Informed baseline subtraction of proteomic mass spectrometry data aided by a novel sliding window algorithm.

BACKGROUND: Proteomic matrix-assisted laser desorption/ionisation (MALDI) linear time-of-flight (TOF) mass spectrometry (MS) may be used to produce protein profiles from biological samples with the aim of discovering biomarkers for disease. However, the raw protein profiles suffer from several sources of bias or systematic variation which need to be removed via pre-processing before meaningful downstream analysis of the data can be undertaken. Baseline subtraction, an early pre-processing step that removes the non-peptide signal from the spectra, is complicated by the following: (i) each spectrum has, on average, wider peaks for peptides with higher mass-to-charge ratios (m/z), and (ii) the time-consuming and error-prone trial-and-error process for optimising the baseline subtraction input arguments. With reference to the aforementioned complications, we present an automated pipeline that includes (i) a novel 'continuous' line segment algorithm that efficiently operates over data with a transformed m/z-axis to remove the relationship between peptide mass and peak width, and (ii) an input-free algorithm to estimate peak widths on the transformed m/z scale. RESULTS: The automated baseline subtraction method was deployed on six publicly available proteomic MS datasets using six different m/z-axis transformations. Optimality of the automated baseline subtraction pipeline was assessed quantitatively using the mean absolute scaled error (MASE) when compared to a gold-standard baseline subtracted signal. Several of the transformations investigated were able to reduce, if not entirely remove, the peak width and peak location relationship resulting in near-optimal baseline subtraction using the automated pipeline. The proposed novel 'continuous' line segment algorithm is shown to far outperform naive sliding window algorithms with regard to the computational time required. The improvement in computational time was at least four-fold on real MALDI TOF-MS data and at least an order of magnitude on many simulated datasets. CONCLUSIONS: The advantages of the proposed pipeline include informed and data specific input arguments for baseline subtraction methods, the avoidance of time-intensive and subjective piecewise baseline subtraction, and the ability to automate baseline subtraction completely. Moreover, individual steps can be adopted as stand-alone routines.

Disability and Self-care Living Strategies Among Adults Living With HIV During the COVID-19 Pandemic.

BackgroundEvents associated with the COVID-19 pandemic, such as physical distancing, closure of community services, postponement of health appointments, and loss of employment can lead to social isolation, financial uncertainty, and interruption of antiretroviral adherence, resulting in additional health-related challenges (disability) experienced among adults living with chronic illness such as HIV. 'Living strategies' is a concept derived from the perspective of people living with HIV, defined as behaviors, attitudes and beliefs adopted by people living with HIV to help deal with disability associated with HIV and multi-morbidity. Our aim was to describe disability among adults living with HIV and self-care living strategies used during the COVID-19 pandemic. MethodsAdults living with HIV in Toronto, Ontario, Canada, including some with pre-pandemic HIV Disability Questionnaire (HDQ) data, completed a cross-sectional web-based survey between June-August 2020. The survey included the HDQ and questions about self-care living strategy use during the pandemic. We compared disability (HDQ) scores prior to versus during the pandemic using paired t-tests. We reported the proportion of participants who engaged in various living strategies at least 'a few times a week' or 'everyday' during the pandemic. ResultsOf the 63 respondents, 84% were men, median age 57 years, and 62% lived alone. During the pandemic the greatest disability severity was in the uncertainty (median 30; Interquartile range (IQR): 16, 43) and mental-emotional (25; IQR: 14, 41) domains. Among the 51 participants with pre-pandemic data, HDQ severity scores were significantly greater (worse) during the pandemic (vs prior) in all domains. Greatest change from prior to during the pandemic was in the mental-emotional domain for presence (17.7; p<0.001), severity (11.4; p<0.001), and episodic nature (9.3; p<0.05) of disability. Most participants (>60%) reported engaging a 'few times a week' or 'everyday' in self-care strategies associated with maintaining sense of control and adopting positive attitudes and beliefs. ConclusionsPeople living with HIV reported high levels of uncertainty and mental-emotional health challenges during the pandemic. Disability increased across all HDQ dimensions, with the greatest worsening in the mental-emotional health domain. Results provide an understanding of disability and self-care strategy use during the COVID-19 pandemic.

Barriers and facilitators to participation in work among Canadian women living with HIV/AIDS.

BACKGROUND: The impact of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) on the participation of women in paid/unpaid work is a little understood phenomenon. PURPOSE: A research study exploring the lived experiences of Canadian women's engagement in paid/unpaid work and the barriers and facilitators mediating this phenomenon. METHOD: Study design employed a phenomenological approach using data subanalysis of transcripts, double coded for agreement and to ensure saturation of themes. RESULTS: Analysis of the data revealed an overarching theme of engagement mediated by interacting forces with eight subthemes: active management, agency constrained by structure, the nature of supports, HIV/AIDS sequelae, work as a galvanizing force, the presence of children, the element of fear, and negotiation of self. IMPLICATIONS: Insights gained indicate a need for further education, resources, supports, and policy changes at the systems level. Occupational therapy is positioned to broaden the role of rehabilitation in the context of HIV/AIDS, episodic disability, and work participation.

HIV and rehabilitation: development of a conceptual framework for curriculum planning.

The overall purpose of this paper is to present the development of a conceptual framework of existing HIV curricula and educational resources on to inform future curriculum planning for the education of rehabilitation professionals on rehabilitation in the context of HIV/AIDS. We conducted a scoping review of the literature from 1980 onwards to identify existing HIV curricula and resources used with current or future health professionals. Preliminary findings were reviewed with a national Advisory Committee and a framework was developed to inform future curriculum planning. The Conceptual Framework of Existing HIV Curricula for Health Professionals classified curricula based on whether it was interprofessional or uniprofessional, and targeted to rehabilitation professionals or more broadly included other health professionals. This framework consisted of four intersecting components that represented different types of curricula: (a) interprofessional HIV curricula specific to rehabilitation professionals, (b) uniprofessional HIV curricula specific to rehabilitation professionals, (c) interprofessional HIV curricula for health professionals, and (d) uniprofessional HIV curricula for health professionals. Evidence from the framework suggested that an interprofessional HIV curriculum designed for rehabilitation professionals may be an ideal model from which to build future HIV rehabilitation curricula. In summary, a range of HIV curricula exist that vary in the type of educational approach and the range of health professionals targeted. Future development, implementation, and evaluation of an interprofessional education curriculum will help to increase knowledge and capacity among current and future rehabilitation professionals so that they may better meet the needs of people living with HIV/AIDS in Canada.

Genetic regulators of myelopoiesis and leukemic signaling identified by gene profiling and linear modeling.

Mechanisms controlling the balance between proliferation and self-renewal versus growth suppression and differentiation during normal and leukemic myelopoiesis are not understood. We have used the bi-potent FDB1 myeloid cell line model, which is responsive to myelopoietic cytokines and activated mutants of the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, having differential signaling and leukemogenic activity. This model is suited to large-scale gene-profiling, and we have used a factorial time-course design to generate a substantial and powerful data set. Linear modeling was used to identify gene-expression changes associated with continued proliferation, differentiation, or leukemic receptor signaling. We focused on the changing transcription factor profile, defined a set of novel genes with potential to regulate myeloid growth and differentiation, and demonstrated that the FDB1 cell line model is responsive to forced expression of oncogenes identified in this study. We also identified gene-expression changes associated specifically with the leukemic GM-CSF receptor mutant, V449E. Signaling from this receptor mutant down-regulates CCAAT/enhancer-binding protein alpha (C/EBPalpha) target genes and generates changes characteristic of a specific acute myeloid leukemia signature, defined previously by gene-expression profiling and associated with C/EBPalpha mutations.

A meeting of minds: interdisciplinary research in the health sciences in Canada.

Brought together by the newly formed Canadian Academy of Health Sciences (CAHS), recognized national leaders in the 6 health sciences disciplines consider the environment for conducting interdisciplinary health research (IDHR) in Canada. Based on first-hand knowledge and thoughtful reflection, the authors argue that although much progress has been made in support of IDHR in Canada, the practical experience of researchers does not always bear this out. This article examines government, industry and academia to identify the cultural and structural characteristics that demand, promote or prevent IDHR in each sector. At its heart is the question, How can universities best support and enhance IDHR, not only for the benefit of science, but also to meet the growing needs of industry and government for intellectual capital? Focusing on the predominant health sciences disciplines, the authors define IDHR as a team of researchers, solidly grounded in their respective disciplines, who come together around an important and challenging health issue, the research question for which is determined by a shared understanding in an interactive and iterative process. In addition, they suggest that IDHR is directly linked to translational research, which is the application of basic science to clinical practice and the generation of scientific questions through clinical observation. This analysis of academic, industry and government sectors is not intended to offer rigorous data on the current state of IDHR in Canada. Rather, the goal is to stimulate research-policy dialogue by suggesting a number of immediate measures that can help promote IDHR in Canada. Recommended measures to support IDHR are aimed at better resourcing and recognition (by universities and granting agencies), along with novel approaches to training, such as government-and industry-based studentships. In addition, we recommend that professional organizations reconsider their policies on publication and governance. Although intended to maintain professional scopes of practice, these policies also serve to entrench disciplinary boundaries in research. We conclude by suggesting a number of research questions for a more rigorous assessment of the climate for IDHR in Canada. We call for an inventory and comparative analysis of academic centres, institutes and consortiums in Canada that strive to facilitate IDHR; an examination of the impact of professional organizations on health research, and on IDHR in particular; and a systematic review of research training opportunities that promote IDHR, with a view to identifying and replicating proven models.

The Shoulder Pain and Disability Index demonstrates factor, construct and longitudinal validity.

BACKGROUND: The Shoulder Pain and Disability Index (SPADI) is a self-report measure developed to evaluate patients with shoulder pathology. While some validation has been conducted, broader analyses are indicated. This study determined aspects of cross-sectional and longitudinal validity of the SPADI. METHODS: Community volunteers (n = 129) who self-identified as having shoulder pain were enrolled. Patients were examined by a physical therapist using a standardized assessment process to insure that their pain was musculoskeletal in nature. This included examination of pain reported during active and passive shoulder motion as reported on a visual analogue pain scale. Patients completed the SPADI, the Coping Strategies Questionnaire (CSQ) and the Sickness Impact Profile (SIP) at a baseline assessment and again 3 and 6 months later. Factor analysis with varimax rotation was used to assess subscale structure. Expectations regarding convergent and divergent subscales of CSQ and SIP were determined a priori and analysed using Pearson correlations. Constructed hypotheses that patients with a specific diagnosis or on pain medication would demonstrate higher SPADI scores were tested. Correlations between the observed changes recorded across different instruments were used to assess longitudinal validity. RESULTS: The internal consistencies of the SPADI subscales were high (alpha > 0.92). Factor analysis with varimax rotation indicated that the majority of items fell into 2 factors that represent pain and disability. Two difficult functional items tended to align with pain items. Higher pain and disability was correlated to passive or negative coping strategies, i.e., praying/hoping, catastrophizing on the CSQ. The correlations between subscales of the SPADI and SIP were low with divergent subscales and low to moderate with convergent subscales. Correlations, r > 0.60, were observed between the SPADI and pain reported on a VAS pain scale during active and passive movement. The two constructed validity hypotheses (on diagnosis and use of pain medications) were both supported (p < 0.01). The SPADI demonstrated significant changes over time, but these were poorly correlated to the SIP or CSQ suggesting that these scales measure different parameters. CONCLUSION: The SPADI is a valid measure to assess pain and disability in community-based patients reporting shoulder pain due to musculoskeletal pathology.

A Mixed-Methods Outcome Evaluation of a Mentorship Intervention for Canadian Nurses in HIV Care.

We assessed the impact of an HIV care mentorship intervention on knowledge, attitudes, and practices with nurses and people living with HIV (PLWH) in Canada. We implemented the intervention in two urban and two rural sites with 16 mentors (eight experienced HIV nurses and eight PLWH) and 40 mentees (nurses with limited HIV experience). The 6- to 12-month intervention included face-to-face workshops and monthly meetings. Using a mixed-methods approach, participants completed pre- and postintervention questionnaires and engaged in semistructured interviews at intervention initiation, mid-point, and completion. Data from 28 mentees (70%) and 14 mentors (87%) were included in the quantitative analysis. We analyzed questionnaire data using McNemar test, and interview data using content analysis. Results indicated positive changes in knowledge, attitudes, and practices among nurse mentees, with qualitative interviews highlighting mechanisms by which change occurred. Mentorship interventions have the potential to engage and educate nurses in HIV treatment and care.

The angiographic and clinical benefits of mibefradil in the coronary slow flow phenomenon.

OBJECTIVES: The aim of the study was to assess the angiographic and clinical benefits of the calcium T-channel blocker, mibefradil, in the coronary slow flow phenomenon (CSFP). BACKGROUND: The CSFP is characterized by delayed vessel opacification on angiography (Thrombolysis In Myocardial Infarction [TIMI]-2 flow) in the absence of obstructive epicardial coronary disease and is often associated with recurrent chest pain. METHODS: A total of 10 CSFP patients (46 +/- 9 years) underwent angiography before and 30 min after 50 mg mibefradil; off-line blinded analysis of angiographic data included comparisons of epicardial vessel diameter, TIMI flow grade and TIMI frame count. We also performed a randomized, double-blind, placebo-controlled, cross-over study to examine the long-term efficacy of mibefradil 100 mg/day on the frequency of total angina, prolonged angina (i.e., persisting >20 min) episodes, and sublingual nitrate consumption, during consecutive one-month treatment periods in 20 patients (age 51 +/- 12 years) with the CSFP. RESULTS: Without changing epicardial vessel diameter or rate-pressure product, mibefradil reduced the number of vessels exhibiting TIMI-2 flow from 18 to 5; furthermore, mibefradil significantly improved the TIMI frame count only in those vessels exhibiting TIMI-2 flow (28 +/- 18%, p < 0.005). Compared with placebo, mibefradil significantly reduced total angina frequency by 56% (p < 0.001), prolonged episodes of angina by 74% (p < 0.001), and sublingual nitrate consumption by 59% (p < 0.01); furthermore, mibefradil improved physical quality of life as assessed by the Health Outcome Study Short Form-36. CONCLUSIONS: These angiographic and clinical improvements produced by mibefradil support a microspastic pathogenesis of the CSFP.

Understanding the experience of HIV/AIDS for women: implications for occupational therapists.

BACKGROUND: Within the past few years, HIV/AIDS has shifted from being an acute, palliative disease to one that is more chronic and episodic in nature. This shift has major implications for the role of occupational therapy in women's lives. Very few studies, however, have examined the perspective of women living with HIV/AIDS from an occupational therapy perspective. PURPOSE: This qualitative study was designed to examine the experiences of five women living with HIV/AIDS in Southern Ontario and to begin to explore the implications of these findings for occupational therapy. METHOD: Through the implementation of five in-depth interviews, a phenomenological approach was used to explore the lived experience of women with HIV/AIDS. RESULTS: Four main themes emerged: fearing disclosure, experiencing challenges (physical and psychological), having supportive networks, and coping positively with being HIV positive (spirituality and opportunity for living and learning). PRACTICE IMPLICATIONS: There are several potential roles for occupational therapy in working with women who are living with HIV/AIDS More studies need to be pursued in this area of rehabilitation.

Online interprofessional health sciences education: From theory to practice.

Online learning (e-learning) has a nascent but established history. Its application to interprofessional education (IPE), however, is relatively new. Over the past 2 decades the Internet has been used increasingly to mediate education. We have come past the point of "should we use the Internet for education" to "how should we use the Internet for education." Research has begun on the optimal development of online learning environments to support IPE. Developing online IPE should follow best practices in e-learning generally, though there are some special considerations for acknowledging the interprofessional context and clinical environments that online IPE is designed to support. The design, development, and deployment of effective online IPE must therefore pay special attention to the particular constraints of the health care worker educational matrix, both pre- and postlicensure. In this article we outline the design of online, interprofessional health sciences education. Our work has involved 4 educational and 4 clinical service institutions. We establish the context in which we situate our development activities that created learning modules designed to support IPE and its transfer into new interprofessional health care practices. We illustrate some best practices for the design of effective online IPE, and show how this design can create effective learning for IPE. Challenges exist regarding the full implementation of interprofessional clinical practice that are beginning to be met by coordinated efforts of multiple health care education silos.

Using a sampling strategy to address psychometric challenges in tutorial-based assessments.

INTRODUCTION: Tutorial-based assessment, despite providing a good match with the philosophy adopted by educational programmes that emphasize small group learning, remains one of the greatest challenges for educators working in this context. The current study was performed in an attempt to assess the psychometric characteristics of tutorial-based evaluation upon adopting a multiple sampling approach that requires minimal recording of observations. METHOD: After reviewing the literature, a simple 3-item evaluation form was created. The items were "Professional Behaviour," "Contribution to Group Process," and "Contribution to Group Content." Explicit definition of these items was provided on an evaluation form. Twenty five tutors in five different programmes were asked to use the form to evaluate their students (N=169) after every tutorial over the course of an academic unit. Each item was rated using a 10-point scale. RESULTS: Cronbach's alpha revealed an appropriate internal consistency in all five programmes. Test-retest reliability of any single rating was low, but the reliability of the average rating was at least 0.75 in all cases. The construct validity of the tool was supported by the observation of increasing ratings over the course of the academic unit and by the finding that more senior students received higher ratings than more junior students. CONCLUSION: Consistent with the context specificity phenomenon, the adoption of a "minimal observations often" approach to tutorial-based assessment appears to maintain better psychometric characteristics than do attempts to assess tutorial performance using more comprehensive measurement tools.

Defining the effect and mediators of two knowledge translation strategies designed to alter knowledge, intent and clinical utilization of rehabilitation outcome measures: a study protocol [NCT00298727].

BACKGROUND: A substantial number of valid outcome measures have been developed to measure health in adult musculoskeletal and childhood disability. Regrettably, national initiatives have merely resulted in changes in attitude, while utilization remains unacceptably low. This study will compare the effectiveness and mediators of two different knowledge transfer (KT) interventions in terms of their impact on changing knowledge and behavior (utilization and clinical reasoning) related to health outcome measures. METHOD/DESIGN: Physical and occupational therapists (n = 144) will be recruited in partnership with the national professional associations to evaluate two different KT interventions with the same curriculum: 1) Stakeholder-Hosted Interactive Problem-Based Seminar (SHIPS), and 2) Online Problem-Based course (e-PBL). SHIPS will consist of face-to-face problem-based learning (PBL) for 2 1/2 days with outcome measure developers as facilitators, using six problems generated in consultation with participants. The e-PBL will consist of a 6-week web-based course with six generic problems developed by content experts. SHIPS will be conducted in three urban centers in Canada. Participants will be block-allocated by a minimization procedure to either of the two interventions to minimize any prognostic differences. Trained evaluators at each site will conduct chart audits and chart-stimulated recall. Trained interviewers will conduct semi-structured interviews focused on identifying critical elements in KT and implementing practice changes. Interviews will be transcribed verbatim. Baseline predictors including demographics, knowledge, attitudes/barriers regarding outcome measures, and Readiness to Change will be assessed by self-report. Immediately post-intervention and 6 months later, these will be re-administered. Primary qualitative and quantitative evaluations will be conducted 6-months post-intervention to assess the relative effectiveness of KT interventions and to identify elements that contribute to changing clinical behavior. Chart audits will determine the utilization of outcome measures (counts). Incorporation of outcome measures into clinical reasoning will be assessed using an innovative technique: chart-stimulated recall. DISCUSSION: A strategy for optimal transfer of health outcome measures into practice will be developed and shared with multiple disciplines involved in primary and specialty management of musculoskeletal and childhood disability.