Malaria protection due to sickle haemoglobin depends on parasite genotype.

Host genetic factors can confer resistance against malaria1, raising the question of whether this has led to evolutionary adaptation of parasite populations. Here we searched for association between candidate host and parasite genetic variants in 3,346 Gambian and Kenyan children with severe malaria caused by Plasmodium falciparum. We identified a strong association between sickle haemoglobin (HbS) in the host and three regions of the parasite genome, which is not explained by population structure or other covariates, and which is replicated in additional samples. The HbS-associated alleles include nonsynonymous variants in the gene for the acyl-CoA synthetase family member2-4 PfACS8 on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The alleles are in strong linkage disequilibrium and have frequencies that covary with the frequency of HbS across populations, in particular being much more common in Africa than other parts of the world. The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci. These findings open up a new avenue of enquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in African P. falciparum populations.

Mixed Zirconium Phosphate Bis-Phosphonomethyl Glycine from Nanocrystalline α-Zirconium Phosphate: A Tailored Suite for Gold Nanoparticles.

A novel synthetic approach was investigated for the preparation of nanoplatelets of mixed zirconium phosphate bis-phosphonomethyl glycine, ZPGly, by the reaction of a gel of nanocrystalline α-type zirconium phosphate with N,N-bis-phosphonomethyl glycine, H3Gly. The syntheses were carried out in the absence of hydrofluoric acid by changing both the reagent relative amounts and temperature. An H3Gly/Zr molar ratio >2 did not significantly improve the degree of crystallinity of the materials, while an increase of temperature from 80 °C to 120 °C improved the crystallinity; the best result was obtained with H3Gly/Zr molar ratio = 2 and with a temperature reaction of 120 °C. The sample consisted of nanoplatelets with the size in the range 20-40 nm, and it was successfully exfoliated by treatment with a solution of methylamine. By treatment of the ZPGly colloidal dispersions with HAuCl4, a color change from white to red-violet was observed, indicating the formation of gold nanoparticles. The size and morphology of the gold particles were affected by the degree of crystallinity and, in turn, by the composition of the ZPGly support. As a matter of fact, large micrometric Au particles with a cubo-octahedral morphology were obtained by using the less crystalline ZPGly_R2-80 sample, while interconnected Au particles, with a size of about 16 nm, were obtained by using ZPGly_R2-120. The samples exhibited an absorption maximum in the visible region due to the surface plasmon resonance of gold nanoparticles.

Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea.

The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants' genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites' drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance.

Agronomic potential of two different glass-based materials as novel inorganic slow-release iron fertilizers.

BACKGROUND: Large amounts of chemical fertilizers are still currently used to compensate the soil nutrients scarcity in order to increase and sustain crop yield with consequent rising of environmental pollution and health problems. To mitigate these environmental risks, fertilizers with slow-release behaviours have been developed. The aim of this study was to assess the agronomic potential of two different glass-based materials (by-products from the ceramic sector) as inorganic slow-release iron (Fe) fertilizers. RESULTS: The X-ray powder diffraction confirmed the presence of amorphous structure and the richness in Fe of the investigated materials. The solubility analysis highlighted the slow Fe release from the glassy network and that the maximum of the Fe release was at alkaline pH suggesting their potential use as slow-release Fe fertilizers, especially in calcareous soils. The pot and leaching experiments demonstrated that although the glass-based materials increased the amount of soil available Fe, we did not observe Fe leaching and plant toxicity. This fact would suggest their reliability to increase soil fertility without negative effects on the environment. CONCLUSION: The use of glass-based materials, specifically by-products from the ceramic sectors, as inorganic slow-release Fe fertilizers can be sustained. The tests performed at three different pH conditions testified the slow-release behaviour of the tested materials and underlined that the Fe release increases at alkaline environment. Therefore, the present study pointed out the glass-based materials by products from the ceramic sector as novel slow-release and environmental-friendly fertilizers in agriculture. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial.

BACKGROUND: Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalarial drug resistance. METHODS: In this multicentre, open-label, randomised trial, we recruited patients with uncomplicated P falciparum malaria at 18 hospitals and health clinics in eight countries. Eligible patients were aged 2-65 years, with acute, uncomplicated P falciparum malaria alone or mixed with non-falciparum species, and a temperature of 37·5°C or higher, or a history of fever in the past 24 h. Patients were randomly assigned (1:1) to one of two treatments using block randomisation, depending on their location: in Thailand, Cambodia, Vietnam, and Myanmar patients were assigned to either dihydroartemisinin-piperaquine or dihydroartemisinin-piperaquine plus mefloquine; at three sites in Cambodia they were assigned to either artesunate-mefloquine or dihydroartemisinin-piperaquine plus mefloquine; and in Laos, Myanmar, Bangladesh, India, and the Democratic Republic of the Congo they were assigned to either artemether-lumefantrine or artemether-lumefantrine plus amodiaquine. All drugs were administered orally and doses varied by drug combination and site. Patients were followed-up weekly for 42 days. The primary endpoint was efficacy, defined by 42-day PCR-corrected adequate clinical and parasitological response. Primary analysis was by intention to treat. A detailed assessment of safety and tolerability of the study drugs was done in all patients randomly assigned to treatment. This study is registered at ClinicalTrials.gov, NCT02453308, and is complete. FINDINGS: Between Aug 7, 2015, and Feb 8, 2018, 1100 patients were given either dihydroartemisinin-piperaquine (183 [17%]), dihydroartemisinin-piperaquine plus mefloquine (269 [24%]), artesunate-mefloquine (73 [7%]), artemether-lumefantrine (289 [26%]), or artemether-lumefantrine plus amodiaquine (286 [26%]). The median age was 23 years (IQR 13 to 34) and 854 (78%) of 1100 patients were male. In Cambodia, Thailand, and Vietnam the 42-day PCR-corrected efficacy after dihydroartemisinin-piperaquine plus mefloquine was 98% (149 of 152; 95% CI 94 to 100) and after dihydroartemisinin-piperaquine was 48% (67 of 141; 95% CI 39 to 56; risk difference 51%, 95% CI 42 to 59; p<0·0001). Efficacy of dihydroartemisinin-piperaquine plus mefloquine in the three sites in Myanmar was 91% (42 of 46; 95% CI 79 to 98) versus 100% (42 of 42; 95% CI 92 to 100) after dihydroartemisinin-piperaquine (risk difference 9%, 95% CI 1 to 17; p=0·12). The 42-day PCR corrected efficacy of dihydroartemisinin-piperaquine plus mefloquine (96% [68 of 71; 95% CI 88 to 99]) was non-inferior to that of artesunate-mefloquine (95% [69 of 73; 95% CI 87 to 99]) in three sites in Cambodia (risk difference 1%; 95% CI -6 to 8; p=1·00). The overall 42-day PCR-corrected efficacy of artemether-lumefantrine plus amodiaquine (98% [281 of 286; 95% CI 97 to 99]) was similar to that of artemether-lumefantrine (97% [279 of 289; 95% CI 94 to 98]; risk difference 2%, 95% CI -1 to 4; p=0·30). Both TACTs were well tolerated, although early vomiting (within 1 h) was more frequent after dihydroartemisinin-piperaquine plus mefloquine (30 [3·8%] of 794) than after dihydroartemisinin-piperaquine (eight [1·5%] of 543; p=0·012). Vomiting after artemether-lumefantrine plus amodiaquine (22 [1·3%] of 1703) and artemether-lumefantrine (11 [0·6%] of 1721) was infrequent. Adding amodiaquine to artemether-lumefantrine extended the electrocardiogram corrected QT interval (mean increase at 52 h compared with baseline of 8·8 ms [SD 18·6] vs 0·9 ms [16·1]; p<0·01) but adding mefloquine to dihydroartemisinin-piperaquine did not (mean increase of 22·1 ms [SD 19·2] for dihydroartemisinin-piperaquine vs 20·8 ms [SD 17·8] for dihydroartemisinin-piperaquine plus mefloquine; p=0·50). INTERPRETATION: Dihydroartemisinin-piperaquine plus mefloquine and artemether-lumefantrine plus amodiaquine TACTs are efficacious, well tolerated, and safe treatments of uncomplicated P falciparum malaria, including in areas with artemisinin and ACT partner-drug resistance. FUNDING: UK Department for International Development, Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and US National Institutes of Health.

In†Situ X-ray Diffraction Investigation of the Crystallisation of Perfluorinated CeIV -Based Metal-Organic Frameworks with UiO-66 and MIL-140 Architectures*.

We report on the results of an in situ synchrotron powder X-ray diffraction study of the crystallisation in aqueous medium of two recently discovered perfluorinated CeIV -based metal-organic frameworks (MOFs), analogues of the already well investigated ZrIV -based UiO-66 and MIL-140A, namely, F4_UiO-66(Ce) and F4_MIL-140A(Ce). The two MOFs were originally obtained in pure form in similar conditions, using ammonium cerium nitrate and tetrafluoroterephthalic acid as reagents, and small variations of the reaction parameters were found to yield mixed phases. Here, we investigate the crystallisation of these compounds, varying parameters such as temperature, amount of the protonation modulator nitric acid and amount of the coordination modulator acetic acid. When only HNO3 is present in the reaction environment, only F4_MIL-140A(Ce) is obtained. Heating preferentially accelerates nucleation, which becomes rate determining below 57 °C. Upon addition of AcOH to the system, alongside HNO3 , mixed-phased products are obtained. F4_UiO-66(Ce) is always formed faster, and no interconversion between the two phases occurs. In the case of F4_UiO-66(Ce), crystal growth is always the rate-determining step. A higher amount of HNO3 favours the formation of F4_MIL-140A(Ce), whereas increasing the amount of AcOH favours the formation of F4_UiO-66(Ce). Based on the in situ results, a new optimised route to achieving a pure, high-quality F4_MIL-140A(Ce) phase in mild conditions (60 °C, 1 h) is also identified.

"Shake 'n Bake" Route to Functionalized Zr-UiO-66 Metal-Organic Frameworks.

We report a novel synthetic procedure for the high-yield synthesis of metal-organic frameworks (MOFs) with fcu topology with a UiO-66-like structure starting from a range of commercial ZrIV precursors and various substituted dicarboxylic linkers. The syntheses are carried out by grinding in a ball mill the starting reagents, namely, Zr salts and the dicarboxylic linkers, in the presence of a small amount of acetic acid and water (1 mL total volume for 1 mmol of each reagent), followed by incubation at either room temperature or 120 °C. Such a simple "shake 'n bake" procedure, inspired by the solid-state reaction of inorganic materials, such as oxides, avoids the use of large amounts of solvents generally used for the syntheses of Zr-MOF. Acidity of the linkers and the amount of water are found to be crucial factors in affording materials of quality comparable to that of products obtained under solvo- or hydrothermal conditions.

FLASH: a next-generation CRISPR diagnostic for multiplexed detection of antimicrobial resistance sequences.

The growing prevalence of deadly microbes with resistance to previously life-saving drug therapies is a dire threat to human health. Detection of low abundance pathogen sequences remains a challenge for metagenomic Next Generation Sequencing (NGS). We introduce FLASH (Finding Low Abundance Sequences by Hybridization), a next-generation CRISPR/Cas9 diagnostic method that takes advantage of the efficiency, specificity and flexibility of Cas9 to enrich for a programmed set of sequences. FLASH-NGS achieves up to 5 orders of magnitude of enrichment and sub-attomolar gene detection with minimal background. We provide an open-source software tool (FLASHit) for guide RNA design. Here we applied it to detection of antimicrobial resistance genes in respiratory fluid and dried blood spots, but FLASH-NGS is applicable to all areas that rely on multiplex PCR.

Development of a Smart Leg Splint by Using New Sensor Technologies and New Therapy Possibilities.

Nowadays, after suffering a fracture in an upper or lower limb, a plaster cast is placed on the affected limb. It is a very old and efficient technique for recovery from an injury that has not had significant changes since its origin. This project aims to develop a new low-cost smart 3D printed splint concept by using new sensing techniques. Two rapidly evolving Advanced Manufacturing (AM) technologies will be used: 3D scanning and 3D printing, thus combining engineering, medicine and materials evolution. The splint will include new small and lightweight sensors to detect any problem during the treatment process. Previous studies have already incorporated this kind of sensor for medical purposes. However, in this study it is implemented with a new concept: the possibility of applying treatments during the immobilization process and obtaining information from the sensors to modify the treatment. Due to this, rehabilitation treatments like infrared, ultrasounds or electroshock may be applied during the treatment, and the sensors (as it is showed in the study) will be able to detect changes during the rehabilitation process. Data of the pressure, temperature, humidity and colour of the skin will be collected in real time and sent to a mobile device so that they can be consulted remotely by a specialist. Moreover, it would be possible to include these data into the Internet of Things movement. This way, all the collected data might be compared and studied in order to find the best treatment for each kind of injury. It will be necessary to use a biocompatible material, submersible and suitable for contact with skin. These materials make it necessary to control the conditions in which the splint is produced, to assure that the properties are maintained. This development, makes it possible to design a new methodology that will help to provide faster and easier treatment.

Development of copy number assays for detection and surveillance of piperaquine resistance associated plasmepsin 2/3 copy number variation in Plasmodium falciparum.

BACKGROUND: Long regarded as an epicenter of drug-resistant malaria, Southeast Asia continues to provide new challenges to the control of Plasmodium falciparum malaria. Recently, resistance to the artemisinin combination therapy partner drug piperaquine has been observed in multiple locations across Southeast Asia. Genetic studies have identified single nucleotide polymorphisms as well as copy number variations in the plasmepsin 2 and plasmepsin 3 genes, which encode haemoglobin-degrading proteases that associate with clinical and in vitro piperaquine resistance. RESULTS: To accurately and quickly determine the presence of copy number variations in the plasmepsin 2/3 genes in field isolates, this study developed a quantitative PCR assay using TaqMan probes. Copy number estimates were validated using a separate SYBR green-based quantitative PCR assay as well as a novel PCR-based breakpoint assay to detect the hybrid gene product. Field samples from 2012 to 2015 across three sites in Cambodia were tested using DNA extracted from dried blood spots and whole blood to monitor the extent of plasmepsin 2/3 gene amplifications, as well as amplifications in the multidrug resistance transporter 1 gene (pfmdr1), a marker of mefloquine resistance. This study found high concordance across all methods of copy number detection. For samples derived from dried blood spots, a success rate greater than 80% was found in each assay, with more recent samples performing better. Evidence of extensive plasmepsin 2/3 copy number amplifications was observed in Pursat (94%, 2015) (Western Cambodia) and Preah Vihear (87%, 2014) (Northern Cambodia), and lower levels in Ratanakiri (16%, 2014) (Eastern Cambodia). A shift was observed from two copies of plasmepsin 2 in Pursat in 2013 to three copies in 2014-2015 (25% to 64%). Pfmdr1 amplifications were absent in all samples from Preah Vihear and Ratanakiri in 2014 and absent in Pursat in 2015. CONCLUSIONS: The multiplex TaqMan assay is a robust tool for monitoring both plasmepsin 2/3 and pfmdr1 copy number variations in field isolates, and the SYBR-green and breakpoint assays are useful for monitoring plasmepsin 2/3 amplifications. This study shows increasing levels of plasmepsin 2 copy numbers across Cambodia from 2012 to 2015 and a complete reversion of multicopy pfmdr1 parasites to single copy parasites in all study locations.

Development of a Smart Splint to Monitor Different Parameters during the Treatment Process.

For certain musculoskeletal complex rupture injuries, the only treatment available is the use of immobilization splints. This type of treatment usually causes discomfort and certain setbacks in patients. In addition, other complications are usually generated at the vascular, muscular, or articular level. Currently, there is a really possible alternative that would solve these problems and even allows a faster and better recovery. This is possible thanks to the application of engineering on additive manufacturing techniques and the use of biocompatible materials available in the market. This study proposes the use of these materials and techniques, including sensor integration inside the splints. The main parameters considered to be studied are pressure, humidity, and temperature. These aspects are combined and analyzed to determine any kind of unexpected evolution of the treatment. This way, it will be possible to monitor some signals that would be studied to detect problems that are associated to the very initial stage of the treatment. The goal of this study is to generate a smart splint by using biomaterials and engineering techniques based on the advanced manufacturing and sensor system, for clinical purposes. The results show that the prototype of the smart splint allows to get data when it is placed over the arm of a patient. Two temperatures are read during the treatment: in contact with the skin and between skin and splint. The humidity variations due to sweat inside the splint are also read by a humidity sensor. A pressure sensor detects slight changes of pressure inside the splint. In addition, an infrared sensor has been included as a presence detector.

Genomic Analysis of Plasmodium vivax in Southern Ethiopia Reveals Selective Pressures in Multiple Parasite Mechanisms.

The Horn of Africa harbors the largest reservoir of Plasmodium vivax in the continent. Most of sub-Saharan Africa has remained relatively vivax-free due to a high prevalence of the human Duffy-negative trait, but the emergence of strains able to invade Duffy-negative reticulocytes poses a major public health threat. We undertook the first population genomic investigation of P. vivax from the region, comparing the genomes of 24 Ethiopian isolates against data from Southeast Asia to identify important local adaptions. The prevalence of the Duffy binding protein amplification in Ethiopia was 79%, potentially reflecting adaptation to Duffy negativity. There was also evidence of selection in a region upstream of the chloroquine resistance transporter, a putative chloroquine-resistance determinant. Strong signals of selection were observed in genes involved in immune evasion and regulation of gene expression, highlighting the need for a multifaceted intervention approach to combat P. vivax in the region.

Experimental Comparison on Dental BioTribological Pairs Zirconia/Zirconia and Zirconia/Natural Tooth by Using a Reciprocating Tribometer.

The application of tribology in dentistry is growing rapidly, intense research has been conducted to develop an understanding of dental tribology for better selection of artificial materials and dental implant design. Dental biotribology, has been one of the most important branches in biotribology in recent years. The aim of this research is to investigate the tribological performances in the tooth-to-tooth contact and material-to-natural tooth contact (zirconia vs. zirconia and natural tooth vs. zirconia). The presented research was carried out by testing the above mentioned tribological pairs with the use of a reciprocating tribometer under lubricated conditions (artificial saliva). The normal force used in the tests was 20 N the time for each test was of 60 min. The stroke length was 2 mm, according to the range of displacement used in scientific literature. The wear mass loss evaluation was evaluated by using a gravimetric method. In order to characterize the wear mechanisms, present in the worn surfaces after each of tribo-tests, a topographic analysis was carried with a 3D non-contact optical profiler. The results show that the minimum value of the COF is obtained in the case of Zirconia vs. Zirconia tribo-couple. The results on the wear mass loss show a very low wear rate when coupling in tribological condition natural tooth with a ceramic restoration (a mean value of 0.5 mg was found). This rate is even lower when the contact is between two artificial zirconia teeth.

Oral appliance for Obstructive Sleep Apnea: Prototyping and Optimization of the Mandibular Protrusion Device.

Obstructive Sleep apnea is a public health problem. This disease is associated with daytime sleepiness, increased motor vehicle accidents, heart failure and stroke. Treatment options include weight loss, positive airway pressure, pharyngeal and orthognatic surgery. However, selected patients have good response to oral appliances devices that intended to protrude and stabilize the mandible mechanically during the night in order to reduce the collapsibility of the upper airway. Selection of patients includes primary snoring, mild, moderate and positional apnea. The perfect mandibular advance device has not yet been designed. For these reasons, the objective of this paper is to present a new thermoadjustable chair-side oral appliance. Device integrates the best characteristics of custom made and boils and bite previous designs and minimizes inconveniences and possible side effects. The device is a titratable mandibular advancement appliance. It consists of two independent prefabricated trays adaptable to the shape of adult dental arch and linked to each other by a protrusion mechanism. Each tray contains a hard outer shell and a soft thermoplastic resin inner body. The position of the jaw can be adjusted by moving an aluminum rack into, or out from, the guide so the ratchet may get locked into a certain position ensuring the length of the mechanism. The protrusion mechanism is fixed to the splint using small rings that are articulated over a "t" button. Our prototype satisfies the requirements of an effective oral appliance, in terms of retention, comfort, safety and efficacy. It is easy to fit, durable, low cost, quickly titratable, not bulky and easy cleaning. Thermoplastic appliances are specially used like a predictor of treatment response in apnea patients. The device described is a cost-effective introduction to mandibular advancement technology. A qualified dentist or trained sleep doctor could mitigate dental side effects and reduce their incidence.

Novel Technique Based on Fused Filament Fabrication (FFF) and Robocasting to Create Composite Medical Parts.

The purpose for this study is to obtain a new composite manufacturing system based on Additive Manufacturing techniques that allows the creation of parts for the medical industry. These pieces will be resistant, lightweight and may have geometries more complex than those created with traditional systems of composite material. The new system is based on the union of two heads on a 3D Rep-Rap printer. One of the heads is an extruder head of thermoplastic Fused Filament Fabrication (FFF) and the other is a dosing head, based on the Robocasting technique, designed to be assembled on the 3D printer. Thermoplastics material and epoxy resin will be used. The alternate printing of both materials generates a piece of composite material. This new technique will allow to increase the structural properties of the piece in the XY plane. The new additive manufacturing system allows to obtain mechanical improvements both in the modulus of elasticity and in the tensile strength. Increase the modulus of elasticity of a value between 50 and 80% depending on the thermoplastic filament used. In the same way the tensile strength has increased between 50 and 60%. The improvement in the strength / weight ratio allows to this new additive manufacturing system to create medical pieces in which the lightness and resistance are its main characteristic, such as orthopedic prostheses.The results show that the use of FFF together with Robocasting, as a manufacturing process for end-use parts, generates an additional advantage that had not been considered until now. The combination of a thermoplastic and an epoxy resin opens a new path in the additive manufacturing since it allows creating pieces with new qualities without being conditioned by the design.

Design of a Functional Splint for Rehabilitation of Achilles Tendon Injury Using Advanced Manufacturing (AM) Techniques. Implementation Study.

The use of conventional immobilization splints can cause a lot of mishaps and discomfort in patients. In addition, it is common the generation of muscle, joint and vascular complications arising from the application of classic restraint devices in this phase of treatment. Currently, it is being observed that these problems could be solved with the use of Advanced Manufacturing techniques based on Additive Manufacturing (AM), industrial digitalization and reverse engineering for the realization of individualized immobilization splints. The present study proposes to give these splints a functional character in their design adapting them to a specific pathology, in this case to the partial rupture of Achilles tendon. It also provides a comparison against the use of conventional plaster splints as an improvement factor for their definitive implementation considering the initial sanitary use for which they were designed. In this way, there have been created therapeutic windows that allow the application of rehabilitation techniques, being the treatment that would be carried out developed in parallel. The designed splint has been made in FilaFlex and Polycarbonate, materials that guarantee comfort and resistance at the same time. In addition, an optimization in terms of material has been executed, lightening the splint and reducing environmental impact and manufacturing costs. As a result of this preliminary study, a prototype on scale printed in PLA has been generated.

Geometric Model for the Postural Characterization in the Sagital Plane of Lumbar Raquis.

The individual's posture is the physical expression of his body. It is modified throughout life and it is determined by the particular anatomical characteristics that directly affect the biomechanics of the spine. The typing of the spinal curvature is important for the knowledge of body posture. The possibility of having a method for the systematic postural characterization of the spine is an essential objective resource in order to obtain normal or control patterns of the spinal morphology of the population. A widely accepted methodology of morphological characterization of the spine is a necessary requirement for the establishment of preventive criteria for spinal pathologies based on epidemiological population studies. It also represents a necessary requirement for the classification of individuals, based on the biomechanical, orthopaedic or ergonomic criteria necessary for disciplines such as sports, industrial design or sports performance. The present study proposes the development of a morphological postural model of the spine in the lumbar region. The model is based on a system of measurement of objective and comparable parameters by means of X-ray analysis, in order to characterize its morphology in the sagittal plane. The comparison of the results in a population of 47 individuals allowed the possibility to carry out a statistical study on three morphological parameters: sacral angle (α1); reversal angle (α2) and degree of lordosis (DL). The statistical hypothesis that the results behave according to a normal distribution with p < 0.05 is relevant and allows the systematization and postural modelling of the individual.

Behavior under Load of A Human Shoulder: Finite Element Simulation and Analysis.

Most musculoskeletal injuries occur during the work routines in different areas, due to repetitive and sustained movements, they are often located in the shoulder. For workers in the building sector, the repetitive movements and displacements occur under load and unnatural postures of the shoulder joint. For this reason, this study aims to model in 3D the biological components which form the shoulder joint for the later finite element analysis. Three cases with different loads have been considered for this study. Due to a linear and isotropic joint approach it has been possible to evaluate the tensions in the main components of the shoulders: muscles, tendons and ligaments. The methodology used allowed obtaining an improved mesh of the shoulder joint to analyse real situations with finite element method analysis with applications in the field of sports medicine, work, etc. Furthermore, the simplification adopted for modelling the joint muscles, as 1D elements in the finite element model has made it possible to establish different positions of human joint without mesh again each of the studied positions. The results are consistent with the states of applied loads. In fact, the maximum stresses in bones are in the insertion areas of the ligaments. Due to the static positions of the joint under study, the muscles do not support high stresses. According to the stresses distribution, the maximum values are in the zones of tendons. From the result analysis, it is observed how the stresses distribution in the cartilage area maintains coherence with reality since the maximum stresses appear in the lower half of the cartilage. In this area in which the Humerus-scapula contact is greater, the compression tensions are greater.

Monitoring an Analysis of Perturbations in Fusion Deposition Modelling (FDM) Processes for the Use of Biomaterials.

During an FDM production process, there are different external disturbances to the characteristics of the machine that can affect to the production process. These disturbances will cause the final result differs from the desired one. Moreover, these disturbances, such as temperature or chamber humidity, are extremely important in case of using biocompatible materials. The use of these kind of materials with not controlled environment, can cause them to modify or loss of their properties; what will make the product unusable. Apart from these external disturbances, the conditions of the machine to which the material is subjected must also be considered, such as temperature, vibrations or extrusion speed. The monitoring of all these data will allow to know the conditions to which the product was exposed during the process. In this way, it will be able to verify the validity of the final product. For these reasons, the purpose of this work is to monitor the conditions of production of structures with biocompatible materials by fused deposition modelling (FDM) technique. This monitoring will allow us to obtain a report that guarantee the technical and geometrical characteristics of the model and the biomaterial properties. The parameters chosen to be monitored are: Diameter of filament use, temperature in extrusion nozzle, ambient temperature in closed chamber, ambient humidity in closed chamber. The obtained results, after collected and analysing the data, present variations of up to 3% in the temperature of the nozzle of the extruder with respect to set temperature. In the case of the filament diameter the difference with respect to the value provided from the filament supplier is of 13,7%. In addition, the results show how the ambient humidity in closed chamber has changed by 2 percentage points and the ambient temperature in closed chamber has been increased 6,52 °C with respect to the set values.

Panoptes: web-based exploration of large scale genome variation data.

MOTIVATION: The size and complexity of modern large-scale genome variation studies demand novel approaches for exploring and sharing the data. In order to unlock the potential of these data for a broad audience of scientists with various areas of expertise, a unified exploration framework is required that is accessible, coherent and user-friendly. RESULTS: Panoptes is an open-source software framework for collaborative visual exploration of large-scale genome variation data and associated metadata in a web browser. It relies on technology choices that allow it to operate in near real-time on very large datasets. It can be used to browse rich, hybrid content in a coherent way, and offers interactive visual analytics approaches to assist the exploration. We illustrate its application using genome variation data of Anopheles gambiae, Plasmodium falciparum and Plasmodium vivax. AVAILABILITY AND IMPLEMENTATION: Freely available at https://github.com/cggh/panoptes, under the GNU Affero General Public License. CONTACT: paul.vauterin@gmail.com.