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Background: Mapping of health-related quality-of-life measures to health utility values can facilitate cost-utility evaluation. Regression-based methods tend to lead to shrinkage of variance. This study aims to map the Medical Outcomes Study HIV Health Survey (MOS-HIV) to EuroQoL 5 Dimensions (EQ-5D-3 L) utility index, and to characterize the performance of three mapping methods, including ordinary least squares (OLS), equi-percentile method (EPM), and a recently proposed method called Mean Rank Method (MRM). Methods: This is a secondary analysis of data from a randomized HIV treatment trial. Baseline data from 421 participants were used to develop mapping functions. Follow-up data from 236 participants was used to validate the mapping functions. Results: In the training dataset, MRM and OLS, but not EPM, reproduced the observed mean utility (0.731). MRM, OLS and EPM under-estimated the standard deviation by 0.3, 26.6 and 1.7%, respectively. MRM had the lowest mean absolute error (0.143) and highest intraclass correlation coefficient (0.723) with the observed utility values, whereas OLS had the lowest mean squared error (0.038) and highest R-squared (0.542). Regressing the MRM- and OLS-mapped utility values upon body mass index and log-viral load gave covariate associations comparable to those estimated from the observed utility data (all P > 0.10). EPM did not achieve this property. Findings from the validation data were similar. Conclusions: Functions are available for mapping the MOS-HIV to the EQ-5D-3 L utility values. MRM and OLS were comparable in terms of agreement with the observed utility values at the individual level. MRM had better performance at the group level in terms of describing the utility distribution. Trial registration: NCT00988039. Registered 30 September 2009., The EARNEST trial was funded by the European and Developing Countries Clinical Trials Partnership (EDCTP, Grant Code: IP.2007.33011.003) with contributions from the Medical Research Council, UK; Institito de Salud Carlos III, Spain (Grant A107/90015); Irish Aid, Ireland; Swedish International Development Cooperation Agency (SIDA), Sweden; Instituto Superiore di Sanita (ISS), Italy; The World Health Organisation; and Merck, USA. Substantive in-kind contributions were made by the Medical Research Council Clinical Trials Unit, UK [MC_UU_12023/23], CINECA, Bologna, Italy, Janssen Diagnostics, Beerse, Belgium; GSK/ViiV Healthcare Ltd., UK; Abbott Laboratories, USA. Trial medication was donated by AbbVie, Merck, Pfizer, GSK and Gilead. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi

Electrospinning is historically related to tissue engineering due to its ability to produce nano-/microscale fibrous materials with mechanical and functional properties that are extremely similar to those of the extracellular matrix of living tissues. The general interest in electrospun fibrous matrices has recently expanded to cancer research both as scaffolds for in vitro cancer modelling and as patches for in vivo therapeutic delivery. In this review, we examine electrospinning by providing a brief description of the process and overview of most materials used in this process, discussing the effect of changing the process parameters on fiber conformations and assemblies. Then, we describe two different applications of electrospinning in service of cancer research: firstly, as three-dimensional (3D) fibrous materials for generating in vitro pre-clinical cancer models; and secondly, as patches encapsulating anticancer agents for in vivo delivery., 8 pages, 7 figures

In this work, the feasibility of sterilizing a water suspension of poly-3-hexylthiophene nanoparticles (P3HT-NPs) is investigated using ionizing radiation, either gamma-rays or high-energy electrons (e-beam). It is found that regardless of the irradiation source, the size, polydispersity, aggregation stability, and morphology of the NPs are not affected by the treatment. Furthermore, the impact of ionizing radiation on the physicochemical properties of NPs at different absorbed radiation doses (10-25 kGy) and dose rates (kGy time(-1)) is evaluated through different spectroscopic techniques. The results indicate that delivering a high dose of radiations (25 kGy) at a high dose rate, that is, kGy s(-1), as achieved by e-beam irradiation, preserves the characteristics of the polymeric NPs. Differently, the same radiation dose but delivered at a lower dose rate, that is, kGy h(-1), as attained by using a gamma-source, can modify the physicochemical properties of the polymer. Sterility tests indicate that an absorbed dose of 10 kGy, delivered either with gamma-rays or e-beam, is already sufficient for effective sterilization of the colloidal suspension and for reducing the endotoxin content. Finally, NPs irradiated at different doses, exhibit the same cytocompatibility and cell internalization characteristics in human neuroblastoma SH-SY5Y cells of NPs prepared under aseptic conditions.

Nanotechnology offers innovative tools for the design of biomimetic nanocarriers for targeted cancer therapy. These nano-systems present several advantages such as cargo’s protection and modulation of its release, inclusion of stimuli-responsive elements, and enhanced tumoral accumulation. All together, these nano-systems suffer low therapeutic efficacy in vivo because organisms can recognize and remove foreign nanomaterials. To overcome this important issue, different modifications on nanoparticle surfaces were exploited in order to reach the desired therapeutic efficacy eliciting, also, the response of immune system against cancer cells. For this reason, more recently, a new strategy involving cell membrane-covered nanoparticles for biomedical application has been attracting increasing attention. Membranes from red blood cells, platelets, leukocytes, tumor, and stem cells, have been exploited as biomimetic coatings of nanoparticles for evading clearance or stimulated immune system by maintaining in the same way their targeting capability. In this review, the use of different cell sources as coating of biomimetic nanocarriers for cancer therapy is discussed.

Since 2012, PMTCT Option B+ has been recommended by the World Health Organization to reduce vertical transmission but numerous adherence challenges remain. We conducted a qualitative study at baseline using six focus group discussions and 14 in-depth interviews to explore knowledge, beliefs, attitudes and challenges towards the Option B+ strategy for PMTCT among HIV-infected pregnant and post-partum women and health workers engaged in Uganda's national Option B+ PMTCT programme. Data were analysed using a thematic approach to capture latent and manifest content with the social ecological model as a theoretic foundation in order to make contextual sense of key stakeholders' needs for an effective Option B+ intervention. Overall, among all study participants, we found multi-level barriers to adhering to Option B+ cutting across all levels of the social ecological model. In line with the model, our study revealed barriers at personal, relational, organizational and societal levels. Some personal beliefs such as that the baby's health is more important that the mother's, organizational (negative attitudes and behaviour of health workers), structural such as poverty, work conflicts, fear and lack of disclosure related to community stigma were all critical obstacles to women adhering to the Option B+ programme. We found that both health workers and participants in the programme have a relatively clear understanding of the benefits of adhering to their treatment; though a more nuanced understanding and thus emphasis in counselling on side effects, is critical to helping patients adhere.

Summary of the ideaOur idea is focused on the development of “monoclonal-type” plastic antibodies based on Molecularly Imprinted Polymers (MIPs) able to selectively bind a portion of the novel coronavirus SARS-CoV-2 spike protein to block its function and, thus, the infection process. Molecular Imprinting, indeed, represents a very promising and attractive technology for the synthesis of MIPs characterized by specific recognition abilities for a target molecule. Given these characteristics, MIPs can be considered tailor-made synthetic antibodies obtained by a templating process.In the present study, the developed imprinted polymeric nanoparticles were characterized in terms of particles size and distribution by Dynamic Light Scattering (DLS) and the imprinting effect and selectivity were investigated by performing binding experiments using the receptor-binding domain (RBD) of the novel coronavirus and the RBD of SARS-CoV spike protein, respectively. Finally, the hemocompatibility of the prepared MIP-based plastic antibodies was also evaluated.

Background The ‘Primary HIV Prevention among Pregnant and Lactating Ugandan Women’ (PRIMAL) randomized controlled trial aimed to assess an enhanced counseling strategy linked to extended postpartum repeat HIV testing and enhanced counseling among 820 HIV-negative pregnant and lactating women aged 18–49 years and 410 of their male partners to address the first pillar of the WHO Global Strategy for the Prevention of Mother-to-Child HIV transmission (PMTCT). This paper presents findings of qualitative studies aimed at evaluating participants’ and service providers’ perceptions on the acceptability and feasibility of the intervention and at understanding the effects of the intervention on risk reduction, couple communication, and emotional support from women’s partners. Methods PRIMAL Study participants were enrolled from two antenatal care clinics and randomized 1:1 to an intervention or control arm. Both arms received repeat sexually transmitted infections (STI) and HIV testing at enrolment, labor and delivery, and at 3, 6, 12, 18 and 24 months postpartum. The intervention consisted of enhanced quarterly counseling on HIV risk reduction, couple communication, family planning and nutrition delivered by study counselors through up to 24 months post-partum. Control participants received repeat standard post-test counseling. Qualitative data were collected from intervention women participants, counsellors and midwives at baseline, midline and end of the study through 18 focus group discussions and 44 key informant interviews. Data analysis followed a thematic approach using framework analysis and a matrix-based system for organizing, reducing, and synthesizing data. Results At baseline, FGD participants mentioned multiple sexual partners and lack of condom use as the main risks for pregnant and lactating women to acquire HIV. The main reasons for having multiple sexual partners were 1) the cultural practice not to have sex in the late pre-natal and early post-natal period; 2) increased sexual desire during pregnancy; 3) alcohol abuse; 4) poverty; and 5) conflict in couples. Consistent condom use at baseline was limited due to lack of knowledge and low acceptance of condom use in couples. The majority of intervention participants enrolled as couples felt enhanced counselling improved understanding, faithfulness, mutual support and appreciation within their couple. Another benefit mentioned by participants was improvement of couple communication and negotiation, as well as daily decision-making around sexual needs, family planning and condom use. Participants stressed the importance of providing counselling services to all couples. Conclusion This study shows that enhanced individual and couple counselling linked to extended repeat HIV and STI testing and focusing on HIV prevention, couple communication, family planning and nutrition is a feasible and acceptable intervention that could enhance risk reduction programs among pregnant and lactating women. Trial registration ClinicalTrials.gov registration number NCT01882998, date of registration 21st June 2013.

Our aim was to investigate variability for salt tolerance in a collection of Panicum coloratum var. makarikariense of INTA EEA Rafaela, Argentina. Panicum coloratum is a C4 perennial grass to be potentially used to increase forage production in areas affected by abiotic factors which reduce their productivity. We evaluated the response of half-sib families from different accessions to increasing salt concentrations under growth chamber conditions. Germination percentage (GP), GP (% of control) and index of germination decreased with increasing salinity, while mean germination time increased (P

Control of motion of drops on solid surfaces and their mechanism is relevant in many nanotechnology processes and water vapour harvesting practices. Biomimetic strategies comprise designing topographic and chemical heterogeneities on solid surfaces, which can pin and steer drops towards required specific locations. Herein, a simple approach to realize ‘‘confined smart’’ liquid drops on surfaces with hydrophilic regions surrounded by superhydrophilic boundaries upon applying a CF4/Ar plasma to a microstructured silicon substrate is presented. The key property of confinement was controlled topographically under simple selective patterning of SU-8 and chemically by plasma modification. Surface chemical and morphological modification of plasma on the SU-8 patterned silicon surfaces were evaluated. Moreover behaviour at the underwater solid/ liquid interface and in underwater oil wettability were investigated. According to this approach, the proposed platform is suitable for biological and chemical applications, for capturing drops for Lab-on-a-chip devices or water harvesting applications.

This study presents an analysis of the course of the agrarian conflicts that existed in Brazil, from 1940 to 2015, which placed the political-ideological centrality of the forces existing in the Brazilian rural sphere. The study is divided into two issues. a) The first, Social division of labor (Mészáros 2004) in the rural area due to the expansion of big rural properties, transforming the land for work into a land for business, opening a sequence of conflicts with peasants. b) The second refers to the analysis of data collected and organized by the Pastoral Land Commission (CPT in Portuguese), identifying agrarian conflicts in Brazil since 1985. The data offered until the year 2015 served as a meeting point to the history of Brazil, marked by its contradictions and memories, which at the same time, remaining alive, as if it is willing to continue to be an eternal present (Jameson 2002), through its structures of spoliation and conflict. Brazil entered the 21st century with large debts to be paid related to the 19th century. One of the biggest debits is the land issue. A question derived from these struggles, and not very simple to answer, is: does the number of families and areas involved in the conflicts change the national land structure in its productive and political aspects? Nowadays, these actions are organized by historical subjects, transforming individual demands into collective proposals in which social subjects perceive themselves as a political force and consolidate knowledge in a permanent educational process. Conflict data registered by the CPT (1985-2016) indicate that there was no change in popular demands for land property and use, and this may also indicate that there was no change in the Brazilian land structure

Metabolic Syndrome is becoming more common and it is characterized by an excess intake of energy, readily available carbohydrates and fats that result in postprandial hyperglycemia and hyperlipidemia. In the treatment of Metabolic Syndrome, a diet characterized by functional food, high fiber intake and low glycemic index is recommended. The aim of this research was to study in vitro the beneficial and biological properties of black rice cultivated in Sibari plain, a particular area of the region of Calabria, and verify if the climatic conditions of this area influence the composition of this pigmented rice. The antioxidant activity was investigated by performing the DPPH radical scavenging assay, while the free phenolic content of CBR extract was measured by Folin Ciocalteu’s assay and the obtained results were expressed as mg of gallic acid equivalent/ mg of extract. In order to establish the anti-inflammatory effect of CBR extract, its reactivity towards nitric oxide (NO) was evaluated, while, its anti-hypertensive activity was studied by determining the ACE activity inhibition. CBR extract suppress, also, pancreatic lipase activity with an IC50 value of 34.3 µg/ml and it decreases cellular lipid accumulation by about 60%. Finally, its hypoglycemic effect was evaluated by measuring the inhibiting activity towards α-glucosidase and α-amylase enzymes. The obtained results demonstrate that this kind of black rice owns different beneficial properties, which make it a functional food that could improve metabolic disorders of MS.

This paper reports on the observation of the sidereal large-scale anisotropy of cosmic rays using data collected by the ARGO-YBJ experiment over 5 years (2008-2012). This analysis extends previous work limited to the period from 2008 January to 2009 December, near the minimum of solar activity between cycles 23 and 24. With the new data sample, the period of solar cycle 24 from near minimum to maximum is investigated. A new method is used to improve the energy reconstruction, allowing us to cover a much wider energy range, from 4 to 520 TeV. Below 100 TeV, the anisotropy is dominated by two wide regions, the so-called “tail-in” and “loss-cone” features. At higher energies, a dramatic change of the morphology is confirmed. The yearly time dependence of the anisotropy is investigated. Finally, no noticeable variation of cosmic-ray anisotropy with solar activity is observed for a median energy of 7 TeV.

DAMPE (DArk Matter Particle Explorer) is a spaceborne high-energy cosmic ray and gamma-ray detector , successfully launched in December 2015. It is designed to probe astroparticle physics in the broad energy range from few GeV to 100 TeV. The scientific goals of DAMPE include the identification of possible signatures of Dark Matter annihilation or decay, the study of the origin and propagation mechanisms of cosmic-ray particles, and gamma-ray astronomy . DAMPE consists of four sub-detectors: a plastic scintillator strip detector, a Silicon–Tungsten tracKer–converter (STK), a BGO calorimeter and a neutron detector . The STK is composed of six double layers of single-sided silicon micro-strip detectors interleaved with three layers of tungsten for photon conversions into electron–positron pairs . The STK is a crucial component of DAMPE, allowing to determine the direction of incoming photons, to reconstruct tracks of cosmic rays and to estimate their absolute charge (Z). We present the in-flight performance of the STK based on two years of in-flight DAMPE data, which includes the noise behavior, signal response, thermal and mechanical stability, alignment and position resolution.

Background In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events. Methods and findings In a 2×2×2 factorial open-label parallel-group trial, treatment-naive adults, adolescents, and children >5 years old infected with HIV, with cluster of differentiation 4 (CD4) 0.7) and despite significantly greater VL suppression with raltegravir-intensified ART at 4 weeks (343/836 [41.0%] versus 113/841 [13.4%] with standard ART, p < 0.001) and 12 weeks (567/789 [71.9%] versus 415/803 [51.7%] with standard ART, p < 0.001). Through 48 weeks, there was no evidence of differences in mortality (aHR = 0.98 [95% CI 0.76–1.28], p = 0.91); in serious (aHR = 0.99 [0.81–1.21], p = 0.88), grade-4 (aHR = 0.88 [0.71–1.09], p = 0.29), or ART-modifying (aHR = 0.90 [0.63–1.27], p = 0.54) adverse events (the latter occurring in 59 [6.5%] participants with raltegravir-intensified ART versus 66 [7.3%] with standard ART); in events judged compatible with IRIS (occurring in 89 [9.9%] participants with raltegravir-intensified ART versus 86 [9.5%] with standard ART, p = 0.79) or in hospitalisations (aHR = 0.94 [95% CI 0.76–1.17], p = 0.59). At 12 weeks, one and two raltegravir-intensified participants had predicted intermediate-level and high-level raltegravir resistance, respectively. At 48 weeks, the nucleoside reverse transcriptase inhibitor (NRTI) mutation K219E/Q (p = 0.004) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations K101E/P (p = 0.03) and P225H (p = 0.007) were less common in virus from participants with raltegravir-intensified ART, with weak evidence of less intermediate- or high-level resistance to tenofovir (p = 0.06), abacavir (p = 0.08), and rilpivirine (p = 0.07). Limitations of the study include limited clinical, radiological, and/or microbiological information for some participants, reflecting available services at the centres, and lack of baseline genotypes. Conclusions Although 12 weeks of raltegravir intensification was well tolerated and reduced HIV viraemia significantly faster than standard triple-drug ART during the time of greatest risk for early death, this strategy did not reduce mortality or clinical events in this group and is not warranted. There was no excess of IRIS-compatible events, suggesting that integrase inhibitors can be used safely as part of standard triple-drug first-line therapy in severely immunocompromised individuals. Trial registration ClinicalTrials.gov NCT01825031.

Background Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage. Methods We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilita Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated prothrombin time (aPTT), international normalized ratio (INR), creatinine, and blood urea nitrogen (BUN) were recorded. Patients were followed up from admission until death or discharge. Results One hundred patients (49 survivors and 51 nonsurvivors) were included in the analysis. Unadjusted analysis to compare survivors and nonsurvivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in nonsurvivors than in survivors. Multivariable mixed-effects models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT, and INR. In contrast, no direct linear association was found between viremia and either creatinine, BUN, or bilirubin. Conclusions This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not find strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease.

Purpose Drug-induced sedation endoscopy (DISE) classification systems have been used to assess anatomical findings on upper airway obstruction, and decide and plan surgical treatments and act as a predictor for surgical treatment outcome for obstructive sleep apnoea management. The first objective is to identify if there is a universally accepted DISE grading and classification system for analysing DISE findings. The second objective is to identify if there is one DISE grading and classification treatment planning framework for deciding appropriate surgical treatment for obstructive sleep apnoea (OSA). The third objective is to identify if there is one DISE grading and classification treatment outcome framework for determining the likelihood of success for a given OSA surgical intervention. Methods A systematic review was performed to identify new and significantly modified DISE classification systems: concept, advantages and disadvantages. Results Fourteen studies proposing a new DISE classification system and three studies proposing a significantly modified DISE classification were identified. None of the studies were based on randomised control trials. Conclusion DISE is an objective method for visualising upper airway obstruction. The classification and assessment of clinical findings based on DISE is highly subjective due to the increasing number of DISE classification systems. Hence, this creates a growing divergence in surgical treatment planning and treatment outcome. Further research on a universally accepted objective DISE assessment is critically needed.

Drug-induced sedation endoscopy (DISE) classification systems play a significant role in clinical analysis based on DISE findings, treatment decision process, treatment planning process and fundamentally in treatment outcomes. However, there is a major problem: there is no universally agreed DISE classification system. Hence, for the same DISE examination different DISE classification systems can be used to: assess anatomic findings, decide and plan different treatments. Hence, this leads to different treatment outcomes. The key objective of this study is to propose uDISE model: universal drug-induced sedation endoscopy (DISE) classification system. Set theory and relational mapping was used to develop a DISE classification system based on anatomical structures/level; degree of severity; and configuration of obstruction and its relationship with existing DISE classification systems. uDISE model consists of seven anatomical sites (nose, velum, tonsils, lateral pharyngeal wall/oropharynx, tongue base, epiglottis and larynx), three degrees of obstructive severity (none, partial and complete), three configurations of obstruction (anteroposterior, lateral and circumferential) and a severity index. uDISE model was mapped to four existing DISE classification systems: Pringle and Croft grading system, VOTE, NOHL and P-T-L-Tb-E. uDISE model provides a methodology for mapping different DISE findings based on different classification systems into one common DISE assessments format. This provides a framework for comparing different DISE assessments, treatment plan and treatment outcome irrespective of DISE classification system used. Further research is required to establish a complete relational mapping between uDISE model and other existing DISE classification systems.

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: The Lancet Commission on Global Surgery established the Three Delays framework, categorising delays in accessing timely surgical care into delays in seeking care (First Delay), reaching care (Second Delay), and receiving care (Third Delay). Globally, knowledge gaps regarding delays for fracture care, and the lack of large prospective studies informed the rationale for our international observational study. We investigated delays in hospital admission as a surrogate for accessing timely fracture care and explored factors associated with delayed hospital admission. Methods: In this prospective observational substudy of the ongoing International Orthopaedic Multicenter Study in Fracture Care (INORMUS), we enrolled patients with fracture across 49 hospitals in 18 low-income and middle-income countries, categorised into the regions of China, Africa, India, south and east Asia, and Latin America. Eligible patients were aged 18 years or older and had been admitted to a hospital within 3 months of sustaining an orthopaedic trauma. We collected demographic injury data and time to hospital admission. Our primary outcome was the number of patients with open and closed fractures who were delayed in their admission to a treating hospital. Delays for patients with open fractures were defined as being more than 2 h from the time of injury (in accordance with the Lancet Commission on Global Surgery) and for those with closed fractures as being a delay of more than 24 h. Secondary outcomes were reasons for delay for all patients with either open or closed fractures who were delayed for more than 24 h. We did logistic regression analyses to identify risk factors of delays of more than 2 h in patients with open fractures and delays of more than 24 h in patients with closed fractures. Logistic regressions were adjusted for region, age, employment, urban living, health insurance, interfacility referral, method of transportation, number of fractures, mechanism of injury, and fracture location. We further calculated adjusted relative risk (RR) from adjusted odds ratios, adjusted for the same variables. This study was registered with ClinicalTrials.gov, NCT02150980, and is ongoing. Findings: Between April 3, 2014, and May 10, 2019, we enrolled 31 255 patients with fractures, with a median age of 45 years (IQR 31–62), of whom 19 937 (63·8%) were men, and 14 524 (46·5%) had lower limb fractures, making them the most common fractures. Of 5256 patients with open fractures, 3778 (71·9%) were not admitted to hospital within 2 h. Of 25 999 patients with closed fractures, 7141 (27·5%) were delayed by more than 24 h. Of all regions, Latin America had the greatest proportions of patients with delays (173 [88·7%] of 195 patients with open fractures; 426 [44·7%] of 952 with closed fractures). Among patients delayed by more than 24 h, the most common reason for delays were interfacility referrals (3755 [47·7%] of 7875) and Third Delays (cumulatively interfacility referral and delay in emergency department: 3974 [50·5%]), while Second Delays (delays in reaching care) were the least common (423 [5·4%]). Compared with other methods of transportation (eg, walking, rickshaw), ambulances led to delay in transporting patients with open fractures to a treating hospital (adjusted RR 0·66, 99% CI 0·46–0·93). Compared with patients with closed lower limb fractures, patients with closed spine (adjusted RR 2·47, 99% CI 2·17–2·81) and pelvic (1·35, 1·10–1·66) fractures were most likely to have delays of more than 24 h before admission to hospital. Interpretation: In low-income and middle-income countries, timely hospital admission remains largely inaccessible, especially among patients with open fractures. Reducing hospital-based delays in receiving care, and, in particular, improving interfacility referral systems are the most substantial tools for reducing delays in admissions to hospital. Funding: National Health and Medical Research Council of Australia, Canadian Institutes of Health Research, McMaster Surgical Associates, and Hamilton Health Sciences.

- Label: OBJECTIVES NlmCategory: OBJECTIVE content: A Demographic and Health Platform was established in Magude in 2015, prior to the deployment of a project aiming to evaluate the feasibility of malaria elimination in southern Mozambique, named the Magude project. This platform aimed to inform the design, implementation and evaluation of the Magude project, through the identification of households and population; and the collection of demographic, health and malaria information. - Label: SETTING NlmCategory: METHODS content: Magude is a rural district of southern Mozambique which borders South Africa. It has nine peripheral health facilities and one referral health centre with an inpatient ward. - Label: INTERVENTION NlmCategory: METHODS content: "A baseline census enumerated and geolocated all the households, and their resident and non-resident members, collecting demographic and socio-economic information, and data on the coverage and usage of malaria control tools. Inpatient and outpatient data during the 5\xE2\x80\x89years (2010 to 2014) before the survey were obtained from the district health authorities. The demographic platform was updated in 2016." - Label: RESULTS NlmCategory: RESULTS content: "The baseline census conducted in 2015 reported 48\xE2\x80\x89448 (92.1%) residents and 4133 (7.9%) non-residents, and 10\xE2\x80\x89965 households. Magude's population is predominantly young, half of the population has no formal education and the main economic activities are agriculture and fishing. Houses are mainly built with traditional non-durable materials and have poor sanitation facilities. Between 2010 and 2014, malaria was the most common cause of all-age inpatient discharges (representing 20% to 40% of all discharges), followed by HIV (12% to 22%) and anaemia (12% to 15%). In early 2015, all-age bed-net usage was between 21.8% and 27.1%\xE2\x80\x89and the reported coverage of indoor residual spraying varied across the district between 30.7% and 79%." - Label: CONCLUSION NlmCategory: CONCLUSIONS content: This study revealed that Magude has limited socio-economic conditions, poor access to healthcare services and low coverage of malaria vector control interventions. Thus, Magude represented an area where it is most pressing to demonstrate the feasibility of malaria elimination. - Label: TRIAL REGISTRATION NUMBER NlmCategory: BACKGROUND content: NCT02914145; Pre-results.

Background: In cancer research, studying cell motility is fundamental to investigate cancer invasion and drug resistance. In solid tumors constituted by a huge stroma component, such as pancreatic ductal adenocarcinoma (PDAC), the ability to quantify cell movement and interactions is mandatory to better understand the complex crosstalk between cancer and stroma cells. In PDAC, the pancreatic stellate cells (PSCs) are the principal source of dense fibrotic stroma: these closely interact with the PDAC cells to create a facilitating tumor microenvironment that supports local and distant tumor progression through the secretion and/or the response to a number of cytokines that globally increase cancer invasiveness; moreover, the dense tumor microenvironment contributes to resistance to chemotherapy and radiation therapy. Recent studies have established that targeting the stromal compartment in PDAC may lead to promising outcomes. Unfortunately, significant improvements in the overall survival of patients have not been realized in more than four decades, in part because of the lack of relevant preclinical models. Methods: To infer interactions existing between stromal and cancer cells in complex 3D environments, we developed a novel platform that combines time-lapse fluorescence microscopy, automated image detection, and extensive statistical analysis. To better mimic in situ PDAC, we created a hydrogel-based (Matrigel, collagen) model that allows cell tracking in 4 dimensions (x, y, z, t), not possible in 2D, using a mixed population of L3.6PL pancreatic cancer cells and PSCs at a ratio of 25% and 75%, respectively. To precisely identify the two populations and facilitate automatic cell detection, cells were transfected with GFP and mCherry vectors. Once in the 3D conformation, the cocultures were monitored through time-lapse confocal microscopy (CLSM) in controlled conditions, and the dataset containing the temporal evolution of the cells was processed by statistical tools. Results: Key to our approach was the generation of new machine learning-driven automated inferential protocols that resulted in the high-resolution imaging of the strength of the interactions between cells, as well as the potential presence of local chemokine gradients. In our ongoing studies, both commercial PDAC cell lines and pancreatic stellate cells were used to establish the model system. We are currently adopting the model to take full advantage of patient-derived PDAC cells established using the conditionally reprogrammed cells technique, mixed with patient-matched stellate cells. Since cell migration is a hallmark of cancer, we believe that this platform could be used as a reliable and reproducible approach for studying single-cell migration and invasion also in patient-derived models. The research leading to these results received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 759959, ERC-StG “INTERCELLMED”). Citation Format: Marta Maria Cavo, Francesco Alemanno, Donatella Delle Cave, Eliana D'Amone, Adriano Barra, Enza Lonardo, Erika Parasido, Chris Albanese, Loretta Laureana del Mercato. Quantifying stroma-tumor cell interactions in three-dimensional cell culture systems [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A48.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.