The case for routine cervical mediastinoscopy prior to radical surgery for malignant pleural mesothelioma

Objectives: To assess whether cervical mediastinoscopy is necessary before radical resection of malignant pleural mesothelioma (MPM). Methods: Patients who underwent radical excision of MPM in a 48-month period were prospectively followed for evidence of disease recurrence and death. Histological evidence of extra pleural lymph node metastases was correlated with survival. Lymph node size at intraoperative lymphadenectomy was correlated with the presence of metastatic tumour. Results: The 55 patients who underwent radical resection (51 extra pleural pneumonectomies and 4 radical pleurectomies) comprised 50 men and 5 women with a median age of 58 years, range 41-70. Histological examination revealed 50 epithelioid, four biphasic and one sarcomatoid histology. Postoperative IMIG T stage was stage I 4, II 11, III 30 and IV 10. Postoperatively the 17 patients with metastases to the extra pleural lymph nodes had significantly shorter survival (median 4.4 months, 95% CI 3.2-5.4) than those without (median survival 16.3 months, 95% CI 11.6-21.0) P=0.012 Kaplan-Meier analysis. Seventy-seven extra pleural lymph nodes without metastases were measured with a mean long axis diameter of 16.9 mm (range 4-55) ; 22 positive nodes had a mean long axis diameter of 15.2 mm (range 6-30). In 15 of the 17 patients with positive extra pleural nodes, the nodes could have been biopsied at cervical mediastinoscopy. Conclusions: This study confirms that extra pleural nodal metastases are related to poor survival. Pathological nodal involvement cannot be predicted from nodal dimensions. These data suggest that all patients being considered for radical resection of MPM should preferentially undergo preoperative cervical mediastinoscopy irrespective of radiological findings. © 2003 Elsevier B.V. All rights reserved.

Timing and source constraints on the relationship between mafic and felsic intrusions in the Emeiashan large igneous province

Several I- and A-type granite, syenite plutons and spatially associated, giant Fe–Ti–V deposit-bearing mafic ultramafic layered intrusions occur in the Pan–Xi(Panzhihua–Xichang) area within the inner zone of the Emeishan large igneous province (ELIP). These complexes are interpreted to be related to the Emeishan mantle plume. We present LA-ICP-MS and SIMS zircon U–Pb ages and Hf–Nd isotopic compositions for the gabbros, syenites and granites from these complexes. The dating shows that the age of the felsic intrusive magmatism (256.2 ± 3.0–259.8 ± 1.6 Ma) is indistinguishable from that of the mafic intrusive magmatism (255.4 ± 3.1–259.5 ± 2.7 Ma) and represents the final phase of a continuous magmatic episode that lasted no more than 10 Myr. The upper gabbros in the mafic–ultramafic intrusions are generally more isotopically enriched (lower eNd and eHf) than the middle and lower gabbros, suggesting that the upper gabbros have experienced a higher level of crustal contamination than the lower gabbros. The significantly positive eHf(t) values of the A-type granites and syenites (+4.9 to +10.8) are higher than those of the upper gabbros of the associated mafic intrusion, which shows that they cannot be derived by fractional crystallization of these bodies. They are however identical to those of the mafic enclaves (+7.0 to +11.4) and middle and lower gabbros, implying that they are cogenetic. We suggest that they were generated by fractionation of large-volume, plume-related basaltic magmas that ponded deep in the crust. The deep-seated magma chamber erupted in two stages: the first near a density minimum in the basaltic fractionation trend and the second during the final stage of fractionation when the magma was a low density Fe-poor, Si-rich felsic magma. The basaltic magmas emplaced in the shallowlevel magma chambers differentiated to form mafic–ultramafic layered intrusions accompanied by a small amount of crustal assimilation through roof melting. Evolved A-type granites (synenites and syenodiorites) were produced dominantly by crystallization in the deep crustal magma chamber. In contrast, the I-type granites have negative eNd(t) [-6.3 to -7.5] and eHf(t) [-1.3 to -6.7] values, with the Nd model ages (T Nd DM2) of 1.63-1.67 Ga and Hf model ages (T Hf DM2) of 1.56-1.58 Ga, suggesting that they were mainly derived from partial melting of Mesoproterozoic crust. In combination with previous studies, this study also shows that plume activity not only gave rise to reworking of ancient crust, but also significant growth of juvenile crust in the center of the ELIP.

Weekly cisplatin concurrently with radiotherapy in head and neck squamous cell cancer : a retrospective analysis of a tertiary institute experience

Radiotherapy combined with three weekly 100 mg/m2 of cisplatin is the accepted standard of care in head and neck squamous cell carcinoma. However, this regimen is associated with severe toxicities with devastating effects on patients. Alternative protocols like weekly 40 mg/m2 have been used in an attempt to reduce toxicities. The main objective of the present study is to identify the dose intensities and toxicities of weekly cisplatin in patients treated in a tertiary centre over a 12 month period. Included patients had squamous cell carcinoma arising in the oral cavity, oropharynx, larynx, or hypopharynx. Patients were excluded if they had nasopharyngeal squamous cell carcinoma, distant metastasis or if they had prior treatment for head and neck cancer excluding neck dissection. During the study period, 52 patients met the inclusion criteria and their data were retrospectively obtained from the patients' database of St James hospital, Dublin. The median age of the study cohort was 54 years (range 33-73). Of the patients, 40 (76.9 %) were male and 12 (20.1 %) were female. The primary tumour sites were as follows: oral cavity and oropharynx in 38 (73 %), larynx in 10 (19 %), and hypopharynx in 4 (8 %). In total, 33 (63.5 %) patients had stage IV disease, while 19 (36.5 %) had stage III disease. Treatment was definitive in 35 (67 %) patients and adjuvant in 17 (35 %). Full-dose radiotherapy was achieved in 50 (96 %) patients. Only 22 (42.3 %) patients completed the intended six cycles of chemotherapy. Cumulative dose of 200 mg/m2 or more was reached in 37 (71 %) patients. The acute adverse effects included grades 3 and 4 mucositis, which occurred in 22 (43.3 %) and 6 patients (12 %), respectively. Grade 3 and 4 neutropenia occurred in six (11.5 %) and three (5.7 %) patients, respectively. The only other haematological toxicity was grade 3 anaemia in 20 (38.4 %) patients. There was no grade 3 or 4 renal toxicity among the study cohort, although grade 2 was observed in six (11.5 %) patients. Death occurred in one patient due to neutropenic septicaemia. In conclusion, weekly cisplatin is associated with moderate to severe toxicities and might lead to suboptimal chemotherapy delivery. More prospective clinical studies are required to determine the optimal chemoradiation regimen in head and neck squamous cell carcinoma.

A pilot study exploring Australian general practice nurses roles, responsibilities and professional development needs in well and sick child care

Aim Explore practice nurses' (PNs) role in child health and development, and advising parents about child health issues. Background Introduction of the four-year-old child health check into general practice in 2008 placed additional responsibilities on PNs in child health and wellness. This study explores their readiness to expand their practice into this area. Design Integrated mixed method design, self-report survey. Method A purpose-developed questionnaire explored demographics, child health roles and responsibilities, difficulties encountered, professional development needs, barriers and facilitators, and professional development activities undertaken in the past year. Surveys were posted to 218 PNs in one rural Division of General Practice (DGP) in Queensland, Australia; 29 responded. Results PNs reported a significant role in well and sick child care (93.1%) though few had a paediatric/child health background (14.3%). Roles included immunisations (92.3%), child health checks (65.4%), general child health and development (26.9%), asthma (23.1%), feeding (15.4%), fever (11.5%), settling/sleeping (11.5%). PNs were interested in learning more about (81.5%) and incorporating more child health into their practice (81.5%). Professional development in childhood growth and development (80.0%), health and illness (60.0%) and advising new mothers (20.0%) was needed. Conclusions PNs play a substantial role in child health, are unprepared for the complexities of this role and have preferred methods for undertaking professional development to address knowledge deficits. Implications for practice PNs are unprepared for an advanced role in child health and wellness. Significant gaps in their knowledge to support this role were identified. This ever-expanding role requires close monitoring to ensure knowledge precedes expectations to practice.

Why are there Different Age Related Trends for Different Chemicals?

Persistent organic pollutants (POPs) such as dioxins, PCBs, persistent organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs) as well as perfluorinated compounds (PFCs) and triclosan are ubiquitous in the human population. In Australia, we have pooled and subsequently analysed over 10 000 human serum samples for the determination of these chemicals by age group (0–0.5; 0.6–1; 1.1–1.5; 1.6–2; 2.1–2.5; 2.6–3; 3.1–3.5; 3.6–4; 4.1–6; 6.1–9; 9.1–12; 12.1–15; 16–30; 31–45; 46–60 and >60 years) and gender. The results of this analysis were then used to assess the trends of these different chemicals as a function of age, gender and to a lesser extent region. Our data demonstrate clear chemical specific age trends. In particular we demonstrate that for the traditional POPs there is an increase in body burden with age whereas the opposite is true for chemicals such as PBDEs. For PFCs we find chemical specific age trends that vary from compound to compound. For triclosan we show that no apparent age trend is observable. The results of the study and its implications to the collection and archiving of samples for retrospective analysis are discussed.

Direct detection of additives and degradation products from polymers by liquid extraction surface analysis employing chip-based nanospray mass spectrometry

RATIONALE: Polymer-based surface coatings in outdoor applications experience accelerated degradation due to exposure to solar radiation, oxygen and atmospheric pollutants. These deleterious agents cause undesirable changes to the aesthetic and mechanical properties of the polymer, reducing its lifetime. The use of antioxidants such as hindered amine light stabilisers (HALS) retards these degradative processes; however, mechanisms for HALS action and polymer degradation are poorly understood. METHODS: Detection of the HALS TINUVINW123 (bis(1-octyloxy-2,2,6,6-tetramethyl-4-piperidyl) sebacate) and the polymer degradation products directly from a polyester-based coil coating was achieved by liquid extraction surface analysis (LESA) coupled to a triple quadrupole QTRAPW 5500 mass spectrometer. The detection of TINUVINW123 and melamine was confirmed by the characteristic fragmentation pattern observed in LESA-MS/MS spectra that was identical to that reported for authentic samples. RESULTS: Analysis of an unstabilised coil coating by LESA-MS after exposure to 4 years of outdoor field testing revealed the presence of melamine (1,3,5-triazine-2,4,6-triamine) as a polymer degradation product at elevated levels. Changes to the physical appearance of the coil coating, including powder-like deposits on the coating's surface, were observed to coincide with melamine deposits and are indicative of the phenomenon known as polymer ' blooming'. CONCLUSIONS: For the first time, in situ detection of analytes from a thermoset polymer coating was accomplished without any sample preparation, providing advantages over traditional extraction-analysis approaches and some contemporary ambient MS methods. Detection of HALS and polymer degradation products such as melamine provides insight into the mechanisms by which degradation occurs and suggests LESA-MS is a powerful new tool for polymer analysis. Copyright (C) 2012 John Wiley & Sons, Ltd.

The 10 Australian ecosystems most vulnerable to tipping points

We identify the 10 major terrestrial and marine ecosystems in Australia most vulnerable to tipping points, in which modest environmental changes can cause disproportionately large changes in ecosystem properties. To accomplish this we independently surveyed the coauthors of this paper to produce a list of candidate ecosystems, and then refined this list during a 2-day workshop. The list includes (1) elevationally restricted mountain ecosystems, (2) tropical savannas, (3) coastal floodplains and wetlands, (4) coral reefs, (5) drier rainforests, (6) wetlands and floodplains in the Murray-Darling Basin, (7) the Mediterranean ecosystems of southwestern Australia, (8) offshore islands, (9) temperate eucalypt forests, and (10) salt marshes and mangroves. Some of these ecosystems are vulnerable to widespread phase-changes that could fundamentally alter ecosystem properties such as habitat structure, species composition, fire regimes, or carbon storage. Others appear susceptible to major changes across only part of their geographic range, whereas yet others are susceptible to a large-scale decline of key biotic components, such as small mammals or stream-dwelling amphibians. For each ecosystem we consider the intrinsic features and external drivers that render it susceptible to tipping points, and identify subtypes of the ecosystem that we deem to be especially vulnerable. © 2011 Elsevier Ltd.

Prenylated Alkylbisphenols from Grevillea whiteana

Eleven new bisresorcinols including four mixtures each of two isomers and one resorcinol/phloroglucinol derivative, together with five known resorcinols have been isolated from the ethyl acetate extract of sterns of Grevillea whiteana. The new Compounds were identified as 4-(3-hydroxy-3-methylbutyl)grebustol-B (10a), 4'-(3-hydroxy-3-methylbutyl)grebustol-B (10b), 4-(4-hydroxy-3-methylbutyl)grebustol-B (2a) and 4'-(4-hydroxy-3-methylbutyl) rebustol-B (2b), 2,2-dimethyldihydropyrano grebustol-B (11a) and iso-2,2-dimethyldihydropyranogrebustol-B (11b), 2,2-dimethyl-3 xi-hydroxydihydropyranogrebustol-B (7a) and iso-2,2-dimethyl-3 xi-hydroxydihydropyranogrebustol-B (7b), 15-(2-(4-hydroxy-3-methylbutyl)-resorcinol-5-yl)-1-(phloroglucinolyl )-9(Z)pentadecen-one (whiteanone) (4), 5,5'-(hexadecan-diyl)bisresorcinol (12) and 2-methyl-5,5'-(8(Z)hexadecen-1,16-diyl)bisresorcinol (9). This is the first record of pyranobisresorcinols in the genus and the first report of a phloroglucinol terminal Phenolic unit in any Grevillea species.

Photoelectron spectroscopy of HCCN- and HCNC- reveals the quasilinear triplet carbenes, HCCN and HCNC

Negative ion photoelectron spectroscopy has been used to study the HCCN- and HCNC- ions. The electron affinities (EA) of cyanocarbene have been measured to be EA(HCCN (X) over tilde (3)Sigma(-)=2.003+/-0.014 eV and EA(DCCN (X) over tilde (3)Sigma(-))=2.009+/-0.020 eV. Photodetachment of HCCN- to HCCN (X) over tilde (3)Sigma(-) shows a 0.4 eV long vibrational progression in nu(5), the H-CCN bending mode; the HCCN- photoelectron spectra reveal excitations up to 10 quanta in nu(5). The term energies for the excited singlet state are found to be T-0(HCCN (a) over tilde (1)A('))=0.515+/-0.016 eV and T-0(DCCN (a) over tilde (1)A('))=0.518+/-0.027 eV. For the isocyanocarbene, the two lowest states switch and HCNC has a singlet ground state and an excited triplet state. The electron affinities are EA(HCNC (X) over tilde (1)A('))=1.883+/-0.013 eV and EA((X) over tilde (1)A(') DCNC)=1.877+/-0.010 eV. The term energy for the excited triplet state is T-0(HCNC (a) over tilde (3)A("))=0.050+/-0.028 eV and T-0(DCNC (a) over tilde (3)A("))=0.063+/-0.030 eV. Proton transfer kinetics in a flowing afterglow apparatus were used to re-measure the enthalpy of deprotonation of CH3NC to be Delta(acid)H(298)(CH3NC)=383.6+/-0.6 kcal mol(-1). The acidity/EA thermodynamic cycle was used to deduce D-0(H-CHCN)=104+/-2 kcal mol(-1) [Delta(f)H(0)(HCCN)=110+/-4 kcal mol(-1)] and D-0(H-CHNC)=106+/-4 kcal mol(-1) [Delta(f)H(0)(HCNC)=133+/-5 kcal mol(-1)]. (C) 2002 American Institute of Physics.

Physical activity guidelines and preschooler's obesity status

Aim The benefits of promoting physical activity (PA) in counteracting the high prevalence of childhood obesity have become increasingly important in the past decade. The aim of this study was to examine the association between compliance of daily PA recommendations and the risk of being overweight or obese in preschool-aged children. Methods The sample comprised 607 children aged 4–6 years, recruited from kindergartens located in the metropolitan area of Porto, Portugal. Preschooler’s body mass index was classified according to International Obesity Task Force. PA was assessed during 7 consecutive days by accelerometer. Children were classified as meeting or not meeting PA recommendations based on two guidelines: (i) at least 3 h per day of total PA (TPA); and (ii) at least 1 h per day of moderate to vigorous PA (MVPA). Results The prevalence of overweight and obesity was 23.5 and 10.6% in girls and 17.2 and 8.9% in boys. In all, 90.2 and 97.3% of girls met the 1 h MVPA and 3 h TPA recommendations, respectively. In all, 96.2 and 99.4% boys met the 1 h MVPA and 3 h TPA recommendations, respectively. Boys were significantly more likely to achieve the 1 h MVPA and 3 h TPA recommendations than girls (P0.001). Not meeting the 1 h MVPA guideline was associated with obesity status (OR: 3.8; IC: 1.3–10.4), in girls, but not boys. No other statistically significant associations were found. Discussion These findings suggest that over 90% of children met the recommended guidelines. There is an association with low levels of MVPA and higher obesity status among preschool girls. Further, longitudinal studies are needed to confirm these data.

Calibration and evaluation of an objective measure of physical activity in pre-school children

Background The purposes of this study were 1) to establish accelerometer count cutoffs to categorize activity intensity of 3 to 5-y old-children and 2) to evaluate the accelerometer as a measure of children’s physical activity in preschool settings. Methods While wearing an ActiGraph accelerometer, 16 preschool children performed five, 3-min structured activities. Receiver Operating Characteristic (ROC) curve analyses identified count cutoffs for four physical activity intensities. In 9 preschools, 281 children wore an ActiGraph during observations performed by three trained observers (interobserver reli-ability = 0.91 to 0.98). Results Separate count cutoffs for 3, 4, and 5-y olds were established. Sensitivity and specificity for the count cutoffs ranged from 86.7% to 100.0% and 66.7% to 100.0%, respectively. ActiGraph counts/15 s were different among all activities (P < 0.05) except the two sitting activities. Correlations between observed and ActiGraph intensity categorizations at the preschools ranged from 0.46 to 0.70 (P < 0.001). Conclusions The ActiGraph count cutoffs established and validated in this study can be used to objectively categorize the time that preschool-age children spend in different physical activity intensity levels.

Calibration and comparison of accelerometer cut points in preschool children

Objective The present study aimed to develop accelerometer cut points to classify physical activities (PA) by intensity in preschoolers and to investigate discrepancies in PA levels when applying various accelerometer cut points. Methods To calibrate the accelerometer, 18 preschoolers (5.8 +/- 0.4 years) performed eleven structured activities and one free play session while wearing a GT1M ActiGraph accelerometer using 15 s epochs. The structured activities were chosen based on the direct observation system Children's Activity Rating Scale (CARS) while the criterion measure of PA intensity during free play was provided using a second-by-second observation protocol (modified CARS). Receiver Operating Characteristic (ROC) curve analyses were used to determine the accelerometer cut points. To examine the classification differences, accelerometer data of four consecutive days from 114 preschoolers (5.5 +/- 0.3 years) were classified by intensity according to previously published and the newly developed accelerometer cut points. Differences in predicted PA levels were evaluated using repeated measures ANOVA and Chi Square test. Results Cut points were identified at 373 counts/15 s for light (sensitivity: 86%; specificity: 91%; Area under ROC curve: 0.95), 585 counts/15 s for moderate (87%; 82%; 0.91) and 881 counts/15 s for vigorous PA (88%; 91%; 0.94). Further, applying various accelerometer cut points to the same data resulted in statistically and biologically significant differences in PA. Conclusions Accelerometer cut points were developed with good discriminatory power for differentiating between PA levels in preschoolers and the choice of accelerometer cut points can result in large discrepancies.

Accelerometer validity and placement for detection of changes in physical activity in dogs under controlled conditions on a treadmill

The objective of the research was to determine the optimal location and method of attachment for accelerometer-based motion sensors, and to validate their ability to differentiate rest and increases in speed in healthy dogs moving on a treadmill. Two accelerometers were placed on a harness between the scapulae of dogs with one in a pouch and one directly attached to the harness. Two additional accelerometers were placed (pouched and not pouched) ventrally on the dog's collar. Data were recorded in 1. s epochs with dogs moving in stages lasting 3. min each on a treadmill: (1) at rest, lateral recumbency, (2) treadmill at 0% slope, 3. km/h, (3) treadmill at 0% slope, 5. km/h, (4) treadmill at 0% slope, 7. km/h, (5) treadmill at 5% slope, 5. km/h, and; (6) treadmill at 5% slope, 7. km/h. Only the harness with the accelerometer in a pouch along the dorsal midline yielded statistically significant increases (P< 0.05) in vector magnitude as walking speed of the dogs increased (5-7. km/h) while on the treadmill. Statistically significant increases in vector magnitude were detected in the dogs as the walking speed increased from 5 to 7. km/h, however, changes in vector magnitude were not detected when activity intensity was increased as a result of walking up a 5% grade. Accelerometers are a valid and objective tool able to discriminate between and monitor different levels of activity in dogs in terms of speed of movement but not in energy expenditure that occurs with movement up hill.

Objectively measured physical activity behavior in children attending a half day preschool program

Obesity rates are increasing in children of all ages, and reduced physical activity (PA) is a likely contributor to this trend. Little is known about the physical activity behavior of preschool-age children, or about the influence of preschool attendance on physical activity. Purpose The purpose of this study was to quantify the physical activity levels of children attending a center-based half-day preschool program. Methods Forty-two 3-to-5-year old children (Mean age = 4.0 ± 0.7, 54.8% Male, Mean BMI = 16.5 ± 5.5, Mean BMI %tile = 52.1 ± 33.5) from four class groups (two morning and two afternoon), wore an Actigraph 7164 accelerometer for the entire halfday program (including classroom learning experiences, snack and recess time) 2 times per week, for 10 weeks (20 activity monitoring records in total). Activity counts for each 5-sec interval were uploaded to a customized data reduction program to determine total counts, minutes of moderate PA (MPA) (3–5.9 METs), and minutes of vigorous PA (VPA) (> = 6 METs) per session. Counts were categorized as either MPA or VPA using the cutpoints developed by Sirard and colleagues (2001). Results Across the four 2.5 hour programs, the average MPA, VPA and total counts (× 103) were 12.4 ± 3.1 minutes, 18.3 ± 4.6 minutes, and 171.1 ± 29.7 counts, respectively. Thus, on average, children accumulated just over 12 minutes of moderateto-vigorous PA per hour of program attendance. The PA variables did not differ significantly by gender, weight status, or time of day. There were, however, significant age differences, with 3-year-olds exhibiting significantly less PA than their 4- and 5-year-old counterparts. Conclusions These results suggest that young children are relatively lowactive while attending preschool. Accordingly, interventions to increase movement opportunities during the preschool day are warranted.

Pteridine-, thymidine-, choline- and imidazole-derived alkaloids from the Australian ascidian, Leptoclinides durus

Four new acylated pteridine alkaloids, duramidines A-D, two new acylated thymidine alkaloids, leptoclinidines A and B, two new 1-acylglyceryl-3-(O- carboxyhydroxymethylcholine) alkaloids, durabetaines A and B, three new 1,3-dimethyl-5-methylsulfanylimidazole alkaloids, leptoclinidamines D-F, and the known alkaloids leptoclinidamines B and C and 6-bromo-1H-indolo-3-yl-oxoacetic acid methyl ester were isolated from the Australian ascidian Leptoclinides durus. The duramidines are the first pteridine alkaloids, possessing a three carbon side chain esterified at C-1′ with a 4-hydroxy-2′- methoxycinnamic acid, and are either hydroxylated or sulfated at C-2′. The leptoclinidines are the first 3′-indole-3-carboxylic acid ester derivatives of thymidine to be reported in the literature. The durabetaines are the first glyceryl-3-(O-carboxyhydroxymethylcholine) alkaloids to be reported from an animal source and are also the only known derivatives from this class to be acylated with aromatic carboxylic acids. MS and NMR data analysis established the structures of the new compounds. All compounds were shown to be inactive when tested for cytotoxic activity against prostate (LNCaP) and breast (MDA-MB-231) cancer cell lines and antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus.