The phase diagram of Ti-6Al-4V at high-pressures and high-temperatures.

We report results from a series of diamond-anvil-cell synchrotron x-ray diffraction and large-volume-press experiments, and calculations, to investigate the phase diagram of commercial polycrystalline high-strength Ti-6Al-4V alloy in pressure-temperature space. Up to ∼30 GPa and 886 K, Ti-6Al-4V is found to be stable in the hexagonal-close-packed, orαphase. The effect of temperature on the volume expansion and compressibility ofα-Ti-6Al-4V is modest. The martensiticα→ω(hexagonal) transition occurs at ∼30 GPa, with both phases coexisting until at ∼38-40 GPa the transition to theωphase is completed. Between 300 K and 844 K theα→ωtransition appears to be independent of temperature.ω-Ti-6Al-4V is stable to ∼91 GPa and 844 K, the highest combined pressure and temperature reached in these experiments. Pressure-volume-temperature equations-of-state for theαandωphases of Ti-6Al-4V are generated and found to be similar to pure Ti. A pronounced hysteresis is observed in theω-Ti-6Al-4V on decompression, with the hexagonal structure reverting back to theαphase at pressures below ∼9 GPa at room temperature, and at a higher pressure at elevated temperatures. Based on our data, we estimate the Ti-6Al-4Vα-ß-ωtriple point to occur at ∼900 K and 30 GPa, in good agreement with our calculations.

The high-pressure, high-temperature phase diagram of cerium.

We present an experimental study of the high-pressure, high-temperature behaviour of cerium up to ∼22 GPa and 820 K using angle-dispersive x-ray diffraction and external resistive heating. Studies above 820 K were prevented by chemical reactions between the samples and the diamond anvils of the pressure cells. We unambiguously measure the stability region of the orthorhombic oC4 phase and find it reaches its apex at 7.1 GPa and 650 K. We locate the α-cF4-oC4-tI2 triple point at 6.1 GPa and 640 K, 1 GPa below the location of the apex of the oC4 phase, and 1-2 GPa lower than previously reported. We find the α-cF4 → tI2 phase boundary to have a positive gradient of 280 K (GPa)-1, less steep than the 670 K (GPa)-1 reported previously, and find the oC4 → tI2 phase boundary to lie at higher temperatures than previously found. We also find variations as large as 2-3 GPa in the transition pressures at which the oC4 → tI2 transition takes place at a given temperature, the reasons for which remain unclear. Finally, we find no evidence that the α-cF4 → tI2 is not second order at all temperatures up to 820 K.

High-pressure/high-temperature phase diagram of zinc.

The phase diagram of zinc (Zn) has been explored up to 140 GPa and 6000 K, by combining optical observations, x-ray diffraction, and ab initio calculations. In the pressure range covered by this study, Zn is found to retain a hexagonal close-packed (hcp) crystal symmetry up to the melting temperature. The known decrease of the axial ratio (c/a) of the hcp phase of Zn under compression is observed in x-ray diffraction experiments from 300 K up to the melting temperature. The pressure at which c/a reaches [Formula: see text] (≈10 GPa) is slightly affected by temperature. When this axial ratio is reached, we observed that single crystals of Zn, formed at high temperature, break into multiple poly-crystals. In addition, a noticeable change in the pressure dependence of c/a takes place at the same pressure. Both phenomena could be caused by an isomorphic second-order phase transition induced by pressure in Zn. The reported melt curve extends previous results from 24 to 135 GPa. The pressure dependence obtained for the melting temperature is accurately described up to 135 GPa by using a Simon-Glatzel equation: [Formula: see text], where P is the pressure in GPa. The determined melt curve agrees with previous low-pressure studies and with shock-wave experiments, with a melting temperature of 5060(30) K at 135 GPa. Finally, a thermal equation of state is reported, which at room-temperature agrees with the literature.

Stochastically modulated inter-pulse intervals to increase the efficiency of functional electrical stimulation cycling.

INTRODUCTION: Functional electrical stimulation cycling has various health benefits, but the mechanical power output and efficiency are very low compared to volitional muscle activation. Stimulation with variable frequency showed significantly higher power output values in experiments with a knee dynamometer. The aim of the present work was to compare stochastic modulation of inter-pulse interval to constant inter-pulse interval stimulation during functional electrical stimulation cycling. METHODS: Seventeen able-bodied subjects participated (n = 17). Quadriceps and hamstring muscle groups were stimulated with two activation patterns: P1-constant frequency, P2-stochastic inter-pulse interval. Power output was measured on functional electrical stimulation ergometer. RESULTS: Overall, mean power output with the stochastically modulated pattern P2 was lower than with P1 (12.57 ± 3.74 W vs. 11.44 ± 3.81 W, P1 vs. P2, p = 0.022), but no significant differences during the first 30 s and the last 30 s were observed. CONCLUSIONS: This study showed that stimulation strategies that use randomized modulation of inter-pulse intervals can negatively affect power output generation during functional electrical stimulation cycling. To minimise voluntary contractions, power measurement and assessment should be focused on the periods where only the quadriceps are stimulated.

Ultrafast X-Ray Diffraction Studies of the Phase Transitions and Equation of State of Scandium Shock Compressed to 82 GPa.

Using x-ray diffraction at the Linac Coherent Light Source x-ray free-electron laser, we have determined simultaneously and self-consistently the phase transitions and equation of state (EOS) of the lightest transition metal, scandium, under shock compression. On compression scandium undergoes a structural phase transition between 32 and 35 GPa to the same bcc structure seen at high temperatures at ambient pressures, and then a further transition at 46 GPa to the incommensurate host-guest polymorph found above 21 GPa in static compression at room temperature. Shock melting of the host-guest phase is observed between 53 and 72 GPa with the disappearance of Bragg scattering and the growth of a broad asymmetric diffraction peak from the high-density liquid.

Improving Medicine Use for Children: A Global Imperative.

Professionals committed to optimal medical care of children recognize the need to increase future availability of thoroughly validated medicinal treatments. This will only be achieved through expanded efforts of pediatric clinical pharmacologists and clinical pharmacists equipped with the necessary skills in relevant research and educational methods. Recent research has demonstrated a shortfall in the human resource pool, particularly in low- and lower-middle-income countries where a majority of children under 14 years of age reside.

An International Asset Map of Clinicians, Educators, and Researchers Pursuing Better Medicine Use in Children: Initial Findings.

The world's 1.89 billion children (age 0-14) too frequently receive treatments that have not been validated through clinical pharmacology research, especially in low- and middle-income countries. Initial findings from an international asset map of professionals and clinician scientists available to address the needs for education, research, and treatment support suggest a critical shortage of clinical pharmacologists, clinical pharmacists, and other professionals with advanced training in the evaluation of therapies for childhood conditions and illnesses. A total of 497 individuals responded to a survey conducted between May 2015 and February 2016. An alarming signal is apparent showing that, while the overall resource pool is unquestionably limited, 87% of relevant qualified personnel are located in high-income countries. The data suggest an urgent need for targeted training in pediatric clinical pharmacology, with particular focus on the needs in Africa, Latin America, and most of Asia.

Thallium under extreme compression.

We present a combined theoretical and experimental study of the high-pressure behavior of thallium. X-ray diffraction experiments have been carried out at room temperature (RT) up to 125 GPa using diamond-anvil cells (DACs), nearly doubling the pressure range of previous experiments. We have confirmed the hcp-fcc transition at 3.5 GPa and determined that the fcc structure remains stable up to the highest pressure attained in the experiments. In addition, HP-HT experiments have been performed up to 8 GPa and 700 K by using a combination of XRD and a resistively heated DAC. Information on the phase boundaries is obtained, as well as crystallographic information on the HT bcc phase. The equation of state (EOS) for different phases is reported. Ab initio calculations have also been carried out considering several potential high-pressure structures. They are consistent with the experimental results and predict that, among the structures considered in the calculations, the fcc structure of thallium is stable up to 4.3 TPa. Calculations also predict the post-fcc phase to have a close-packed orthorhombic structure above 4.3 TPa.

Prevalence of Ethanol Use Among Pregnant Women in Southwestern Uganda.

Introduction The prevalence of ethanol use in many Sub-Saharan African countries is high, but little research exists on use during pregnancy. The objective of this study was to assess the prevalence and predictors of ethanol use among pregnant women in Southwestern Uganda. Methods This descriptive, cross-sectional study was conducted in the maternity ward at Mbarara Regional Referral Hospital (MRRH). All pregnant women giving birth at MRRH between September 23, 2013 and November 23, 2013 were eligible for enrollment. The primary outcome was the proportion of women with ethanol use during pregnancy as determined by self-report. Secondary outcomes included the proportion with positive fatty acid ethyl ester (FAEE) results (indicating ethanol use) and positive TWEAK questionnaire results (indicating possible problem drinking). Predictors of ethanol use were assessed and stratified by patterns of ethanol intake. Results Overall, 505 mother-child dyads enrolled in the study. The proportion of women who reported any ethanol use during pregnancy was 16 % (n = 81, 95 % CI 13-19 %) and the prevalence of heavy drinking 6.3 % (n = 32, 95 % CI 3.8-7.9 %). The strongest predictor of use during pregnancy was pre-pregnancy use, with maternal education as a protective factor. Few neonates (n = 11, 2 %) tested positive for FAEE > 2.00 nmol/g in meconium. The TWEAK questionnaire captured 75 % of women who reported moderate/heavy drinking and aligned more with self-reported ethanol use than meconium results. Conclusions The substantial prevalence and clear predictors of ethanol use suggest that legislative action and educational interventions to increase awareness of potential harms could assist in efforts to decrease use during pregnancy in Southwestern Uganda.

Changes in Post-Stroke Gait Biomechanics Induced by One Session of Gait Training.

The objective of this study was to determine whether one session of targeted locomotor training can induce measurable improvements in the post-stroke gait impairments. Thirteen individuals with chronic post-stroke hemiparesis participated in one locomotor training session combining fast treadmill training and functional electrical stimulation (FES) of ankle dorsi- and plantar-flexor muscles. Three dimensional gait analysis was performed to assess within-session changes (after versus before training) in gait biomechanics at the subject's self-selected speed without FES. Our results showed that one session of locomotor training resulted in significant improvements in peak anterior ground reaction force (AGRF) and AGRF integral for the paretic leg. Additionally, individual subject data showed that a majority of study participants demonstrated improvements in the primary outcome variables following the training session. This study demonstrates, for the first time, that a single session of intense, targeted post-stroke locomotor retraining can induce significant improvements in post-stroke gait biomechanics. We posit that the within-session changes induced by a single exposure to gait training can be used to predict whether an individual is responsive to a particular gait intervention, and aid with the development of individualized gait retraining strategies. Future studies are needed to determine whether these single-session improvements in biomechanics are accompanied by short-term changes in corticospinal excitability, and whether single-session responses can serve as predictors for the longer-term effects of the intervention with other targeted gait interventions.

Pediatric clinical drug trials in low-income countries: key ethical issues.

Potential child participants in clinical research trials in low-income countries are often vulnerable because of poverty, high morbidity and mortality, inadequate education, and varied local cultural norms. However, vulnerability by itself must not be accepted as an obstacle blocking children from the health benefits that may accrue as an outcome of sound clinical research. As greater emphasis is placed on evidence-based treatment of children, it should be anticipated that there will be a growing call for agreement on principles to guide clinical investigations in low-income countries. There is now general acceptance of the view that children must be protected from non-evidence-based interventions and from substandard treatments. The questions remaining relate to how best to stimulate clinical research activity that will serve the needs of infants, children, and youth in developing countries and how best to assign priority to ethically sound research that will meet their clinical requirements. In low-income countries, 39 % of citizens are 13 years of age or younger, and consequently it is certain that clinical investigations of some new therapeutic products will be conducted there more frequently. This review offers some suggestions for approaches that will help to achieve more effective ethical consideration, including (1) improving the quality of research ethics boards; (2) fostering collaborative partnerships among important stakeholders; (3) making concerted efforts to build capacity; (4) improving the quality of the consent and waiver process; and (5) developing improved governance for harmonized ethics platforms. Continuing support by international organizations is required to sustain the establishment and maintenance of stronger research ethics boards to protect children enrolled in clinical trials. This review underscores the importance of developing a culture of solidarity and true partnership between developed and low-income country organizations, which will allow all those involved, and especially child patients, to benefit from the advancement of therapeutics.

Exercise lowers postprandial glucose but not fasting glucose in type 2 diabetes: a meta-analysis of studies using continuous glucose monitoring.

Exercise has repeatedly been shown to improve glycemic control as assessed by glycated hemoglobin. However, changes in glycated hemoglobin do not provide information regarding which aspects of glycemic control have been altered. The purpose of this systematic review was to examine the effect of exercise as assessed by continuous glucose monitoring systems (CGMS) in type 2 diabetes. Databases (PubMed, Medline, EMBASE) were searched up to February 2013. Eligible studies had participants with type 2 diabetes complete standardized exercise protocols and used CGMS to measure changes in glycemic control. Randomized controlled trials, crossover trials and studies with pre-post designs were included. Average glucose concentration, daily time spent in hyperglycemia or hypoglycemia, and fasting glucose concentration were compared between exercise and control conditions. Eleven studies met the inclusion criteria and were included in the review. Eight studies had short-term (≤2 weeks) exercise interventions, whereas three studies had a longer-term intervention (all >2 months). The types of exercises utilized included aerobic, resistance and a combination of the two. The eight short-term studies were included in quantitative analysis. Exercise significantly decreased average glucose concentrations (-0.8 mmol/L, p < 0.01) and daily time spent in hyperglycemia (-129 minutes, p < 0.01), but did not significantly affect daily time spent in hypoglycemia (-3 minutes, p = 0.47) or fasting glucose (-0.3 mmol/L, p = 0.13). The four randomized crossover trials had similar findings compared to studies with pre-post designs. Exercise consistently reduced average glucose concentrations and time spent in hyperglycemia despite not significantly affecting outcomes such as fasting glucose and hypoglycemia.

Gender differences in drug bioequivalence: time to rethink practices.

Currently, bioequivalence (BE) studies are carried out exclusively in males, assuming that intrasubject variabilities are similar between the sexes. This article challenges this hypothesis on the basis of available evidence and urges that studies of BE of sufficient power be undertaken in women also for all generic drugs aimed at women.

HER3 targeting of adenovirus by fiber modification increases infection of breast cancer cells in vitro, but not following intratumoral injection in mice.

Despite the tremendous potential of adenovirus (Ad) as a delivery vector for cancer gene therapy, its use in clinical settings has been limited, mainly as a result of the limited infectivity in many tumors and the wide tissue tropism associated with Ad. To modify the tropism of the virus, we have inserted the epidermal growth factor-like domain of the human heregulin-α (HRG) into the HI loop of Ad5 fiber. This insertion had no adverse effect on fiber trimerization nor did it affect incorporation of the modified fiber into infectious viral particles. Virions bearing modified fiber displayed growth characteristics and viral yields indistinguishable from those of wild-type (wt) virus. Most importantly, HRG-tagged virions showed enhanced infection of cells expressing the cognate receptors HER3/ErbB3 and HER4/ErbB4. This was significantly reduced in the presence of soluble HRG. Furthermore, HER3-expressing Chinese hamster ovary (CHO) cells were transduced by the HRG-modified virus, but not by wt virus. In contrast, CHO cells expressing the coxsackie-Ad receptor were transduced with both viruses. However, infection of an in vivo breast cancer xenograft model after intratumoral injection was similar with both viruses, suggesting that the tumor microenvironment and/or the route of delivery have important roles in infection of target cells with fiber-modified Ads.

Skeletal and hormonal responses to vitamin D supplementation during sunlight deprivation in Antarctic expeditioners.

UNLABELLED: Sunlight deprivation results in vitamin D deficiency but serum vitamin D levels can be maintained above 50 nmol/L when supplemented with 50,000 IU at least every alternate month. INTRODUCTION: Antarctic expeditioners are exposed to prolonged sunlight deprivation resulting in vitamin D deficiency. We hypothesised that monthly dosing of 50,000 IU vitamin D (~1,600 IU daily) will increase serum 25-hydroxyvitamin D (25(OH)D), suppress parathyroid hormone (PTH) and improve bone mineral density (BMD), 50,000 IU alternate months (~800 IU daily) will maintain these measures, while a single 50,000 IU dose pre-departure (~1,00 IU daily) will not be protective. METHODS: This was a randomised double-blind study involving 110 healthy adults: 91 males, mean age 41 years (range 24-65 years) working in Antarctica for up to 12 months, who we administered 50,000 IU vitamin D3 monthly, alternate months or a single dose pre-departure. Serum 25(OH)D, PTH, osteocalcin, CTx and calcium were assessed at baseline, mid- and end of expedition. Proximal femur and lumbar spine BMD were assessed pre- and post-expedition. RESULTS: Baseline 25(OH)D was 59 ± 14 nmol/L. By mid-expedition, 25(OH)D increased by 7 nmol/L in those supplemented monthly (p < 0.05) and remained unchanged in those supplemented in alternate months. In those given a single dose pre-departure, 25(OH)D decreased by 8 nmol/L (p < 0.05) and PTH increased by 27% (p < 0.09). Serum osteocalcin increased by ~22% in all groups but BMD remained unchanged. If serum 25(OH)D was >50 nmol/L at baseline, 25(OH)D was maintained above this level with all regimens. If 25(OH)D was <50 nmol/L at baseline, monthly or alternate month regimens were needed to achieve levels >50 nmol/L, the single pre-departure dose was ineffective. CONCLUSION: During sunlight deprivation of up to 12 months, serum 25(OH)D levels can be maintained above 50 nmol/L when expeditioners are provided with 50,000 I U at least every alternate month.

Escape and survival of Corophium volutator and Ilyanassa obsoleta exposed to freshwater and chlorothalonil.

The behavioural response and survival of marine mud snails and mud shrimp exposed to freshwater and the fungicide chlorothalonil (tetrachloroisophthalonitrile) was investigated. Amphipods were less tolerant of lower salinity than snails, with 50 and 76% survival associated with 5 and 0% seawater in freshwater, respectively. However, 50% of snails displayed a defence mechanism by retracting within their shell when exposed to 70% freshwater. Both species displayed an avoidance to chlorothalonil spiked at >100 ng/g and/or >100 ng/mL in sediments and seawater, respectively. The avoidance response of amphipods was observed along with a reduced swimming ability and increased lipid content. Snails displayed a higher susceptibility to physical stress, with an increased number unable to twist from being on their shell to their foot, and with longer righting time. Behaviour was affected at chlorothalonil concentrations of 0.001-0.01 ng/g and/or ng/mL, with a variability that could be due to degradation by the microbial community. Ascertaining the latter observations requires state-of-the-art chemical analyses.

A review of glaucoma treatment in Scotland 1994-2004.

OBJECTIVE: This study evaluated the changing trends in glaucoma management in Scotland between 1994 and 2004. METHODS: A retrospective analysis of national health statistics in Scotland from 1994 to 2004. The Scottish morbidity record was used to collect information on all episodes of trabeculectomy. Data on number of prescriptions were gathered for individual drugs and also for groups of active ingredient. The population likely to have glaucoma (PLG) was calculated from estimates of prevalence in individuals aged 40 years and older, based on published epidemiological studies. The outcome measures were trabeculectomy rates, corrected for population likely to be at risk of glaucoma (PLG), and prescribing volume and cost for glaucoma medications. RESULTS: Trabeculectomy rates have fallen by 67% from 46 per 1,000 PLG in 1994 to 15.4 per 1,000 PLG in 2004. Over the same time period, the population likely to be at risk of glaucoma (PLG) increased by 16.6%. The cost of prescribing has increased by 122% over 11 years compared with an increase in number of items per 1,000 PLG by 27.5%. In 1994, beta-blockers accounted for 65.2% of prescribed drugs but by 2004 this had dropped to 33%. Since their introduction, the prescribing of prostaglandin analogues has increased rapidly and in 2004, they accounted for 39.4% of prescribed drugs. CONCLUSION: The increasing use of prostaglandin analogues has led to an increase in prescribing rates and a rapid increase in cost. At the same time, prescribing of beta-blockers has declined and trabeculectomy rates have fallen.

The aging population and Natural Occurring Retirement Communities (NORCs); local government, healthy aging, and healthy-NORCs.

BACKGROUND: The term Naturally Occurring Retirement Communities (NORCs) has been used since the 1980s. NORCs are defined as communities where people remain or move to when they retire. NORCs develop 'naturally', meaning that seniors tend to remain or move there when they retire, although the residences and physical environment were not constructed for a senior population. The term, Healthy-NORC, has been introduced and is associated with healthy aging. OBJECTIVES/METHODS: We describe how demographic trends will facilitate a dramatic growth in NORCs. Acknowledging the 'Determinants of Health' model, we suggest that some determinants impact people differently at different ages. We also suggest that more attention be focused on the impact of physical/social environments on health, and that some determinants of health are particularly relevant for seniors. We argue that NORCs exist on a spectrum, from NORC to H-NORC, and that health benefits for seniors increase as NORCs adopt additional characteristics associated with improved senior health. We also illustrate H-NORC research methods and policy options for local governments. RESULTS/CONCLUSION: Compared to the provision of additional medical and social services, H-NORCs represent a low-cost approach to facilitating healthy aging. Municipal governments can promote healthy aging and should pursue policies that will stimulate H-NORC development.