Coupled Sublattice Melting and Charge-Order Transition in Two Dimensions.

Two-dimensional melting is one of the most fascinating and poorly understood phase transitions in nature. Theoretical investigations often point to a two-step melting scenario involving unbinding of topological defects at two distinct temperatures. Here, we report on a novel melting transition of a charge-ordered K-Sn alloy monolayer on a silicon substrate. Melting starts with short-range positional fluctuations in the K sublattice while maintaining long-range order, followed by longer-range K diffusion over small domains, and ultimately resulting in a molten sublattice. Concomitantly, the charge order of the Sn host lattice collapses in a multistep process with both displacive and order-disorder transition characteristics. Our combined experimental and theoretical analysis provides a rare insight into the atomistic processes of a multistep melting transition of a two-dimensional materials system.

Description, characterization, and evaluation of an online social networking community: the American Cancer Society's Cancer Survivors Network®.

PURPOSE: To describe (a) the conceptualization, purpose, and features of The American Cancer Society's Cancer Survivors Network® (CSN; http://csn.cancer.org ), (b) the ongoing two-phase evaluation process of CSN, and (c) the characteristics of CSN members. METHODS: An online opt-in self-report survey of CSN members (N = 4762) was conducted and digital metrics of site use were collected. RESULTS: Annually, CSN attracts over 3.6 million unique users from over 200 countries/territories. Most commonly used site features are discussion boards (81.1%), the search function (63.8%), and the member resource library (50.2%). The survey sample is mostly female (69.6%), non-Hispanic white (84.1%), and self-identified as a cancer survivor (49.8%), or both cancer survivor and cancer caregiver (31.9%). A larger number of survey respondents reported head and neck cancer (12.5%), relative to cancer incidence/prevalence data. CONCLUSIONS: The volume of CSN traffic suggests high demand among cancer survivors and caregivers for informational and/or emotional support from other cancer survivors and caregivers. CSN may be particularly beneficial for individuals with rare cancers. Furthermore, this study documents a group of individuals whose cancer experience is multifaceted (e.g., survivors became caregivers or vice versa), and for whom CSN has the capacity to provide support at multiple points during their cancer experiences. IMPLICATIONS FOR CANCER SURVIVORS: CSN is a free, internet-based social networking site available to all cancer survivors and caregivers, worldwide. Evaluation of the site is ongoing and will be used to inform improvements to usability, reach, recruitment, retention, and potential health impact(s) of this valuable resource.

Prevalence of exon 11 internal tandem duplications in the C-KIT proto-oncogene in Australian canine mast cell tumours.

OBJECTIVE: To measure the prevalence of internal tandem duplications (ITDs) in exon 11 of the proto-oncogene C-KIT in a sample of Australian cutaneous canine mast cell tumours (MCTs) drawn from general practice and to evaluate relationships between tumour mutation status and prognostic factors including signalment, tumour histological grade, tumour anatomical location and tumour size. METHODS: C-KIT exon 11 ITDs were detected by PCR in DNA extracted from formalin-fixed, paraffin-embedded canine MCTs sourced from three veterinary diagnostic laboratories in Adelaide and Melbourne. Tumours were graded according to two different systems (Patnaik and Kiupel systems) by board-certified anatomical pathologists blinded to the PCR results. Relationships between tumour mutation status and prognostic factors were evaluated using a generalised binary logistic regression analysis. RESULTS: ITDs were identified in 13 of 74 cutaneous canine MCT samples, giving an overall prevalence of 17.6% (95% confidence interval: 8.9-26.2%). ITDs were detected in 10 of 18 Patnaik grade III MCTs (55.6%) and 11 of 22 Kiupel high-grade MCTs (50%). Wald chi-square analysis revealed that detection of tumour ITDs was significantly associated with both Patnaik's and Kiupel's histologic grading systems (each: P < 0.001). The presence of the ITDs in MCTs was not associated with signalment, tumour anatomical location or tumour size. CONCLUSION: The prevalence of C-KIT exon 11 ITDs in Australian canine MCTs is similar to the prevalence in overseas canine populations (overall prevalence in Australia approximately 18%). ITDs were more frequently identified in higher grade MCTs.

Evaluation of a capacity building clinical educational model for oral health clinicians treating very young children.

OBJECTIVE: There are significant levels of dental caries in Australian school-aged children, with children aged five years having a mean dmft of 1.3. It has also been identified that, in general, oral health clinicians lack confidence to treat very young children and this study aimed to increase capacity of public sector oral health clinicians to treat preschool children. BASIC RESEARCH DESIGN: An educational program was developed, implemented and evaluated for its capability to increase the confidence and knowledge of oral health clinicians and dental assistants in providing oral care for children aged 12 months to 5 years. RESULTS: In 2011 and 2012, the course was delivered to 36 clinicians (22 dentists, 12 dental therapists, and two oral health therapists) and showed increases in their confidence and knowledge for participants when providing dental procedures to preschool children. CONCLUSIONS: The educational program that was developed and implemented has met its objective of increasing the knowledge and confidence of practicing oral health clinicians and dental assistants in the management of preschool children. Strategies to further enhance the outcomes of this educational program have been proposed.

Short-term effects of military fog oil on the fountain darter (Etheostoma fonticola).

Toxicity tests evaluated chronic and sublethal effects of fog oil (FO) on a freshwater endangered fish. FO is released during military training as an obscurant smoke that can drift into aquatic habitats. Fountain darters, Etheostoma fonticola, of four distinct life stages were exposed under laboratory conditions to three forms of FO. FO was vaporized into smoke and allowed to settle onto water, violently agitated with water, and dosed onto water followed by photo-oxidization by ultraviolet irradiation. Single smoke exposures of spawning adult fish did not affect egg production, egg viability, or adult fish survival in 21-day tests. Multiple daily smoke exposures induced mortality after 5 days for larvae fish. Larvae and juvenile fish were more sensitive than eggs in 96-h lethal concentration (LC50) tests with FO­water mixtures and photo-oxidized FO. Water-soluble FO components photo-modified by ultraviolet radiation were the most toxic, thus indicating the value of examining weathering and aging of chemicals for the best determination of environmental impact.

Potential lost productivity resulting from the global burden of uncorrected refractive error.

OBJECTIVE: To estimate the potential global economic productivity loss associated with the existing burden of visual impairment from uncorrected refractive error (URE). METHODS: Conservative assumptions and national population, epidemiological and economic data were used to estimate the purchasing power parity-adjusted gross domestic product (PPP-adjusted GDP) loss for all individuals with impaired vision and blindness, and for individuals with normal sight who provide them with informal care. FINDINGS: An estimated 158.1 million cases of visual impairment resulted from uncorrected or undercorrected refractive error in 2007; of these, 8.7 million were blind. We estimated the global economic productivity loss in international dollars (I$) associated with this burden at I$ 427.7 billion before, and I$ 268.8 billion after, adjustment for country-specific labour force participation and employment rates. With the same adjustment, but assuming no economic productivity for individuals aged > 50 years, we estimated the potential productivity loss at I$ 121.4 billion. CONCLUSION: Even under the most conservative assumptions, the total estimated productivity loss, in $I, associated with visual impairment from URE is approximately a thousand times greater than the global number of cases. The cost of scaling up existing refractive services to meet this burden is unknown, but if each affected individual were to be provided with appropriate eyeglasses for less than I$ 1000, a net economic gain may be attainable.

Advanced MRI in the management of adult gliomas.

Gliomas are a heterogeneous group that account for approximately 86% of primary brain neoplasms, and include astrocytic and oligodendroglial tumours, as well as a variety of less common histopathological subtypes. Magnetic resonance imaging has become the accepted mode of imaging for the clinical management of these tumours. MRI features bear close resemblance to the histopathology grading and prognosis of these tumours. Currently, conventional MRI is used to aid diagnosis, plan neurosurgical approaches, and monitor response to therapy and disease progression. More recent developments in the field of MRI include MR spectroscopy, perfusion MRI, diffusion-weighted imaging, intraoperative MRI and functional MRI. These newer techniques have been adopted with varying success in the management of adult gliomas. This review focuses on the application of advanced MR imaging in the clinical management of adult gliomas.

Cortical bone viscoelasticity and fixation strength of press-fit femoral stems: an in-vitro model.

Cementless total hip femoral components rely on press-fit for initial stability and bone healing and remodeling for secondary fixation. However, the determinants of satisfactory press-fit are not well understood. In previous studies, human cortical bone loaded circumferentially to simulate press-fit exhibited viscoelastic, or time dependent, behavior. The effect of bone viscoelastic behavior on the initial stability of press-fit stems is not known. Therefore, in the current study, push-out loads of cylindrical stems press-fit into reamed cadaver diaphyseal femoral specimens were measured immediately after assembly and 24 h with stem-bone diametral interference and stem surface treatment as independent variables. It was hypothesized that stem-bone interference would result in a viscoelastic response of bone that would decrease push-out load thereby impairing initial press-fit stability. Results showed that push-out load significantly decreased over a 24 h period due to bone viscoelasticity. It was also found that high and low push-out loads occurred at relatively small amounts of stem-bone interference, but a relationship between stem-bone interference and push-out load could not be determined due to variability among specimens. On the basis of this model, it was concluded that press-fit fixation can occur at relatively low levels of diametral interference and that stem-bone interference elicits viscoelastic response that reduces stem stability over time. From a clinical perspective, these results suggest that there could be large variations in initial press-fit fixation among patients.

MRS of oligodendroglial tumors: correlation with histopathology and genetic subtypes.

BACKGROUND: Oligodendroglial neoplasms with combined loss of chromosomes 1p and 19q may have a good prognosis and respond to procarbazine-lomustine (CCNU)-vincristine (PCV) chemotherapy. OBJECTIVE: To determine whether single voxel magnetic resonance spectroscopy (SV-MRS) obtained through routine clinical practice distinguishes between histopathologic and genetic subtypes of oligodendroglial tumors. METHODS: Forty-eight patients with oligodendroglial tumors (19 oligodendrogliomas and 29 oligoastrocytomas) underwent molecular genetic analysis to determine allelic imbalance in chromosomes 1p36 and 19q13. SV-MRS was obtained pretherapy to determine tumor metabolite ratios. RESULTS: Grade III oligodendroglial tumors had higher choline (Mann-Whitney; p = 0.002), methyl lipid (Mann-Whitney; p = 0.002), and combined methylene lipid and lactate ratios (Mann-Whitney; p < 0.001) than grade II tumors. Lactate did not distinguish between tumor types (Fisher exact test; p = 0.342) or grade (Fisher exact test; p = 0.452). There were no significant associations when tumors were analyzed according to histopathology or genetic subtypes. CONCLUSION: As a noninvasive diagnostic tool used in routine clinical practice, SV-MRS has the potential benefit of determining oligodendroglial tumor grade but not subtypes classified by histopathology or molecular genetics. MRS may be useful for determining the timing of therapy but is unlikely to predict chemosensitivity.

An orientation distribution function for trabecular bone.

We describe a new method for quantifying the orientation of trabecular bone from three-dimensional images. Trabecular lattices from five human vertebrae were decomposed into individual trabecular elements, and the orientation, mass, and thickness of each element were recorded. Continuous functions that described the total mass (M(phi,theta)) and mean thickness (tau(phi,theta)) of all trabeculae as a function of orientation were derived. The results were compared with experimental measurements of the elastic modulus in three principal anatomic directions. A power law scaling relationship between the anisotropies in mass and elastic modulus was observed; the scaling exponent was 1.41 (R2=0.88). As expected, the preponderance of trabecular mass was oriented along the cranial-caudal direction; on average, there was 3.4 times more mass oriented vertically than horizontally. Moreover, the vertical trabeculae were 30% thicker, on average, than the horizontal trabeculae. The vertical trabecular thickness was inversely related to connectivity (R2=0.70; P=0.07), suggesting a possible organization into either few, thick trabeculae or many thin trabeculae. The method, which accounts for the mechanical connectedness of the lattice, provides a rapid way to both visualize and quantify the three-dimensional organization of trabecular bone.

Identification, genomic organization, and mRNA expression of LACTB, encoding a serine beta-lactamase-like protein with an amino-terminal transmembrane domain.

Database searching with bacterial serine beta-lactamases identified mouse expressed sequence tags (ESTs) with significant similarity scores.The cloned mouse cDNA encodes a novel 551-amino-acid protein, LACTB, with a predicted amino-terminal transmembrane domain but no signal peptide. It contains an active site motif related to C-class beta-lactamases. Homologues were detected in sequence data from human, rat, cow, rabbit, pig, toad, zebrafish, and Caenorhabditis elegans, but not in Saccharomyces cerevisiae or Drosophila melanogaster. The genes were mapped to human chromosome 15q22.1 and mouse chromosome 9. Sequencing of a 14.7-kb fragment of mouse genomic DNA defined six exons. A virtual human cDNA and a 549-residue protein, predicted from unfinished genomic sequence, showed the same intron/exon structure. Northern blot analysis showed expression of the 2.3-kb mRNA predominantly in mouse liver and human skeletal muscle. This is the first reported vertebrate example of this microbial peptidase family.

S1 screw bending moment with posterior spinal instrumentation across the lumbosacral junction after unilateral iliac crest harvest.

STUDY DESIGN: A biomechanical study comparing fixation across the lumbosacral junction. OBJECTIVES: To determine which long posterior construct across the lumbosacral junction produces the least bending moment on the S1 screw when only one ilium is available for fixation. SUMMARY OF BACKGROUND DATA: Recent in vitro studies have demonstrated the benefit of anterior support and fixation into the ilium when instrumenting a long posterior construct across the lumbosacral junction. METHODS: Four L2-sacrum constructs were tested on six synthetic models of the lumbar spine and pelvis simulating that the right ilium had been harvested. Construct 1: L2-S1 bilateral screws. Construct 2: L2-S1 + left iliac bolt. Construct 3: L2-S1 + left iliac bolt + right S2 screw. Construct 4: L2-S1 + bilateral S2 screws. The four constructs were then retested with an anterior L5-S1 strut. A flexion-extension moment was applied across each construct, and the moment at the left and right S1 pedicle screw was measured with internal strain gauges. RESULTS: Iliac bolt fixation was found to significantly decrease the flexion-extension moment on the ipsilateral S1 screw by 70% and the contralateral screw by 26%. An anterior L5-S1 strut significantly decreased the S1 screw flexion-extension moment by 33%. Anterior support at L5-S1 provided no statistical decrease in the flexion-extension moment when bilateral posterior fixation beyond S1 was present with either a unilateral iliac bolt and contralateral S2 screw, or bilateral S2 screws. CONCLUSIONS: There is a significant decrease in the flexion-extension moment on the S1 screw when extending long posterior constructs to either the ilium or S2 sacral screw. There is no biomechanical advantage of the iliac bolt over the S2 screw in decreasing the moment on the S1 screw in flexion and extension. Adding anterior support to long posterior constructs significantly decreases the moment on the S1 screw. Adding distal posterior fixation to either the ilium or S2 decreases the moment on S1 screws more than adding anterior support. Further, adding anterior support when bilateral distal fixation past S1 is already present does not significantly decrease the moment on the S1 screws in flexion and extension.

Does the aggressive use of polyvalent antivenin for rattlesnake bites result in serious acute side effects?

OBJECTIVE: To determine the incidence and severity of acute side effects from the use of polyvalent antivenin in victims of rattlesnake bites. DESIGN: We retrospectively reviewed the records of all patients who presented with rattlesnake bites to a university teaching hospital during an 11-year period. From patient medical records, we extracted demographic data, clinical measurements, and outcomes during emergency department evaluation and subsequent hospitalization. Data regarding serum sickness were not collected. OUTCOME MEASURES: Primary outcome variables were the occurrence of immediate hypersensitivity reaction to antivenin, the type of reaction, permanent disability at hospital discharge, and mortality. RESULTS: We identified a total of 73 patients with rattlesnake bites during the study period. Bite envenomation was graded as nonenvenomated, 7 patients (10%); mild, 23 patients (32%); moderate, 32 patients (44%); and severe, 11 patients (15%). We identified 65 patients who received antivenin. Antivenin doses ranged from 1 to 30 vials per patient (mean, 12.0 +/- 6.0), for a total of 777 vials. In 43 patients (66%), 10 or more vials of antivenin were given. The mean number of vials of antivenin given to each snakebite grade were as follows: mild, 8.4 (+/-4.0); moderate, 11.8 (+/-5.7); and severe, 18.7 (+/-6.3). No deaths, amputations, or permanent disability from snakebite occurred in the patients receiving antivenin. Acute side effects of antivenin-occurring within the first 6 hours after administration-were seen in 12 patients (18%; 95% confidence interval, 10%-30%). Acute side effects consisted solely of urticaria in all but 1 patient (2%; 95% confidence interval, 0%-8%). This patient had a history of previous antivenin reaction and required a short course of intravenous epinephrine for blood pressure support. No other complications occurred. CONCLUSION: The administration of polyvalent Crotalidae antivenin is safe. Acute hypersensitivity, when it occurs, consists solely in most cases of urticaria. Serious side effects are uncommon.

Three-dimensional microimaging (MRmicroI and microCT), finite element modeling, and rapid prototyping provide unique insights into bone architecture in osteoporosis.

With the proportion of elderly people increasing in many countries, osteoporosis has become a growing public health problem, with rising medical, social, and economic consequences. It is well recognized that a combination of low bone mass and the deterioration of the trabecular architecture underlies osteoporotic fractures. A comprehensive understanding of the relationships between bone mass, the three-dimensional (3D) architecture of bone and bone function is fundamental to the study of new and existing therapies for osteoporosis. Detailed analysis of 3D trabecular architecture, using high-resolution digital imaging techniques such as magnetic resonance microimaging (MRmicroI), micro-computed tomography (microCT), and direct image analysis, has become feasible only recently. Rapid prototyping technology is used to replicate the complex trabecular architecture on a macroscopic scale for visual or biomechanical analysis. Further, a complete set of 3D image data provides a basis for finite element modeling (FEM) to predict mechanical properties. The goal of this paper is to describe how we can integrate three-dimensional microimaging and image analysis techniques for quantitation of trabecular bone architecture, FEM for virtual biomechanics, and rapid prototyping for enhanced visualization. The integration of these techniques provide us with an unique ability to investigate the role of bone architecture in osteoporotic fractures and to support the development of new therapies.

Neurotoxic Abeta peptides increase oxidative stress in vivo through NMDA-receptor and nitric-oxide-synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro.

Beta amyloid (Abeta) peptides accumulate in Alzheimer's disease and are neurotoxic possibly through the production of oxygen free radicals. Using brain microdialysis we characterized the ability of Abeta to increase oxygen radical production in vivo. The 1-40 Abeta fragment increased 2,3-dehydroxybenzoic acid efflux more than the 1-28 fragment, in a manner dependent on nitric oxide synthase and NMDA receptor channels. We then examined the effects of Abeta peptides on mitochondrial function in vitro. Induction of the mitochondrial permeability transition in isolated rat liver mitochondria by Abeta(25-35) and Abeta(35-25) exhibited dose dependency and required calcium and phosphate. Cyclosporin A prevented the transition as did ruthenium red, chlorpromazine, or N-ethylmaleimide. ADP and magnesium delayed the onset of mitochondrial permeability transition. Electron microscopy confirmed the presence of Abeta aggregates and swollen mitochondria and preservation of mitochondrial structure by inhibitors of mitochondrial permeability transition. Cytochrome c oxidase (COX) activity was selectively inhibited by Abeta(25-35) but not by Abeta(35-25). Neurotoxic Abeta peptide can increase oxidative stress in vivo through mechanisms involving NMDA receptors and nitric oxide sythase. Increased intracellular Abeta levels can further exacerbate the genetically driven complex IV defect in sporadic Alzheimer's disease and may precipitate mitochondrial permeability transition opening. In combination, our results provide potential mechanisms to support the feed-forward hypothesis of Abeta neurotoxicity.

Sequencing, tissue distribution and chromosomal assignment of a novel ubiquitin-specific protease USP23.

We have identified human and mouse cDNAs encoding a novel ubiquitin-specific protease designated USP23. Both cDNAs encode a 62-kDa protein containing the highly conserved His and Cys domains characteristic of the C19 cysteine protease family of ubiquitin-specific processing proteases (UCH-2). Human tissue Northern blots revealed USP23 to be ubiquitously expressed, whereas USP12, its closest human paralogue, displayed a more restricted expression pattern. The human USP23 gene mapped to chromosome 1q22.

Identification of a novel aspartic protease (Asp 2) as beta-secretase.

The Alzheimer's disease beta-amyloid peptide (Abeta) is produced by excision from the type 1 integral membrane glycoprotein amyloid precursor protein (APP) by the sequential actions of beta- and then gamma-secretases. Here we report that Asp 2, a novel transmembrane aspartic protease, has the key activities expected of beta-secretase. Transient expression of Asp 2 in cells expressing APP causes an increase in the secretion of the N-terminal fragment of APP and an increase in the cell-associated C-terminal beta-secretase APP fragment. Mutation of either of the putative catalytic aspartyl residues in Asp 2 abrogates the production of the fragments characteristic of cleavage at the beta-secretase site. The enzyme is present in normal and Alzheimer's disease (AD) brain and is also found in cell lines known to produce Abeta. Asp 2 localizes to the Golgi/endoplasmic reticulum in transfected cells and shows clear colocalization with APP in cells stably expressing the 751-amino-acid isoform of APP.

Molecular interaction of Agouti protein and Agouti-related protein with human melanocortin receptors.

Agouti protein and the Agouti-related protein (AGRP) are antagonists of the melanocortin-3 receptor and melanocortin-4 receptor. Both proteins contain 10 cysteines in the C-terminal domain arranged in five disulfide bonds. One possible arrangement of the disulfide bonds predicts an octapeptide loop, and the chemical properties of four residues within this loop (residues 111-114 in human AGRP) bear striking resemblance to those of several melanocortin peptides, including alpha-MSH, MT-II, and SHU-9119. We showed that cyclic synthetic octapeptides based on the sequence of this loop from Agouti protein or human AGRP are functional antagonists of the human melanocortin-4 receptor. All peptides had a lower affinity for the melanocortin-3 receptor than for the melanocortin-4 receptor. Substitution of serines for cysteines resulted in linear peptides which had reduced binding affinities for both receptors. Mutational analysis of human AGRP indicated that its C-terminal domain is functionally equivalent to the intact human AGRP. The RFF111-113 triplet appears to be the most critical portion of AGRP in determining the binding affinity for both melanocortin-3 and melanocortin-4 receptors. These data strongly suggest that the loop defined by Cys-110 and Cys-117 is critical in determining the antagonist activity of human AGRP. Our data provide indirect evidence for the suggestion that the Cys-110 to Cys-117 octapeptide loop of human AGRP mimics the conformation of alpha-MSH, MT-II, and SHU-9119.