vitro and significant changes in numerous molecular signatures, including upregulation of inflammatory signaling pathways. Additionally, we found downregulation of genes involved in extracellular matrix organization and osteoblastogenesis in leukemia-associated MSCs. This study provides cellular and molecular insights into the role of MSCs during B-ALL progression

Preclinical efficacy of azacitidine and venetoclax for infant KMT2A-rearranged acute lymphoblastic leukemia reveals a new therapeutic strategy

Infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have a dismal prognosis. Survival outcomes have remained static in recent decades despite treatment intensification and novel therapies are urgently required. KMT2A-rearranged infant ALL cells are characterized by an abundance of promoter hypermethylation and exhibit high BCL-2 expression, highlighting potential for therapeutic targeting. Here, we show that hypomethylating agents exhibit in vitro additivity when combined with most conventional chemotherapeutic agents. However, in a subset of samples an antagonistic effect was seen between several agents. This was most evident when hypomethylating agents were combined with methotrexate, with upregulation of ATP-binding cassette transporters identified as a potential mechanism. Single agent treatment with azacitidine and decitabine significantly prolonged in vivo survival in KMT2A-rearranged infant ALL xenografts. Treatment of KMT2A-rearranged infant ALL cell lines with azacitidine and decitabine led to differential genome-wide DNA methylation, changes in gene expression and thermal proteome profiling revealed the target protein-binding landscape of these agents. The selective BCL-2 inhibitor, venetoclax, exhibited in vitro additivity in combination with hypomethylating or conventional chemotherapeutic agents. The addition of venetoclax to azacitidine resulted in a significant in vivo survival advantage indicating the therapeutic potential of this combination to improve outcome for infants with KMT2A-rearranged ALL

Combined distributed turbo coding and space frequency block coding techniques

The distributed space-time (frequency) coding and distributed channel turbo coding used independently represent two cooperative techniques that can provide increased throughput and spectral efficiency at an imposed maximum Bit Error Rate (BER) and delay required from the new generation of cellular networks. This paper proposes two cooperative algorithms that employ jointly the two types of techniques, analyzes their BER and spectral efficiency performances versus the qualities of the channels involved, and presents some conclusions regarding the adaptive employment of these algorithms. © 2010 V. Bota et al.FP7/ICT/2007/21547

Combined distributed turbo coding and space frequency block coding techniques

The distributed space-time (frequency) coding and distributed channel turbo coding used independently represent two cooperative techniques that can provide increased throughput and spectral efficiency at an imposed maximum Bit Error Rate (BER) and delay required from the new generation of cellular networks. This paper proposes two cooperative algorithms that employ jointly the two types of techniques, analyzes their BER and spectral efficiency performances versus the qualities of the channels involved, and presents some conclusions regarding the adaptive employment of these algorithms. © 2010 V. Bota et al.FP7/ICT/2007/21547

Insights into the cultured bacterial fraction of corals

Bacteria associated with coral hosts are diverse and abundant, with recent studies suggesting involvement of these symbionts in host resilience to anthropogenic stress. Despite their putative importance, the work dedicated to culturing coral-associated bacteria has received little attention. Combining published and unpublished data, here we report a comprehensive overview of the diversity and function of culturable bacteria isolated from corals originating from tropical, temperate, and cold-water habitats. A total of 3,055 isolates from 52 studies were considered by our metasurvey. Of these, 1,045 had full-length 16S rRNA gene sequences, spanning 138 formally described and 12 putatively novel bacterial genera across the Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria phyla. We performed comparative genomic analysis using the available genomes of 74 strains and identified potential signatures of beneficial bacterium-coral symbioses among the strains. Our analysis revealed \u3e 400 biosynthetic gene clusters that underlie the biosynthesis of antioxidant, antimicrobial, cytotoxic, and other secondary metabolites. Moreover, we uncovered genomic features-not previously described for coral-bacterium symbioses-potentially involved in host colonization and host-symbiont recognition, antiviral defense mechanisms, and/or integrated metabolic interactions, which we suggest as novel targets for the screening of coral probiotics. Our results highlight the importance of bacterial cultures to elucidate coral holobiont functioning and guide the selection of probiotic candidates to promote coral resilience and improve holistic and customized reef restoration and rehabilitation efforts

Combined distributed turbo coding and space frequency block coding techniques

The distributed space-time (frequency) coding and distributed channel turbo coding used independently represent two cooperative techniques that can provide increased throughput and spectral efficiency at an imposed maximum Bit Error Rate (BER) and delay required from the new generation of cellular networks. This paper proposes two cooperative algorithms that employ jointly the two types of techniques, analyzes their BER and spectral efficiency performances versus the qualities of the channels involved, and presents some conclusions regarding the adaptive employment of these algorithms. © 2010 V. Bota et al.FP7/ICT/2007/21547

What are emergency ambulance services doing to meet the needs of people who call frequently? A national survey of current practice in the United Kingdom

Background Emergency ambulance services are integral to providing a service for those with unplanned urgent and life-threatening health conditions. However, high use of the service by a small minority of patients is a concern. Our objectives were to describe: service-wide and local policies or pathways for people classified as Frequent Caller; call volume; and results of any audit or evaluation. Method We conducted a national survey of current practice in ambulance services in relation to the management of people who call the emergency ambulance service frequently using a structured questionnaire for completion by email and telephone interview. We analysed responses using a descriptive and thematic approach. Results Twelve of 13 UK ambulance services responded. Most services used nationally agreed definitions for ‘Frequent Caller’, with 600–900 people meeting this classification each month. Service-wide policies were in place, with local variations. Models of care varied from within-service care where calls are flagged in the call centre; contact made with callers; and their General Practitioner (GP) with an aim of discouraging further calls, to case management through cross-service, multi-disciplinary team meetings aiming to resolve callers’ needs. Although data were available related to volume of calls and number of callers meeting the threshold for definition as Frequent Caller, no formal audits or evaluations were reported. Conclusions Ambulance services are under pressure to meet challenging response times for high acuity patients. Tensions are apparent in the provision of care to patients who have complex needs and call frequently. Multi-disciplinary case management approaches may help to provide appropriate care, and reduce demand on emergency services. However, there is currently inadequate evidence to inform commissioning, policy or practice development