Multiple cutout optimization in composite plates using evolutionary structural optimization

The optimization of cutouts in composite plates was investigated by implementing a procedure known as Evolutionary Structural Optimization. Perforations were introduced into a finite element mesh of the plate from which one or more cutouts of a predetermined size were evolved. In the examples presented, plates were rejected from around each evolving cutout based on a predefined rejection criterion. The Limiting ply within each plate element around the cutout was determined based on the Tsai-Hill failure criterion. Finite element plates with values below the product of the average Tsai-Hill number and a rejection criterion were subsequently removed. This process was iterated until a steady state was reached and the rejection criterion was then incremented by an evolutionary rate and the above steps repeated until the desired cutout area was achieved. Various plates with differing lay-up and loading parameters were investigated to demonstrate the generality and robustness of this optimization procedure.

Buckling mode transition in hat-stiffened composite panels loaded in uniaxial compression

A combined experimental and analytical study of a hat-stiffened carbon-fibre composite panel loaded in uniaxial compression was investigated. A buckling mode transition was observed in the panel's skin bay which was not captured using non-linear finite-element analysis. Good correlation between experimental and numerical strain and displacement results was achieved in the prebuckling and initial postbuckling region of the loading history. A Marguerre-type Rayleigh-Ritz energy method was applied to the skin bay using representative displacement functions of permissible mode shapes to explain the mode transition phenomenon. The central criterion of this method was based on the assumption that a change in mode shape occurred such that the total potential energy of the structure was maintained at a minimum. The ultimate strength of the panel was limited by the column buckling strength of the hat-stiffeners.

Shape optimization of interior cutouts in composite panels

This paper presents validated results of the optimization of cutouts in laminated carbon-fibre composite panels by adapting a recently developed optimization procedure known as Evolutionary Structural Optimization (ESO). An initial small cutout was introduced into each finite element model and elements were removed from around this cutout based on a predefined rejection criterion. In the examples presented, the limiting ply within each plate element around the cutout was determined based on the Tsai-Hill failure index. Plates with values below the product of the average Tsai-Hill number and a rejection ratio (RR) were subsequently removed. This process was iterated until a steady state was reached and the RR was then incremented by an evolutionary rate (ER). The above steps were repeated until a cutout of a desired area was achieved.

Postbuckling Behaviour of Hat Stiffened Thin Skinned Carbon Fibre Composite Panels

The results of a combined experimental and numerical study of hat-stiffened co-cured carbon-fibre composite panels loaded in uniaxial compression are presented. All panels consisted of two integrated stiffeners separated by an eight-ply thick skin bay of lay-up [*45/0190], . The effects of a 100 mm circular cutout in the skin was also investigated. The ultimate strength of all panels was governed by the load carrying capacity of the stiffeners. A change in the skin's buckling mode-shape was also observed for all panels loaded deep in the postbuckling region. The strains induced at the interior free-edge were not found to be critical. Non-linear finite element results correlated well with the prebuckling and initial postbuckling strain and displacements results obtained by experiment.

Drug and light delivery strategies for photodynamic antimicrobial chemotherapy (PACT) of pulmonary pathogens:a pilot study

Pulmonary disease is the main cause of morbidity and mortality in cystic fibrosis (CF) suffers, with multidrug-resistant Pseudomonas aeruginosa and Burkholderia cepacia complex as problematic pathogens in terms of recurrent and unremitting infections. Novel treatment of pulmonary infection is required to improve the prognosis and quality of life for chronically infected patients. Photodynamic antimicrobial chemotherapy (PACT) is a treatment combining exposure to a light reactive drug, with light of a wavelength specific for activation of the drug, in order to induce cell death of bacteria. Previous studies have demonstrated the susceptibility of CF pathogens to PACT in vitro. However, for the treatment to be of clinical use, light and photosensitizer must be able to be delivered successfully to the target tissue. This preliminary study assessed the potential for delivery of 635 nm light and methylene blue to the lung using an ex vivo and in vitro lung model. Using a fibre-optic light delivery device coupled to a helium-neon laser, up to 11% of the total light dose penetrated through full thickness pulmonary parenchymal tissue, which indicates potential for multiple lobe irradiation in vivo. The mass median aerodynamic diameter (MMAD) of particles generated via methylene blue solution nebulisation was 4.40 µm, which is suitable for targeting the site of infection within the CF lung. The results of this study demonstrate the ability of light and methylene blue to be delivered to the site of infection in the CF lung. PACT remains a viable option for selective killing of CF lung pathogens.

Structure-based design of HSPA5 inhibitors: From peptide to small molecule inhibitors

We identified nine small-molecule hit compounds of Heat shock 70 kDa protein 5 (HSPA5) from cascade in silico screening based on the binding modes of the tetrapeptides derived from the peptide substrate or inhibitors of Escherichia coli HSP70. Two compounds exhibit promising inhibition activities from cancer cell viability and tumor inhibition assays. The binding modes of the hit compounds provide a platform for development of selective small molecule inhibitors of HSPA5. (C) 2013 Elsevier Ltd. All rights reserved.

Slower postnatal growth is associated with delayed cerebral cortical maturation in preterm newborns

Slower postnatal growth is an important predictor of adverse neurodevelopmental outcomes in infants born preterm. However, the relationship between postnatal growth and cortical development remains largely unknown. Therefore, we examined the association between neonatal growth and diffusion tensor imaging measures of microstructural cortical development in infants born very preterm. Participants were 95 neonates born between 24 and 32 weeks gestational age studied twice with diffusion tensor imaging: scan 1 at a median of 32.1 weeks (interquartile range, 30.4 to 33.6) and scan 2 at a median of 40.3 weeks (interquartile range, 38.7 to 42.7). Fractional anisotropy and eigenvalues were recorded from 15 anatomically defined cortical regions. Weight, head circumference, and length were recorded at birth and at the time of each scan. Growth between scans was examined in relation to diffusion tensor imaging measures at scans 1 and 2, accounting for gestational age, birth weight, sex, postmenstrual age, known brain injury (white matter injury, intraventricular hemorrhage, and cerebellar hemorrhage), and neonatal illness (patent ductus arteriosus, days intubated, infection, and necrotizing enterocolitis). Impaired weight, length, and head growth were associated with delayed microstructural development of the cortical gray matter (fractional anisotropy: P <0.001), but not white matter (fractional anisotropy: P = 0.529), after accounting for prenatal growth, neonatal illness, and brain injury. Avoiding growth impairment during neonatal care may allow cortical development to proceed optimally and, ultimately, may provide an opportunity to reduce neurological disabilities related to preterm birth.

Score for neonatal acute physiology-II and neonatal pain predict corticospinal tract development in premature newborns

Premature infants are at risk for adverse motor outcomes, including cerebral palsy and developmental coordination disorder. The purpose of this study was to examine the relationship of antenatal, perinatal, and postnatal risk factors for abnormal development of the corticospinal tract, the major voluntary motor pathway, during the neonatal period. In a prospective cohort study, 126 premature neonates (24-32 weeks' gestational age) underwent serial brain imaging near birth and at term-equivalent age. With diffusion tensor tractography, mean diffusivity and fractional anisotropy of the corticospinal tract were measured to reflect microstructural development. Generalized estimating equation models examined associations of risk factors on corticospinal tract development. The perinatal risk factor of greater early illness severity (as measured by the Score for Neonatal Acute Physiology-II [SNAP-II]) was associated with a slower rise in fractional anisotropy of the corticospinal tract (P = 0.02), even after correcting for gestational age at birth and postnatal risk factors (P = 0.009). Consistent with previous findings, neonatal pain adjusted for morphine and postnatal infection were also associated with a slower rise in fractional anisotropy of the corticospinal tract (P = 0.03 and 0.02, respectively). Lessening illness severity in the first hours of life might offer potential to improve motor pathway development in premature newborns.

Neonatal pain in relation to postnatal growth in infants born very preterm

Procedural pain is associated with poorer neurodevelopment in infants born very preterm (= 32 weeks gestational age), however, the etiology is unclear. Animal studies have demonstrated that early environmental stress leads to slower postnatal growth; however, it is unknown whether neonatal pain-related stress affects postnatal growth in infants born very preterm. The aim of this study was to examine whether greater neonatal pain (number of skin-breaking procedures adjusted for medical confounders) is related to decreased postnatal growth (weight and head circumference [HC] percentiles) early in life and at term-equivalent age in infants born very preterm. Participants were n=78 preterm infants born = 32 weeks gestational age, followed prospectively since birth. Infants were weighed and HC measured at birth, early in life (median: 32 weeks [interquartile range 30.7-33.6]) and at term-equivalent age (40 weeks [interquartile range 38.6-42.6]). Weight and HC percentiles were computed from sex-specific British Columbia population-based data. Greater neonatal pain predicted lower body weight (Wald ?(2)=7.36, P=0.01) and HC (Wald ?(2)=4.36, P=0.04) percentiles at 32 weeks postconceptional age, after adjusting for birth weight percentile and postnatal risk factors of illness severity, duration of mechanical ventilation, infection, and morphine and corticosteroid exposure. However, later neonatal infection predicted lower weight percentile at term (Wald ?(2)=5.09, P=0.02). Infants born very preterm undergo repetitive procedural pain during a period of physiological immaturity that appears to impact postnatal growth, and may activate a downstream cascade of stress signaling that affects later growth in the neonatal intensive care unit.

Procedural pain and brain development in premature newborns

Objective: Preterm infants are exposed to multiple painful procedures in the neonatal intensive care unit (NICU) during a period of rapid brain development. Our aim was to examine relationships between procedural pain in the NICU and early brain development in very preterm infants.

Methods: Infants born very preterm (N ¼ 86; 24–32 weeks gestational age) were followed prospectively from birth, and studied with magnetic resonance imaging, 3-dimensional magnetic resonance spectroscopic imaging, and diffusion tensor imaging: scan 1 early in life (median, 32.1 weeks) and scan 2 at term-equivalent age (median, 40 weeks). We calculated N-acetylaspartate to choline ratios (NAA/choline), lactate to choline ratios, average diffusivity, and white matter fractional anisotropy (FA) from up to 7 white and 4 subcortical gray matter regions of interest. Procedural pain was quantified as the number of skin-breaking events from birth to term or scan 2. Data were
analyzed using generalized estimating equation modeling adjusting for clinical confounders such as illness severity, morphine exposure, brain injury, and surgery.

Results: After comprehensively adjusting for multiple clinical factors, greater neonatal procedural pain was associated with reduced white matter FA (b ¼ 0.0002, p ¼ 0.028) and reduced subcortical gray matter NAA/choline (b ¼ 0.0006, p ¼ 0.004). Reduced FA was predicted by early pain (before scan 1), whereas lower NAA/choline was predicted by pain exposure throughout the neonatal course, suggesting a primary and early effect on subcortical structures with secondary white matter changes.

Interpretation: Early procedural pain in very preterm infants may contribute to impaired brain development.