On the origins of fatigue strength in crystalline metallic materials.

Metallic materials experience irreversible deformation with increasing applied stress, manifested in localized slip events that result in fatigue failure upon repeated cycling. We discerned the physical origins of fatigue strength in a large set of face-centered cubic, hexagonal close-packed, and body-centered cubic metallic materials by considering cyclic deformation processes at nanometer resolution over large volumes of individual materials at the earliest stages of cycling. We identified quantitative relations between the yield strength and the ultimate tensile strength, fatigue strength, and physical characteristics of early slip localization events. The fatigue strength of metallic alloys that deform by slip could be predicted by the amplitude of slip localization during the first cycle of loading. Our observations provide a physical basis for well-known empirical fatigue laws and enable a rapid method of predicting fatigue strength as reflected by measurement of slip localization amplitude.

Multi-modal Dataset of a Polycrystalline Metallic Material: 3D Microstructure and Deformation Fields.

The development of high-fidelity mechanical property prediction models for the design of polycrystalline materials relies on large volumes of microstructural feature data. Concurrently, at these same scales, the deformation fields that develop during mechanical loading can be highly heterogeneous. Spatially correlated measurements of 3D microstructure and the ensuing deformation fields at the micro-scale would provide highly valuable insight into the relationship between microstructure and macroscopic mechanical response. They would also provide direct validation for numerical simulations that can guide and speed up the design of new materials and microstructures. However, to date, such data have been rare. Here, a one-of-a-kind, multi-modal dataset is presented that combines recent state-of-the-art experimental developments in 3D tomography and high-resolution deformation field measurements.

The origin and stability of nanostructural hierarchy in crystalline solids.

The structural hierarchy exhibited by materials on more than one length scale can play a major part in determining bulk material properties. Understanding the hierarchical structure can lead to new materials with physical properties tailored for specific applications. We have used a combined experimental and phase-field modeling approach to explore such a hierarchical structure at nanoscale for enhanced coarsening resistance of ordered γ' precipitates in an experimental, multicomponent, high-refractory nickel-base superalloy. The hierarchical microstructure formed experimentally in this alloy is composed of a γ matrix with γ' precipitates that contain embedded, spherical γ precipitates, which do not directionally coarsen during high-temperature annealing but do delay coarsening of the larger γ' precipitates. Chemical mapping via atom probe tomography suggests that the supersaturation of Co, Ru, and Re in the γ' phase is the driving force for the phase separation, leading to the formation of this hierarchical microstructure. Representative phase-field modeling highlights the importance of larger γ' precipitates to promote stability of the embedded γ phase and to delay coarsening of the encompassing γ' precipitates. Our results suggest that the hierarchical material design has the potential to influence the high-temperature stability of precipitate strengthened metallic materials.

Forward models for extending the mechanical damage evaluation capability of resonant ultrasound spectroscopy.

Finite element (FE) modeling has been coupled with resonant ultrasound spectroscopy (RUS) for nondestructive evaluation (NDE) of high temperature damage induced by mechanical loading. Forward FE models predict mode-specific changes in resonance frequencies (ΔfR), inform RUS measurements of mode-type, and identify diagnostic resonance modes sensitive to individual or multiple concurrent damage mechanisms. The magnitude of modeled ΔfR correlate very well with the magnitude of measured ΔfR from RUS, affording quantitative assessments of damage. This approach was employed to study creep damage in a polycrystalline Ni-based superalloy (Mar-M247) at 950°C. After iterative applications of creep strains up to 8.8%, RUS measurements recorded ΔfR that correspond to the accumulation of plastic deformation and cracks in the gauge section of a cylindrical dog-bone specimen. Of the first 50 resonance modes that occur, ranging from 3 to 220kHz, modes classified as longitudinal bending were most sensitive to creep damage while transverse bending modes were found to be largely unaffected. Measure to model comparisons of ΔfR show that the deformation experienced by the specimen during creep, specifically uniform elongation of the gauge section, is responsible for a majority of the measured ΔfR until at least 6.1% creep strain. After 8.8% strain considerable surface cracking along the gauge section of the dog-bone was observed, for which FE models indicate low-frequency longitudinal bending modes are significantly affected. Key differences between historical implementations of RUS for NDE and the FE model-based framework developed herein are discussed, with attention to general implementation of a FE model-based framework for NDE of damage.

Retinopathy of prematurity in a cohort of neonates at Groote Schuur Hospital, Cape Town, South Africa.

BACKGROUND: Severe retinopathy of prematurity (ROP) can cause blindness. Before 2016, resource limitations precluded routine screening for ROP at Groote Schuur Hospital (GSH), Cape Town, South Africa. Previous pilot studies at GSH found no patients with ROP requiring treatment; however, improved preterm infant survival may affect the prevalence. OBJECTIVES: To determine the prevalence and severity of ROP, describe potential risk factors, and assess the feasibility of ROP screening. METHODS: Infants with a birth weight (BW) of <1 251 g or a gestational age (GA) of ≤31 weeks were screened from November 2012 to May 2013. RESULTS: Three hundred and thirteen ROP examinations were performed in 135 of 191 eligible infants. The mean GA and BW were 30.1 weeks (standard deviation (SD) 1.9) and 1 056 g (SD 172), respectively. ROP was diagnosed in 40 infants (29.6%); 8 (5.9%) had severe ROP and 2 (1.5%) received laser treatment. Infants with ROP had a lower mean GA (29.2 weeks (SD 1.6) v. 30.5 weeks (SD 1.9)) (p<0.002) and a lower mean BW (988 g (SD 181) v. 1 085 g (SD 160)) (p=0.001) than those without ROP. Infants weighing <1 000 g had a 2.5 times higher risk than those with a BW of ≥1 000 g of having ROP (95% confidence interval 1.05 - 5.90; p=0.03). Blood transfusions (p<0.002) and late-onset sepsis (p=0.024) were strongly associated with ROP. Screening was completed in 91.1% (123/135) of the infants. CONCLUSIONS: The prevalence and severity of ROP have increased at GSH. The strong association between ROP, BW and GA suggests that infants with lower BWs and GAs should be prioritised for screening in our resource-limited setting.

Adjunctive use of intravitreal dexamethasone in presumed bacterial endophthalmitis: a randomised trial.

AIM: To evaluate the use of intravitreal dexamethasone as adjunctive therapy in the treatment of presumed bacterial endophthalmitis. Design Prospective, double masked, randomised placebo-controlled clinical trial. METHODS: Patients with 'post cataract surgery', 'bleb-related' and 'other' endophthalmitis were grouped and randomised to receive intravitreal ceftazidime (2.225 mg/0.1 ml), vancomycin (1 mg/0.1 ml), and either dexamethasone (0.4 mg/0.1) or placebo. All underwent vitreous and aqueous sampling for microbiological analysis. Injections were repeated after 48 h if necessary. The primary outcome measure was Snellen visual acuity on presentation, within the first 14 days post injection, and at 2-4 months. RESULTS: 62 patients completed the protocol from 2001 to 2005. Thirty patients received intravitreal dexamethasone and 32 received intravitreal placebo. There was no statistically significant difference in the visual outcomes of either group with a mean 2.79 Snellen lines improvement of the intravitreal dexamethasone group versus 1.8 lines in the placebo group. Subgroup analysis suggested a clinical trend to better visual acuity in the post cataract steroid subgroup with mean 4.1 lines improvement versus 2.7 in the placebo group (p=0.33). No adverse events attributable to the dexamethasone were reported. CONCLUSIONS: Intravitreal dexamethasone appears safe and may be of benefit in post cataract surgery bacterial endophthalmitis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic.

BACKGROUND: Renal colic is a common cause of acute severe pain. Both opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for treatment, but the relative efficacy of these drugs is uncertain. OBJECTIVES: To examine the benefits and disadvantages of NSAIDs and opioids for the management of pain in acute renal colic. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register (May 2003), the Cochrane Central Register of Randomised Controlled Trials (CENTRAL - The Cochrane Library issue 2, 2003), MEDLINE (1966 - 31 January 2003), EMBASE (1980 - 31 January 2003) and handsearched reference lists of retrieved articles. Most recent search date: January 2005 SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any opioid with any NSAID, regardless of dose or route of administration were included. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. Subgroup analysis by study quality, drug type and drug route have been performed where possible to explore reasons for heterogeneity. MAIN RESULTS: Twenty trials from nine countries with a total of 1613 participants were identified. Both NSAIDs and opioids lead to clinically significant falls in patient-reported pain scores. Due to unexplained heterogeneity these results could not be pooled although 10/13 studies reported lower pain scores in patients receiving NSAIDs. Patients treated with NSAIDs were significantly less likely to require rescue medication (RR 0.75, 95% CI 0.61 to 0.93, P = 0.007), though most of these trials used pethidine. The majority of trials showed a higher incidence of adverse events in patients treated with opioids, but there was significant heterogeneity between studies so the results could not be pooled. There was significantly less vomiting in patients treated with NSAIDs (RR 0.35, 95% CI 0.23 to 0.53, P < 0.00001). In particular, patients receiving pethidine had a much higher rate of vomiting compared with patients receiving NSAIDs. Gastrointestinal bleeding and renal impairment were not reported. AUTHORS' CONCLUSIONS: Both NSAIDs and opioids can provide effective analgesia in acute renal colic. Opioids are associated with a higher incidence of adverse events, particularly vomiting. Given the high rate of vomiting associated with the use of opioids, particularly pethidine, and the greater likelihood of requiring further analgesia, we recommend that if an opioid is to be used it should not be pethidine.

Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic.

BACKGROUND: Renal colic is a common cause of acute severe pain. Both opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for treatment, but the relative efficacy of these drugs is uncertain. OBJECTIVES: To examine the benefits and disadvantages of NSAIDs and opioids for the management of pain in acute renal colic. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register (May 2003), the Cochrane Central Register of Randomised Controlled Trials (CENTRAL - The Cochrane Library issue 2, 2003), MEDLINE (1966 - 31 January 2003), EMBASE (1980 - 31 January 2003) and handsearched reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any opioid with any NSAID, regardless of dose or route of administration were included. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. Subgroup analysis by study quality, drug type and drug route have been performed where possible to explore reasons for heterogeneity. MAIN RESULTS: Twenty trials from nine countries with a total of 1613 participants were identified. Both NSAIDs and opioids lead to clinically significant falls in patient-reported pain scores. Due to unexplained heterogeneity these results could not be pooled although 10/13 studies reported lower pain scores in patients receiving NSAIDs. Patients treated with NSAIDs were significantly less likely to require rescue medication (RR 0.75, 95% CI 0.61 to 0.93, P = 0.007), though most of these trials used pethidine. The majority of trials showed a higher incidence of adverse events in patients treated with opioids, but there was significant heterogeneity between studies so the results could not be pooled. There was significantly less vomiting in patients treated with NSAIDs (RR 0.35, 95% CI 0.23 to 0.53, P < 0.00001). In particular, patients receiving pethidine had a much higher rate of vomiting compared with patients receiving NSAIDs. Gastrointestinal bleeding and renal impairment were not reported. REVIEWER'S CONCLUSIONS: Both NSAIDs and opioids can provide effective analgesia in acute renal colic. Opioids are associated with a higher incidence of adverse events, particularly vomiting. Given the high rate of vomiting associated with the use of opioids, particularly pethidine, and the greater likelihood of requiring further analgesia, we recommend that if an opioid is to be used it should not be pethidine.

NLite laser: nonablative wrinkle reduction.

The NLite laser is promoted as a tool for painless wrinkle reduction without side effects, posttreatment care, "downtime," or complications. However, with only 1 published study, limited scientific data are available. The authors report generally disappointing clinical results based on personal experience and a survey of 8 physicians who were among the first in Dallas to incorporate NLite technology into their practices. (Aesthetic Surg J 2001;21:371-372.).

Progressive tension sutures: a technique to reduce local complications in abdominoplasty.

Abdominoplasty has evolved as a very effective and satisfactory procedure, especially when combined with liposuction and the repair of diastasis recti. However, local complications, including hematoma and seroma formation, flap necrosis, and hypertrophic scars, continue to plague this procedure. The authors present a relatively simple and reproducible technique that allows extensive liposuction in conjunction with abdominoplasty; they think this technique reduces the incidence of local complications. This technique, the use of progressive tension sutures, has been used in their practice for more than 15 years. A retrospective review of 65 consecutive abdominoplasty patients demonstrates a very low local complication rate when compared with historical controls. In this series of both full and modified abdominoplasty patients who were followed for an average of 18 months, the authors had no hematomas, seromas, or skin flap necrosis.

Feasibility trial of postoperative radiotherapy and cisplatin followed by three courses of 5-FU and cisplatin in patients with resected head and neck cancer: a Southwest Oncology Group study.

BACKGROUND: Appropriate adjuvant chemotherapy for resected head and neck cancer patients has yet to be defined. Multiple trials have noted trends toward improved disease-free survival and local control. The Southwest Oncology Group undertook a feasibility trial of postoperative cisplatin and radiotherapy followed by three cycles of cisplatin and 5-fluorouracil. METHODS: Patients with resected stage III or IV head and neck cancer received cisplatin, 100 mg/m2, on days 1, 22, and 43 of radiotherapy. This therapy was followed by three cycles of cisplatin, 100 mg/m2 or last tolerated dose, and 5-fluorouracil, 1000 mg/m2, on days 1 to 4 every 21 days. RESULTS: Seventy-two patients from 22 institutions were registered; 68 were evaluable. Sixty-eight patients received radiotherapy. Only 25 of 68 patients (36.7%) were able to complete all six cycles of chemotherapy. Forty-three of 68 patients (63%) completed all three cycles with radiotherapy. Toxicities were tolerable. One toxic death occurred. CONCLUSIONS: It is not feasible to deliver six cycles of chemotherapy postoperatively in the sequence described. Compliance issues need further exploration to define effective adjuvant chemotherapy for head and neck patients.

Planktonic/sessile dimorphism of polysaccharide-encapsulated sphingomonads.

Sphingomonads have acquired diverse metabolic activities to inhabit a wide range of environments. Several strains of Sphingomonas display phenotypic dimorphism and can adopt either a planktonic or sessile behavior in liquid media. The sessile state is marked by the presence of a viscous exopolysaccharide capsule. Specific types of these capsular polysaccharides are harvested from large-scale fermentations for use as rheology modifiers in many industrial and food applications. Sensing of environmental stimuli and genetic control over synthesis of the capsule are key events in alternating between these two phenotypes.

Assignment of biochemical functions to glycosyl transferase genes which are essential for biosynthesis of exopolysaccharides in Sphingomonas strain S88 and Rhizobium leguminosarum.

Glycosyl transferases which recognize identical substrates (nucleotide-sugars and lipid-linked carbohydrates) can substitute for one another in bacterial polysaccharide biosynthesis, even if the enzymes originate in different genera of bacteria. This substitution can be used to identify the substrate specificities of uncharacterized transferase genes. The spsK gene of Sphingomonas strain S88 and the pssDE genes of Rhizobium leguminosarum were identified as encoding glucuronosyl-(B1-->4)-glucosyl transferases based on reciprocal genetic complementation of mutations in the spsK gene and the pssDE genes by segments of cloned DNA and by the SpsK-dependent incorporation of radioactive glucose (Glc) and glucuronic acid (GlcA) into lipid-linked disaccharides in EDTA-permeabilized cells. By contrast, glycosyl transferases which form alternative sugar linkages to the same substrate caused inhibition of polysaccharide synthesis or were deleterious or lethal in a foreign host. The negative effects also suggested specific substrate requirements: we propose that spsL codes for a glucosyl-(beta1-->4)-glucuronosyl transferase in Sphingomonas and that pssC codes for a glucuronosyl-(beta1-->4)-glucuronosyl transferase in R. leguminosarum. Finally, the complementation results indicate the order of attachment of sphingan main-chain sugars to the C55-isoprenylphosphate carrier as -Glc-GlcA-Glc-isoprenylpyrophosphate.

Production of xanthan gum by Sphingomonas bacteria carrying genes from Xanthomonas campestris.

Twelve genes coding for assembly, acetylation, pyruvylation, polymerization, and secretion of the polysaccharide xanthan gum are clustered together on the chromosome of the bacterium Xanthomonas campestris. These genes (gumBCDEFGHIJKLM) are sufficient for synthesis of xanthan gum when placed in bacteria from a different genus, Sphingomonas. The polysaccharide from the recombinant microorganism is largely indistinguishable, structurally and functionally, from native xanthan gum. These results demonstrate that a complex pathway for biosynthesis of a specific polysaccharide can be acquired by a single inter-generic transfer of genes between bacteria. This suggests the biological and commercial feasibility of synthesizing xanthan gum or other polysaccharides in non-native hosts.

Linkage of genes essential for synthesis of a polysaccharide capsule in Sphingomonas strain S88.

Several structurally related capsular polysaccharides that are secreted by members of the genus Sphingomonas are being developed as aqueous rheological control agents for diverse industrial and food applications. They include gellan (S-60), welan (S-130), rhamsan (S-194), S-657, S-88, S-198, S-7, and NW-11. We refer to these polysaccharides as sphingans, after the genus name. This paper characterizes the first gene cluster isolated from a Sphingomonas species (S88) that is required for capsule synthesis. Overlapping DNA segments which spanned about 50 kbp of S88 DNA restored the synthesis of sphingan S-88 in capsule-negative mutants. The mutations were mapped into functional complementation groups, and the contiguous nucleotide sequence for the 29-kbp cluster was determined. The genetic complementation map and the DNA sequences were interpreted as an extended multicistronic locus containing genes essential for the assembly and secretion of polysaccharide S-88. Many of the deduced amino acid sequences were similar to gene products from other polysaccharide-secreting bacteria such as Rhizobium meliloti (succinoglycan), Xanthomonas campestris (xanthan gum), and Salmonella enterica (O antigen). The S88 locus contained a four-gene operon for the biosynthesis of dTDP-L-rhamnose, an essential precursor for the sphingans. Unexpectedly, there were also two genes for secretion of a lytic or toxin-like protein nested within the polysaccharide cluster. The conservation and linkage of genes that code for a defensive capsule and genes for secretion of an offensive lysin or toxin suggest a heretofore unknown pathogenic life history for Sphingomonas strain S88.

Mechanism of bacitracin resistance in gram-negative bacteria that synthesize exopolysaccharides.

Four representative species from three genera of gram-negative bacteria that secrete exopolysaccharides acquired resistance to the antibiotic bacitracin by stopping synthesis of the exopolysaccharide. Xanthomonas campestris, Sphingomonas strains S-88 and NW11, and Escherichia coli K-12 secrete xanthan gum, sphingans S-88 and NW11, and colanic acid, respectively. The gumD gene in X. campestris is required to attach glucose-P to C55-isoprenyl phosphate, the first step in the assembly of xanthan. A recombinant plasmid carrying the gumD gene of X. campestris restored polysaccharide synthesis to bacitracin-resistant exopolysaccharide-negative mutants of X. campestris and Sphingomonas strains. Similarly, a newly cloned gene (spsB) from strain S-88 restored xanthan synthesis to the same X. campestris mutants. However, the intergeneric complementation did not extend to mutants of E. coli that were both resistant to bacitracin and nonproducers of colanic acid. The genetic results also suggest mechanisms for assembling the sphingans which have commercial potential as gelling and viscosifying agents.

Sphinganase, a new endoglycanase that cleaves specific members of the gellan family of polysaccharides.

A sporeforming gram-positive aerobic bacterium was isolated from soil and shown to secrete an endoglycanase that cleaves the tetrasaccharide backbone structure of specific members within the gellan family of related bacterial exopolysaccharides. We refer to these polysaccharides as sphingans. The structures of the sphingans differ by the type and position of side groups that are attached to the backbone. The new enzyme named sphinganase degrades welan, gellan, deacylated gellan, and polysaccharides S-88, S-7, and S-198. However, the enzyme does not attack rhamsan or polysaccharide NW11. Methods for growing the bacteria, isolating the enzyme, and assaying sphinganase activity are presented, and uses for the enzyme are proposed.