Steps towards collective sustainability in biomedical research

The optimism surrounding multistakeholder research initiatives does not match the clear view of policies that are needed to exploit the potential of these collaborations. Here we propose some action items that stem from the integration between research advancements with the perspectives of patient-advocacy organizations, academia, and industry

Presenting evidence-based health information for people with multiple sclerosis : the IN-DEEP project protocol

Background - Increasingly, evidence-based health information, in particular evidence from systematic reviews, is being made available to lay audiences, in addition to health professionals. Research efforts have focused on different formats for the lay presentation of health information. However, there is a paucity of data on how patients integrate evidence-based health information with other factors such as their preferences for information and experiences with information-seeking. The aim of this project is to explore how people with multiple sclerosis (MS) integrate health information with their needs, experiences, preferences and values and how these factors can be incorporated into an online resource of evidence-based health information provision for people with MS and their families.Methods - This project is an Australian-Italian collaboration between researchers, MS societies and people with MS. Using a four-stage mixed methods design, a model will be developed for presenting evidence-based health information on the Internet for people with MS and their families. This evidence-based health information will draw upon systematic reviews of MS interventions from The Cochrane Library. Each stage of the project will build on the last. After conducting focus groups with people with MS and their family members (Stage 1), we will develop a model for summarising and presenting Cochrane MS reviews that is integrated with supporting information to aid understanding and decision making. This will be reviewed and finalised with people with MS, family members, health professionals and MS Society staff (Stage 2), before being uploaded to the Internet and evaluated (Stages 3 and 4).Discussion - This project aims to produce accessible and meaningful evidence-based health information about MS for use in the varied decision making and management situations people encounter in everyday life. It is expected that the findings will be relevant to broader efforts to provide evidence-based health information for patients and the general public. The international collaboration also permits exploration of cultural differences that could inform international practice.<br /

Increasing prevalence of multiple sclerosis in Tuscany: a study based on validated administrative data

AIMS Italy is a high-risk area for Multiple Sclerosis (MS) with a prevalence of around 140/105 (2009) with the exception of Sardinia, with about 224 cases/105 (2009). Nowadays, in Italy, prevalence is absolutely higher than the above estimates. Indeed, prevalence is rising due to annual incidence that is higher than annual mortality. In Tuscany a population MS register has been founded but, to date, it’s not yet completed. To monitor disease epidemiology, comorbidities and care pathways, but also to describe the disease burden and to plan its prevention, treatment and management strategies and resource allocation, population-based studies are preferable. Administrative data offer a unique opportunity for population-based prevalence study of chronic diseases such as MS. Our aim is to update the prevalence of MS in Tuscany and to demonstrate its progressive increment. METHODS The prevalence was calculated using a case-finding algorithm based on administrative data: hospitalization, specific MS drug dispensing, disease-specific exemptions from patient copayment, home and residential long-term care and inhabitant registry. To test algorithm sensitivity, we used a true-positive reference cohort of 302 MS patients from the Tuscan MS register. To test algorithm specificity, we used a general population cohort of 2,644,094 individuals who were presumably not affected by MS (who had never effectuated either cranial or spinal cord CT scan or MRI and had never received a neurological outpatient visit within the NHS). We calculated prevalence on three consecutive years (2011, 2012, 2013). RESULTS At prevalence date (31 December), we identified 6,890 cases in 2011, 7,057 in 2012 and 7,330 in 2013 with a rate of 187.9, 191.1 and 195.4/105, respectively. The female:male ratio slightly increased from 2.0 in 2011 to 2.1 in 2012-2013. The sensitivity of algorithm was 98% and its specificity was 99.99%. DISCUSSION We found a progressive increment of prevalence that confirmed our hypothesis of increasing prevalence. Although our validity study demonstrated a high level of sensibility, we could miss some patients, especially individuals with a severe MS, who did not access the healthcare system and who did not use the DMDs included in our algorithm. CONCLUSIONS We confirmed that Tuscany is a high-risk area for MS and that the prevalence is increasing over time. Despite some limitations, we also demonstrated that our algorithm can accurately identify patients and this cohort is suitable to monitor care pathways. Our future aim is to create an integrated dataset with administrative and clinical data from MS register

Resolución de casos de agitación mediante una estrategia lagrangiana-euleriana en una fase con conservación de masa

Se presentan soluciones de casos de agitación de líquidos viscosos en recipientes cerrados sometidos a aceleraciones horizontales armónicas durante largos períodos de tiempo, en los cuales los errores por pérdida de volumen del fluido afectan sensiblemente los resultados. Se emplea una metodología basada en el método de los elementos finitos para la simulación de flujo con superficie libre que considera únicamente la fase líquida, a través de una estrategia del tipo lagrangiana-euleriana en el cual el dominio cambia de forma de acuerdo con los desplazamientos que sufre la superficie libre (L. Battaglia et al., Mecánica Computacional, Vol. XXVI, pp. 1013-1030, 2007), ampliada con una técnica de control de volumen presentada aquí, que permite realizar cálculos a largo plazo, por ejemplo, de decenas a cientos de períodos de oscilación. Las soluciones obtenidas son validadas mediante la comparación con resultados experimentales y numéricos.Publicado en: Mecánica Computacional vol. XXXV, no. 27.Facultad de Ingenierí

Simulación numérica de agitación con Level Set aplicado a un caso de estudio

El siguiente trabajo tiene como objetivo estudiar la agitación en el interior de un recipiente rectangular con una división interior rígida, sometido a una aceleración horizontal armónica. El caso numérico consiste en el flujo a dos fases, aire y agua, y es abordado mediante una metodología de level set con elementos finitos estabilizados, resolviendo tres instancias en cada paso de tiempo: (i) el campo de flujo, mediante la solución de las ecuaciones de Navier-Stokes; (ii) el transporte de la función de level set, resolviendo un problema de advección; y (iii) la renormalización de la función de level set, para mantener la regularidad de este campo. Los resultados de las simulaciones son comparados con las mediciones de desplazamiento de la superficie libre obtenidas en los experimentos en laboratorio.Publicado en: Mecánica Computacional vol. XXXV, no. 27.Facultad de Ingenierí

A nuclear factor Y interacting protein of the GRAS family is required for nodule organogenesis, infection thread progression, and lateral root growth

A C subunit of the heterotrimeric nuclear factor Y (NF-YC1) was shown to play a key role in nodule organogenesis and bacterial infection during the nitrogen fixing symbiosis established between common bean (Phaseolus vulgaris) and Rhizobium etli. To identify other proteins involved in this process, we used the yeast (Saccharomyces cerevisiae) two-hybrid system to screen for NFYC1- interacting proteins. One of the positive clones encodes a member of the Phytochrome A Signal Transduction1 subfamily of GRAS (for Gibberellic Acid-Insensitive (GAI), Repressor of GAI, and Scarecrow) transcription factors. The protein, named Scarecrow-like13 Involved in Nodulation (SIN1), localizes both to the nucleus and the cytoplasm, but in transgenic Nicotiana benthamiana cells, bimolecular fluorescence complementation suggested that the interaction with NF-YC1 takes place predominantly in the nucleus. SIN1 is expressed in aerial and root tissues, with higher levels in roots and nodules. Posttranscriptional gene silencing of SIN1 using RNA interference (RNAi) showed that the product of this gene is involved in lateral root elongation. However, root cell organization, density of lateral roots, and the length of root hairs were not affected by SIN1 RNAi. In addition, the expression of the RNAi of SIN1 led to a marked reduction in the number and size of nodules formed upon inoculation with R. etli and affected the progression of infection threads toward the nodule primordia. Expression of NF-YA1 and the G2/M transition cell cycle genes CYCLIN B and Cell Division Cycle2 was reduced in SIN1 RNAi roots. These data suggest that SIN1 plays a role in lateral root elongation and the establishment of root symbiosis in common bean.Facultad de Ciencias Exacta

Motor imagery as a function of disease severity in multiple sclerosis: An fMRI study

Motor imagery (MI) is defined as mental execution without any actual movement. While healthy adults usually show temporal equivalence, i.e., isochrony, between the mental simulation of an action and its actual performance, neurological disorders are associated with anisochrony. Unlike in patients with stroke and Parkinson disease, only a few studies have investigated differences of MI ability in multiple sclerosis (MS). However, the relationship among disease severity, anisochrony and brain activation patterns during MI has not been investigated yet. Here, we propose to investigate MI in MS patients using fMRI during a behavioral task executed with dominant/non-dominant hand and to evaluate whether anisochrony is associated with disease severity. Thirty-seven right-handed MS patients, 17 with clinically isolated syndrome (CIS) suggestive of MS and 20 with relapsing-remitting MS (RR-MS) and 20 right-handed healthy controls (HC) underwent fMRI during a motor task consisting in the actual or imaged movement of squeezing a foam ball with the dominant and non-dominant hand. The same tasks were performed outside the MRI room to record the number of actual and imagined ball squeezes, and calculate an Index of performance (IP) based on the ratio between actual and imagined movements. IP showed that a progressive loss of ability in simulating actions (i.e., anisochrony) more pronounced for non-dominant hand, was found as function of the disease course. Moreover, anisochrony was associated with activation of occipito-parieto-frontal areas that were more extensive at the early stages of the disease, probably in order to counteract the changes due to MS. However, the neural engagement of compensatory brain areas becomes more difficult with more challenging tasks, i.e., dominant vs. non-dominant hand, with a consequent deficit in behavioral performance. These results show a strict association between MI performance and disease severity, suggesting that, at early stages of the disease, anisochrony in MI could be considered as surrogate behavioral marker of MS severity

Prevention and cure of rhinogenous deafness at the Thermal Baths ?Bagni delle Galleraie?

Introduction. Hearing is foundamental for human social life.Secretory Otitis Media (SOM) is the most important cause oftrasmissive hypoacusis in early childhood.Methods. The Hygiene Institute in the University of Siena incollaboration with the Thermal Baths ?Bagni delleGalleraie? proposed a prevention and cure campaign ofrhinogenous deafness in June 2002 in some primary schoolsin the Colle val D?Elsa district. A sample of 87 children wasinvolved in the study (average age of 5,64 ± 1,41 years). Onentering the thermal baths a questionnaire was administeredto the parents, to point out possible risk factors. Results.Results. Among the 87 children, 28 cases of SOM and 21cases of severe tubal disorder were found. Only 19 cases out of 49 were already known to the parents and only 28 joinedthe study and were examined for three years consecutively. Discussion. Out of the 35 children examined in 2002, 28 returned to ?The Galleraie? for the two following years. Theyrepeated the thermal cure for two years as a preventive measure. At present they are not affected by SOM and during thewinters suffered a lower number of infections in the primaryairways and took less antibiotics.Conclusions. Our study focuses on infant school childrenbecause of their critical age for linguistic and social development. Early diagnosis and therapy prevent any negativesocial development

Upper limb motor rehabilitation impacts white matter microstructure in multiple sclerosis

Upper limb impairments can occur in patients with multiple sclerosis, affecting daily living activities; however there is at present no definite agreement on the best rehabilitation treatment strategy to pursue. Moreover, motor training has been shown to induce changes in white matter architecture in healthy subjects.This study aimed at evaluating the motor behavioral and white matter microstructural changes following a 2-month upper limb motor rehabilitation treatment based on task-oriented exercises in patients with multiple sclerosis.Thirty patients (18 females and 12 males; age. = 43.3. ±. 8.7. years) in a stable phase of the disease presenting with mild or moderate upper limb sensorimotor deficits were randomized into two groups of 15 patients each. Both groups underwent twenty 1-hour treatment sessions, three times a week. The "treatment group" received an active motor rehabilitation treatment, based on voluntary exercises including task-oriented exercises, while the "control group" underwent passive mobilization of the shoulder, elbow, wrist and fingers.Before and after the rehabilitation protocols, motor performance was evaluated in all patients with standard tests. Additionally, finger motor performance accuracy was assessed by an engineered glove.In the same sessions, every patient underwent diffusion tensor imaging to obtain parametric maps of fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. The mean value of each parameter was separately calculated within regions of interest including the fiber bundles connecting brain areas involved in voluntary movement control: the corpus callosum, the corticospinal tracts and the superior longitudinal fasciculi.The two rehabilitation protocols induced similar effects on unimanual motor performance, but the bimanual coordination task revealed that the residual coordination abilities were maintained in the treated patients while they significantly worsened in the control group (p. = 0.002). Further, in the treatment group white matter integrity in the corpus callosum and corticospinal tracts was preserved while a microstructural integrity worsening was found in the control group (fractional anisotropy of the corpus callosum and corticospinal tracts: p. = 0.033 and p. = 0.022; radial diffusivity of the corpus callosum and corticospinal tracts: p. = 0.004 and p. = 0.008). Conversely, a significant increase of radial diffusivity was observed in the superior longitudinal fasciculi in both groups (p. = 0.02), indicating lack of treatment effects on this structure, showing damage progression likely due to a demyelination process.All these findings indicate the importance of administering, when possible, a rehabilitation treatment consisting of voluntary movements. We also demonstrated that the beneficial effects of a rehabilitation treatment are task-dependent and selective in their target; this becomes crucial towards the implementation of tailored rehabilitative approaches. © 2013 The Authors

Presenting evidence-based health information for people with multiple sclerosis: the IN-DEEP project protocol.

BACKGROUND: Increasingly, evidence-based health information, in particular evidence from systematic reviews, is being made available to lay audiences, in addition to health professionals. Research efforts have focused on different formats for the lay presentation of health information. However, there is a paucity of data on how patients integrate evidence-based health information with other factors such as their preferences for information and experiences with information-seeking. The aim of this project is to explore how people with multiple sclerosis (MS) integrate health information with their needs, experiences, preferences and values and how these factors can be incorporated into an online resource of evidence-based health information provision for people with MS and their families. METHODS: This project is an Australian-Italian collaboration between researchers, MS societies and people with MS. Using a four-stage mixed methods design, a model will be developed for presenting evidence-based health information on the Internet for people with MS and their families. This evidence-based health information will draw upon systematic reviews of MS interventions from The Cochrane Library. Each stage of the project will build on the last. After conducting focus groups with people with MS and their family members (Stage 1), we will develop a model for summarising and presenting Cochrane MS reviews that is integrated with supporting information to aid understanding and decision making. This will be reviewed and finalised with people with MS, family members, health professionals and MS Society staff (Stage 2), before being uploaded to the Internet and evaluated (Stages 3 and 4). DISCUSSION: This project aims to produce accessible and meaningful evidence-based health information about MS for use in the varied decision making and management situations people encounter in everyday life. It is expected that the findings will be relevant to broader efforts to provide evidence-based health information for patients and the general public. The international collaboration also permits exploration of cultural differences that could inform international practice