Exploring the limits of prolonged apnoea with high-flow nasal oxygen: an observational study.

High-flow nasal oxygen is increasingly used for oxygenation during apnoea. Extending apnoea duration using this technique has mainly been investigated during minor laryngeal surgery, but it is unclear how long it can be administered for before it should be discontinued due to acidosis. We aimed to describe the dynamics of arterial blood gases during apnoeic oxygenation with high-flow nasal oxygen with jaw thrust only, to explore the limits of this technique. We included adult orthopaedic patients scheduled for general anaesthesia. After pre-oxygenation, anaesthesia with neuromuscular blockade was induced and high-flow nasal oxygen (70 l.min-1 ) was continued with jaw thrust as the only means of airway management, with monitoring of vital signs and arterial blood gas sampling every 5 minutes. Apnoeic oxygenation with high-flow nasal oxygen was discontinued when arterial carbon dioxide tension (PaCO2 ) exceeded 12 kPa or pH fell to 7.15. This technique was used in 35 patients and median (IQR [range]) apnoea time was 25 (20-30 [20-45]) min and was discontinued in all patients when pH fell to 7.15. The mean (SD) PaCO2 increase was 0.25 (0.06) kPa.min-1 but it varied substantially (range 0.13-0.35 kPa.min-1 ). Mean (SD) arterial oxygen tension was 48.6 (11.8) kPa when high-flow nasal oxygen was stopped. Patients with apnoea time > 25 minutes were significantly older (p = 0.025). We conclude that apnoeic oxygenation with high-flow nasal oxygen resulted in a significant respiratory acidosis that varies substantially on the individual level, but oxygenation was maintained.

Genital and anal Chlamydia trachomatis bacterial load in concurrently infected women: a cross-sectional study.

OBJECTIVES: Most international STI guidelines recommend Chlamydia trachomatis anorectal testing in women after self-reported sexual exposure or symptoms in women. However, it has been shown that the prevalence of anorectal C. trachomatis is as high (7%-17 %) in women who do not report anorectal intercourse (AI) as in women who do. This study assessed the correlation between the genital and anorectal C. trachomatis load in concurrently infected women for increased microbiological insight. METHODS: A convenience sample of 105 women with a concurrent (genital and anorectal) C. trachomatis infection was included from the STI clinic in South Limburg, the Netherlands. Women provided self-collected vaginal and anorectal swabs. The C. trachomatis load was quantified with qPCR and the human cell load was assessed to ensure sample adequacy. Genital and anorectal C. trachomatis loads were divided into tertiles for comparison. The χ2 test and linear regression were used to compare genital and anorectal C. trachomatis loads and identify determinants associated with load. RESULTS: The overall median C. trachomatis load was higher in genital (median 5.3 log10C. trachomatis/ml) than anorectal samples (median 3.4, p ≤ 0.001), but both loads were within the same range. The genital and anal load categories were not related within one woman (p = 0.99), both in women with and without AI. The anorectal C. trachomatis load was in the same or higher load category than the genital load in 56% of women without AI, and 79% of women with AI. CONCLUSIONS: Although no cut-off for clinical relevance is known, an anorectal C. trachomatis load in the same or higher load category than the genital C. trachomatis load is likely to be clinically relevant. Other measurements should also be taken into account, such as leucocytes or bacterial viability to distinguish infection from contamination or exposure.

Nanostructured Stealth Surfaces for Visible and Near-Infrared Light.

So far, all previous attempts to apply nanostructures for perfect transmission have not achieved maximum transmittance beyond 99.5% due to the limited regularity of the nanoscale surface geometry: too low for many high-end applications. Here we demonstrate a nanostructured stealth surface, with minimal reflectance (<0.02%) and maximal transmittance (>99.8%) for a wavelength range, covering visible and near-infrared. Compared to multilayer thin film coatings for near-infrared applications our antireflective surfaces operate within a much broader wavelength range, are mechanical stable to resist human touch or contamination, show a 44% higher laser-induced damage threshold, and are suitable for bended interfaces such as microlenses as well.

Combination therapy for multidrug-resistant cytomegalovirus disease.

Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches.

Comparative analysis of assays for detection of cell-mediated immunity toward cytomegalovirus and M. tuberculosis in samples from deceased organ donors.

Cell-mediated immunity assays could be valuable for risk assessment of organ donors, but no data exist on their feasibility in deceased donors. In this study, 105 deceased donors (52.3 ± 16.9 years) were screened at the time of organ procurement. Pathogen-specific stimulation was performed using a cytomegalovirus (CMV) lysate, tuberculin (purified protein derivative [PPD]) and soluble Mycobacterium tuberculosis-specific ESAT-6/CFP-10 proteins in combination with an in-house fluorescence-activated cell sorting (FACS) assay or commercial assay formats (QuantiFERON-CMV/TB for ELISA, T-SPOT.TB for ELISPOT). CMV-IgG antibody titers were determined as gold standard for CMV infection; 51.4% of samples were CMV seropositive. Indeterminate results were observed in 47.6% of ELISA, 12.5% of FACS and 0% of ELISPOT assays. Agreement with serology was highest for FACS (95.6%, κ = 0.91), followed by ELISPOT (84.0%, κ = 0.68) and ELISA (80.0%, κ = 0.60). Agreement between ELISA and serology increased if the CMV lysate was used as stimulus (96.7%, κ = 0.92). Among the T cell assays, agreement between ELISPOT and FACS was highest (κ = 0.70). PPD-positive results among valid samples differed between assays (26.5% for ELISA, 23.1% for FACS and 50.5% for ELISPOT); 2.0% were QuantiFERON-TB positive, 3.3% were ESAT-6/CFP-10-positive in FACS and 13.4% were positive in the T-SPOT.TB assay. In conclusion, cellular immunity may be analyzed from samples of deceased donors, although the assays differ in the rate of positivity and indeterminate results.

BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication.

BK polyomavirus (BKPyV) infection is widespread and typically asymptomatic during childhood, but may cause nephropathy in kidney transplant recipients. However, there is only limited knowledge on BKPyV-specific immunity in children and adults, and its role in BKPyV-replication and disease posttransplant. We therefore characterized BKPyV-specific immunity from 122 immunocompetent individuals (1-84 years), 38 adult kidney recipients with (n = 14) and without BKPyV-associated complications (n = 24), and 25 hemodialysis (HD) patients. Blood samples were stimulated with overlapping peptides of BKPyV large-T antigen and VP1 followed by flow-cytometric analysis of activated CD4 T cells expressing interferon-γ, IL-2 and tumor necrosis factor-α. Antibody-levels were determined using enzyme-linked immunosorbent assay. Both BKPyV-IgG levels and BKPyV-specific CD4 T cell frequencies were age-dependent (p = 0.0059) with maximum levels between 20 and 30 years (0.042%, interquartile range 0.05%). Transplant recipients showed a significantly higher BKPyV-specific T cell prevalence (57.9%) compared to age-matched controls (21.7%) or HD patients (28%, p = 0.017). Clinically relevant BKPyV-replication was associated with elevated frequencies of BKPyV-specific T cells (p = 0.0002), but decreased percentage of cells expressing multiple cytokines (p = 0.009). In conclusion, BKPyV-specific cellular immunity reflects phases of active BKPyV-replication either after primary infection in childhood or during reactivation after transplantation. Combined analysis of BKPyV-specific T cell functionality and viral loads may improve individual risk assessment.

Analysis of two sequential SARS-CoV-2 outbreaks on a haematology-oncology ward and the role of infection prevention.

Two SARS-CoV-2 nosocomial outbreaks occurred on the haematology ward of our hospital. Patients on the ward were at high risk for severe infection because of their immunocompromised status. Whole Genome Sequencing proved transmission of a particular SARS-CoV-2 variant in each outbreak. The first outbreak (20 patients/31 healthcare workers (HCW)) occurred in November 2020 and was caused by a variant belonging to lineage B.1.221. At that time, there were still uncertainties on mode of transmission of SARS-CoV-2, and vaccines nor therapy were available. Despite HCW wearing II-R masks in all patient contacts and FFP-2 masks during aerosol generating procedures (AGP), the outbreak continued. Therefore, extra measures were introduced. Firstly, regular PCR-screening of asymptomatic patients and HCW; positive patients were isolated and positive HCW were excluded from work as a rule and they were only allowed to resume their work if a follow-up PCR CT-value was ≥30 and were asymptomatic or having only mild symptoms. Secondly, the use of FFP-2 masks was expanded to some long-lasting, close-contact, non-AGPs. After implementing these measures, the incidence of new cases declined gradually. Thirty-seven percent of patients died due to COVID-19. The second outbreak (10 patients/2 HCW) was caused by the highly transmissible omicron BA.1 variant and occurred in February 2022, where transmission occurred on shared rooms despite the extra infection control measures. It was controlled much faster, and the clinical impact was low as the majority of patients was vaccinated; no patients died and symptoms were relatively mild in both patients and HCW.

PD-1 analysis on CD28(-) CD27(-) CD4 T cells allows stimulation-independent assessment of CMV viremic episodes in transplant recipients.

Expression of the inhibitory receptor programmed death 1 (PD-1) on cytomegalovirus (CMV)-specific CD4 T cells defines a phenotype associated with CMV viremia in transplant recipients. Moreover, CD28(-) CD27(-) double negativity is known as a typical phenotype of CMV-specific CD4 T cells. Therefore, the co-expression of inhibitory receptors on CD28(-) CD27(-) CD4 T cells was assessed as a rapid, stimulation-independent parameter for monitoring CMV complications after transplantation. Ninety-three controls, 67 hemodialysis patients and 81 renal transplant recipients were recruited in a cross-sectional and longitudinal manner. CMV-specific CD4 T cell levels quantified after stimulation were compared to levels of CD28(-) CD27(-) CD4 T cells. PD-1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression on CD28(-) CD27(-) CD4 T cells were related to viremia. A percentage of ≥0.44% CD28(-) CD27(-) CD4 T cells defined CMV seropositivity (93.3% sensitivity, 97.1% specificity), and their frequencies correlated strongly with CMV-specific CD4 T cell levels after stimulation (r = 0.73, p < 0.0001). Highest PD-1 expression levels on CD28(-) CD27(-) CD4 T cells were observed in patients with primary CMV viremia and reactivation (p < 0.0001), whereas CTLA-4 expression was only elevated during primary CMV viremia (p < 0.05). Longitudinal analysis showed a significant increase in PD-1 expression in relation to viremia (p < 0.001), whereas changes in nonviremic patients were nonsignificant. In conclusion, increased PD-1 expression on CD28(-) CD27(-) CD4 T cells correlates with CMV viremia in transplant recipients and may serve as a specific, stimulation-independent parameter to guide duration of antiviral therapy.

Blockade of programmed death receptor-1 signaling restores expression of mostly proinflammatory cytokines in anergic cytomegalovirus-specific T cells.

BACKGROUND: Programmed death receptor-1 (PD-1) compromises cytomegalovirus (CMV)-specific T-cell responses and has been linked to CMV viremia after transplantation. An impaired functional and proliferative capacity of PD-1-positive CMV-specific T cells may be reversed by the antibody-mediated blockade of PD-1 signaling. However, knowledge is limited on changes in "cytokinome" expression profiles associated with reversal of functional exhaustion. METHODS: The "cytokinome" was analyzed by 27-plex Luminex technology comparing renal transplant recipients with low (n = 5) and high (n = 5) PD-1 expression on CMV-specific T cells. The effect of blocking PD-1 by PD-ligand (PD-L) antibodies on restoration of cytokine expression was examined. RESULTS: CMV-specific cytokine release and proliferation was lower in patients with high PD-1 expression on CMV-specific T cells. Antibody-mediated blockade of PD-L in CMV-stimulated samples restored expression levels of interleukin (IL)-1ß, IL-2, IL-6, IL-9, IL-10, granulocyte colony-stimulating factor, interferon-γ, macrophage inflammatory protein-1α, and tumor necrosis factor-α. By contrast, no profound effect was observed for controls or patients with low PD-1 expression, or in staphylococcal enterotoxin B-stimulated cells. CONCLUSION: Taken together, this pilot study provides evidence that a high PD-1 expression on CMV-specific T cells actively impairs proliferation and "cytokinome" responses in an antigen-specific manner. Importantly, blockade of PD-L restores CMV-specific T-cell proliferation and expression of a panel of different proinflammatory and/or type 1 cytokines, suggesting a common but as yet unknown regulatory principle. We conclude that PD-1 exhaustion is reversible and potentially amenable to therapeutic ex vivo and possibly in vivo manipulation. However, detailed knowledge of the differential effects on the "cytokinome" will be necessary to increase the safety and the efficacy of such manipulations.

Chlamydia trachomatis intra-bacterial and total plasmid copy number in clinical urogenital samples.

Chlamydia trachomatis (CT) increases its plasmid numbers when stressed, as occurs in clinical trachoma samples. Most CT tests target the plasmid to increase the test sensitivity, but some only target the chromosome. We investigated clinical urogenital samples for total plasmid copy numbers to assess its diagnostic value and intra-bacterial plasmid copy numbers to assess its natural variation. Both plasmid and chromosome copies were quantified using qPCR, and the plasmid:chromosome ratio (PCr) calculated in two cohorts: (1) 383 urogenital samples for the total PCR (tPCr), and (2) 42 vaginal swabs, with one half treated with propium-monoazide (PMA) to prevent the quantification of extracellular DNA and the other half untreated to allow for both tPCr and intra-bacterial PCr (iPCr) quantification. Mann-Whitney U tests compared PCr between samples, in relation to age and gender. Cohort 1: tPCr varied greatly (1-677, median 16). Median tPCr was significantly higher in urines than vaginal swabs (32 vs. 11, p < 0.001). Cohort 2: iPCr was more stable than tPCr (range 0.1-3 vs. 1-11). To conclude, tPCr in urogenital samples was much more variable than previously described. Transport time and temperature influences DNA degradation, impacting chromosomal DNA more than plasmids and urine more than vaginal samples. Data supports a plasmid target in CT screening assays to increase clinical sensitivity.

PD-1 expression and IL-2 loss of cytomegalovirus- specific T cells correlates with viremia and reversible functional anergy.

Cytomegalovirus (CMV) represents a major cause of infectious complications after transplantation. Recently, chronic infections with lymphocyte choriomeningitis virus (LCMV), HIV or HCV were shown to be associated with functionally exhausted T cells characterized by high expression of the programmed death (PD)-1 molecule and altered cytokine expression patterns. We therefore hypothesized that functional exhaustion of CMV-specific CD4 T cells may determine impaired CMV control in patients after renal transplantation. In viremic transplant recipients, a significantly higher proportion of CMV-specific CD4 T cells was PD-1 positive (median 40.9%, 17.0-88.7%) as compared to nonviremic transplant patients (8.8%, 0.8-80.5%), dialysis patients (8.8%, 0-36.7%) or controls (3.2%, 0.3-15.4%, p < 0.0001). In line with functional impairment, PD-1-positive T cells produced significantly less IFNgamma as compared to PD-1-negative T cells (p < 0.0001). Moreover, unlike controls or nonviremic patients, CMV-specific T cells from viremic patients showed a significant loss of IL-2 production (p < 0.0001). Interestingly, functional anergy of CMV-specific CD4 T cells was reversible in that antibody-mediated blockade of PD-1 signaling with its ligands PD-L1/-L2 led to an up to 10-fold increase in CMV-specific proliferation. In conclusion, expression of PD-1 defines a reversible defect of CMV-specific CD4 T cells that is associated with viremia, and blocking PD-1 signaling may provide a potential target for enhancing the function of exhausted T cells in chronic CMV infection.

Both stiff and compliant: morphological and biomechanical adaptations of stick insect antennae for tactile exploration.

Active tactile exploration behaviour is constrained to a large extent by the morphological and biomechanical properties of the animal's somatosensory system. In the model organism Carausius morosus, the main tactile sensory organs are long, thin, seemingly delicate, but very robust antennae. Previous studies have shown that these antennae are compliant under contact, yet stiff enough to maintain a straight shape during active exploration. Overcritical damping of the flagellum, on the other hand, allows for a rapid return to the straight shape after release of contact. Which roles do the morphological and biomechanical adaptations of the flagellum play in determining these special mechanical properties? To investigate this question, we used a combination of biomechanical experiments and numerical modelling. A set of four finite-element (FE) model variants was derived to investigate the effect of the distinct geometrical and material properties of the flagellum on its static (bending) and dynamic (damping) characteristics. The results of our numerical simulations show that the tapered shape of the flagellum had the strongest influence on its static biomechanical behaviour. The annulated structure and thickness gradient affected the deformability of the flagellum to a lesser degree. The inner endocuticle layer of the flagellum was confirmed to be essential for explaining the strongly damped return behaviour of the antenna. By highlighting the significance of two out of the four main structural features of the insect flagellum, our study provides a basis for mechanical design of biomimetic touch sensors tuned to become maximally flexible while quickly resuming a straight shape after contact.

Micropuncture study of hypertonic mannitol diuresis in the proximal and distal tubule of the dog kidney.

Fractional reabsorption of water, sodium, and potassium at proximal and distal tubular sites within the nephron was studied by recollection-micropuncture experiments on dogs undergoing hypertonic mannitol diuresis. After an initial control hydropenic phase, 16% mannitol in modified Ringer's solution was administered intravenously, resulting in marked increases in fractional excretion of water (28.7%), sodium (12.6%), and potassium (63.9%). Inulin clearance decreased significantly from 35.1 to 25.2 ml/min. Analysis of paired micropuncture data revealed a significant decrease in tubule fluid to plasma (TF:P) inulin ratios in both the proximal tubule (1.63-1.45) and distal tubule (5.38-1.94). There was also a significant decrease in proximal TF:P sodium ratios (0.99-0.93) and potassium ratios (1.05-0.98). Distal TF:P sodium ratios, in contrast, rose significantly (0.38-0.59), while TF:P potassium ratios tended towards unity whether initially greater or less than one. Fractional reabsorption of sodium and water decreased by 5% and 10% respectively in the proximal tubule, but to a lesser extent than the resulting increases in fractional urinary excretion. The nonreabsorbed fraction, however, had increased sharply at the point of distal puncture for water (32%), sodium (26%), and potassium (26%), indicating a large inhibitory effect within the loop of Henle in addition to the smaller proximal effects.

Micropuncture study of diuretic effects on sodium and calcium reabsorption in the dog nephron.

A close relationship has been observed between the clearance rates of sodium and calcium under a variety of diuretic conditions. The thiazide diuretics act differently in dissociating the renal tubular reabsorption of sodium and calcium. This phenomenon has been further investigated using recollection micropuncture and clearance techniques in a group of 14 dogs subjected to three consecutive experimental phases: expansion to 3% of body weight (BWt) with Ringer's solution, chlorothiazide infusion at 20 mg/kg/h, and furosemide in a prime of 10 mg/kg/ and a 10 mg/kg/h infusion. Diuretic losses were balanced with infusion of equal volumes of Ringer's solution throughout the experiment. Chlorothiazide increased the fractional excretion (FE) of sodium almost threefold while FE(Ca) was not significantly altered. Furosemide increased FE(Na) and FE(Ca) to an approximately equal, and more marked, degree. This dissociation of sodium and calcium reabsorption after chlorothiazide was also evident in the superficial distal tubule, where (tubule fluid/plasma sodium) (TF/P(Na)) increased from 0.32 to 0.49 (P < 0.01) and TF/(ultrafiltrate)UF(Ca) was unchanged (0.35-0.31). Furosemide markedly reduced the transtubular concentration gradient for both sodium (0.86) and calcium (0.94). TF/P(Inul in) decreased progressively from 3.79 to 2.78 to 2.33 in three phases. In the late proximal tubule, chlorothiazide induced a fall of TF/P(Inul in) from 1.57 to 1.44 (P < 0.01), but the ratio TF/UF(Ca): TF/P(Na) was unchanged. Furosemide had no significant proximal effect. It is concluded that acute administration of chlorothiazide reduces sodium reabsorption in the distal hephron, presumably the cortical diluting segment, without affecting calcium reabsorption.

Effect of magnesium deficiency on renal magnesium and calcium transport in the rat.

Recollection of micropuncture experiments were performed on acutely thyroparathyroidectomized rats rendered magnesium deficient by dietary deprivation. Urinary magnesium excretion fell from a control of 15 to 3% of the filtered load after magnesium restriction. The loop of Henle, presumably the thick ascending limb, was the major modulator for renal magnesium homeostasis. The transport capacity for magnesium, however, was less in deficient rats than control animals. Absolute magnesium reabsorption increased with acute infusions of magnesium chloride but was always less in magnesium-deficient rats than control rats for any given filtered load, which suggests either a defect of a resetting of the reabsorption mechanism. Recollection micropuncture demonstrated that this was a characteristic of the loop of Henle. Proximal magnesium reabsorption remained unchanged at 15% of the filtered load and was unaffected by magnesium deficiency or acute magnesium repletion. Distal tubular magnesium reabsorption was limited during depletion and increased to a similar extent in control and deficient rats with enhanced magnesium delivery. Calcium reabsorption was not altered in magnesium deficiency; however, elevations of extracellular magnesium resulted in a specific inhibition of calcium reabsorption within the loop of Henle. These data suggest that overall control of renal magnesium reabsorption occurs within the loop of Henle and that the proximal tubule reabsorbs a constant fraction of the filtered load despite variations in body magnesium status.

Micropuncture studies of sodium transport in the remnant kidney of the dog. The effect of graded volume expansion.

Proximal and distal tubule micropuncture studies were performed to examine the response to graded extracellular volume (ECV) expansion in 10 normal dogs (stage I), 11 dogs with a unilateral remnant kidney (stage II), and 7 dogs with a remnant kidney after removal of the contralateral kidney (stage III). Before ECV expansion in stage III, there was a suggestive reduction in proximal tubule as well as loop fractional reabsorption of sodium. After ECV expansion to 3% body weight proximal tubule reabsorption was depressed in all groups of animals, while little further inhibition was observed in this segment with additional expansion to 10% body weight. In contrast, the fraction of filtered sodium remaining in the distal tubule rose progressively in all three groups after graded ECV expansion, suggesting that the graded natriuretic response found in the final urine was largely due to a similar response in the loop of Henle rather than that in the proximal tubule. The distal tubule response of the remnant kidney in both stages II and III was greater than that in stage I. These data indicate that although enhanced sodium excretion per nephron in chronic renal failure may be related to uremia, its exaggerated response to ECV expansion is due, at least in part, to certain as yet unidentified intrarenal factors consequent to reduction in functioning renal mass.

Stiffness distribution in insect cuticle: a continuous or a discontinuous profile?

Insect cuticle is a biological composite with a high degree of complexity in terms of both architecture and material composition. Given the complex morphology of many insect body parts, finite-element (FE) models play an important role in the analysis and interpretation of biomechanical measurements, taken by either macroscopic or nanoscopic techniques. Many previous studies show that the interpretation of nanoindentation measurements of this layered composite material is very challenging. To develop accurate FE models, it is of particular interest to understand more about the variations in the stiffness through the thickness of the cuticle. Considering the difficulties of making direct measurements, in this study, we use the FE method to analyse previously published data and address this issue numerically. For this purpose, sets of continuous or discontinuous stiffness profiles through the thickness of the cuticle were mathematically described. The obtained profiles were assigned to models developed based on the cuticle of three insect species with different geometries and layer configurations. The models were then used to simulate the mechanical behaviour of insect cuticles subjected to nanoindentation experiments. Our results show that FE models with discontinuous exponential stiffness gradients along their thickness were able to predict the stress and deformation states in insect cuticle very well. Our results further suggest that, for more accurate measurements and interpretation of nanoindentation test data, the ratio of the indentation depth to cuticle thickness should be limited to 7% rather than the traditional '10% rule'. The results of this study thus might be useful to provide a deeper insight into the biomechanical consequences of the distinct material distribution in insect cuticle and also to form a basis for more realistic modelling of this complex natural composite.

Wing cross veins: an efficient biomechanical strategy to mitigate fatigue failure of insect cuticle.

Locust wings are able to sustain millions of cycles of mechanical loading during the lifetime of the insect. Previous studies have shown that cross veins play an important role in delaying crack propagation in the wings. Do cross veins thus also influence the fatigue behaviour of the wings? Since many important fatigue parameters are not experimentally accessible in a small biological sample, here we use the finite element (FE) method to address this question numerically. Our FE model combines a linear elastic material model, a direct cyclic approach and the Paris law and shows results which are in very good agreement with previously reported experimental data. The obtained results of our study show that cross veins indeed enhance the durability of the wings by temporarily stopping cracks. The cross veins further distribute the stress over a larger area and therefore minimize stress concentrations. In addition, our work indicates that locust hind wings have an endurance limit of about 40% of the ultimate tensile strength of the wing material, which is comparable to many engineering materials. The comparison of the results of the computational study with predictions of two most commonly used fatigue failure criteria further indicates that the Goodman criterion can be used to roughly predict the failure of the insect wing. The methodological framework presented in our study could provide a basis for future research on fatigue of insect cuticle and other biological composite structures.

Effect of hyperbaric oxygen on the cytotoxicity of adriamycin and nitrogen mustard in cultured Burkitt's lymphoma cells.

The effects of hyperbaric oxygen (HPO) exposure on the cytotoxicity of Adriamycin (ADM) and nitrogen mustard have been examined in Burkitt's lymphoma cells (P3J) in vitro. Exposure of cells to 3 atmospheres of pressure HPO for 2 hr produces inhibition of DNA synthesis and mitosis. Simultaneous exposure to HPO and ADM results in decreased cytotoxicity compared to drug treatment alone. However, exposure to ADM (0.15 microgram/ml) 2 to 8 hr before or after HPO produces an increase in drug effect. There is no potentiation of lower ADM concentrations. Cytotoxicity is increased when cells are exposed to HPO during, before, or after exposure to nitrogen mustard (NSC 762) (0.15 and 0.25 microgram/ml). Lower nitrogen mustard (NSC 762) concentrations are not potentiated. HPO potentiation of antineoplastic agents appears to depend upon the agent studied, the concentration of the agent, and the scheduling of the drug and HPO exposure.

Effect of microstructure on the mechanical and damping behaviour of dragonfly wing veins.

Insect wing veins are biological composites of chitin and protein arranged in a complex lamellar configuration. Although these hierarchical structures are found in many 'venous wings' of insects, very little is known about their physical and mechanical characteristics. For the first time, we carried out a systematic comparative study to gain a better understanding of the influence of microstructure on the mechanical characteristics and damping behaviour of the veins. Morphological data have been used to develop a series of three-dimensional numerical models with different material properties and geometries. Finite-element analysis has been employed to simulate the mechanical response of the models under different loading conditions. The modelling strategy used in this study enabled us to determine the effects selectively induced by resilin, friction between layers, shape of the cross section, material composition and layered structure on the stiffness and damping characteristics of wing veins. Numerical simulations suggest that although the presence of the resilin-dominated endocuticle layer results in a much higher flexibility of wing veins, the dumbbell-shaped cross section increases their bending rigidity. Our study further shows that the rubber-like cuticle, friction between layers and material gradient-based design contribute to the higher damping capacity of veins. The results of this study can serve as a reference for the design of novel bioinspired composite structures.