Development and operation of a pixel segmented liquid-filled linear array for radiotherapy quality assurance

A liquid isooctane (C$_{8}$H$_{18}$) filled ionization linear array for radiotherapy quality assurance has been designed, built and tested. The detector consists of 128 pixels, each of them with an area of 1.7 mm $\times$ 1.7 mm and a gap of 0.5 mm. The small pixel size makes the detector ideal for high gradient beam profiles like those present in Intensity Modulated Radiation Therapy (IMRT) and radiosurgery. As read-out electronics we use the X-Ray Data Acquisition System (XDAS) with the Xchip developed by the CCLRC. Studies concerning the collection efficiency dependence on the polarization voltage and on the dose rate have been made in order to optimize the device operation. In the first tests we have studied dose rate and energy dependences, and signal reproducibility. Dose rate dependence was found lower than 2.5 % up to 5 Gy min$^{-1}$, and energy dependence lower than 2.1 % up to 20 cm depth in solid water. Output factors and penumbras for several rectangular fields have been measured with the linear array and were compared with the results obtained with a 0.125 cm$^{3}$ air ionization chamber and radiographic film, respectively. Finally, we have acquired profiles for an IMRT field and for a virtual wedge. These profiles have also been compared with radiographic film measurements. All the comparisons show a good correspondence. Signal reproducibility was within a 2% during the test period (around three months). The device has proved its capability to verify on-line therapy beams with good spatial resolution and signal to noise ratio.Comment: 16 pages, 12 figures Submitted to Phys. Med. Bio

Neutron Beam Effects on Spin Exchange Polarized He-3

We have observed depolarization effects when high intensity cold neutron beams are incident on alkali-metal-spin-exchange polarized He-3 cells used as neutron spin filters. This was first observed as a reduction of the maximum attainable He-3 polarization and was attributed to a decrease of alkali-metal polarization, which led us to directly measure alkali-metal polarization and spin relaxation over a range of neutron fluxes at LANSCE and ILL. The data reveal a new alkali-metal spin-relaxation mechanism that approximately scales as the square root of the neutron capture-flux density incident on the cell. This is consistent with an effect proportional to the recombination-limited ion concentration, but is much larger than expected from earlier work.Comment: submitted to Physical Review Letter

The Identification of Potential Therapeutic Targets for Cutaneous Squamous Cell Carcinoma

We performed a small interfering RNA screen to identify targets for cutaneous squamous cell carcinoma (cSCC) therapy in the ubiquitin/ubiquitin-like system. We provide evidence for selective anti-cSCC activity of knockdown of the E3 ubiquitin ligase MARCH4, the ATPase p97/VCP, the deubiquitinating enzyme USP8, the cullin-RING ligase (CRL) 4 substrate receptor CDT2/DTL, and components of the anaphase-promoting complex/cyclosome (APC/C). Specifically attenuating CRL4CDT2 by CDT2 knockdown can be more potent in killing cSCC cells than targeting CRLs or CRL4s in general by RBX1 or DDB1 depletion. Suppression of the APC/C or forced APC/C activation by targeting its repressor EMI1 are both potential therapeutic approaches. We observed that cSCC cells can be selectively killed by small-molecule inhibitors of USP8 (DUBs-IN-3/compound 22c) and the NEDD8 E1 activating enzyme/CRLs (MLN4924/pevonedistat). A substantial proportion of cSCC cell lines are very highly MLN4924-sensitive. Pathways that respond to defects in proteostasis are involved in the anti-cSCC activity of p97 suppression. Targeting USP8 can reduce the expression of growth factor receptors that participate in cSCC development. EMI1 and CDT2 depletion can selectively cause DNA re-replication and DNA damage in cSCC cells

Short- and long-term cause-specific survival of patients with inflammatory breast cancer

BACKGROUND: Inflammatory breast cancer (IBC) had been perceived to have a poor prognosis. Oncologists were not enthusiastic in the past to give aggressive treatment. Single institution studies tend to have small patient numbers and limited years of follow-up. Most studies do not report 10-, 15- or 20-year results. METHODS: Data was obtained from the population-based database of the Surveillance, Epidemiology, and End Results program of the National Cancer Institute from 1975–1995 using SEER*Stat5.0 software. This period of 21 years was divided into 7 periods of 3 years each. The years were chosen so that there was adequate follow-up information to 2000. ICD-O-2 histology 8530/3 was used to define IBC. The lognormal model was used for statistical analysis. RESULTS: A total of 1684 patients were analyzed, of which 84% were white, 11% were African Americans, and 5% belonged to other races. Age distribution was < 30 years in 1%, 30–40 in 11%, 40–50 in 22%, 50–60 in 24%, 60–70 in 21%, and > 70 in 21%. The lognormal model was validated for 1975–77 and for 1978–80, since the 10-, 15- and 20-year cause-specific survival (CSS) rates, could be calculated using the Kaplan-Meier method with data available in 2000. The data were then used to estimate the 10-, 15- and 20-year CSS rates for the more recent years, and to study the trend of improvement in survival. There were increasing incidences of IBC: 134 patients in the 1975–77 period to 416 patients in the 1993–95 period. The corresponding 20-year CSS increased from 9% to 20% respectively with standard errors of less than 4%. CONCLUSION: The improvement of survival during the study period may be due to introduction of more aggressive treatments. However, there seem to be no further increase of long-term CSS, which should encourage oncologists to find even more effective treatments. Because of small numbers of patients, randomized studies will be difficult to conduct. The SEER population-based database will yield the best possible estimate of the trend in improvement of survival for patients with IBC

Single crewing in English and Welsh policing: frequency and associations with violence towards and injuries in officers

There is limited contemporary evidence concerning whether single crewing – the deployment of unaccompanied police officers – presents a risk to officer safety. This exploratory self-report study examined the frequency of single crewing in England and Wales and associations with violence-related variables. Officers represented by the Police Federation of England and Wales contributed survey data on four forms of violent victimisation and injuries requiring medical attention arising from workrelated violence experienced over the 12 months to February 2016. Respondents for whom crewing was applicable to their role indicated the frequency with which they had been single crewed during the same period. Pearson’s χ 2 tests were used to characterise socio- and occupational-demographic factors associated with single crewing, violence, and injuries. Associations between single crewing frequency and the target variables were assessed using adjusted binary logistic regression to generate odds ratios and 95% confidence intervals. Among the 11,397 respondents who indicated that crewing was applicable to their role, 53% were often and 21% always single crewed. Relative to those who were never single crewed, the odds of being subjected to verbal insults and verbal threats were significantly elevated in officers who were often or always single crewed. The odds of physical attacks and injuries requiring medical attention were significantly elevated in officers who were always single crewed. There was no association between single crewing frequency and physical attacks with a weapon. These initial cross-sectional findings suggest that tailored crewing options might represent a means by which to reduce violence towards police officers. Keywords: crewing, injury, police, violence

Prey choice, provisioning behaviour, and effects of early nutrition on nestling phenotype of titmice

[EN] It is generally assumed that blue and great tits (Cyanistes caeruleus, Parus major) compete for the same type of food (Lepidoptera larvae) during the breeding season and that the former have some advantage because they are usually earlier and can exploit small caterpillars that are often more abundant and are not consumed by great tits. However, it is not clear whether, when confronted with similar circumstances (e.g., nestling demand), blue and great tits show similar preferences for a particular caterpillar type. In this 2-y study, we compare the diet of both tit species in detail by controlling for hatching date and brood size. We also examine how the contribution of caterpillars and spiders to the diet is related to nestling development. A positive relationship was found between the percentage of spiders in the diet and nestling tarsus length in both species, reinforcing the idea that neonatal nutrition could have a strong influence on nestling phenotype (e.g., offspring size). Such a correlation may arise because spiders contain a high level of taurine, an essential nutrient in the early development of young, and/or this prey type contains more calcium than other food items, which may affect the rate of nestling bone mineralization. Blue tits fed their young double the number of tortricid larvae in comparison with great tits, whereas the latter showed a clear preference for noctuids and exploited, with a low frequency, a type of larvae not consumed by blue tits, hairy caterpillars (Lasiocampidae). Our results point to resource partitioning by these species in this forest ecosystem and contribute to a better understanding of feeding ecology of titmice, which is particularly timely in a global warming context [FR] Il est généralement admis que les mésanges bleues (Cyanistes caeruleus) et les mésanges charbonnières (Parus major) se font compétition pour le même type de nourriture (larves de lépidoptères) durant la période de reproduction. Il est également admis que les mésanges bleues possèdent un certain avantage, car elles se reproduisent plus tôt et mangent de petites chenilles souvent plus abondantes qui ne sont pas consommées par les mésanges charbonnières. Cependant, il n'est pas clair si dans les mêmes conditions (ex. de demande en nourriture des oisillons), les mésanges bleues et charbonnières préfèrent les mêmes types de chenilles. Dans cette étude de 2 ans, nous avons comparé en détail les régimes alimentaires des 2 espèces de mésanges en contrôlant pour la date de ponte et la taille de la couvée. Nous avons aussi examiné si les contributions des chenilles et des araignées au régime alimentaire étaient reliées au développement des oisillons. Chez les 2 espèces, une relation positive a été trouvée entre le pourcentage d'araignées dans le régime alimentaire et la longueur du tarse des oisillons renforçant ainsi l'idée que la nutrition néonatale peut avoir une grande influence sur le phénotype des oisillons (ex. la taille des jeunes). Une telle corrélation peut résulter du fait que les araignées ont un taux élevé de taurine, un nutriment essentiel au développement précoce des jeunes, et/ou que ce type de proie contient plus de calcium que d'autres aliments ce qui peut influencer le taux de minéralisation des os chez les oisillons. Les mésanges bleues ont nourri leurs jeunes avec deux fois plus de larves de tortricidés que les mésanges charbonnières qui elles ont montré une nette préférence pour les noctuidés. Ces dernières ont aussi consommé, quoique peu fréquemment, des livrées (Lasiocampidae), un type de larves boudé par les mésanges bleues. Nos résultats pointent vers une division des ressources entre ces espèces dans cet écosystème forestier et contribuent à une meilleure compréhension de l'écologie alimentaire des mésanges ce qui est particulièrement utile dans un contexte de réchauffement climatiqueV. García-Navas was supported by a FPI predoctoral fellowship (Spanish Ministry of Science and Innovation (MICINN)-European Social Fund). This study was financed by the MICINN (grant reference: GCL2007-61395)Peer Reviewe

Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum

Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism

Disease-specific survival for limited-stage small-cell lung cancer affected by statistical method of assessment

BACKGROUND: In general, prognosis and impact of prognostic/predictive factors are assessed with Kaplan-Meier plots and/or the Cox proportional hazard model. There might be substantive differences from the results using these models for the same patients, if different statistical methods were used, for example, Boag log-normal (cure-rate model), or log-normal survival analysis. METHODS: Cohort of 244 limited-stage small-cell lung cancer patients, were accrued between 1981 and 1998, and followed to the end of 2005. The endpoint was death with or from lung cancer, for disease-specific survival (DSS). DSS at 1-, 3- and 5-years, with 95% confidence limits, are reported for all patients using the Boag, Kaplan-Meier, Cox, and log-normal survival analysis methods. Factors with significant effects on DSS were identified with step-wise forward multivariate Cox and log-normal survival analyses. Then, DSS was ascertained for patients with specific characteristics defined by these factors. RESULTS: The median follow-up of those alive was 9.5 years. The lack of events after 1966 days precluded comparison after 5 years. DSS assessed by the four methods in the full cohort differed by 0–2% at 1 year, 0–12% at 3 years, and 0–1% at 5 years. Log-normal survival analysis indicated DSS of 38% at 3 years, 10–12% higher than with other methods; univariate 95% confidence limits were non-overlapping. Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction significantly impacted DSS. DSS assessed by the Cox and log-normal survival analysis methods for four clinical risk groups differed by 1–6% at 1 year, 15–26% at 3 years, and 0–12% at 5 years; multivariate 95% confidence limits were overlapping in all instances. CONCLUSION: Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction all significantly impacted DSS. Apparent DSS for patients was influenced by the statistical methods of assessment. This would be clinically relevant in the development or improvement of clinical management strategies