Radiocarbon test for demographic events in written and oral history.

We extend an established simulation-based method to test for significant short-duration (1-2 centuries) demographic events known from one documented historical and one oral historical context. Case study 1 extrapolates population data from the Western historical tradition using historically derived demographic data from the catastrophic European Black Death/bubonic plague (Yersinia pestis). We find a corresponding statistically significant drop in absolute population using an extended version of a previously published simulation method. Case study 2 uses this refined simulation method to test for a settlement gap identified in oral historical records of descendant Tsimshian First Nations communities from the Prince Rupert Harbour region of the Pacific Northwest region of British Columbia, Canada. Using a regional database of n = 523 radiocarbon dates, we find a significant drop in relative population using the extended simulation-based method consistent with Tsimshian oral records. We conclude that our technical refinement extends the utility of radiocarbon simulation methods and can provide a rigorous test of demographic predictions derived from a range of historical sources.

Thermally induced amorphous to amorphous transition in hot-compressed silica glass.

In situ Raman and Brillouin light scattering techniques were used to study thermally induced high-density amorphous (HDA) to low-density amorphous (LDA) transition in silica glass densified in hot compression (up to 8 GPa at 1100 °C). Hot-compressed silica samples are shown to retain structural and mechanical stability through 600 °C or greater, with reduced sensitivity in elastic response to temperature as compared with pristine silica glass. Given sufficient thermal energy to overcome the energy barrier, the compacted structure of the HDA silica reverts back to the LDA state. The onset temperature for the HDA to LDA transition depends on the degree of densification during hot compression, commencing at lower temperatures for samples with higher density, but all finishing within a temperature range of 250-300 °C. Our studies show that the HDA to LDA transition at high temperatures in hot-compressed samples is different from the gradual changes starting from room temperature in cold-compressed silica glass, indicating greater structural homogeneity achieved by hot compression. Furthermore, the structure and properties of hot-compressed silica glass change continuously during the thermally induced HDA to LDA transition, in contrast to the abrupt and first-order-like polyamorphic transitions in amorphous ice. Different HDA to LDA transition mechanisms in amorphous silica and amorphous ice are explained by their different energy landscapes.

Carbon Nanomaterials for Treating Osteoporotic Vertebral Fractures.

PURPOSE OF REVIEW: To identify the use of carbon nanomaterials in bone regeneration and present new data on the regenerative capacity of bone tissue in osteopenic rats treated with graphene nanoribbons (GNRs). RECENT FINDINGS: The results show that the physical and chemical properties of the nanomaterials are suitable for the fabrication of scaffolds intended for bone regeneration. The in vitro tests suggested a non-toxicity of the GNRs as well as improved biocompatibility and bone mineralization activity. Here, for the first time, we evaluated the potential of GNRs in remodeling and repairing bone defects in osteoporotic animal models in vivo. Interestingly, bone mineralization and the initiation of the remodeling cycle by osteoclasts/osteoblasts were observed after the implantation of GNRs, thus implying healthy bone remodeling when using GNRs. This study, therefore, has opened our perspectives and certainly calls for more attention to the use of carbon nanomaterials for a wide range of osteoporosis applications.

Pressure-enabled phonon engineering in metals.

We present a combined first-principles and experimental study of the electrical resistivity in aluminum and copper samples under pressures up to 2 GPa. The calculations are based on first-principles density functional perturbation theory, whereas the experimental setup uses a solid media piston-cylinder apparatus at room temperature. We find that upon pressurizing each metal, the phonon spectra are blue-shifted and the net electron-phonon interaction is suppressed relative to the unstrained crystal. This reduction in electron-phonon scattering results in a decrease in the electrical resistivity under pressure, which is more pronounced for aluminum than for copper. We show that density functional perturbation theory can be used to accurately predict the pressure response of the electrical resistivity in these metals. This work demonstrates how the phonon spectra in metals can be engineered through pressure to achieve more attractive electrical properties.

The effect of 14 weeks of vitamin D3 supplementation on antimicrobial peptides and proteins in athletes.

Heavy training is associated with increased respiratory infection risk and antimicrobial proteins are important in defence against oral and respiratory tract infections. We examined the effect of 14 weeks of vitamin D3 supplementation (5000 IU/day) on the resting plasma cathelicidin concentration and the salivary secretion rates of secretory immunoglobulin A (SIgA), cathelicidin, lactoferrin and lysozyme in athletes during a winter training period. Blood and saliva were obtained at the start of the study from 39 healthy men who were randomly allocated to vitamin D3 supplement or placebo. Blood samples were also collected at the end of the study; saliva samples were collected after 7 and 14 weeks. Plasma total 25(OH)D concentration increased by 130% in the vitamin D3 group and decreased by 43% in the placebo group (both P = 0.001). The percentage change of plasma cathelicidin concentration in the vitamin D3 group was higher than in the placebo group (P = 0.025). Only in the vitamin D3 group, the saliva SIgA and cathelicidin secretion rates increased over time (both P = 0.03). A daily 5000 IU vitamin D3 supplement has a beneficial effect in up-regulating the expression of SIgA and cathelicidin in athletes during a winter training period, which could improve resistance to respiratory infections.

The FACIT-AI, a new tool for assessing symptoms associated with malignant ascites.

OBJECTIVE: The objectives of this study are to assess the clinical relevance and validity of the Functional Assessment of Chronic Illness Therapy-Ascites Index (FACIT-AI) in women with ovarian cancer and malignant ascites, and to modify the instrument guided by qualitative feedback from patients with recurrent malignant ascites. METHODS: Fourteen adult female patients with recurrent symptomatic malignant ascites were enrolled from three centers. All completed an open-ended symptom list to identify their primary concerns regarding their condition. They then completed a draft 10-item FACIT-AI questionnaire created from expert input. Eleven patients provided comments regarding the FACIT-AI questionnaire using a written feedback format. Three patients participated in a "think-aloud" cognitive debriefing interview to ensure patient comprehension of questionnaire items. RESULTS: Of the first 11 patients surveyed, 7 believed that the draft FACIT-AI contained all important symptoms associated with malignant ascites. Responses from the remaining 4 patients revealed three symptoms that 2 or more patients nominated for inclusion: urinary frequency, constipation and emotional distress. These items were added to the original FACIT-AI to produce a 13-item index of symptoms associated with malignant ascites. CONCLUSIONS: The 13-item FACIT-AI has content validity among women with malignant ascites associated with ovarian cancer. It is available for use in clinical research or practice, with the expectation that more will be learned about its performance and interpretation over time.

40Ar retention in the terrestrial planets.

The solid Earth is widely believed to have lost its original gases through a combination of early catastrophic release and regulated output over geologic time. In principle, the abundance of 40Ar in the atmosphere represents the time-integrated loss of gases from the interior, thought to occur through partial melting in the mantle followed by melt ascent to the surface and gas exsolution. Here we present data that reveal two major difficulties with this simple magmatic degassing scenario--argon seems to be compatible in the major phases of the terrestrial planets, and argon diffusion in these phases is slow at upper-mantle conditions. These results challenge the common belief that the upper mantle is nearly degassed of 40Ar, and they call into question the suitability of 40Ar as a monitor of planetary degassing. An alternative to magmatism is needed to release argon to the atmosphere, with one possibility being hydration of oceanic lithosphere consisting of relatively argon-rich olivine and orthopyroxene.

Palliative care.

These guidelines were developed and updated by an interdisciplinary group of experts based on clinical experience and available scientific evidence. The goal of these guidelines is to help patients with cancer experience the best quality of life possible throughout the illness trajectory by providing guidance for the primary oncology team for symptom screening, assessment, palliative care interventions, reassessment, and afterdeath care. Palliative care should be initiated by the primary oncology team and augmented by collaboration with an interdisciplinary team of palliative care experts.

A study of cathodoluminescence and trace element compositional zoning in natural quartz from volcanic rocks: mapping titanium content in quartz.

This article concerns application of cathodoluminescence (CL) spectroscopy to volcanic quartz and its utility in assessing variation in trace quantities of Ti within individual crystals. CL spectroscopy provides useful details of intragrain compositional variability and structure but generally limited quantitative information on element abundances. Microbeam analysis can provide such information but is time-consuming and costly, particularly if large numbers of analyses are required. To maximize advantages of both approaches, natural and synthetic quartz crystals were studied using high-resolution hyperspectral CL imaging (1.2-5.0 eV range) combined with analysis via laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS). Spectral intensities can be deconvolved into three principal contributions (1.93, 2.19, and 2.72 eV), for which intensity of the latter peak was found to correlate directly with Ti concentration. Quantitative maps of Ti variation can be produced by calibration of the CL spectral data against relatively few analytical points. Such maps provide useful information concerning intragrain zoning or heterogeneity of Ti contents with the sensitivity of LA-ICPMS analysis and spatial resolution of electron microprobe analysis.

Methylnaltrexone for opioid-induced constipation in advanced illness.

BACKGROUND: Constipation is a distressing side effect of opioid treatment. As a quaternary amine, methylnaltrexone, a mu-opioid-receptor antagonist, has restricted ability to cross the blood-brain barrier. We investigated the safety and efficacy of subcutaneous methylnaltrexone for treating opioid-induced constipation in patients with advanced illness. METHODS: A total of 133 patients who had received opioids for 2 or more weeks and who had received stable doses of opioids and laxatives for 3 or more days without relief of opioid-induced constipation were randomly assigned to receive subcutaneous methylnaltrexone (at a dose of 0.15 mg per kilogram of body weight) or placebo every other day for 2 weeks. Coprimary outcomes were laxation (defecation) within 4 hours after the first dose of the study drug and laxation within 4 hours after two or more of the first four doses. Patients who completed this phase were eligible to enter a 3-month, open-label extension trial. RESULTS: In the methylnaltrexone group, 48% of patients had laxation within 4 hours after the first study dose, as compared with 15% in the placebo group, and 52% had laxation without the use of a rescue laxative within 4 hours after two or more of the first four doses, as compared with 8% in the placebo group (P<0.001 for both comparisons). The response rate remained consistent throughout the extension trial. The median time to laxation was significantly shorter in the methylnaltrexone group than in the placebo group. Evidence of withdrawal mediated by central nervous system opioid receptors or changes in pain scores was not observed. Abdominal pain and flatulence were the most common adverse events. CONCLUSIONS: Subcutaneous methylnaltrexone rapidly induced laxation in patients with advanced illness and opioid-induced constipation. Treatment did not appear to affect central analgesia or precipitate opioid withdrawal. (Clinical Trials.gov number, NCT00402038 [ClinicalTrials.gov].).

PMMA-silica nanocomposite coating: Effective corrosion protection and biocompatibility for a Ti6Al4V alloy.

Ti6Al4V is the mostly applied metallic alloy for orthopedic and dental implants, however, its lack of osseointegration and poor long-term corrosion resistance often leads to a secondary surgical intervention, recovery delay and toxicity to the surrounding tissue. As a potential solution of these issues poly(methyl methacrylate)-silicon dioxide (PMMA-silica) coatings have been applied on a Ti6Al4V alloy to act simultaneously as an anticorrosive barrier and bioactive film. The nanocomposite, composed of PMMA covalently bonded to the silica phase through 3-(trimethoxysilyl)propyl methacrylate (MPTS), has been synthesized combining the sol-gel process with radical polymerization of methyl methacrylate. The 5 µm thick coatings deposited on Ti6Al4V have a smooth surface, are homogeneous, transparent, free of pores and cracks, and show a strong adhesion to the metallic substrate (11.6 MPa). Electrochemical impedance spectroscopy results proved an excellent anticorrosive performance of the coating, with an impedance modulus of 26 GΩ cm2 and long-term durability in simulated body fluid (SBF) solution. Moreover, after 21 days of immersion in SBF, the PMMA-silica coating presented apatite crystal deposits, which suggests in vivo bone bioactivity. This was confirmed by biological characterization showing enhanced osteoblast proliferation, explained by the increased surface free energy and protein adsorption. The obtained results suggest that PMMA-silica hybrids can act in a dual role as efficient anticorrosive and bioactive coating for Ti6Al4V alloys.

Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients.

Methylnaltrexone, a peripheral mu-opioid receptor antagonist with restricted ability to cross the blood-brain barrier, may relieve opioid-induced constipation (OIC) without reversing analgesia. A total of 154 patients with advanced illness and OIC enrolled in a double-blind, randomized, placebo-controlled trial, with optional open-label phases (up to 4 months) in hospice and palliative care centers during 2003-2005. They received a single subcutaneous injection of methylnaltrexone (0.15 mg/kg or 0.3 mg/kg) or placebo. Laxation response within 4 hours was 62% and 58% for methylnaltrexone 0.15 mg/kg and 0.3 mg/kg, respectively, compared with 14% for placebo (P < 0.0001; each dose vs placebo). Approximately half of the methylnaltrexone responders defecated within 30 minutes of dosing. Open-label phase response rates mirrored those for methylnaltrexone during the double-blind phase.There was no change in pain scores or evidence of central opioid withdrawal.The most common adverse events (AEs) were abdominal pain and flatulence.Three patients had serious AEs attributed to methylnaltrexone. Subcutaneous methylnaltrexone was efficacious in rapidly inducing laxation and was generally well tolerated in patients with advanced illness and OIC.

The Expanded Evidence-Centered Design (e-ECD) for Learning and Assessment Systems: A Framework for Incorporating Learning Goals and Processes Within Assessment Design.

Evidence-centered design (ECD) is a framework for the design and development of assessments that ensures consideration and collection of validity evidence from the onset of the test design. Blending learning and assessment requires integrating aspects of learning at the same level of rigor as aspects of testing. In this paper, we describe an expansion to the ECD framework (termed e-ECD) such that it includes the specifications of the relevant aspects of learning at each of the three core models in the ECD, as well as making room for specifying the relationship between learning and assessment within the system. The framework proposed here does not assume a specific learning theory or particular learning goals, rather it allows for their inclusion within an assessment framework, such that they can be articulated by researchers or assessment developers that wish to focus on learning.

Dual effective core-shell electrospun scaffolds: Promoting osteoblast maturation and reducing bacteria activity.

Herein, we electrospun ultrathin core-shell fibers based on polycaprolactone (PCL), polyethylene glycol (PEG), gelatin and osteogenic growth peptide (OGP), and evaluated their potential to upregulate human osteoblast cells (hFOB) and to reduce Gram-positive and Gram-negative bacteria. We also evaluated the fiber morphology, chemical structure and peptide delivery efficacy. The employment of core-shell fibers compared to fibers without a core-shell showed improved mechanical strength, comparable to the strength of pure PCL, as well as improved hydrophilicity and wettability. The careful selection of polymer combination and core-shell strategy promoted a controlled and sustained release of OGP. Moreover, increased calcium deposition (CD) (1.3-fold) and alkaline phosphate (ALP) activity was observed when hFOBs were cultivated onto core-shell fibers loaded with OGP after 21 days of culture. Our developed scaffolds were also able to reduce the amount of Pseudomonas aeruginosa (ATCC 25668) bacteria by a factor of two compared to raw PCL without the use of any antibiotics. All of these results demonstrate a promising potential of the developed core-shell electrospun scaffolds based on PCL:PEG:Gelatin:OGP for numerous bone tissue applications.

Opioid-induced bowel dysfunction.

Opioid-induced bowel dysfunction is a distressing condition that may persist indefinitely in the clinical setting. As we understand more about normal gastrointestinal (GI) physiology, we are also beginning to understand more fully how opioids cause bowel dysfunction. Current therapeutic interventions for opioid-induced bowel dysfunction can be burdensome and sometimes lack efficacy. Systemic opioid antagonists administered orally can induce laxation, but can unpredictably induce systemic or local GI tract withdrawal symptoms. Two new investigational agents, alvimopan and methylnaltrexone, are peripherally acting opioid antagonists that do not cross the blood-brain barrier. Studies to date show promise that these agents may relieve opioid-induced bowel dysfunction in a well-tolerated manner without reversing central analgesia.

Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study.

Methylnaltrexone, a peripherally-acting quaternary opioid antagonist, is an investigational treatment for opioid-induced constipation in patients with advanced illness. This randomized, parallel-group, repeated dose, dose-ranging trial included a double-blind phase for one week followed by an open-label phase for a maximum of three weeks. Opioid-treated patients with advanced illness who met criteria for opioid-induced constipation despite laxative therapy were potentially eligible. Double-blind treatment occurred on Days 1, 3, and 5; open-label therapy could be administered as often as every other day. The initial dose range of 1mg, 5mg, or 12.5mg was extended by adding a 20mg group during the study while still maintaining the double blind; the initial open-label dose of 5mg could be titrated. The primary outcome was a laxation response within four hours after the first dose. Thirty-three patients received at least one dose of methylnaltrexone. Only one of 10 patients (10%) who received the 1mg dose experienced laxation within four hours of dosing. The median time to laxation was >48 hours for the 1mg dose group, compared to 1.26 hours for all patients receiving >or=5mg (P=0.0003). There was no apparent dose-response above 5mg. Most adverse events were related to the gastrointestinal system, were mild, and did not lead to discontinuation. In conclusion, methylnaltrexone relieved opioid-induced constipation at doses >or=5mg in patients with advanced illness, and did not reduce analgesia or cause opioid withdrawal symptoms.

The symptomatic relief of dyspnea.

Dyspnea is a common symptom that causes considerable suffering in cancer patients. Although some knowledge of the sensory information that is transduced to the brain during dyspnea exists, we still have only a rudimentary understanding of the subjective perception of this symptom. There appear to be many parallels between pain and dyspnea. Consistent with this fact, there is growing evidence that opioids are safe and effective and should be considered front-line therapy for symptomatic relief of dyspnea. In addition to opioids, there are other important pharmacologic and nonpharmacologic tools with varying degrees of support that can be considered for symptomatic relief. Importantly, because dyspnea is a subjective symptom that occurs in a unique individual, the optimal treatment of dyspnea will always entail an understanding of, and support for, a patient's other sources of psychosocial, spiritual, and/or existential suffering.

Synthesis and study of cell-penetrating peptide-modified gold nanoparticles.

BACKGROUND: In nanomedicine, gold nanoparticles (AuNPs) have demonstrated versatile therapeutic efficiencies and, in particular, have been developed for the treatment of various cancers due to their high selectivity in killing cancer, not healthy, cells. METHODS: In this study, AuNPs were conjugated with the cell-penetrating peptide Cys-(Arg)8-Asp-Ser (CRRRRRRRRGDS) by direct cross-linking of the cysteine's thiol group to the gold surface and a fibronectin-derived RGD group was also used due to its efficacy toward cancer cell targeting and possible promotion of healthy fibroblast functions. RESULTS: Ultraviolet-visible absorbance spectrum and transmission electron microscope images of the synthesized peptide-capped AuNPs (PEP-AuNPs) validated the formation of AuNP aggregates. The presence of peptides on AuNPs was confirmed by Fourier transform infrared spectroscopy and quantified by a bicinchoninic acid assay. After being modified with the arginine-rich peptide, the AuNPs possessed a positive charge, as their zeta potential increased from -23.81±8.43 mV to 8 mV on average. In this manner, an easy method to conjugate AuNPs was shown here. Further, MTS assays were performed using healthy human dermal fibroblasts. After 24 hours of treatment with PEP-AuNPs, the cell density increased dramatically to around 25,000 cells/cm2. Results further showed a very high half-maximal inhibitory concentration of 69.2 µM for the PEP-AuNPs (indicating low toxicity). CONCLUSION: The results showed for the first time the ability of PEP-AuNPs to promote human dermal fibroblast cell viability, which after further investigation, may show an ability to replace cancerous tissue with healthy soft tissue.

Micro-Nanofibrillar Polycaprolactone Scaffolds as Translatable Osteoconductive Grafts for the Treatment of Musculoskeletal Defects without Infection.

The treatment of musculoskeletal defects is currently limited by the tissue-regenerative materials available to orthopedic surgeons: autologous bone grafts only have a finite amount of harvestable material within a given patient, while allografts are prone to severe immunological complications and host rejection. With this motivation, the production of poly(ε-caprolactone) (PCL) scaffolds as synthetic, biomimetic biomaterials was investigated, with a specific focus on potential orthopedic translation. PCL scaffolds were produced through three different fabrication techniques: electrospinning (ES), rotary jet spinning (RJS), and airbrush (AB). ES and RJS were observed to produce microfibrillar scaffolds, while all AB products were nanofibrous. Osteoblast viability, within the PCL scaffolds, and the osteogenic phenotype were assessed in vitro through a combination of adherence, metabolic activity, proliferation, gene expression, alkaline phosphatase bioactivity, and calcium deposition assays. While the polymeric scaffolds induced slight reductions in initial osteoblast adhesion and metabolic activity, seeded cells were able to proliferate and demonstrate the bone formation phenotype. AB products demonstrated reduced bacterial surface colonization when inoculated with both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacterial strains, in comparison to the microfibrous ES and RJS products, without any small-molecule antibiotics, antimicrobial peptides, or reactive nanomaterials included during scaffold synthesis.