Structural studies of analgesics and their interactions. VII. Stereoisomerism and disorder in the structure of oxyphenbutazone monohydrate

Oxyphenbutazone, C19H20N203, a metabolite and perhaps the active form of phenylbutazone, is a widely used non-narcotic analgesic and anti-inflammatory pyrazolidinedione derivative. The monohydrate of the compound crystallizes in the triclinic space group Pi with two molecules in a unit cell of dimensions a -- 9.491 (4), b = 10.261 (5), c = 11.036 (3)A and ¢~ = 72.2 (1), fl = 64.3 (1), 7 = 73.0 (1) °. The structure was solved by direct methods and refined to an R value of 0.107 for 1498 observed reflections. The butyl group in the molecule is disordered. The hydroxyl group occupies two sites with unequal occupancies. On account of the asymmetry at the two N atoms and one of the C atoms in the central five-membered ring, the molecule can exist in eight isomeric states, of which four are sterically unfavourable. The disorder in the position of the hydroxyl group can be readily explained on the basis of the existence, with unequal abundances, of all four sterically favourable isomers.The bond lengths and angles in the molecule are similar to those in phenylbutazone. The crystal structure is stabilized by van der Waals interactions, and O-H... O hydrogen bonds involving the carbonyl and the hydroxyl groups as well as a water molecule.

Genetic and environmental influences on migraine: a twin study across six countries

Migraine is a common neurovascular brain disorder that is manifested in recurrent episodes of disabling headache. The aim of the present study was to compare the prevalence and heritability of migraine across six of the countries that participate in GenomEUtwin project including a total number of 29,717 twin pairs. Migraine was assessed by questionnaires that differed between most countries. It was most prevalent in Danish and Dutch females (32% and 34%, respectively), whereas the lowest prevalence was found in the younger and older Finnish cohorts (13% and 10%, respectively). The estimated genetic variance (heritability) was significant and the same between sexes in all countries. Heritability ranged from 34% to 57%, with lowest estimates in Australia, and highest estimates in the older cohort of Finland, the Netherlands, and Denmark. There was some indication that part of the genetic variance was non-additive, but this was significant in Sweden only. In addition to genetic factors, environmental effects that are non-shared between members of a twin pair contributed to the liability of migraine. After migraine definitions are homogenized among the participating countries, the GenomEUtwin project will provide a powerful resource to identify the genes involved in migraine.

Evidence for an X-linked genetic component in familial typical migraine

Migraine is a common complex disorder that shows strong familial aggregation. There is a general increased prevalence of migraine in females compared with males, with recent studies indicating that migraine affects 18% of females compared with 6% of males. This preponderance of females among migraine sufferers coupled with evidence of an increased risk of migraine in first degree relatives of male probands but not in relatives of female probands suggests the possibility of an X-linked dominant gene. We report here the localization of a typical migraine susceptibility locus to the X chromosome. Of three large multigenerational migraine pedigrees two families showed significant excess allele sharing to Xq markers (P = 0.031 and P = 0.012). Overall analysis of data from all three pedigrees gave significant evidence in support of linkage and heterogeneity (HLOD = 3.1). These findings provide conclusive evidence that familial typical migraine is a heterogeneous disorder. We suggest that the localization of a migraine susceptibility locus to the X chromosome could in part explain the increased risk of migraine in relatives of male probands and may be involved in the increased female prevalence of this disorder.

Phosphine resistance in Sitophilus oryzae (L.) from eastern Australia: Inheritance, fitness and prevalence

The inheritance and fitness of phosphine resistance was investigated in an Australian strain of the rice weevil, Sitophilus oryzae (L.), as well as its prevalence in eastern Australia. This type of knowledge may provide insights in to the development of phosphine resistance in this species with the potential for better management. This strain was 12.2 × resistant at the LC50 level based on results for adults exposed for 20 h. Data from the testing of F1 adults from the reciprocal crosses (R♀ × S♂ and S♀ × R♂) showed that resistance was autosomal and inherited as an incompletely recessive trait with a degree of dominance of -0.88. The dose-response data for the F1 × S and F1 × R test crosses, and the F2 progeny were compared with predicted dose-response assuming monogenic recessive inheritance, and the results were consistent with resistance being conferred by one major gene. There was no evidence of fitness cost based on the frequency of susceptible phenotypes in hybridized populations that were reared for seven generations without exposure to phosphine. Lack of fitness cost suggests that resistant alleles will tend to persist in field populations that have undergone selection even if selection pressure is removed. Discriminating dose tests on 107 population samples collected from farms from 2006 to 2010 show that populations containing insects with the weak resistant phenotype are common in eastern Australia, although the frequency of resistant phenotypes within samples was typically low. The prevalence of resistance is a warning that this species has been subject to considerable selection pressure and that effective resistance management practices are needed to address this problem. Crown Copyright © 2014.

Field inoculation with arbuscular-mycorrhizal fungi overcomes phosphorus and zinc deficiencies of linseed (Linum usitatissimum) in a vertisol subject to long-fallow disorder

Long-fallow disorder is expressed as exacerbated deficiencies of phosphorus (P) and/or zinc (Zn) in field crops growing after long periods of weed-free fallow. The hypothesis that arbuscular-mycorrhizal fungi (AMF) improve the P and Zn nutrition, and thereby biomass production and seed yield of linseed (Linum usitatissimum) was tested in a field experiment. A factorial combination of treatments consisting of +/- fumigation, +/- AMF inoculation with Glomus spp., +/- P and +/- Zn fertilisers was used on a long-fallowed vertisol. The use of such methods allowed an absolute comparison of plants growing with and without AMF in the field for the first time in a soil disposed to long-fallow disorder. Plant biomass, height, P and Zn concentrations and contents, boll number and final seed yield were (a) least in fumigated soil with negligible AMF colonisation of the roots, (b) low initially in long-fallow soil but increased with time as AMF colonisation of the roots developed, and (c) greatest in soil inoculated with AMF cultures. The results showed for the first time in the field that inflows of both P and Zn into linseed roots were highly dependent on %AMF-colonisation (R-2 = 0.95 for P and 0.85 for Zn, P < 0.001) in a soil disposed to long-fallow disorder. Relative field mycorrhizal dependencies without and with P+Zn fertiliser were 85 % and 86 % for biomass and 68 % and 52 % for seed yield respectively. This research showed in the field that AMF greatly improved the P and Zn nutrition, biomass production and seed yield of linseed growing in a soil disposed to long-fallow disorder. The level of mycorrhizal colonisation of plants suffering from long-fallow disorder can increase during the growing season resulting in improved plant growth and residual AMF inoculum in the soil, and thus it is important for growers to recognise the cause and not terminate a poor crop prematurely in order to sow another. Other positive management options to reduce long fallows and foster AMF include adoption of conservation tillage and opportunity cropping.

Patterns of service utilisation within Australian hepatology clinics: High prevalence of advanced liver disease

Accepted Article Abstract Background: Liver diseases in Australia are estimated to affect 6 million people with a societal cost of $51 billion annually. Information about utilization of specialist hepatology care is critical in informing policy makers about the requirements for delivery of hepatology-related health care. Aims: This study examined etiology and severity of liver disease seen in a tertiary hospital hepatology clinic, as well as resource utilisation patterns. Methods: A longitudinal cohort study included consecutive patients booked in hepatology outpatient clinics during a 3 month period. Subsequent outpatient appointments for these patients over the following 12 months were then recorded. Results: During the initial 3 month period 1471 appointments were scheduled with a hepatologist, 1136 of which were attended. 21% of patients were “new cases”. Hepatitis B (HBV) was the most common disease etiology for new cases (37%). Advanced disease at presentation varied between etiology, with HBV (5%), Hepatitis C (HCV) (31%), non-alcoholic fatty liver disease (NAFLD) (46%) and alcoholic liver disease (ALD) (72%). Most patients (83%) attended multiple hepatology appointments, and a range of referrals patterns for procedures, investigations and other specialty assessments were observed. Conclusions: There is a high prevalence of HBV in new case referrals. Patients with HCV, NAFLD and ALD have a high prevalence of advanced liver disease at referral, requiring ongoing surveillance for development of decompensated liver disease and liver cancer. These findings that describe patterns of health service utilisation among patients with liver disease provide useful information for planning sustainable health service provision for this clinical population

Prevalence and incidence of shoulder and neck dysfunction after neck dissection: A systematic review

Background: Head and neck cancer is a debilitating disease. Not only can the primary tumour cause painful swallowing and speech difficulties, the treatments required to manage it can impact on neck and shoulder musculoskeletal function. In particular, those patients who undergo neck dissection surgery to remove lymph nodes from the neck can acquire accessory nerve injury during the procedure and a resultant loss of shoulder/neck motion, strength and function. Despite changes to surgical techniques that can protect the nerve, patients still report problems post-operatively.

Prevalence and potential fitness cost of weak phosphine resistance in Tribolium castaneum (Herbst) in eastern Australia

The prevalence of resistance to phosphine in the rust-red flour beetle, Tribolium castaneum, from eastern Australia was investigated, as well as the potential fitness cost of this type of resistance. Discriminating dose tests on 115 population samples collected from farms from 2006 to 2010 showed that populations containing insects with the weakly resistant phenotype are common in eastern Australia (65.2 of samples), although the frequency of resistant phenotypes within samples was typically low (median of 2.3). The population cage approach was used to investigate the possibility that carrying the alleles for weak resistance incurs a fitness cost. Hybridized populations were initiated using a resistant strain and either of two different susceptible strains. There was no evidence of a fitness cost based on the frequency of susceptible phenotypes in hybridized populations that were reared for seven generations without exposure to phosphine. This suggests that resistant alleles will tend to persist in field populations that have undergone selection even if selection pressure is removed. The prevalence of resistance is a warning that this species has been subject to considerable selection pressure and that effective resistance management practices are needed to address this problem. The resistance prevalence data also provide a basis against which to measure management success.

Structural Studies of Analgesics and Their Interactions. VIII.* Rotational Isomerism and Disorder in the Crystal Structure of Meelofenamie Acid

Meclofenamic acid, C I4HIICI2NO2, probably the most potent among analgesic fenamates, crystallizes in the triclinic space group P1, with a = 8.569 (5), b = 8.954(8), c -- 9.371 (4) A, ct = 103.0 (2), fl -- 103.5 (2), y = 92.4 (2) ° , Z = 2, D m = 1.43 (4), D c = 1.41 Mg m -3. The structure was solved by direct methods and refined to R = 0.135 for 1062 observed reflections. The anthranilic acid moiety in the molecule is nearly planar and is nearly perpendicular to the 2,6-dichloro-3-methylphenyl group. The molecules, which exist as hydrogen-bonded dimers, have an internal hydrogen bond involving the imino and the carboxyl groups. The methyl group is disordered and occupies two positions with unequal occupancies. The disorder can be satisfactorily explained in terms of the rotational isomerism of the 2,6-dichloro-3-methylphenyl group about the bond which connects it to the anthranilic acid moiety and the observed occupancies on the basis of packing considerations.

Making and changing wills: Prevalence, predictors, and triggers

Wills are important social, economic, and legal documents. Yet little is known about current will making practices and intentions. A comprehensive national database on the prevalence of will making in Australia was developed to identify who is or is not most likely to draw up a will and triggers for making and changing wills. A national survey of 2,405 adults aged above 18 years was administered by telephone in August and September 2012. Fifty-nine percent of the Australian adult population has a valid will, and the likelihood of will making increases with age and estate value. Efforts to get organized, especially in combination with life stage and asset changes trigger will making; procrastination, rather than a strong resistance, appears to explain not making a will. Understanding will making is timely in the context of predicted significant intergenerational transfers of wealth, changing demographics, and a renewed emphasis on retirement planning.

A systematic review of instruments for assessment of capacity in activities of daily living in children with developmental co-ordination disorder

Children with developmental co-ordination disorder (DCD) face evident motor difficulties in activities of daily living (ADL). Assessment of their capacity in ADL is essential for diagnosis and intervention, in order to limit the daily consequences of the disorder. The aim of this study is to systematically review potential instruments for standardized and objective assessment of children's capacity in ADL, suited for children with DCD. As a first step, databases of MEDLINE, EMBASE, CINAHL and PsycINFO were searched to identify studies that described instruments with potential for assessment of capacity in ADL. Second, instruments were included for review when two independent reviewers agreed that the instruments: (1) are standardized and objective; (2) assess at activity level and comprise items that reflect ADL, and; (3) are applicable to school-aged children that can move independently. Out of 1507 publications, 66 publications were selected, describing 39 instruments. Seven of these instruments were found to fulfil the criteria and were included for review: the Bruininks-Oseretsky Test of Motor Performance-2 (BOT2); the Do-Eat (Do-Eat); the Movement Assessment Battery for Children-2 (MABC2); the school-Assessment of Motor and Process Skills (schoolAMPS); the Tuffts Assessment of Motor Performance (TAMP); the Test of Gross Motor Development (TGMD); and the Functional Independence Measure for Children (WeeFIM). As a third step, for the included instruments, suitability for children with DCD was discussed based on the ADL comprised, ecological validity and other psychometric properties. We concluded that current instruments do not provide comprehensive and ecologically valid assessment of capacity in ADL as required for children with DCD.

Activities of daily living in children with developmental coordination disorder: Performance, learning, and participation

Background Children with developmental coordination disorder (DCD) face evident motor difficulties in daily functioning. Little is known, however, about their difficulties in specific activities of daily living (ADL). Objective The purposes of this study were: (1) to investigate differences between children with DCD and their peers with typical development for ADL performance, learning, and participation, and (2) to explore the predictive values of these aspects. Design. This was a cross-sectional study. Methods In both a clinical sample of children diagnosed with DCD (n=25 [21 male, 4 female], age range=5-8 years) and a group of peers with typical development (25 matched controls), the children’s parents completed the DCDDaily-Q. Differences in scores between the groups were investigated using t tests for performance and participation and Pearson chi-square analysis for learning. Multiple regression analyses were performed to explore the predictive values of performance, learning, and participation. Results Compared with their peers, children with DCD showed poor performance of ADL and less frequent participation in some ADL. Children with DCD demonstrated heterogeneous patterns of performance (poor in 10%-80% of the items) and learning (delayed in 0%-100% of the items). In the DCD group, delays in learning of ADL were a predictor for poor performance of ADL, and poor performance of ADL was a predictor for less frequent participation in ADL compared with the control group. Limitations A limited number of children with DCD were addressed in this study. Conclusions This study highlights the impact of DCD on children’s daily lives and the need for tailored intervention.

Development and psychometric properties of the DCDDaily: a new test for clinical assessment of capacity in activities of daily living in children with developmental coordination disorder

Objective To develop the DCDDaily, an instrument for objective and standardized clinical assessment of capacity in activities of daily living (ADL) in children with developmental coordination disorder (DCD), and to investigate its usability, reliability, and validity. Subjects Five to eight-year-old children with and without DCD. Main measures The DCDDaily was developed based on thorough review of the literature and extensive expert involvement. To investigate the usability (assessment time and feasibility), reliability (internal consistency and repeatability), and validity (concurrent and discriminant validity) of the DCDDaily, children were assessed with the DCDDaily and the Movement Assessment Battery for Children-2 Test, and their parents filled in the Movement Assessment Battery for Children-2 Checklist and Developmental Coordination Disorder Questionnaire. Results 459 children were assessed (DCD group, n = 55; normative reference group, n = 404). Assessment was possible within 30 minutes and in any clinical setting. For internal consistency, Cronbach’s α = 0.83. Intraclass correlation = 0.87 for test–retest reliability and 0.89 for inter-rater reliability. Concurrent correlations with Movement Assessment Battery for Children-2 Test and questionnaires were ρ = −0.494, 0.239, and −0.284, p < 0.001. Discriminant validity measures showed significantly worse performance in the DCD group than in the control group (mean (SD) score 33 (5.6) versus 26 (4.3), p < 0.001). The area under curve characteristic = 0.872, sensitivity and specificity were 80%. Conclusions The DCDDaily is a valid and reliable instrument for clinical assessment of capacity in ADL, that is feasible for use in clinical practice.

Scoping study for a national survey of the prevalence of child abuse and neglect

This is a report produced as a result of a study commissioned by the Australian Government Royal Commission into Institutional Responses to Child Sexual Abuse.