Embedded sensors of the smartphones offer opportunities for granular, patient-autonomous measurements of neurological dysfunctions for disease identification, management, and for drug development. We ...hypothesized that aggregating data from two simple smartphone tests of fine finger movements with differing contribution of specific neurological domains (i.e., strength & cerebellar functions, vision, and reaction time) will allow establishment of secondary outcomes that reflect domain-specific deficit. This hypothesis was tested by assessing correlations of smartphone-derived outcomes with relevant parts of neurological examination in multiple sclerosis (MS) patients. We developed MS test suite on Android platform, consisting of several simple functional tests. This paper compares cross-sectional and longitudinal performance of Finger tapping and Balloon popping tests by 76 MS patients and 19 healthy volunteers (HV). The primary outcomes of smartphone tests, the average number of taps (per two 10-s intervals) and the average number of pops (per two 26-s intervals) differentiated MS from HV with similar power to traditional, investigator-administered test of fine finger movements, 9-hole peg test (9HPT). Additionally, the secondary outcomes identified patients with predominant cerebellar dysfunction, motor fatigue and poor eye-hand coordination and/or reaction time, as evidenced by significant correlations between these derived outcomes and relevant parts of neurological examination. The intra-individual variance in longitudinal sampling was low. In the time necessary for performing 9HPT, smartphone tests provide much richer and reliable measurements of several distinct neurological functions. These data suggest that combing more creatively-construed smartphone apps may one day recreate the entire neurological examination.
BACKGROUND Serum neurofilament light chain (sNFL) is becoming an important biomarker of neuro-axonal injury. Though sNFL correlates with CSF NFL (cNFL), 40% to 60% of variance remains unexplained. We ...aimed to mathematically adjust sNFL to strengthen its clinical value.METHODS We measured NFL in a blinded fashion in 1138 matched CSF and serum samples from 571 patients. Multiple linear regression (MLR) models constructed in the training cohort were validated in an independent cohort.RESULTS An MLR model that included age, blood urea nitrogen, alkaline phosphatase, creatinine, and weight improved correlations of cNFL with sNFL (from R2 = 0.57 to 0.67). Covariate adjustment significantly improved the correlation of sNFL with the number of contrast-enhancing lesions (from R2 = 0.18 to 0.28; 36% improvement) in the validation cohort of patients with multiple sclerosis (MS). Unexpectedly, only sNFL, but not cNFL, weakly but significantly correlated with cross-sectional MS severity outcomes. Investigating 2 nonoverlapping hypotheses, we showed that patients with proportionally higher sNFL to cNFL had higher clinical and radiological evidence of spinal cord (SC) injury and probably released NFL from peripheral axons into blood, bypassing the CSF.CONCLUSION sNFL captures 2 sources of axonal injury, central and peripheral, the latter reflecting SC damage, which primarily drives disability progression in MS.TRIAL REGISTRATION ClinicalTrials.gov NCT00794352.FUNDING Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH (AI001242 and AI001243).
Alice Mossie Brues (1913–2007) SANDFORD, MARY K.; KILGORE, LYNN; DUFOUR, DARNA L. ...
American anthropologist,
March 2008, Letnik:
110, Številka:
1
Journal Article
Recenzirano
In a career that spanned almost seven decades, she became best known for her innovative research involving the genetics of modern human variation and her use of computers to simulate natural ...selection, genetic drift, mutation, and gene flow.
•Idebenone is well-tolerated over two-year extended use.•Idebenone did not inhibit disability accumulation in a two-year baseline-versus treatment placebo-controlled trial.•GDF15 is a potential CSF ...biomarker of mitochondrial dysfunction in MS.
Multiple sclerosis (MS) is a chronic, immune-mediated neurodegenerative disorder of the central nervous system (CNS). While current MS therapies target the inflammatory processes, no treatment explicitly targets mitochondrial dysfunction and resulting axonal loss. Therefore, the aim of this study was to determine whether idebenone inhibits mitochondrial dysfunction and accumulation of disability in primary progressive MS (PPMS) and to enhance understanding of pathogenic mechanisms of PPMS progression using cerebrospinal fluid (CSF) biomarkers.
The double-blind, placebo-controlled Phase I/II clinical trial of Idebenone in patients with Primary Progressive MS (IPPoMS; NCT00950248) was an adaptively designed, baseline-versus-treatment, placebo-controlled, CSF-biomarker-supported trial. Based on interim analysis of the 1-year pre-treatment data, change in the area under the curve of Combinatorial Weight-Adjusted Disability Score (CombiWISE) became the primary outcome, with >80% power to detect ≥40% efficacy with 28 patients/arm treated for 2 years in baseline versus treatment paradigm. Changes in traditional disability scales and in brain ventricular volume were secondary outcomes. Exploratory outcomes included CSF biomarkers of mitochondrial dysfunction (Growth/differentiation factor 15 GDF15 and lactate), axonal damage (neurofilament light chain NFL), innate immunity (sCD14), blood brain barrier leakage (albumin quotient) and retinal nerve fiber layer thinning.
Idebenone was well tolerated but did not inhibit disability progression or CNS tissue destruction. Concentrations of GDF15, secreted predominantly by astrocytes and choroid plexus epithelium in vitro, increased after exposure to mitochondrial toxin rotenone, validating the ability of this biomarker to measure intrathecal mitochondrial damage. CSF GDF15 levels correlated strongly with age and MS patients had CSF levels of GDF15 significantly above age-adjusted healthy volunteers, with highest levels measured in PPMS. Idebenone did not change CSF GDF15 levels.
Mitochondrial dysfunction exceeding normal aging reflected by age-adjusted CSF GDF15 is present in the majority of PPMS patients, but it is not inhibited by idebenone.
In this article we report on the results of our attempts to locate and
study shaft-and-chamber tombs in the Municipality of Puerto Vallarta on
the southern (Jalisco) side of the Banderas Valley of ...coastal West Mexico
and to place these tombs in the broader context of burial practices in
this area during a time corresponding to the Late Preclassic and Early
Classic of Mesoamerica. We located and studied nine sites where
shaft-and-chamber tombs had reportedly been discovered and looted, but
here we focus on three (El Reparito, El Pozo de Doña Amparo, and La
Pedrera) where we were able to excavate un-looted as well as partially
looted shaft-and-chamber tombs. In the process we obtained evidence of (1)
the location and type of soil selected for the excavation of such tombs;
(2) variation in the form and content of the shafts and tomb chambers; (3)
the tools used for digging and the manner of sealing such tombs; (4)
chronological placement of the tombs; (5) burial of infants, sub-adults,
and adults in the chambers; (5) pathology in the pre-Hispanic population
responsible for such tombs; (6) cremation of bodies and their curation for
different periods of time before incineration; and (7) alternative forms
of interment along with shaft-and-chamber tombs in the same cemetery.
Also, the data obtained lend support for the idea that the Ameca River and
the Banderas Valley formed a “soft frontier” at this time
between fairly distinct pre-Hispanic cultural traditions found to the
north and to the south of the river, an area in which there was some
intermixing of these traditions.
Objective
To develop a sensitive neurological disability scale for broad utilization in clinical practice.
Methods
We employed advances of mobile computing to develop an iPad‐based App for convenient ...documentation of the neurological examination into a secure, cloud‐linked database. We included features present in four traditional neuroimmunological disability scales and codified their automatic computation. By combining spatial distribution of the neurological deficit with quantitative or semiquantitative rating of its severity we developed a new summary score (called NeurEx; ranging from 0 to 1349 with minimal measurable change of 0.25) and compared its performance with clinician‐ and App‐computed traditional clinical scales.
Results
In the cross‐sectional comparison of 906 neurological examinations, the variance between App‐computed and clinician‐scored disability scales was comparable to the variance between rating of the identical neurological examination by multiple sclerosis (MS)‐trained clinicians. By eliminating rating ambiguity, App‐computed scales achieved greater accuracy in measuring disability progression over time (n = 191 patients studied over 880.6 patient‐years). The NeurEx score had no apparent ceiling effect and more than 200‐fold higher sensitivity for detecting a measurable yearly disability progression (i.e., median progression slope of 8.13 relative to minimum detectable change of 0.25) than Expanded Disability Status Scale (EDSS) with a median yearly progression slope of 0.071 that is lower than the minimal measurable change on EDSS of 0.5.
Interpretation
NeurEx can be used as a highly sensitive outcome measure in neuroimmunology. The App can be easily modified for use in other areas of neurology and it can bridge private practice practitioners to academic centers in multicenter research studies.
Elemental hair concentrations were obtained from 168 mummified individuals recovered during excavations of cementeries S and R (A.D. 550-1450), at Kulubnarti, Republic of the Sudan (Van Gerven et ...al., 1981). Concentrations of calcium (Ca), magnesium (Mg), strontium (Sr), manganese (Mn), zinc (Zn), iron (Fe), and copper (Cu) were determined using inductively coupled plasma emission spectrometry (ICP) (Sandford, 1984; Sandford et al., 1983). Following univariate statistical reanalyses of these data (Sandford and Kissling, 1993a, b), we applied principal component analysis and multidimensional scaling to clarify their multivariate structure. Similar underlying associations were revealed in the two cemeteries. The first principal component, consisting of Mg, Ca, Sr, and Mn, may reflect inherent chemical similarities coupled with specific dietary factors (e.g., vegetation intakes) and physiological processes (e.g., bone remodeling). The second principal component, a contrast between Fe and Zn, may be due to their competitive relationship during absorption. The third principal component consists of Cu alone (in cemetery S), and Cu and Fe (in cemetery R), suggesting utilization of animal protein and an underlying synergism between Cu and Fe, respectively. Multidimensional scaling substantiates a three-dimensional model for describing elemental covariation. While interpretation of the first two dimensions was analogous to those of the first two principal components, the third dimension may represent antagonism between pairs of elements during absorption, transport and/or utilization (cemetery R: Cu vs. Zn; cemetery S: Cu vs. Zn, Fe vs. Mn). While these results provide the most persuasive evidence to date that elemental hair concentrations from this population reflect chiefly biogenic processes, isolation of diagenetic and exogenous effects requires further investigation through controlled studies.
TRACE ELEMENT ANALYSIS Farnum, Julie; Sandford, Mary K.
Encyclopedia of Archaeology,
2008, 20080000, Letnik:
3
Reference, Book Chapter
Evaluation of dietary components and the general health of early peoples has been advanced through the use of analyses of skeletal materials for major, minor, and trace elements. Early work, during ...the 1970s, optimistically focused on developing new analytical techniques and baseline data. Three basic approaches to trace element studies involved the analysis of single elements (such as lead or iron), multiple elements, and ratios of elements (such as strontium and calcium). The use of multiple methods of analysis for the same set of samples, coupled with statistical methods and cautious interpretations, can yield useful data. The data collected from archaeological remains are often put into context by comparing it with data gained from living modern peoples. Used together, this information can shed light on archaeological diet, lifestyles, and health, and, in some cases, expand our knowledge of modern health.
One hundred sixty eight hair samples recovered from two Christian era Nubian cemeteries (550-1450) were subjected to analysis of major and trace elements. Concentrations of magnesium, calcium, ...strontium, iron, zinc, copper and manganese were determined using inductively coupled plasma spectrometry. Mean levels of each element determined from the Nubian hair compare closely to those documented for modern samples and likely reflect a number of important environmental and biological factors affecting the population. Specifically, the present results provide a quantitative method for assessing the nutritional and disease factors contributing to cribra orbitalia (porotic hyperostosis), a frequent pathology in Nubian remains attributed to iron deficiency anemia. A comparison of iron levels between infants and children with and without cribra orbitalia demonstrates a significantly lower iron level for the affected group. In addition, concentrations of magnesium are also significantly lower for the Nubian subadults with cribra orbitalia. This new finding is consistent with clinical observations in which anemia has been produced in magnesium deficient animals, including humans. A reduction in magnesium lends further support to the hypothesis that age-specific stress stemming from weaning practices, parasitic infection and inadequate diet contributed to cribra orbitalia and its associated anemia in ancient Nubia.
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