Ultrafast laser parallel microdrilling using multiple annular beams generated by a spatial light modulator

Ultrafast laser parallel microdrilling using diffractive multiple annular beam patterns is demonstrated in this paper. The annular beam was generated by diffractive axicon computer generated holograms (CGHs) using a spatial light modulator. The diameter of the annular beam can be easily adjusted by varying the radius of the smallest ring in the axicon. Multiple annular beams with arbitrary arrangement and multiple annular beam arrays were generated by superimposing an axicon CGH onto a grating and lenses algorithm calculated multi-beam CGH and a binary Dammann grating CGH, respectively. Microholes were drilled through a 0.03 mm thick stainless steel foil using the multiple annular beams. By avoiding huge laser output attenuation and mechanical annular scanning, the processing is ~200 times faster than the normal single beam processing

‘Children awaken by playing’: a qualitative exploration of caregivers’ norms, beliefs and practices related to young children’s learning and early childhood development in rural Burkina Faso

INTRODUCTION: Evidence suggests that responsive caregiving and early learning activities positively impact developmental outcomes, with positive effects throughout the life course. Early childhood development interventions should align with local values, beliefs and resources but there has been little research of caregiver beliefs and perspectives on development and learning, especially in sub-Saharan Africa. This qualitative study explored norms, beliefs, practices and aspirations around child development of caregivers of young children in rural Burkina Faso. METHODS: We conducted 32 in-depth interviews with mothers and fathers of young children and 24 focus group discussions with mothers, fathers and grandmothers, which included trying behaviours and reporting on experiences. The research informed the development of Scaling Up Nurturing Care, a Radio Intervention to Stimulate Early Childhood Development (SUNRISE), an early child development radio intervention. RESULTS: Caregivers described a process of 'awakening', through which children become aware of themselves and the world around them.Perceptions of the timing of awakening varied, but the ability to learn was thought to increase as children became older and more awake. Consequently, talking and playing with babies and younger children were perceived to have little developmental impact. Caregivers said children's interactions with them, alongside God-given intelligence, was believed to impact later behaviour and development. Caregivers felt their role in helping their children achieve later in life was to pay for education, save money, provide advice and be good role models. Interaction and learning activities were not specifically mentioned. Caregivers who trialled interaction and learning activities reported positive experiences for themselves and their child, but interactions were often caregiver led and directive and play was often physical. Key barriers to carrying out the behaviours were poverty and a lack of time. CONCLUSIONS: Exploring early childhood beliefs and practices can reveal important sociocultural beliefs which, if incorporated into programme planning and implementation, could help achieve more impactful, acceptable and equitable programmes. TRIAL REGISTRATION NUMBER: NCT05335395

The influence of systemic inflammation, dietary intake and stage of disease on rate of weight loss in patients with gastro-oesophageal cancer

Although weight loss is often a dominant symptom in patients with upper gastrointestinal malignancy, there is a lack of objective evidence describing changes in nutritional status and potential associations between weight loss, food intake, markers of systemic inflammation and stage of disease in such patients. Two hundred and twenty patients diagnosed with gastric/oesophageal cancer were studied. Patients underwent nutritional assessment consisting of calculation of body mass index, measurement of weight loss, dysphagia scoring and estimation of dietary intake. Serum acute-phase protein concentrations were determined by enzyme-linked immunosorbent assay. In all, 182 (83%) patients had lost weight at diagnosis (median loss, 7% body weight). Weight loss was associated with poor performance status, advanced disease stage, dysphagia, reduced dietary intake and elevated serum C-reactive protein (CRP) concentrations. Multiple regression identified dietary intake (estimate of effect, 38%), serum CRP concentrations (estimate of effect, 34%) and stage of disease (estimate of effect, 28%) as independent variables in determining degree of weight loss. Mechanisms other than reduced dietary intake or mechanical obstruction by the tumour appear to be involved in the nutritional decline in patients with gastro-oesophageal malignancy. Recognition that systemic inflammation plays a role in nutritional depletion may inform the development of appropriate therapeutic strategies to ameliorate weight loss, making patients more tolerant of cancer-modifying treatments such as chemotherapy

The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

Femtosecond laser internal structuring of materials using a spatial light modulator

Femtosecond laser pulses are of particular interest for internal modification of transperent materials as they enable nonlinear absorption due to the extremly high intensity in the focal volume. Since output from commercial laser sources currently exceeds single beam process requirements, parallel processing with multiple beams could provide a route to up-scaling processing speed and establish cost-effectiveness. The use of spatial light modulators, driven by fast computer-generated holograms for splitting a parent laser beam into a number of beamlets and digitally manipulate their positions and the laser intensity is demonstrated. With successful blocking of the zero order beam and subsequent focusing of the diffracted beams inside transperant materials, high throughput dynamic 2D/3D refractive index modification of polymer and glass substrates with a gain factor G > 20 has been achieved. Fundamental IR (775nm) femtosecond laser pulses were employed to produce optical components. For example, thick volume gratings written with more than 20 beams have 1st order diffraction efficiency η > 60%, indicating a refractive index change Δn ≈ 1.6x10-4. Characterization by microscopic examination and light coupling tests revealed the extent of resolution, process quality and assisted quantification of the process speed gain. The benefits and current limitations of this technique are discussed in detail

Toll-Like Receptor 2 Induced Angiogenesis and Invasion Is Mediated through the Tie2 Signalling Pathway in Rheumatoid Arthritis

BACKGROUND: Angiogenesis is a critical early event in inflammatory arthritis, facilitating leukocyte migration into the synovium resulting in invasion and destruction of articular cartilage and bone. This study investigates the effect of TLR2 on angiogenesis, EC adhesion and invasion using microvascular endothelial cells and RA whole tissue synovial explants ex-vivo. METHODS: Microvascular endothelial cells (HMVEC) and RA synovial explants ex vivo were cultured with the TLR2 ligand, Pam3CSK4 (1 µg/ml). Angiopoietin 2 (Ang2), Tie2 and TLR2 expression in RA synovial tissue was assessed by immunohistology. HMVEC tube formation was assessed using Matrigel matrix assays. Ang2 was measured by ELISA. ICAM-1 cell surface expression was assessed by flow cytometry. Cell migration was assessed by wound repair scratch assays. ECM invasion, MMP-2 and -9 expression were assessed using transwell invasion chambers and zymography. To examine if the angiopoietin/Tie2 signalling pathway mediates TLR2 induced EC tube formation, invasion and migration assays were performed in the presence of a specific neutralising anti-Tie2mAb (10 ug/ml) and matched IgG isotype control Ab (10 ug/ml). RESULTS: Ang2 and Tie2 were localised to RA synovial blood vessels, and TLR2 was localised to RA synovial blood vessels, sub-lining infiltrates and the lining layer. Pam3CSK4 significantly increased angiogenic tube formation (p<0.05), and upregulated Ang2 production in HMVEC (p<0.05) and RA synovial explants (p<0.05). Pam3CSK4 induced cell surface expression of ICAM-1, from basal level of 149±54 (MFI) to 617±103 (p<0.01). TLR-2 activation induced an 8.8±2.8 fold increase in cell invasion compared to control (p<0.05). Pam3CSK4 also induced HMVEC cell migration and induced MMP-2 and -9 from RA synovial explants. Neutralisation of the Ang2 receptor, Tie2 significantly inhibited Pam3CSK4-induced EC tube formation and invasion (p<0.05). CONCLUSION: TLR2 activation promotes angiogenesis, cell adhesion and invasion, effects that are in part mediated through the Tie2 signalling pathway, key mechanisms involved in the pathogenesis of RA

Analysis of C3 Suggests Three Periods of Positive Selection Events and Different Evolutionary Patterns between Fish and Mammals

BACKGROUND: The third complement component (C3) is a central protein of the complement system conserved from fish to mammals. It also showed distinct characteristics in different animal groups. Striking features of the fish complement system were unveiled, including prominent levels of extrahepatic expression and isotypic diversity of the complement components. The evidences of the involvement of complement system in the enhancement of B and T cell responses found in mammals indicated that the complement system also serves as a bridge between the innate and adaptive responses. For the reasons mentioned above, it is interesting to explore the evolutionary process of C3 genes and to investigate whether the huge differences between aquatic and terrestrial environments affected the C3 evolution between fish and mammals. METHODOLOGY/PRINCIPAL FINDINGS: Analysis revealed that these two groups of animals had experienced different evolution patterns. The mammalian C3 genes were under purifying selection pressure while the positive selection pressure was detected in fish C3 genes. Three periods of positive selection events of C3 genes were also detected. Two happened on the ancestral lineages to all vertebrates and mammals, respectively, one happened on early period of fish evolutionary history. CONCLUSIONS/SIGNIFICANCE: Three periods of positive selection events had happened on C3 genes during history and the fish and mammals C3 genes experience different evolutionary patterns for their distinct living environments