Colorectal cancer survival in the USA and Europe: a CONCORD high-resolution study.

OBJECTIVES: To assess the extent to which stage at diagnosis and adherence to treatment guidelines may explain the persistent differences in colorectal cancer survival between the USA and Europe. DESIGN: A high-resolution study using detailed clinical data on Dukes' stage, diagnostic procedures, treatment and follow-up, collected directly from medical records by trained abstractors under a single protocol, with standardised quality control and central statistical analysis. SETTING AND PARTICIPANTS: 21 population-based registries in seven US states and nine European countries provided data for random samples comprising 12 523 adults (15-99 years) diagnosed with colorectal cancer during 1996-1998. OUTCOME MEASURES: Logistic regression models were used to compare adherence to 'standard care' in the USA and Europe. Net survival and excess risk of death were estimated with flexible parametric models. RESULTS: The proportion of Dukes' A and B tumours was similar in the USA and Europe, while that of Dukes' C was more frequent in the USA (38% vs 21%) and of Dukes' D more frequent in Europe (22% vs 10%). Resection with curative intent was more frequent in the USA (85% vs 75%). Elderly patients (75-99 years) were 70-90% less likely to receive radiotherapy and chemotherapy. Age-standardised 5-year net survival was similar in the USA (58%) and Northern and Western Europe (54-56%) and lowest in Eastern Europe (42%). The mean excess hazard up to 5 years after diagnosis was highest in Eastern Europe, especially among elderly patients and those with Dukes' D tumours. CONCLUSIONS: The wide differences in colorectal cancer survival between Europe and the USA in the late 1990s are probably attributable to earlier stage and more extensive use of surgery and adjuvant treatment in the USA. Elderly patients with colorectal cancer received surgery, chemotherapy or radiotherapy less often than younger patients, despite evidence that they could also have benefited.

Analysis and quantification of vitamin D metabolites in serum by ultra-performance liquid chromatography coupled to tandem mass spectrometry and high-resolution mass spectrometry: a method comparison and validation.

RATIONALE: The aim of the work was to develop and validate a method for the quantification of vitamin D metabolites in serum using ultra-high-pressure liquid chromatography coupled to mass spectrometry (LC/MS), and to validate a high-resolution mass spectrometry (LC/HRMS) approach against a tandem mass spectrometry (LC/MS/MS) approach using a large clinical sample set. METHODS: A fast, accurate and reliable method for the quantification of the vitamin D metabolites, 25-hydroxyvitamin D2 (25OH-D2) and 25-hydroxyvitamin D3 (25OH-D3), in human serum was developed and validated. The C3 epimer of 25OH-D3 (3-epi-25OH-D3) was also separated from 25OH-D3. The samples were rapidly prepared via a protein precipitation step followed by solid-phase extraction (SPE) using an HLB μelution plate. Quantification was performed using both LC/MS/MS and LC/HRMS systems. RESULTS: Recovery, matrix effect, inter- and intra-day reproducibility were assessed. Lower limits of quantification (LLOQs) were determined for both 25OH-D2 and 25OH-D3 for the LC/MS/MS approach (6.2 and 3.4 µg/L, respectively) and the LC/HRMS approach (2.1 and 1.7 µg/L, respectively). A Passing & Bablok fit was determined between both approaches for 25OH-D3 on 662 clinical samples (1.11 + 1.06x). It was also shown that results can be affected by the inclusion of the isomer 3-epi-25OH-D3. CONCLUSIONS: Quantification of the relevant vitamin D metabolites was successfully developed and validated here. It was shown that LC/HRMS is an accurate, powerful and easy to use approach for quantification within clinical laboratories. Finally, the results here suggest that it is important to separate 3-epi-25OH-D3 from 25OH-D3. Copyright © 2012 John Wiley & Sons, Ltd.

Detection of possible variant forms of hemoglobin in HbA1c measurements by chromatography liquid ion exchange high resolution (HPLC)

Background: The glycosylated hemoglobin (HbA1c) is used to help monitor the degree of a diabetic’s hyperglycemia. Security and accuracy of the methods used in its detection are affected by variants forms of Hb or elevations in levels of Fetal Hb (HbF). These interference are the result of a change in the haemoglobin total net charge of the variant due of a substitution of one amino acid in the remaining amino terminal of the beta chain. International Standardization for HbA1c values (NGSP) not include interference assessment as part of the certification program. Therefore, the effect of each variant or the lifting of the HbF on HbA1c result should be examined in each sample depending on the detected variant and the method used for the detection of the same. The objectives were: to describe the possible variants of Hb and their interference in HbA1c measurement by our method, after the implementation of a computer program for their detection. To identify some variants detected by chromatography liquid ion exchange high resolution (HPLC) with DNA molecular sequencing.

Tonotopic gradients in human primary auditory cortex: concurring evidence from high-resolution 7 t and 3 t FMRI.

The tonotopic representations within the primary auditory cortex (PAC) have been successfully mapped with ultra-high field fMRI. Here, we compared the reliability of this tonotopic mapping paradigm at 7 T with 1.5 mm spatial resolution with maps acquired at 3 T with the same stimulation paradigm, but with spatial resolutions of 1.8 and 2.4 mm. For all subjects, the mirror-symmetric gradients within PAC were highly similar at 7 T and 3 T and across renderings at different spatial resolutions; albeit with lower percent signal changes at 3 T. In contrast, the frequency maps outside PAC tended to suffer from a reduced BOLD contrast-to-noise ratio at 3 T for a 1.8 mm voxel size, while robust at 2.4 mm and at 1.5 mm at 7 T. Overall, our results showed the robustness of the phase-encoding paradigm used here to map tonotopic representations across scanners.

Conflict resolution and evolution of social structures in insect societies

In colonies of social Hymenoptera (which include all ants, as well as some wasp and bee species), only queens reproduce whereas workers generally perform other tasks. The evolution of worker's reproductive altruism can be explained by kin selection, which states that workers can indirectly transmit copies of their genes by helping the reproduction of relatives. The relatedness between queens and workers may however be low, particularly when there are multiple queens per colony, which limits the transmission of copies of workers genes and increases potential conflicts between colony members. In this thesis, we investigated the link between social structure variations and conflicts, and explored the mechanisms involved in variation of colony queen number in ants. According to kin selection, workers should rear the brood they are most related to. In social Hymenoptera, males are haploid whereas females (workers and queens) are diploid. As a result, workers can be up to three times more related to females than males in some colonies, where they should consequently favour the production of females. In contrast, queens are equally related to daughters and sons in all types of colonies and therefore should favour a balanced sex ratio. In a meta-analysis across all studies of social Hymenoptera, we showed that colony sex ratio is generally largely influenced by workers. Hence, the evolution of social structures where queens and workers are equally related to males and females may contribute to decrease the conflict between the two castes over colony sex ratio. Another conflict between queens and workers can occur over male production. Many species contain workers that still have the ability to lay haploid eggs. In some social structures, workers are on average more related to sons of queens than to sons of other workers. As a result, workers should eliminate worker-laid eggs to favour queen-laid eggs. We showed that in the ant Formica selysi, workers eliminate more worker-laid than queen-laid eggs, independently of colony social structure. These results therefore suggest that worker policing can evolve independently from relatedness, potentially because of costs of worker reproduction at the colony-level. Colony queen number is a key parameter that influences relatedness between group members. Queen body size is generally linked to the success of independent colony foundation by single queens and may influence the number of queens in the new colony. In the ant F. selysi, single-queen colonies produce larger queens than multiple-queen colonies. We showed that this association results from genes or maternal effects transmitted to the eggs. However, we also found that queens produced in colonies of the two social forms did not differ in their general ability to found new colonies independently. Queen body size may also influence queen dispersal ability and constrain small queens to be re-adopted in their original nest after mating at proximity. We tested the acceptance of new queens in another ant species, Formica paralugubris, which has numerous queens per colony. Our results show that workers do not discriminate between nestmate and foreign queens, and more generally accept new queens at a limited rate. To conclude, this thesis shows that mechanisms influencing variation in colony queen number and the influence of these changes on conflict resolution are complex. Data gathered in this thesis therefore constitute a solid background for further research on the evolution and the maintenance of complex organisations in insect societies.

Couples' Resolution of an Infertility Diagnosis Before Undergoing in Vitro Fertilization

Although the use of assisted reproductive technology has today become more familiar, the suffering associated with the experience of infertility remains. This study assesses the emotional resolution of couples faced with an infertility diagnosis by examining their narratives. Fifty-seven couples were recruited from fertility clinics to participate in a semistructured interview prior to in vitro fertilization. Two aspects of the couples' reactions to the infertility diagnosis were assessed: (1) each individual's capacity to acknowledge the emotional reality of the diagnosis (diagnosis resolution) and (2) the couple's ability to construct a shared meaning of the infertility diagnosis experience (narrative co-construction). Associations between these aspects and self-reported marital satisfaction, infertility-related stress, and diagnosis-related variables were analyzed. 73.7% of women and 61.4% of men had acknowledged the emotional reality of the diagnosis, and their scores for narrative co-construction were comparable to reference samples. Marital satisfaction, but not infertility-related stress, was associated with diagnosis resolution and narrative co-construction. The results indicate the importance of detecting couples with fewer individual and marital resources needed to face the reality of the diagnosis. A couple's capacity to perceive the infertility diagnosis as a shared problem is also essential for dealing with this common life event.

Towards a connectome mapping pipeline for neonates using high-resolution MP2RAGE and DTI

Exploring the anatomical and functional connectivities between different regions of the brain (the "Connectome") is a core challenge in neuroscience. While robust methods are available for the adult brain, mapping the connectome in neonates is highly challenging. The purpose of this pilot study is to present a methodological approach for analyzing structural connectivity of a neonate brain and to exploit the MP2RAGE sequence with its advantageous contrast properties

Using a Parameterization of a Radiative Transfer Model to Build High-Resolution Maps of Typical Clear-Sky UV Index in Catalonia, Spain

To perform a climatic analysis of the annual UV index (UVI) variations in Catalonia, Spain (northeast of the Iberian Peninsula), a new simple parameterization scheme is presented based on a multilayer radiative transfer model. The parameterization performs fast UVI calculations for a wide range of cloudless and snow-free situations and can be applied anywhere. The following parameters are considered: solar zenith angle, total ozone column, altitude, aerosol optical depth, and single-scattering albedo. A sensitivity analysis is presented to justify this choice with special attention to aerosol information. Comparisons with the base model show good agreement, most of all for the most common cases, giving an absolute error within 0.2 in the UVI for a wide range of cases considered. Two tests are done to show the performance of the parameterization against UVI measurements. One uses data from a high-quality spectroradiometer from Lauder, New Zealand [45.04°S, 169.684°E, 370 m above mean sea level (MSL)], where there is a low presence of aerosols. The other uses data from a Robertson–Berger-type meter from Girona, Spain (41.97°N, 2.82°E, 100 m MSL), where there is more aerosol load and where it has been possible to study the effect of aerosol information on the model versus measurement comparison. The parameterization is applied to a climatic analysis of the annual UVI variation in Catalonia, showing the contributions of solar zenith angle, ozone, and aerosols. High-resolution seasonal maps of typical UV index values in Catalonia are presented

Noninvasive functional and structural exploration of human subcortical structures with high resolution

Projecte de recerca elaborat a partir d’una estada al Max Planck Institute for Human Cognitive and Brain Sciences, Alemanya, entre 2010 i 2012. El principal objectiu d’aquest projecte era estudiar en detall les estructures subcorticals, en concret, el rol dels ganglis basals en control cognitiu durant processament lingüístic i no-lingüístic. Per tal d’assolir una diferenciació minuciosa en els diferents nuclis dels ganglis basals s’utilitzà ressonància magnètica d’ultra-alt camp i alta resolució (7T-MRI). El còrtex prefrontal lateral i els ganglis basals treballant conjuntament per a mitjançar memòria de treball i la regulació “top-down” de la cognició. Aquest circuit regula l’equilibri entre respostes automàtiques i d’alt-ordre cognitiu. Es crearen tres condicions experimentals principals: frases/seqüències noambigües, no-gramatical i ambigües. Les frases/seqüències no-ambigües haurien de provocar una resposta automàtica, mentre les frases/seqüències ambigües i no-gramaticals produïren un conflicte amb la resposta automàtica, i per tant, requeririen una resposta de d’alt-ordre cognitiu. Dins del domini de la resposta de control, la ambigüitat i no-gramaticalitat representen dues dimensions diferents de la resolució de conflicte, mentre per una frase/seqüència temporalment ambigua existeix una interpretació correcte, aquest no és el cas per a les frases/seqüències no-gramaticals. A més, el disseny experimental incloïa una manipulació lingüística i nolingüística, la qual posà a prova la hipòtesi que els efectes són de domini-general; així com una manipulació semàntica i sintàctica que avaluà les diferències entre el processament d’ambigüitat/error “intrínseca” vs. “estructural”. Els resultats del primer experiment (sintax-lingüístic) mostraren un gradient rostroventralcaudodorsal de control cognitiu dins del nucli caudat, això és, les regions més rostrals sostenint els nivells més alts de processament cognitiu

The future key role of LC-high-resolution-MS analyses in clinical laboratories: a focus on quantification.

For the last decade, high-resolution (HR)-MS has been associated with qualitative analyses while triple quadrupole MS has been associated with routine quantitative analyses. However, a shift of this paradigm is taking place: quantitative and qualitative analyses will be increasingly performed by HR-MS, and it will become the common 'language' for most mass spectrometrists. Most analyses will be performed by full-scan acquisitions recording 'all' ions entering the HR-MS with subsequent construction of narrow-width extracted-ion chromatograms. Ions will be available for absolute quantification, profiling and data mining. In parallel to quantification, metabotyping will be the next step in clinical LC-MS analyses because it should help in personalized medicine. This article is aimed to help analytical chemists who perform targeted quantitative acquisitions with triple quadrupole MS make the transition to quantitative and qualitative analyses using HR-MS. Guidelines for the acceptance criteria of mass accuracy and for the determination of mass extraction windows in quantitative analyses are proposed.

High-resolution seismic images of potentially seismogenic structures beneath the northwest Canterbury Plains, New Zealand

The transpressional boundary between the Australian and Pacific plates in the central South Island of New Zealand comprises the Alpine Fault and a broad region of distributed strain concentrated in the Southern Alps but encompassing regions further to the east, including the northwest Canterbury Plains. Low to moderate levels of seismicity (e. g., 2 > M 5 events since 1974 and 2 > M 4.0 in 2009) and Holocene sediments offset or disrupted along rare exposed active fault segments are evidence for ongoing tectonism in the northwest plains, the surface topography of which is remarkably flat and even. Because the geology underlying the late Quaternary alluvial fan deposits that carpet most of the plains is not established, the detailed tectonic evolution of this region and the potential for larger earthquakes is only poorly understood. To address these issues, we have processed and interpreted high-resolution (2.5 m subsurface sampling interval) seismic data acquired along lines strategically located relative to extensive rock exposures to the north, west, and southwest and rare exposures to the east. Geological information provided by these rock exposures offer important constraints on the interpretation of the seismic data. The processed seismic reflection sections image a variably thick layer of generally undisturbed younger (i.e., < 24 ka) Quaternary alluvial sediments unconformably overlying an older (> 59 ka) Quaternary sedimentary sequence that shows evidence of moderate faulting and folding during and subsequent to deposition. These Quaternary units are in unconformable contact with Late Cretaceous-Tertiary interbedded sedimentary and volcanic rocks that are highly faulted, folded, and tilted. The lowest imaged unit is largely reflection-free Permian Triassic basement rocks. Quaternary-age deformation has affected all the rocks underlying the younger alluvial sediments, and there is evidence for ongoing deformation. Eight primary and numerous secondary faults as well as a major anticlinal fold are revealed on the seismic sections. Folded sedimentary and volcanic units are observed in the hanging walls and footwalls of most faults. Five of the primary faults represent plausible extensions of mapped faults, three of which are active. The major anticlinal fold is the probable continuation of known active structure. A magnitude 7.1 earthquake occurred on 4 September 2010 near the southeastern edge of our study area. This predominantly right-lateral strike-slip event and numerous aftershocks (ten with magnitudes >= 5 within one week of the main event) highlight the primary message of our paper: that the generally flat and topographically featureless Canterbury Plains is underlain by a network of active faults that have the potential to generate significant earthquakes.

Early detection of microcirculatory perfusion changes with a high resolution, real time laser Doppler imaging camera--frostbite case study.

A 41-year-old male presented with severe frostbite that was monitored clinically and with a new laser Doppler imaging (LDI) camera that records arbitrary microcirculatory perfusion units (1-256 arbitrary perfusion units (APU's)). LDI monitoring detected perfusion differences in hand and foot not seen visually. On day 4-5 after injury, LDI showed that while fingers did not experience any significant perfusion change (average of 31±25 APUs on day 5), the patient's left big toe did (from 17±29 APUs day 4 to 103±55 APUs day 5). These changes in regional perfusion were not detectable by visual examination. On day 53 postinjury, all fingers with reduced perfusion by LDI were amputated, while the toe could be salvaged. This case clearly demonstrates that insufficient microcirculatory perfusion can be identified using LDI in ways which visual examination alone does not permit, allowing prognosis of clinical outcomes. Such information may also be used to develop improved treatment approaches.

Are patterns of bone loss in anorexic and postmenopausal women similar? Preliminary results using high resolution peripheral computed tomography.

This study intended to compare bone density and architecture in three groups of women: young women with anorexia nervosa (AN), an age-matched control group of young women, and healthy late postmenopausal women. Three-dimensional peripheral quantitative high resolution computed-tomography (HR-pQCT) at the ultradistal radius, a technology providing measures of cortical and trabecular bone density and microarchitecture, was performed in the three cohorts. Thirty-six women with AN aged 18-30years (mean duration of AN: 5.8years), 83 healthy late postmenopausal women aged 70-81 as well as 30 age-matched healthy young women were assessed. The overall cortical and trabecular bone density (D100), the absolute thickness of the cortical bone (CTh), and the absolute number of trabecules per area (TbN) were significantly lower in AN patients compared with healthy young women. The absolute number of trabecules per area (TbN) in AN and postmenopausal women was similar, but significantly lower than in healthy young women. The comparison between AN patients and post-menopausal women is of interest because the latter reach bone peak mass around the middle of the fertile age span whereas the former usually lose bone before reaching optimal bone density and structure. This study shows that bone mineral density and bone compacta thickness in AN are lower than those in controls but still higher than those in postmenopause. Bone compacta density in AN is similar as in controls. However, bone inner structure in AN is degraded to a similar extent as in postmenopause. This last finding is particularly troubling.