[Gradual approach for the etiological diagnosis of the neurocognitive disorder]. / Approche graduelle pour le diagnostic étiologique des troubles neurocognitifs.

Neurocognitive disorders (TNC) are of a public health concern. An early and accurate diagnosis is important to tailor a personalised care. We illustrate the importance of a graduated etiological diagnostic approach centered on the clinical presentation employing the case of a patient with a progressive neurovisual disorder suggestive of a common form of Alzheimer's disease. The results of the CSF biomarkers analysis argue against this diagnosis and justifies seeking a Lewy body disease as a differential diagnosis even if all the clinical criteria are initially incomplete. In this article, we illustrate the progressive and graduated approach in the use of complementary medical tests available for reliable and early diagnosis in order to optimise the care plan and predict clinical progress and needs.

Les troubles neurocognitifs (TNC) sont un enjeu de santé publique. Un diagnostic précoce et précis est important pour une prise en charge personnalisée. Nous illustrons l'intérêt d'une démarche diagnostique étiologique graduelle centrée sur la clinique à partir du cas d'un patient atteint d'un trouble neurovisuel progressif suggérant une forme commune de maladie d'Alzheimer. L'analyse des biomarqueurs du LCR argumente en défaveur de ce diagnostic et justifie de rechercher comme diagnostic différentiel une maladie à corps de Lewy même si l'ensemble des critères cliniques sont initialement incomplets. Nous discutons dans cet article la démarche progressive et graduelle dans l'emploi des examens complémentaires à disposition pour un diagnostic fiable et précoce afin d'optimiser le plan de soins et de prédire l'évolution clinique et les besoins.

Biocultural vulnerability exposes threats of culturally important species.

There are growing calls for conservation frameworks that, rather than breaking the relations between people and other parts of nature, capture place-based relationships that have supported social-ecological systems over the long term. Biocultural approaches propose actions based on biological conservation priorities and cultural values aligned with local priorities, but mechanisms that allow their global uptake are missing. We propose a framework to globally assess the biocultural status of specific components of nature that matter to people and apply it to culturally important species (CIS). Drawing on a literature review and a survey, we identified 385 wild species, mostly plants, which are culturally important. CIS predominate among Indigenous peoples (57%) and ethnic groups (21%). CIS have a larger proportion of Data-Deficient species (41%) than the full set of International Union for Conservation of Nature (IUCN) species (12%), underscoring the disregard of cultural considerations in biological research. Combining information on CIS biological conservation status (IUCN threatened status) and cultural status (language vitality), we found that more CIS are culturally Vulnerable or Endangered than they are biologically and that there is a higher share of bioculturally Endangered or Vulnerable CIS than of either biologically or culturally Endangered CIS measured separately. Bioculturally Endangered or Vulnerable CIS are particularly predominant among Indigenous peoples, arguably because of the high levels of cultural loss among them. The deliberate connection between biological and cultural values, as developed in our "biocultural status" metric, provides an actionable way to guide decisions and operationalize global actions oriented to enhance place-based practices with demonstrated long-term sustainability.

Matches and mismatches between the global distribution of major food crops and climate suitability.

Over the course of history, humans have moved crops from their regions of origin to new locations across the world. The social, cultural and economic drivers of these movements have generated differences not only between current distributions of crops and their climatic origins, but also between crop distributions and climate suitability for their production. Although these mismatches are particularly important to inform agricultural strategies on climate change adaptation, they have, to date, not been quantified consistently at the global level. Here, we show that the relationships between the distributions of 12 major food crops and climate suitability for their yields display strong variation globally. After investigating the role of biophysical, socio-economic and historical factors, we report that high-income world regions display a better match between crop distribution and climate suitability. In addition, although crops are farmed predominantly in the same climatic range as their wild progenitors, climate suitability is not necessarily higher there, a pattern that reflects the legacy of domestication history on current crop distribution. Our results reveal how far the global distribution of major crops diverges from their climatic optima and call for greater consideration of the multiple dimensions of the crop socio-ecological niche in climate change adaptive strategies.

Cultivate biodiversity to harvest food security and sustainability.

A confluence of discoveries in ecology and agriculture suggests that biodiversity can help address the sustainability problems facing modern intensive agriculture. Here we explore several questions related to this possibility. Can increases in national crop diversity help increase the stability and security of national food systems? Can practices based on greater crop biodiversity produce yields that compete with those obtained through the long-standing, high-input monoculture model? What are the appropriate levels and combinations of crops to be used? We highlight recent research that suggests it is time to begin unlocking the agricultural potential of biodiversity - from the level of crop genetic diversity to species diversity - and to do so on spatial scales from individual fields to nations. Recent research suggests that the biodiversification of agriculture may lead to greater and more stable yields, decrease land clearing, and lower the use of harmful agrochemicals.

Complementary mechanisms stabilize national food production.

Ensuring the temporal stability of national food production is crucial for avoiding sharp drops in domestic food availability. The average stability of individual crop yields and asynchrony among crop yield fluctuations are two candidate mechanisms to stabilize national food production. However, the quantification of their respective influence on the stability of national food production is lacking, as is the identification of the factors regulating both mechanisms. Using yield data for 138 crops and 115 countries over a 50-year period, we first show that the stability of total national yield mostly relies on the fluctuations of the yield of crops covering the largest share of cropland. The average yield stability of these crops exert a stabilizing effect on national food production that is twice as important as the one of the asynchronous yield fluctuations among them. Climate variability reduces the stability of national food production by synchronizing yield fluctuations among crops and destabilizing the yield of individual crops. However, our results suggest that increasing crop diversity can counteract the synchronizing effects of climate variability by enhancing asynchronous dynamics among crops. Irrigation can promote the average stability of individual crop yields but cannot compensate for the destabilizing effect of climate variability. Considering both the response of each crop to climatic variations and the dynamics emerging from crop baskets will help agricultural policies to ensure stable food supply at the national level.

National food production stabilized by crop diversity.

Increasing global food demand, low grain reserves and climate change threaten the stability of food systems on national to global scales1-5. Policies to increase yields, irrigation and tolerance of crops to drought have been proposed as stability-enhancing solutions1,6,7. Here we evaluate a complementary possibility-that greater diversity of crops at the national level may increase the year-to-year stability of the total national harvest of all crops combined. We test this crop diversity-stability hypothesis using 5 decades of data on annual yields of 176 crop species in 91 nations. We find that greater effective diversity of crops at the national level is associated with increased temporal stability of total national harvest. Crop diversity has stabilizing effects that are similar in magnitude to the observed destabilizing effects of variability in precipitation. This greater stability reflects markedly lower frequencies of years with sharp harvest losses. Diversity effects remained robust after statistically controlling for irrigation, fertilization, precipitation, temperature and other variables, and are consistent with the variance-scaling characteristics of individual crops required by theory8,9 for diversity to lead to stability. Ensuring stable food supplies is a challenge that will probably require multiple solutions. Our results suggest that increasing national effective crop diversity may be an additional way to address this challenge.

Species insurance trumps spatial insurance in stabilizing biomass of a marine macroalgal metacommunity.

Because natural ecosystems are complex, it is difficult to predict how their variability scales across space and levels of organization. The species-insurance hypothesis predicts that asynchronous dynamics among species should reduce variability when biomass is aggregated either from local species populations to local multispecies communities, or from metapopulations to metacommunities. Similarly, the spatial-insurance hypothesis predicts that asynchronous spatial dynamics among either local populations or local communities should stabilize metapopulation biomass and metacommunity biomass, respectively. In combination, both species and spatial insurance reduce variation in metacommunity biomass over time, yet these insurances are rarely considered together in natural systems. We partitioned the extent that species insurance and spatial insurance reduced the annual variation in macroalgal biomass in a southern California kelp forest. We quantified variability and synchrony at two levels of organization (population and community) and two spatial scales (local plots and region) and quantified the strength of species and spatial insurance by comparing observed variability and synchrony in aggregate biomass to null models of independent species or spatial dynamics based on cyclic-shift permutation. Spatial insurance was weak, presumably because large-scale oceanographic processes in the study region led to high spatial synchrony at both population- and community-level biomass. Species insurance was stronger due to asynchronous dynamics among the metapopulations of a few common species. In particular, a regional decline in the dominant understory kelp species Pterygophora californica was compensated for by the rise of three subdominant species. These compensatory dynamics were associated with positive values of the Pacific Decadal Oscillation, indicating that differential species tolerances to warmer temperature and nutrient-poor conditions may underlie species insurance in this system. Our results illustrate how species insurance can stabilize aggregate community properties in natural ecosystems where environmental conditions vary over broad spatial scales.

The Surales, Self-Organized Earth-Mound Landscapes Made by Earthworms in a Seasonal Tropical Wetland.

The formation, functioning and emergent properties of patterned landscapes have recently drawn increased attention, notably in semi-arid ecosystems. We describe and analyze a set of similarly spectacular landforms in seasonal tropical wetlands. Surales landscapes, comprised of densely packed, regularly spaced mounds, cover large areas of the Orinoco Llanos. Although descriptions of surales date back to the 1940's, their ecology is virtually unknown. From data on soil physical and chemical properties, soil macrofauna, vegetation and aerial imagery, we provide evidence of the spatial extent of surales and how they form and develop. Mounds are largely comprised of earthworm casts. Recognizable, recently produced casts account for up to one-half of total soil mass. Locally, mounds are relatively constant in size, but vary greatly across sites in diameter (0.5-5 m) and height (from 0.3 m to over 2 m). This variation appears to reflect a chronosequence of surales formation and growth. Mound shape (round to labyrinth) varies across elevational gradients. Mounds are initiated when large earthworms feed in shallowly flooded soils, depositing casts that form 'towers' above water level. Using permanent galleries, each earthworm returns repeatedly to the same spot to deposit casts and to respire. Over time, the tower becomes a mound. Because each earthworm has a restricted foraging radius, there is net movement of soil to the mound from the surrounding area. As the mound grows, its basin thus becomes deeper, making initiation of a new mound nearby more difficult. When mounds already initiated are situated close together, the basin between them is filled and mounds coalesce to form larger composite mounds. Over time, this process produces mounds up to 5 m in diameter and 2 m tall. Our results suggest that one earthworm species drives self-organizing processes that produce keystone structures determining ecosystem functioning and development.

Historical dynamics in ecosystem service bundles.

Managing multiple ecosystem services (ES), including addressing trade-offs between services and preventing ecological surprises, is among the most pressing areas for sustainability research. These challenges require ES research to go beyond the currently common approach of snapshot studies limited to one or two services at a single point in time. We used a spatiotemporal approach to examine changes in nine ES and their relationships from 1971 to 2006 across 131 municipalities in a mixed-use landscape in Quebec, Canada. We show how an approach that incorporates time and space can improve our understanding of ES dynamics. We found an increase in the provision of most services through time; however, provision of ES was not uniformly enhanced at all locations. Instead, each municipality specialized in providing a bundle (set of positively correlated ES) dominated by just a few services. The trajectory of bundle formation was related to changes in agricultural policy and global trends; local biophysical and socioeconomic characteristics explained the bundles' increasing spatial clustering. Relationships between services varied through time, with some provisioning and cultural services shifting from a trade-off or no relationship in 1971 to an apparent synergistic relationship by 2006. By implementing a spatiotemporal perspective on multiple services, we provide clear evidence of the dynamic nature of ES interactions and contribute to identifying processes and drivers behind these changing relationships. Our study raises questions about using snapshots of ES provision at a single point in time to build our understanding of ES relationships in complex and dynamic social-ecological systems.

Spectrum of digoxin-induced ocular toxicity: a case report and literature review.

BACKGROUND: Digoxin intoxication results in predominantly digestive, cardiac and neurological symptoms. This case is outstanding in that the intoxication occurred in a nonagenarian and induced severe, extensively documented visual symptoms as well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for a whole month despite close medical follow-up, illustrating the difficulty in recognizing drug-induced effects in a polymorbid patient. CASE PRESENTATION: Digoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 ml/min. Over the following 2-3 weeks she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia, dyschromatopsia, aggravated pre-existing formed visual hallucinations and proprioceptive illusions. She saw her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, she was admitted to the emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml (reference range 0.8-2 ng/ml). After stopping digoxin, general symptoms resolved in a few days, but visual complaints persisted. Examination by the ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS cataract, and dry age-related macular degeneration (ARMD). Computerized static perimetry showed non-specific diffuse alterations suggestive of either bilateral retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed moderate diffuse rod and cone dysfunction and multifocal ERG revealed central loss of function OU. Visual symptoms progressively improved over the next 2 months, but multifocal ERG did not. The patient was finally discharged home after a 5 week hospital stay. CONCLUSION: This case is a reminder of a complication of digoxin treatment to be considered by any treating physician. If digoxin is prescribed in a vulnerable patient, close monitoring is mandatory. In general, when facing a new health problem in a polymorbid patient, it is crucial to elicit a complete history, with all recent drug changes and detailed complaints, and to include a drug adverse reaction in the differential diagnosis.

[Pharmacovigilance update]. / Pharmacovigilance.

The main pharmacovigilance updates in 2014 are reviewed. Ivabradine: increased risk of cardiovascular death and myocardial infarction in patients with symptomatic angina treated with high dosages. Clopidogrel: rare observations of acquired hemophilia. Orlistat: may reduce the absorption of HIV antiretrovirals. Ponatinib: increased risk of arteriopathy and thrombosis. Axitinib: significant risk of heart failure (class effect). Tocilizumab: possible causal relationship with the emergence or aggravation of psoriasis. Lithium: hypercalcemia and hyperparathyroidism commonly observed. Sildenalfil: suspected causal association with melanoma, so far not proven, Methylphenidate: rare observations of priapism. St John's wort (Hypericum): reduced effectiveness of hormonal contraceptives, including implants.

Intermittent hemodialysis treatment in cefepime-induced neurotoxicity: case report, pharmacokinetic modeling, and review of the literature.

Cefepime is a broad-spectrum cephalosporin indicated for in-hospital treatment of severe infections. Acute neurotoxicity, an increasingly recognized adverse effect of this drug in an overdose, predominantly affects patients with reduced renal function. Although dialytic approaches have been advocated to treat this condition, their role in this indication remains unclear. We report the case of an 88-year-old female patient with impaired renal function who developed life-threatening neurologic symptoms during cefepime therapy. She was treated with two intermittent 3-hour high-flux, high-efficiency hemodialysis sessions. Serial pre-, post-, and peridialytic (pre- and postfilter) serum cefepime concentrations were measured. Pharmacokinetic modeling showed that this dialytic strategy allowed for serum cefepime concentrations to return to the estimated nontoxic range 15 hours earlier than would have been the case without an intervention. The patient made a full clinical recovery over the next 48 hours. We conclude that at least 1 session of intermittent hemodialysis may shorten the time to return to the nontoxic range in severe clinically patent intoxication. It should be considered early in its clinical course pending chemical confirmation, even in frail elderly patients. Careful dosage adjustment and a high index of suspicion are essential in this population.

[Hospitality for elderly patients in the emergency department]. / Seniors aux urgences, une question d'hospitalité?

Demographic evolution results in a growing use of emergency department by elderly patients. They require special care to avoid any further degradation of cognitive and functional abilities already compromised by the disease or injury that led them to hospital in the first place. Through a clinical case, we list the risks related to the care of these particular patients in the emergency department. Early recognition of those risks and careful management of these patients' specific needs can significantly contribute to reduce lengths of stay, an important outcome from both the individual patient's and society's perspective.

[Pharmacovigilance update]. / Pharmacovigilance.

The main pharmacovigilance updates in 2013 are reviewed. Nitrofurantoin: lower efficacy and an increased risk of adverse events when creatinine clearance is below 60 ml/min. Dabigatran: contraindicated in patients with mechanical heart valves. Azithromycin: QT prolongation and increased risk of death. Zolpidem: towards a lower dosage. Roflumilast: avoid in patients known or at risk for mood disorders. Retigabine: indication restricted to last-line use and new monitoring requirements after reports of pigment changes in retina and other tissues. Telaprevir and rituximab: severe mucocutaneous reactions. Fingolimod: rare cases of progressive multifocal leucoencephalopathy. Tolvaptan: potential for hepatotoxicity. Nicotinic acid/laropiprant: suspension of marketing authorization as benefits no longer outweigh risks.

[Drug-induced adverse events in the elderly: a traveler's guide]. / Guide pratique des effets indésirables médicamenteux chez les seniors.

Elderly people are prone to drug-induced adverse events (AEs), which often manifest as an atypical clinical picture. The differential diagnosis of any new symptom or alteration in the general state of health in the elderly must, therefore, include AEs. This article offers a practical tool designed to help clinicians to rapidly identify which drugs may induce which kind of frequent symptoms or syndromes.

[Principles for the assessment and management of polymorbid elderly patients: a guide for clinicians]. / Principes d'evaluation et de prise en charge des patients agés polymorbides: guide a l'intention des cliniciens.

Providing care to multimorbid older patients is complex, not only because of the coexistence of multiple chronic conditions, but also because of their frequent intrication with psychological and social problems. This article describes a guide for clinicians to assess and manage multimorbid older patients. This guide was adapted from the work of a group of expert US geriatricians. It proposes seven steps: identification of the main problem; identification of patients' preferences; setting of goals of care; estimation of life expectancy; identification of relevant evidence in the literature; revision of the plan of care; and discussion of the options with the patient. The use of this guide is illustrated by a clinical case.

The cost of myrmecophytism: insights from allometry of stem secondary growth.

BACKGROUND AND AIMS: Plant defence traits against herbivores incur production costs that are usually difficult to measure. However, estimating these costs is a prerequisite for characterizing the plant defence strategy as a whole. Myrmecophytes are plants that provide symbiotic ants with specialized nesting cavities, called domatia, in exchange for protection against herbivores. In the particular case of stem domatia, production of extra wood seems to be the only associated cost, making this indirect defence trait a particularly suitable model for estimating the cost of defence. METHODS: Measurements were made of growth pattern and cumulative production cost of domatia over secondary growth in the myrmecophyte Leonardoxa africana subsp. africana, whose internodes display both a solid basal segment and a hollow distal part (the domatium), thus allowing paired comparison of investment in wood. KEY RESULTS: Previous studies showed that 'overconstruction' of the hollow part of internodes during primary growth is needed for mechanical support. In this study, it is shown that the relationship between the woody cross-sectional area of the solid and hollow parts of internodes is negatively allometric at the beginning of secondary growth and nearly isometric later on. Thus, in hollow stems, the first phase of slow secondary growth compensates for the 'overconstruction' of the ring of wood during primary growth. Moreover, the cumulative production cost of a domatium (estimated as the additional volume of wood required for a hollow stem compared with a solid one) is very high at the beginning of secondary growth and then quickly tends to zero. CONCLUSIONS: Making domatia incurs high costs early in ontogeny, costs that are then amortized later in development of stems and of individual plants. Characterizing ontogenetic variation of the net cost of this peculiar defence mechanism will help us build more accurate theoretical models of resource allocation in myrmecophytes.