A computationally tractable birth-death model that combines phylogenetic and epidemiological data.

Inferring the dynamics of pathogen transmission during an outbreak is an important problem in infectious disease epidemiology. In mathematical epidemiology, estimates are often informed by time series of confirmed cases, while in phylodynamics genetic sequences of the pathogen, sampled through time, are the primary data source. Each type of data provides different, and potentially complementary, insight. Recent studies have recognised that combining data sources can improve estimates of the transmission rate and the number of infected individuals. However, inference methods are typically highly specialised and field-specific and are either computationally prohibitive or require intensive simulation, limiting their real-time utility. We present a novel birth-death phylogenetic model and derive a tractable analytic approximation of its likelihood, the computational complexity of which is linear in the size of the dataset. This approach combines epidemiological and phylodynamic data to produce estimates of key parameters of transmission dynamics and the unobserved prevalence. Using simulated data, we show (a) that the approximation agrees well with existing methods, (b) validate the claim of linear complexity and (c) explore robustness to model misspecification. This approximation facilitates inference on large datasets, which is increasingly important as large genomic sequence datasets become commonplace.

Impact of anthropometry training and feasibility of 3D imaging on anthropometry data quality among children under five years in a postmortem setting.

BACKGROUND: The Child Health and Mortality Prevention Surveillance Network (CHAMPS) identifies causes of under-5 mortality in high mortality countries. OBJECTIVE: To address challenges in postmortem nutritional assessment, we evaluated the impact of anthropometry training and the feasibility of 3D imaging on data quality within the CHAMPS Kenya site. DESIGN: Staff were trained using World Health Organization (WHO)-recommended manual anthropometry equipment and novel 3D imaging methods to collect postmortem measurements. Following training, 76 deceased children were measured in duplicate and were compared to measurements of 75 pre-training deceased children. Outcomes included measures of data quality (standard deviations of anthropometric indices and digit preference scores (DPS)), precision (absolute and relative technical errors of measurement, TEMs or rTEMs), and accuracy (Bland-Altman plots). WHO growth standards were used to produce anthropometric indices. Post-training surveys and in-depth interviews collected qualitative feedback on measurer experience with performing manual anthropometry and ease of using 3D imaging software. RESULTS: Manual anthropometry data quality improved after training, as indicated by DPS. Standard deviations of anthropometric indices exceeded limits for high data quality when using the WHO growth standards. Reliability of measurements post-training was high as indicated by rTEMs below 1.5%. 3D imaging was highly correlated with manual measurements; however, on average 3D scans overestimated length and head circumference by 1.61 cm and 2.27 cm, respectively. Site staff preferred manual anthropometry to 3D imaging, as the imaging technology required adequate lighting and additional considerations when performing the measurements. CONCLUSIONS: Manual anthropometry was feasible and reliable postmortem in the presence of rigor mortis. 3D imaging may be an accurate alternative to manual anthropometry, but technology adjustments are needed to ensure accuracy and usability.

Accuracy and reliability of a low-cost, handheld 3D imaging system for child anthropometry.

The usefulness of anthropometry to define childhood malnutrition is undermined by poor measurement quality, which led to calls for new measurement approaches. We evaluated the ability of a 3D imaging system to correctly measure child stature (length or height), head circumference and arm circumference. In 2016-7 we recruited and measured children at 20 facilities in and around metro Atlanta, Georgia, USA; including at daycare, higher education, religious, and medical facilities. We selected recruitment sites to reflect a generally representative population of Atlanta and to oversample newborns and children under two years of age. Using convenience sampling, a total of 474 children 0-5 years of age who were apparently healthy and who were present at the time of data collection were included in the analysis. Two anthropometrists each took repeated manual measures and repeated 3D scans of each child. We evaluated the reliability and accuracy of 3D scan-derived measurements against manual measurements. The mean child age was 26 months, and 48% of children were female. Based on reported race and ethnicity, the sample was 42% Black, 28% White, 8% Asian, 21% multiple races, other or race not reported; and 16% Hispanic. Measurement reliability of repeated 3D scans was within 1 mm of manual measurement reliability for stature, head circumference and arm circumference. We found systematic bias when analyzing accuracy-on average 3D imaging overestimated stature and head circumference by 6 mm and 3 mm respectively, and underestimated arm circumference by 2 mm. The 3D imaging system used in this study is reliable, low-cost, portable, and can handle movement; making it ideal for use in routine nutritional assessment. However, additional research, particularly on accuracy, and further development of the scanning and processing software is needed before making policy and clinical practice recommendations on the routine use of 3D imaging for child anthropometry.

Mechanical loads at the knee joint during deep flexion.

There is a lack of fundamental information on the knee biomechanics in deep flexion beyond 90 degrees. In this study, mechanical loads during activities requiring deep flexion were quantified on normal knees from 19 subjects, and compared with those in walking and stair climbing. The deep flexion activities generate larger net quadriceps moments (6.9-13.5% body weight into height) and net posterior forces (58.3-67.8% body weight) than routine ambulatory activities. Moreover, the peak net moments and the net posterior forces were generated between 90 degrees and 150 degrees of flexion. The large moments and forces will result in high stress at high angles of flexion. These loads can influence pathological changes to the joint and are important considerations for reconstructive procedures of the knee. The posterior cruciate ligament should have a substantial role during deep flexion, since there was a large posterior load that must be sustained at the knee. The mechanics of the knee in deep flexion are likely a factor causing problems of posterior instability in current total knee arthroplasty. Thus, it is important to consider the magnitude of the loads at the knee in the treatment of patients that commonly perform deep flexion during activities of daily living.

A framework for the in vivo pathomechanics of osteoarthritis at the knee.

The in vivo pathomechanics of osteoarthritis (OA) at the knee is described in a framework that is based on an analysis of studies describing assays of biomarkers, cartilage morphology, and human function (gait analysis). The framework is divided into an Initiation Phase and a Progression Phase. The Initiation Phase is associated with kinematic changes that shift load bearing to infrequently loaded regions of the cartilage that cannot accommodate the loads. The Progression Phase is defined following cartilage breakdown. During the Progression Phase, the disease progresses more rapidly with increased load. While this framework was developed from an analysis of in vivo pathomechanics, it also explains how the convergence of biological, morphological, and neuromuscular changes to the musculoskeletal system during aging or during menopause lead to the increased rate of idiopathic OA with aging. Understanding the in vivo response of articular cartilage to its physical environment requires an integrated view of the problem that considers functional, anatomical, and biological interactions. The integrated in vivo framework presented here will be helpful for the interpretation of laboratory experiments as well as for the development of new methods for the evaluation of OA at the knee.