A comparative study on approximate entropy measure and poincaré plot indexes of minimum foot clearance variability in the elderly during walking

Background: Trip-related falls which is a major problem in the elderly population, might be linked to declines in the balance control function due to ageing. Minimum foot clearance (MFC) which provides a more sensitive measure of the motor function of the locomotor system, has been identified as a potential gait parameter associated with trip-related falls in older population. This paper proposes nonlinear indexes (approximate entropy (ApEn) and Poincaré plot indexes) of MFC variability and investigates the relationship of MFC with derived indexes of elderly gait patterns. The main aim is to find MFC variability indexes that well correlate with balance impairments. Methods: MFC data during treadmill walking for 14 healthy elderly and 10 elderly participants with balance problems and a history of falls (falls risk) were analysed using a PEAK-2D motion analysis system. ApEn and Poincaré plot indexes of all MFC data sets were calculated and compared. Results: Significant relationships of mean MFC with Poincaré plot indexes (SD1, SD2) and ApEn (r = 0.70, p < 0.05; r = 0.86, p < 0.01; r = 0.74, p < 0.05) were found in the falls-risk elderly group. On the other hand, such relationships were absent in the healthy elderly group. In contrast, the ApEn values of MFC data series were significantly (p < 0.05) correlated with Poincaré plot indexes of MFC in the healthy elderly group, whereas correlations were absent in the falls-risk group. The ApEn values in the falls-risk group (mean ApEn = 0.18 ± 0.03) was significantly (p < 0.05) higher than that in the healthy group (mean ApEn = 0.13 ± 0.13). The higher ApEn values in the falls-risk group might indicate increased irregularities and randomness in their gait patterns and an indication of loss of gait control mechanism. ApEn values of randomly shuffled MFC data of falls risk subjects did not show any significant relationship with mean MFC. Conclusion: Results have implication for quantifying gait dynamics in normal and pathological conditions, thus could be useful for the early diagnosis of at-risk gait. Further research should provide important information on whether falls prevention intervention can improve the gait performance of falls risk elderly by monitoring the change in MFC variability indexes

A comparative study on approximate entropy measure and poincaré plot indexes of minimum foot clearance variability in the elderly during walking

Background: Trip-related falls which is a major problem in the elderly population, might be linked to declines in the balance control function due to ageing. Minimum foot clearance (MFC) which provides a more sensitive measure of the motor function of the locomotor system, has been identified as a potential gait parameter associated with trip-related falls in older population. This paper proposes nonlinear indexes (approximate entropy (ApEn) and Poincaré plot indexes) of MFC variability and investigates the relationship of MFC with derived indexes of elderly gait patterns. The main aim is to find MFC variability indexes that well correlate with balance impairments. Methods: MFC data during treadmill walking for 14 healthy elderly and 10 elderly participants with balance problems and a history of falls (falls risk) were analysed using a PEAK-2D motion analysis system. ApEn and Poincaré plot indexes of all MFC data sets were calculated and compared. Results: Significant relationships of mean MFC with Poincaré plot indexes (SD1, SD2) and ApEn (r = 0.70, p < 0.05; r = 0.86, p < 0.01; r = 0.74, p < 0.05) were found in the falls-risk elderly group. On the other hand, such relationships were absent in the healthy elderly group. In contrast, the ApEn values of MFC data series were significantly (p < 0.05) correlated with Poincaré plot indexes of MFC in the healthy elderly group, whereas correlations were absent in the falls-risk group. The ApEn values in the falls-risk group (mean ApEn = 0.18 ± 0.03) was significantly (p < 0.05) higher than that in the healthy group (mean ApEn = 0.13 ± 0.13). The higher ApEn values in the falls-risk group might indicate increased irregularities and randomness in their gait patterns and an indication of loss of gait control mechanism. ApEn values of randomly shuffled MFC data of falls risk subjects did not show any significant relationship with mean MFC. Conclusion: Results have implication for quantifying gait dynamics in normal and pathological conditions, thus could be useful for the early diagnosis of at-risk gait. Further research should provide important information on whether falls prevention intervention can improve the gait performance of falls risk elderly by monitoring the change in MFC variability indexes

Psychological impact of visible differences in patients with congenital craniofacial anomalies

© 2015, Singh and Moss; licensee Springer. Background: Patients with craniofacial anomalies often have appearance concerns and related social anxiety which can affect their quality of life. This study assessed the psychological impact of facial and dental appearance in patients with craniofacial anomalies in comparison to a general population control group. Methods: The study involved 102 adult patients (51% male) with congenital craniofacial anomalies and 102 controls (49% male). Both groups completed the Nepali version of Derriford Appearance Scale (DAS) and the Psychological Impact of Dental Aesthetic Questionnaire (PIDAQ) in a clinical setting to assess appearance-related distress, avoidance, and anxiety. Results: There was a significant difference between patients and controls on both PIDAQ (mean score for patients 33.25 ± 9.45 while for controls 27.52 ± 5.67, p < 0.001) and DAS59 scores (mean score for patients 159.16 ± 31.54 while for controls 77.64 ± 6.57, p < 0.001), indicating that patients experienced greater negative psychological impact of living with their appearance (PIDAQ) and more appearance-related distress (DAS) than controls. DAS scores were not associated with gender. There was no association of the place of residence (rural vs. urban) with PIDAQ or DAS59 scores. Conclusions: There is a significant psychological impact of altered facial and dental appearance in patients with craniofacial anomalies compared to controls. There was no effect of locality (rural/urban) on the psychological impact of facial and dental appearance in patients

A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis

<p>Abstract</p> <p>Background</p> <p>Long-term immunosuppression is often required in myasthenia gravis (MG). There are no published trials using methotrexate (MTX) in MG. The steroid-sparing efficacy of azathioprine (AZA) has been demonstrated after 18-months of starting therapy. However, AZA is considered expensive in Africa. We evaluated the steroid-sparing efficacy of MTX (17.5 mg weekly) compared with AZA (2.5 mg/kg daily) in subjects recently diagnosed with generalized MG by assessing their average monthly prednisone requirements.</p> <p>Methods</p> <p>The primary outcome was the average daily prednisone requirement by month between the two groups. Prednisone was given at the lowest dose to manage MG symptoms and adjusted as required according to protocol. Single-blinded assessments were performed 3-monthly for 2-years to determine the quantitative MG score and the MG activities of daily living score in order to determine those with minimal manifestations of MG.</p> <p>Results</p> <p>Thirty-one subjects (AZA n = 15; MTX n = 16) satisfied the inclusion criteria but only 24 were randomized. Baseline characteristics were similar. There was no difference between the AZA- and MTX-groups in respect of prednisone dosing (apart from months 10 and 12), in quantitative MG Score improvement, proportions in sustained remission, frequencies of MG relapses, or adverse reactions and/or withdrawals. The MTX-group received lower prednisone doses between month 10 (p = 0.047) and month 12 (p = 0.039). At month 12 the prednisone dose per kilogram bodyweight in the MTX-group (0.15 mg/kg) was half that of the AZA-group (0.31 mg/kg)(p = 0.019).</p> <p>Conclusions</p> <p>This study provides evidence that in patients with generalized MG methotrexate is an effective steroid-sparing agent 10 months after treatment initiation. Our data suggests that in generalized MG methotrexate has similar efficacy and tolerability to azathioprine and may be the drug of choice in financially constrained health systems.</p> <p>Trial registration</p> <p>SANCTR:DOH-27-0411-2436</p

Comparing mutation calls in fixed tumour samples between the Affymetrix OncoScan® Array and PCR based next-generation sequencing

Background: The importance of accurate and affordable mutation calling in fixed pathology samples is becoming increasingly important as we move into the era of personalised medicine. The Affymetrix OncoScan® Array platform is designed to produce actionable mutation calls in archival material. Methods: We compared calls made using the OncoScan platform with calls made using a custom designed PCR panel followed by next-generation sequencing (NGS), in order to benchmark the sensitivity and specificity of the OncoScan calls in a large cohort of fixed tumour samples. 392 fixed, clinical samples were sequenced, encompassing 641 PCR regions, 403 putative positive calls and 1528 putative negative calls. Results: A small number of mutations could not be validated, either due to large indels or pseudogenes impairing parts of the NGS pipeline. For the remainder, if calls were filtered according to simple quality metrics, both sensitivity and specificity for the OncoScan platform were over 98%. This applied even to samples with poorer sample quality and lower variant allele frequency (5–10%) than product claims indicated. Conclusions: This benchmarking study will be useful to users and potential users of this platform, who wish to compare technologies or interpret their own results

Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0

Quantitative Deep Sequencing Reveals Dynamic HIV-1 Escape and Large Population Shifts during CCR5 Antagonist Therapy In Vivo

High-throughput sequencing platforms provide an approach for detecting rare HIV-1 variants and documenting more fully quasispecies diversity. We applied this technology to the V3 loop-coding region of env in samples collected from 4 chronically HIV-infected subjects in whom CCR5 antagonist (vicriviroc [VVC]) therapy failed. Between 25,000–140,000 amplified sequences were obtained per sample. Profound baseline V3 loop sequence heterogeneity existed; predicted CXCR4-using populations were identified in a largely CCR5-using population. The V3 loop forms associated with subsequent virologic failure, either through CXCR4 use or the emergence of high-level VVC resistance, were present as minor variants at 0.8–2.8% of baseline samples. Extreme, rapid shifts in population frequencies toward these forms occurred, and deep sequencing provided a detailed view of the rapid evolutionary impact of VVC selection. Greater V3 diversity was observed post-selection. This previously unreported degree of V3 loop sequence diversity has implications for viral pathogenesis, vaccine design, and the optimal use of HIV-1 CCR5 antagonists

Broadly Neutralizing Human Anti-HIV Antibody 2G12 Is Effective in Protection against Mucosal SHIV Challenge Even at Low Serum Neutralizing Titers

Developing an immunogen that elicits broadly neutralizing antibodies (bNAbs) is an elusive but important goal of HIV vaccine research, especially after the recent failure of the leading T cell based HIV vaccine in human efficacy trials. Even if such an immunogen can be developed, most animal model studies indicate that high serum neutralizing concentrations of bNAbs are required to provide significant benefit in typical protection experiments. One possible exception is provided by the anti-glycan bNAb 2G12, which has been reported to protect macaques against CXCR4-using SHIV challenge at relatively low serum neutralizing titers. Here, we investigated the ability of 2G12 administered intravenously (i.v.) to protect against vaginal challenge of rhesus macaques with the CCR5-using SHIVSF162P3. The results show that, at 2G12 serum neutralizing titers of the order of 1∶1 (IC90), 3/5 antibody-treated animals were protected with sterilizing immunity, i.e. no detectable virus replication following challenge; one animal showed a delayed and lowered primary viremia and the other animal showed a course of infection similar to 4 control animals. This result contrasts strongly with the typically high titers observed for protection by other neutralizing antibodies, including the bNAb b12. We compared b12 and 2G12 for characteristics that might explain the differences in protective ability relative to neutralizing activity. We found no evidence to suggest that 2G12 transudation to the vaginal surface was significantly superior to b12. We also observed that the ability of 2G12 to inhibit virus replication in target cells through antibody-mediated effector cell activity in vitro was equivalent or inferior to b12. The results raise the possibility that some epitopes on HIV may be better vaccine targets than others and support targeting the glycan shield of the envelope

Search for the decay modes D^0 → e^+e^-, D^0 → μ^+μ^-, and D^0 → e^±μ∓

We present searches for the rare decay modes D^0→e^+e^-, D^0→μ^+μ^-, and D^0→e^±μ^∓ in continuum e^+e^-→cc events recorded by the BABAR detector in a data sample that corresponds to an integrated luminosity of 468  fb^(-1). These decays are highly Glashow–Iliopoulos–Maiani suppressed but may be enhanced in several extensions of the standard model. Our observed event yields are consistent with the expected backgrounds. An excess is seen in the D^0→μ^+μ^- channel, although the observed yield is consistent with an upward background fluctuation at the 5% level. Using the Feldman–Cousins method, we set the following 90% confidence level intervals on the branching fractions: B(D^0→e^+e^-)<1.7×10^(-7), B(D^0→μ^+μ^-) within [0.6,8.1]×10^(-7), and B(D^0→e^±μ^∓)<3.3×10^(-7)

Evidence for an excess of B -> D(*) Tau Nu decays

Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.Comment: Expanded section on systematics, text corrections, improved the format of Figure 2 and included the effect of the change of the Tau polarization due to the charged Higg