An investigation of the potential of DIP-STR markers for DNA mixture analyses

The genetic characterization of unbalanced mixed stains remains an important area where improvement is imperative. In fact, using the standard tools of forensic DNA profiling (i.e., STR markers), the profile of the minor contributor in mixed DNA stains cannot be successfully detected if its quantitative share of DNA is less than 10% of the mixed trace. This is due to the fact that the major contributor's profile "masks" that of the minor contributor. Besides known remedies to this problem, such as Y-STR analysis, a new compound genetic marker that consists of a Deletion/Insertion Polymorphism (DIP) linked to a Short Tandem Repeat (STR) polymorphism, has recently been developed and proposed [1]. These novel markers are called DIP-STR markers. This paper compares, from a statistical and forensic perspective, the potential usefulness of these novel DIP-STR markers (i) with traditional STR markers in cases of moderately unbalanced mixtures, and (ii) with Y-STR markers in cases of female-male mixtures. This is done through a comparison of the distribution of 100,000 likelihood ratio values obtained using each method on simulated mixtures. This procedure is performed assuming, in turn, the prosecution's and the defence's point of view.

Rapid prototyping of compliant human aortic roots for assessment of valved stents.

Adequate in-vitro training in valved stents deployment as well as testing of the latter devices requires compliant real-size models of the human aortic root. The casting methods utilized up to now are multi-step, time consuming and complicated. We pursued a goal of building a flexible 3D model in a single-step procedure. We created a precise 3D CAD model of a human aortic root using previously published anatomical and geometrical data and printed it using a novel rapid prototyping system developed by the Fab@Home project. As a material for 3D fabrication we used common house-hold silicone and afterwards dip-coated several models with dispersion silicone one or two times. To assess the production precision we compared the size of the final product with the CAD model. Compliance of the models was measured and compared with native porcine aortic root. Total fabrication time was 3 h and 20 min. Dip-coating one or two times with dispersion silicone if applied took one or two extra days, respectively. The error in dimensions of non-coated aortic root model compared to the CAD design was <3.0% along X, Y-axes and 4.1% along Z-axis. Compliance of a non-coated model as judged by the changes of radius values in the radial direction by 16.39% is significantly different (P<0.001) from native aortic tissue--23.54% at the pressure of 80-100 mmHg. Rapid prototyping of compliant, life-size anatomical models with the Fab@Home 3D printer is feasible--it is very quick compared to previous casting methods.

Time constant of the cerebral arterial bed in normal subjects.

The time constant of cerebral arterial bed (in brief time constant) is a product of brain arterial compliance (C(a)) and resistance (CVR). We tested the hypothesis that in normal subjects, changes in end-tidal CO(2) (EtCO(2)) affect the value of the time constant. C(a) and CVR were estimated using mathematical transformations of arterial pressure (ABP) and transcranial Doppler (TCD) cerebral blood flow velocity waveforms. Responses of the time constant to controlled changes in EtCO(2) were compared in 34 young volunteers. Hypercapnia shortened the time constant (0.22 s [0.17, 0.26] vs. 0.16 s [0.13, 0.20]; p = 0.000001), while hypocapnia lengthened the time constant (0.22 s [0.17, 0.26] vs. 0.23 s [0.19, 0.32]; p < 0.0032). The time constant was negatively correlated with changes in EtCO(2) (R(partial) = -0.68, p < 0.000001). This was associated with a decrease in CVR when EtCO(2) increased (R(partial) = -0.80, p < 0.000001) and C(a) remained independent of changes in EtCO(2). C(a) was negatively correlated with mean ABP (R(partial) = -0.68, p < 0.000001). In summary, the time constant shortens with increasing EtCO(2). Its potential role in cerebrovascular investigations needs further studies.

Trends and determinants of time in bed in Geneva, Switzerland

STUDY OBJECTIVES: There is limited information regarding sleep duration and determinants in Switzerland. We aimed to assess the trends and determinants of time in bed as a proxy for sleep duration in the Swiss canton of Geneva. METHODS: Data from repeated, independent cross-sectional representative samples of adults (≥ 18 years) of the Geneva population were collected between 2005 and 2011. Self-reported time in bed, education, monthly income, and nationality were assessed by questionnaire. RESULTS: Data from 3,853 participants (50% women, 51.7 ± 10.9 years) were analyzed. No significant trend was observed between 2005 and 2011 regarding time in bed or the prevalence of short (≤ 6 h/day) and long (> 9 h/day) time in bed. Elderly participants reported a longer time in bed (year-adjusted mean ± standard error: 7.67 ± 0.02, 7.82 ± 0.03, and 8.41 ± 0.04 h/day for 35-50, 50-65, and 65+ years, respectively, p < 0.001), while shorter time in bed was reported by non-Swiss participants (7.77 ± 0.03 vs. 7.92 ± 0.03 h/day for Swiss nationals, p < 0.001), participants with higher education (7.92 ± 0.02 for non-university vs. 7.74 ± 0.03 h/day for university, p < 0.001) or higher income (8.10 ± 0.04, 7.84 ± 0.03, and 7.70 ± 0.03 h/day for < 5,000 SFr; 5,000-9,500 SFr, and > 9,500 SFr, respectively, p < 0.001). Multivariable-adjusted polytomous logistic regression showed short and long time in bed to be positively associated with obesity and negatively associated with income. CONCLUSION: In a Swiss adult population, sleep duration as assessed by time in bed did not change significantly between 2005 and 2011. Both clinical and socioeconomic factors influence time in bed.

Sex of College Students Moderates Associations among Bedtime, Time in Bed, and Circadian Phase Angle.

Sex differences in circadian rhythms have been reported with some conflicting results. The timing of sleep and length of time in bed have not been considered, however, in previous such studies. The current study has 3 major aims: (1) replicate previous studies in a large sample of young adults for sex differences in sleep patterns and dim light melatonin onset (DLMO) phase; (2) in a subsample constrained by matching across sex for bedtime and time in bed, confirm sex differences in DLMO and phase angle of DLMO to bedtime; (3) explore sex differences in the influence of sleep timing and length of time in bed on phase angle. A total of 356 first-year Brown University students (207 women) aged 17.7 to 21.4 years (mean = 18.8 years, SD = 0.4 years) were included in these analyses. Wake time was the only sleep variable that showed a sex difference. DLMO phase was earlier in women than men and phase angle wider in women than men. Shorter time in bed was associated with wider phase angle in women and men. In men, however, a 3-way interaction indicated that phase angles were influenced by both bedtime and time in bed; a complex interaction was not found for women. These analyses in a large sample of young adults on self-selected schedules confirm a sex difference in wake time, circadian phase, and the association between circadian phase and reported bedtime. A complex interaction with length of time in bed occurred for men but not women. We propose that these sex differences likely indicate fundamental differences in the biology of the sleep and circadian timing systems as well as in behavioral choices.

Early mobilization out of bed after ischaemic stroke reduces severe complications but not cerebral blood flow: a randomized controlled pilot trial.

OBJECTIVE: To evaluate whether early mobilization after acute ischaemic stroke is better than delayed mobilization with regard to medical complications and if it is safe in relation to neurological function and cerebral blood flow. DESIGN: Randomized controlled pilot trial of early versus delayed mobilization out of bed with incidence of severe complications as the primary outcome. SETTING: Acute stroke unit in the neurology department of a University Hospital. PARTICIPANTS: Fifty patients after ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score >6 were recruited. INTERVENTION: All patients were treated with physiotherapy immediately after their admission. In the early protocol patients were mobilized out of bed after 52 hours, in the delayed protocol after seven days. RESULTS: Eight out of 50 randomized patients were excluded from the per-protocol analysis because of early transfer to other hospitals. There were 2 (8%) severe complications in the 25 early mobilization patients and 8 (47%) in the 17 delayed mobilization patients (P < 0.006). There were no differences in the total number of complications or in clinical outcome. In the 26 patients (62%) who underwent serial transcranial Doppler ultrasonography, no blood flow differences were found. CONCLUSION: We found an apparent reduction in severe complications and no increase in total complications with an early mobilization protocol after acute ischaemic stroke. No influence on neurological three-month outcomes or on cerebral blood flow was seen. These results justify larger trials comparing mobilization protocols with possibly even faster mobilization out of bed than explored here.

Modelling hydrodynamics in the Rio Parana, Argentina : an evaluation and inter-comparison of reduced-complexity and physics based models applied to a large sand-bed river

Depth-averaged velocities and unit discharges within a 30 km reach of one of the world's largest rivers, the Rio Parana, Argentina, were simulated using three hydrodynamic models with different process representations: a reduced complexity (RC) model that neglects most of the physics governing fluid flow, a two-dimensional model based on the shallow water equations, and a three-dimensional model based on the Reynolds-averaged Navier-Stokes equations. Row characteristics simulated using all three models were compared with data obtained by acoustic Doppler current profiler surveys at four cross sections within the study reach. This analysis demonstrates that, surprisingly, the performance of the RC model is generally equal to, and in some instances better than, that of the physics based models in terms of the statistical agreement between simulated and measured flow properties. In addition, in contrast to previous applications of RC models, the present study demonstrates that the RC model can successfully predict measured flow velocities. The strong performance of the RC model reflects, in part, the simplicity of the depth-averaged mean flow patterns within the study reach and the dominant role of channel-scale topographic features in controlling the flow dynamics. Moreover, the very low water surface slopes that typify large sand-bed rivers enable flow depths to be estimated reliably in the RC model using a simple fixed-lid planar water surface approximation. This approach overcomes a major problem encountered in the application of RC models in environments characterised by shallow flows and steep bed gradients. The RC model is four orders of magnitude faster than the physics based models when performing steady-state hydrodynamic calculations. However, the iterative nature of the RC model calculations implies a reduction in computational efficiency relative to some other RC models. A further implication of this is that, if used to simulate channel morphodynamics, the present RC model may offer only a marginal advantage in terms of computational efficiency over approaches based on the shallow water equations. These observations illustrate the trade off between model realism and efficiency that is a key consideration in RC modelling. Moreover, this outcome highlights a need to rethink the use of RC morphodynamic models in fluvial geomorphology and to move away from existing grid-based approaches, such as the popular cellular automata (CA) models, that remain essentially reductionist in nature. In the case of the world's largest sand-bed rivers, this might be achieved by implementing the RC model outlined here as one element within a hierarchical modelling framework that would enable computationally efficient simulation of the morphodynamics of large rivers over millennial time scales. (C) 2012 Elsevier B.V. All rights reserved.

Iontophoresis: from the lab to the bed side.

Pioneer work on iontophoresis undertaken by David Maurice during the 1970s and 1980s laid the initial groundwork for its potential implementation as a promising ocular therapeutic modality. A better understanding of tissue interactions within the eye during electric current application, along with better designs of drug delivery devices have enabled us to pursue David Maurice's original ideas and take them from the bench to the bed side. In the present study we demonstrate the potential application of an iontophoresis device (Eyegate, Optis, France) for the treatment of certain human eye diseases. Seventeen patients received a penetrating keratoplasty (PKP) at various intervals before presentation with active graft rejection in our clinic and were treated using this iontophoresis device. Methylprednisolone sodium succinate (MP) 62.5 mg/ml was infused within the Eyegate ocular probe container and an electrical current of 1.5 mA was delivered for 4 min with the negative pole connected to the ocular probe. Patients were treated on an ambulatory basis and received a standard course of three iontophoresis applications given once a day over 3 consecutive days. After treatment, 15 of the 17 treated eyes (88%) demonstrated a complete reversal of the rejection processes. In two eyes, only a partial and temporary improvement was observed. The mean best corrected visual acuity of all 17 patients during the last follow up visit was 0.37 +/- 0.2 compared to 0.06 +/- 0.05 before initiation of the iontophoresis treatment. The mean follow-up time was 13.7 months with a range of 5-29 months for the 17 patients. No significant side-effects associated with the iontophoresis treatment were observed. Thus, for the management of active corneal graft rejection, iontophoresis of MP can be an alternative to very frequent instillations of eye drops, or to pulsed intravenous therapy of corticosteroids.

Can the impact of bed closure in intensive care units be reliably monitored?

OBJECTIVE: To assess the properties of various indicators aimed at monitoring the impact on the activity and patient outcome of a bed closure in a surgical intensive care unit (ICU). DESIGN: Comparison before and after the intervention. SETTING: A surgical ICU at a university hospital. PATIENTS: All patients admitted to the unit over two periods of 10 months. INTERVENTION: Closure of one bed out of 17. MEASUREMENTS AND RESULTS: Activity and outcome indicators in the ICU and the structures upstream from it (emergency department, operative theater, recovery room) and downstream from it (intermediate care units). After the bed closure, the monthly medians of admitted patients and ICU hospital days increased from 107 (interquartile range 94-112) to 113 (106-121, P=0.07) and from 360 (325-443) to 395 (345-436, P=0.48), respectively, along with the linear trend observed in our institution. All indicators of workload, patient severity, and outcome remained stable except for SAPS II score, emergency admissions, and ICU readmissions, which increased not only transiently but also on a mid-term basis (10 months), indicating that the process of patient care delivery was no longer predictable. CONCLUSIONS: Health care systems, including ICUs, are extraordinary flexible, and can adapt to multiple external constraints without altering commonly used activity and outcome indicators. It is therefore necessary to set up multiple indicators to be able to reliably monitor the impact of external interventions and intervene rapidly when the system is no longer under control.

Quadrant/octant sequencing and the role of coherent structures in bed load sediment entrainment

To permit the tracking of turbulent flow structures in an Eulerian frame from single-point measurements, we make use of a generalization of conventional two-dimensional quadrant analysis to three-dimensional octants. We characterize flow structures using the sequences of these octants and show how significance may be attached to particular sequences using statistical mull models. We analyze an example experiment and show how a particular dominant flow structure can be identified from the conditional probability of octant sequences. The frequency of this structure corresponds to the dominant peak in the velocity spectra and exerts a high proportion of the total shear stress. We link this structure explicitly to the propensity for sediment entrainment and show that greater insight into sediment entrainment can be obtained by disaggregating those octants that occur within the identified macroturbulence structure from those that do not. Hence, this work goes beyond critiques of Reynolds stress approaches to bed load entrainment that highlight the importance of outward interactions, to identifying and prioritizing the quadrants/octants that define particular flow structures. Key Points <list list-type=''bulleted'' id=''jgrf20196-list-0001''> <list-item id=''jgrf20196-li-0001''>A new method for analysing single point velocity data is presented <list-item id=''jgrf20196-li-0002''>Flow structures are identified by a sequence of flow states (termed octants) <list-item id=''jgrf20196-li-0003''>The identified structure exerts high stresses and causes bed-load entrainment