Search results for: international training program in pedagogy

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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Authors: Maria João Ferreira, Natalia Sierra-Garcia, Javier Cremades, Carla António, Ana M. Rodrigues, Helena Silva, Ângela Cunha

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Salicornia ramosissima, a halophyte that grows naturally in coastal areas of the northern hemisphere, is often considered the most promising halophyte candidate for extensive crop cultivation and saline agriculture practices. The expanding interest in this plant surpasses its use as gourmet food and includes their potential application as a source of bioactive compounds for the pharmaceutical industry. Despite growing well in saline soils, sustainable and ecologically friendly techniques to enhance crop production and the nutritional value of this plant are still needed. The root microbiome of S. ramosissima proved to be a source of taxonomically diverse plant growth-promoting bacteria (PGPB). Halotolerant strains of Bacillus, Salinicola, Pseudomonas, and Brevibacterium, among other genera, exhibit a broad spectrum of plant-growth promotion traits [e.g., 3-indole acetic acid (IAA), 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, siderophores, phosphate solubilization, Nitrogen fixation] and express a wide range of extracellular enzyme activities. In this work, three plant growth-promoting bacteria strains (Brevibacterium casei EB3, Pseudomonas oryzihabitans RL18, and Bacillus aryabhattai SP20) isolated from the rhizosphere and the endosphere of S. ramosissima roots from different saltmarshes along the Portuguese coast were inoculated in S. ramosissima seeds. Plants germinated from inoculated seeds were grown for three months in pots filled with a mixture of perlite and estuarine sediment (1:1) in greenhouse conditions and later transferred to a growth chamber, where they were maintained two months with controlled photoperiod, temperature, and humidity. Pots were placed on trays containing the irrigation solution (Hoagland’s solution 20% added with 10‰ marine salt). Before reaching the flowering stage, plants were collected, and the fresh and dry weight of aerial parts was determined. Non-inoculated seeds were used as a negative control. Selected dried stems from the most promising treatments were later analyzed by GC-TOF-MS for primary metabolite composition. The efficiency of inoculation and persistence of the inoculum was assessed by Next Generation Sequencing. Inoculations with single strain EB3 and co-inoculations with EB3+RL18 and EB3+RL18+SP20 (All treatment) resulted in significantly higher biomass production (fresh and dry weight) compared to non-inoculated plants. Considering fresh weight alone, inoculation with isolates SP20 and RL18 also caused a significant positive effect. Combined inoculation with the consortia SP20+EB3 or SP20+RL18 did not significantly improve biomass production. The analysis of the profile of primary metabolites will provide clues on the mechanisms by which the growth-enhancement effect of the inoculants operates in the plants. These results sustain promising prospects for the use of rhizospheric and endophytic PGPB as biofertilizers, reducing environmental impacts and operational costs of agrochemicals and contributing to the sustainability and cost-effectiveness of saline agriculture. Acknowledgments: This work was supported by project Rhizomis PTDC/BIA-MIC/29736/2017 financed by Fundação para a Ciência e Tecnologia (FCT) through the Regional Operational Program of the Center (02/SAICT/2017) with FEDER funds (European Regional Development Fund, FNR, and OE) and by FCT through CESAM (UIDP/50017/2020 + UIDB/50017/2020), LAQV-REQUIMTE (UIDB/50006/2020). We also acknowledge FCT/FSE for the financial support to Maria João Ferreira through a PhD grant (PD/BD/150363/2019). We are grateful to Horta dos Peixinhos for their help and support during sampling and seed collection. We also thank Glória Pinto for her collaboration providing us the use of the growth chambers during the final months of the experiment and Enrique Mateos-Naranjo and Jennifer Mesa-Marín of the Departamento de Biología Vegetal y Ecología, the University of Sevilla for their advice regarding the growth of salicornia plants in greenhouse conditions.

Keywords: halophytes, PGPB, rhizosphere engineering, biofertilizers, primary metabolite profiling, plant inoculation, Salicornia ramosissima

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Authors: Humaira Maheen, Elizabeth Hoban, Catherine Bennette

Abstract:

Background: Globally, role of Community Health Workers (CHW) as front line disaster health work force is underutilized. Developing countries which are at risk of natural disasters or humanitarian emergencies should lay down effective strategies especially to ensure adequate access to maternity care during crisis situation by using CHW as they are local, trained, and most of them possess a good relationship with the community. The Minimum Initial Service Package (MISP) is a set of universal guidelines that addresses women’s reproductive health needs during the first phase of an emergency. According to the MISP, pregnant women should have access to a skilled birth attendant and adequate transportation arrangements so they can access a maternity care facility. Pakistan is one of the few countries which has been severely affected by a number of natural disaster as well as humanitarian emergencies in last decade. Pakistan has a young and structured National Disaster Management System in place, where District Authorities play a vital role in disaster management. The District Health Department develops the contingency health plan for an emergency situation and implements it under the existing district health human resources (health workers and medical staff at the health facility) and infrastructure (health care facilities). Methods: A mixed methods study was conducted in rural villages of Sindh adjacent to the river Indus, and included in-depth interviews with 15 women who gave birth during the floods, structured interviews with 668 women who were pregnant during 2010-2014, and in-depth interviews with 25 community health workers (CHW) and 30 key informants. Results: Women said that giving birth in the relief camps during the floods was one of the most challenging times of their life. The district health department didn’t make transportation arrangement for labouring women from relief camp to the nearest health care facility. As a result 91.2% women gave birth in temporary shelters with the help of a traditional birth attendant (Dai) with no clean physical space available to birth. Of the 332 women who were pregnant at the time of the floods, 26 had adverse birth outcomes; 10 had miscarriages, 14 had stillbirths and there were four neonatal deaths. Conclusion: The district health department was not able to provide access to adequate maternity care during according to the international standard during the floods in 2011. We propose a model where CHWs will be used as frontline maternity care providers during any emergency or disaster situations in Pakistan. A separate "birthing station" should be mandatory in all district relief camps, managed by CHWs. Community midwives (CMW) would and the Lady Health Workers (LHW) would provide antenatal and postnatal care alongside, vaccination for pregnant women, neonates and children under five. There must be an ambulance facility for emergency obstetric cases and all district health facilities should have at least two medical staff identified and trained for emergency obstetric management. The District Health Department must provide clean birthing kits and regular and emergency contraceptives in the relief camps. Methods: A mixed methods study was conducted in rural villages of Sindh adjacent to the river Indus, and included in-depth interviews with 15 women who gave birth during the floods, structured interviews with 668 women who were pregnant during 2010-2014, and in-depth interviews with 25 community health workers (CHW) and 30 key informants. Results: Women said that giving birth in the relief camps during the floods was one of the most challenging times of their life. Nearly 91.2% women gave birth in temporary shelters with the help of a traditional birth attendant (Dai) with no clean physical space available to birth, and the health camp was mostly accessed by men and always overcrowded. There was no obstetric trained medical staff in the health camps or transportation provided to take women with complications to the nearest health facility. The rate of adverse outcome following disaster was 22.2% (95% CI: 8.62% – 42.2%) amongst 27 women who did not evacuate as compare to 7.91% (95% CI: 5.03% – 11.8%) among 278 women who lived in relief camp study participants. There were 27 women who evacuated on pre-flood warning and had 0% rate of adverse outcome. Conclusion: We propose a model where CHWs will be used as frontline maternity care providers during any emergency or disaster situations in Pakistan. A separate "birthing station" should be mandatory in all district relief camps, managed by CHWs. Community midwives (CMW) would and the Lady Health Workers (LHW) would provide antenatal and postnatal care alongside, vaccination for pregnant women, neonates and children under five. There must be an ambulance facility for emergency obstetric cases and all district health facilities should have at least two medical staff identified and trained for emergency obstetric management. The District Health Department must provide clean birthing kits and regular and emergency contraceptives in the relief camps.

Keywords: natural disaster, maternity care model, rural, Pakistan, community health workers

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Authors: Alba Prats-Bisbe, Jaume López-Carballo, David Leno-Colorado, Alberto García Molina, Alicia Romero Marquez, Elena Hernández Pena, Eloy Opisso Salleras, Raimon Jané Campos

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Neurological disorders are a leading cause of disability and premature mortality worldwide. Neurorehabilitation (NRHB) is a clinical process aimed at reducing functional impairment, promoting societal participation, and improving the quality of life for affected individuals. Virtual reality (VR) technology is emerging as a promising NRHB support tool. Its immersive nature fosters a strong sense of agency and embodiment, motivating patients to engage in meaningful tasks and increasing adherence to therapy. However, the clinical benefits of VR interventions are challenging to determine due to the high heterogeneity among health applications. This study explores a stepwise development approach for creating VR-based tools to assist individuals with neurological disorders in medical practice, aiming to enhance reproducibility, facilitate comparison, and promote the generalization of findings. Building on previous research, the step-by-step methodology encompasses: Needs Identification– conducting cross-disciplinary meetings to brainstorm problems, solutions, and address barriers. Intervention Definition– target population, set goals, and conceptualize the VR system (equipment and environments). Material Selection and Placement– choose appropriate hardware and software, place the device within the hospital setting, and test equipment. Co-design– collaboratively create VR environments, user interfaces, and data management strategies. Prototyping– develop VR prototypes, conduct user testing, and make iterative redesigns. Usability and Feasibility Assessment– design protocols and conduct trials with stakeholders in the hospital setting. Efficacy Assessment– conduct clinical trials to evaluate outcomes and long-term effects. Cost-Effectiveness Validation– assess reproducibility, sustainability, and balance between costs and benefits. NRHB is complex due to the multifaceted needs of patients and the interdisciplinary healthcare architecture. VR has the potential to support various applications, such as motor skill training, cognitive tasks, pain management, unilateral spatial neglect (diagnosis and treatment), mirror therapy, and ecologically valid activities of daily living. Following this methodology was crucial for launching a VR-based system in a real hospital environment. Collaboration with neuropsychologists lead to develop A) a VR-based tool for cognitive rehabilitation in patients with acquired brain injury (ABI). The system comprises a head-mounted display (HTC Vive Pro Eye) and 7 tasks targeting attention, memory, and executive functions. A desktop application facilitates session configuration, while database records in-game variables. The VR tool's usability and feasibility were demonstrated in proof-of-concept trials with 20 patients, and effectiveness is being tested through a clinical protocol with 12 patients completing 24-session treatment. Another case involved collaboration with nurses and paediatric physiatrists to create B) a VR-based distraction tool during invasive techniques. The goal is to alleviate pain and anxiety associated with botulinum toxin (BTX) injections, blood tests, or intravenous placements. An all-in-one headset (HTC Vive Focus 3) deploys 360º videos to improve the experience for paediatric patients and their families. This study presents a framework for developing clinically relevant and technologically feasible VR-based support tools for hospital settings. Despite differences in patient type, intervention purpose, and VR system, the methodology demonstrates usability, viability, reproducibility and preliminary clinical benefits. It highlights the importance approach centred on clinician and patient needs for any aspect of NRHB within a real hospital setting.

Keywords: neurological disorders, neurorehabilitation, stepwise development approach, virtual reality

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Authors: Krishna Raj Regmi

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A “Climate change adaptation and disaster risk management for sustainable agriculture” project was implemented in Nepal, a Himalayan country during 2008 to 2013 sponsored jointly by Food and Agriculture Organization (FAO) and United Nations Development Programme (UNDP), Nepal. The paper is based on the results and findings of this joint pilot project. The climate change events such as increased intensity of erratic rains in short spells, trend of prolonged drought, gradual rise in temperature in the higher elevations and occurrence of cold and hot waves in Terai (lower plains) has led to flash floods, massive erosion in the hills particularly in Churia range and drying of water sources. These recurring natural and climate-induced disasters are causing heavy damages through sedimentation and inundation of agricultural lands, crops, livestock, infrastructures and rural settlements in the downstream plains and thus reducing agriculture productivity and food security in the country. About 65% of the cultivated land in Nepal is rainfed with drought-prone characteristics and stabilization of agricultural production and productivity in these tracts will be possible through adoption of rainfed and drought-tolerant technologies as well as efficient soil-water management by the local communities. The adaptation and mitigation technologies and options identified by the project for soil erosion, flash floods and landslide control are on-farm watershed management, sloping land agriculture technologies (SALT), agro-forestry practices, agri-silvi-pastoral management, hedge-row contour planting, bio-engineering along slopes and river banks, plantation of multi-purpose trees and management of degraded waste land including sandy river-bed flood plains. The stress tolerant technologies with respect to drought, floods and temperature stress for efficient utilization of nutrient, soil, water and other resources for increased productivity are adoption of stress tolerant crop varieties and breeds of animals, indigenous proven technologies, mixed and inter-cropping systems, system of rice/wheat intensification (SRI), direct rice seeding, double transplanting of rice, off-season vegetable production and regular management of nurseries, orchards and animal sheds. The alternate energy use options and resource conservation practices for use by local communities are installation of bio-gas plants and clean stoves (Chulla range) for mitigation of green house gas (GHG) emissions, use of organic manures and bio-pesticides, jatropha cultivation, green manuring in rice fields and minimum/zero tillage practices for marshy lands. The efficient water management practices for increasing productivity of crops and livestock are use of micro-irrigation practices, construction of water conservation and water harvesting ponds, use of overhead water tanks and Thai jars for rain water harvesting and rehabilitation of on-farm irrigation systems. Initiation of some works on community-based early warning system, strengthening of met stations and disaster database management has made genuine efforts in providing disaster-tailored early warning, meteorological and insurance services to the local communities. Contingent planning is recommended to develop coping strategies and capacities of local communities to adopt necessary changes in the cropping patterns and practices in relation to adverse climatic and disaster risk conditions. At the end, adoption of awareness raising and capacity development activities (technical and institutional) and networking on climate-induced disaster and risks through training, visits and knowledge sharing workshops, dissemination of technical know-how and technologies, conduct of farmers' field schools, development of extension materials and their displays are being promoted. However, there is still need of strong coordination and linkage between agriculture, environment, forestry, meteorology, irrigation, climate-induced pro-active disaster preparedness and research at the ministry, department and district level for up-scaling, implementation and institutionalization of climate change and disaster risk management activities and adaptation mitigation options in agriculture for sustainable livelihoods of the communities.

Keywords: climate change adaptation, disaster risk management, soil-water management practices, sustainable agriculture

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