335 research outputs found
Combined flow-focus and self-assembly routes for the formation of lipid stabilized oil-shelled microbubbles
Lipid and polymer stabilized microbubbles are used in medicine as contrast agents for ultrasound imaging and are being developed for the delivery of water soluble drugs to diseased areas of the body. However, many new therapeutics exhibit poor water solubility or stability, which has led to the requirement for the development of effective hydrophobic drug delivery systems. This study presents a new method to produce microbubbles coated with an oil layer capable of encapsulating hydrophobic drugs and suitable for targeted, triggered drug release. This new method utilizes highly controllable flow-focusing microfluidics with lipid oil nanodroplets self-assembling and spreading at gas–aqueous interfaces. Oil layer inside microbubbles were produced with diameters of 2.4±0.3 μm (s.d., 1.6 μm) and at concentrations up to 106 bubbles per milliliter. The mechanism of oil layer inside microbubble assembly and stability were characterized using methods including contact angle measurements, quartz crystal microbalance with dissipation monitoring and fluorescence resonance energy transfer imaging
A novel accelerometry-based algorithm for the detection of step durations over short episodes of gait in healthy elderly.
Background: The assessment of short episodes of gait is clinically relevant and easily implemented, especially given limited space and time requirements. BFS (body-fixed-sensors) are small, lightweight and easy to wear sensors, which allow the assessment of gait at relative low cost and with low interference. Thus, the assessment with BFS of short episodes of gait, extracted from dailylife physical activity or measured in a standardised and supervised setting, may add value in the study of gait quality of the elderly. The aim of this study was to evaluate the accuracy of a novel algorithm based on acceleration signals recorded at different human locations (lower back and heels) for the detection of step durations over short episodes of gait in healthy elderly subjects.Methods: Twenty healthy elderly subjects (73.7 ± 7.9 years old) walked twice a distance of 5 m, wearing a BFS on the lower back, and on the outside of each heel. Moreover, an optoelectronic three-dimensional (3D) motion tracking system was used to detect step durations. A novel algorithm is presented for the detection of step durations from low-back and heel acceleration signals separately. The accuracy of the algorithm was assessed by comparing absolute differences in step duration between the three methods: step detection from the optoelectronic 3D motion tracking system, step detection from the application of the novel algorithm to low-back accelerations, and step detection from the application of the novel algorithm to heel accelerations.Results: The proposed algorithm successfully detected all the steps, without false positives and without false negatives. Absolute average differences in step duration within trials and across subjects were calculated for each comparison, between low-back accelerations and the optoelectronic system were on average 22.4 ± 7.6 ms (4.0 ± 1.3 % of average step duration), between heel accelerations and the optoelectronic system were on average 20.7 ± 11.8 ms (3.7 ± 1.9 %), and between low-back accelerations and heel accelerations were on average 27.8 ± 15.1 ms (4.9 ± 2.5 % of average step duration).Conclusions: This study showed that the presented novel algorithm detects step durations over short episodes of gait in healthy elderly subjects with acceptable accuracy from low-back and heel accelerations, which provides opportunities to extract a range of gait parameters from short episodes of gait
Quantum Principal Bundles and Corresponding Gauge Theories
A generalization of classical gauge theory is presented, in the framework of
a noncommutative-geometric formalism of quantum principal bundles over smooth
manifolds. Quantum counterparts of classical gauge bundles, and classical gauge
transformations, are introduced and investigated. A natural differential
calculus on quantum gauge bundles is constructed and analyzed. Kinematical and
dynamical properties of corresponding gauge theories are discussed.Comment: 28 pages, AMS-LaTe
Technology for monitoring everyday prosthesis use: a systematic review
BACKGROUND
Understanding how prostheses are used in everyday life is central to the design, provision and evaluation of
prosthetic devices and associated services. This paper reviews the scientific literature on methodologies and
technologies that have been used to assess the daily use of both upper- and lower-limb prostheses. It discusses
the types of studies that have been undertaken, the technologies used to monitor physical activity, the benefits
of monitoring daily living and the barriers to long-term monitoring.
METHODS
A systematic literature search was conducted in PubMed, Web of Science, Scopus, CINAHL and EMBASE of
studies that monitored the activity of prosthesis-users during daily-living.
RESULTS
60 lower-limb studies and 9 upper-limb studies were identified for inclusion in the review. The first studies in
the lower-limb field date from the 1990s and the number has increased steadily since the early 2000s. In contrast,
the studies in the upper-limb field have only begun to emerge over the past few years. The early lower-limb
studies focused on the development or validation of actimeters, algorithms and/or scores for activity
classification. However, most of the recent lower-limb studies used activity monitoring to compare prosthetic components. The lower-limb studies mainly used step-counts as their only measure of activity, focusing on the
amount of activity, not the type and quality of movements. In comparison, the small number of upper-limb
studies were fairly evenly spread between development of algorithms, comparison of everyday activity to
clinical scores, and comparison of different prosthesis user populations. Most upper-limb papers reported the
degree of symmetry in activity levels between the arm with the prosthesis and the intact arm.
CONCLUSIONS
Activity monitoring technology used in conjunction with clinical scores and user feedback, offers significant
insights into how prostheses are used and whether they meet the user’s requirements. However, the cost, limited
battery-life and lack of availability in many countries mean that using sensors to understand the daily use of
prostheses and the types of activity being performed has not yet become a feasible standard clinical practice.
This review provides recommendations for the research and clinical communities to advance this area for the
benefit of prosthesis users
Donor Lymphocyte Infusions After Allogeneic Stem Cell Transplantation in Acute Leukemia: A Survey From the Gruppo Italiano Trapianto Midollo Osseo (GITMO)
We conducted a retrospective multicenter study including pediatric and adult patients with acute leukemia (AL) who received donor lymphocyte infusions (DLIs) after allogeneic hematopoietic stem cell transplantation (HCT) between January 1, 2010 and December 31, 2015, in order to determine the efficacy and toxicity of the immune treatment. Two hundred fifty-two patients, median age 45.1 years (1.6\u201373.4), were enrolled from 34 Italian transplant centers. The underlying disease was acute myeloid leukemia in 180 cases (71%). Donors were HLA identical or 1 locus mismatched sibling (40%), unrelated (40%), or haploidentical (20%). The first DLI was administered at a median time of 258 days (55\u20133,784) after HCT. The main indication for DLI was leukemia relapse (73%), followed by mixed chimerism (17%), and pre-emptive/prophylactic use (10%). Ninety-six patients (38%) received one single infusion, whereas 65 (26%), 42 (17%), and 49 patients (19%) received 2, 3, or 654 infusions, respectively, with a median of 31 days between two subsequent DLIs. Forty percent of evaluable patients received no treatment before the first DLI, whereas radiotherapy, conventional chemotherapy or targeted treatments were administered in 3, 39, and 18%, respectively. In informative patients, a few severe adverse events were reported: grade III\u2013IV graft versus host disease (GVHD) (3%), grade III\u2013IV hematological toxicity (11%), and DLI-related mortality (9%). Forty-six patients (18%) received a second HCT after a median of 232 days (32\u20131,390) from the first DLI. With a median follow-up of 461 days (2\u20133,255) after the first DLI, 1-, 3-, and 5- year overall survival (OS) of the whole group from start of DLI treatment was 55, 39, and 33%, respectively. In multivariate analysis, older recipient age, and transplants from haploidentical donors significantly reduced OS, whereas DLI for mixed chimerism or as pre-emptive/prophylactic treatment compared to DLI for AL relapse and a schedule including more than one DLI significantly prolonged OS. This GITMO survey confirms that DLI administration in absence of overt hematological relapse and multiple infusions are associated with a favorable outcome in AL patients. DLI from haploidentical donors had a poor outcome and may represent an area of further investigation
Donor Lymphocyte Infusions After Allogeneic Stem Cell Transplantation in Acute Leukemia: A Survey From the Gruppo Italiano Trapianto Midollo Osseo (GITMO)
Medically unexplained pain complaints are associated with underlying unrecognized mood disorders in primary care
<p>Abstract</p> <p>Background</p> <p>Patients with chronic pain frequently display comorbid depression, but the impact of this concurrence is often underestimated and mistreated. The aim of this study was to determine the prevalence of unrecognized major depression and other mood disorders and comorbid unexplained chronic pain in primary care settings and to explore the associated factors.</p> <p>Also, to compare the use of health services by patients with unexplained chronic pain, both with and without mood disorder comorbidity.</p> <p>Methods</p> <p>A cross-sectional study was carried out in a sample of primary care centers. 3189 patients consulting for "unexplained chronic pain" were assessed by the Visual Analogue Scales (VAS) and the Primary Care Evaluation of Mental Disorders (PRIME-MD) questionnaire.</p> <p>Results</p> <p>We report: a) a high prevalence of unrecognized mood disorders in patients suffering from unexplained chronic pain complaints (80.4%: CI 95%: 79.0%; 81.8%); b) a greater susceptibility of women to mood disorders (OR adjusted = 1.48; CI 95%:1.22; 1.81); c) a direct relationship between the prevalence of mood disorders and the duration of pain (OR adjusted = 1.01; CI 95%: 1.01; 1.02) d) a higher comorbidity with depression if the pain etiology was unknown (OR adjusted = 1.74; CI 95%: 1.45; 2.10) and, e) an increased use of health care services in patients with such a comorbidity (p < 0.0001).</p> <p>Conclusions</p> <p>The prevalence of undiagnosed mood disorders in patients with unexplained chronic pain in primary care is very high, leading to dissatisfaction with treatment processes and poorer outcomes. Consequently, it seems necessary to explore this condition more regularly in general practice in order to reach accurate diagnoses and to select the appropriate treatment.</p
Rare Variants in 48 Genes Account for 42% of Cases of Epilepsy With or Without Neurodevelopmental Delay in 246 Pediatric Patients
In order to characterize the genetic architecture of epilepsy in a pediatric population from the Iberian Peninsula (including the Canary Islands), we conducted targeted exome sequencing of 246 patients with infantile-onset seizures with or without neurodevelopmental delay. We detected 107 variants in 48 different genes, which were implicated in neuronal excitability, neurodevelopment, synaptic transmission, and metabolic pathways. In 104 cases (42%) we detected variant(s) that we classified as pathogenic or likely pathogenic. Of the 48 mutated genes, 32 were dominant, 8 recessive and 8 X-linked. Of the patients for whom family studies could be performed and in whom pathogenic variants were identified in dominant or X-linked genes, 82% carried de novo mutations. The involvement of small copy number variations (CNVs) is 9%. The use of progressively updated custom panels with high mean vertical coverage enabled establishment of a definitive diagnosis in a large proportion of cases (42%) and detection of CNVs (even duplications) with high fidelity. In 10.5% of patients we detected associations that are pending confirmation via functional and/or familial studies. Our findings had important consequences for the clinical management of the probands, since a large proportion of the cohort had been clinically misdiagnosed, and their families were subsequently able to avail of genetic counseling. In some cases, a more appropriate treatment was selected for the patient in question, or an inappropriate treatment discontinued. Our findings suggest the existence of modifier genes that may explain the incomplete penetrance of some epilepsy-related genes. We discuss possible reasons for non-diagnosis and future research directions. Further studies will be required to uncover the roles of structural variants, epimutations, and oligogenic inheritance in epilepsy, thereby providing a more complete molecular picture of this disease. In summary, given the broad phenotypic spectrum of most epilepsy-related genes, efficient genomic tools like the targeted exome sequencing panel described here are essential for early diagnosis and treatment, and should be implemented as first-tier diagnostic tools for children with epilepsy without a clear etiologic basis
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