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Chemotherapy; Non–small cell lung cancer; RET inhibitors Quimioteràpia; Càncer de pulmó de cèl·lules no petites; Inhibidors de RET Quimioterapia; Cáncer de pulmón de células no pequeñas; Inhibidores de RET Introduction Nearly 1% to 2% of NSCLCs harbor RET fusions. Characterization of this rare population is still incomplete. Methods This retrospective multicenter study included patients with any-stage RET positive (RET+) NSCLC from 31 cancer centers. Molecular profiling included DNA/RNA sequencing or fluorescence in situ hybridization analyses. Clinicobiological features and treatment outcomes (per investigator) with surgery, chemotherapy (CT), immune checkpoint blockers (ICBs), CT-ICB, multityrosine kinase inhibitors, and RET inhibitors (RETis) were evaluated. Results For 218 patients included between February 2012 and April 2022, median age was 63 years, 56% were females, 93% had adenocarcinoma, and 41% were smokers. The most frequent fusion partner was KIF5B (72%). Median tumor mutational burden was 2.5 (range: 1–4) mutations per megabase, and median programmed death-ligand 1 expression was 10% (range: 0%–55%). The most common metastatic sites were the lung (50%), bone (43%), and pleura (40%). Central nervous system metastases were found at diagnosis of advanced NSCLC in 21% of the patients and at last follow-up or death in 31%. Overall response rate and median progression-free survival were 55% and 8.7 months with platinum doublet, 26% and 3.6 months with single-agent CT, 46% and 9.6 months with CT-ICB, 23% and 3.1 months with ICB, 37% and 3 months with multityrosine kinase inhibitor, and 76% and 16.2 months with RETi, respectively. Median overall survival was longer in patients treated with RETi versus no RETi (50.6 mo [37.7–72.1] versus 16.3 mo [12.7–28.8], p < 0.0001). Conclusions Patients with RET+ NSCLC have mainly thoracic and bone disease and low tumor mutational burden and programmed death-ligand 1 expression. RETi markedly improved survival, whereas ICB may be active in selected patients. Writing assistance was provided by Mrs. Sarah Mackenzie. Dr. Marinello was the recipient for the grant for DUERTECC/EURONCO (Diplôme Universitaire Européen de Recherche Translationnelle Et Clinique en Cancérologie). Dr. Mezquita received support from the Contrato Juan Rodes 2020 (ISCIII, Ministry of Health); Ayuda de la Acción Estratégica en Salud-ISCIII FIS 2021 (PI21/01653); Ayuda SEOM-Juan Rodés 2020. Dr. Cortellini acknowledges the support from the National Institute for Health Research Imperial Biomedical Research Centre. Dr. Pinato acknowledges the support from the Wellcome Trust Strategic Fund (PS3416), Associazione Italiana per la Ricerca sul Cancro (Associazione Italiana per la Ricerca sul Cancro MFAG Grant ID 25697), National Institute for Health Research Imperial Biomedical Research Centre, Imperial Experimental Cancer Medicine Centre, and the Imperial College Tissue Bank.

BACKGROUND: Restoration of muscular strength is predicated on restoration of muscle length. The purpose of this study was to describe infraspinatus and deltoid length preoperative to reverse total shoulder arthroplasty (RTSA) to guide distalization and lateralization to restore preoperative muscle length. METHODS: This was a retrospective radiographic study. On preoperative computed tomographic imaging we measured infraspinatus length. On preoperative x-ray we measured deltoid length. For all measurements, reliability was first established by comparing measurements between two observers and intra-class correlation coefficients (ICCs) were calculated. We then calculated descriptive statistics for these muscular lengths and developed a formula to predict these muscular lengths from patient demographics. RESULTS: We measured infraspinatus length in 97 patients and deltoid length in 108 patients. Inter-rater reliability was excellent, with all ICCs >0.886. Mean±standard deviation infraspinatus length was 15.5±1.3 cm but ranged from 12.6 to 18.9 cm, while deltoid length was 16.2±1.7 cm but ranged from 12.5 to 20.2 cm. Both infraspinatus (r=0.775, p

Introduction: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. Methods: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. Results: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models.

This paper presents a test of a methodology to describe the shape of true and accidental coincidence gamma-ray spectra. The effect of the coincidence summing was enhanced by using a 50 kBq 22Na source in a NaI well counter. The spectra were described by convoluting Monte Carlo simulated spectra in a spreadsheet for true, as well accidental coincidence summing. In this paper we show that applying convolution techniques to the MCNP simulated probability spectra, not only allows a reconstruction of the shape of the true coincidence spectrum, but the simulations also prove to be an invaluable tool to understand the continuum in the spectra made up of double and even triple random coincidences. Each of these summing processes was used to generate so-called standard spectra that may be used in a full-spectrum analysis of the measured spectra to quantitatively derive the contributions of each of the summing processes. For the case presented it is shown that the accidental coincidences can be accounted for to a 0.1% level, a considerable improvement to the precision in previous papers.

Objective To determine the interrater reliability of the Preschool Movement Assessment (PMA), a unique field-based assessment tool for use by early childhood professionals in preschool settings. Methods A total of 123 preschool children, aged 3–5years, were assessed by 6 trained raters using the PMA tool in an intervention. Interrater agreement on individual items of the PMA was determined using the kappa (κ) and intraclass correlation coefficient statistics. Results Weighted κ values were 0.82–0.96, indicating excellent agreement for all constructs of the PMA. The 95% confidence intervals indicated that all weighted κ’s were statistically significant. The intraclass correlation coefficient for the PMA total score was 0.97. Conclusions and Implications After additional developmental research, the tool might serve to establish and support a minimum level of functional movements that should be attained before a child enters grade school.

This paper describes and discusses fifteen years (1999–2013) of continuous hourly atmospheric radon (222Rn) monitoring at the coastal low-altitude Southern Hemisphere Cape Point Station in South Africa. A strong seasonal cycle is evident in the observed radon concentrations, with maxima during the winter months, when air masses arriving at the Cape Point station from over the African continental surface are more frequently observed, and minima during the summer months, when an oceanic fetch is predominant. An atmospheric mean radon activity concentration of 676 ± 2 mBq/m3 is found over the 15-year record, having a strongly skewed distribution that exhibits a large number of events falling into a compact range of low values (corresponding to oceanic air masses), and a smaller number of events with high radon values spread over a wide range (corresponding to continental air masses). The mean radon concentration from continental air masses (1 004 ± 6 mBq/m3) is about two times higher compared to oceanic air masses (479 ± 3 mBq/m3). The number of atmospheric radon events observed is strongly dependent on the wind direction. A power spectral Fast Fourier Transform analysis of the 15-year radon time series reveals prominent peaks at semi-diurnal, diurnal and annual timescales. Two inter-annual radon periodicities have been established, the diurnal 0.98 ± 0.04 day−1 and half-diurnal 2.07 ± 0.15 day−1. The annual peak reflects major seasonal changes in the patterns of offshore versus onshore flow associated with regional/hemispheric circulation patterns, whereas the diurnal and semi-diurnal peaks together reflect the influence of local nocturnal radon build-up over land, and the interplay between mesoscale sea/land breezes. The winter-time diurnal radon concentration had a significant decrease of about 200 mBq/m3 (17%) while the summer-time diurnal radon concentration revealed nearly no changes. A slow decline in the higher radon percentiles (75th and 95th) for the winter and spring seasons is found over the 15-year data set, with most of the change occurring in the first 9 years (1999–2007). This observed inter-annual decline appears to be associated with changes in the frequency of air masses having originated from over the African continental surfaces, and no significant trend is found in the lower radon percentiles associated with oceanic air masses. The general decrease of atmospheric radon-associated with continental air-masses at Cape Point could be attributed to changing meteorological conditions, possibly driven by climate change.

The utilization of intramedullary devices in the surgical fixation of hip fractures is increasing. Although intramedullary devices offer many advantages in the treatment of these injuries, they are also associated with a unique set of potential complications, particularly during preparation of the femoral canal. Cardiac dysrhythmia resulting from reaming the femoral canal is rare and has not been previously described in detail in the literature. We present the case of a 69-year-old male with an infected right cephalomedullary femoral nail who underwent removal of hardware and experienced reproducible, transient asystolic cardiac arrest during reaming of the femoral canal and offer potential explanations for this event.

Background We report the first study examining the clinical, numerical and biological properties of circulating tumor cells according to molecular subtypes of non-small-cell lung cancer. Patients and methods 125 patients with treatment-naive stage IIIb-IV NSCLC were prospectively recruited for CellSearch analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim +) CTCs with clinical characteristics, tumor genotype, and survival were assessed. Results 51/125 patients (40.8%) were total CTC+ and 26/125 (20.8%) were vim CTC+ at baseline. Multivariate analysis showed patients with ≥5 total CTCs had significantly reduced OS (HR 0.55, 95% CI 0.33-0.92, P = 0.022) but not PFS (HR 0.68, 95% CI 0.42-1.1, P = 0.118) compared to patients with

Thymic neoplasms are rare malignant tumours, for which the mainstay of treatment is surgical resection. Platinum-based chemotherapy remains the principal treatment in metastatic tumours, with no standard second-line option. Many genes implicated in tumour onset, growth and metastases have been demonstrated to be therapeutic targets in thymic malignancies. Other current efforts to improve outcomes are based on a better understanding of the stromal compartment and tumour microenvironment, facilitating novel therapeutic approaches such as angiogenesis inhibition and immunotherapy. This review seeks to explore the present cutting edge for systemic treatment of advanced thymic neoplasms, examining novel agents under clinical investigation such as cytotoxic therapies, targeted therapies and immunotherapy. Based on the literature review we have selected potential treatment schemes, which could be used in daily clinical practice as second-line treatment.

Ex situ atomic force microscopy and x-ray photoelectron spectroscopy are employed to characterise the adsorption of calcium phosphate from an aqueous solution of CaCl2.H2O and KH2PO4 onto rutile-TiO2(110) and α-Al2O3(0001). Prior to immersion, the substrates underwent wet chemical preparation to produce well-defined surfaces. Calcium phosphate adsorption is observed on both rutile-TiO2(110) and α-Al2O3(0001), with atomic force microscopy images indicating island-type growth. In contrast to other studies on less well-defined TiO2 and Al2O3 substrates, the induction period for calcium phosphate nucleation appears to be comparable on these two surfaces. - An ex situ study of the adsorption of calcium phosphate from solution onto TiO2(110) and Al2O3(0001)

Loss of genetic variation is an increasing problem in many natural populations as a result of population fragmentation, inbreeding, and genetic drift, which may lead to inbreeding depression and subsequent “extinction vortices”. In such cases, outbreeding offers a potential population saviour from extinction. Here we compare offspring viability between an experimentally founded outbred island population of sand lizards Lacerta agilis, and an inbred mainland source population on the Swedish West coast. We have studied the mainland population for over a decade during which >4000 offspring from >500 parents were monitored. We conducted an outbreeding experiment in which lizards from the mainland population with relatively low genetic variation were crossbred with lizards from distant populations that lack gene flow. The resulting 454 offspring were introduced to an otherwise uninhabited island with ideal sand lizard habitat. A survey of the island two decades later showed that offspring produced by females from the experimentally founded population had 13% higher hatching success (99.3% versus 86.4%) and elimination of the malformations occurring in 21% of clutches in the mainland source population. These results co-occur with higher genetic diversity. We conclude that outbreeding improved offspring viability in our island population ca 5–6 generations after the founding event, that is, with sustained viability effects at a time when heterotic effects are expected to have subsided.

Lyme disease is emerging in Canada because of northward range expansion of the tick vector Ixodes scapularis. It is hypothesised that I. scapularis feeding on passerine birds migrating north in spring are important in founding new I. scapularis populations leading to northward range expansion. However, there are no studies on how far north I. scapularis may be carried, only inferences from passive tick surveillance. We used stable hydrogen isotope (δ(2)H) analysis of rectrices collected from northward migrating, I. scapularis-carrying, passerine birds captured in Canada to estimate how far north I. scapularis may be carried. Rectrices are usually grown close to breeding sites and their δ(2)H values reflect those in the environment, which vary strongly with latitude in North America. Passerines usually return to their breeding or natal sites so δ(2)H values of rectrices of northward migrating birds can identify the likely latitudinal bands of their intended destinations. In 2006 we analysed δ(2)H from rectrices of 73 I. scapularis-carrying birds captured at five migration monitoring stations, mainly from southern Ontario. Values of δ(2)H ranged from -33 to -124‰, suggesting 19/71 (26.7%) birds were destined for latitude band B (the most southerly part of Ontario), 40/71 (56.3%) birds were destined for band C (which extends from southern Ontario, Quebec and the Maritimes to southern James Bay) and 12/71 (16.9%) birds were destined for bands D and E (which extend from northern Ontario and Quebec into the southern Canadian Arctic). This indicates that many I. scapularis-carrying migratory birds in spring have destinations far north in Canada, including some farther north than the current region of climatic suitability for I. scapularis. These findings support the hypothesis that I. scapularis may continue to be spread north by spring migrating passerines. Some thrush species may be particularly implicated in far northward dispersion of I. scapularis.

Variation in song structure and song production of birds are thought to relate to variation of both androgen levels and neural nuclei in the song system, as typically these nuclei are larger in males than in females, vary in size among males and are sensitive to steroid hormones. We investigated the relationships among song and note structure, singing rate, androgen levels and the sizes of two song nuclei, the higher vocal centre (HVC) and the robust nucleus of the arcopallium (RA) in male and female red-backed fairy-wrens, Malurus melanocephalus. Males of this duetting species express three discrete reproductive phenotypes that differ in plumage colour and behaviour. Although HVC and RA structure differed between the sexes, there were no sex differences in note structure and complexity of songs, although females differed from some male types in song rate and frequency characteristics. Both auxiliary males and females had significantly lower androgen levels than the two breeding male phenotypes. Male reproductive phenotypes had similar song characteristics and HVC and RA structure, but differed in androgen levels. Sexes and male phenotypes varied in song rate, but these differences did not correspond to differences in androgen levels. Thus, sex differences in song nuclei anatomy and androgen levels were not associated with differences in song structure and singing rate; and, the differences in androgen levels among male phenotypes were not reflected in differences in singing rate, song structure or the song nuclei. We conclude that, similar to other recent findings, the sexes of the red-backed fairy-wren can produce similar song and express similar singing behaviour despite differences in song system structure and circulating androgen levels; singing and song system anatomy appear not to be part of the suite of traits associated with differences in androgen levels in male red-backed fairy-wrens.

The implications of quantum information technology for cybersecurity and strategic stability seem worrisome. In theory, an adversary with a quantum computer could defeat the asymmetric encryption protocols that underwrite internet security, while an adversary using quantum communications guaranteed secure by the laws of physics could deny intelligence warning of surprise attack. To assess these claims, this article first develops a general political logic of cryptology grounded in the bargaining model of war, which understands uncertainty as an important cause of war and institutions as an important source of information. Cryptology of any technological vintage is shaped by both aspects of this logic, with ambiguous implications for strategic stability. In practice, strategic interaction between intelligence competitors using real quantum systems implemented in fallible human organizations will mitigate the impact of quantum computing. The upshot is that the revolutionary scientific innovation of quantum computing will probably have only marginal political impact, in part because the fields of cryptology and computing have already undergone important transformations in recent decades.

SummaryDuring embryogenesis, melanoblasts proliferate and migrate ventrally through the developing dermis and epidermis as single cells. Targeted deletion of Rac1 in melanoblasts during embryogenesis causes defects in migration, cell-cycle progression, and cytokinesis. Rac1 null cells migrate markedly less efficiently, but surprisingly, global steering, crossing the dermal/epidermal junction, and homing to hair follicles occur normally. Melanoblasts navigate in the epidermis using two classes of protrusion: short stubs and long pseudopods. Short stubs are distinct from blebs and are driven by actin assembly but are independent of Rac1, Arp2/3 complex, myosin, or microtubules. Rac1 positively regulates the frequency of initiation of long pseudopods, which promote migration speed and directional plasticity. Scar/WAVE and Arp2/3 complex drive actin assembly for long pseudopod extension, which also depends on microtubule dynamics. Myosin contractility balances the extension of long pseudopods by effecting retraction and allowing force generation for movement through the complex 3D epidermal environment.

Although some group-living animals dynamically modify sexual signals in response to changes in social or reproductive status, this ability is often limited by constraints inherent in the mechanism of signal production. In birds, for example, inflexible moult schedules may restrict the ability to rapidly modify plumage-based signals. In such cases, more flexible secondary signals such as skin, eye, or bill coloration (e.g. soft parts) could potentially be used to achieve dynamic signalling. We addressed the degree to which free-living red-backed fairy-wrens, Malurus melanocephalus, can dynamically update both plumage and soft part signals when status suddenly changes, and how this may be achieved. In this cooperatively breeding passerine, dominant breeding males are distinguished from socially subordinate nonbreeding auxiliary males by the presence of nuptial plumage, dark bills and large sperm storage organs. Following an experimentally induced shift in status from auxiliary to breeder, males showed rapid increases in excreted androgen metabolites. Although they showed no overall change in nuptial plumage colour, several experimental males developed red nuptial feathers on the back following feather plucking, indicating that they had the capacity to develop bright nuptial plumage but were constrained from doing so by the moult schedule. In contrast, experimental males showed a rapid darkening of their bills, reflecting their newly acquired breeding status. These findings (1) provide experimental evidence that status affects physiologically controlled visual signals in free-living birds, (2) suggest that this linkage is mediated by testosterone and (3) illustrate how secondary ornaments may be used in dynamic signalling when the primary signalling modality is constrained.

Aim To identify current practices within paediatric radiology in the UK with regard to the use of prophylactic medication, prior to administering intravenous (IV) radiocontrast medium (RCM). In addition, the pre-injection risk management strategies of the departments questioned was to be evaluated, and using consensus opinion, a protocol for managing patients identified as being at high risk for an adverse reaction to RCM was to be outlined. Materials and methods An online survey of paediatric radiology consultants representing all geographic regions of the UK was carried out. The questions asked included an assessment of the risk factors for adverse reactions to RCM, and how such reactions are anticipated and managed. The questionnaire asked about the perceived indications for, and the use of prophylactic medication prior to RCM administration. Results A response rate of 51% was achieved. The majority of respondents felt that a history of previous RCM reaction was an indication to administer prophylactic drugs prior to a further dose of RCM. No other risk factor was believed to require prophylactic medication. Conclusion Using information obtained from the survey, a literature search was performed to assess the evidence available in support of each practice. A protocol was devised to identify children at risk of an adverse reaction to RCM, and guide the use of prophylactic medication in this group of patients. The survey highlighted considerable variability in the risk-assessment and management practices within paediatric radiology in the UK. The derived protocol may guide radiologists’ management of children at risk for an RCM reaction.

Ultrafast time-resolved UV–visible absorption spectroscopy has been used to study four model azo dyes and five commercial azo dyes. All of the dyes have been found to show strong bleaching of their ground-state absorption bands on photoexcitation, with recovery lifetimes of 1–5 ps in aqueous solution that are attributed to rapid and efficient non-radiative decay; two commercial azo dyes deposited in cellophane have been found to show an additional longer-lived component with a lifetime of >50 ps that is attributed to the effects of intermolecular interactions with the cellulosic environment.

Androgens regulate male reproductive behaviour and may be a mechanistic link between sexual signals and physiological condition. However, the role of these hormones in regulating prenuptial moult and male plumage signals of passerine birds is unclear. In the red-backed fairy-wren, Malurus melanocephalus, plumage colour is a sexually selected trait and males express three reproductive phenotypes: males can breed in bright red and black plumage or in dull brown plumage, or assume dull plumage and act as nonbreeding auxiliaries; each phenotype differs in parental and reproductive behaviour. We found that plasma androgen concentrations differed significantly between male phenotypes, with red/black breeding males having the highest levels and auxiliaries having the lowest levels across all nesting stages. These hormonal differences were also present during the prebreeding moult when nuptial plumage is acquired. Males also differed significantly in body condition during moult based on the phenotype acquired in the subsequent breeding season, with red/black breeding males being in the best condition and auxiliaries being in the poorest condition. Moreover, androgen concentrations were positively correlated with body condition during prenuptial moult. Thus, in this species, androgens may determine plumage coloration and provide a link between the expression of sexual signals and body condition.

Measurement of radon in water by gamma-ray spectrometry using a HPGe detector has been investigated to determine aquifer characteristics. The radon activity concentration is determined by taking the weighted average of the concentrations derived from gamma-ray lines associated with (214)Pb and (214)Bi decay. The role of accurate radon data to representatively sample aquifers was also investigated by studying a semi-cased borehole. A simplified physical model describing the change of radon concentration with the pumping time, reproduces the data and predicts the time for representative sampling of the aquifer.

Density functional theory suggests that the formal 2-electron oxidation of sulfides, RR′S, to sulfoxides, RR2′ S {double bond, long} O by the model MnV{double bond, long}O catalyst, [(TACN)MnV O(OH)2]+, proceeds in two quite distinct 1-electron steps. Transfer of the first electron is barrierless and generates a sulfur radical cation, antiferromagnetically coupled to a MnIV centre via a covalent μ-oxo bridge. The second electron-transfer step is accompanied by migration of the oxygen atom to the sulfur centre, and is rate-determining. The absence of a barrier in the first step, where a sulfur radical is formed, means that the presence of electron-donating or withdrawing substituents on the sulfide has only a minor impact on the rate of reaction. © 2007 Elsevier B.V. All rights reserved.

Manganese(III) tetrakis(2,6-dichloro-3-sulfonatophenyl)porphyrin (1) and manganese(III) tetrakis[tetrafluoro-4-(trimethylammoniumyl)phenyl]porphyrin (2), in homogeneous solution and supported on modified silica surfaces, have been used as catalysts for the oxidation of pentane and cyclohexane with iodosylbenzene. The effects of reaction solvent, catalyst support and dioxygen on the oxidation yields and product distributions have been studied. The reactions under nitrogen show a high selectivity for alcohol formation whereas in air ketones become significant products, indicating the participation of dioxygen in the formation of the ketones. Competitive oxidations of pentane and perdeuteropentane give kinetic isotope effects (kH/kD) of 6.9 ± 1.3 for both pentan-2-ol and -3-ol formation. The results are in accord with a mechanism in which an initial hydrogen atom-abstraction from the alkane by the active oxidant, an oxomanganese(V) species, gives a solvent-caged alkyl radical and a hydroxymanganese(IV) porphyrin. All the products can be accounted by partitioning of the carbon radicals between ‘in cage’ reaction to give alcohol and ‘cage escape’ leading to products typical of free alkyl radicals. The effect of solvent viscosity on this partitioning of the carbon radicals has been probed with the radical trap bromotrichloromethane.

The oxidation of phenols, cinnamic acids and methyl aryl sulfides by hydrogen peroxide, using three catalyst systems, [L2Mn2IV(μ-O)3](PF6)2, L = 1,4,7-trimethyl-1,4,7-triazacyclononane; [LMnIV(OMe)3(PF6); and MnII/L/H2O2, have been studied. The results from a combination of spectroscopic and kinetic studies, coupled with Hammett correlations and 18O labelling experiments, suggest that with each system the active oxidant is an electrophilic, mononuclear oxo-manganese (V) species. The influence of additives that can act as co-ligands for the manganese species has been investigated, with a view to controlling the activity/selectivity of the active oxidant. The two-step, sulfide–sulfoxide–sulfone, oxidation shows an unusual switch in the philicity of the active oxidant from electrophilic in the first step to nucleophilic in the second. Mechanisms for the oxidations are proposed.

A mechanistic study of organosulfide oxidation by H 2 O 2 , using a dinuclear manganese complex as the catalyst, has revealed an unusual switch in the philicity of the oxidant for the first and the second oxygen transfer steps; this switch has been exploited to tune selectivity for each of the products.

A dynamic population model of Ixodes scapularis, the vector of a number of tick-borne zoonoses in North America, was developed to simulate effects of temperature on tick survival and seasonality. Tick development rates were modelled as temperature-dependent time delays, calculated using mean monthly normal temperature data from specific meteorological stations. Temperature also influenced host-finding success in the model. Using data from stations near endemic populations of I. scapularis, the model reached repeatable, stable, cyclical equilibria with seasonal activity of different instars being very close to that observed in the field. In simulations run using data from meteorological stations in central and eastern Canada, the maximum equilibrium numbers of ticks declined the further north was the station location, and simulated populations died out at more northerly stations. Tick die-out at northern latitudes was due to a steady increase in mortality of all life stages with decreasing temperature rather than a specific threshold event in phenology of one life stage. By linear regression we investigated mean annual numbers of degree-days0 degrees C (DD0 degrees C) as a readily mapped index of the temperature conditions at the meteorological stations providing temperature data for the model. Maximum numbers of ticks at equilibrium were strongly associated with the mean DD0 degrees C (r20.96, P0.001), when the Province of origin of the meteorological station was accounted for (QuebecOntario, beta=103, P0.001). The intercepts of the regression models provided theoretical limits for the establishment of I. scapularis in Canada. Maps of these limits suggested that the range of southeast Canada where temperature conditions are currently suitable for the tick, is much wider than the existing distribution of I. scapularis, implying that there is potential for spread. Future applications of the model in investigating climate change effects on I. scapularis are discussed.

This paper reports an HPLC–MS/MS investigation of praziquantel (anthelmintic agent) oxidation by iodosylbenzene in an organic medium, using iron(III) tetraarylporphyrins (where aryl = phenyl, pentafluorophenyl, 2-nitrophenyl, 2-trifluoromethylphenyl and mesityl) and manganese(III) tetraphenylporphyrin as catalysts. The majority of the oxidation products have been identified by sequential MS and NMR analyses. The selectivities of the oxidations by these cytochrome P-450 models are studied and compared. Time dependent reaction profiles suggest that with all the catalysts, the initial oxidation occurs predominantly at the 7-position. With Fe(T2TFMPP)Cl the yield and selectivity (64%) for 7-hydroxypraziquantel remain high even after 24 h reaction, whereas with the other catalysts this initial product is further oxidized to di- and trihydroxypraziquantel. The Fe(TFPP)Cl system results in the higher yield (11%) of cis - and trans -4′-hydroxypraziquantel, the major metabolites from in vivo and in vitro metabolism of praziquantel by cytochrome P-450 monooxygenases.

l,4,7-Trimethyl-l,4,7-triazacyclononane (TMTACN), MnSO4 and H2O2, in basic aqueous acetonitrile, is an effective system for the epoxidation of cinnamic acid. The influence of a selection of organic additives, potential co-ligands for the manganese species, on the reactions has been studied by UV–vis spectroscopy and ESI-MS. The mechanism of the most efficient system, with added oxalic acid, has been investigated in more detail using cinnamic acid and seven of its 3- or 4-substituted derivatives. A Hammett correlation of rate data shows that the active oxidant is electrophilic (ρ value −0.63). Oxygen ( 18 O ) labelling experiments reveal that H2O2 and not H2O is the source of the oxygen in the epoxide. Possible mechanisms for the reactions are discussed.

The exhalation of radon from the large mine dumps at the gold mines in South Africa is a potential health hazard. Determination of radon fluxes from these dumpsites is problematic due to the scatter in the data in time and place and the cost involved in getting a representative sample. gamma-ray spectroscopic analysis of soil samples from a dumpsite indicates that as much as 30% of the formed radon may escape, resulting in a disturbance to the secular equilibrium of the U-238 decay series. A method is proposed to quantitatively assess the radon flux from such dumpsites by using a mobile gamma-ray detector system. (C) 2003 Elsevier B.V. All rights reserved.

Increasing evidence supports a role for glycated insulin in the insulin-resistant state of type 2 diabetes. We measured 24-hour profiles of plasma glycated insulin, using a novel radioimmunoassay (RIA), to evaluate the effects of meal stimulation and intermittent fasting on circulating concentrations of plasma glycated insulin in type 2 diabetes. Patients (n = 6; hemoglobin A(1c) [HbA(1c)], 7.2% +/- 0.6%; fasting plasma glucose, 7.4 +/- 0.7 mmol/L; body mass index [BMI], 35.7 +/- 3.5 kg/m(2); age, 56.3 +/- 4.4 years) were admitted for 24 hours and received a standardized meal regimen. Half-hourly venous samples were taken for plasma glycated insulin, glucose, insulin, and C-peptide concentrations between 8 Am and midnight and 2-hourly overnight. The mean plasma glycated insulin concentration over 24 hours was 27.8 +/- 1.2 pmol/L with a mean ratio of insulin:glycated insulin of 11:1. Circulating glucose, insulin, C-peptide, and glycated insulin followed a basal and meal-related pattern with most prominent increments following breakfast, lunch, and evening meal, respectively. The mean concentrations of glycated insulin during the morning, afternoon, evening, and night-time periods were 24.4 +/- 2.5, 28.7 +/- 2.3, 31.1 +/- 2.1, and 26.2 +/- 1.5 pmol/L, respectively, giving significantly higher molar ratios of insulin:glycated insulin of 18.0:1, 14.2:1, and 12.7:1 compared with 7.01 at night (P < 0.01 to P < 0.001). These data demonstrate that glycated insulin circulates at relatively high concentrations in type 2 diabetes with a diurnal pattern of basal and meal-stimulated release. A higher proportion of glycated insulin circulates at night suggestive of differences in metabolic clearance compared with native insulin. (C) 2003 Elsevier Inc. All rights reserved.

We report findings of a 2-year study (1996–1997) surveying breeding birds in lacustrine habitats of northern Wisconsin, USA. This area has seen marked increases in lakeshore housing development in recent years, and other studies indicate significant lakeshore habitat alteration. We paired developed and undeveloped lakes of similar physical characteristics and performed point-counts around the perimeter of each to assess bird community structure. Our results showed no significant differences between developed and undeveloped lakes in bird abundance, richness or species diversity. However, several species and some resource-guilds were commonly associated with one lake-type or the other. We found a significantly higher diversity of diet guilds on developed lakes. Significant declines in the prevalence of insectivorous and ground-nesting birds were documented on developed lakes, contrasting with increased prevalence of seed-eating birds and deciduous-tree nesting birds. Levels of development on lakeshores in northern Wisconsin appear to affect the composition of avian communities, which is of concern for the health of these forested lacustrine habitats. We outline several factors associated with development which may be linked to these observed bird community changes and suggest measures landowners might take to minimize impact on native breeding bird communities. # 2002 Published by Elsevier Science Ltd.

This paper discusses the optimisation of a high performance, low cost 0.13 μm CMOS technology with a view on its further scaling to the 100 nm technology node. The focus is mainly on gate oxide (thickness and nitridation method), deep junction implants and annealing. It is shown that in order to take the full benefit of gate oxide thinning, low energy boron implants and spike rapid thermal anneal are mandatory for pMOS devices. The same route gives also promising results for nMOS transistors when gate predoping is used to reduce gate depletion.

Objectives: To review patterns of physical and sexual abuse in cohorts of sexual offenders and nonsexual offenders with intellectual disability. Method: Forty-six sexual offenders were compared with 48 male nonsexual offenders in relation to their experiences of sexual and physical abuse in childhood. Comprehensive assessments were taken over a period of at least one year, and were conducted independently by a range of professionals. Results: Thirty-eight percent of the sexual offenders and 12.7% of the nonsexual offenders had experienced sexual abuse, while 13% of the sexual offenders and 33% of the nonsexual offenders had experienced physical abuse. Conclusions: Sexual abuse seems a significant variable in the history of sexual offenders, while physical abuse seems a significant variable in the history of nonsexual offenders. The results support the view that the “cycle of abuse” is neither inevitable nor an adequate explanation of future offending.

Using C 1s, N 1s and O 1s scanned-energy mode photoelectron diffraction the local adsorption geometry of a Ni(1 1 1) (2√3×2√3) R 30° surface phase formed by benzene and NO coadsorption has been investigated. The benzene and NO coverages were estimated to correspond to 1.00 and 1.25 molecules per surface unit mesh. The benzene molecules are found to adopt bridge sites essentially the same as those adopted by adsorbed benzene alone at low coverages in a disordered state (but different from that adopted in the higher coverage ordered (√7×√7) R 19° phase). NO molecules occupy mainly ‘hcp’ hollow sites (directly above a second layer Ni atoms) but with fractional occupation of ‘fcc’ hollow sites (directly above a third layer of Ni atoms). These results suggest that in the saturated Ni(1 1 1) (2√3×2√3) R 30°–C 6 H 6 +2NO phase which has been proposed previously, the NO molecules probably occupy hcp and fcc hollows equally.