Efficient production of a high-performance dispersion strengthened, multi-principal element alloy.

Additive manufacturing currently facilitates new avenues for materials discovery that have not been fully explored. In this study we reveal how additive manufacturing can be leveraged to produce dispersion strengthened (DS), multi-principal element alloys (MPEA) without the use of traditional mechanical alloying or chemical reactions. This new processing technique employed resonant acoustic mixing to coat an equiatomic NiCoCr powder with nano-scale yttrium oxides. Then, through laser powder bed fusion (L-PBF), the coated powder was successfully consolidated into 99.9% dense parts. Microstructural analysis confirmed the successful incorporation and dispersion of nano-scale oxides throughout the build volume. Furthermore, high temperature mechanical testing of the DS alloys showed significant improvements in strength and ductility over the baseline NiCoCr. As a result, this recently discovered processing route opens a new alloy design and production path that is synergistic between additive manufacturing and dispersion strengthening, possibly enabling a new generation of high-performance alloys.

Patient perspectives on Peyronie's disease: results of poststudy interviews from a phase 2 trial of collagenase clostridium histolyticum.

Intralesional injection of collagenase clostridium histolyticum (CCH) improves Peyronie's disease (PD) symptoms; however, patient perspectives regarding PD and CCH treatment have not been fully elucidated. This cross-sectional qualitative study included heterosexual men with PD who received ≥1 injection of study medication and had ≥1 posttreatment Peyronie's Disease Questionnaire (PDQ) assessment during a prior phase 2b clinical trial. These patients were "responders" if they reported (as part of the Global Assessment of the PDQ) that overall symptoms and effects of PD had at least "improved in a small but important way" after CCH therapy. Among 45 patients interviewed, penile bending or curvature was the most common and bothersome PD symptom reported (by 97.8% and 48.9% of patients, respectively). Patients indicated that multiple alterations were necessary in their sex lives because of penile symptoms and specified that these changes impacted their emotional health and partner relationship. Treatment with CCH improved PD symptoms (44.4%), frequency of or ability to have vaginal intercourse (22.2%) and partner relationship (22.2%), particularly among responders. Given that physical, psychologic and sexual function are impacted by PD, clinical trials that evaluate treatments for PD should include patient-reported outcome measures (e.g., the PDQ) to assess overall well-being after treatment.

An early modern human presence in Sumatra 73,000-63,000 years ago.

Genetic evidence for anatomically modern humans (AMH) out of Africa before 75 thousand years ago (ka) and in island southeast Asia (ISEA) before 60 ka (93-61 ka) predates accepted archaeological records of occupation in the region. Claims that AMH arrived in ISEA before 60 ka (ref. 4) have been supported only by equivocal or non-skeletal evidence. AMH evidence from this period is rare and lacks robust chronologies owing to a lack of direct dating applications, poor preservation and/or excavation strategies and questionable taxonomic identifications. Lida Ajer is a Sumatran Pleistocene cave with a rich rainforest fauna associated with fossil human teeth. The importance of the site is unclear owing to unsupported taxonomic identification of these fossils and uncertainties regarding the age of the deposit, therefore it is rarely considered in models of human dispersal. Here we reinvestigate Lida Ajer to identify the teeth confidently and establish a robust chronology using an integrated dating approach. Using enamel-dentine junction morphology, enamel thickness and comparative morphology, we show that the teeth are unequivocally AMH. Luminescence and uranium-series techniques applied to bone-bearing sediments and speleothems, and coupled uranium-series and electron spin resonance dating of mammalian teeth, place modern humans in Sumatra between 73 and 63 ka. This age is consistent with biostratigraphic estimations, palaeoclimate and sea-level reconstructions, and genetic evidence for a pre-60 ka arrival of AMH into ISEA. Lida Ajer represents, to our knowledge, the earliest evidence of rainforest occupation by AMH, and underscores the importance of reassessing the timing and environmental context of the dispersal of modern humans out of Africa.

On the origin of extraordinary cyclic strengthening of the austenitic stainless steel Sanicro 25 during fatigue at 700°C.

The origin of the extraordinary strengthening of the highly-alloyed austenitic stainless steel Sanicro 25 during cyclic loading at 700°C was investigated by use of advanced scanning transmission electron microscopy (STEM). Along with substantial change of dislocation structure, nucleation of two distinct populations of nanoparticles was revealed. Fully coherent Cu-rich nanoparticles were observed homogeneously dispersed with high density along with nanometer-sized incoherent NbC carbides precipitating on dislocations during cyclic loading. Probe-corrected HAADF STEM imaging was used to characterize the atomic structure of nanoparticles. Compositional analysis was conducted using both EELS and high spatial resolution EDS. High temperature exposure induced precipitation of a high density of coherent Cu-rich nanoparticles while strain-induced nucleation of incoherent NbC nanoparticles leads to retardation of dislocation movement. The pinning effects and associated obstacles to dislocation motion prevent recovery and formation of the localized low-energy cellular structures. As a consequence, the alloy exhibits remarkable cyclic hardening at elevated temperature.

Phase transformation strengthening of high-temperature superalloys.

Decades of research has been focused on improving the high-temperature properties of nickel-based superalloys, an essential class of materials used in the hot section of jet turbine engines, allowing increased engine efficiency and reduced CO2 emissions. Here we introduce a new 'phase-transformation strengthening' mechanism that resists high-temperature creep deformation in nickel-based superalloys, where specific alloying elements inhibit the deleterious deformation mode of nanotwinning at temperatures above 700 °C. Ultra-high-resolution structure and composition analysis via scanning transmission electron microscopy, combined with density functional theory calculations, reveals that a superalloy with higher concentrations of the elements titanium, tantalum and niobium encourage a shear-induced solid-state transformation from the γ' to η phase along stacking faults in γ' precipitates, which would normally be the precursors of deformation twins. This nanoscale η phase creates a low-energy structure that inhibits thickening of stacking faults into twins, leading to significant improvement in creep properties.

The development of biofilm architecture.

We extend the one-dimensional polymer solution theory of bacterial biofilm growth described by Winstanley et al. (2011 Proc. R. Soc. A467, 1449-1467 (doi:10.1098/rspa.2010.0327)) to deal with the problem of the growth of a patch of biofilm in more than one lateral dimension. The extension is non-trivial, as it requires consideration of the rheology of the polymer phase. We use a novel asymptotic technique to reduce the model to a free-boundary problem governed by the equations of Stokes flow with non-standard boundary conditions. We then consider the stability of laterally uniform biofilm growth, and show that the model predicts spatial instability; this is confirmed by a direct numerical solution of the governing equations. The instability results in cusp formation at the biofilm surface and provides an explanation for the common observation of patterned biofilm architectures.

Subglacial swamps.

The existence of both water and sediment at the bed of ice streams is well documented, but there is a lack of fundamental understanding about the mechanisms of ice, water and sediment interaction. We pose a model to describe subglacial water flow below ice sheets, in the presence of a deformable sediment layer. Water flows in a rough-bedded film; the ice is supported by larger clasts, but there is a millimetric water layer submerging the smaller particles. Partial differential equations describing the water film are derived from a description of the dynamics of ice, water and mobile sediment. We assume that sediment transport is possible, either as fluvial bedload, but more significantly by ice-driven shearing and by internal squeezing. This provides an instability mechanism for rivulet formation; in the model, downstream sediment transport is compensated by lateral squeezing of till towards the incipient streams. We show that the model predicts the formation of shallow, swamp-like streams, with a typical depth of the order of centimetres. The swamps are stable features, typically with a width of the order of tens to hundreds of metres.

Subglacial hydrology and the formation of ice streams.

Antarctic ice streams are associated with pressurized subglacial meltwater but the role this water plays in the dynamics of the streams is not known. To address this, we present a model of subglacial water flow below ice sheets, and particularly below ice streams. The base-level flow is fed by subglacial melting and is presumed to take the form of a rough-bedded film, in which the ice is supported by larger clasts, but there is a millimetric water film which submerges the smaller particles. A model for the film is given by two coupled partial differential equations, representing mass conservation of water and ice closure. We assume that there is no sediment transport and solve for water film depth and effective pressure. This is coupled to a vertically integrated, higher order model for ice-sheet dynamics. If there is a sufficiently small amount of meltwater produced (e.g. if ice flux is low), the distributed film and ice sheet are stable, whereas for larger amounts of melt the ice-water system can become unstable, and ice streams form spontaneously as a consequence. We show that this can be explained in terms of a multi-valued sliding law, which arises from a simplified, one-dimensional analysis of the coupled model.

Factors associated with quality of life among women with fecal incontinence.

INTRODUCTION AND HYPOTHESIS: Fecal incontinence (FI) is a distressing, highly prevalent condition affecting quality of life (QOL). The aim of our study was to identify predictors of moderate/severe health-related QOL among women with FI. METHODS: Data were collected from women presenting to a multispecialty clinic from January 2005 to July 2009 with FI. All completed questionnaires on demographics and validated instruments including the Fecal Incontinence Quality of Life Instrument (FIQL), Patient Health Questionnaire (PHQ) for depression, and Fecal Incontinence Severity Index (FISI). Logistic regression was used to identify factors associated with moderate/severe FI. RESULTS: The study included 226 women with an average age of 59.2 years (SD = 14.1); 92 % were Caucasian, 67 % were married, and the average body mass index was 30.0 (SD = 8.6). Their QOL was moderately/severely affected by FI in 35.6 %. Mean overall FIQL score was 2.5 (SD = 0.8). Median QOL subscale measures were: lifestyle = 2.7 (SD = 1.0), coping = 2.09 (SD = 0.9), depression = 2.8 (SD = 1.0), and embarrassment = 2.2 (SD = 0.9). Average FISI score was 31.6 (SD = 15.7) and average depression score on the PHQ was 8.93 (SD = 8.1). In univariate analyses, diabetes, irritable bowel symptoms, prior hysterectomy, history of previous medical care for FI, higher FISI and PHQ scores were associated with moderate/severe FIQL scores (p < 0.05). Higher PHQ scores and prior hysterectomy significantly predicted moderate/severe QOL in logistic regression analysis (p < 0.05). CONCLUSIONS: We confirm that women with higher depression scores and prior hysterectomy have moderate/severe QOL impairment. When evaluating FI, screening for depression should be undertaken.

Factors associated with symptom severity in women presenting with fecal incontinence.

BACKGROUND: Fecal incontinence (FI) affects 2-12% of the US population. Identification of factors associated with worsening symptoms has important implications for prevention and treatment. OBJECTIVE: The aim of our study is to assess factors associated with symptom severity in women presenting with FI. DATA SOURCES: This was a prospective survey study. STUDY SELECTION: Patients presenting to the Michigan Bowel Control Program Clinic for FI were prospectively enrolled between May 2005 and May 2009. MAIN OUTCOME MEASURES: Factors associated with fecal incontinence severity. RESULTS: Data on 231 women was analyzed with a mean age of 59.2 years (SD = 14.2) and mean BMI of 30.0 (SD = 8.6); 92% were white. Mean FISI score was 32.4 (SD = 15.3). Two-thirds of patients had a type 1-4 stool on the Bristol stool scale. Forty-one percent of subjects complained of urinary incontinence, 56.2% had an episiotomy, 29% had an operative delivery, and 15.1% reported a severe laceration with childbirth. The majority of patients (86.1%) reported FI for greater than 1 year, and 65.4% had previously sought care for FI. Bivariate analysis revealed that diabetes, IBS, urinary incontinence, history of operative delivery or severe laceration, fecal urgency, longer history of symptoms, previous health care for FI, and belief in treatment were positively associated with worse FISI score. In multiple linear regression analysis, increased FI symptom severity was shown to be associated with fecal urgency (0.0004), history of episiotomy (0.04), urinary incontinence (0.02), and diabetes mellitus (0.004). LIMITATIONS: This was a cross-sectional survey study performed at a Tertiary care center. CONCLUSION: Patients with a history of episiotomy, diabetes, urinary incontinence, and fecal urgency have increased FI symptom severity. Proactive screening of patients with these medical histories is needed.

Fine-scale spatial and temporal variations in diets of the pipefish Stigmatopora nigra within seagrass patches.

Diets of the pipefish Stigmatopora nigra were analysed to determine if food availability was causing S. nigra to distribute according to habitat edge effects. Gut analysis found little difference in the diets of S. nigra at the edge and interior of seagrass patches, regardless of time of day or season. Fish diets did, however, vary with seagrass density: S. nigra in denser seagrass consumed more harpacticoid copepods and fewer planktonic copepods. The lack of difference in prey eaten by S. nigra at the edge and interior of patches suggests either that food was not determining S. nigra distribution patterns within patches or that differences in fish densities across patches meant that relative fish-prey densities were similar at edge and interior positions. Alternatively, any edge effects in diet might be masked by gradients in seagrass structure.

Dental development of the Taï Forest chimpanzees revisited.

Developmental studies consistently suggest that teeth are more buffered from the environment than other skeletal elements. The surprising finding of late tooth eruption in wild chimpanzees (Zihlman et al., 2004) warrants reassessment in a broader study of crown and root formation. Here we re-examine the skeletal collection of Taï Forest juvenile chimpanzees using radiography and physical examination. Several new individuals are included, along with genetic and histological assessments of questionable identities. Only half of the Taï juveniles employed by Zihlman et al. (2004) have age of death known with accuracy sufficient for precise comparisons with captive chimpanzees. One key individual in the former study, misidentified during field recovery as Xindra (age 8.3), is re-identified as Goshu (age 6.4). For crown formation we find that onset and duration greatly overlap captive chimpanzees, whereas root development may be more susceptible to acceleration in captive individuals. Kuykendall's (1996) equation relating captive tooth formation stage to age gives reasonable estimates of young wild subjects' true ages. Direct comparisons of tooth eruption ages are limited. A key 3.76 year-old individual likely possessed an emerging mandibular M1 at death (previously estimated from the maxillary molar as occurring at 4.1 years). Wild individuals appear to fall near the middle or latter half of captive eruption ranges. While minor developmental differences are apparent in some comparisons, our reanalysis does not show an "unambiguous pattern" of slower tooth formation in this wild environment. These data do not undermine recent developmental studies of the comparative life histories of fossil hominins.

Brief communication: dental development and enamel thickness in the Lakonis Neanderthal molar.

Developmental and structural affinities between modern human and Neanderthal dental remains continue to be a subject of debate as well as their utility for informing assessments of life history and taxonomy. Excavation of the Middle Paleolithic cave site Lakonis in southern Greece has yielded a lower third molar (LKH 1). Here, we detail the crown development and enamel thickness of the distal cusps of the LKH 1 specimen, which has been classified as a Neanderthal based on the presence of an anterior fovea and mid-trigonid crest. Crown formation was determined using standard histological techniques, and enamel thickness was measured from a virtual plane of section. Developmental differences include thinner cuspal enamel and a lower periodicity than modern humans. Crown formation in the LKH 1 hypoconid is estimated to be 2.6-2.7 years, which is shorter than modern human times. The LKH 1 hypoconid also shows a more rapid overall crown extension rate than modern humans. Relative enamel thickness was approximately half that of a modern human sample mean; enamel on the distal cusps of modern human third molars is extremely thick in absolute and relative terms. These findings are consistent with recent studies that demonstrate differences in crown development, tissue proportions, and enamel thickness between Neanderthals and modern humans. Although overlap in some developmental variables may be found, the results of this and other studies suggest that Neanderthal molars formed in shorter periods of time than modern humans, due in part to thinner enamel and faster crown extension rates.

Three-dimensional molar enamel distribution and thickness in Australopithecus and Paranthropus.

Thick molar enamel is among the few diagnostic characters of hominins which are measurable in fossil specimens. Despite a long history of study and characterization of Paranthropus molars as relatively 'hyper-thick', only a few tooth fragments and controlled planes of section (designed to be proxies of whole-crown thickness) have been measured. Here, we measure molar enamel thickness in Australopithecus africanus and Paranthropus robustus using accurate microtomographic methods, recording the whole-crown distribution of enamel. Both taxa have relatively thick enamel, but are thinner than previously characterized based on two-dimensional measurements. Three-dimensional measurements show that P. robustus enamel is not hyper-thick, and A. africanus enamel is relatively thinner than that of recent humans. Interspecific differences in the whole-crown distribution of enamel thickness influence cross-sectional measurements such that enamel thickness is exaggerated in two-dimensional sections of A. africanus and P. robustus molars. As such, two-dimensional enamel thickness measurements in australopiths are not reliable proxies for the three-dimensional data they are meant to represent. The three-dimensional distribution of enamel thickness shows different patterns among species, and is more useful for the interpretation of functional adaptations than single summary measures of enamel thickness.

Molar enamel thickness and dentine horn height in Gigantopithecus blacki.

Absolutely thick molar enamel is consistent with large body size estimates and dietary inferences about Gigantopithecus blacki, which focus on tough or fibrous vegetation. In this study, 10 G. blacki molars demonstrating various stages of attrition were imaged using high-resolution microtomography. Three-dimensional average enamel thickness and relative enamel thickness measurements were recorded on the least worn molars within the sample (n = 2). Seven molars were also virtually sectioned through the mesial cusps and two-dimensional enamel thickness and dentine horn height measurements were recorded. Gigantopithecus has the thickest enamel of any fossil or extant primate in terms of absolute thickness. Relative (size-scaled) measures of enamel thickness, however, support a thick characterization (i.e., not "hyper-thick"); G. blacki relative enamel thickness overlaps slightly with Pongo and completely with Homo. Gigantopithecus blacki dentine horns are relatively short, similar to (but shorter than) those of Pongo, which in turn are shorter than those of humans and African apes. Gigantopithecus blacki molar enamel (and to a lesser extent, that of Pongo pygmaeus) is distributed relatively evenly across the occlusal surface compared with the more complex distribution of enamel thickness in Homo sapiens. The combination of evenly distributed occlusal enamel and relatively short dentine horns in G. blacki results in a flat and low-cusped occlusal surface suitable to grinding tough or fibrous food objects. This suite of molar morphologies is also found to varying degrees in Pongo and Sivapithecus, but not in African apes and humans, and may be diagnostic of subfamily Ponginae.

Molar development in common chimpanzees (Pan troglodytes).

Numerous studies have reported on enamel and dentine development in hominoid molars, although little is known about intraspecific incremental feature variation. Furthermore, a recent histological study suggested that there is little or no time between age at chimpanzee crown completion and age at molar eruption, which is unlikely given that root growth is necessary for tooth eruption. The study presented here redefines growth standards for chimpanzee molar teeth and examines variation in incremental features. The periodicity of Retzius lines in a relatively large sample was found to be 6 or 7 days. The number of Retzius lines and cuspal enamel thickness both vary within a cusp type, among cusps, and among molars, resulting in marked variation in formation time. Daily secretion rate is consistent within analogous cuspal zones (inner, middle, and outer enamel) within and among cusp types and among molar types. Significantly increasing trends are found from inner to outer cuspal enamel (3 to 5 microns/day). Cuspal initiation and completion sequences also vary, although sequences for mandibular molar cusps are more consistent. Cusp-specific formation time ranges from approximately 2 to 3 years, increasing from M1 to M2, and often decreasing from M2 to M3. These times are intermediate between radiographic studies and a previous histological study, although both formation time within cusps and overlap between molars vary considerably. Cusp-specific (coronal) extension rates range from approximately 4 to 9 microns/day, and root extension rates in the first 5 mm of roots range from 3 to 9 microns/day. These rates are greater in M1 than in M2 or M3, and they are greater in mandibular molars than in respective maxillary molars. This significant enlargement of comparative data on nonhuman primate incremental development demonstrates that developmental variation among cusp and molar types should be considered during interpretations and comparisons of small samples of fossil hominins and hominoids.

FLASH is an essential component of Cajal bodies.

Cajal bodies are small nuclear organelles with a number of nuclear functions. Here we show that FLICE-associated huge protein (FLASH), originally described as a component of the apoptosis signaling pathway, is mainly localized in Cajal bodies and is essential for their structure. Reduction in FLASH expression by short hairpin RNA results in disruption of the normal architecture of the Cajal body and relocalization of its components. Because the function of FLASH in the apoptosis receptor signaling pathway has been strongly questioned, we have now identified a clear function for this protein.

Modern human molar enamel thickness and enamel-dentine junction shape.

This study examines cross-sections of molar crowns in a diverse modern human sample to quantify variation in enamel thickness and enamel-dentine junction (EDJ) shape. Histological sections were generated from molars sectioned buccolingually across mesial cusps. Enamel cap area, dentine area, EDJ length, and bi-cervical diameter were measured on micrographs using a digitizing tablet. Nine landmarks along the EDJ were defined, and X and Y coordinates were digitized in order to quantify EDJ shape. Upper molars show greater values for the components of enamel thickness, leading to significantly greater average enamel thickness than in lower molars. Average enamel thickness increased significantly from M1 to M3 in both molar rows, due to significantly increasing enamel cap area in upper molars, and decreasing dentine area in lower molars. Differences in EDJ shape were found among maxillary molars in combined and individual populations. Sex differences were also found; males showed significantly greater dentine area, EDJ length, and bi-cervical diameters in certain tooth types, which resulted in females having significantly thicker average enamel. Differences in enamel thickness and EDJ shape within molars were also found among populations, although few consistent trends were evident. This study demonstrates that enamel thickness and EDJ shape vary among molars, between sexes, and among populations; these factors must be considered in the categorization and comparison of ape and human molars, particularly when isolated teeth or fossil taxa are included. Human relative enamel thickness encompasses most values reported for fossil apes and humans, suggesting limited taxonomic value when considered alone.

Experimental determination of the periodicity of incremental features in enamel.

Vital labelling of hard tissues was used to examine the periodicity of features of dental enamel microstructure. Fluorescent labels were administered pre- and postnatally to developing macaques (Macaca nemestrina), which were identified histologically in dentine and related to accentuated lines in enamel, allowing for counts of features within known-period intervals. This study demonstrates that cross-striations represent a daily rhythm in enamel secretion, and suggests that intradian lines are the result of a similar 12-h rhythm. Retzius lines were found to have a regular periodicity within individual dentitions, and laminations appear to represent a daily rhythm that also shows 12-h subdivisions. The inclusion of intradian lines and laminations represents the first empirical evidence for their periodicities in primates; these features frequently complicate precise measurements of secretion rate and Retzius line periodicity, which are necessary for determination of crown formation time. The biological basis of incremental feature formation is not completely understood; long-period features may result from interactions between short-period rhythms, although this does not explain the known range of Retzius line periodicities within humans or among primates. Studies of the genetic, neurological and hormonal basis of incremental feature formation are needed to provide more insight into their physiological and structural basis.

The accuracy of histological assessments of dental development and age at death.

Histological analyses of dental development have been conducted for several decades despite few studies assessing the accuracy of such methods. Using known-period incremental features, the crown formation time and age at death of five pig-tailed macaques (Macaca nemestrina) were estimated with standard histological techniques and compared with known ages. Estimates of age at death ranged from 8.6% underestimations to 15.0% overestimations, with an average 3.5% overestimate and a 7.2% average absolute difference. Several sources of error were identified relating to preparation quality and section obliquity. These results demonstrate that histological analyses of dental development involving counts and measurements of short- and long-period incremental features may yield accurate estimates, particularly in well-prepared material. Values from oblique sections (or most naturally fractured teeth) should be regarded with caution, as obliquity leads to inflated cuspal enamel formation time and underestimated imbricational formation time. Additionally, Shellis's formula for extension rate and crown formation time estimation was tested, which significantly overestimated crown formation time due to underestimated extension rate. It is suggested that Shellis' method should not be applied to teeth with short, rapid periods of development, and further study is necessary to validate this application in other material.