Clinical significance of BPI-ANCA in patients with cystic fibrosis: a single center prospective study.

Recurrent pulmonary exacerbation due to infection and inflammation remain the major cause of mortality and morbidity in patients with cystic fibrosis (CF). Increased levels of BPI-ANCA have been linked to Pseudomonas colonization and pulmonary exacerbations in patients with CF. The majority of these studies were done in Europe, and it is unclear whether similar findings are true in CF patients who lives in United States. In our single center study of 47 patients with CF, the prevalence of BPI-ANCA was 19% at baseline and 15% at annual follow-up visit. Overall, there were no statistical differences noted in FEV1 and frequency of pulmonary exacerbations in CF patients who were positive for BPI-ANCA compared to those who were negative for BPI-ANCA. The role of BPI-ANCA in patients with CF still remains unclear.

Measurement of C1-Inhibitor function alone is sufficient for diagnosis of hereditary angioedema.

The World Allergy Organisiation/European Academy of Allergy and Clinical Immunology (WAO/EAACI) 2017/2018 guidelines recommend measuring complement4 levels, followed by C1-inhibitor level and function for diagnosis of hereditary angioedema (HAE). We analysed 6 months' worth of data generated in our laboratory which is a specialist regional immunology service and also provides laboratory service for the Barts Health immunology department, which is a GA2LEN/HAEi-Angioedema Centre of Excellence and Reference (ACARE) and hence, investigates a large number of patients for HAE. We found that an efficient and sensitive approach for laboratory diagnosis of HAE is to only test the C1-inhibitor function. This approach had a sensitivity of 100% and reduced the cost of laboratory investigations for HAE diagnosis by 45%.

Development of an Atomic-Oxygen-Erosion-Resistant, Alumina-Fiber-Reinforced, Fluorinated Polybenzoxazine Composite for Low-Earth Orbital Applications.

An atomic-oxygen-erosion-resistant fluorinated benzoxazine resin and composite were developed. The benzoxazine resin, abbreviated as "BAF-oda-fu," consists of four benzoxazine rings, and was synthesized from bisphenol AF (BAF), 4,4'-oxydianiline (oda), furfurylamine (fu), and paraformaldehyde. The resin was characterized by infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (1H NMR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). An analysis of the solvent-washed product showed a technical grade purity (>95%) and a yield of approximately 85%. Subsequent polymerization of the resin was successfully performed by heating step-wise and opening the benzoxazine rings to form a crosslinked network. Thermal analyses showed a melting temperature of 115 °C and polymerization temperature of 238 °C, both being characteristic values of benzoxazine monomers. The benzoxazine resin was also blended with polyoctahedral sisesquoxane (POSS) and reinforced with alumina fibers. The Tg of the resin, as determined by DMA of the composite, could reach as high as 308 °C when post-curing and the POSS additive were utilized. The low-Earth orbit atomic-oxygen erosion rate was simulated by an RF plasma asher/etcher. The atomic-oxygen resistance of poly(BAF-oda-fu) fell along an established trend line based on its fluorine content.

An open repository of real-time COVID-19 indicators.

The COVID-19 pandemic presented enormous data challenges in the United States. Policy makers, epidemiological modelers, and health researchers all require up-to-date data on the pandemic and relevant public behavior, ideally at fine spatial and temporal resolution. The COVIDcast API is our attempt to fill this need: Operational since April 2020, it provides open access to both traditional public health surveillance signals (cases, deaths, and hospitalizations) and many auxiliary indicators of COVID-19 activity, such as signals extracted from deidentified medical claims data, massive online surveys, cell phone mobility data, and internet search trends. These are available at a fine geographic resolution (mostly at the county level) and are updated daily. The COVIDcast API also tracks all revisions to historical data, allowing modelers to account for the frequent revisions and backfill that are common for many public health data sources. All of the data are available in a common format through the API and accompanying R and Python software packages. This paper describes the data sources and signals, and provides examples demonstrating that the auxiliary signals in the COVIDcast API present information relevant to tracking COVID activity, augmenting traditional public health reporting and empowering research and decision-making.

Prevalence and predictors of bone health among perinatally HIV-infected adolescents.

OBJECTIVES: Long-term complications of HIV including low bone mineral density remain a concern. We studied the prevalence and predictors of low bone mineral density among South African perinatally HIV-infected adolescents (PHIVA) on antiretroviral therapy (ART). DESIGN: Cross-sectional analysis. METHODS: Bone health was evaluated by measuring the calcaneus stiffness index among PHIVA on ART. Low stiffness index was defined as z-score less than -2 SD compared with age-matched and sex-matched HIV-uninfected adolescents (HIV-). RESULT: Overall, 407 PHIVA (median age: 14 years; 50.4% female; median age at ART initiation: 4.2 years) and 92 HIV- (median age: 13.7 years; 54.4% female) were included. Median duration on ART was 9.8 years (interquartile range 6.8-11.5) with 38% initiating ART at 2 years or less of age. Stiffness index was lower in PHIVA (-0.19 vs. 0.43, P ≤ 0.001), respectively. During puberty, mean stiffness index increased with Tanner Stage in both PHIVA and HIV- but these increases were larger among HIV-; Tanner Stage II-III (96 vs. 101, P = 0.009) and Tanner Stage IV-V (104 vs. 112, P = 0.001). Among PHIVA, 52 (13%) had low stiffness index. After adjusting for age, sex and Tanner Stage, use of lopinavir/ritonavir [odds ratio (OR) = 2.31, P = 0.012] and viral load more than 50 copies/ml (OR = 2.06, P = 0.023) were associated with increased risk of low stiffness index, while use of efavirenz (OR = 0.41, P = 0.009) was associated with decreased risk of low stiffness index. CONCLUSION: Stiffness index was a significantly lower in PHIVA than in HIV-, especially during puberty. Among PHIVA, detectable viral load and use of lopinavir/ritonavir were risk factors for low stiffness index. Further longitudinal studies are important to determine the clinical implications.

Structure and Performance of Benzoxazine Composites for Space Radiation Shielding.

Innovative multifunctional materials that combine structural functionality with other spacecraft subsystem functions have been identified as a key enabling technology for future deep space missions. In this work, we report the structure and performance of multifunctional polymer matrix composites developed for aerospace applications that require both structural functionality and space radiation shielding. Composites comprised of ultra-high molecular weight polyethylene (UHMWPE) fiber reinforcement and a hydrogen-rich polybenzoxazine matrix are prepared using a low-pressure vacuum bagging process. The polybenzoxazine matrix is derived from a novel benzoxazine resin that possesses a unique combination of attributes: high hydrogen concentration for shielding against galactic cosmic rays (GCR), low polymerization temperature to prevent damage to UHMWPE fibers during composite fabrication, long shelf-life, and low viscosity to improve flow during molding. Dynamic mechanical analysis (DMA) is used to study rheological and thermomechanical properties. Composite mechanical properties, obtained using several standardized tests, are reported. Improvement in composite stiffness, through the addition of carbon fiber skin layers, is investigated. Radiation shielding performance is evaluated using computer-based simulations. The composites demonstrate clear advantages over benchmark materials in terms of combined structural and radiation shielding performance.

Validation prediction: a flexible protocol to increase efficiency of automated acoustic processing for wildlife research.

Automated recognition is increasingly used to extract species detections from audio recordings; however, the time required to manually review each detection can be prohibitive. We developed a flexible protocol called "validation prediction" that uses machine learning to predict whether recognizer detections are true or false positives and can be applied to any recognizer type, ecological application, or analytical approach. Validation prediction uses a predictable relationship between recognizer score and the energy of an acoustic signal but can also incorporate any other ecological or spectral predictors (e.g., time of day, dominant frequency) that will help separate true from false-positive recognizer detections. First, we documented the relationship between recognizer score and the energy of an acoustic signal for two different recognizer algorithm types (hidden Markov models and convolutional neural networks). Next, we demonstrated our protocol using a case study of two species, the Common Nighthawk (Chordeiles minor) and Ovenbird (Seiurus aurocapilla). We reduced the number of detections that required validation by 75.7% and 42.9%, respectively, while retaining at least 98% of the true-positive detections. Validation prediction substantially improves the efficiency of using automated recognition on acoustic data sets. Our method can be of use to wildlife monitoring and research programs and will facilitate using automated recognition to mine bioacoustic data sets.

Publisher Correction: On the issue of transparency and reproducibility in nanomedicine.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Publisher Correction: On the issue of transparency and reproducibility in nanomedicine.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Phase analysis single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) detects dyssynchrony in myocardial scar and increases specificity of MPI.

BACKGROUND: Myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) is commonly used to assess patients with cardiovascular disease. However, in certain scenarios, it may have limited specificity in the identification of hemodynamically significant coronary artery disease (e.g., false positive), potentially resulting in additional unnecessary testing and treatment. Phase analysis (PA) is an emerging, highly reproducible quantitative technology that can differentiate normal myocardial activation (synchrony) from myocardial scar (dyssynchrony). The objective of this study is to determine if PA can improve the specificity SPECT MPI. METHODS: An initial cohort of 340 patients (derivation cohort), referred for SPECT-MPI, was prospectively enrolled. Resting MPI studies were assessed for resting perfusion defects (scar). These were utilized as the reference standard for scar. Subsequently, we collected a second independent validation cohort of 138 patients and tested the potential of PA to reclassify patients for the diagnosis of "scar" or "no scar." Patients were assigned to three categories depending upon their pre-test probability of scar based on multiple clinical and imaging parameters: ≤ 10% (no scar), 11-74% (indeterminate), and ≥ 75% (scar). The ability of PA variables to reclassify patients with scar to a higher group and those without scar to a lower group was then determined using the net reclassification index (NRI). RESULTS: Entropy (≥ 59%) was independently associated with scar in both patient cohorts with an odds ratio greater than five. Furthermore, when added to multiple clinical/imaging variables, the use of entropy significantly improved the area under the curve for assessment of scar (0.67 vs. 0.59, p = 0.04). The use of entropy correctly reclassified 24% of patients without scar, by clinical model, to a lower risk category (as determined by pre-test probability) with an overall NRI of 18% in this validation cohort. DISCUSSION: The use of PA entropy can improve the specificity of SPECT MPI and may serve as a useful adjunctive tool to the interpreting physician. The current study determined the optimal PA parameters to detect scar (derivation cohort) and applied these parameters to a second, independent, patient group and noted that entropy (≥ 59%) was independently associated with scar in both patient cohorts. Therefore, PA, which requires no additional imaging time or radiation, enhances the diagnostic capabilities of SPECT MPI. CONCLUSION: The use of PA entropy significantly improved the specificity of SPECT MPI and could influence the labeling of a patient as having or not having myocardial scar and thereby may influence not only diagnostic reporting but also potentially prognostic determination and therapeutic decision-making.

Quantification of human C1 esterase inhibitor protein using an automated turbidimetric immunoassay.

BACKGROUND: Impaired levels or function of C1 inhibitor (C1-INH) results in angioedema due to increased bradykinin. It is important to distinguish between angioedema related to C1-INH deficiency and that caused by other mechanisms, as treatment options are different. In hereditary (HAE) and acquired (AAE) angioedema, C1-INH concentration is measured to aid patient diagnosis. Here, we describe an automated turbidimetric assay to measure C1-INH concentration on the Optilite® analyzer. METHODS: Linearity, precision, and interference were established over a range of C1-INH concentrations. The 95th percentile reference interval was generated from 120 healthy adult donors. To compare the Optilite C1-INH assay with a predicate assay used in a clinical laboratory, samples sent for C1-INH investigation were used. The predicate results were provided to allow comparison. RESULTS: The Optilite C1-INH assay was linear across the measuring range at the standard sample dilution. Intra and interassay variability was <6%. The 95th percentile adult reference interval for the assay was 0.21-0.38 g/L. There was a strong correlation between the Optilite concentrations and those generated with the predicate assay (R2  = 0.94, P < 0.0001, slope y = 0.83x). All patients with Type I HAE (n = 24) and AAE (n = 3) tested had concentrations below the measuring range in both assays, while all patients with unspecified angioedema (UAE), not diagnosed with HAE or AAE had values within the reference range. CONCLUSION: The Optilite assay allows the automated and precise quantification of C1-INH concentrations in patient samples. It could therefore be used as a tool to aid the investigation of patients with angioedema.

Development of Hydrogen-Rich Benzoxazine Resins with Low Polymerization Temperature for Space Radiation Shielding.

A systematic study has been carried out to develop a material with significant protection properties from galactic cosmic radiation and solar energetic particles. The research focused on the development of hydrogen-rich benzoxazines, which are particularly effective for shielding against such radiation. Newly developed benzoxazine resin can be polymerized at 120 °C, which meets the low-temperature processing requirements for use with ultrahigh molecular weight polyethylene (UHMWPE) fiber, a hydrogen-rich composite reinforcement. This highly reactive benzoxazine resin also exhibits low viscosity and good shelf-life. The structure of the benzoxazine monomer is confirmed by proton nuclear magnetic resonance and Fourier transform infrared spectroscopy. Polymerization behavior and thermal properties are evaluated by differential scanning calorimetry and thermogravimetric analysis. Dynamic mechanical analysis is used to study chemorheological properties of the benzoxazine monomer, rheological properties of the cross-linked polybenzoxazine, and rheological properties of UHMWPE-reinforced polybenzoxazine composites. The theoretical radiation shielding capability of the composite is also evaluated using computer-based simulations.

Reaction pathways in atomistic models of thin film growth.

The atomistic processes that form the basis of thin film growth often involve complex multi-atom movements of atoms or groups of atoms on or close to the surface of a substrate. These transitions and their pathways are often difficult to predict in advance. By using an adaptive kinetic Monte Carlo (AKMC) approach, many complex mechanisms can be identified so that the growth processes can be understood and ultimately controlled. Here the AKMC technique is briefly described along with some special adaptions that can speed up the simulations when, for example, the transition barriers are small. Examples are given of such complex processes that occur in different material systems especially for the growth of metals and metallic oxides.

Lack of Frank Agrammatism in the Nonfluent Agrammatic Variant of Primary Progressive Aphasia.

BACKGROUND/AIMS: Frank agrammatism, defined as the omission and/or substitution of grammatical morphemes with associated grammatical errors, is variably reported in patients with nonfluent variant primary progressive aphasia (nfPPA). This study addressed whether frank agrammatism is typical in agrammatic nfPPA patients when this feature is not required for diagnosis. METHOD: We assessed grammatical production in 9 patients who satisfied current diagnostic criteria. Although the focus was agrammatism, motor speech skills were also evaluated to determine whether dysfluency arose primarily from apraxia of speech (AOS), instead of, or in addition to, agrammatism. Volumetric MRI analyses provided impartial imaging-supported diagnosis. RESULTS: The majority of cases exhibited neither frank agrammatism nor AOS. CONCLUSION: There are nfPPA patients with imaging-supported diagnosis and preserved motor speech skills who do not exhibit frank agrammatism, and this may persist beyond the earliest stages of the illness. Because absence of frank agrammatism is a subsidiary diagnostic feature in the logopenic variant of PPA, this result has implications for differentiation of the nonfluent and logopenic variants, and indicates that PPA patients with nonfluent speech in the absence of frank agrammatism or AOS do not necessarily have the logopenic variant.

Child deaths in South Africa: Lessons from the child death review pilot.

South Africa (SA) has not met the child mortality target for the Millennium Development Goals, despite having invested substantially in programmes and policies to achieve these targets. The scale-up of the prevention of mother-to-child transmission programmes reduced HIV transmission from mother to child, but this has not been sustained owing to limitations in community-based child health services. Child mortality has declined, but has now plateaued. Children continue to die from preventable and treatable causes of death. Current data sources are incomplete, and do not provide information on deaths occurring out of health facilities. The child death review (CDR) pilot explores the pattern of child deaths and informs prevention strategies to improve child survival in SA. In this editorial we draw on the conclusions of the CDR pilot, where multiagency teams were established to investigate non-natural and unexpected deaths referred to two mortuary sites in order to strengthen child health and protection response systems and to prevent child deaths.

The South African child death review pilot: A multiagency approach to strengthen healthcare and protection for children.

BACKGROUND: Child mortality trends in South Africa (SA) show a decrease, but remain high and appear to have plateaued. To attain the new sustainable development goals, we need a better understanding of causes of death and the associated factors. OBJECTIVES: To describe the SA child death review (CDR) pilot, the pattern of child deaths reviewed and the factors associated with these deaths. METHODS: CDR teams were established at two pilot sites, Salt River mortuary (Western Cape Province) and Phoenix mortuary (KwaZulu-Natal Province). All child deaths were reviewed by a multidisciplinary team at the pilot sites for the period 1 January 2014 - 31 December 2014. RESULTS: The CDR pilot reviewed 711 cases. Over half (53.3%) were natural deaths, as opposed to 42.6% non-natural deaths. Most infant deaths (83.9%) were due to natural causes, while 91.7% of deaths in the 15 - 17-year-old age group were due to injuries. The leading cause of deaths reviewed (30.8%) was respiratory tract infection (RTI), mainly among infants (51.6%). Homicide was the second most common cause of death and affected children of all ages, with the highest burden (52.8%) in the 15 - 17-year age group. Child abuse and neglect accounted for 11.3% of deaths. RTI was shown to be more likely after the neonatal period (odds ratio (OR) 2.92; p<0.000) and in preterm infants (OR 1.98; p=0.005). CONCLUSIONS: CDR teams have been effective in improving identification of the causes of out-of-hospital deaths, as well as by identifying remediable factors critical to reducing child deaths further.

The National Eclipse Weather Experiment: use and evaluation of a citizen science tool for schools outreach.

The National Eclipse Weather Experiment (NEWEx) was a citizen science project for atmospheric data collection from the partial solar eclipse of 20 March 20. Its role as a tool for schools outreach is discussed here, in seeking to bridge the gap between self-identification with the role of a scientist and engagement with science, technology, engineering and mathematics subjects. (The science data generated have had other uses beyond this, explored elsewhere.) We describe the design of webforms for weather data collection, and the use of several external partners for the dissemination of the project nationwide. We estimate that up to 3500 pupils and teachers took part in this experiment, through the 127 schools postcodes identified in the data submission. Further analysis revealed that 43.3% of the schools were primary schools and 35.4% were secondary. In total, 96.3% of participants reported themselves as 'captivated' or 'inspired' by NEWEx. We also found that 60% of the schools that took part in the experiment lie within the highest quintiles of engagement with higher education, which emphasizes the need for the scientific community to be creative when using citizen science projects to target hard-to-reach audiences.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'.

A Review and Proposed Approach to the Neutrophilic Dermatoses of Childhood.

Neutrophilic dermatoses (NDs) are inflammatory skin conditions that are not associated with infection. The classification and clinical approach to these conditions in children is poorly described. This review classifies these conditions into five nosological subtypes: Sweet's syndrome, pyoderma gangrenosum, aseptic pustules, neutrophilic urticarial dermatoses, and Marshall's syndrome. In addition, we review the various secondary diseases that need to be excluded in the clinical management of the NDs of childhood, with a focus on the autoinflammatory conditions that the reader may not be familiar with. We propose a practical clinical approach to these disorders.