The moderating role of psychological resilience in the relationship between fear of COVID-19 and psychological distress, in a cohort of rural and regional healthcare workers. During major lockdowns in Victoria, Australia 2020-2021.

The emergence of the COVID-19 pandemic resulted in substantial pressures for healthcare workers across the world. The association between fear of COVID-19 and psychological distress, and the role of psychological resilience have gained research interest. The current study aimed to investigate the cross-sectional association between fear of COVID-19 and psychological distress, in Australian rural/regional healthcare workers and determine whether resilience modifies this association. Most participants were nurses (38.0%), mean age was 44.9 years, and 80.5% were female (N = 1313). An adjusted logistic regression analysis showed that the highest tertile of the Fear of COVID-19 scale was associated with higher odds of moderate to severe symptoms of anxiety (OR = 3.72, 95% CI = 2.27, 6.11; p < 0.001) and depression (OR = 3.48, 95% CI = 2.30, 5.28; p < 0.001). Healthcare workers with high level of fear of COVID-19 and low level of resilience were much more likely to report moderate to severe symptoms of anxiety (OR = 12.27, 95% CI = 6.65-22.65, p < 0.001) and depression (OR = 12.21, 95% CI = 6.93-21.50, p < 0.001) when compared to healthcare workers with low level of fear of COVID-19 and high level of resilience. A cross-sectional design was used and therefore cause and effect between fear of COVID-19 and psychological distress cannot be inferred. Longitudinal research is needed to investigate the possible causal relationship. These findings highlight the potential mental health effects of fear of COVID-19 on HCWs and demonstrate the importance of resilience as a possible moderator of these effects.

Upconversion Nanoparticles as Imaging Agents for Dental Caries.

Dental caries (cavities) is the most prevalent disease worldwide; however, current detection methods suffer from issues associated with sensitivity, subjective interpretations, and false positive identification of carious lesions. Therefore, there is a great need for the development of more sensitive, noninvasive imaging methods. The 30 nm core@shell NaYF4; Yb20%, Er2%@NaYF4 upconversion nanoparticles (UCNPs), exhibiting strong upconversion emission from erbium upon excitation at 975 nm, were used in the imaging of locations of demineralized enamel and oral biofilm formation for the detection of dental caries. UCNPs were modified with poly(acrylic acid) (PAA) or poly-d-lysine (PDL), and targeting peptides were conjugated to their surface with affinity for either hydroxyapatite (HA), the material dentin is composed of, or the caries causing bacteria Streptococcus mutans. A statistical difference in the binding of targeted vs nontargeted UCNPs to HA was observed after 15 min, using both upconversion fluorescence of UCNP (p < 0.001) and elemental analysis (p = 0.0091). Additionally, using the HA targeted UCNPs, holes drilled in the enamel of bovine teeth with diameters of 1.0 and 0.5 mm were visible by the green emission after a 20 min incubation with no observable nonspecific binding. A statistical difference was also observed in the binding of targeted versus nontargeted UCNPs to S. mutans biofilms. This difference was observed after 15 min, using the fluorescence measurements (p = 0.0125), and only 10 min (p < 0.001) using elemental analysis via ICP-OES measurements of Y3+ concentration present in the biofilms. These results highlight the potential of these UCNPs for use in noninvasive imaging diagnosis of oral disease.

Learning by doing and creation of the shared discovery curriculum.

BACKGROUND: The Michigan State College of Human Medicine began as an experiment to teach medical students in community-based settings and to create a primary care workforce for the state. Decades later, CHM faced internal and external challenges that spurred creation of a new curriculum - the Share Discovery Curriculum - founded on learning by doing and other learning theories. METHODS: A curricular design group (CDG) developed guiding principles for reform. Based on this, pedagogies and structures were selected to achieve this vision and developed into a curricular structure. Components of the first-year curriculum were piloted with a group of students and faculty members. RESULTS: Six guiding principles were endorsed, grounded in learning theories such as Dewey's Learning by Doing. Based upon these, several key features of the new curriculum emerged: learning communities; one-on-one coaches for students; symptom-based presentations for content; simulation, authentic clinical tasks, flipped classrooms, and modified practice-based learning as primary teaching modalities; early, integrated clinical and scientific learning; milestones as course learning objectives; and a multidimensional, competency-based assessment system. DISCUSSION: The process and outcomes described here are intended as an exemplar for schools undertaking curricular change. Early stakeholder engagement, faculty development, sustainable administrative systems, and managing complexity are core to the success of such endeavors.

Growth in basic science knowledge in first-year medical school and USMLE Step 1 results: a longitudinal investigation at one school.

PURPOSE: Our US medical school uses National Board of Medical Examiners (NBME) tests as progress tests during the pre-clerkship curriculum to assess students. In this study, we examined students' growth patterns using progress tests in the first year of medical school to identify students at risk for failing United States Medical Licensing Examination (USMLE) Step 1. METHOD: Growth Mixture Modeling (GMM) was used to examine the growth trajectories based on NBME progress test scores in the first year of medical school. Achieving a passing score on the USMLE Step 1 at the end of the second year of medical school was used as the distal outcome, controlling for Medical College Admissions Test (MCAT) scores and underrepresented in medicine (URiM) status. RESULTS: A total of 518 students from a US medical school were included in the analysis. Five different growth patterns were identified based on students' NBME test results. Seventy-eight students identified in Group 1 had the lowest starting NBME test score (mean = 33.6, 95% CI 32.0-35.2) and lowest growth rate (mean = 2.30, 95% CI 2.06-2.53). All 26 students who failed Step 1 at the end of the second year were in Group 1 (failing rate = 33%). Meanwhile Group 4 (n = 65 students) had moderate starting NBME test scores (mean = 37.9, 95% CI 36.3-39.0) but the highest growth rate with mean slope at 6.07 (95% CI 5.40-6.73). This group of students achieved significant higher USMLE Step1 scores comparing with the 3 other groups of students (P < 0.05). CONCLUSIONS: Our study found students had heterogeneous growth patterns in progress test results in their first year of medical school. Growth patterns were highly predictive of USMLE step 1 results. This study can provide performance benchmarks for our future students to assess their progress and for medical educators to identify students who need support and guidance.

Mealtime Support: A Pilot Case Series study of an Effective, Cost-saving Outpatient Hunger-Based Feeding Program for Tube Dependency.

Tube feeding is essential for children who cannot meet nutritional requirements orally. Over time, this can lead to tube dependency with negative impacts on the quality of life of children and families. Objective: We aimed to examine the efficacy of a multidisciplinary child-led, hunger-based approach called "Mealtime Support" at the Stollery Children's Hospital in Edmonton. Nutritional outcomes, parental satisfaction, and cost implications were evaluated over 9 months postprogram completion per child. Methods: The ambulatory meal program was delivered 2-3 times a day, for 2 weeks, by an occupational therapist and dietitian, under medical supervision. Hunger was promoted by reducing tube fed calories by 80% before commencement. Caregivers completed 12-question subjective surveys pre- and postintervention. Microcosting methods compared costs between the program and ongoing tube feeding. Results: From 2016 to 2017, 6 children were enrolled and 5 completed the program. At 1-month postintervention, 4/5 of the children were 100% orally fed. Parents reported improvement in mealtime struggles (P = 0.005), reduction in worry about their child's eating (P = 0.005), and improvement in their child's appetite/variety foods eaten (P = 0.004). Over 2 years, the potential cost savings were estimated at $43,471.00. By 6 months, all feeding tubes were removed. Conclusions: Mealtime support was safe and successful in reducing tube dependency and cost-effective compared to no intervention or hospital based programs, which suggests that there is a need to develop and fund Canadian outpatient feeding programs.

Loddon Mallee healthcare worker COVID-19 study-protocol for a prospective cohort study examining the health and well-being of rural Australian healthcare workers during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic is creating immense psychosocial disturbance. While global, broad-based research is being conducted, little is known about the effects of the COVID-19 pandemic on health and well-being or how protective and resilience factors influence the human response in Australian rural and regional communities. Rural and regional communities often have less resources to deal with such public health emergencies and face additional environmental adversity. Healthcare workers, including those in rural and regional areas, have felt the immediate impacts of COVID-19 in a multitude of ways and these impacts will continue for years to come. Therefore, this study aims to describe and understand the impacts of the COVID-19 pandemic on the rural and regional healthcare workforce within the Loddon Mallee region, Victoria, Australia. METHODS AND ANALYSIS: This prospective cohort of rural and regional healthcare workers will be recruited and followed over 3 years to examine the effects of the COVID-19 pandemic on their health and well-being. Self-administered online questionnaires will be administered every 6 months for a 36-month period. Multiple outcomes will be assessed; however, the primary outcomes are emotional health and well-being and psychological resilience. Emotional health and well-being will be measured using validated instruments that will assess multiple domains of the emotional health and well-being continuum.Linear and logistic regression and latent growth curve modelling will be used to examine the association between baseline and follow-up participant emotional health, well-being and resilience while adjusting for potentially time-varying confounding variables. Participant characteristics measured at baseline will also be tested for association with incident health, morbidity, mortality and health service utilisation outcomes at follow-up. ETHICS AND DISSEMINATION: Ethical approval has been obtained through the Bendigo Health Human Research Ethics Committee. The study findings will be disseminated through international conferences, international peer-reviewed journals and social media. TRIAL REGISTRATION NUMBER: ACTRN12620001269921.

Using Markov chain model to evaluate medical students' trajectory on progress tests and predict USMLE step 1 scores---a retrospective cohort study in one medical school.

BACKGROUND: Medical students must meet curricular expectations and pass national licensing examinations to become physicians. However, no previous studies explicitly modeled stages of medical students acquiring basic science knowledge. In this study, we employed an innovative statistical model to characterize students' growth using progress testing results over time and predict licensing examination performance. METHODS: All students matriculated from 2016 to 2017 in our medical school with USMLE Step 1 test scores were included in this retrospective cohort study (N = 358). Markov chain method was employed to: 1) identify latent states of acquiring scientific knowledge based on progress tests and 2) estimate students' transition probabilities between states. The primary outcome of this study, United States Medical Licensing Examination (USMLE) Step 1 performance, were predicted based on students' estimated probabilities in each latent state identified by Markov chain model. RESULTS: Four latent states were identified based on students' progress test results: Novice, Advanced Beginner I, Advanced Beginner II and Competent States. At the end of the first year, students predicted to remain in the Novice state had lower mean Step 1 scores compared to those in the Competent state (209, SD = 14.8 versus 255, SD = 10.8 respectively) and had more first attempt failures (11.5% versus 0%). On regression analysis, it is found that at the end of the first year, if there was 10% higher chance staying in Novice State, Step 1 scores will be predicted 2.0 points lower (95% CI: 0.85-2.81 with P < .01); while 10% higher chance in Competent State, Step 1scores will be predicted 4.3 points higher (95% CI: 2.92-5.19 with P < .01). Similar findings were also found at the end of second year medical school. CONCLUSIONS: Using the Markov chain model to analyze longitudinal progress test performance offers a flexible and effective estimation method to identify students' transitions across latent stages for acquiring scientific knowledge. The results can help identify students who are at-risk for licensing examination failure and may benefit from targeted academic support.

Victorian Lung Cancer Service Redesign Project: impacts of a quality improvement collaborative on timeliness and management in lung cancer.

BACKGROUND: Lung cancer management is characterised by a high disease burden, poor survival and substantial variation in management and outcomes. Service redesign provides opportunities for quality improvement (QI) and this improvement may be leveraged across multiple sites using QI collaboration. AIM: This initiative targeted Quality Improvement (QI) in lung cancer management, engaging a QI collaborative using service redesign methodologies in five Victorian hospitals. QI targets included timeliness from referral and diagnosis to treatment, multi-disciplinary meeting (MDM) presentation and supportive care screening. Redesign strategies targeted process sustainability through enhanced team capability. METHODS: This study engaged a prospective quality improvement cohort design targeting newly diagnosed tissue confirmed lung cancer with 6-month pre-intervention period and 6-month redesign implementation period, between September 2016 and August 2017, evaluated using Interrupted Time Series Analysis. Hospital sites included three regional and two metropolitan hospitals in Victoria. QI redesign targeted time intervals from referral to first specialist appointment (FSA), referral to diagnosis, diagnosis to first treatment (any intent), MDM documented in medical records and Supportive Care Screening Tool documented in medical records. RESULTS: There was a marked reduction in referral to FSA interval across all sites, with median (interquartile range) falling from 6 (0-15) to 4 (1-10) days, and proportion seen by a specialist within 14 days increased from 74.3% to 84.2%. The interval between diagnosis and treatment was not substantively changed in the 6-month implementation period. The proportion of subjects with documented presentation to the MDM increased from 61% to 67%. The proportion for which Supportive Care Screening documentation remained low at 26.3% post-intervention. CONCLUSIONS: Data-driven redesign initiatives enable identification and analysis of clinical practice variation and may be utilised to enhance timeliness of cancer care and improve local data service capabilities.

Timeliness of cancer care in a regional Victorian health service: A comparison of high-volume (Lung) and low-volume (oesophagogastric) tumour streams.

BACKGROUND: Timeliness of cancer care is vital for improved survival and quality of life of patients. Service and care centralisation at larger-volume centres has been associated with improved outcomes. However, there is a lack of systematic data on the impact of tumour stream volume on timeliness of care. AIMS: To investigate and compare timeliness of care for lung cancer, a high-volume (more commonly diagnosed) tumour stream, and oesophagogastric (OG) cancer, a low-volume (less commonly diagnosed) tumour stream, at a regional health service in Victoria, Australia. METHODS: A retrospective cohort study comprising random samples of 75 people newly diagnosed with lung cancer (International Classification of Diseases and Related Health Problems-10 [ICD-10] diagnosis codes C34 in the Victorian Cancer Registry [VCR]) and 50 people newly diagnosed with OG cancer (ICD-10 diagnosis codes C15 or C16 in VCR) at one regional Victorian health service between 2016 and 2017. Binary logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between patient factors and suboptimal timeliness of care. RESULTS: In comparison to OG cancer patients, lung cancer patients had reduced odds of suboptimal timeliness of care in reference to times outside OCP for referral to diagnosis (OR [95% CI] = 0.34 [0.14 to 0.83]) but increased odds of suboptimal timeliness for diagnosis to treatment (OR [95% CI] = 2.48 [1.01 to 6.09]). CONCLUSION: In the low-volume OG cancer stream, patients had longer wait times from referral to an MDM, where treatment decisions occur, but shorter time to commencement of first treatment. Conversely in the high-volume lung cancer group, there was delayed initiation of first treatment following presentation at MDM. There is need to explore ways to fast-track MDM presentation and commencement of therapy among people diagnosed with low-volume and high-volume cancers, respectively.

Medical Student Progress Examination Performance and Its Relationship With Metacognition, Critical Thinking, and Self-Regulated Learning Strategies.

PURPOSE: Metacognition and critical thinking are essential for academic success. The relationship between these components and medical student learning, as assessed with progress examinations, informs curriculum development and efforts to ensure learning progression of all students. This study assessed learning mechanisms by modeling medical students' progress test performance longitudinally at Michigan State University College of Human Medicine. METHOD: Medical students' (n = 184) medical knowledge was assessed 5 times from fall 2017 through spring 2019 using the Comprehensive Basic Science Examination (CBSE). Structural equation modeling was conducted to investigate associations between 3 latent structures-metacognitive awareness, critical thinking, and self-regulation-and their relationship with students' initial CBSE scores and growth in such scores. The authors measured metacognitive knowledge and regulation by the Metacognitive Awareness Inventory, critical thinking skills by the Watson-Glaser Critical Thinking Appraisal, and self-regulation by the Learning and Study Strategies Inventory. RESULTS: Students' aggregate performance on 5 CBSE scores grew 31.0% the first semester, 16.5% the second semester, 30.1% the third semester, and 22.4% the last semester. Critical thinking had a significant positive relationship with initial performance (JOURNAL/acmed/04.03/00001888-202102000-00048/inline-graphic1/v/2021-01-22T214722Z/r/image-tiff1.956, P < .001), self-regulation had a significant positive relationship with growth (JOURNAL/acmed/04.03/00001888-202102000-00048/inline-graphic2/v/2021-01-22T214722Z/r/image-tiff3.287, P < .05), and metacognitive awareness had a negative relationship with growth of student performance in the progress test (JOURNAL/acmed/04.03/00001888-202102000-00048/inline-graphic3/v/2021-01-22T214722Z/r/image-tiff-3.426, P < .01). CONCLUSIONS: This structural equation framework is useful for examining the relationships among 3 latent structures-critical thinking, metacognition, and self-regulation-and their relationships with students' progress scores in academic achievement. The initial status of progress examination scores was explained by students' critical thinking ability, but their learning growth on the progress scores was explained by their self-regulation and metacognitive ability. These findings help explain student performance on standardized progress examinations and can aid in interventions to promote student success.

Assessing the growth in clinical skills using a progress clinical skills examination.

BACKGROUND: This study evaluates the generalizability of an eight-station progress clinical skills examination and assesses the growth in performance for six clinical skills domains among first- and second-year medical students over four time points during the academic year. METHODS: We conducted a generalizability study for longitudinal and cross-sectional comparisons and assessed growth in six clinical skill domains via repeated measures ANOVA over the first and second year of medical school. RESULTS: The generalizability of the examination domain scores was low but consistent with previous studies of data gathering and communication skills. Variations in case difficulty across administrations of the examination made it difficult to assess longitudinal growth. It was possible to compare students at different training levels and the interaction of training level and growth. Second-year students outperformed first-year students, but first-year students' clinical skills performance grew faster than second-year students narrowing the gap in clinical skills over the students' first year of medical school. CONCLUSIONS: Case specificity limits the ability to assess longitudinal growth in clinical skills through progress testing. Providing students with early clinical skills training and authentic clinical experiences appears to result in the rapid growth of clinical skills during the first year of medical school.

Exploring the relationship between body mass index, mental health and outcomes of a regional physiotherapy-led post-arthroplasty review clinic.

OBJECTIVE: To determine whether 12-month hip and knee outcomes of a regional arthroplasty clinic were comparable to results from metropolitan-based clinics, and to explore a possible relationship between body mass index and depression to identify groups at risk of not achieving optimal outcomes. DESIGN: A prospective observational study. SETTING: A regional physiotherapy-led post-arthroplasty review clinic. PARTICIPANTS: Patients after hip or knee replacement. INTERVENTIONS: Patients underwent either total hip or total knee joint arthroplasty. MAIN OUTCOME MEASURES: SF-12 Health Survey, Oxford Hip/Knee Scale, 10-minute walk test, knee range of motion, body mass index and the Hospital Anxiety and Depression Scale. RESULTS: Physical outcomes were comparable to those reported by metropolitan-based clinics. People with a high body mass index showed most improvement in the severity of depression compared to those with a lower body mass index. CONCLUSION: It is important to consider the long-term effects of obesity on arthroplasty outcomes.

Mass Spectrometric Determination of Protein Ubiquitination.

Mass spectrometric methods of determining protein ubiquitination are described. Characteristic mass shifts and fragment ions indicating ubiquitinated lysine residues in tryptic and gluC digests are discussed. When a ubiquitinated protein is enzymatically digested, a portion of the ubiquitin side chain remains attached to the modified lysine. This "tag" can be used to distinguish a ubiquitinated peptide from the unmodified version, and can be incorporated into automated database searching. Several tags are discussed, the GGK and LRGGK tags, resulting from complete and incomplete tryptic digestion of the protein, and the STLHLVLRLRGG tag from a gluC-digested protein.A ubiquitinated peptide has two N-termini-one from the original peptide and the other from the ubiquitin side chain. Thus, it is possible to have two series of b ions and y ions, the additional series is the one that includes fragments containing portions of the ubiquitin side chain, and any diagnostic ions for the modification must include portions of this side chain. Fragment ions involving any part of the "normal" peptide will vary in mass according to the peptide being modified and will therefore not be of general diagnostic use. These diagnostic ions, found through examination of the MS/MS spectra of model ubiquitinated tryptic and gluC peptides, have not previously been reported. These ions can be used to trigger precursor ion scanning in automated MS/MS data acquisition scanning modes.

Attendance, engagement and performance in a medical school curriculum: early findings from competency-based progress testing in a new medical school curriculum.

INTRODUCTION: Medical students often do not value attending in-person large group sessions. It is also not clear from prior research whether attendance at large group sessions impact on performance in medical school. The goal of this study was to assess the relationship between voluntary attendance in large group sessions organized as a "flipped classroom" in a new innovative curriculum and students' mastery of clinical applications of basic science knowledge. METHODOLOGY: Our students' ability to apply basic science knowledge to clinical problems is assessed via progress testing using three methodologies: a locally developed multiple-choice examination, written examination developed through the National Board of Medical Examiners (NBME) Customized Assessment Services Program and post encounter questions included in a clinical skills examination. We analyzed the relationship between voluntary attendance at weekly large group "flipped classroom" sessions and the students' performance on examinations given at four intervals over the initial 24-week module of the medical school curriculum. RESULTS: Complete data were available for 167 students. A total of 82 students (49.1%) attended all large group sessions, 65 students (38.9%) missed one or two sessions and 20 students (12.0%) missed three or more sessions. There were no difference between the students in the groups on their medical admission (MCAT) examination scores. The growth in performance from each time point until the next was statistically significant. There was no statistically significant difference in growth between the students who had no absences and those who had one or two absences. Students who missed three or more sessions performed significantly lower than their peers over the 24 week module and were more likely to score one or more standard deviations below the class mean on the assessments. CONCLUSIONS: We found no relationship between attendance and MCAT scores suggesting the differences in performance on the progress tests was not due to initial differences in knowledge or reasoning skills. While the study was not experimental, it suggests large group sessions using a "flipped classroom" approach to provide reinforcement, feedback and practice may be effective for increasing learning and retention in the application of basic science knowledge among first year medical students.

Health information exchanges--Unfulfilled promise as a data source for clinical research.

OBJECTIVE: To determine the use of health information exchange organizations (HIEs) to support and conduct clinical research. MATERIALS AND METHODS: This scoping review included US-based studies published between January 2003 and March 2014 that used data from an HIE to address at least one of three categories of research: clinical or epidemiological research, financial evaluation, or utilization of health services. Eligibility was not restricted to research on HIEs. Studies with research questions outside of the evaluation of HIEs themselves were sought. RESULTS: Eighteen articles met final study inclusion criteria from an initial list of 847 hits. Fifteen studies addressed a clinical or epidemiological research question, 6 addressed a financial consideration, and 8 addressed a utilization issue. Considerable overlap was found among the research categories: 13 articles addressed more than one category. Of the eighteen included studies, only two used HIE data to answer a research objective that was NOT specific to HIE use. Research designs were varied and ranged from observational studies, such as cohort and cross-sectional studies, to randomized trials. The 18 articles represent the involvement of a small number of HIEs; 7 of the studies were from a single HIE. DISCUSSION: This review demonstrates that HIE-provided information is available and used to answer clinical or epidemiological, financial, or utilization-based research questions; however, the majority of the studies using HIE data are done with the primary goal of evaluating the use and impact of HIEs on health care delivery and outcomes. As HIEs mature and become integrated parts of the health care industry, the authors anticipate that fewer studies will be published that describe or validate the role of HIEs, and more will use HIEs as multi-institutional data sources for conducting clinical research and improving health services and clinical outcomes. CONCLUSION: Articles identified in this review indicate the limited extent that HIE data are being used for clinical research outside of the evaluation of HIEs themselves, as well as the limited number of specific HIEs that are involved in generating published research. Significant barriers exist that prevent HIEs from developing into an invaluable resource for clinical research including technological infrastructure limitations, business processes limiting secondary use of data, and lack of participating provider support. Research to better understand challenges to developing the necessary infrastructure and policies to foster HIE engagement in research would be valuable as HIEs represent an opportunity to engage non-traditional health care provider research partners.

Randomized controlled trial of the effect of additional functional exercise during slow-stream rehabilitation in a regional center.

OBJECTIVE: To evaluate whether adding functional exercise training to standard physiotherapy during residential slow-stream rehabilitation (SSR) improves discharge outcomes and functional ability. DESIGN: Randomized controlled trial. SETTING: A regional hospital. PARTICIPANTS: Older people (N=60) admitted to SSR. INTERVENTION: All participants received standard physiotherapy. An individualized functional incidental training (FIT) program was implemented for intervention participants consisting of 4 extra episodes of functional exercise daily for the period of SSR. Research assistants visited twice weekly to practice and progress FIT programs. MAIN OUTCOME MEASURES: Outcome measures included discharge destination, participant-expected discharge destination, and functional tests of the Berg Balance Scale (BBS), de Morton Mobility Index (DEMMI), and 5 times sit-to-stand test (FTSTS) at admission and discharge. RESULTS: Fifty-two participants completed the study. At baseline, the SSR group achieved higher scores on the BBS, DEMMI, and FTSTS. There was no significant difference in discharge destination between groups (P=.305). The difference in functional change between groups from admission to discharge on the BBS, DEMMI, and FTSTS was not significant. Participant-expected discharge destination was significantly associated with eventual discharge destination (χ1(2)=8.40, P=.004). CONCLUSIONS: Adding FIT to standard physiotherapy did not improve discharge outcomes and did not have a statistically significant effect on function, but may have a small effect on balance. Patient expected and actual discharge destinations were associated.

Subzero temperature chromatography and top-down mass spectrometry for protein higher-order structure characterization: method validation and application to therapeutic antibodies.

Characterization of the higher-order structure and structural dynamics of proteins is crucial for in-depth understanding of their functions. Amide hydrogen/deuterium exchange (HDX), monitored by mass spectrometry (MS), is now a popular technique for measuring protein higher-order structural changes. Although the proteolysis-based HDX-MS approach is most commonly used, the "top-down" approach, which fragments intact proteins directly using electron-based dissociation, is becoming an important alternative and has several advantages. However, the commonly used top-down strategies are direct-infusion based and thus can only be used with volatile buffers. This has meant that the "top-down" approach could not be used for studying proteins under physiological conditions-the very conditions which are often very important for preserving a protein's native structure and function. More complex proteins such as those with disulfide bonds present another challenge. Therefore, there is significant interest in developing novel top-down HDX methods that are applicable to all types of protein samples. In this paper, we show how top-down electron capture dissociation and subzero temperature HPLC can be combined and used for this purpose. This method keeps the back-exchange level as low as 2% and has no limitations in terms of protein type and sample solution conditions. Close to single-residue level protein structural information can be generated. The new method is validated through comparison with NMR data using calmodulin as a model protein. Its capability of determining structural changes in therapeutic antibodies (Herceptin) is also demonstrated.