Using Electronic Technology to Improve Clinical Care -- Results from a Before-after Cluster Trial to Evaluate Assessment and Classification of Sick Children According to Integrated Management of Childhood Illness (IMCI) Protocol in Tanzania.

Poor adherence to the Integrated Management of Childhood Illness (IMCI) protocol reduces the potential impact on under-five morbidity and mortality. Electronic technology could improve adherence; however there are few studies demonstrating the benefits of such technology in a resource-poor settings. This study estimates the impact of electronic technology on adherence to the IMCI protocols as compared to the current paper-based protocols in Tanzania. In four districts in Tanzania, 18 clinics were randomly selected for inclusion. At each site, observers documented critical parts of the clinical assessment of children aged 2 months to 5 years. The first set of observations occurred during examination of children using paper-based IMCI (pIMCI) and the next set of observations occurred during examination using the electronic IMCI (eIMCI). Children were re-examined by an IMCI expert and the diagnoses were compared. A total of 1221 children (671 paper, 550 electronic) were observed. For all ten critical IMCI items included in both systems, adherence to the protocol was greater for eIMCI than for pIMCI. The proportion assessed under pIMCI ranged from 61% to 98% compared to 92% to 100% under eIMCI (p < 0.05 for each of the ten assessment items). Use of electronic systems improved the completeness of assessment of children with acute illness in Tanzania. With the before-after nature of the design, potential for temporal confounding is the primary limitation. However, the data collection for both phases occurred over a short period (one month) and so temporal confounding was expected to be minimal. The results suggest that the use of electronic IMCI protocols can improve the completeness and consistency of clinical assessments and future studies will examine the long-term health and health systems impact of eIMCI

Airway resistance at maximum inhalation as a marker of asthma and airway hyperresponsiveness

<p>Abstract</p> <p>Background</p> <p>Asthmatics exhibit reduced airway dilation at maximal inspiration, likely due to structural differences in airway walls and/or functional differences in airway smooth muscle, factors that may also increase airway responsiveness to bronchoconstricting stimuli. The goal of this study was to test the hypothesis that the minimal airway resistance achievable during a maximal inspiration (R_min) is abnormally elevated in subjects with airway hyperresponsiveness.</p> <p>Methods</p> <p>The R_minwas measured in 34 nonasthmatic and 35 asthmatic subjects using forced oscillations at 8 Hz. R_minand spirometric indices were measured before and after bronchodilation (albuterol) and bronchoconstriction (methacholine). A preliminary study of 84 healthy subjects first established height dependence of baseline R_minvalues.</p> <p>Results</p> <p>Asthmatics had a higher baseline R_min% predicted than nonasthmatic subjects (134 ± 33 vs. 109 ± 19 % predicted, p = 0.0004). Sensitivity-specificity analysis using receiver operating characteristic curves indicated that baseline R_minwas able to identify subjects with airway hyperresponsiveness (PC₂₀< 16 mg/mL) better than most spirometric indices (Area under curve = 0.85, 0.78, and 0.87 for R_min% predicted, FEV₁% predicted, and FEF_25-75% predicted, respectively). Also, 80% of the subjects with baseline R_min< 100% predicted did not have airway hyperresponsiveness while 100% of subjects with R_min> 145% predicted had hyperresponsive airways, regardless of clinical classification as asthmatic or nonasthmatic.</p> <p>Conclusions</p> <p>These findings suggest that baseline R_min, a measurement that is easier to perform than spirometry, performs as well as or better than standard spirometric indices in distinguishing subjects with airway hyperresponsiveness from those without hyperresponsive airways. The relationship of baseline R_minto asthma and airway hyperresponsiveness likely reflects a causal relation between conditions that stiffen airway walls and hyperresponsiveness. In conjunction with symptom history, R_mincould provide a clinically useful tool for assessing asthma and monitoring response to treatment.</p

Characterisation of GLUT4 trafficking in HeLa cells: Comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes

Insulin-stimulated glucose transport is a characteristic property of adipocytes and muscle cells and involves the regulated delivery of glucose transporter (GLUT4)- containing vesicles from intracellular stores to the cell surface. Fusion of these vesicles results in increased numbers of GLUT4 molecules at the cell surface. In an attempt to overcome some of the limitations associated with both primary and cultured adipocytes, we expressed an epitope- and GFP-tagged version of GLUT4 (HA–GLUT4–GFP) in HeLa cells. Here we report the characterisation of this system compared to 3T3-L1 adipocytes. We show that insulin promotes translocation of HA–GLUT4–GFP to the surface of both cell types with similar kinetics using orthologous trafficking machinery. While the magnitude of the insulin-stimulated translocation of GLUT4 is smaller than mouse 3T3-L1 adipocytes, HeLa cells offer a useful, experimentally tractable, human model system. Here, we exemplify their utility through a small-scale siRNA screen to identify GOSR1 and YKT6 as potential novel regulators of GLUT4 trafficking in human cells

Improving the management of pain from advanced cancer in the community: study protocol for a pragmatic multi-centre randomised controlled trial

Introduction: For patients with advanced cancer, research shows that pain is frequent, burdensome and undertreated. Evidence-based approaches to support cancer pain management have been developed but have not been implemented within the context of the UK National Health Service. This protocol is for a pragmatic multi-centre randomised controlled trial to assess feasibility, acceptability, effectiveness and cost effectiveness for a multi-component intervention for pain management in patients with advanced cancer. Methods and Analysis: This trial will assess the feasibility of implementation and uptake of evidence based interventions, developed and piloted as part of the IMPACCT Programme grant, into routine clinical practice and determine whether there are potential differences with respect to patient rated pain, patient pain knowledge and experience, healthcare use, quality of life, and cost effectiveness. 160 patients will receive either the intervention (usual care plus supported self-management) delivered within the oncology clinic and palliative care services by locally assigned community palliative care nurses, consisting of a self-management educational intervention and eHealth intervention for routine pain assessment and monitoring; or usual care. The primary outcomes are to assess implementation and uptake of the interventions, and differences in terms of pain severity. Secondary outcomes include pain interference, participant pain knowledge and experience, and cost effectiveness. Outcome assessment will be blinded and patient reported outcome measures collected via post at 6 and 12 weeks following randomisation. Ethics and Dissemination: This RCT has the potential to significantly influence NHS service delivery to community based patients with pain from advanced cancer. We aim to provide definitive evidence of whether two simple interventions delivered by community palliative care nurse in palliative care that support-self-management are clinically and cost effective additions to standard community palliative care

Key Rotation for Authenticated Encryption

A common requirement in practice is to periodically rotate the keys used to encrypt stored data. Systems used by Amazon and Google do so using a hybrid encryption technique which is eminently practical but has questionable security in the face of key compromises and does not provide full key rotation. Meanwhile, symmetric updatable encryption schemes (introduced by Boneh et al. CRYPTO 2013) support full key rotation without performing decryption: ciphertexts created under one key can be rotated to ciphertexts created under a different key with the help of a re-encryption token. By design, the tokens do not leak information about keys or plaintexts and so can be given to storage providers without compromising security. But the prior work of Boneh et al. addresses relatively weak confidentiality goals and does not consider integrity at all. Moreover, as we show, a subtle issue with their concrete scheme obviates a security proof even for confidentiality against passive attacks. This paper presents a systematic study of updatable Authenticated Encryption (AE). We provide a set of security notions that strengthen those in prior work. These notions enable us to tease out real-world security requirements of different strengths and build schemes that satisfy them efficiently. We show that the hybrid approach currently used in industry achieves relatively weak forms of confidentiality and integrity, but can be modified at low cost to meet our stronger confidentiality and integrity goals. This leads to a practical scheme that has negligible overhead beyond conventional AE. We then introduce re-encryption indistinguishability, a security notion that formally captures the idea of fully refreshing keys upon rotation. We show how to repair the scheme of Boneh et al., attaining our stronger confidentiality notion. We also show how to extend the scheme to provide integrity, and we prove that it meets our re- encryption indistinguishability notion. Finally, we discuss how to instantiate our scheme efficiently using off-the-shelf cryptographic components (AE, hashing, elliptic curves). We report on the performance of a prototype implementation, showing that fully secure key rotations can be performed at a throughput of approximately 116 kB/s

New D1-D5-P geometries from string amplitudes

We derive the long range supergravity fields sourced by a D1-D5-P bound state from disk amplitudes for massless closed string emission. We suggest that since the parameter controlling the string perturbation expansion for this calculation decreases with distance from the bound state, the resulting asymptotic fields are valid even in the regime of parameters in which there is a classical black hole solution with the same charges. The supergravity fields differ from the black hole solution by multipole moments and are more general than those contained within known classes of solutions in the literature, whilst still preserving four supersymmetries. Our results support the conjecture that the black hole solution should be interpreted as a coarse-grained description rather than an exact description of the gravitational field sourced by D1-D5-P bound states in this regime of parameters.Comment: 48 pages, 2 figures, v2: typos correcte

Clinical Value of Prognostic Instruments to Identify Patients with an Increased Risk for Osteoporotic Fractures: Systematic Review

There is a plethora of evidence available studying the association of risk profiles and the development of osteoporotic fractures. The small number of out-of-sample validations, the large variety of study characteristics, outcomes and follow-up periods impedes from deriving robust summaries and from conclusions regarding the clinical performance of many tools. First and foremost, future activity in this field should aim at reaching a consensus among clinical experts in respect to the existing instruments. Then we call for careful validations and expedient adaptations for local circumstances of the most promising candidates

Dietary differences between elderly Iranians living in Sweden and Iran a cross-sectional comparative study

<p>Abstract</p> <p>Background</p> <p>During the last decades, global migration has increased and many immigrant groups have a higher prevalence than the native born population of several cardiovascular disease risk factors, including poor dietary habits. However, it is uncertain if dietary habits in immigrant populations reflect dietary habits in their country of origin or if the current diet is a consequence of the migration and possible change of dietary habits. The aim of this study was to examine possible dietary differences between elderly Iranians living in Stockholm, Sweden with elderly Iranians living in Tehran, Iran, taking into account sex, age, marital status, and education.</p> <p>Methods</p> <p>Dietary intakes were assessed by semi - quantitative food frequency questionnaire in a cross-sectional study of 121 Iranians living in Stockholm and 52 Iranians living in Tehran, aged 60-80. Differences in dietary habits between the two groups was analysed by bootstrapped regression analyses with 1000 replications.</p> <p>Results</p> <p>Iranians living in Sweden had significantly higher intake of protein, total fat, fiber than Iranians living in Iran, but lower consumption of carbohydrates. The observed differences in intake of macronutrients were reflected in consumed amount of all food items, which were higher among Iranians living in Iran with the exception of bread and grain consumption which was lower.</p> <p>Conclusions</p> <p>There are general differences in dietary habits between Iranians living in Iran and Iranians living in Sweden. Parts of observed differences in dietary habits may reflect a favourable adoption process to the Swedish dietary habits after migration. Meanwhile other differences are point of concern in light of the high prevalence of overweight, among Iranians living in Sweden and can have unfavourable impact in particular in the context of cardiovascular health.</p

Abnormal joint torque patterns exhibited by chronic stroke subjects while walking with a prescribed physiological gait pattern

<p>Abstract</p> <p>Background</p> <p>It is well documented that individuals with chronic stroke often exhibit considerable gait impairments that significantly impact their quality of life. While stroke subjects often walk asymmetrically, we sought to investigate whether prescribing near normal physiological gait patterns with the use of the Lokomat robotic gait-orthosis could help ameliorate asymmetries in gait, specifically, promote similar ankle, knee, and hip joint torques in both lower extremities. We hypothesized that hemiparetic stroke subjects would demonstrate significant differences in total joint torques in both the frontal and sagittal planes compared to non-disabled subjects despite walking under normal gait kinematic trajectories.</p> <p>Methods</p> <p>A motion analysis system was used to track the kinematic patterns of the pelvis and legs of 10 chronic hemiparetic stroke subjects and 5 age matched controls as they walked in the Lokomat. The subject's legs were attached to the Lokomat using instrumented shank and thigh cuffs while instrumented footlifters were applied to the impaired foot of stroke subjects to aid with foot clearance during swing. With minimal body-weight support, subjects walked at 2.5 km/hr on an instrumented treadmill capable of measuring ground reaction forces. Through a custom inverse dynamics model, the ankle, knee, and hip joint torques were calculated in both the frontal and sagittal planes. A single factor ANOVA was used to investigate differences in joint torques between control, unimpaired, and impaired legs at various points in the gait cycle.</p> <p>Results</p> <p>While the kinematic patterns of the stroke subjects were quite similar to those of the control subjects, the kinetic patterns were very different. During stance phase, the unimpaired limb of stroke subjects produced greater hip extension and knee flexion torques than the control group. At pre-swing, stroke subjects inappropriately extended their impaired knee, while during swing they tended to abduct their impaired leg, both being typical abnormal torque synergy patterns common to stroke gait.</p> <p>Conclusion</p> <p>Despite the Lokomat guiding stroke subjects through physiologically symmetric kinematic gait patterns, abnormal asymmetric joint torque patterns are still generated. These differences from the control group are characteristic of the hip hike and circumduction strategy employed by stroke subjects.</p

Alternative Promoters Influence Alternative Splicing at the Genomic Level

Background: More and more experiments have shown that transcription and mRNA processing are not two independent events but are tightly coupled to each other. Both promoter and transcription rate were found to influence alternative splicing. More than half of human genes have alternative promoters, but it is still not clear why there are so many alternative promoters and what their biological roles are. Methodology/Principal Findings: In this study, we explored whether there is a functional correlation between alternative promoters and alternative splicing by a genome-wide analysis of human and mouse genes. We constructed a large data set of genes with alternative promoter and alternative splicing annotations. By analyzing these genes, we showed that genes with alternative promoters tended to demonstrate alternative splicing compare to genes with single promoter, and, genes with more alternative promoters tend to have more alternative splicing variants. Furthermore, transcripts from different alternative promoters tended to splice differently. Conclusions/Significance: Thus at the genomic level, alternative promoters are positively correlated with alternativ