Construction of effective disposable biosensors for point of care testing of nitrite

© 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

NEW MICROFLUIDIC SYSTEM TO INCREASE ROBUSTNESS OF ELECTRODE PERFORMANCE AND DEVELOP POINT-OF-CARE HEMATOCRIT DEVICE

The present dissertation aimed to develop a new microfluidic system for a point-of-care hematocrit device. Stabilization of microfluidic systems via surfactant additives and integration of semipermeable SnakeSkin® membranes was investigated. Both methods stabilized the microfluidic systems by controlling electrolysis bubbles. Surfactant additives, Triton X-100 and SDS stabilized promoted faster bubble detachment at electrode surfaces by lowering surface tension and decreased gas bubble formation by increasing gas solubility. The SnakeSkin® membranes blocked bubbles from entering the microchannel and thus less disturbance to the electric field by bubbles occurred in the microchannel. Platinum electrode performance was improved by carbonizing electrode surface using red blood cells. Irreversibly adsorbed RBCs lysed on platinum electrode surfaces and formed porous carbon layers while current response measurements. The formed carbon layers increase the platinum electrode surface area and thus electrode performance was improved by 140 %. The microfluidic system was simplified by employing DC field to use as a platform for a point-of-care hematocrit device. Feasibility of the microfluidic system for hematocrit determination was shown via current response measurements of red blood cell suspensions in phosphate buffered saline and plasma media. The linear trendline of current responses over red blood cell concentration was obtained in both phosphate buffered saline and plasma media. This research suggested that a new and simple microfluidic system could be a promising solution to develop an inexpensive and reliable point-of-care hematocrit device.

Test of a Smock System on CPR Primary Emergency Measures and Medical Errors During Simulated Emergencies

Rates of survival of victims of sudden cardiac arrest (SCA) using cardio pulmonary resuscitation (CPR) have shown little improvement over the past three decades. Since registered nurses (RNs) comprise the largest group of healthcare providers in U.S. hospitals, it is essential that they are competent in performing the four primary measures (compression, ventilation, medication administration, and defibrillation) of CPR in order to improve survival rates of SCA patients. The purpose of this experimental study was to test a color-coded SMOCK system on:1) time to implement emergency patient care measures 2) technical skills performance 3) number of medical errors, and 4) team performance during simulated CPR exercises. The study sample was 260 RNs (M 40 years, SD=11.6) with work experience as an RN (M 7.25 years, SD=9.42).Nurses were allocated to a control or intervention arm consisting of 20 groups of 5-8 RNs per arm for a total of 130 RNs in each arm. Nurses in each study arm were given clinical scenarios requiring emergency CPR. Nurses in the intervention group wore different color labeled aprons (smocks) indicating their role assignment (medications, ventilation, compression, defibrillation, etc) on the code team during CPR. Findings indicated that the intervention using color-labeled smocks for pre-assigned roles had a significant effect on the time nurses started compressions (t=3.03, p=0.005), ventilations (t=2.86, p=0.004) and defibrillations (t=2.00, p=.05) when compared to the controls using the standard of care. In performing technical skills, nurses in the intervention groups performed compressions and ventilations significantly better than those in the control groups. The control groups made significantly (t=-2.61, p=0.013) more total errors (7.55 SD 1.54) than the intervention group (5.60, SD 1.90). There were no significant differences in team performance measures between the groups. Study findings indicate use of colored labeled smocks during CPR emergencies resulted in: shorter times to start emergency CPR; reduced errors; more technical skills completed successfully; and no differences in team performance.

Electrochemical Immunosensing of Cortisol in an Automated Microfluidic System Towards Point-of-Care Applications

This dissertation describes the development of a label-free, electrochemical immunosensing platform integrated into a low-cost microfluidic system for the sensitive, selective and accurate detection of cortisol, a steroid hormone co-related with many physiological disorders. Abnormal levels of cortisol is indicative of conditions such as Cushing’s syndrome, Addison’s disease, adrenal insufficiencies and more recently post-traumatic stress disorder (PTSD). Electrochemical detection of immuno-complex formation is utilized for the sensitive detection of Cortisol using Anti-Cortisol antibodies immobilized on sensing electrodes. Electrochemical detection techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) have been utilized for the characterization and sensing of the label-free detection of Cortisol. The utilization of nanomaterial’s as the immobilizing matrix for Anti-cortisol antibodies that leads to improved sensor response has been explored. A hybrid nano-composite of Polyanaline-Ag/AgO film has been fabricated onto Au substrate using electrophoretic deposition for the preparation of electrochemical immunosening of cortisol. Using a conventional 3-electrode electrochemical cell, a linear sensing range of 1pM to 1µM at a sensitivity of 66µA/M and detection limit of 0.64pg/mL has been demonstrated for detection of cortisol. Alternately, a self-assembled monolayer (SAM) of dithiobis(succinimidylpropionte) (DTSP) has been fabricated for the modification of sensing electrode to immobilize with Anti-Cortisol antibodies. To increase the sensitivity at lower detection limit and to develop a point-of-care sensing platform, the DTSP-SAM has been fabricated on micromachined interdigitated microelectrodes (µIDE). Detection of cortisol is demonstrated at a sensitivity of 20.7µA/M and detection limit of 10pg/mL for a linear sensing range of 10pM to 200nM using the µIDE’s. A simple, low-cost microfluidic system is designed using low-temperature co-fired ceramics (LTCC) technology for the integration of the electrochemical cortisol immunosensor and automation of the immunoassay. For the first time, the non-specific adsorption of analyte on LTCC has been characterized for microfluidic applications. The design, fabrication technique and fluidic characterization of the immunoassay are presented. The DTSP-SAM based electrochemical immunosensor on µIDE is integrated into the LTCC microfluidic system and cortisol detection is achieved in the microfluidic system in a fully automated assay. The fully automated microfluidic immunosensor hold great promise for accurate, sensitive detection of cortisol in point-of-care applications.

Linearity analysis and comparison study on the epoc® point-of-care blood analysis system in cardiopulmonary bypass patients

The epoc® blood analysis system (Epocal Inc., Ottawa, Ontario, Canada) is a newly developed in vitro diagnostic hand-held analyzer for testing whole blood samples at point-of-care, which provides blood gas, electrolytes, ionized calcium, glucose, lactate, and hematocrit/calculated hemoglobin rapidly. The analytical performance of the epoc® system was evaluated in a tertiary hospital, see related research article “Analytical evaluation of the epoc® point-of-care blood analysis system in cardiopulmonary bypass patients” [1]. Data presented are the linearity analysis for 9 parameters and the comparison study in 40 cardiopulmonary bypass patients on 3 epoc® meters, Instrumentation Laboratory GEM4000, Abbott iSTAT, Nova CCX, and Roche Accu-Chek Inform II and Performa glucose meters.

Quality in palliative care from the patient perspective : Instrument development, perceptions of care received and the importance of care

The overall aim was to investigate the quality of palliative care from the patient perspective, to adapt and psychometrically evaluate the Quality from Patients’ Perspective instrument specific to palliative care (QPP-PC) and investigate the relationship between the combination of person- and organization-related conditions and patients’ perceptions of care quality. Methods: In the systematic literature review (I), 23 studies from 6 databases and reference lists in 2014 were synthesized by integrative thematic analysis. The quantitative studies (II–IV) had cross-sectional designs including 191 patients (73% RR) from hospice inpatient care, hospice day care, palliative units in nursing homes and home care in 2013–2014. A modified version of QPP was used. Additionally, person- and organization-related conditions were assessed. Psychometric evaluation, descriptive and inferential statistics were used. Main findings: Patients’ preferences for palliative care included living a meaningful life and responsive healthcare personnel, care environment and organization of care (I). The QPP-PC was developed, comprising 12 factors (49 items), 3 single items and 4 dimensions: medical–technical competence, physical–technical conditions, identity–oriented approach, and socio-cultural atmosphere (II). QPP-PC measured patients’ perceived reality (PR) and subjective importance (SI) of care quality. PR differed across settings, but SI did not (III). All settings exhibited areas of strength and for improvement (II, III). Person-related conditions seemed to be related to SI, and person- and organization-related conditions to PR, explaining 18–30 and 22-29% respectively of the variance (IV). Conclusions: The patient perspective of care quality (SI and PR) should be integrated into daily care and improvement initiatives in palliative care. The QPP-PC can measure patients’ perceptions of care quality. Registered nurses and other healthcare personnel need awareness of person- and organization-related conditions to provide high-quality person-centred care.

Feeling existentially touched - A phenomenological notion of the well-being of elderly living in special housing accommodation from the perspective of care professionals

This article presents a phenomenological analysis of interview material, in which 12 care professionals in elderly care reflect on the elderly's well-being within the frame of special housing accommodation. The perspective of the care professionals is of special interest. The findings show that the well-being is characterized as the elderly's feelings of being existentially touched. The well-being is an existential experience of being acknowledged as a human being and is an approach that classifies the elderly's needs as those of having, loving, and being. The meaning of the phenomenon is elucidated by the constituents: (1) to feel the freedom of choice, (2) to feel pleasure, and (3) to feel closeness to someone or something. The findings contribute new understanding of well-being in the elderly care by its existential dimension of the well-being as "just being'' and of doing things in order to experience meaningfulness. Accordingly, the well-being of the elderly as it is seen from the perspective of the care professionals involves both carers' subjectivity and intersubjectivity between the care professional and the elderly. An implication for promoting elderly's well-being is to develop awareness of these existential dimensions.

When a Change in Level of Care Results in a Transfer Between Programs

This project was chosen to investigate the criteria, process, procedures and policies in place for transferring patients of the Charleston Dorchester Mental Health Center between programs due to a change in their level of care in efforts to make the process more consistent and prevent or reduce gaps in care for patients.

Methodology of Care Humanitude in Promoting Self-care in Dependent People: An Integrative Review

Abstract. The aging of the population has led to an increase in the prevalence of chronic degenerative diseases and dependence. We need to implement humanized health care that will improve the quality of life and well-being of these people and help maintain their autonomy and self-care. Objective: To identify the implications of the caring in Humanitude in promoting self-care in the dependent person. Methods: Integrative review of the literature of the period between 2007 and 2015, using the databases Medline, EBSCO and Google Scholar. In using the PI[C]OD methodology and criteria for inclusion and exclusion, we obtained 54 items where 7 were selected for analysis. Results: There are several health benefits in the promotion of self-care, by ap-plying the Humanitude caring philosophy, mainly regarding the relationship be-tween the nurse and the patient. Conclusions: It is essential to develop further studies focused on the implications of caring in Humanitude in self-care in the dependent person.

Behaviour disorders and teacher negligence

The purpose of this paper is to examine the legal implications of the continuing rise in the number of school children diagnosed with behaviour disorders. Not only are teachers now subject to a dense grid of legal regulation, they are also increasingly vulnerable to actions in tort. It will be argued here that as more and more children are labelled ‘disordered’, the duty of care become more onerous, and hence harder for teachers to meet. As a consequence, teachers are more likely to face claims of negligence. It is concluded that while the schooling system needs to retain a healthy scepticism about each new pathologising disorder that seeks special status for its sufferers, it also needs to provide greater training and resources for teachers regarding disorder management. It is also concluded that recent changes to negligence law regarding the issue of ‘reasonable foreseeability’ within breach of duty of care, may not be as significant as might have been hoped by the teaching community. Indeed, the elevated standard of care required by the increasing numbers of disordered pupils, places teachers in an ever more difficult legal position.

Behaviour disorders and the negligent teacher

The purpose of this paper is to examine the legal implications of the continuing rise in the number of school children diagnosed with behaviour disorders. Not only are teachers now subject to a dense grid of legal regulation, they are also increasingly vulnerable to actions in tort. It will be argued here that as more and more children are labelled ‘disordered’, then the concomitant duty of care requirements for teachers becomes more onerous. As a consequence, teachers are less likely to be able to defend themselves against claims of negligence. It is concluded that while the schooling system needs to retain a healthy scepticism about each new pathologising disorder that seeks special status for its sufferers, it also needs to provide greater training and resources for teachers regarding disorder management. It is also concluded that recent changes to negligence law regarding the issue of ‘reasonable foreseeability’ within breach of duty of care, may not be as significant as might have been hoped by the teaching community. Indeed, the elevated standard of care, as required by increasing numbers of disordered pupils, place teachers in an ever more difficult legal position.

XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenografts

Mebendazole (MBZ) was identified as a promising therapeutic on the basis of its ability to induce apoptosis in melanoma cell lines through a B-cell lymphoma 2 (BCL2)-dependent mechanism. We now show that in a human xenograft melanoma model, oral MBZ is as effective as the current standard of care temozolomide in reducing tumor growth. Inhibition of melanoma growth in vivo is accompanied by phosphorylation of BCL2 and decreased levels of X-linked inhibitor of apoptosis (XIAP). Reduced expression of XIAP on treatment with MBZ is partially mediated by its proteasomal degradation. Furthermore, exposure of melanoma cells to MBZ promotes the interaction of SMAC/DIABLO with XIAP, thereby alleviating XIAP's inhibition on apoptosis. XIAP expression on exposure to MBZ is indicative of sensitivity to MBZ as MBZ-resistant cells do not show reduced levels of XIAP after treatment. Resistance to MBZ can be reversed partially by siRNA knockdown of cellular levels of XIAP. Our data indicate that MBZ is a promising antimelanoma agent on the basis of its effects on key antiapoptotic proteins.

Outcomes in gastric and junctional cancer using neoadjuvant and adjuvant chemotherapy (epirubicin, oxaliplatin, and capecitabine) and radical surgery

Background The MAGIC/UK Medical Research Council (MRC) trial set the standard of care for treatment of resectable gastric and junctional adenocarcinoma, demonstrating that perioperative chemotherapy with epirubicin, cisplatin and 5-fluorouracil (ECF) confers a survival benefit over surgery alone. The randomized ECF for advanced and locally advanced esophagogastric cancer (REAL-2) trial showed that, in the metastatic setting, the EOX regimen (epirubicin, oxaliplatin and capecitabine) is as effective as ECF, with a favourable toxicity profile. Methods Consecutive patients with resectable gastric or junctional adenocarcinoma treated with perioperative EOX, between 2007 and 2012, were retrospectively analysed. Results Fifty-nine patients (12 female, 47 male), commenced EOX therapy; 47 underwent surgery. A good pathological response was seen in 34 %, (16/47). Disease recurrence occurred in 19 patients (19/47, 40 %). Median overall survival was 22 months, with 4-year survival of 47 %. Chemotoxicities were consistent with those previously reported for this regimen. Conclusion This study in a high-volume centre demonstrates that EOX in resectable gastric and junctional adenocarcinoma is associated with a reasonable safety profile, and efficacy consistent with that reported for ECF.