It is frequently necessary to assess children with little or no schooling to determine their level of cognitive functioning, especially in developing countries. It is not possible, however, to assume ...that assessments will hold equal validity for children with and without the experience of schooling. The authors, therefore, set out to create a battery of tests suitable for both schooled and unschooled children. They assessed 973 schooled and 645 unschooled children in rural coastal Kenya using culturally adapted cognitive tests. Significant effects of age and schooling were found on all tests. On some tests (verbal knowledge, speeded figure matching, and pattern copying), unschooled children did not improve as much with age as schooled children. The effects of length of exposure to schooling and of age were greater than that of initial enrollment in school. The authors conclude that it is possible to assess unschooled children, but test batteries must be carefully constructed and standardized.
Although digital mobility outcomes (DMOs) can be readily calculated from real-world data collected with wearable devices and ad-hoc algorithms, technical validation is still required. The aim of this ...paper is to comparatively assess and validate DMOs estimated using real-world gait data from six different cohorts, focusing on gait sequence detection, foot initial contact detection (ICD), cadence (CAD) and stride length (SL) estimates.
Twenty healthy older adults, 20 people with Parkinson's disease, 20 with multiple sclerosis, 19 with proximal femoral fracture, 17 with chronic obstructive pulmonary disease and 12 with congestive heart failure were monitored for 2.5 h in the real-world, using a single wearable device worn on the lower back. A reference system combining inertial modules with distance sensors and pressure insoles was used for comparison of DMOs from the single wearable device. We assessed and validated three algorithms for gait sequence detection, four for ICD, three for CAD and four for SL by concurrently comparing their performances (e.g., accuracy, specificity, sensitivity, absolute and relative errors). Additionally, the effects of walking bout (WB) speed and duration on algorithm performance were investigated.
We identified two cohort-specific top performing algorithms for gait sequence detection and CAD, and a single best for ICD and SL. Best gait sequence detection algorithms showed good performances (sensitivity > 0.73, positive predictive values > 0.75, specificity > 0.95, accuracy > 0.94). ICD and CAD algorithms presented excellent results, with sensitivity > 0.79, positive predictive values > 0.89 and relative errors < 11% for ICD and < 8.5% for CAD. The best identified SL algorithm showed lower performances than other DMOs (absolute error < 0.21 m). Lower performances across all DMOs were found for the cohort with most severe gait impairments (proximal femoral fracture). Algorithms' performances were lower for short walking bouts; slower gait speeds (< 0.5 m/s) resulted in reduced performance of the CAD and SL algorithms.
Overall, the identified algorithms enabled a robust estimation of key DMOs. Our findings showed that the choice of algorithm for estimation of gait sequence detection and CAD should be cohort-specific (e.g., slow walkers and with gait impairments). Short walking bout length and slow walking speed worsened algorithms' performances. Trial registration ISRCTN - 12246987.
The ability of bacteriophage (phage), abundant within the gastrointestinal microbiome, to regulate bacterial populations within the same micro-environment offers prophylactic and therapeutic ...opportunities. Bacteria and phage have both been shown to interact intimately with mucin, and these interactions invariably effect the outcomes of phage predation within the intestine. To better understand the influence of the gastrointestinal micro-environment on phage predation, we employed enclosed, in vitro systems to investigate the roles of mucin concentration and agitation as a function of phage type and number on bacterial killing. Using two lytic coliphage, T4 and PhiX174, bacterial viability was quantified following exposure to phages at different multiplicities of infection (MOI) within increasing, physiological levels of mucin (0-4%) with and without agitation. Comparison of bacterial viability outcomes demonstrated that at low MOI, agitation in combination with higher mucin concentration (>2%) inhibited phage predation by both phages. However, when MOI was increased, PhiX predation was recovered regardless of mucin concentration or agitation. In contrast, only constant agitation of samples containing a high MOI of T4 demonstrated phage predation; briefly agitated samples remained hindered. Our results demonstrate that each phage-bacteria pairing is uniquely influenced by environmental factors, and these should be considered when determining the potential efficacy of phage predation under homeostatic or therapeutic circumstances.
Abstract
We investigate the morphology of the stellar distribution (SD) in a sample of Milky Way–like galaxies in the TNG50 simulation. Using a local in shell iterative method as the main approach, ...we explicitly show evidence of twisting (in about 52% of halos) and stretching (in 48% of them) in real space. This is matched with the reorientation observed in the eigenvectors of the inertia tensor and gives us a clear picture of having a reoriented SD. We make a comparison between the shape profile of the dark matter (DM) halo and SD and quite remarkably see that their radial profiles are fairly close, especially at small galactocentric radii, where the stellar disk is located. This implies that the DM halo is somewhat aligned with stars in response to the baryonic potential. The level of alignment mostly decreases away from the center. We study the impact of substructures in the orbital circularity parameter. It is demonstrated that in some cases, faraway substructures are counterrotating compared with the central stars and may flip the sign of total angular momentum and thus the orbital circularity parameter. Truncating them above 150 kpc, however, retains the disky structure of the galaxy as per initial selection. Including the impact of substructures in the shape of stars, we explicitly show that their contribution is subdominant. Overlaying our theoretical results on the observational constraints from previous literature, we establish fair agreement.
A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well ...established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fatty acids) are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fatty acids, including short-chain and certain unsaturated fatty acids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system.
We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin ...resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist in its elimination.
This study compared standard of care testing (SOC) to BioFire® FilmArray® Pneumonia
plus
Panel (PN
plus
). PN
plus
detects 15 bacteria with semiquantitative log bin values, 7 antibiotic resistance ...markers, three atypical bacteria (AB), and eight viral classes directly from bronchoalveolar lavage-like specimens (BLS) and sputum-like specimens (SLS). Fifty-two laboratories from 13 European countries and Israel tested 1234 BLS and 1242 SLS with PN
plus
and SOC. Detection rates and number of pathogens/samples were compared for PN
plus
pathogens. PN
plus
bin values and SOC quantities were compared. Three thousand two hundred sixty-two bacteria in PN
plus
were detected by PN
plus
and/or SOC. SOC detected 57.1% compared to 95.8% for PN
plus
(
p
≤ 0.0001). PN
plus
semiquantitative bin values were less than SOC, equal to SOC, or greater than SOC in 5.1%, 25.4%, and 69.6% of results, respectively. PN
plus
bin values were on average ≥ 1 log than SOC values (58.5% 1–2 logs; 11.0% 3–4 logs). PN
plus
identified 98.2% of MRSA and SOC 55.6%. SOC detected 73/103 AB (70.9%) and 134/631 viruses (21.2%). PN
plus
detected 93/103 AB (90.3%) and 618/631 viruses (97.9%) (
p
≤ 0.0001). PN
plus
and SOC mean number of pathogens/samples were 1.99 and 1.44, respectively. All gram-negative resistance markers were detected. PN
plus
and SOC results were fully or partially concordant for 49.1% and 26.4% of specimens, respectively. PN
plus
was highly sensitive and detected more potential pneumonia pathogens than SOC. Semiquantification may assist in understanding pathogen significance. As PN
plus
generates results in approximately 1 h, PN
plus
has potential to direct antimicrobial therapy in near real time and improve antimicrobial stewardship and patient outcomes.
Live recombinant viral vectors based on adenoviruses and poxviruses are among the most promising platforms for development of new vaccines against diseases such as malaria, tuberculosis, and ...HIV-AIDS. Vaccines based on live viruses must remain infectious to be effective, so therefore need continuous refrigeration to maintain stability and viability, a requirement that can be costly and difficult, especially in developing countries. The sugars sucrose and trehalose are commonly used as stabilizing agents and cryoprotectants for biological products. Here, we have exploited the ability of these sugars to vitrify on desiccation to develop a thermostabilization technique for live viral vaccine vectors. By slowly drying vaccines suspended in solutions of these disaccharide stabilizers onto a filter-like support membrane at ambient temperature, an ultrathin glass is deposited on the fibers of the inert matrix. Immobilization of two recombinant vaccine vectors-E1/E3-deleted human adenovirus type 5 and modified vaccinia virus Ankara-in this glass on the membranes enabled complete recovery of viral titer and immunogenicity after storage at up to 45 degrees C for 6 months and even longer with minimal losses. Furthermore, the membrane carrying the stabilized vaccine can be incorporated into a holder attached to a syringe for almost simultaneous reconstitution and injection at point of use. The technology may potentially be developed for the deployment of viral vector-based biopharmaceuticals in resource-poor settings.
The challenge confronting those seeking to understand the institutional dimensions of global environmental change and patterns of land-use and land-cover change is to find effective methods for ...analyzing the dynamics of socio-ecological systems. Such systems exhibit a number of characteristics that pose problems for the most commonly used statistical techniques and may require additional and innovative analytic tools. This article explores options available to researchers working in this field and recommends a strategy for achieving scientific progress. Statistical procedures developed in other fields of study are often helpful in addressing challenges arising in research into global change. Accordingly, we start with an assessment of some of the enhanced statistical techniques that are available for the study of socio-ecological systems. By themselves, however, even the most advanced statistical models cannot solve all the problems that arise in efforts to explain institutional effectiveness and patterns of land-use and land-cover change. We therefore proceed to an exploration of additional analytic techniques, including configurational comparisons and meta-analyses; case studies, counterfactuals, and narratives; and systems analysis and simulations. Our goal is to create a portfolio of complementary methods or, in other words, a tool kit for understanding complex human-environment interactions. When the results obtained through the use of two or more techniques converge, confidence in the robustness of key findings rises. Contradictory results, on the other hand, signal a need for additional analysis.
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