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Publication
Journal: Drug Testing and Analysis
January/19/2011
Abstract
The detection of drug abuse in horseracing often requires knowledge of drug metabolism, especially if urine is the matrix of choice. In this study, equine liver/lung microsomes/S9 tissue fractions were used to study the phase I metabolism of eight drugs of relevance to equine drug surveillance (acepromazine, azaperone, celecoxib, fentanyl, fluphenazine, mepivacaine, methylphenidate and tripelennamine). In vitro samples were analyzed qualitatively alongside samples originating from in vivo administrations using LC-MS on a high resolution accurate mass Thermo Orbitrap Discovery instrument and by LC-MS/MS on an Applied Biosystems Sciex 5500 Q Trap.Using high resolution accurate mass full-scan analysis on the Orbitrap, the in vitro systems were found to generate at least the two most abundant phase I metabolites observed in vitro for all eight drugs studied. In the majority of cases, in vitro experiments were also able to generate the minor in vivo metabolites and sometimes metabolites that were only observed in vitro. More detailed analyses of fentanyl incubates using LC-MS/MS showed that it was possible to generate good quality spectra from the metabolites generated in vitro. These data support the suggestion of using in vitro incubates as metabolite reference material in place of in vivo post-administration samples in accordance with new qualitative identification guidelines in the 2009 International Laboratory Accreditation Cooperation-G7 (ILAC-G7) document.In summary, the in vitro and in vivo phase I metabolism results reported herein compare well and demonstrate the potential of in vitro studies to compliment, refine and reduce the existing equine in vivo paradigm.
Publication
Journal: Lab on a Chip - Miniaturisation for Chemistry and Biology
July/6/2009
Abstract
We used inline, micro-evaporators to concentrate and transport DNA targets to a nanoliter single molecule fluorescence detection chamber for subsequent molecular beacon probe hybridization and analysis. This use of solvent removal as a unique means of target transport in a microanalytical platform led to a greater than 5000-fold concentration enhancement and detection limits that pushed below the femtomolar barrier commonly reported using confocal fluorescence detection. This simple microliter-to-nanoliter interconnect for single molecule counting analysis resolved several common limitations, including the need for excessive fluorescent probe concentrations at low target levels and inefficiencies in direct handling of highly dilute biological samples. In this report, the hundreds of bacteria-specific DNA molecules contained in approximately 25 microliters of a 50 aM sample were shuttled to a four nanoliter detection chamber through micro-evaporation. Here, the previously undetectable targets were enhanced to the pM regime and underwent probe hybridization and highly-efficient fluorescent event analysis via microfluidic recirculation through the confocal detection volume. This use of microfluidics in a single molecule detection (SMD) platform delivered unmatched sensitivity and introduced compliment technologies that may serve to bring SMD to more widespread use in replacing conventional methodologies for detecting rare target biomolecules in both research and clinical labs.
Publication
Journal: BMC Musculoskeletal Disorders
November/21/2017
Abstract
BACKGROUND
Physiotherapy rehabilitation following surgical reconstruction to the Anterior Cruciate Ligament (ACL) can take up to 12 months to complete. Given the lengthy rehabilitation process, a blended intervention can be used to compliment face-to-face physiotherapy with a digital exercise intervention. In this study, we used TRAK, a web-based tool that has been developed to support knee rehabilitation, which provides individually tailored exercise programs with videos, instructions and progress logs for each exercise, relevant health information and a contact option that allows a patient to email a physiotherapist for additional support. The aim of this study was to evaluate the acceptability of TRAK-based blended intervention in post ACL reconstruction rehabilitation.
METHODS
A qualitative research design using semi-structured interviews was used on a convenience sample of participants following an ACL reconstruction, and their treating physiotherapists, in a London NHS hospital. Participants were asked to use TRAK alongside face-to-face physiotherapy for 16 weeks. Interviews were carried out, audio recorded, transcribed verbatim and coded by two researchers independently. Data were analyzed using thematic analysis.
RESULTS
Of the 25 individuals that were approached to be part of the study, 24 consented, comprising 8 females and 16 males, mean age 30 years. 17 individuals used TRAK for 16 weeks and were available for interview. Four physiotherapists were also interviewed. The six main themes identified from patients were: the experience of TRAK rehabilitation, personal characteristics for engagement, strengths and weaknesses of the intervention, TRAK in the future and attitudes to digital healthcare. The main themes from the physiotherapist interviews were: potential benefits, availability of resources and service organization to support use of TRAK.
CONCLUSIONS
TRAK was found to be an acceptable method of delivering ACL rehabilitation alongside face-to-face physiotherapy. Patients reported that TRAK, specifically the videos, increased their confidence and motivation with their rehabilitation. They identified ways in which TRAK could be developed in the future to meet technological expectations and further support rehabilitation. For Physiotherapists time and availability of computers affected acceptability. Organization of care to support integration of digital exercise interventions such as TRAK into a blended approach to rehabilitation is required.
Publication
Journal: BMC Bioinformatics
June/2/2010
Abstract
BACKGROUND
Recombinant protein production is a useful biotechnology to produce a large quantity of highly soluble proteins. Currently, the most widely used production system is to fuse a target protein into different vectors in Escherichia coli (E. coli). However, the production efficacy of different vectors varies for different target proteins. Trial-and-error is still the common practice to find out the efficacy of a vector for a given target protein. Previous studies are limited in that they assumed that proteins would be over-expressed and focused only on the solubility of expressed proteins. In fact, many pairings of vectors and proteins result in no expression.
RESULTS
In this study, we applied machine learning to train prediction models to predict whether a pairing of vector-protein will express or not express in E. coli. For expressed cases, the models further predict whether the expressed proteins would be soluble. We collected a set of real cases from the clients of our recombinant protein production core facility, where six different vectors were designed and studied. This set of cases is used in both training and evaluation of our models. We evaluate three different models based on the support vector machines (SVM) and their ensembles. Unlike many previous works, these models consider the sequence of the target protein as well as the sequence of the whole fusion vector as the features. We show that a model that classifies a case into one of the three classes (no expression, inclusion body and soluble) outperforms a model that considers the nested structure of the three classes, while a model that can take advantage of the hierarchical structure of the three classes performs slight worse but comparably to the best model. Meanwhile, compared to previous works, we show that the prediction accuracy of our best method still performs the best. Lastly, we briefly present two methods to use the trained model in the design of the recombinant protein production systems to improve the chance of high soluble protein production.
CONCLUSIONS
In this paper, we show that a machine learning approach to the prediction of the efficacy of a vector for a target protein in a recombinant protein production system is promising and may compliment traditional knowledge-driven study of the efficacy. We will release our program to share with other labs in the public domain when this paper is published.
Publication
Journal: Osteoporosis International
April/8/2020
Abstract
The International Osteoporosis Foundation (IOF) Capture the Fracture® Campaign with the Fragility Fracture Network (FFN) and National Osteoporosis Foundation (NOF) has developed eleven patient-level key performance indicators (KPIs) for fracture liaison services (FLSs) to guide quality improvement.Fracture Liaison Services (FLSs) are recommended worldwide to reduce fracture risk after a sentinel fracture. Given not every FLS is automatically effective, the IOF Capture the Fracture working group has developed and implemented the Best Practice Framework to assess the organisational components of an FLS. We have now developed a complimentary KPI set that extends this assessment of performance to the patient level.The Capture the Fracture working group in collaboration with the Fragility Fracture Network Secondary Fragility Fracture Special Interest Group and National Osteoporosis Foundation adapted existing metrics from the UK-based Fracture Liaison Service Database Audit to develop a patient-level KPI set for FLSs.Eleven KPIs were selected. The proportion of patients: with non-spinal fractures; with spine fractures (detected clinically and radiologically); assessed for fracture risk within 12 weeks of sentinel fracture; having DXA assessment within 12 weeks of sentinel fracture; having falls risk assessment; recommended anti-osteoporosis medication; commenced of strength and balance exercise intervention within 16 weeks of sentinel fracture; monitored within 16 weeks of sentinel fracture; started anti-osteoporosis medication within 16 weeks of sentinel fracture; prescribed anti-osteoporosis medication 52 weeks after sentinel fracture. The final KPI measures data completeness for each of the other KPIs. For these indicators, levels of achievement were set at the < 50%, 50-80% and > 80% levels except for treatment recommendation where a level of 50% was used.This KPI set compliments the existing Best Practice Framework to support FLSs to examine their own performance using patient-level data. By using this KPI set for local quality improvement cycles, FLSs will be able to efficiently realise the full potential of secondary fracture prevention and improved clinical outcomes for their local populations.
Publication
Journal: Frontiers in Immunology
November/11/2019
Abstract
Primary immunodeficiencies are heritable disorders of immune function. CD19 is a B cell co-receptor important for B cell development, and CD19 deficiency is a known genetic risk factor for a rare form of primary immunodeficiency known as "common variable immunodeficiency" (CVID); an antibody deficiency resulting in low levels of serum IgG and IgA. Enteropathies are commonly observed in CVID patients but the underlying reason for this is undefined. Here, we utilize CD19-/- mice as a model of CVID to test the hypothesis that antibody deficiency negatively impacts gut physiology under steady-state conditions. As anticipated, immune phenotyping experiments demonstrate that CD19-/- mice develop a severe B cell deficiency in gut-associated lymphoid tissues that result in significant reductions to antibody concentrations in the gut lumen. Antibody deficiency was associated with defective anti-commensal IgA responses and the outgrowth of anaerobic bacteria in the gut. Expansion of anaerobic bacteria coincides with the development of a chronic inflammatory condition in the gut of CD19-/- mice that results in an intestinal malabsorption characterized by defects in lipid metabolism and transport. Administration of the antibiotic metronidazole to target anaerobic members of the microbiota rescues mice from disease indicating that intestinal malabsorption is a microbiota-dependent phenomenon. Finally, intestinal malabsorption in CD19-/- mice is a gluten-sensitive enteropathy as exposure to a gluten-free diet also significantly reduces disease severity in CD19-/- mice. Collectively, these results support an effect of antibody deficiency on steady-state gut physiology that compliment emerging data from human studies linking IgA deficiency with non-infectious complications associated with CVID. They also demonstrate that CD19-/- mice are a useful model for studying the role of B cell deficiency and gut dysbiosis on gluten-sensitive enteropathies; a rapidly emerging group of diseases in humans with an unknown etiology.
Publication
Journal: journal of prevention of Alzheimer's disease, The
February/3/2020
Abstract
The European Prevention of Alzheimer's Dementia (EPAD) Programme is a pan-European project whose objective is to deliver a platform, adaptive, Phase 2 proof of concept (PoC) trial for the secondary prevention of Alzheimer's dementia. A component of this platform is the Longitudinal Cohort Study (LCS) which acts as a readiness cohort for the PoC Trial as well as generating data for disease modelling work in the preclinical and prodromal phases of Alzheimer's dementia.The first data wave has been collected, quality checked, released and now available for analysis to answer numerous research questions. Here we describe the results from key variables in the EPAD LCS with the objective of using these results to compliment analyses of these data in the future.EPAD LCS is a cohort study whose primary objective is as a readiness cohort for the EPAD PoC Trial. As such recruitment is not capped at any particular number but will continue to facilitate delivery of the EPAD PoC Trial. Research Participants are seen annually (with an additional 6 month visit in the first year).The EPAD Trial Delivery Network comprises currently 21 centres across Europe.Research participants are included if they are over 50 years old and do not have a diagnosis of dementia.All research participants undergo multiple assessments to fully characterise the biology of Alzheimer's disease and relate this to risk factors (both fixed and modifiable) and biomarker expression of disease through brain imaging, fluid samples (CSF, blood, urine and saliva), cognitive performance, functional abilities and neuropsychiatric symptomatology.V500.0 represents the first 500 research participants baselined into EPAD LCS. The mean age was 66.4 (SD=6.7) and 47.8% were male. The data was split for presentation into 4 groups: [1] CDR=0 and Amyloid + (preclinical AD), [2] CDR=0 and Amyloid -, [3] CDR=0.5 and Amyloid + (prodromal AD) and [4] CDR=0.5 and Amyloid -.The EPAD LCS is achieving its primary objective of trial readiness and the structured approach to data release as manifest by this first data release of V500.0 will assist researchers to describe and compare their findings as well as in systematic reviews and meta-analyses. It is anticipated given current recruitment rates that V1500.0 data release will take place in Autumn 2019. V500.1 (when the 1 year follow up is completed on the V500.0 (sub)cohort will be in Autumn 2019 also.
Publication
Journal: Clinical Oral Investigations
October/16/2017
Abstract
OBJECTIVE
To evaluate in long-term periods the destruction of periodontal tissues and bacterial colonization induced by oral gavage with periodontopathogens or ligature experimental periodontal disease models.
METHODS
Forty-eight C57BL/6 J mice were divided into four groups: group C: negative control; group L: ligature; group G-Pg: oral gavage with Porphyromonas gingivalis; and group G-PgFn: oral gavage with Porphyromonas gingivalis associated with Fusobacterium nucleatum. Mice were infected by oral gavage five times in 2-day intervals. After 45 and 60 days, animals were sacrificed and the immune-inflammatory response in the periodontal tissue was assessed by stereometric analysis. The alveolar bone loss was evaluated by live microcomputed tomography and histometric analysis. qPCR was used to confirm the bacterial colonization in all the groups. Data were analyzed using the Kruskal-Wallis, Wilcoxon, and ANOVA tests, at 5 % of significance level.
RESULTS
Ligature model induced inflammation and bone resorption characterized by increased number of inflammatory cells and decreased number of fibroblasts, followed by advanced alveolar bone loss at 45 and 60 days (p < 0.05). Bacterial colonization in groups G-Pg and G-PgFn was confirmed by qPCR but inflammation and bone resorption were not observed (p < 0.05).
CONCLUSIONS
The ligature model but not the oral gavage models were effective to induce inflammation and bone loss in long-term periods. Pg colonization was observed in all models of experimental periodontal disease induction, independent of tissue alterations. These mice models of periodontitis validates, compliments, and enhances published PD models that utilize ligature or oral gavage and supports the importance of a successful colonization of a susceptible host, a bacterial invasion into vulnerable tissue, and host-bacterial interactions that lead to tissue destruction.
CONCLUSIONS
The ligature model was an effective approach to induce inflammation and bone loss similar to human periodontitis, but the oral gavage models were not efficient in inducing periodontal inflammation and tissue destruction in the conditions studied. Ligature models can provide a basis for future interventional studies that contribute to the understanding of the disease pathogenesis and the complex host response to microbial challenge.
Publication
Journal: Human Movement Science
February/27/2007
Abstract
This study investigated spiral drawing performance as an indicator of fine motor function, as well as to gain insight into adaptive movement strategies used by people with multiple sclerosis (MS). Seven people with MS, nine younger controls (mean age of 20) and eight older controls (mean age of 40) drew spirals on a graphics tablet at a comfortable speed and size. Spirography (i.e., a subjective visual assessment of the static trace) revealed indications of reduced control of the pen for people with MS. Analysis of the movements showed that people with MS tended to draw the spirals slower and with less pen pressure than controls. All groups increased their speed and pressure along with spiral size, but this increase was much steeper for the controls. MS participants drew spirals with more variability around an ideal trajectory, highlighting fine motor control degradation. MS patients tended to use a smaller scaling ratio, resulting in smaller spirals for a given number of revolutions. The younger and older control groups drew the spirals in a similar manner, and age was not a significant factor in any of the analyses. It is argued that the relatively lower pressure used, and slower, smaller movements (particularly during the more difficult outer sections of the spiral) are in part an adaptive strategy used to reduce movement variability. These results demonstrate the utility of the analysis of spiral movements as an objective technique for assessing motor control degradation, which can compliment the subjective rating based on the static pen trace. As such, it can provide further insight into the biomechanical strategies used when performing fine movements.
Publication
Journal: Journal of Neural Engineering
May/27/2013
Abstract
Eye movements are highly correlated with motor intentions and are often retained by patients with serious motor deficiencies. Despite this, eye tracking is not widely used as control interface for movement in impaired patients due to poor signal interpretation and lack of control flexibility. We propose that tracking the gaze position in 3D rather than 2D provides a considerably richer signal for human machine interfaces by allowing direct interaction with the environment rather than via computer displays. We demonstrate here that by using mass-produced video-game hardware, it is possible to produce an ultra-low-cost binocular eye-tracker with comparable performance to commercial systems, yet 800 times cheaper. Our head-mounted system has 30 USD material costs and operates at over 120 Hz sampling rate with a 0.5-1 degree of visual angle resolution. We perform 2D and 3D gaze estimation, controlling a real-time volumetric cursor essential for driving complex user interfaces. Our approach yields an information throughput of 43 bits s(-1), more than ten times that of invasive and semi-invasive brain-machine interfaces (BMIs) that are vastly more expensive. Unlike many BMIs our system yields effective real-time closed loop control of devices (10 ms latency), after just ten minutes of training, which we demonstrate through a novel BMI benchmark--the control of the video arcade game 'Pong'.
Publication
Journal: Journal of Applied Behavior Analysis
October/27/1983
Abstract
This study developed and evaluated a social skills training program for institutionalized mildly or moderately retarded and dually diagnosed individuals. Social skills were conceptualized as requiring an action or reaction within six skill areas: compliments, social interactions, politeness, criticism, social confrontation, and questions/answers. The program taught social skills using a commercially available table game, Sorry, and a specially designed card deck. Each card represented one of the skill areas and was designed to train either an actor or reactor response. The program featured response specific feedback, self-monitoring, individualized reinforcers, and individualized performance criterion levels. A multiple baseline across two groups (N = 3 per group) revealed that the game contingencies increased social skills in all targeted areas. After training, the subjects displayed their newly learned skills at or above their trained levels in two different settings with novel persons present. Although untargeted, the complexity of the subjects' responses increased across conditions, since there was a steady increase in the number of words they used per response. The program appears to be a viable means of training social skills since it uses standardized training procedures, requires only one facilitator, and is in itself a social situation that may encourage interactions with peers, cooperation, competition, and politeness.
Publication
Journal: Pediatric Emergency Care
September/25/1991
Abstract
We conducted an analysis of all communications received from patients or their families by the director of a pediatric emergency department over a three-year period, during which approximately 150,000 visits occurred. Communications were characterized as complaint or compliment and subclassified by type: waiting time, staff attitude, quality of medical care, and billing. Chi 2 analysis was used to identify factors that predisposed to complaint or compliment and to identify the subtype. After quality-of-care issues, complaints stemmed most often from billing issues or waiting time for care for nonurgent disorders (especially medical problems), while complimentary letters most frequently addressed staff attitude and quality of care. The problems that we identified might be addressed by providing families improved access to non-emergency department care sources, education regarding the role of an emergency department, and better explanation of billing procedures during the registration process. Additionally, our findings serve as a reminder that many parents appreciate the care given to their children, particularly for life-threatening emergencies.
Publication
Journal: Laboratory Investigation
January/12/2000
Abstract
A connection between the apoptotic cell clearance system and the acquired immune system was studied in vivo. When fluorescence-labeled apoptotic HL-60 cells were inoculated into footpads of guinea pigs and rabbits, monocyte/ macrophage infiltration rapidly occurred and subsequently the apoptotic cells as well as the macrophages disappeared from the lesion by 48 hours without any macroscopical signs of inflammation. Inversely, the fluorescent cell debris, which had been engulfed by the macrophages, appeared and chronologically increased in the draining lymphatics and the popliteal lymph nodes by 48 hours. Subsequently, proliferation of T and B lymphocytes in the popliteal lymph nodes was observed. Secondary inoculation of HL-60 cells in the flank skin of guinea pigs on day 3 after the initial inoculation induced an acute immunologic dermatitis with erythema, edema, vascular permeability enhancement, and polymorphonuclear leukocyte infiltration. In vitro characterizations demonstrated the presence of compliment dependent cytotoxic IgM antibody against HL-60 cells in their sera. The infiltration of monocytes/macrophages at the apoptotic cell injection site and the subsequent production of the anti-HL-60 cell IgM antibodies were significantly suppressed by in situ injections of anti-S19 ribosomal protein rabbit antibodies. These results indicated that the serial events with the rapid apoptotic cell clearance by macrophages, the macrophage migration to lymph nodes, and the antigen presentation to T lymphocytes by the macrophages acquire immunity against apoptotic cells. It was also indicated that the S19 ribosomal protein dimer was the major chemotactic factor in the initial monocyte/macrophage infiltration to apoptotic cells.
Publication
Journal: Journal of Mathematical Biology
September/5/2001
Abstract
A class of truncated unimodal discrete-time single species models for which low or high densities result in extinction in the following generation are considered. A classification of the dynamics of these maps into five types is proven: (i) extinction in finite time for all initial densities, (ii) semistability in which all orbits tend toward the origin or a semistable fixed point, (iii) bistability for which the origin and an interval bounded away from the origin are attracting, (iv) chaotic semistability in which there is an interval of chaotic dynamics whose compliment lies in the origin's basin of attraction and (v) essential extinction in which almost every (but not every) initial population density leads to extinction in finite time. Applying these results to the Logistic, Ricker and generalized Beverton-Holt maps with constant harvesting rates, two birfurcations are shown to lead to sudden population disappearances: a saddle node bifurcation corresponding to a transition from bistability to extinction and a chaotic blue sky catastrophe corresponding to a transition from bistability to essential extinction.
Publication
Journal: BMC Medical Education
July/3/2016
Abstract
BACKGROUND
Many undergraduate and graduate-entry health science curricula have incorporated training in motivational interviewing (MI). However, to effectively teach skills that will remain with students after they graduate is challenging. The aims of this study were to find out self-assessed MI skills of health students and whether reflecting on the results can promote transformative learning.
METHODS
Thirty-six Australian occupational therapy and physiotherapy students were taught the principles of MI, asked to conduct a motivational interview, transcribe it, self-rate it using the Motivational Interviewing Treatment Integrity (MITI) tool and reflect on the experience. Student MI skills were measured using the reported MITI subscores. Student assignments and a focus group discussion were analysed to explore the student experience using the MITI tool and self-reflection to improve their understanding of MI principles.
RESULTS
Students found MI challenging, although identified the MITI tool as useful for promoting self-reflection and to isolate MI skills. Students self-assessed their MI skills as competent and higher than scores expected from beginners.
CONCLUSIONS
The results inform educational programs on how MI skills can be developed for health professional students and can result in transformative learning. Students may over-state their MI skills and strategies to reduce this, including peer review, are discussed. Structured self-reflection, using tools such as the MITI can promote awareness of MI skills and compliment didactic teaching methods.
Publication
Journal: Endocrinology and Metabolism
January/20/2016
Abstract
Vertebral fractures and trabecular bone loss have dominated thinking and research into the pathogenesis and the structural basis of bone fragility during the last 70 years. However, 80% of all fractures are non-vertebral and occur at regions assembled using large amounts of cortical bone; only 20% of fractures are vertebral. Moreover, ~80% of the skeleton is cortical and ~70% of all bone loss is cortical even though trabecular bone is lost more rapidly than cortical bone. Bone is lost because remodelling becomes unbalanced after midlife. Most cortical bone loss occurs by intracortical, not endocortical remodelling. Each remodelling event removes more bone than deposited enlarging existing canals which eventually coalesce eroding and thinning the cortex from 'within.' Thus, there is a need to study the decay of cortical as well as trabecular bone, and to develop drugs that restore the strength of both types of bone. It is now possible to accurately quantify cortical porosity and trabecular decay in vivo. The challenges still to be met are to determine whether measurement of porosity identifies persons at risk for fracture, whether this approach is compliments information obtained using bone densitometry, and whether changes in cortical porosity and other microstructural traits have the sensitivity to serve as surrogates of treatment success or failure.
Authors
Publication
Journal: Brain Research
May/31/2007
Abstract
The mouse Engrailed genes, En1 and En2, play an important role in the development of the cerebellum from its inception at the mid/hindbrain boundary in early embryonic development through cell type specification events and beyond. In the absence of En1, the cerebellum and caudal midbrain fail to develop normally--a phenotype that we have previously reported to be strain dependent. On the 129/S1 strain background, En1 null alleles lead to mid/hindbrain failure, whereas on the C57BL/6 background, En1 deficiency is compatible with near normal cerebellar development. We have pursued this dramatic effect of genetic background by performing a genetic modifier screen through F1 backcross and F1 intercross matings. The backcross has yielded two strong candidate intervals with suggestive linkage to a third region. Moreover, variations in rescue frequency among subgroups within the backcross indicate gender and parent of origin influences on rescue penetrance. The intercross data reveal locus heterogeneity of the En1 modifiers, with more than one compliment of C57BL/6 and 129/S1 alleles capable of mediating the rescue phenotype. These findings highlight the complexity and plasticity of gene networks involved in brain development.
Publication
Journal: Nephrology Dialysis Transplantation
July/8/2007
Publication
Journal: Biophysical Journal
August/22/2017
Abstract
Kinesin processivity, defined as the average number of steps that occur per interaction with a microtubule, is an important biophysical determinant of the motor's intracellular capabilities. Despite its fundamental importance to the diversity of tasks that kinesins carry out in cells, no existing quantitative model fully explains how structural differences between kinesins alter kinetic rates in the ATPase cycle to produce functional changes in processivity. Here we use high-resolution single-molecule microscopy to directly observe the stepping behavior of kinesin-1 and -2 family motors with different length neck-linker domains. We characterize a one-head-bound posthydrolysis vulnerable state where a kinetic race occurs between attachment of the tethered head to its next binding site and detachment of the bound head from the microtubule. We find that greater processivity is correlated with faster attachment of the tethered head from this vulnerable state. In compliment, we show that slowing detachment from this vulnerable state by strengthening motor-microtubule electrostatic interactions also increases processivity. Furthermore, we provide evidence that attachment of the tethered head is irreversible, suggesting a first passage model for exit from the vulnerable state. Overall, our results provide a kinetic framework for explaining kinesin processivity and for mapping structural differences to functional differences in diverse kinesin isoforms.
Publication
Journal: Journal of the European Academy of Dermatology and Venereology
May/5/2008
Abstract
Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by the L1, L2 and L3 serotypes of Chlamydia trachomatis. The disease has been in the spotlight recently because of recent outbreaks in Europe as well as the USA. A unique feature of the recent outbreaks has been that most cases have been caused by the L2 strain. Another unique feature of these outbreaks is the fact that most cases have occurred in men having sex with men, and most patients have presented with proctitis. Interestingly, most recent cases have occurred in human immunodeficiency virus-seropositive patients. Usually, the disease is divided into three phases: the primary stage characterized by a self-healing papule, the secondary stage characterized by proctitis or lymphadenopathy and the tertiary stage characterized by lymphedema and anal strictures. Tests used for diagnosis include polymerase chain reactions and compliment fixation tests. The treatment of choice is doxycycline.
Authors
Publication
Journal: Patient Education and Counseling
July/2/2008
Abstract
OBJECTIVE
This study compared differences in nurse and patient communication profiles between two telehealth modes: telephone and videophone, and evaluated longitudinal changes in communication, nurse perceptions, and patient satisfaction.
METHODS
Subjects were enrolled in a randomized controlled clinical trial evaluating a 90-day home-based intervention for heart failure. Telephone (n=14) and videophone (n=14) interactions were audio taped and analyzed using the Roter Interaction Analysis System.
RESULTS
Nurses were more likely to use open-ended questions, back-channel responses, friendly jokes, and checks for understanding on the telephone compared to videophone. Compliments given and partnership were more common on the videophone. Patients were more likely to give lifestyle information and approval comments on the telephone, and used more closed-ended questions on the videophone. Nurses perceptions of the interactions were not different between the telephone and videophone, nor did their perceptions change significantly over the course of the intervention. There were no significant differences in patient satisfaction between the telephone and videophone.
CONCLUSIONS
The results of this study did not support use of a videophone over the telephone.
CONCLUSIONS
It is critical to match technologies to patient needs and use the least complex technology possible. When considering use a videophone, health care providers should critically examine the trade-offs between additional complexities with the added value of the visual interaction.
Publication
Journal: Orthopedic Clinics of North America
February/7/2007
Abstract
Sex is defined as the classification of living things according to their chromosomal compliment. Gender is defined as a person's self-representation as a male or female or how social institutions respond to that person on the basis of his or her gender presentation. One frequently divides the topic or dimorphism into the biologic response inherent in their sex and the environmental response that might be better termed "gender differences." Clinicians have anecdotally agreed for years that patellofemoral disorders are more common in women. Given the difficulty in classifying patellofemoral disorders, literature support for this assumption is meager. For the purposes of this article we divide patellofemoral disorders into three categories: patellofemoral pain, patellofemoral instability, and patellofemoral arthritis. possible sex difference in these disorders are reviewed.
Publication
Journal: Social Psychiatry and Psychiatric Epidemiology
September/27/2012
Abstract
BACKGROUND
Cleckley asserted in 1941 that psychopathic personalities are found in the community as well as prisons. Subtypes of abnormal personality may be identifiable in the general population using contemporary measures of psychopathy.
METHODS
Cluster analysis of PCL:SV scores using the four-facet model with a representative sample of 624 adults aged 16-74 years living in households interviewed in the second of a two-phase survey in Great Britain.
RESULTS
Analysis confirmed an optimum 5-cluster solution and existence in the general population of prototypical or criminal psychopaths, non-psychopathic habitual criminals, and "successful psychopaths". Two additional clusters were identified, one uniquely characterised by impulsive/irresponsible (Facet 3) items and the other by social failure associated with low scores on each facet.
CONCLUSIONS
The study confirmed previously hypothesised and two new subtypes of psychopathy within the general population. This prototypical classification may compliment existing typologies during clinical assessment following further refinement.
Publication
Journal: Ultrasound in Obstetrics and Gynecology
September/15/2010
Abstract
OBJECTIVE
To assess the potential value of an early (first-trimester) ultrasound examination in depicting fetal anomalies by transabdominal (TAS) and transvaginal (TVS) sonography, to compare it with the traditional mid-trimester anomaly ultrasound examination and to evaluate the degree of patient acceptance of early sonography by the transvaginal route.
METHODS
In this prospective study over a 5-year period (January 2002 to January 2007) 2876 pregnant women underwent a 13-14-week ultrasound examination. The scan was performed by TAS at first and then, if a full fetal anatomical survey was not achieved, by TVS. A mid-trimester fetal anatomy scan was then performed in patients who had not dropped out, miscarried or undergone pregnancy termination (n = 2834).
RESULTS
In the early scan, analyzable data for 2876 TAS and 1357 TVS examinations showed that TVS was significantly better in visualizing the cranium, spine, stomach, kidneys, bladder and upper and lower limbs (P < 0.001). Complete fetal anatomical surveys were achieved by TAS in 64% of cases versus 82% of the cases in which it was attempted by TVS (P < 0.001). Patient body mass index significantly affected the ability of the sonographer to achieve a complete anatomical survey by both TAS and TVS (P < 0.001 and P = 0.004, respectively). The duration of the scan was significantly longer using TVS. The heart and kidneys were not properly visualized in 42% and 27% of cases, respectively, at the 13-week scan compared with 1.6% and 0% at the mid-trimester scan. The total number of cases in which anomalies were detected was 31. At the first-trimester scan, anomalies were detected in 21 fetuses and in 14 of these cases the parents chose pregnancy termination. At the second-trimester scan, anomalies were detected in 17 fetuses: 10 new anomalous cases along with seven cases already detected in the first-trimester scan.
CONCLUSIONS
Besides its importance in screening for chromosomal abnormalities, the early scan has great potential in visualizing with precision fetal anatomy. TVS can be used to compliment difficult TAS examinations; however, patients do not always agree to undergo TVS. The mid-trimester scan remains crucial for detailed fetal anatomical survey.
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