Early retinal differentiation of human pluripotent stem cells in microwell suspension cultures

OBJECTIVE: To develop a microwell suspension platform for the adaption of attached stem cell differentiation protocols into mixed suspension culture. RESULTS: We adapted an adherent protocol for the retinal differentiation of human induced pluripotent stem cells (hiPSCs) using a two-step protocol. Establishing the optimum embryoid body (EB) starting size and shaking speed resulted in the translation of the original adherent process into suspension culture. Embryoid bodies expanded in size as the culture progressed resulting in the expression of characteristic markers of early (Rx, Six and Otx2) and late (Crx, Nrl and Rhodopsin) retinal differentiation. The new process also eliminated the use of matrigel, an animal-derived extracellular matrix coating. CONCLUSIONS: Shaking microwells offer a fast and cost-effective method for proof-of-concept studies to establish whether pluripotent stem cell differentiation processes can be translated into mixed suspension culture

Application of submodular optimization to single machine scheduling with controllable processing times subject to release dates and deadlines

In this paper, we study a scheduling problem on a single machine, provided that the jobs have individual release dates and deadlines, and the processing times are controllable. The objective is to find a feasible schedule that minimizes the total cost of reducing the processing times. We reformulate the problem in terms of maximizing a linear function over a submodular polyhedron intersected with a box. For the latter problem of submodular optimization, we develop a recursive decomposition algorithm and apply it to solving the single machine scheduling problem to achieve the best possible running time

Role of polymorphisms of the inflammatory response genes and DC-SIGNR in genetic susceptibility to SARS and other infections.

Research Fund for the Control of Infectious Diseases: Research Dissemination Reports (Series 2)1. A genetic risk-association study involving more than 1200 subjects showed individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS infection. 2. This was supported by in vitro binding studies that demonstrated homozygous L-SIGN, compared to heterozygous, had higher binding capacity for SARS coronavirus (SARS-CoV), with higher proteasome-dependent viral degradation. In contrast, homozygous L-SIGN demonstrated lower binding capacity for HIV1-gp120.3. Genetic-association studies for single nucleotide polymorphisms of the inflammatory response genes, namely TNF-alpha, INF-alpha, INF-beta, INF-gamma, IL1-alpha, IL1-beta, IL-4, IL-6 and iNOS, failed to show a significant association with SARS clinical outcomes or susceptibility.published_or_final_versio

Functional role of ICAM-3 polymorphism in genetic susceptibility to SARS infection.

Key Messages 1. Severe acute respiratory syndrome (SARS) patients who are homozygous for intercellular adhesion molecule-3 (ICAM-3) Gly143 showed significant association with higher lactate dehydrogenase levels and lower total white blood cell counts on admission. 2. In vitro functional studies demonstrated low level binding of ICAM-3 to DC-SIGN and a wide variation in T-cell response of the wild-type ICAM-3 genotype.published_or_final_versio

Association of a single nucleotide polymorphism in the CD209 (DC-SIGN) promoter with SARS severity.

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Automated ventricular systems segmentation in brain CT images by combining low-level segmentation and high-level template matching

<p>Abstract</p> <p>Background</p> <p>Accurate analysis of CT brain scans is vital for diagnosis and treatment of Traumatic Brain Injuries (TBI). Automatic processing of these CT brain scans could speed up the decision making process, lower the cost of healthcare, and reduce the chance of human error. In this paper, we focus on automatic processing of CT brain images to segment and identify the ventricular systems. The segmentation of ventricles provides quantitative measures on the changes of ventricles in the brain that form vital diagnosis information.</p> <p>Methods</p> <p>First all CT slices are aligned by detecting the ideal midlines in all images. The initial estimation of the ideal midline of the brain is found based on skull symmetry and then the initial estimate is further refined using detected anatomical features. Then a two-step method is used for ventricle segmentation. First a low-level segmentation on each pixel is applied on the CT images. For this step, both Iterated Conditional Mode (ICM) and Maximum A Posteriori Spatial Probability (MASP) are evaluated and compared. The second step applies template matching algorithm to identify objects in the initial low-level segmentation as ventricles. Experiments for ventricle segmentation are conducted using a relatively large CT dataset containing mild and severe TBI cases.</p> <p>Results</p> <p>Experiments show that the acceptable rate of the ideal midline detection is over 95%. Two measurements are defined to evaluate ventricle recognition results. The first measure is a sensitivity-like measure and the second is a false positive-like measure. For the first measurement, the rate is 100% indicating that all ventricles are identified in all slices. The false positives-like measurement is 8.59%. We also point out the similarities and differences between ICM and MASP algorithms through both mathematically relationships and segmentation results on CT images.</p> <p>Conclusion</p> <p>The experiments show the reliability of the proposed algorithms. The novelty of the proposed method lies in its incorporation of anatomical features for ideal midline detection and the two-step ventricle segmentation method. Our method offers the following improvements over existing approaches: accurate detection of the ideal midline and accurate recognition of ventricles using both anatomical features and spatial templates derived from Magnetic Resonance Images.</p

Implementation of a standardized protocol to manage elderly patients with low energy pelvic fractures: can service improvement be expected?

Purpose: The incidence of low energy pelvic fractures (FPFs) in the elderly is increasing. Comorbidities, decreased bone-quality, problematic fracture fixation and poor compliance represent some of their specific difficulties. In the absence of uniform management, a standard operating procedure (SOP) was introduced to our unit, aiming to improve the quality of services provided to these patients. Methods: A cohort study was contacted to test the impact of (1) using a specific clinical algorithm and (2) using different antiosteoporotic drugs. Multivariate regression analysis was used to determine prognostic factors. Study endpoints were the time-to-healing, length-of-stay, return to pre-injury mobility, union status, mortality and complications. Results: A total of 132 elderly patients (≥65 years) admitted during the period 2012–2014 with FPFs were enrolled. High-energy fractures, acetabular fractures, associated trauma affecting mobility, pathological pelvic lesions and operated FPFs were used as exclusion criteria. The majority of included patients were females (108/132; 81.8%), and the mean age was 85.8 years (range 67–108). Use of antiosteoporotics was associated with a shorter time of healing (p = 0.036). Patients treated according to the algorithm showed a significant protection against malunion (p < 0.001). Also, adherence to the algorithm allowed more patients to return to their pre-injury mobility status (p = 0.039). Conclusions: The use of antiosteoporotic medication in elderly patients with fragility pelvic fractures was associated with faster healing, whilst the adherence to a structured clinical pathway led to less malunions and non-unions and return to pre-injury mobility state

Public Health Emergency Preparedness and Response Communications with Health Care Providers: A Literature Review

<p>Abstract</p> <p>Background</p> <p>Health care providers (HCPs) play an important role in public health emergency preparedness and response (PHEPR) so need to be aware of public health threats and emergencies. To inform HCPs, public health issues PHEPR messages that provide guidelines and updates, and facilitate surveillance so HCPs will recognize and control communicable diseases, prevent excess deaths and mitigate suffering. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. We conducted a literature review to investigate the systems and tools used by public health to generate PHEPR communications to HCPs, and to identify specific characteristics of message delivery mechanisms and formats that may be associated with effective PHEPR communications.</p> <p>Methods</p> <p>A systematic review of peer- and non-peer-reviewed literature focused on the following questions: 1) What public health systems exist for communicating PHEPR messages from public health agencies to HCPs? 2) Have these systems been evaluated and, if yes, what criteria were used to evaluate these systems? 3) What have these evaluations discovered about characterizations of the most effective ways for public health agencies to communicate PHEPR messages to HCPs?</p> <p>Results</p> <p>We identified 25 systems or tools for communicating PHEPR messages from public health agencies to HCPs. Few articles assessed PHEPR communication systems or messaging methods or outcomes. Only one study compared the effectiveness of the delivery format, device or message itself. We also discovered that the potential is high for HCPs to experience "message overload" given redundancy of PHEPR messaging in multiple formats and/or through different delivery systems.</p> <p>Conclusions</p> <p>We found that detailed descriptions of PHEPR messaging from public health to HCPs are scarce in the literature and, even when available are rarely evaluated in any systematic fashion. To meet present-day and future information needs for emergency preparedness, more attention needs to be given to evaluating the effectiveness of these systems in a scientifically rigorous manner.</p

Dynamical heating across the Milky Way disc using APOGEE and Gaia

The kinematics of the Milky Way disc as a function of age are well measured at the solar radius, but have not been studied over a wider range of Galactocentric radii. Here, we measure the kinematics of mono-age, mono-[Fe/H] populations in the low and high [α/Fe] discs between 4 ≲ R ≲ 13 kpc and |z| ≲ 2 kpc using 65 719 stars in common between APOGEE DR14 and Gaia DR2 for which we estimate ages using a Bayesian neural network model trained on asteroseismic ages. We determine the vertical and radial velocity dispersions, finding that the low and high [α/Fe] discs display markedly different age–velocity dispersion relations (AVRs) and shapes σz/σR. The high [α/Fe] disc has roughly flat AVRs and constant σz/σR = 0.64 ± 0.04, whereas the low [α/Fe] disc has large variations in this ratio that positively correlate with the mean orbital radius of the population at fixed age. The high [α/Fe] disc component’s flat AVRs and constant σz/σR clearly indicate an entirely different heating history. Outer disc populations also have flatter radial AVRs than those in the inner disc, likely due to the waning effect of spiral arms. Our detailed measurements of AVRs and σz/σR across the disc indicate that low [α/Fe], inner disc (⁠R≲10kpc⁠) stellar populations are likely dynamically heated by both giant molecular clouds and spiral arms, while the observed trends for outer disc populations require a significant contribution from another heating mechanism such as satellite perturbations. We also find that outer disc populations have slightly positive mean vertical and radial velocities likely because they are part of the warped disc