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.

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.

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.

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.

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.

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.

Microvascular decompression for superior oblique myokymia: case report.

BACKGROUND: Superior oblique myokymia (SOM) is a rare disorder in which the patient suffers episodic uniocular torsional eye movement associated with diplopia and oscillopsia . Although the pathophysiology has been narrowed down to erratic discharge of the trochlear nerve, yet the exact etiology remains unclear; a handful of cases have been described in association with an identifiable space occupying lesions or dural AV fistulae. Neurovascular compression theory has been postulated in the early 1980s and to our knowledge, very few reports exist in the literature accrediting this hypothesis in the pathogenesis of superior oblique myokymia. CASE REPORT: We report a case of successful resolution of severe medication refractory SOM following microvascular decompression of the trochlear nerve. The clinical response has been sustained for a follow-up period of 18 months to date. CONCLUSION: Microvascular decompression may be considered as a definitive and least destructive surgical option for the treatment of medication refractory superior oblique myokymia.

The inequity of global healthcare in pediatric rheumatology.

In pediatric rheumatology, global health inequity relates to the uneven distribution of healthcare resources, accessibility, and health outcomes among children with rheumatic conditions across various countries, regions, and socioeconomic groups. This inequity can manifest in various ways. This review article provides an overview of common rheumatic diseases, such as juvenile idiopathic arthritis and systemic lupus erythematosus, which significantly contribute to and are affected by disparities in global healthcare. Subsequently, we delve into the inequalities in accessing patient care, encompassing issues related to diagnosis and treatment. Additionally, we address challenges in educational advancement and identify research gaps within the field of pediatric rheumatology. We also reveal successful global collaborations, such as a Global Task Force for Pediatric Musculoskeletal Health and special working groups among international organizations, aimed at bridging the disparities gap. Through these efforts, we try to enhance understanding, cooperation, and resource allocation to ensure equal access to quality care worldwide for children with rheumatic conditions. Futhermore, we present a case study from Thailand, highlighting their successful initiatives in developing pediatric rheumatology within their healthcare system.

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.

Age and androgen-deprivation therapy on exercise outcomes in men with prostate cancer.

PURPOSE: The purpose of this study is to examine the effects of age (≤ 65 years or >65 years) and androgen-deprivation therapy (ADT, presence or absence) as factors that may predict changes in body composition and fitness following a 24-week exercise program in prostate cancer patients. METHODS: One hundred twenty-one men were randomly allocated to either: (1) aerobic exercise (AE), (2) resistance exercise (RE), or (3) usual care (UC). Body composition was assessed by DXA. Aerobic fitness was assessed through a maximal treadmill test. Muscular strength was assessed by leg extension and bench press using the eight-repetition maximum test. Responses were compared between younger (≤ 65 years) and older (> 65 years) patients with or without ADT. RESULTS: There did not appear to be an interaction between age and ADT on body composition or fitness, nor were there any significant changes in body composition for participants ≤ 65 years. In participants aged >65 years, lean mass decreased in AE (p = 0.013) and UC (p = 0.006), but was preserved in RE. In participants receiving ADT, there was a decrease in lean mass in AE (p = 0.003) and UC (p < 0.001) but not in RE. The non-ADT group did not show any changes in body composition but did show improvements in muscular fitness following resistance training (p < 0.001). CONCLUSION: Changes in body composition and physical fitness following a 24-week exercise program in men with prostate cancer are not influenced by age and/or ADT. Resistance training appears to attenuate the age-related decrease in lean mass and increase in body fat in older patients with prostate cancer and those receiving ADT.

Developing a physician engagement agreement at The Ottawa Hospital: a collaborative approach.

The Ottawa Hospital (TOH) is focused on providing safe, high-quality care to its patients. TOH has identified physician engagement as a critical factor for improving the quality of care they provide. The physician engagement strategy developed at TOH involved a qualitative inquiry into the impediments and facilitators of engagement. Using concurrent focus groups, researchers collected and analyzed the physicians' perspective regarding engagement. A systematic analysis of the verbal data was used to construct a statement of mutual understanding between the physicians and the hospital (physician engagement agreement). The process of developing this agreement is the focus of this article.

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.

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%.

Atomistic surface erosion and thin film growth modelled over realistic time scales.

We present results of atomistic modelling of surface growth and sputtering using a multi-time scale molecular dynamics-on-the-fly kinetic Monte Carlo scheme which allows simulations to be carried out over realistic experimental times. The method uses molecular dynamics to model the fast processes and then calculates the diffusion barriers for the slow processes on-the-fly, without any preconceptions about what transitions might occur. The method is applied to the growth of metal and oxide materials at impact energies typical for both vapour deposition and magnetron sputtering. The method can be used to explain growth processes, such as the filling of vacancies and the formation of stacking faults. By tuning the variable experimental parameters on the computer, a parameter set for optimum crystalline growth can be determined. The method can also be used to model sputtering where the particle interactions with the surface occur at a higher energy. It is shown how a steady state can arise in which interstitial clusters are continuously being formed below the surface during an atom impact event which also recombine or diffuse to the surface between impact events. For fcc metals the near surface region remains basically crystalline during the erosion process with a pitted topography which soon attains a steady state roughness.

Fibrodysplasia ossificans progressiva in South Africa: difficulties in management in a developing country.

Fibrodysplasia ossificans progressiva is a rare genetic disorder in which progressive ossification of connective tissue leads to severe disability. The condition is an autosomal dominant trait, and most of the affected persons represent new mutations for the determinant gene, ACVR1, chromosomal locus 2q23-24. Although fibrodysplasia ossificans progressiva has a worldwide distribution, there are only a few reports of affected persons of indigenous African stock. We studied and documented 3 affected individuals in the African (Xhosa) community from South Africa. In addition to describing the manifestations and natural history of the disorder in Africa, we discuss the challenge of management of this condition in the South African context.

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.

Apathy is not associated with basal ganglia atrophy in frontotemporal dementia.

OBJECTIVE: To determine whether basal ganglia atrophy, known to be associated with apathy in nondementia populations, was associated with presence of apathy in patients with frontotemporal dementia (FTD). METHODS: A cross-sectional case study was conducted at two tertiary dementia care clinics in Toronto, Ontario, Canada. Striatal and thalamic gray matter volumes and apathy measures were collected from 21 subjects with FTD, 6 of whom did not show apathy on the Neuropsychiatric Inventory. RESULTS: No significant differences in gray matter volumes were found between apathetic and nonapathetic groups for the striatum or the thalamus. CONCLUSIONS: Our findings imply that the etiology of apathy seen in patients with FTD differs from that of patients with apathy after acquired injuries to the basal ganglia. Further study is needed to determine whether posterior thalamic atrophy correlates with apathy in FTD or functional imaging techniques might successfully find a relationship between basal ganglia dysfunction and apathy.

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.

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.