Abstract
Satellite remote sensing is becoming a widely used monitoring technique in coastal sciences. Yet, no benchmarking studies exist that compare the performance of popular satellite-derived ...shoreline mapping algorithms against standardized sets of inputs and validation data. Here we present a new benchmarking framework to evaluate the accuracy of shoreline change observations extracted from publicly available satellite imagery (Landsat and Sentinel-2). Accuracy and precision of five established shoreline mapping algorithms are evaluated at four sandy beaches with varying geologic and oceanographic conditions. Comparisons against long-term in situ beach surveys reveal that all algorithms provide horizontal accuracy on the order of 10 m at microtidal sites. However, accuracy deteriorates as the tidal range increases, to more than 20 m for a high-energy macrotidal beach (Truc Vert, France) with complex foreshore morphology. The goal of this open-source, collaborative benchmarking framework is to identify areas of improvement for present algorithms, while providing a stepping stone for testing future developments, and ensuring reproducibility of methods across various research groups and applications.
Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of motavizumab, an ...investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab.
This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged <or=6 months at enrollment or children aged <or=24 months with chronic lung disease of prematurity who received 15 mg/kg palivizumab or motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations.
Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with palivizumab recipients, achieving noninferiority. Motavizumab was superior to palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events.
Children receiving prophylaxis with motavizumab or palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk.
We report a novel technology for the rapid healing of large osseous and chondral defects, based upon the genetic modification of autologous skeletal muscle and fat grafts. These tissues were selected ...because they not only possess mesenchymal progenitor cells and scaffolding properties, but also can be biopsied, genetically modified and returned to the patient in a single operative session. First generation adenovirus vector carrying cDNA encoding human bone morphogenetic protein-2 (Ad.BMP-2) was used for gene transfer to biopsies of muscle and fat. To assess bone healing, the genetically modified ("gene activated") tissues were implanted into 5mm-long critical size, mid-diaphyseal, stabilized defects in the femora of Fischer rats. Unlike control defects, those receiving gene-activated muscle underwent rapid healing, with evidence of radiologic bridging as early as 10 days after implantation and restoration of full mechanical strength by 8 weeks. Histologic analysis suggests that the grafts rapidly differentiated into cartilage, followed by efficient endochondral ossification. Fluorescence in situ hybridization detection of Y-chromosomes following the transfer of male donor muscle into female rats demonstrated that at least some of the osteoblasts of the healed bone were derived from donor muscle. Gene activated fat also healed critical sized defects, but less quickly than muscle and with more variability. Anti-adenovirus antibodies were not detected. Pilot studies in a rabbit osteochondral defect model demonstrated the promise of this technology for healing cartilage defects. Further development of these methods should provide ways to heal bone and cartilage more expeditiously, and at lower cost, than is presently possible.
A balanced t(1;11) translocation that transects the Disrupted in schizophrenia 1 (DISC1) gene shows genome-wide significant linkage for schizophrenia and recurrent major depressive disorder (rMDD) in ...a single large Scottish family, but genome-wide and exome sequencing-based association studies have not supported a role for DISC1 in psychiatric illness. To explore DISC1 in more detail, we sequenced 528 kb of the DISC1 locus in 653 cases and 889 controls. We report 2718 validated single-nucleotide polymorphisms (SNPs) of which 2010 have a minor allele frequency of <1%. Only 38% of these variants are reported in the 1000 Genomes Project European subset. This suggests that many DISC1 SNPs remain undiscovered and are essentially private. Rare coding variants identified exclusively in patients were found in likely functional protein domains. Significant region-wide association was observed between rs16856199 and rMDD (P=0.026, unadjusted P=6.3 × 10(-5), OR=3.48). This was not replicated in additional recurrent major depression samples (replication P=0.11). Combined analysis of both the original and replication set supported the original association (P=0.0058, OR=1.46). Evidence for segregation of this variant with disease in families was limited to those of rMDD individuals referred from primary care. Burden analysis for coding and non-coding variants gave nominal associations with diagnosis and measures of mood and cognition. Together, these observations are likely to generalise to other candidate genes for major mental illness and may thus provide guidelines for the design of future studies.
Viral lower respiratory tract infection (vLRTI) contributes to substantial morbidity and mortality in children. Diagnosis is typically confirmed by reverse transcriptase polymerase chain reaction ...(RT-PCR) of nasopharyngeal specimens in hospitalized patients; however, it is unknown whether nasopharyngeal detection accurately reflects presence of virus in the lower respiratory tract (LRT). This study evaluates agreement between viral detection from nasopharyngeal specimens by RT-PCR compared with metagenomic next-generation RNA sequencing (RNA-Seq) from tracheal aspirates (TAs).
This is an analysis of of a seven-center prospective cohort study.
Seven PICUs within academic children's hospitals in the United States.
Critically ill children (from 1 mo to 18 yr) who required mechanical ventilation via endotracheal tube for greater than or equal to 72 hours.
We evaluated agreement in viral detection between paired upper and LRT samples. Results of clinical nasopharyngeal RT-PCR were compared with TA RNA-Seq. Positive and negative predictive agreement and Cohen's Kappa were used to assess agreement.
Of 295 subjects with paired testing available, 200 (68%) and 210 (71%) had positive viral testing by RT-PCR from nasopharyngeal and RNA-Seq from TA samples, respectively; 184 (62%) were positive by both nasopharyngeal RT-PCR and TA RNA-Seq for a virus, and 69 (23%) were negative by both methods. Nasopharyngeal RT-PCR detected the most abundant virus identified by RNA-Seq in 92.4% of subjects. Among the most frequent viruses detected, respiratory syncytial virus demonstrated the highest degree of concordance (κ = 0.89; 95% CI, 0.83-0.94), whereas rhinovirus/enterovirus demonstrated lower concordance (κ = 0.55; 95% CI, 0.44-0.66). Nasopharyngeal PCR was more likely to detect multiple viruses than TA RNA-Seq (54 18.3% vs 24 8.1%, p ≤ 0.001).
Viral nucleic acid detection in the upper versus LRT reveals good overall agreement, but concordance depends on the virus. Further studies are indicated to determine the utility of LRT sampling or the use of RNA-Seq to determine LRTI etiology.
A polymorphism (Val66Met) in the gene encoding brain-derived neurotrophic factor (BDNF) has previously been associated with impaired hippocampal function and scores on the Logical Memory subtest of ...the Wechsler Memory Scale-Revised (WMS-R). Despite its widespread expression in the brain, there have been few studies examining the role of BDNF on cognitive domains, other than memory. We examined the association between BDNF Val66Met genotype and non-verbal reasoning, as measured by Raven's standard progressive matrices (Raven), in two cohorts of relatively healthy older people, one aged 79 (LBC1921) and the other aged 64 (ABC1936) years. LBC1921 and ABC1936 subjects had reasoning measured at age 11 years, using the Moray House Test (MHT), in the Scottish Mental Surveys of 1932 and 1947, respectively. BDNF genotype was significantly associated with later life Raven scores, controlling for sex, age 11 MHT score and cohort (P = 0.001). MHT, Verbal Fluency and Logical Memory scores were available, in later life, for LBC1921 only. BDNF genotype was significantly associated with age 79 MHT score, controlling for sex and age 11 MHT score (P = 0.016). In both significant associations, Met homozygotes scored significantly higher than heterozygotes and Val homozygotes. This study indicates that BDNF genotype contributes to age-related changes in reasoning skills, which are closely related to general intelligence.
More appropriate and measured use of antibiotics may be achieved using point-of-care (POC) C-reactive protein (CRP) testing, but there is limited evidence of cost-effectiveness in routine practice. A ...decision analytic model was developed to estimate the cost-effectiveness of testing, compared with standard care, in adults presenting in primary care with symptoms of acute respiratory tract infection (ARTI). Analyses considered (1) pragmatic use of testing, reflective of routine clinical practice, and (2) testing according to clinical guidelines. Threshold and scenario analysis were performed to identify cost-effective scenarios. In patients with symptoms of ARTI and based on routine practice, the incremental cost-effectiveness ratios of CRP testing were £19,705 per quality-adjusted-life-year (QALY) gained and £16.07 per antibiotic prescription avoided. Following clinical guideline, CRP testing in patients with lower respiratory tract infections (LRTIs) cost £4390 per QALY gained and £9.31 per antibiotic prescription avoided. At a threshold of £20,000 per QALY, the probabilities of POC CRP testing being cost-effective were 0.49 (ARTI) and 0.84 (LRTI). POC CRP testing as implemented in routine practice is appreciably less cost-effective than when adhering to clinical guidelines. The implications for antibiotic resistance and
infection warrant further investigation.
•Antiviral effects of 20 Brazilian natural compounds were investigated.•Four compounds with potent inhibitory activity on HCV replication were identified.•Antiviral activity was independent of HCV ...genotype.•Antiviral effect was not affected by variants described to confer resistance.•One of the four compounds inhibited HCV IRES-mediated translation.
Compounds extracted from plants can provide an alternative approach to new therapies. They present characteristics such as high chemical diversity, lower cost of production and milder or inexistent side effects compared with conventional treatment. The Brazilian flora represents a vast, largely untapped, resource of potential antiviral compounds. In this study, we investigate the antiviral effects of a panel of natural compounds isolated from Brazilian plants species on hepatitis C virus (HCV) genome replication. To do this we used firefly luciferase-based HCV sub-genomic replicons of genotypes 2a (JFH-1), 1b and 3a and the compounds were assessed for their effects on both HCV replication and cellular toxicity. Initial screening of compounds was performed using the maximum non-toxic concentration and 4 compounds that exhibited a useful therapeutic index (favourable ratio of cytotoxicity to antiviral potency) were selected for extra analysis. The compounds APS (EC50=2.3μM), a natural alkaloid isolated from Maytrenus ilicifolia, and the lignans 3∗43 (EC50=4.0μM), 3∗20 (EC50=8.2μM) and 5∗362 (EC50=38.9μM) from Peperomia blanda dramatically inhibited HCV replication as judged by reductions in luciferase activity and HCV protein expression in both the subgenomic and infectious systems. We further show that these compounds are active against a daclatasvir resistance mutant subgenomic replicon. Consistent with inhibition of genome replication, production of infectious JFH-1 virus was significantly reduced by all 4 compounds. These data are the first description of Brazilian natural compounds possessing anti-HCV activity and further analyses are being performed in order to investigate the mode of action of those compounds.
Background. Associations between trunk muscle composition and physical function have not been examined previously in older adults. We hypothesized that lower trunk muscle area and attenuation (higher ...fat infiltration) are associated with decreased functional capacity. Methods. The study sample consisted of a biracial cohort of well functioning men (739) and women (788) aged 70–79 from the Pittsburgh site of the Health, Aging and Body Composition (Health ABC) study. Computed tomography was used to measure trunk muscle area (cm2) and muscle attenuation (Hounsfield Unit HU) of the following muscle groups: lumbar paraspinals, lateral abdominals, and rectus abdominis. An average score was calculated for both trunk area and attenuation. The Health ABC Physical Performance Battery (PPB) and its individual components (usual and narrow walk, chair stands, and standing balance) were used to measure functional capacity. Results. Linear regression analyses adjusting for demographic factors, height, body fat, thigh muscle composition, disease status, and low back pain (LBP) found that average trunk muscle area was not associated with any element of functional capacity (p >.10), whereas average trunk muscle attenuation was positively associated with the Health ABC Physical Performance Battery (p <.05) and chair stands (p <.001). Participants reporting higher LBP severity during the past year had lower muscle attenuation (p <.001 for trend), but there was no difference in average trunk muscle area according to LBP status. Conclusions. Findings suggest a link between trunk muscle composition and history of LBP as well as reduced functional capacity in older adults. Improving trunk muscle quality may lead to reduced LBP severity and improved functional status.
Objectives: To determine the prevalence of and risk factors for hearing loss in a sample of 2,052 older adults (aged 73–84; 46.9% male, 37.3% black) enrolled in the Health, Aging and Body Composition ...(Health ABC) Study.
Design: Cross‐sectional analysis of a longitudinal cohort study.
Setting: Pittsburgh, Pennsylvania, and Memphis, Tennessee, areas.
Participants: Random sample of Medicare beneficiary subjects enrolled in the Health ABC program from 1997 to 1998. They included 2,052 individuals: 660 white men (32.2%), 631 white women (30.8%), 310 black men (15.1%), and 451 black women (22.0%). Participants ranged in age from 73 to 84, with a mean age of 77.5.
Measurements: Hearing sensitivity was measured using pure‐tone threshold testing. Hearing loss was defined based on two averages of hearing thresholds: 500, 1,000, and 2,000 Hz greater than 25‐decibel (dB) hearing level (HL) (hearing loss); and 2,000, 4,000, and 8,000 Hz greater than 40‐dB HL (high‐frequency hearing loss). Potential hearing loss correlates, including demographics, medical history, ototoxic medication use, occupational noise exposure, and lifestyle factors, were collected via questionnaire.
Results: The prevalence of hearing loss was 59.9%; the prevalence of high‐frequency hearing loss was 76.9%. Hearing loss was most common in white men, followed by white women, black men, and black women. Older age, white race, diabetes mellitus, cerebrovascular disease, smoking, poorer cognitive status, occupational noise exposure, and ear surgery were associated with hearing loss after multivariable adjustment. Race‐ and sex‐specific risk factors included higher blood pressure and occupational noise exposure (white men), poorer cognitive status and smoking (black women), and low total hip bone mineral density (black men). Possible protective factors included salicylate use (overall sample, black men) and moderate alcohol intake (black women).
Conclusion: Hearing loss was extremely common in this population. Because many of the identified hearing loss risk factors are modifiable, some of the burden associated with hearing loss in older people should be preventable.
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