Phylogenetics of Australasian gall flies (Diptera: Fergusoninidae): Evolutionary patterns of host-shifting and gall morphology.

This study investigated host-specificity and phylogenetic relationships in Australian galling flies, Fergusonina Malloch (Diptera: Fergusoninidae), in order to assess diversity and explore the evolutionary history of host plant affiliation and gall morphology. A DNA barcoding approach using COI data from 203 Fergusonina specimens from 5gall types on 56 host plant species indicated 85 presumptive fly species. These exhibited a high degree of host specificity; of the 40 species with multiple representatives, each fed only on a single host genus, 29 (72.5%) were strictly monophagous, and 11 (27.5%) were reared from multiple closely related hosts. COI variation within species was not correlated with either sample size or geographic distance. However variation was greater within oligophagous species, consistent with expectations of the initial stages of host-associated divergence during speciation. Phylogenetic analysis using both nuclear and mitochondrial genes revealed host genus-restricted clades but also clear evidence of multiple colonizations of both host plant genus and host species. With the exception of unilocular peagalls, evolution of gall type was somewhat constrained, but to a lesser degree than host plant association. Unilocular peagalls arose more often than any other gall type, were primarily located at the tips of the phylogeny, and did not form clades comprising more than a few species. For ecological reasons, species of this gall type are predicted to harbor substantially less genetic variation than others, possibly reducing evolutionary flexibility resulting in reduced diversification in unilocular gallers.

Fall in population-based mortality from coronary heart disease negated in people with diabetes mellitus: data from England.

AIMS: Mortality rates for coronary heart disease (CHD) have declined substantially in developed countries. Diabetes mellitus is an important risk factor for CHD; its prevalence is increasing. We aimed to compare trends in population-based mortality for CHD without diabetes on the death certificate with trends for CHD with diabetes on the same certificate. METHODS: Analysis of an all-England dataset with multiple-cause coded mortality records from 1995 to 2010. Analysis of a similar dataset for Oxford, because it has the longest run of multiple-cause coded mortality in England, from 1979. Age-specific and age-standardized mortality rates were calculated. RESULTS: In the all-England dataset, there were 1 772 760 deaths with CHD and no mention of diabetes; and 173 184 deaths with CHD and diabetes on the same death certificate. Of deaths with CHD without a mention of diabetes, rates per million men fell by more than half from 2843 (95% confidence interval: 2822-2862) in 1995 to 1379 (1366-1391) in 2010; and those in women halved from 1324 (1314-1336) to 628 (621-635). Of deaths with CHD and diabetes, rates per million men increased from 194 (188-200) to 215 (210-220); and those for women fell, but only very slightly, from 114 (111-118) to 101 (98-104). The longer run in Oxford, from 1979, showed that rates in men and women without diabetes had fallen by two-thirds; but that rates for CHD with diabetes had not fallen. CONCLUSIONS: The fall in mortality from CHD without diabetes has been spectacular. There has been no comparable fall in mortality from CHD with diabetes.

The evolution and biogeography of the austral horse fly tribe Scionini (Diptera: Tabanidae: Pangoniinae) inferred from multiple mitochondrial and nuclear genes.

Phylogenetic relationships within the Tabanidae are largely unknown, despite their considerable medical and ecological importance. The first robust phylogenetic hypothesis for the horse fly tribe Scionini is provided, completing the systematic placement of all tribes in the subfamily Pangoniinae. The Scionini consists of seven mostly southern hemisphere genera distributed in Australia, New Guinea, New Zealand and South America. A 5757 bp alignment of 6 genes, including mitochondrial (COI and COII), ribosomal (28S) and nuclear (AATS and CAD regions 1, 3 and 4) genes, was analysed for 176 taxa using both Bayesian and maximum likelihood approaches. Results indicate the Scionini are strongly monophyletic, with the exclusion of the only northern hemisphere genus Goniops. The South American genera Fidena, Pityocera and Scione were strongly monophyletic, corresponding to current morphology-based classification schemes. The most widespread genus Scaptia was paraphyletic and formed nine strongly supported monophyletic clades, each corresponding to either the current subgenera or several previously synonymised genera that should be formally resurrected. Molecular results also reveal a newly recognised genus endemic to New Zealand, formerly placed within Scaptia. Divergence time estimation was employed to assess the global biogeographical patterns in the Pangoniinae. These analyses demonstrated that the Scionini are a typical Gondwanan group whose diversification was influenced by the fragmentation of that ancient land mass. Furthermore, results indicate that the Scionini most likely originated in Australia and subsequently radiated to New Zealand and South American by both long distance dispersal and vicariance. The phylogenetic framework of the Scionini provided herein will be valuable for taxonomic revisions of the Tabanidae.

Cancer in patients admitted to hospital with diabetes mellitus aged 30 years and over: record linkage studies.

AIMS/HYPOTHESIS: The aim of this study was to determine the risk of cancer in people admitted to hospital for diabetes mellitus when aged 30 or older. METHODS: This study involved the analysis of two statistical datasets of linked hospital and mortality data, in an area in southern England, between 1963 and 1998 (the Oxford Record Linkage Study, ORLS1) and between 1999 and 2008 (ORLS2). Rates of cancer in the diabetes cohorts were compared with rates of cancer in reference cohorts and expressed as rate ratios. RESULTS: The rate ratio for all cancer in people admitted to hospital with diabetes was 1.01 (95% CI 0.95-1.06, based on 15,898 people with diabetes) for the years 1963-1998; and 1.09 (1.00-1.19, based on 7,771 people with diabetes) in the years 1999-2008. In both datasets, there were significantly high rate ratios for cancers of the liver (ORLS1 and ORLS2, respectively, 2.0 [95% CI 1.4-2.9]; 2.5 [95% CI 1.3-4.3]), pancreas (2.2 [95% CI 1.8-2.7]; 3.5 [95% CI 2.5-4.8]) and uterus (1.5 [95% CI 1.0-2.2]; 2.6 [95% CI 1.4-4.5]). There were significantly low rate ratios for cancer of the prostate (0.6 [95% CI 0.5-0.7]; 0.7 [95% CI 0.5-0.9]) and non-melanoma skin cancer (0.6 [95% CI 0.5-0.8]; 0.8 [95% CI 0.6-0.96]). CONCLUSIONS/INTERPRETATION: Diabetes mellitus was associated with an elevated risk of some site-specific cancers and a reduction of risk of others. Considering the risk in diabetes of all cancers combined, the elevation of risk, if any, is likely to be small and numerically less important than other known complications of diabetes.

Benign breast disease and subsequent breast cancer: English record linkage studies.

BACKGROUND: Benign breast disease (BBD) increases the risk of breast cancer, but details of the relationship would benefit from further study in the UK. METHODS: Analysis of linked statistical abstracts of hospital data, including a cohort of 20 976 women with BBD in an Oxford data set and 89 268 such women in an English national data set. RESULTS: Rate ratios (RRs) for breast cancer, comparing BBD and comparison cohorts in these two data sets, were 2.3 (95% CI: 2.2-2.5) and 3.2 (3.0-3.3), respectively. RRs rose with increasing age at BBD diagnosis and remained elevated for at least 20 years after diagnosis. RRs were particularly high for a relatively small number of cancers occurring in the first few months after BBD diagnosis. CONCLUSIONS: Our findings accord well with those in other large studies, mostly done in the USA, in showing a sustained long-term cancer risk after BBD. They also demonstrate that known long-term risks of disease can be reliably identified from linked routine administrative hospital statistics. Most other studies omit cancers in the first few months after BBD. Such cases-presumably either misdiagnosed or miscoded-merit further study to determine whether in fact they include diagnoses of cancer that were initially missed.

Immune-mediated and chronic inflammatory disease in people with sarcoidosis: disease associations in a large UK database.

BACKGROUND: Sarcoidosis is a multi-system disorder characterised by non-caseating granulomas. Coexistence of sarcoidosis with immune-mediated and chronic inflammatory diseases has been described in case series. However, the coexistence of two different diseases in individuals can occur by chance, even if each of the diseases is rare. AIM: To determine whether sarcoidosis necessitating hospital admission or day-case care coexists with a range of immune-mediated and chronic inflammatory diseases more commonly than expected by chance. DESIGN: Analysis of an epidemiological database of hospital admission and day-case statistics, spanning 30 years. RESULTS: 1510 patients with sarcoidosis were identified (mean age 44 years, median follow-up 19 years) who had been admitted to hospital or day-case care. Significant associations in the sarcoidosis cohort were identified with systemic lupus erythematosus (odds ratio (OR) 8.3; 95% CI 2.7 to 19.4), autoimmune chronic hepatitis (OR 6.7; 95% CI 1.8 to 17.1), multiple sclerosis (OR 3.3; 95% CI 1.7 to 5.6), coeliac disease (OR 3.1; 95% CI 1.01 to 7.3), thyrotoxicosis (OR 2.5; 95% CI 1.4 to 4.0), myxoedema (OR 2.2; 95% CI 1.2 to 3.7) and ulcerative colitis (OR 2.1; 95% CI 1.1 to 3.7). Weaker associations were found for diabetes mellitus with a first admission aged 30-49 years (OR 2.9; 95% CI 2.1 to 4.0) or age >50 (OR 1.7; 95% CI 1.2 to 2.3), but not for people age <30. No significant association with Crohn's disease (OR 1.52; 95% CI 0.61 to 3.14) or primary biliary cirrhosis (OR 3.75; 95% CI 0.77 to 11.0),was found. When all immune-mediated and chronic inflammatory diseases for which associations were sought were combined, the overall rate ratio associated with sarcoidosis was 2.2 (95% CI 1.9 to 2.6). CONCLUSION: This study adds epidemiological evidence to information from clinical reports that there is a connection between sarcoidosis and other immune-mediated and chronic inflammatory diseases.

New stiletto flies in the genus Anabarhynchus Macquart (Diptera: Therevidae) from Kangaroo Island, South Australia.

Anabarhynchus Macquart 1848 is a species-rich genus of stiletto flies (Diptera: Therevidae) belonging to the subfamily Therevinae, with over 113 species described from Australia. These flies are diverse and abundant in Australia's eucalypt woodland and mallee habitats. Here we describe, diagnose and illustrate a further three new Anabarhynchus species in the genus as follows: A. aurantilateralis sp. nov. and A. halmaturinus sp. nov., and A. venabrunneis sp. nov., from Kangaroo Island. These new species bring the total number of described Australian species in the genus to 116, with 13 of these known to occur on Kangaroo Island.

Birth of a biome: insights into the assembly and maintenance of the Australian arid zone biota.

The integration of phylogenetics, phylogeography and palaeoenvironmental studies is providing major insights into the historical forces that have shaped the Earth's biomes. Yet our present view is biased towards arctic and temperate/tropical forest regions, with very little focus on the extensive arid regions of the planet. The Australian arid zone is one of the largest desert landform systems in the world, with a unique, diverse and relatively well-studied biota. With foci on palaeoenvironmental and molecular data, we here review what is known about the assembly and maintenance of this biome in the context of its physical history, and in comparison with other mesic biomes. Aridification of Australia began in the Mid-Miocene, around 15 million years, but fully arid landforms in central Australia appeared much later, around 1-4 million years. Dated molecular phylogenies of diverse taxa show the deepest divergences of arid-adapted taxa from the Mid-Miocene, consistent with the onset of desiccation. There is evidence of arid-adapted taxa evolving from mesic-adapted ancestors, and also of speciation within the arid zone. There is no evidence for an increase in speciation rate during the Pleistocene, and most arid-zone species lineages date to the Pliocene or earlier. The last 0.8 million years have seen major fluctuations of the arid zone, with large areas covered by mobile sand dunes during glacial maxima. Some large, vagile taxa show patterns of recent expansion and migration throughout the arid zone, in parallel with the ice sheet-imposed range shifts in Northern Hemisphere taxa. Yet other taxa show high lineage diversity and strong phylogeographical structure, indicating persistence in multiple localised refugia over several glacial maxima. Similar to the Northern Hemisphere, Pleistocene range shifts have produced suture zones, creating the opportunity for diversification and speciation through hybridisation, polyploidy and parthenogenesis. This review highlights the opportunities that development of arid conditions provides for rapid and diverse evolutionary radiations, and re-enforces the emerging view that Pleistocene environmental change can have diverse impacts on genetic structure and diversity in different biomes. There is a clear need for more detailed and targeted phylogeographical studies of Australia's arid biota and we suggest a framework and a set of a priori hypotheses by which to proceed.

Maternal age and breast cancer risk.

Maternal age at time of birth was investigated as a risk factor for breast cancer in a study of 1,176 matched case-control pairs. There was no pattern of increasing adjusted relative risk of breast cancer with increasing maternal age, nor was the mean maternal age of cases older than that of controls. Similar negative results were found among the subset of subjects up to 35 years old, a group previously found to show marked maternal age effects. Thus previous reports of an association between breast cancer and advanced maternal age may have been due to chance, extraneous factors, or a misleading reliance on unadjusted mean maternal ages, rather than on relative risks.

Trends in operation rates for inguinal hernia over five decades in England: database study.

PURPOSE: We aimed to study trends over time in operation rates for inguinal hernia with and without obstruction over five decades. METHODS: Routine hospital statistics were used to analyse trends in National Health Service hospitals in England (1968-2011). RESULTS: All-England admission rates for elective repair of unobstructed inguinal hernia in males were 240.8 episodes per 100,000 population [95 % confidence interval (CI) 234.5-247.2] in 1968 and were relatively stable until 2003 after which they declined to 217.1 (215.4-218.8) by 2011. However, the stability of the all ages rates masked a large decline in admission rates in the young (e.g. 425 per 100,000 in 1968-1970 in males under 1 year of age, down to 155 per 100,000 in 2007-2011) and a large increase in the elderly (e.g. 247 in 1968-1970 per 100,000 males aged 75-84, up to 799 per 100,000 in 2007-2011). All-England admission rates for obstructed inguinal hernia in males almost halved, from 19.3 episodes (17.4-21.2) in 1968 to 10.7 episodes (10.3-11.0) per 100,000 population in 2011. Admission rates for females gradually declined over time for both unobstructed and obstructed inguinal hernia. CONCLUSION: Hospital admission rates for elective operation on inguinal hernia without obstruction, for all ages combined, have been relatively stable over five decades, but this masked big differences between age groups. Rates of obstructed hernia have declined over time, particularly in the early years covered by the study, and have not shown an increase associated with the recent fall in elective surgery for hernia repair.

INSECT PHYLOGENOMICS. Response to Comment on "Phylogenomics resolves the timing and pattern of insect evolution".

Tong et al. comment on the accuracy of the dating analysis presented in our work on the phylogeny of insects and provide a reanalysis of our data. They replace log-normal priors with uniform priors and add a "roachoid" fossil as a calibration point. Although the reanalysis provides an interesting alternative viewpoint, we maintain that our choices were appropriate.

Close genetic similarity between two sympatric species of tephritid fruit fly reproductively isolated by mating time.

Two sibling species of tephritid fruit fly, Bactrocera tryoni and B. neohumeralis, occur sympatrically throughout the range of B. neohumeralis in Australia. Isolation between the two species appears to be maintained by a difference in mating time: B. tryoni mates at dusk, whereas B. neohumeralis mates during the middle of the day. A morphological difference in humeral callus color also distinguishes the two species. Despite clear phenotypic evidence that B. tryoni and B. neohumeralis are distinct species, genetic differentiation as measured by four markers--nuclear DNA sequences from the white gene and the ribosomal internal transcribed spacer (ITS2), and mitochondrial DNA sequences from the cytochrome b (cytb) and cytochrome oxidase subunit II (COII) genes--is very small. Minor fixed differences occur in the ITS2 sequence, however, in all other cases the two species exhibit a high level of shared polymorphic variation. The close genetic similarity suggests either that speciation has occurred very rapidly and recently in the absence of any mitochondrial DNA sorting or that the sharing of polymorphisms is due to hybridization or introgression. A third species within the tryoni complex, B. aquilonis, is geographically isolated. Bactrocera aquilonis is also genetically very similar, but in this case there is clear differentiation for the mitochondrial loci. The three species form a group of considerable interest for investigation of speciation mechanisms.

Inhaled environmental/occupational irritants and allergens: mechanisms of cardiovascular and systemic responses. Introduction.

The articles in this monograph focus on the mechanisms whereby ambient particulate matter (PM) and co-pollutants deposited in the respiratory tract cause cardiovascular and systemic effects, especially in persons with preexisting conditions such as allergic hyperresponsiveness and pulmonary, cardiac, and vascular diseases. During the past few years, it has become clear that inhaled pollutants cause adverse effects outside the respiratory tract and that these effects may in some cases be more important than respiratory effects. Investigators pursuing traditional approaches to understanding mechanisms of air pollution effects need to be brought together with those outside that community who have expertise in pathogenetic mechanisms by which deposited air pollutants might affect nonrespiratory organs. To this end, a workshop was held and papers were developed from a broad range of scientists having specialized expertise in allergic and cardiovascular physiology. The overall goal of this monograph is to benchmark current thinking and enhance progress toward identifying and understanding the mechanisms by which nonrespiratory health effects occur and, by extension, to facilitate the appropriate management of relationships between air quality and health. This monograph contains a compilation of multidisciplinary research that forms a framework for generating and testing plausible new research hypotheses. Not only will this information stimulate the thinking of researchers, but it will also provide an improved foundation for funding agencies and advisory groups to frame research strategies, programs, and priorities.

Bronchial, alveolar, and vascular-induced anaphylaxis and irritant-induced cardiovascular and pulmonary responses.

We examine the respiratory, bronchomotor, cardiac, and vascular responses to histamine and ragweed allergen delivered to the bronchi or alveoli compartments and the potential role of sensory nerves and reflexes mediating the histamine-induced responses. The masses of aerosols deposited in the bronchi and alveoli were quantitated using radioaerosol techniques. Activation of sensory nerves and/or histamine-induced mediator release were characterized by depositing nedocromil sodium aerosol prior to histamine challenge. The histamine-induced responses due to vagosympathetic transmission were determined by performing bilateral vagotomy. Both histamine and ragweed increased respiratory rate, ventilation, and bronchomotor tone whether deposited in the bronchial or alveolar regions. However, these responses were not elicited when histamine was administered intravenously. Precipitous allergen-induced decreases in heart rate and systolic and diastolic pressure were maximal 72 sec following ragweed deposition in alveolar regions of the lungs. Increases in respiratory rate were mediated via the vagus whether delivered to the bronchi, alveoli, or vasculature. Histamine-induced increases in respiratory rate and bronchomotor tone were attenuated by nedocromil. When histamine was delivered to the alveolar regions, increases in lung resistance appeared to be mediated primarily via the vagus and when delivered to the bronchial airways primarily by its action on smooth muscle or local reflexes. Histamine-induced hypotension and bradycardia appear to be mediated by the direct action of histamine on the cardiovascular system rather than through a vagally mediated reflex.

Theoretic analysis of sites of aerosol deposition in the human lung.

A new model of aerosol deposition in the human lungs has been developed. It incorporates the deposition probability equations of Landahl and Findeisen in the Horsfield Asymmetric Model 1 of the lung. The deposition model takes into account the regional distribution of ventilation by incorporating principles of ventilatory mechanics into the determination of flow distribution in the lung. Calculations are performed for a 4 micrometers aerosol inhaled with a breathing pattern consisting of a 1,000 ml tidal volume and an average inspiratory flow of 500 ml/sec. A ventilation gradient from base to apex of 1.10 is assigned. The results show that deposition by impaction dominates in the large airways, while deposition by sedimentation dominates in the small airways and alveoli. Calculations of surface concentrations of particles deposited in the airways reveal that the segmental and subsegmental bronchi receive the highest concentrations. The gradient of particles deposited per unit lung volume from base to apex equals 1.13 which is very close to the ventilation gradient. The new model is the first attempt to assess the distribution of deposited particles in an asymmetric model of the lung, using a realistic distribution of ventilation.

The characterization of radioaerosol deposition in the healthy lung by histogram distribution analysis.

Thirteen healthy nonsmoking volunteers inhaled an 8.1 micrometers (MMAD) radioaerosol on two occasions. Aerosol deposition pattern within the right lung, as recorded by a gamma camera, was expressed as the 3rd and 4th moments of the distribution histogram (skew and kurtosis) of radioactivity during the first ten minutes after aerosol inhalation. Deposition pattern was also expressed as the percentage of deposited activity retained within the lung at 24 hr (24 hr % retention) and found to be significantly correlated with measures of skew (P less than 0.001). Tests of pulmonary function (FEV1, FVC, and MMFR) were significantly correlated with skew. Correlations were also demonstrated for these pulmonary function tests with 24 hr % retention but at lower levels of significance. Results indicate that changes in measures of forced expiratory airflow in healthy human volunteers influence deposition pattern and that the skew of the distribution of inhaled radioactivity may provide an acceptable index of deposition pattern.

Effects of drugs on mucociliary transport in the trachea and bronchial airways.

Pharmacologically active agents may change transport rates regionally within the airways of the lung, as well as affect the overall magnitude of the clearance of inhaled deposited radioaerosols. To investigate these possibilities the response of ethanol on pulmonary retention was determined and the responses of both the trachea and bronchial airways were measured after either oral administration of metaproterenol or inhalation of sulfuric acid mist. In the healthy nonchallenged lung, the velocity of mucociliary transport in the trachea was related to the percentage of activity cleared from the lung in two hours. Indices representing different portions of the pulmonary retention curve were also correlated. Changes in this interdependence of mucociliary transport within airways were produced by all agents. Metaproterenol increased tracheal mucus velocity but not lung clearance. Alcohol changed pulmonary retention in both magnitude and direction depending on the individual, resulting in an increase in variability of pulmonary mucociliary clearance between persons. Thus, to evaluate the effects of drugs or pollutants on the lower respiratory tract, measurements of mucociliary transport should be made in both the trachea and the bronchial airways.

Aerosol penetration and mucociliary transport in the healthy human lung. Effect of low serum theophylline levels.

The effect of theophylline on the penetration of an inhaled radioaerosol in the lung, bronchial clearance, and tracheal mucociliary transport rate (TMTR) was investigated in 13 healthy volunteers. Following a randomized, double-blind, crossover protocol, subjects ingested 4 mg/kg twice daily of theophylline or placebo for three days which resulted in stable, low therapeutic serum levels. Aerosol penetration, assessed by the skew of the initial distribution of lung radioactivity, was more peripheral (p less than 0.025) with theophylline, indicating bronchodilation that was not detectable by standard pulmonary function tests. The TMTR increased in ten of 13 subjects after theophylline, but not to a significant level. Bronchial clearance was not significantly different with theophylline despite the longer clearance pathway created by the increased peripheral aerosol deposition. This finding suggests that mucus transport rates in the intrapulmonary airways were increased by theophylline.