Clearing the air: Assessing healthcare professionals' awareness of air pollution's health consequences.

Air pollution (AP) significantly jeopardises health, with the Royal College of Physicians accepting the adverse effects of AP are not being sufficiently communicated to patients by healthcare professionals (HCP). To explore HCPs' understanding and attitudes toward AP and its health impacts, we conducted a service evaluation survey in a group of hospital doctors. A questionnaire comprising 20 questions about AP and its health associations was completed by 133 hospital doctors working at University Hospital Southampton NHS Foundation Trust, UK. While 65% (n = 86) of respondents strongly agreed that AP is relevant to health, 79% (n = 105) felt insufficiently trained on AP and its health associations. The survey shows that HCPs' knowledge of AP and its connection to poor health is a major barrier in discussions with patients. Further research is needed to understand whether these views are nationally shared among HCPs and to explore the most effective strategies for enhancing AP awareness.

Biodiscoveries within the Australian plant genus Eremophila based on international and interdisciplinary collaboration: results and perspectives on outstanding ethical dilemmas.

In a cross-continental research initiative, including researchers working in Australia and Denmark, and based on joint external funding by a 3-year grant from the Novo Nordisk Foundation, we have used DNA sequencing, extensive chemical profiling and molecular networking analyses across the entire Eremophila genus to provide new knowledge on the presence of natural products and their bioactivities using polypharmocological screens. Sesquiterpenoids, diterpenoids and dimers of branched-chain fatty acids with previously unknown chemical structures were identified. The collection of plant material from the Eremophila genus was carried out according to a 'bioprospecting agreement' with the Government of Western Australia. We recognize that several Eremophila species hold immense cultural significance to Australia's First Peoples. In spite of our best intentions to ensure that new knowledge gained about the genus Eremophila and any potential future benefits are shared in an equitable manner, in accordance with the Nagoya Protocol, we encounter serious dilemmas and potential conflicts in making benefit sharing with Australia's First Peoples a reality.

Navigating through chemical space and evolutionary time across the Australian continent in plant genus Eremophila.

Eremophila is the largest genus in the plant tribe Myoporeae (Scrophulariaceae) and exhibits incredible morphological diversity across the Australian continent. The Australian Aboriginal Peoples recognize many Eremophila species as important sources of traditional medicine, the most frequently used plant parts being the leaves. Recent phylogenetic studies have revealed complex evolutionary relationships between Eremophila and related genera in the tribe. Unique and structurally diverse metabolites, particularly diterpenoids, are also a feature of plants in this group. To assess the full dimension of the chemical space of the tribe Myoporeae, we investigated the metabolite diversity in a chemo-evolutionary framework applying a combination of molecular phylogenetic and state-of-the-art computational metabolomics tools to build a dataset involving leaf samples from a total of 291 specimens of Eremophila and allied genera. The chemo-evolutionary relationships are expounded into a systematic context by integration of information about leaf morphology (resin and hairiness), environmental factors (pollination and geographical distribution), and medicinal properties (traditional medicinal uses and antibacterial studies), augmenting our understanding of complex interactions in biological systems.

Comparison of short-term complications between unilateral and single-session bilateral surgery for medial patellar luxation in small/medium breed dogs.

OBJECTIVES: To compare the short-term complications of unilateral versus single-session bilateral medial patellar luxation surgery in small dogs. MATERIALS AND METHODS: The medical records of dogs weighing less than 13∙6 kg that underwent medial patellar luxation surgery were reviewed. Dogs were included in one of two groups based on the type of surgery performed (unilateral or single-session bilateral). Postoperative patellar luxation grade and complications were compared between the groups. RESULTS: Two hundred and fifty-one dogs were included. In the bilateral treatment group, there was less improvement in patellar luxation grade and postoperative medial patellar luxation grade was higher. The frequency of major complications was higher in the bilateral group (23%) compared with the unilateral group (12%). CLINICAL SIGNIFICANCE: Single-session bilateral medial patellar luxation surgery was associated with a higher complication rate compared to unilateral surgery in this non-randomised observational study. Staged rather than single-session bilateral surgery should be considered in dogs with bilateral medial patellar luxation to improve clinical outcome and reduce the chance of major complications.

An audit of the management of childhood-onset growth hormone deficiency during young adulthood in Scotland.

BACKGROUND: Adolescents with childhood onset growth hormone deficiency (CO-GHD) require re-evaluation of their growth hormone (GH) axis on attainment of final height to determine eligibility for adult GH therapy (rhGH). AIM: Retrospective multicentre review of management of young adults with CO-GHD in four paediatric centres in Scotland during transition. PATIENTS: Medical records of 130 eligible CO-GHD adolescents (78 males), who attained final height between 2005 and 2013 were reviewed. Median (range) age at initial diagnosis of CO-GHD was 10.7 years (0.1-16.4) with a stimulated GH peak of 2.3 µg/l (0.1-6.5). Median age at initiation of rhGH was 10.8 years (0.4-17.0). RESULTS: Of the 130 CO-GHD adolescents, 74/130(57 %) had GH axis re-evaluation by stimulation tests /IGF-1 measurements. Of those, 61/74 (82 %) remained GHD with 51/74 (69 %) restarting adult rhGH. Predictors of persistent GHD included an organic hypothalamic-pituitary disorder and multiple pituitary hormone deficiencies (MPHD). Of the remaining 56/130 (43 %) patients who were not re-tested, 34/56 (61 %) were transferred to adult services on rhGH without biochemical retesting and 32/34 of these had MPHD. The proportion of adults who were offered rhGH without biochemical re-testing in the four centres ranged between 10 and 50 % of their total cohort. CONCLUSIONS: A substantial proportion of adults with CO-GHD remain GHD, particularly those with MPHD and most opt for treatment with rhGH. Despite clinical guidelines, there is significant variation in the management of CO-GHD in young adulthood across Scotland.

Clinical and laboratory surface finishing procedures for zirconia on opposing human enamel wear: A laboratory study.

AIM: To investigate the effect of laboratory and clinical finishing procedures for zirconia on antagonistic enamel wear. MATERIALS AND METHODS: Forty-eight yttria-tetragonal partially stabilised zirconia (Y-TZP) specimens were prepared and divided into four groups according to their surface preparation: laboratory polished (LP); laboratory polished and glazed (G); clinically adjusted (CA); and clinically adjusted and repolished (CAR). Enamel opposing enamel was used as a control. Pre-testing surface roughness for each group was determined using contact profilometry. Two-body wear resistance tests were conducted using a masticatory simulator. Enamel specimens were subjected to 120,000 cycles in distilled water (frequency 1.6 Hz, loading force of 49 N). Volumetric and vertical enamel losses were measured by superimposition of pre- and post-testing images using a three-dimensional laser scanner and software analysis. Scanning electron microscopy was used for qualitative surface analysis of pre- and post-testing zirconia and enamel surfaces. One-way ANOVA and multiple comparisons with Bonferroni corrections were used for statistical analysis at a significance level of α=0.05. RESULTS: There was no statistical difference in volumetric and vertical enamel loss between CAR, G and LP. CAR produced statistically significantly less volumetric enamel loss compared with CA and control, and statistically significantly less vertical enamel loss compared with CA. Volumetric and vertical enamel loss were highly correlated in all groups. CONCLUSIONS: Enamel wear by clinically ground zirconia is comparable to that of opposing enamel surfaces and greater than clinically repolished zirconia. Repolishing of zirconia restorations following clinical adjustment with diamond burs is effective in reducing antagonistic enamel wear.

Plant virology and next generation sequencing: experiences with a Potyvirus.

Next generation sequencing is quickly emerging as the go-to tool for plant virologists when sequencing whole virus genomes, and undertaking plant metagenomic studies for new virus discoveries. This study aims to compare the genomic and biological properties of Bean yellow mosaic virus (BYMV) (genus Potyvirus), isolates from Lupinus angustifolius plants with black pod syndrome (BPS), systemic necrosis or non-necrotic symptoms, and from two other plant species. When one Clover yellow vein virus (ClYVV) (genus Potyvirus) and 22 BYMV isolates were sequenced on the Illumina HiSeq2000, one new ClYVV and 23 new BYMV sequences were obtained. When the 23 new BYMV genomes were compared with 17 other BYMV genomes available on Genbank, phylogenetic analysis provided strong support for existence of nine phylogenetic groupings. Biological studies involving seven isolates of BYMV and one of ClYVV gave no symptoms or reactions that could be used to distinguish BYMV isolates from L. angustifolius plants with black pod syndrome from other isolates. Here, we propose that the current system of nomenclature based on biological properties be replaced by numbered groups (I-IX). This is because use of whole genomes revealed that the previous phylogenetic grouping system based on partial sequences of virus genomes and original isolation hosts was unsustainable. This study also demonstrated that, where next generation sequencing is used to obtain complete plant virus genomes, consideration needs to be given to issues regarding sample preparation, adequate levels of coverage across a genome and methods of assembly. It also provided important lessons that will be helpful to other plant virologists using next generation sequencing in the future.

Split personality of a Potyvirus: to specialize or not to specialize?

Bean yellow mosaic virus (BYMV), genus Potyvirus, has an extensive natural host range encompassing both dicots and monocots. Its phylogenetic groups were considered to consist of an ancestral generalist group and six specialist groups derived from this generalist group during plant domestication. Recombination was suggested to be playing a role in BYMV's evolution towards host specialization. However, in subsequent phylogenetic analysis of whole genomes, group names based on the original hosts of isolates within each of them were no longer supported. Also, nine groups were found and designated I-IX. Recombination analysis was conducted on the complete coding regions of 33 BYMV genomes and two genomes of the related Clover yellow vein virus (CYVV). This analysis found evidence for 12 firm recombination events within BYMV phylogenetic groups I-VI, but none within groups VII-IX or CYVV. The greatest numbers of recombination events within a sequence (two or three each) occurred in four groups, three which formerly constituted the single ancestral generalist group (I, II and IV), and group VI. The individual sequences in groups III and V had one event each. These findings with whole genomes are consistent with recombination being associated with expanding host ranges, and call into question the proposed role of recombination in the evolution of BYMV, where it was previously suggested to play a role in host specialization. Instead, they (i) indicate that recombination explains the very broad natural host ranges of the three BYMV groups which infect both monocots and dicots (I, II, IV), and (ii) suggest that the three groups with narrow natural host ranges (III, V, VI) which also showed recombination now have the potential to reduce host specificity and broaden their natural host ranges.

A unified perspective on the nature of bonding in pairwise interatomic interactions.

Different classes of ground electronic state pairwise interatomic interactions are referenced to a single canonical potential using explicit transformations. These approaches have been applied to diatomic molecules N2, CO, H2(+), H2, HF, LiH, Mg2, Ca2, O2, the argon dimer, and one-dimensional cuts through multidimensional potentials of OC-HBr, OC-HF, OC-HCCH, OC-HCN, OC-HCl, OC-HI, OC-BrCl, and OC-Cl2 using accurate semiempirically determined interatomic Rydberg-Klein-Rees (RKR) and morphed intermolecular potentials. Different bonding categories are represented in these systems, which vary from van der Waals, halogen bonding, and hydrogen bonding to strongly bound covalent molecules with binding energies covering 3 orders of magnitude from 84.5 to 89,600.6 cm(-1) in ground state dissociation energies. Such approaches were then utilized to give a unified perspective on the nature of bonding in the whole range of diatomic and intermolecular interactions investigated.

A cross-sectional study of the prevalence of cardiac valvular abnormalities in hyperprolactinemic patients treated with ergot-derived dopamine agonists.

CONTEXT: Concern exists in the literature that the long-term use of ergot-derived dopamine agonist drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease. OBJECTIVE: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking dopamine agonists as treatment for lactotrope pituitary tumors and to explore any associations with the cumulative dose of drug used. DESIGN: A cross-sectional echocardiographic study was performed in a large group of patients who were receiving dopamine agonist therapy for hyperprolactinemia. Studies were performed in accordance with the British Society of Echocardiography minimum dataset for a standard adult transthoracic echocardiogram. Poisson regression was used to calculate relative risks according to quartiles of dopamine agonist cumulative dose using the lowest cumulative dose quartile as the reference group. SETTING: Twenty-eight centers of secondary/tertiary endocrine care across the United Kingdom participated in the study. RESULTS: Data from 747 patients (251 males; median age, 42 y; interquartile range [IQR], 34-52 y) were collected. A total of 601 patients had taken cabergoline alone; 36 had been treated with bromocriptine alone; and 110 had received both drugs at some stage. The median cumulative dose for cabergoline was 152 mg (IQR, 50-348 mg), and for bromocriptine it was 7815 mg (IQR, 1764-20 477 mg). A total of 28 cases of moderate valvular stenosis or regurgitation were observed in 24 (3.2%) patients. No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. CONCLUSION: This large UK cross-sectional study does not support a clinically concerning association between the use of dopamine agonists for the treatment of hyperprolactinemia and cardiac valvulopathy.

Rapid development of molecular markers by next-generation sequencing linked to a gene conferring phomopsis stem blight disease resistance for marker-assisted selection in lupin (Lupinus angustifolius L.) breeding.

Selection for phomopsis stem blight disease (PSB) resistance is one of the key objectives in lupin (Lupinus angustifolius L.) breeding programs. A cross was made between cultivar Tanjil (resistant to PSB) and Unicrop (susceptible). The progeny was advanced into F(8) recombinant inbred lines (RILs). The RIL population was phenotyped for PSB disease resistance. Twenty plants from the RIL population representing disease resistance and susceptibility was subjected to next-generation sequencing (NGS)-based restriction site-associated DNA sequencing on the NGS platform Solexa HiSeq2000, which generated 7,241 single nucleotide polymorphisms (SNPs). Thirty-three SNP markers showed the correlation between the marker genotypes and the PSB disease phenotype on the 20 representative plants, which were considered as candidate markers linked to a putative R gene for PSB resistance. Seven candidate markers were converted into sequence-specific PCR markers, which were designated as PhtjM1, PhtjM2, PhtjM3, PhtjM4, PhtjM5, PhtjM6 and PhtjM7. Linkage analysis of the disease phenotyping data and marker genotyping data on a F(8) population containing 187 RILs confirmed that all the seven converted markers were associated with the putative R gene within the genetic distance of 2.1 CentiMorgan (cM). One of the PCR markers, PhtjM3, co-segregated with the R gene. The seven established PCR markers were tested in the 26 historical and current commercial cultivars released in Australia. The numbers of "false positives" (showing the resistance marker allele band but lack of the putative R gene) for each of the seven PCR markers ranged from nil to eight. Markers PhtjM4 and PhtjM7 are recommended in marker-assisted selection for PSB resistance in the Australian national lupin breeding program due to its wide applicability on breeding germplasm and close linkage to the putative R gene. The results demonstrated that application of NGS technology is a rapid and cost-effective approach in development of markers for molecular plant breeding.

Deaths due to differentiated thyroid cancer: a South Island, New Zealand experience: 1984-2009.

AIM: To assess differentiated thyroid cancer (DTC) deaths from the northern half of New Zealand's South Island. METHODS: Retrospective review of Christchurch Hospital Thyroid Clinic and Oncology Department clinical records of resident patients who died of differentiated thyroid cancer of follicular cell origin over the 25-year period 1984-2009. RESULTS: During the 25-year study period 25 patients died from differentiated thyroid cancer. All patients (17 female, 8 male) were Caucasian, with median age 65 years (47-86 years) at presentation. Most (24/25) patients presented with advanced (15 Stage IV, 9 Stage III) disease. Three patients initially presented with cervical lymphadenopathy and four patients with distant metastases--three patients with bone metastases, and one with a pleural effusion. The pathological classification of the tumours included 14 papillary cancers (four were follicular variants), six follicular cancers and five Hurthle cell cancers. The majority of primary tumours were large (>4 cm) and 11 were locally invasive. However one patient had a small (1.3 cm) papillary cancer and presented with a pleural effusion. Surgical removal of the primary tumour was attempted in 24 of the 25 patients, 18 received postoperative radioiodine 131I therapy, and three had external beam radiation therapy. The median survival from diagnosis was 5.5 years (0.2-22 years) with two Stage IV patients (both with Hurthle cell cancers) dying within 4 months. The majority of patients died of metastatic disease but seven died of local disease. CONCLUSIONS: During the 25-year study period, 25 patients died of differentiated thyroid cancer which approximates to one DTC death per year in our region. The median age at diagnosis was 65 years with no patients <45 years of age, and the female to male ration was 2.1:1. Most patients presented with advanced disease--7 patients (28%) had distant metastases. Hurthle cell cancers were over-represented (20%) in our series.

Risk of significant gynaecological pathology in women with glandular neoplasia on cervical cytology.

OBJECTIVE: To review the risk of pre-invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia. METHODS: Review of the case notes of all women referred with cervical cytology reported as ?glandular neoplasia between January 1999 and December 2008 at two UK hospitals: Portsmouth Hospitals NHS Trust and Queen Mary's Hospital Sidcup. The category of 'borderline nuclear change in endocervical cells', result code 8 according to the national health service cancer screening programme (NHSCSP), was excluded from the study. RESULTS: A total of 200 women were identified using the hospitals' pathology computer systems. Invasive carcinoma was found in 48 women (24%): 28 endocervical adenocarcinomas, eight squamous cell carcinomas (SCC), ten endometrial and two ovarian adenocarcinomas. Pre-invasive neoplasia was found in 115 (57.5%), including 14 cervical glandular intraepithelial neoplasia (CGIN), 31 cervical intraepithelial neoplasia (CIN) grade 2/3 and 70 concomitant CGIN and CIN2/3. CIN1/HPV was found in 25, simple endometrial hyperplasia in three and no histological abnormality in three. Thirty-four (70.8%) of 48 invasive carcinomas (of which 23 were endocervical adenocarcinomas) were in asymptomatic women investigated for abnormal cytology. Fourteen of 34 (41.4%) of those with ?glandular neoplasia thought to be endometrial were CGIN or CIN2/3. Colposcopic appearances were normal in 47.6% of women with pure cervical glandular neoplasia (adenocarcinoma or CGIN) compared with 12.8% with squamous cell lesions (CIN2/3 or SCC): P = 0.0001. Thus, colposcopy was more sensitive for detecting squamous cell abnormalities than their glandular counterparts. Although cervical adenocarcinomas are less amenable to prevention by screening than cervical SCC, in our study cervical cytology predominantly detected these abnormalities at their early asymptomatic stages. CONCLUSION: At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.

Paired hydrogen bonds in the hydrogen halide homodimer (HI)2.

The HI homodimer was found to have structural and vibrational properties unlike any other previously studied (HX)(2) system, with X = F, Cl, and Br. The infrared spectrum of (HI)(2) is also observed to be distinctly different from the other members of the series. In addition, the interaction energy of the (HI)(2) dimer has been calculated using the coupled-cluster with singles, doubles, and perturbative triples [CCSD(T)] level of theory. A four-dimensional morphed intermolecular potential has been generated and then morphed using available near infrared and submillimeter spectroscopic data recorded in supersonic jet expansions. The morphed potential is found to have a single global minimum with a symmetric structure having C(2h) symmetry. The equilibrium dissociation energy is found to be 359 cm(-1) with the geometry in Jacobi coordinates of R(e) = 4.35 Å, θ(1) = 43°, θ(2) = 137°, and φ = 180°. The infrared spectrum is characterized by pairs of excited vibrational states resulting from the coupling of the two HI stretching modes. A qualitative model using a quadratic approximation has been fitted to obtain an estimate of this coupling. Furthermore, a morphed intermolecular potential for the vibrationally excited system was also obtained that gives a quantitative estimate of the shift in the potential due to the excitation. The submillimeter analysis is consistent with a ground state having its highest probability as a paired hydrogen bond configuration with R(0) = 4.56372(1) Å and an average angle θ=cos(-1)((1/2)) = 46.40(1)° (between the diatom center of mass∕center of mass axis and direction of each component hydrogen iodide molecule). On monodeuteration, however, the ground state is predicted to undergo an anomalous structural isotope change to an L-shaped HI-DI structure with highest probability at R(0) = 4.51 Å, θ(1) = 83°, θ(2) = 177°, and φ = 180°. These results provide a test for large scale ab initio calculations and have implications for the interpretation of photoinduced chemistry and other properties of the dimer.

Home administration of lanreotide Autogel by patients with acromegaly, or their partners, is safe and effective.

OBJECTIVE: The introduction of ready-to-use lanreotide Autogel has presented the possibility of patients receiving their acromegaly treatment at home. The objective of this study was to assess the ability of patients (or their partners) to administer repeat, unsupervised, injections of lanreotide Autogel without compromising efficacy or safety. DESIGN: Multicentre (10 UK regional endocrine centres), open-label, nonrandomised, controlled study. Patients elected either to receive/administer unsupervised home injections after injection technique training (Test group) or continued to receive injections from a healthcare professional (Control group). Patients received monthly injections of lanreotide Autogel at their established dose. Effects were monitored for up to 40 weeks. PATIENTS: Thirty patients (15 per treatment group) with acromegaly treated with a stable dose of lanreotide Autogel (60, 90 or 120 mg) for > or = 4 months before screening. Measurements The main outcome measure was the proportion of patients/partners who successfully administered injections throughout the study. RESULTS: All Test group patients/partners qualified to administer injections. Fourteen of 15 patients fulfilled all criteria for successful administration of unsupervised injections (95% confidence interval, 70%-99%). Fourteen of 15 Test and 14/15 Control patients maintained growth hormone and IGF-1 control. Local injection tolerability was good for both treatment groups, and safety profiles were similar. All Test group patients continued with unsupervised injections after the study. CONCLUSIONS: Patients with acromegaly or their partners were able to administer lanreotide Autogel injections with no detrimental effect on efficacy and safety; therefore, unsupervised home injections are a viable alternative to healthcare professional injections for suitably motivated patients.

Development of two sequence-specific PCR markers linked to the le gene that reduces pod shattering in narrow-leafed Lupin (Lupinus angustifolius L.)

Wild types of narrow-leaf lupin (Lupinus angustifolius L.) have seed pods that shatter upon maturity, leading to the loss of their seeds before or during the harvest process. Two recessive genes have been incorporated into domesticated cultivars of this species to maximize harvest-ability of the produce. One of these genes is called lentus (le). Two microsatellite - anchored fragment length polymorphism (MFLP) candidate markers were identified as closely linked to the le gene in a recombinant inbred line (RIL) population derived from a domesticated x wild type cross. The candidate MFLP markers were isolated from the gel, re-amplified by PCR, cloned and sequenced. The MFLP polymorphisms were converted into sequence-specific PCR-based markers. Linkage analysis by MapManager indicated that one of the markers, LeM1, was 2.6 centiMorgans (cM) and the other, LeM2, was 1.3 cM from the gene, with both being on the same side. The correlation between the marker genotype and the plant phenotype for the le gene is 95 percent for the Australian cultivars, and approximately 36 percent on wild types tested. These markers may be useful in marker assisted selection for the le gene when introgressing wild material into lupin breeding programs.

Construction of a genetic linkage map using MFLP and identification of molecular markers linked to domestication genes in narrow-leafed lupin (Lupinus angustifolius L.).

A mapping population of F(8)derived recombinant inbred lines (RILs) was established from a cross between a domesticated breeding line 83A:476 and a wild type P27255 in narrow-leaf lupin (Lupinus angustifolius L.). The parents together with the 89 RILs were subjected to DNA fingerprinting using microsatellite-anchored fragment length polymorphism (MFLP) to rapidly generate DNA markers to construct a linkage map. Five hundred and twenty two unique markers of which 21% were co-dominant, were generated and mapped. Phenotypic data for the domestication traits: mollis (soft seeds), leucospermus (white flower and seed colour); Lentus (reduced pod-shattering), iucundis (low alkaloid), Ku (early flowering) and moustache pattern on seed coats; were included. Three to 7 molecular markers were identified within 5 cM of each of these domestication genes. The anthracnose resistance gene Lanr1 was also mapped. Linkage groups were constructed using MapManager version QTXb20, resulting in 21 linkage groups consisting of 7 or more markers. The total map length was 1543 cM, with an average distance of 3.4 cM between adjacent markers. This is the first published map for a lupin species. The map can be exploited for marker assisted selection for genetic improvement in lupin breeding programs.