A survey of molecular line emission towards ultracompact HII regions

We have used the JCMT to survey molecular line emission towards 14 ultracompact HII regions (G5.89, G9.62, G10.30, G10.47, G12.21, G13.87, G29.96, G31.41, G34.26, G43.89, G45.12, G45.45, G45.47, and G75.78). For each source, we observed up to ten 1 GHz bands between 200 and 350 GHz, covering lines of more than 30 species including multiple transitions of CO isotopes, CH3OH, CH3CCH, CH3CN and HCOOCH3, and sulphuretted molecules. The number of transitions detected varied by a factor of 20 between sources; which were chosen following observations of high-excitation ammonia (Cesaroni et al. 1994a) and methyl cyanide (Olmi et al. 1993). In half our sample (the line-poor sources), only (CO)-O-17: (CO)-O-18, SO, (CS)-S-34 and CH3OH were detected. In the line-rich sources, we detected over 150 lines, including high excitation lines of CH3CN, HCOOCH3; C2H5CN, CH3OH, and CH3CCH. We have calculated the physical conditions of the molecular gas. To reproduce the emission from the line-rich sources requires both a hot, dense compact core and an ambient cloud consisting of less dense, cooler gas. The hot cores, which are less than 0.1 pc in size; reach densities of at least 10(8) cm(-3) and temperatures of more than 80 K. The line-poor sources can be modelled without a hot core by a 20-30 K, 10(5) cm(-3) cloud. We find no correlation between the size of the HII region and the current physical conditions in the molecular environment. A comparison with chemical models (Millar et al. 1997) confirms that grain surface chemistry is important in hot cores.

Coxiella burnetii (Q fever) seroprevalence in cattle

Human cases of Q fever appear to be common in Northern Ireland compared to the rest of the British Isles. The purpose of this study was to describe the seroepidemiology of Coxiella burnetii infection in cattle in Northern Ireland in terms of seroprevalence and determinants of infection. A total of 5182 animals (from a stratified systematic random sample of 273 herds) were tested with a commercial C. burnetii phase 2 IgG ELISA. A total of 6.2% of animals and 48.4% of herds tested positively. Results from a multilevel logistic regression model indicated that the odds of cattle being infected with Q fever increased with age, Friesian breed, being from large herds and from dairy herds. Large dairy herd animal prevalence was 12.5% compared to 2.1% for small beef herds. Preliminary seroprevalence in sheep (12.3%), goats (9.3%), pigs (0%) rats (9.7%) and mice (3.2%) using indirect immunofluorescence is reported.

Porcine Circovirus Type 2 Morphogenesis in a Clone Derived from the L35 Lymphoblastoid Cell Line

Porcine circovirus type 2 (PCV2) is the essential infectious agent of post-weaning multisystemic wasting syndrome (PMWS), one of the most important diseases of swine. Although several studies have described different biological properties of the virus, some aspects of its replication cycle, including ultrastructural alterations, remain unknown. The aim of the present study was to describe for the first time a complete morphogenesis study of PCV2 in a clone of the lymphoblastoid L35 cell line at the ultrastructural level using electron microscopy techniques. Cells were infected with PCV2 at a multiplicity of infection of 10 and examined at 0, 6, 12, 24, 48, 60 and 72 h post-infection. PCV2 was internalized by endocytosis, after which the virus aggregated in intracytoplasmic inclusion bodies (ICIs). Subsequently, PCV2 was closely associated with mitochondria, completing a first cytoplasmic phase. The virus entered the nucleus for replication and virus assembly and encapsidation occurred with the participation of the nuclear membrane. Immature virions left the nucleus and formed ICIs in a second cytoplasmic phase. The results suggest that at the end of the replication cycle (between 24 and 48 h), PCV2 was released either by budding of mature virion clusters or by lysis of apoptotic or dead cells. In conclusion, the L35-derived clone represents a suitable in-vitro model for PCV2 morphogenesis studies and characterization of the PCV2 replication cycle. (C) 2010 Elsevier Ltd. All rights reserved.

RNA interference targeting cathepsin B of the carcinogenic liver fluke, Opisthorchis viverrini

Functional genomics have not been reported for Opisthorchis viverrini or the related fish-borne fluke, Clonorchis sinensis. Here we describe the introduction by square wave electroporation of Cy3-labeled small RNA into adult O. viverrini worms. Adult flukes were subjected to square wave electroporation employing a single pulse for 20 ms of 125V in the presence of 50 µg/ml of Cy3-siRNA. The parasites tolerated this manipulation and, at 24 and 48 h after electroporation, fluorescence from the Cy3-siRNA was evident throughout the parenchyma of the worms, with strong fluorescence evident in the guts and reproductive organs of the adult worms. Second, other worms were treated using the same electroporation settings with double stranded RNA targeting an endogenous papain-like cysteine protease, cathepsin B. This manipulation resulted in a significant reduction in specific mRNA levels encoding cathepsin B, and a significant reduction in cathepsin B activity against the diagnostic peptide, Z-Arg-Arg-AMC. This appears to be the first report of introduction of reporter genes into O. viverrini and the first report of experimental RNA interference (RNAi) in this fluke. The findings indicated the presence of an intact RNAi pathway in these parasites which, in turn, provides an opportunity to probe gene functions in this neglected tropical disease pathogen.

Na+/H+ exchange inhibitor cariporide attenuates skeletal muscle infarction when administered before ischemia or reperfusion

Administration of Na(+)/H(+) exchange isoform-1 (NHE-1) inhibitors before ischemia has been shown to attenuate myocardial infarction in several animal models of ischemia-reperfusion injury. However, controversy still exists as to the efficacy of NHE-1 inhibitors in protection of myocardial infarction when administered at the onset of reperfusion. Furthermore, the efficacy of NHE-1 inhibition in protection of skeletal muscle from infarction (necrosis) has not been studied. This information has potential clinical applications in prevention or salvage of skeletal muscle from ischemia-reperfusion injury in elective and trauma reconstructive surgery. The objective of this research project is to test our hypothesis that the NHE-1 inhibitor cariporide is effective in protection of skeletal muscle from infarction when administered at the onset of sustained ischemia or reperfusion and to study the mechanism of action of cariporide. In our studies, we observed that intravenous administration of cariporide 10 min before ischemia (1 or 3 mg/kg) or reperfusion (3 mg/kg) significantly reduced infarction in pig latissimus dorsi muscle flaps compared with the control, when these muscle flaps were subjected to 4 h of ischemia and 48 h of reperfusion (P <0.05; n = 5 pigs/group). Both preischemic and postischemic cariporide treatment (3 mg/kg) induced a significant decrease in muscle myeloperoxidase activity and mitochondrial-free Ca(2+) content and a significant increase in muscle ATP content within 2 h of reperfusion (P <0.05; n = 4 pigs/group). Preischemic and postischemic cariporide treatment (3 mg/kg) also significantly inhibited muscle NHE-1 protein expression within 2 h of reperfusion after 4 h of ischemia, compared with the control (P <0.05; n = 3 pigs/group). These observations support our hypothesis that cariporide attenuates skeletal muscle infarction when administered at the onset of ischemia or reperfusion, and the mechanism involves attenuation of neutrophil accumulation and mitochondrial-free Ca(2+) overload and preservation of ATP synthesis in the early stage of reperfusion.

Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac

The nonsteroidal anti-inflammatory drug diclofenac is extremely toxic to Old World Gyps vultures (median lethal dose -0.1-0.2 mg/kg), evoking visceral gout, renal necrosis, and mortality within a few days of exposure. Unintentional secondary poisoning of vultures that fed upon carcasses of diclofenac-treated livestock decimated populations in the Indian subcontinent. Because of the widespread use of diclofenac and other cyclooxygenase-2 inhibiting drugs, a toxicological study was undertaken in turkey vultures (Cathartes aura) as an initial step in examining sensitivity of New World scavenging birds. Two trials were conducted entailing oral gavage of diclofenac at doses ranging from 0.08 to 25 mg/kg body weight. Birds were observed for 7 d, blood samples were collected for plasma chemistry (predose and 12, 24, and 48 h and 7 d postdose), and select individuals were necropsied. Diclofenac failed to evoke overt signs of toxicity, visceral gout, renal necrosis, or elevate plasma uric acid at concentrations greater than 100 times the estimated median lethal dose reported for Gyps vultures. For turkey vultures receiving 8 or 25 mg/kg, the plasma half-life of diclofenac was estimated to be 6 h, and it was apparently cleared after several days as no residues were detectable in liver or kidney at necropsy. Differential sensitivity among avian species is a hallmark of cyclooxygenase-2 inhibitors, and despite the tolerance of turkey vultures to diclofenac, additional studies in related scavenging species seem warranted.

Children's judgements about pain at age 8-10 years:do extremely low birthweight (<or = 1000 g) children differ from full birthweight peers?

Children's judgements about pain at age 8-10 years were examined comparing two groups of children who had experienced different exposure to nociceptive procedures in the neonatal period: extremely low birthweight (ELBW) <or = 1000 g (N = 47) and full birthweight (FBW) > or = 2500 g (N = 37). The 24 pictures that comprise the Pediatric Pain Inventory, depicting events in four settings: medical, recreational, daily living, and psychosocial, were used as the pain stimuli. The subjects rated pain intensity using the Color Analog Scale and pain affect using the Facial Affective Scale. Child IQ and maternal education were statistically adjusted in group comparisons. Pain intensity and pain affect related to activities of daily living and recreation were significantly higher than psychosocial and medically related pain on both scales in both groups of children. Although the two groups of children did not differ overall in their perceptions of pain intensity or affect, the ELBW children rated medical pain intensity significantly higher than psychosocial pain, unlike the FBW group. Also, duration of neonatal intensive care unit stay for the ELBW children was related to increased pain affect ratings in recreational and daily living settings. Despite altered response to pain in the early years reported by parents, on the whole at 8-10 years of age ELBW children judged pain in pictures similarly to their term peers. However, differences were evident, which suggests that studies are needed of biobehavioural reactivity to pain beyond infancy, as well as research into beliefs, attitudes, and perceptions about pain during the course of childhood in formerly ELBW children.

Pre-validation methods for developing a patient reported outcome instrument

BACKGROUND: Measures that reflect patients' assessment of their health are of increasing importance as outcome measures in randomised controlled trials. The methodological approach used in the pre-validation development of new instruments (item generation, item reduction and question formatting) should be robust and transparent. The totality of the content of existing PRO instruments for a specific condition provides a valuable resource (pool of items) that can be utilised to develop new instruments. Such 'top down' approaches are common, but the explicit pre-validation methods are often poorly reported. This paper presents a systematic and generalisable 5-step pre-validation PRO instrument methodology.

METHODS: The method is illustrated using the example of the Aberdeen Glaucoma Questionnaire (AGQ). The five steps are: 1) Generation of a pool of items; 2) Item de-duplication (three phases); 3) Item reduction (two phases); 4) Assessment of the remaining items' content coverage against a pre-existing theoretical framework appropriate to the objectives of the instrument and the target population (e.g. ICF); and 5) qualitative exploration of the target populations' views of the new instrument and the items it contains.

RESULTS: The AGQ 'item pool' contained 725 items. Three de-duplication phases resulted in reduction of 91, 225 and 48 items respectively. The item reduction phases discarded 70 items and 208 items respectively. The draft AGQ contained 83 items with good content coverage. The qualitative exploration ('think aloud' study) resulted in removal of a further 15 items and refinement to the wording of others. The resultant draft AGQ contained 68 items.

CONCLUSIONS: This study presents a novel methodology for developing a PRO instrument, based on three sources: literature reporting what is important to patient; theoretically coherent framework; and patients' experience of completing the instrument. By systematically accounting for all items dropped after the item generation phase, our method ensures that the AGQ is developed in a transparent, replicable manner and is fit for validation. We recommend this method to enhance the likelihood that new PRO instruments will be appropriate to the research context in which they are used, acceptable to research participants and likely to generate valid data.

Genome-wide association study of urinary albumin excretion rate in patients with type 1 diabetes

Aims/hypothesis: An abnormal urinary albumin excretion rate (AER) is often the first clinically detectable manifestation of diabetic nephropathy. Our aim was to estimate the heritability and to detect genetic variation associated with elevated AER in patients with type 1 diabetes. 
 Methods: The discovery phase genome-wide association study (GWAS) included 1,925 patients with type 1 diabetes and with data on 24 h AER. AER was analysed as a continuous trait and the analysis was stratified by the use of antihypertensive medication. Signals with a p value <10^{−4 were followed up in 3,750 additional patients with type 1 diabetes from seven studies.} 
 Results: The narrow-sense heritability, captured with our genotyping platform, was estimated to explain 27.3% of the total AER variability, and 37.6% after adjustment for covariates. In the discovery stage, five single nucleotide polymorphisms in the GLRA3 gene were strongly associated with albuminuria (p < 5 × 10^{−8). In the replication group, a nominally significant association (p = 0.035) was observed between albuminuria and rs1564939 in GLRA3, but this was in the opposite direction. Sequencing of the surrounding genetic region in 48 Finnish and 48 UK individuals supported the possibility that population-specific rare variants contribute to the synthetic association observed at the common variants in GLRA3. The strongest replication (p = 0.026) was obtained for rs2410601 between the PSD3 and SH2D4A genes. Pathway analysis highlighted natural killer cell mediated immunity processes.} 
 Conclusions/interpretation: This study suggests novel pathways and molecular mechanisms for the pathogenesis of albuminuria in type 1 diabetes.

Optical Coherence Tomography for the Monitoring of Neovascular Age-Related Macular Degeneration: A Systematic Review

Topic

To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition.

Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests.

Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias.

We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%–93%) and 48% (95% CI, 30%–67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias.

There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

Increase in the pharmacological management of Type 2 diabetes with pay-for-performance in primary care in the UK

Aims To determine whether the financial incentives for tight glycaemic control, introduced in the UK as part of a pay-for-performance scheme in 2004, increased the rate at which people with newly diagnosed Type 2 diabetes were started on anti-diabetic medication.

Methods A secondary analysis of data from the General Practice Research Database for the years 1999-2008 was performed using an interrupted time series analysis of the treatment patterns for people newly diagnosed with Type 2 diabetes (n=21 197).

Results Overall, the proportion of people with newly diagnosed diabetes managed without medication 12months after diagnosis was 47% and after 24months it was 40%. The annual rate of initiation of pharmacological treatment within 12months of diagnosis was decreasing before the introduction of the pay-for-performance scheme by 1.2% per year (95% CI -2.0, -0.5%) and increased after the introduction of the scheme by 1.9% per year (95% CI 1.1, 2.7%). The equivalent figures for treatment within 24months of diagnosis were -1.4% (95% CI -2.1, -0.8%) before the scheme was introduced and 1.6% (95% CI 0.8, 2.3%) after the scheme was introduced.

Conclusion The present study suggests that the introduction of financial incentives in 2004 has effected a change in the management of people newly diagnosed with diabetes. We conclude that a greater proportion of people with newly diagnosed diabetes are being initiated on medication within 1 and 2years of diagnosis as a result of the introduction of financial incentives for tight glycaemic control.

Assessing the environmental fate of selected polybrominated diphenyl ethers in the region surrounding the Zhuoshui River of Taiwan based on an Equilibrium Constant fugacity model

Polybrominated diphenyl ethers (PBDEs) are a group of flame retardants that have been in use since the 1970s. They are included in the list of hazardous substances known as persistent organic pollutants (POPs) because they are extremely hazardous to the environment and human health. PBDEs have been extensively used in industry and manufacturing in Taiwan, thus its citizens are at high risk of exposure to these chemicals.
An assessment of the environmental fate of these compounds in the Zhuoshui river and Changhua County regions of western Taiwan, and also including the adjacent area of the Taiwan Strait, was conducted for three high risk congeners, BDE-47, -99 and -209, to obtain information regarding the partitioning, advection, transfer and long range transport potential of the PBDEs in order to identify the level of risk posed by the pollutants in this region.
The results indicate that large amounts of PBDEs presently reside in all model compartments – air, soil, water, and sediment – with particularly high levels found in air and especially in sediment. The high levels found in sediment, particularly for BDE-209, are significant, since there is the threat of these pollutants entering the food chain, either directly through benthic feeding, or through resuspension and subsequent feeding in the pelagic region of the water column which is a distinct possibility in the strong currents found within the Taiwan Strait. Another important result is that a substantial portion of emissions leave the model domain directly through advection, particularly for BDE-47 (58%) and BDE-209 (75%), thus posing a risk to adjacent communities.
Model results were generally in reasonable agreement with available measured concentrations. In air, model concentrations are in reasonably good agreement with available measured values. For both BDE-47 and -99, model concentrations are a factor of 2-3 higher and BDE-209 within the range of measured values. In soil, model results are somewhat less than measured values. In sediment, model results are at the high end of measured values.

The BTA stat test:A tumor marker for the detection of upper tract transitional cell carcinoma

Objectives. To conduct a prospective evaluation to determine the utility of the BTA stat test in the detection of upper tract transitional cell carcinoma (UTTCC). Monitoring for UTTCC currently relies on invasive procedures such as upper tract imaging, ureteral washing cytology (UWC) and/or ureteroscopy, or voided urine cytology (VUC). The BTA stat test is a sensitive qualitative immunoassay that detects human complement factor H-related protein in voided urine.

Methods. A total of 81 patients participated, 27 with histopathologically confirmed UTTCC, 26 with upper tract calculi, and 28 with microscopic hematuria but no evidence of urologic disease. Voided specimens collected before surgery or treatment were tested with the BTA stat test and VUC. UWC was performed in specimens collected by a ureteral catheter.

Results. The BTA stat test was significantly more sensitive and specific than VUC or UWC. The overall sensitivity for each was 82%, 11%, and 48%; the specificity was 89%, 54%, and 33%. The positive predictive value for the BTA stat test was 79% and the negative predictive value was 91%, both the highest of the three tests.

Conclusions. The BTA stat test was superior to VUC and UWC in the detection of UTTCC. These results may support the adoption of a less aggressive follow-up policy when monitoring for UTTCC when the BTA stat result is negative. If cystoscopy is negative and the BTA stat test is positive, upper tract investigations should be expedited and, if the bladder is in place, bladder biopsies performed. (C) 2001, Elsevier Science Inc.

Exercise training protects the LDLI subfraction from oxidation susceptibility in an aged human population

Background Exercise training is considered an effective strategy to improve metabolic disease. Despite this, less is known regarding exercise training in the prevention and susceptibility of LDL subfraction oxidation, particularly in an aged population. 
Methods Eleven aged (55 ± 4 yrs) and twelve young (21 ± 2 yrs) participants were randomly separated into an experimental or control group as follows: young exercise (n = 6); young control (n = 6); aged exercise (n = 6) and aged control (n = 5). The participants assigned to the exercise groups performed 12 weeks of moderate intensity (55–65% VO2max) exercise training. Venous blood was extracted at baseline, and 48 h following 12 weeks of exercise and assayed for a range of metabolites associated with lipid composition and lipoprotein susceptibility to oxidation. 
Results Although there was no difference in the oxidation potential (time ½ max) of LDL I, II or III between groups at baseline (p > 0.05), there was an increase in time ½ max for LDL I following exercise within the aged exercise group (p < 0.05). Moreover, α-tocopherol concentration was selectively lower in the aged exercise group, compared to the young exercise at baseline. The lipid composition of LDL I, LDL II, LDL III, VLDL, HDL2, HDL3 and serum lipid hydroperoxides remained unchanged as a function of exercise training and ageing (p > 0.05). 
Conclusion The primary finding of this study demonstrates that adaptations in LDL resistance to oxidation occur following 12 weeks of exercise training in the aged, and this may be of clinical significance, as oxidation of LDL has been implicated in atherosclerosis.

Quality of reporting of dental survival analyses

To explore the quality of reporting (writing and graphics) of articles that used time-to-event analyses to report dental treatment outcomes. A systematic search of the top 50 dental journals in 2008 produced the sample of articles for this analysis. Articles reporting treatment outcomes with (n = 95) and without (n = 91) time-to-event statistics were reviewed. Survival descriptive words used in the two groups were analysed (Pearson's chi-square). The quality of life tables, survival curves and time-to-event statistics were assessed (Kappa analysed agreement) and explored. Words describing dental outcomes 'over time' were more common in time-to-event compared with control articles (77%, 3%, P < 0.001). Non-specific use of 'rate' was common across both groups. Life tables and survival curves were used by 39% and 48% of the time-to-event articles, with at least one used by 82%. Construction quality was poor: 21% of life tables and 28% of survival curves achieved an acceptable standard. Time-to-event statistical reporting was poor: 3% achieved a high and 59% achieved an acceptable standard. The survival statistic, summary figure and standard error were reported in 76%, 95% and 20% of time-to-event articles. Individual statistical terms and graphic aids were common within and unique to time-to-event articles. Unfortunately, important details were regularly omitted from statistical descriptions and survival figures making the overall quality poor. It is likely this will mean such articles will be incorrectly indexed in databases, missed by searchers and unable to be understood completely if identified.