Hexyl Aminolevulinate-Guided Fluorescence Cystoscopy in the Diagnosis and Follow-up of Patients with Non-Muscle-invasive Bladder Cancer: A Critical Review of the Current Literature.

CONTEXT: Controversy exists regarding the therapeutic benefit and cost effectiveness of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) or hexyl aminolevulinate (HAL) in addition to white-light cystoscopy (WLC) in the management of non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To systematically evaluate evidence regarding the therapeutic benefits and economic considerations of PDD in NMIBC detection and treatment. EVIDENCE ACQUISITION: We performed a critical review of PubMed/Medline, Embase, and the Cochrane Library in October 2012 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) and Standards for the Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forty-four publications were selected for inclusion in this analysis. EVIDENCE SYNTHESIS: Included reports used 5-ALA (in 26 studies), HAL (15 studies), or both (three studies) as photosensitising agents. PDD increased the detection of both papillary tumours (by 7-29%) and flat carcinoma in situ (CIS; by 25-30%) and reduced the rate of residual tumours after transurethral resection of bladder tumour (TURBT; by an average of 20%) compared to WLC alone. Superior recurrence-free survival (RFS) rates and prolonged RFS intervals were reported for PDD, compared to WLC in most studies. PDD did not appear to reduce disease progression. Our findings are limited by tumour heterogeneity and a lack of NMIBC risk stratification in many reports or adjustment for intravesical therapy use in most studies. Although cost effectiveness has been demonstrated for 5-ALA, it has not been studied for HAL. CONCLUSIONS: Moderately strong evidence exists that PDD improves tumour detection and reduces residual disease after TURBT compared with WLC. This has been shown to improve RFS but not progression to more advanced disease. Further work to evaluate cost effectiveness of PDD is required.

Trophic dynamics in the northern Humboldt Current system: insights from stable isotopes and stomach content analyses

The northern Humboldt Current system (NHCS) off Peru is one of the most productive world marine regions. It represents less than 0.1% of the world ocean surface but presently sustains about 10% of the world fish catch, with the Peruvian anchovy or anchoveta Engraulis ringens as emblematic fish resource. Compared with other eastern boundary upwelling systems, the higher fish productivity of the NHCS cannot be explained by a corresponding higher primary productivity. On another hand, the NHCS is the region where El Niño, and climate variability in general, is most notable. Also, surface oxygenated waters overlie an intense and extremely shallow Oxygen Minimum Zone (OMZ). In this context, the main objective of this study is to better understand the trophic flows in the NHCS using both stomach content and stable isotope analyses. The study focuses on a variety of organisms from low trophic levels such as zooplankton to top predators (seabirds and fur seals). The approach combines both long-term and specific studies on emblematic species such as anchoveta, and sardine Sardinops sagax and a more inclusive analysis considering the 'global' food web in the recent years (2008 – 2012) using stable isotope analysis. Revisiting anchovy and sardine we show that whereas phytoplankton largely dominated anchoveta and sardine diets in terms of numerical abundance, the carbon content of prey items indicated that zooplankton was by far the most important dietary component. Indeed for anchovy euphausiids contributed 67.5% of dietary carbon, followed by copepods (26.3%). Selecting the largest prey, the euphausiids, provide an energetic advantage for anchoveta in its ecosystem where oxygen depletion imposes strong metabolic constrain to pelagic fish. Sardine feed on smaller zooplankton than do anchoveta, with sardine diet consisting of smaller copepods and fewer euphausiids than anchoveta diet. Hence, trophic competition between sardine and anchovy in the northern Humboldt Current system is minimized by their partitioning of the zooplankton food resource based on prey size, as has been reported in other systems. These results suggest an ecological role for pelagic fish that challenges previous understanding of their position in the foodweb (zooplanktophagous instead of phytophagous), the functioning and the trophic models of the NHCS. Finally to obtain a more comprehensive vision of the relative trophic position of NHCS main components we used stable isotope analyses. For that purpose we analyzed the δ13C and δ15N stable isotope values of thirteen taxonomic categories collected off Peru from 2008 - 2011, i.e., zooplankton, fish, squids and air-breathing top predators. The δ15N isotope signature was strongly impacted by the species, the body length and the latitude. Along the Peruvian coast, the OMZ get more intense and shallow south of ~7.5ºS impacting the baseline nitrogen stable isotopes. Employing a linear mixed-effects modelling approach taking into account the latitudinal and body length effects, we provide a new vision of the relative trophic position of key ecosystem components. Also we confirm stomach content-based results on anchoveta Engraulis ringens and highlight the potential remarkable importance of an often neglected ecosystem component, the squat lobster Pleuroncodes monodon. Indeed, our results support the hypothesis according to which this species forage to some extent on fish eggs and larvae and can thus predate on the first life stages of exploited species. However, the δ13C values of these two species suggest that anchoveta and squat lobster do not exactly share the same habitat. This would potentially reduce some direct competition and/or predation.

A behavioral ecology of shermen: hidden stories from trajectory data in the Northern Humboldt Current System

This work proposes an original contribution to the understanding of shermen spatial behavior, based on the behavioral ecology and movement ecology paradigms. Through the analysis of Vessel Monitoring System (VMS) data, we characterized the spatial behavior of Peruvian anchovy shermen at di erent scales: (1) the behavioral modes within shing trips (i.e., searching, shing and cruising); (2) the behavioral patterns among shing trips; (3) the behavioral patterns by shing season conditioned by ecosystem scenarios; and (4) the computation of maps of anchovy presence proxy from the spatial patterns of behavioral mode positions. At the rst scale considered, we compared several Markovian (hidden Markov and semi-Markov models) and discriminative models (random forests, support vector machines and arti cial neural networks) for inferring the behavioral modes associated with VMS tracks. The models were trained under a supervised setting and validated using tracks for which behavioral modes were known (from on-board observers records). Hidden semi-Markov models performed better, and were retained for inferring the behavioral modes on the entire VMS dataset. At the second scale considered, each shing trip was characterized by several features, including the time spent within each behavioral mode. Using a clustering analysis, shing trip patterns were classi ed into groups associated to management zones, eet segments and skippers' personalities. At the third scale considered, we analyzed how ecological conditions shaped shermen behavior. By means of co-inertia analyses, we found signi cant associations between shermen, anchovy and environmental spatial dynamics, and shermen behavioral responses were characterized according to contrasted environmental scenarios. At the fourth scale considered, we investigated whether the spatial behavior of shermen re ected to some extent the spatial distribution of anchovy. Finally, this work provides a wider view of shermen behavior: shermen are not only economic agents, but they are also foragers, constrained by ecosystem variability. To conclude, we discuss how these ndings may be of importance for sheries management, collective behavior analyses and end-to-end models.

Trophic ecology of jumbo squid and predatory fishes in the Northern Humboldt Current System

This work provides a contribution to a better understanding of the trophic ecology of important predators in the Northern Humboldt Current System, the jack mackerel (Trachurus murphyi), the chub mackerel (Scomber japonicus) and the jumbo squid (Dosidicus gigas) by the characterization of the highly variable feeding patterns of these species at different spatiotemporal scales. We provided new knowledge on the comparative trophic behaviour of these species, defined as opportunistic in previous investigations. For that purpose we applied a variety of statistical methods to an extensive dataset of 27,188 non-empty stomachs. We defined the spatial organization of the forage fauna of these predators and documented changes in prey composition according to predators’ size and spatiotemporal features of environment. Our results highligh the key role played by the dissolved oxygen. We also deciphered an important paradox on the jumbo squid diet: why do they hardly forage on the huge anchovy (Engraulis ringens) biomass distributed of coastal Peru? We showed that the shallow oxygen minimum zone present off coastal Peru could hamper the co-occurrence of jumbo squids and anchovies. In addition, we proposed a conceptual model on jumbo squid trophic ecology including the ontogenetic cycle, oxygen and prey availability. Moreover we showed that the trophic behaviour of jack mackerel and chub mackerel is adapted to forage on more accessible species such as for example the squat lobster Pleurocondes monodon and Zoea larvae. Besides, both predators present a trophic overlap. But jack mackerel was not as oracious as chub mackerel, contradictorily to what was observed by others authors. Fish diet presented a high spatiotemporal variability, and the shelf break appeared as a strong biogeographical frontier. Diet composition of our fish predators was not necessarily a consistent indicator of changes in prey biomass. El Niño events had a weak effect on the stomach fullness and diet composition of chub mackerel and jack mackerel. Moreover, decadal changes in diet diversity challenged the classic paradigm of positive correlation between species richness and temperature. Finally, the global patterns that we described in this work, illustrated the opportunistic foraging behaviour, life strategies and the high degree of plasticity of these species. Such behaviour allows adaptation to changes in the environment.

Current variables, definitions and endpoints of the European cardiovascular magnetic resonance registry.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly used in daily clinical practice. However, little is known about its clinical utility such as image quality, safety and impact on patient management. In addition, there is limited information about the potential of CMR to acquire prognostic information. METHODS: The European Cardiovascular Magnetic Resonance Registry (EuroCMR Registry) will consist of two parts: 1) Multicenter registry with consecutive enrolment of patients scanned in all participating European CMR centres using web based online case record forms. 2) Prospective clinical follow up of patients with suspected coronary artery disease (CAD) and hypertrophic cardiomyopathy (HCM) every 12 months after enrolment to assess prognostic data. CONCLUSION: The EuroCMR Registry offers an opportunity to provide information about the clinical utility of routine CMR in a large number of cases and a diverse population. Furthermore it has the potential to gather information about the prognostic value of CMR in specific patient populations.

Integrating novel agents into multiple myeloma treatment - current status in Switzerland and treatment recommendations.

The treatment of multiple myeloma has undergone significant changes in the recent past. The arrival of novel agents, especially thalidomide, bortezomib and lenalidomide, has expanded treatment options and patient outcomes are improving significantly. This article summarises the discussions of an expert meeting which was held to debate current treatment practices for multiple myeloma in Switzerland concerning the role of the novel agents and to provide recommendations for their use in different treatment stages based on currently available clinical data. Novel agent combinations for the treatment of newly diagnosed, as well as relapsed multiple myeloma are examined. In addition, the role of novel agents in patients with cytogenetic abnormalities and renal impairment, as well as the management of the most frequent side effects of the novel agents are discussed. The aim of this article is to assist in treatment decisions in daily clinical practice to achieve the best possible outcome for patients with multiple myeloma.

Current developments in the radiotherapy approach to elderly and frail patients with glioblastoma multiforme.

The benefit of postoperative radiotherapy (RT) has been demonstrated in elderly patients aged 65 years or older with glioblastoma multiforme. Hypofractionated RT schedules can reduce the time and morbidity of treatment while maintaining comparable survival outcomes to lengthy conventional RT. Current international randomized clinical trials are studying the optimized hypofractionated RT regimens, hypofractionated RT in comparison with temozolomide chemotherapy and hypofractionated RT in comparison with the same RT plus temozolomide. Given the guarded prognosis of the elderly and frail patients, quality of life and side effects of treatment should be closely examined. As more than half of cancers in the world occur in developing countries, hypofractionated RT could be better utilized as a cost-effective treatment for this group of patients.

Simultaneous Optical Recording in Multiple Cells by Digital Holographic Microscopy of Chloride Current Associated to Activation of the Ligand-Gated Chloride Channel GABA(A) Receptor.

Chloride channels represent a group of targets for major clinical indications. However, molecular screening for chloride channel modulators has proven to be difficult and time-consuming as approaches essentially rely on the use of fluorescent dyes or invasive patch-clamp techniques which do not lend themselves to the screening of large sets of compounds. To address this problem, we have developed a non-invasive optical method, based on digital holographic microcopy (DHM), allowing monitoring of ion channel activity without using any electrode or fluorescent dye. To illustrate this approach, GABA(A) mediated chloride currents have been monitored with DHM. Practically, we show that DHM can non-invasively provide the quantitative determination of transmembrane chloride fluxes mediated by the activation of chloride channels associated with GABA(A) receptors. Indeed through an original algorithm, chloride currents elicited by application of appropriate agonists of the GABA(A) receptor can be derived from the quantitative phase signal recorded with DHM. Finally, chloride currents can be determined and pharmacologically characterized non-invasively simultaneously on a large cellular sampling by DHM.

Measures of health and disease in Africa: are current methods giving us useful information about trends in cardiovascular diseases?

An enormous burst of interest in the public health burden from chronic disease in Africa has emerged as a consequence of efforts to estimate global population health. Detailed estimates are now published for Africa as a whole and each country on the continent. These data have formed the basis for warnings about sharp increases in cardiovascular disease (CVD) in the coming decades. In this essay we briefly examine the trajectory of social development on the continent and its consequences for the epidemiology of CVD and potential control strategies. Since full vital registration has only been implemented in segments of South Africa and the island nations of Seychelles and Mauritius - formally part of WHO-AFRO - mortality data are extremely limited. Numerous sample surveys have been conducted but they often lack standardization or objective measures of health status. Trend data are even less informative. However, using the best quality data available, age-standardized trends in CVD are downward, and in the case of stroke, sharply so. While acknowledging that the extremely limited available data cannot be used as the basis for inference to the continent, we raise the concern that general estimates based on imputation to fill in the missing mortality tables may be even more misleading. No immediate remedies to this problem can be identified, however bilateral collaborative efforts to strength local educational institutions and governmental agencies rank as the highest priority for near term development.

From current immunosuppressive strategies to clinical tolerance of allografts.

In order to prevent allograft rejection, most current immunosuppressive drugs nonspecifically target T-cell activation, clonal expansion or differentiation into effector cells. Experimental models have shown that it is possible to exploit the central and peripheral mechanisms that normally maintain immune homeostasis and tolerance to self-antigens, in order to induce tolerance to alloantigens. Central tolerance results from intrathymic deletion of T cells with high avidity for thymically expressed antigens. Peripheral tolerance to nonself-molecules can be achieved by various mechanisms including deletion of activated/effector T cells, anergy induction and active regulation of effector T cells. In this article, we briefly discuss the pathways of allorecognition and their relevance to current immunosuppressive strategies and to the induction of transplantation tolerance (through haematopoietic mixed chimerism, depleting protocols, costimulatory blockade and regulatory T cells). We then review the prospect of clinical applicability of these protocols in solid organ transplantation.

Concept de first responders en Suisse romande: état des lieux et perspectives [Concept of first responders in Western Switzerland: current situation and future perspectives].

The notion of "First Responder" (FR) refers to the system of first-aid volunteers who act to initiate the first-aid care before the classical emergency help arrives. In 2011, the French-speaking Switzerland counts 19 groups, divided up between four cantons (Fribourg, Vaud, Neuchâtel, Valais). The geographical distribution of those FR shows the stakes of these peripherical areas, with the accessibility difficulties for the emergency services, and a low demography of ambulances and doctors. The number of interventions carried out by the FR has significantly increased during the last years. The association of a quality formation, an excellent knowledge of the ground and a quick intervention has a positive impact on the survival of the patients with vital emergency or traumatic conditions.

A current-mode interface circuit for a piezoresistive pressure sensor

An interfacing circuit for piezoresistive pressure sensors based on CMOS current conveyors is presented. The main advantages of the proposed interfacing circuit include the use of a single piezoresistor, the capability of offset compensation, and a versatile current-mode configuration, with current output and current or voltage input. Experimental tests confirm linear relation of output voltage versus piezoresistance variation.