Validation of wind measurements from a multirotor RPAS-mounted ultrasonic wind sensor using a ground-based LiDAR system

The aim of this research was to establish the validity of wind measurements from on board a multirotor Remotely Piloted Aircraft System (RPAS) for the purposes of wind monitoring applications. A custom-built hexacopter RPAS recorded wind speed and direction by means of an onboard ultrasonic wind sensor, whilst operating in the inherently highly stochastic nature of open field atmospheric conditions. Experimental data were collected during open field hovering flights subject to different ambient conditions with free stream horizontal wind speeds reaching up to 12 m/s. Flights were conducted at different altitudes above ground level and in proximity to a Light Detection and Ranging (LiDAR) remote wind measurement unit that was used as a low-resolution reference meteorological station. Very good correlation was obtained between the RPAS and LiDAR unit for both wind speed and wind direction measurements across all hovering flight altitudes. The RPAS-based wind speed measurements were found to have a consistent 1 m/s positive offset, whilst the RPAS-based wind direction readings had a 6.16◦ negative offset. These were potentially caused by differences in the localized wind fields between the LiDAR and RPAS measuring positions, as well as by localized RPAS rotor-induced air flows for wind speed measurements and potential slight misalignments in the instruments’ reference datum for wind direction readings.peer-reviewe

Patient and Surrogate Views of Community Consultation for Emergency Research

ObjectivePretrial community consultation (CC) is required for emergency research conducted under an exception from informed consent (EFIC) in the United States. CC remains controversial and challenging, and minimal data exist regarding the views of individuals enrolled in EFIC trials on this process. It is important to know whether participants perceive CC to be meaningful and, if so, whom they believe should be consulted.MethodsWe conducted a secondary analysis of data from two studies interviewing patients and surrogates of two recent EFIC trials (PEER‐RAMPART and PEER‐ProTECT). These interviews included similar open‐ and closed‐ended questions regarding participants’ views of the importance of CC, the rationale for their responses, and their views regarding which populations should be included in consultation efforts. A template analytic strategy was used for qualitative analysis of textual data, and descriptive statistics were tabulated to characterize demographic data and instances of major themes.ResultsNinety percent of participants perceived CC to be valuable. Participants’ reasons for finding CC valuable clustered in two categories: 1) as a method of informing the public about the trial to be conducted and 2) as a way of obtaining input and feedback from the community. Participants cited the medical community (43%) and individuals with a connection to the study condition (41%) as the most important groups to involve in consultation efforts; only 5% suggested consulting the general public in the area where the research will be conducted.ConclusionParticipants in EFIC trials and their decision makers generally valued CC as a method of informing and seeking input from the community. Participants felt that the most appropriate groups to consult were the medical community and individuals with connections to the condition under study. Consultation efforts focused on these two groups, rather than the general public, may be more efficient and more meaningful to individuals involved in EFIC trials. These findings also reinforce the importance of the distinction between public disclosure and CC.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139974/1/acem13265-sup-0001-DataSupplementS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139974/2/acem13265_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139974/3/acem13265.pd

Valutazione di alcune performance diagnostiche di kit ELISA per la diagnosi sierologica di Anemia Infettiva Equina (AIE)

Data on evaluation of some diagnostic parameters of all ELISA kits available in Italy for the serodiagnosis of AIE are presented and discussed. Ten laboratories were involved using a panel of 30 sera ran with 4 commercial kits and 2 in-house kits. Kits were also evaluated using a panel of sera from vaccinated animals at different days post vaccination (p.v.). All sera were also tested in agar gel immunodiffusion (AGID). The parameters evaluated were: diagnostic sensitivity (DSe) and specificity (DSp), Cohen K, weighted Cohen K, coefficient of variation (CV), accordance, concordance. Analysis of these parameters indicates that all kits have a higher sensitivity than AGID, even if a complete evaluation, as indicated by OIE (1) should be carried out

Evidence-based guideline : unexplained infertility

The GDG would like to acknowledge the help of many clinicians and professional organizations who refereed the content of the guideline and submitted helpful comments to the draft version. Special thanks to the steering committee of the ESHRE SIG Andrology for the feedback on the formulations of the key questions and the final draft of the guideline.Peer reviewe

Effect of intravenous clarithromycin in patients with sepsis, respiratory and multiple organ dysfunction syndrome: a randomized clinical trial.

Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) - 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35-3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06-0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55

Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathway and extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs n = 42, periventricular control n = 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response

The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. In the CNS, TSC is characterized by cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGAs). SEGAs may lead to impaired circulation of CSF resulting in hydrocephalus and raised intracranial pressure in patients with TSC. Currently, surgical resection and mTORC1 inhibitors are the recommended treatment options for patients with SEGA. In the present study, high-throughput RNA-sequencing (SEGAs n = 19, periventricular control n = 8) was used in combination with computational approaches to unravel the complexity of SEGA development. We identified 9400 mRNAs and 94 microRNAs differentially expressed in SEGAs compared to control tissue. The SEGA transcriptome profile was enriched for the mitogen-activated protein kinase (MAPK) pathway, a major regulator of cell proliferation and survival. Analysis at the protein level confirmed that extracellular signal-regulated kinase (ERK) is activated in SEGAs. Subsequently, the inhibition of ERK independently of mTORC1 blockade decreased efficiently the proliferation of primary patient-derived SEGA cultures. Furthermore, we found that LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5 were overexpressed at both gene and protein levels in SEGA compared to control tissue. Taken together LAMTOR1-5 can form a complex, known as the 'Ragulator' complex, which is known to activate both mTORC1 and MAPK/ERK pathways. Overall, this study shows that the MAPK/ERK pathway could be used as a target for treatment independent of, or in combination with mTORC1 inhibitors for TSC patients. Moreover, our study provides initial evidence of a possible link between the constitutive activated mTORC1 pathway and a secondary driver pathway of tumour growth

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London