Recruitment and results of a pilot trial of vitamin D supplementation in the general population of Australia

Context: The benefits of high serum levels of 25-hydroxyvitamin D [25(OH)D] are unclear. Trials are needed to establish an appropriate evidence base. Objective: We plan to conduct a large-scale trial of vitamin D supplementation for the reduction of cancer incidence and overall mortality and report here the methods and results of a pilot trial established to inform its design. Design: Pilot D-Health was a randomized trial carried out in a general community setting with 12 months intervention and follow-up. Participants: Participants were 60- to 84-yr-old residents of one of the four eastern Australian states who did not have any vitamin D-related disorders and who were not taking more than 400 IU supplementary vitamin D per day. A total of 644 participants were randomized, and 615 completed the study (two persons withdrew because of nonserious adverse events). Interventions: The interventions were monthly doses of placebo or 30,000 or 60,000 IU vitamin D3. Main Outcomes: The main outcomes were the recruitment rate and changes in serum 25(OH)D. Results: Ten percent of those approached were recruited. At baseline, the mean 25(OH)D was 42 nmol/liter in all three study arms. The mean change in 25(OH)D in the placebo group was 0.12 nmol/liter, compared with changes of 22 and 36 nmol/liter in the 30,000- and 60,000-IU groups, respectively. Conclusions: The D-Health pilot has shown that a large trial is feasible in Australia and that a dose of 2000 IU/d will be needed to ensure that a large proportion of the population reaches the target serum 25(OH)D level. Copyright © 2012 by The Endocrine Society.

Vitamin D status and skin cancer risk independent of time outdoors : 11-year prospective study in and Australian community

Vitamin D may have anti-skin cancer effects, but population-based evidence is lacking. We therefore assessed associations between vitamin D status and skin cancer risk in an Australian subtropical community. We analyzed prospective skin cancer incidence for 11 years following baseline assessment of serum 25(OH)-vitamin D in 1,191 adults (average age 54 years) and used multivariable logistic regression analysis to adjust risk estimates for age, sex, detailed assessments of usual time spent outdoors, phenotypic characteristics, and other possible confounders. Participants with serum 25(OH)-vitamin D concentrations above 75 nmol  l(-1) versus those below 75 nmol  l(-1) more often developed basal cell carcinoma (odds ratio (OR)=1.51 (95% confidence interval (CI): 1.10-2.07, P=0.01) and melanoma (OR=2.71 (95% CI: 0.98-7.48, P=0.05)). Squamous cell carcinoma incidence tended to be lower in persons with serum 25(OH)-vitamin D concentrations above 75 nmol  l(-1) compared with those below 75 nmol  l(-1) (OR=0.67 (95% CI: 0.44-1.03, P=0.07)). Vitamin D status was not associated with skin cancer incidence when participants were classified as above or below 50 nmol  l(-1) 25(OH)-vitamin D. Our findings do not indicate that the carcinogenicity of high sun exposure can be counteracted by high vitamin D status. High sun exposure is to be avoided as a means to achieve high vitamin D status.

Predicting vitamin D deficiency in older Australian adults

OBJECTIVE There has been a dramatic increase in vitamin D testing in Australia in recent years, prompting calls for targeted testing. We sought to develop a model to identify people most at risk of vitamin D deficiency. DESIGN AND PARTICIPANTS This is a cross-sectional study of 644 60- to 84-year-old participants, 95% of whom were Caucasian, who took part in a pilot randomized controlled trial of vitamin D supplementation. MEASUREMENTS Baseline 25(OH)D was measured using the Diasorin Liaison platform. Vitamin D insufficiency and deficiency were defined using 50 and 25 nmol/l as cut-points, respectively. A questionnaire was used to obtain information on demographic characteristics and lifestyle factors. We used multivariate logistic regression to predict low vitamin D and calculated the net benefit of using the model compared with 'test-all' and 'test-none' strategies. RESULTS The mean serum 25(OH)D was 42 (SD 14) nmol/1. Seventy-five per cent of participants were vitamin D insufficient and 10% deficient. Serum 25(OH)D was positively correlated with time outdoors, physical activity, vitamin D intake and ambient UVR, and inversely correlated with age, BMI and poor self-reported health status. These predictors explained approximately 21% of the variance in serum 25(OH)D. The area under the ROC curve predicting vitamin D deficiency was 0·82. Net benefit for the prediction model was higher than that for the 'test-all' strategy at all probability thresholds and higher than the 'test-none' strategy for probabilities up to 60%. CONCLUSION Our model could predict vitamin D deficiency with reasonable accuracy, but it needs to be validated in other populations before being implemented.

The AusD Study: A population-based study of the determinants of serum 25-hydroxyvitamin D concentration across a broad latitude range

Observational studies suggest that people with a high serum 25-hydroxyvitamin D (25(OH)D) concentration may have reduced risk of chronic diseases such as osteoporosis, multiple sclerosis, type 1 diabetes, cardiovascular disease, and some cancers. The AusD Study (A Quantitative Assessment of Solar UV Exposure for Vitamin D Synthesis in Australian Adults) was conducted to clarify the relationships between ultraviolet (UV) radiation exposure, dietary intake of vitamin D, and serum 25(OH)D concentration among Australian adults residing in Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S), and Hobart (42.8°S). Participants aged 18-75 years were recruited from the Australian Electoral Roll between 2009 and 2010. Measurements were made of height, weight, waist:hip ratio, skin, hair, and eye color, blood pressure, and grip strength. Participants completed a questionnaire on sun exposure and vitamin D intake, together with 10 days of personal UV dosimetry and an associated sun-exposure and physical-activity diary that was temporally linked to a blood test for measurement of 25(OH)D concentration. Ambient solar UV radiation was also monitored at all study sites. We collected comprehensive, high-quality data from 1,002 participants (459 males, 543 females) assessed simultaneously across a range of latitudes and through all seasons. Here we describe the scientific and methodological issues considered in designing the AusD Study.

Effect of vitamin D supplementation on antibiotic use : a randomized controlled trial

BACKGROUND: Observational data suggested that supplementation with vitamin D could reduce risk of infection, but trial data are inconsistent. OBJECTIVE: We aimed to examine the effect of oral vitamin D supplementation on antibiotic use. DESIGN: We conducted a post hoc analysis of data from pilot D-Health, which is a randomized trial carried out in a general community setting between October 2010 and February 2012. A total of 644 Australian residents aged 60-84 y were randomly assigned to receive monthly doses of a placebo (n = 214) or 30,000 (n = 215) or 60,000 (n = 215) IU oral cholecalciferol for ≤12 mo. Antibiotics prescribed during the intervention period were ascertained by linkage with pharmacy records through the national health insurance scheme (Medicare Australia). RESULTS: People who were randomly assigned 60,000 IU cholecalciferol had nonsignificant 28% lower risk of having antibiotics prescribed at least once than did people in the placebo group (RR: 0.72; 95% CI: 0.48, 1.07). In analyses stratified by age, in subjects aged ≥70 y, there was a significant reduction in antibiotic use in the high-dose vitamin D compared with placebo groups (RR: 0.53; 95% CI: 0.32, 0.90), whereas there was no effect in participants <70 y old (RR: 1.07; 95% CI: 0.58, 1.97) (P-interaction = 0.1). CONCLUSION: Although this study was a post hoc analysis and statistically nonsignificant, this trial lends some support to the hypothesis that supplementation with 60,000 IU vitamin D/mo is associated with lower risk of infection, particularly in older adults. The trial was registered at the Australian New Zealand Clinical Trials Registry (anzctr.org.au) as ACTRN12609001063202.

Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis : protocol for a randomised controlled trial

Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW(135)) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and >= 6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged >= 6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine-related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged >= 6 years; and vaccine safety. Discussion As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.

The contributions of solar ultraviolet radiation exposure and other determinants to Serum 25-Hydroxyvitamin D concentrations in Australian adults : the AusD study

The Quantitative Assessment of Solar UV [ultraviolet] Exposure for Vitamin D Synthesis in Australian Adults (AusD) Study aimed to better define the relationship between sun exposure and serum 25-hydroxyvitamin D (25(OH)D) concentration. Cross-sectional data were collected between May 2009 and December 2010 from 1,002 participants aged 18-75 years in 4 Australian sites spanning 24° of latitude. Participants completed the following: 1) questionnaires on sun exposure, dietary vitamin D intake, and vitamin D supplementation; 2) 10 days of personal ultraviolet radiation dosimetry; 3) a sun exposure and physical activity diary; and 4) clinical measurements and blood collection for 25(OH)D determination. Our multiple regression model described 40% of the variance in 25(OH)D concentration; modifiable behavioral factors contributed 52% of the explained variance, and environmental and demographic or constitutional variables contributed 38% and 10%, respectively. The amount of skin exposed was the single strongest contributor to the explained variance (27%), followed by location (20%), season (17%), personal ultraviolet radiation exposure (8%), vitamin D supplementation (7%), body mass index (weight (kg)/height (m)2) (4%), and physical activity (4%). Modifiable behavioral factors strongly influence serum 25(OH)D concentrations in Australian adults. In addition, latitude was a strong determinant of the relative contribution of different behavioral factors.

Crystalline A-DNA: The X-Ray Analysis of the Fragment d(G-G-T-A-T-A-C-C)

An A-DNA type double helical conformation was observed in the single crystal X-ray structure of the octamer d(G-G-T-A-T-A-C-C), 1, and its 5-bromouracil-containing analogue, 2. The structure of the isomorphous crystals (space group P61) was solved by a search technique based on packing criteria and R-factor calculations, with use of only low order data. At the present stage of refinement the R factors are 31 % for 1 and 28 % for 2 at a resolution of 2.25 A (0.225 nm). The molecules interact through their minor grooves by hydrogen bonding and base to sugar van der Waals contacts. The stable A conformation observed in the crystal may have some structural relevance to promoter regions where the T-A-T-A sequence is frequently found.

Le processus de travail d'une correspondante: une étude observationnelle

Pro gradu -tutkielman aiheena on kirjeenvaihtajan työprosessi. Tutkielma kuuluu kääntämisen sosiologian piiriin. Tutkimuksen kohteena oli Helsingin Sanomien Pariisin-kirjeenvaihtaja Minna Nalbantoglu, jonka työskentelyä tutkielman tekijä havainnoi Pariisissa viiden päivän ajan syyskuussa 2006. Tutkimuksen päämetodina oli tapaustutkimus, jonka lisäksi tutkimuksessa käytettiin metodina haastattelua ja havainnointia sekä dokumenttien, tallenteiden ja työnäytteiden analysointia. Tutkimuksen aineisto muodostui havaintomuistiinpanoista, kirjeenvaihtajan haastattelusta, ääneenajatteluprotokollista, haastattelunauhoista, kirjeenvaihtajan tuottamista artikkeleista, kirjeenvaihtajan käyttämistä lähteistä ja juttupäiväkirjoista. Tutkielman tarkoituksena oli muodostaa kokonaiskuva kirjeenvaihtajan työprosessista. Tavoitteena oli vastata seuraavin kysymyksiin: 1) Miten ja millä kriteereillä kirjeenvaihtaja valitsee Helsingin Sanomien lukijoille välitettävät uutiset? 2) Miten uutinen tuotetaan? 3) Minkälaista kääntämistä tai käännöseditointia (transediting) kirjeenvaihtajan työssä esiintyy? Tutkimustulokset on analysoitu viiden käsitteen avulla, jotka ovat uutiskriteerit, uutisen tuottamisprosessi, kääntäminen, käännöseditointi ja portinvartiointi (gatekeeping). Ensimmäiseen tutkimuskysymykseen vastattiin analysoimalla kirjeenvaihtajan tutkimusviikon aikana tuottamia artikkeleita Johan Galtungin ja Mari Holmboe Rugen (1965) klassisten uutiskriteerien avulla, joita täydennettiin Judy McGregorin (2002) päivitetyillä uutiskriteereillä. Toiseen tutkimuskysymykseen vastattiin kuvailemalla uutisten tuottamisprosessia. Samalla selvitettiin, mitä lähteitä kirjeenvaihtaja oli käyttänyt jutuissansa. Kolmatta tutkimuskysymystä varten artikkelit analysoitiin Teun A. van Dijkin (1988) uutisen tuottamisprosessin tutkimista varten kehittämällä mallilla. Van Dijkin mallin avulla määriteltiin, mikä tekstinkäsittelystrategia on kääntämistä ja mitkä käännöseditointia. Analyysin perusteella todettiin, että tekstin tuottamisprosessissa esiintyy myös uuden tekstin luomista ja tuotantoa yksikielisen materiaalin pohjalta. Kääntäminen ja käännöseditointi (Karen Stetting 1989) -käsitteitä pohdittiin ennen analyysia työn teoriaosuudessa. Uutisaiheiden analyysin perusteella todettiin, että mitä enemmän tapahtuma täyttää uutiskriteereitä, sitä todennäköisemmin se valitaan uutiseksi. Niin ikään mitä enemmän tapahtuma täyttää McGregorin päivittämiä uutiskriteereitä, sitä todennäköisemmin se valitaan uutiseksi. Analysoitujen uutisten määrä oli kuitenkin pieni, eikä tuloksia voida pitää kuin suuntaa-antavina. Artikkeleiden lähteenä oli käytetty lähinnä haastatteluita, lehtiartikkeleita ja uutistoimistojen sähkeitä. Muiden lähteiden käyttö oli satunnaista. Lähteiden ja käännösstrategioiden välillä ei havaittu korrelaatiota. Eniten käytetty tekstinkäsittelystrategia oli tiivistäminen. Käännöseditoinnin osuus oli yli puolet artikkeleiden tekstistä (keskiarvo 62 %) ja kääntämisen osuus vain kahdeksan prosenttia. Tutkimuksen perusteella käännöseditointi-käsitteen käyttö on perusteltua puhuttaessa kyseisen kirjeenvaihtajan työstä. Tutkimuksen perusteella on kehitetty uusi portinvartiointimalli, joka pohjautuu van Dijkin uutisen tuottamisprosessimalliin. Mallin avulla voidaan analysoida uutisen tuottamisprosessia ja päätellä, minkä verran kääntämistä ja käännöseditointia työssä esiintyy. Mallia ehdotetaan sovellettavaksi paitsi muiden kirjeenvaihtajien niin myös monikielisen materiaalin parissa työskentelevien toimittajien työn sekä uutiskääntämisen analysointiin.

Improvement in the voltage grading (axial and radial) of the generator column of a Van de Graaf generator by the use of a resistor chain

It is well known that the use of a series of resistors, connected between the equipotential rings of a Van de Graaff generator, improves the axial voltage grading of the generator. The work reported in this paper shows how the resistor chain also improves the radial voltage gradient. The electrolytic field mapping technique was adopted in the present work.

X-ray studies on crystalline complexes involving amino acids and peptides. XV. Crystal structures of L-lysine D-glutamate and L-lysine D-aspartate monohydrate and the effect of chirality on molecular aggregation

L-Lysine D-glutamate crystallizes in the monoclinic space group P2(1) with a = 4.902, b = 30.719, c = 9.679 A, beta = 90 degrees and Z = 4. The crystals of L-lysine D-aspartate monohydrate belong to the orthorhombic space group P2(1)2(1)2(1) with a = 5.458, b = 7.152, c = 36.022 A and Z = 4. The structures were solved by the direct methods and refined to R values of 0.125 and 0.040 respectively for 1412 and 1503 observed reflections. The glutamate complex is highly pseudosymmetric. The lysine molecules in it assume a conformation with the side chain staggered between the alpha-amino and the alpha-carboxylate groups. The interactions of the side chain amino groups of lysine in the two complexes are such that they form infinite sequences containing alternating amino and carboxylate groups. The molecular aggregation in the glutamate complex is very similar to that observed in L-arginine D-aspartate and L-arginine D-glutamate trihydrate, with the formation of double layers consisting of both types of molecules. In contrast to the situation in the other three LD complexes, the unlike molecules in L-lysine D-aspartate monohydrate aggregate into alternating layers as in the case of most LL complexes. The arrangement of molecules in the lysine layer is nearly the same as in L-lysine L-aspartate, with head-to-tail sequences as the central feature. The arrangement of aspartate ions in the layers containing them is, however, somewhat unusual. Thus the comparison between the LL and the LD complexes analyzed so far indicates that the reversal of chirality of one of the components in a complex leads to profound changes in molecular aggregation, but these changes could be of more than one type.

8-(3-methylphenoxy)-16H-dinaphtho[2,1-d;1',2'-g][1,3,2]dioxaphosphocine 8-oxide

In the title compound, C28H21O4P, the eight-membered heterocyclic dioxaphosphocine ring has a distorted boat conformation, with the phosphoryl O atom axial and the phenoxy group equatorial. The P=O distance is 1.451 (1) Angstrom and the average length of the three P-O bonds is 1.573 (1) Angstrom. The phenyl ring is nearly perpendicular to both naphthalene planes, making dihedral angles of 91.30 (3) and 97.65 (5)degrees with them. The angle between the two naphthalene planes is 67.73 (3)degrees. The crystal structure is stabilized by van der Waals interactions.

Germanane: a Low Effective Mass and High Bandgap 2-D Channel Material for Future FETs

We investigate the electronic properties of Germanane and analyze its importance as 2-D channel material in switching devices. Considering two types of morphologies, namely, chair and boat, we study the real band structure, the effective mass variation, and the complex band structure of unstrained Germanane by density-functional theory. The chair morphology turns out to be a more effective channel material for switching devices than the boat morphology. Furthermore, we study the effect of elastic strain, van der Waals force, and vertical electric field on these band structure properties. Due to its very low effective mass with relatively high-energy bandgap, in comparison with the other 2-D materials, Germanane appears to provide superior performance in switching device applications.

Dense network of O-H ... O and C-H ... O interactions in the solid state structure of n-pentyl-2-chloro-2-deoxy-alpha-D-manno-sept 3-uloside

Single crystal X-ray structural analysis of a septanoside, namely, n-pentyl-2-chloro-2-deoxy sept-3-uloside (1) provides many finer details of the molecular structure, in addition to its preferred twist-chair conformation, namely, (TC3,4)-T-5,6 conformation. Structural analysis reveals a dense network of O-H...O, C-H...O and van der Waals interactions that stabilize interdigitized, planar bi-layer structure of the crystal lattice. (C) 2014 Elsevier Ltd. All rights reserved.