Comparability between wearable inertial sensors and an electronic walkway for spatiotemporal and relative phase data in young children aged 6-11 years.

BACKGROUND: Approaches to gait analysis are evolving rapidly and now include a wide range of options: from e-patches to video platforms to wearable inertial measurement unit systems. Newer options for gait analysis are generally more inclusive for the assessment of children, more cost effective and easier to administer. However, there is limited data on the comparability of newer systems with more established traditional approaches in young children. RESEARCH QUESTION: To determine comparability between the Physilog®5 wearable inertial sensor and GAITRite® electronic walkway for spatiotemporal (stride length, time and velocity, cadence) and relative phase (double support time, stance, swing, loading, foot flat and push off) data in young children. METHODS: A total 34 typically developing participants (41% female) aged 6-11 years old median age 8.99 years old (interquartile range 2.83) were assessed walking at self-selected speed over the GAITRite® electronic walkway while concurrently wearing shoe-attached Physilog®5 IMU sensors. Level of agreement was analysed by Lin's concordance correlation coefficient (CCC), Bland-Altman plots and 95% limit of agreement. Systematic bias was assessed using 95% confidence interval of the mean difference. RESULTS: Excellent to almost perfect agreement was observed between systems for spatiotemporal metrics: cadence (CCC=0.996), stride length (CCC=0.993), stride time (CCC=0.996), stride velocity (CCC=0.988). The relative phase metrics adjusted for stride velocity showed improved comparability when compared to the unadjusted metrics: swing adjusted (adj) (CCC=0.635); stance adj (CCC: 0.879); loading adj: (CCC=0.626). SIGNIFICANCE: Spatiotemporal metrics are highly compatible across GAITRite® electronic walkway and Physilog®5 IMU systems in young children. Relative phase metrics were somewhat compatible between systems when adjusted for stride velocity.

Population-based cohort study of oral contraceptive use and risk of depression.

AIM: Research on the effect of oral contraceptive (OC) use on the risk of depression shows inconsistent findings, especially in adult OC users. One possible reason for this inconsistency is the omission of women who discontinue OCs due to adverse mood effects, leading to healthy user bias. To address this issue, we aim to estimate the risk of depression that is associated with the initiation of OCs as well as the effect of OC use on lifetime risk of depression. METHODS: This is a population-based cohort study based on data from 264,557 women from the UK Biobank. Incidence of depression was addressed via interviews, inpatient hospital or primary care data. The hazard ratio (HR) between OC use and incident depression was estimated by multivariable Cox regression with OC use as a time-varying exposure. To validate causality, we examined familial confounding in 7,354 sibling pairs. RESULTS: We observed that the first 2 years of OC use were associated with a higher rate of depression compared to never users (HR = 1.71, 95% confidence interval [CI]: 1.55-1.88). Although the risk was not as pronounced beyond the first 2 years, ever OC use was still associated with an increased lifetime risk of depression (HR = 1.05, 95% CI: 1.01-1.09). Previous OC use were associated with a higher rate of depression compared to never users, with adolescent OC users driving the increased hazard (HR = 1.18, 95% CI: 1.12-1.25). No significant association were observed among adult OC users who had previously used OCs (HR = 1.00, 95% CI: 0.95-1.04). Notably, the sibling analysis provided further evidence for a causal effect of OC use on the risk of depression. CONCLUSIONS: Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life. Our results are consistent with a causal relationship between OC use and depression, as supported by the sibling analysis. This study highlights the importance of considering the healthy user bias as well as family-level confounding in studies of OC use and mental health outcomes. Physicians and patients should be aware of this potential risk when considering OCs, and individualized risk-benefit assessments should be conducted.

Provision of High Protein Foods Slows the Age-Related Decline in Nutritional Status in Aged Care Residents: A Cluster-Randomised Controlled Trial.

OBJECTIVES: Malnutrition, particularly protein insufficiency, is common in institutionalised older adults and increases morbidity, mortality, and costs. We aimed to determine whether 12 months supplementation using high-protein foods (milk, cheese, yoghurt) prevents malnutrition in older adults. DESIGN: Cluster randomised control study. SETTING: Sixty Australian aged care facilities. PARTICIPANTS: Older adults living in aged care homes (n=654, mean age 86.7±7.2 years, 72% females). Intervention Facilities randomly allocated to a high-protein (n=30 intervention) or regular (n=30 controls) menu. MEASUREMENTS: Nutritional status assessed using the Mini Nutrition Assessment (MNA) tool and fasting morning blood samples (n=302) assayed for haemoglobin (Hb) and albumin. Food intake was monitored 3-monthly using visual plate waste assessment. Measurements at baseline and month 12 were analysed using random effects model accounting for clustering (facility), repeated measure and confounders. RESULTS: Addition of 11g of protein as 1.5 servings of high-protein foods daily preserved nutritional status that deteriorated in controls [MNA screen (-0.68, 95%CI: -1.03, -0.32, p<0.001) and total (-0.90, 95%CI: -1.45, -0.35, p=0.001) scores], resulting in group differences in MNA screen (0.62, 95%CI: 0.17, 1.06, p=0.007) and total (0.81, 95%CI: 0.11, 1.51, p=0.023) scores and group difference in Hb (3.60g/L, 95%CI: 0.18, 7.03, p=0.039), the net result of preservation with intervention (0.19g/L, 95%CI: -2.04, 2.42, p=0.896) and a decline in controls (-3.41g/L, 95%CI: -6.01, -0.82, p=0.010). No group differences were observed for serum albumin. CONCLUSION: Consumption of high-protein foods is a pragmatic approach to maintaining nutritional status in older adults in aged-care.

Mechanistic insights into efficient peroxymonosulfate activation by NiCo layered double hydroxides.

The efficient removal of organic refractory pollutants such as dyes and antibiotics in wastewater is crucial for protecting the environment and human health. In this work, a NiCo-layered double hydroxide (NiCo-LDH) with a uniform microspherical, hierarchical structure and a high surface area was successfully synthesized as an effective peroxymonosulfate (PMS) activator for the degradation of various organic dyes and antibiotics. The influence of various parameters on the catalytic activity of the NiCo-LDH was determined. Radical scavenger studies unveiled the major reactive oxygen species (ROSs) generated in the NiCo-LDH/PSM system to be 1O2, SO4•-, and O2•-. Ex-situ X-ray photoelectron spectroscopy (XPS) analysis uncovered the role of Co sites and oxygen vacancy as active sites and revealed the reversible redox properties of NiCo-LDH based on Co2+/Co3+ cycles. The activation mechanism and Rhodamine B (RhB) degradation pathways were experimentally studied and proposed. The NiCo-LDH is highly versatile, reusable and stable as shown by post-catalysis characterizations. This work shows the excellent catalysis performances and provides insights into the activation mechanism of PMS by NiCo-LDH for organic pollutant remediation.

Validation of shoe-worn Gait Up Physilog®5 wearable inertial sensors in adolescents.

BACKGROUND: Gait Up Physilog® wearable inertial sensors are a powerful alternative to traditional laboratory-based gait assessment for children with gait impairment. To build clinician trust in these devices and ultimately facilitate their use outside confined spaces, studies have examined performance of previous versions of Physilog® wearable inertial sensors but predominant focus has been on older adults. Despite their different gait patterns and behavioural/cognitive profiles, there are limited studies in children. RESEARCH QUESTION: To determine whether key spatiotemporal gait parameters (stride length, time and velocity) collected by shoe-worn Physilog®5 sensors in a hallway assessment protocol are a valid method of gait assessment in typically developing adolescents aged 12-15 years. METHODS: A total 30 typically developing participants (50 % female) median age 13.7 (interquartile range 2.34) were assessed in an exploratory study whilst walking at self-selected speed over the GAITRite® electronic walkway, concurrently wearing Physilog®5 sensors. Concurrent validity was analysed by Lin's concordance correlation coefficient (CCC), Bland-Altman plots and 95 % limit of agreement. Systematic bias was assessed using 95 % confidence interval of the mean difference. RESULTS: Mean stride data demonstrated substantial agreement for stride length (CCC = 0.975) and stride velocity (CCC = 0.979) to almost perfect agreement for stride time (CCC > 0.996). Agreement between the technologies for individual stride-to-stride data remained high for stride time (CCC = 0.952); yet reduced for stride length (CCC = 0.868) and stride velocity (CCC = 0.877). Male/female differences in performance of the technology were observed for stride velocity, favouring females. SIGNIFICANCE: Physilog®5 inertial sensors accurately measure walking in adolescents, with stride time the most accurately detected parameter. This demonstrates that wearables can be used by researchers and clinicians working with adolescent groups as an alternative to fixed systems. These findings will ultimately pave the way to using wearables for assessments with children outside of the laboratory environment.

Effect of dietary sources of calcium and protein on hip fractures and falls in older adults in residential care: cluster randomised controlled trial.

OBJECTIVE: To assess the antifracture efficacy and safety of a nutritional intervention in institutionalised older adults replete in vitamin D but with mean intakes of 600 mg/day calcium and <1 g/kg body weight protein/day. DESIGN: Two year cluster randomised controlled trial. SETTING: 60 accredited residential aged care facilities in Australia housing predominantly ambulant residents. PARTICIPANTS: 7195 permanent residents (4920 (68%) female; mean age 86.0 (SD 8.2) years). INTERVENTION: Facilities were stratified by location and organisation, with 30 facilities randomised to provide residents with additional milk, yoghurt, and cheese that contained 562 (166) mg/day calcium and 12 (6) g/day protein achieving a total intake of 1142 (353) mg calcium/day and 69 (15) g/day protein (1.1 g/kg body weight). The 30 control facilities maintained their usual menus, with residents consuming 700 (247) mg/day calcium and 58 (14) g/day protein (0.9 g/kg body weight). MAIN OUTCOME MEASURES: Group differences in incidence of fractures, falls, and all cause mortality. RESULTS: Data from 27 intervention facilities and 29 control facilities were analysed. A total of 324 fractures (135 hip fractures), 4302 falls, and 1974 deaths were observed. The intervention was associated with risk reductions of 33% for all fractures (121 v 203; hazard ratio 0.67, 95% confidence interval 0.48 to 0.93; P=0.02), 46% for hip fractures (42 v 93; 0.54, 0.35 to 0.83; P=0.005), and 11% for falls (1879 v 2423; 0.89, 0.78 to 0.98; P=0.04). The risk reduction for hip fractures and falls achieved significance at five months (P=0.02) and three months (P=0.004), respectively. Mortality was unchanged (900 v 1074; hazard ratio 1.01, 0.43 to 3.08). CONCLUSIONS: Improving calcium and protein intakes by using dairy foods is a readily accessible intervention that reduces the risk of falls and fractures commonly occurring in aged care residents. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000228785.

An evaluation of the Chesapeake Bay management strategy to improve water quality in small agricultural watersheds.

Chesapeake Bay water quality has been a concern since 1970. In rural areas, agriculture is the dominant N and P source, and the voluntary application of best management practices (BMPs) is the primary management tool. Here we test the hypothesis that the current management approach of primarily voluntary, untargeted BMP implementation is insufficient to create detectable, widespread reductions in N, P, and total suspended solid (TSS) concentrations in agricultural watersheds of the Choptank basin, a tributary of Chesapeake Bay. To test this hypothesis, we assessed BMP implementation and sampled water quality on participating farms, at intermediate streams within each watershed, and at watershed outlets of four watersheds from 2013 to 2014. We also present water quality data from 2003 to 2014 at the outlets of 12 additional agricultural and one forested watershed and survey-directed interviews of farmers. By the end of 2014, large numbers of BMPs, both structural and cultural, had been implemented. Of the 16 agricultural watersheds, 50% showed significant decreases in baseflow N, 37.5% showed no changes, and 12.5% showed increasing TN. Baseflow P significantly decreased at just one watershed, increased at one, and remained stable at 14. Stormflow N was similar to baseflow, but stormflow P was 5 times higher than baseflow. These data partially support our hypothesis. Surveys suggested farmers considered themselves responsible for the quality of water leaving their farms, but out-of-pocket cost was the major impediment to further BMP adoption. We suggest that greater outreach and more financial support for farmers to implement BMPs is required to increase the types and densities of BMPs needed to achieve regional water quality goals.

Validation of the Job Content Questionnaire among hospital nurses in Vietnam.

OBJECTIVES: The aim of this study was to examine the reliability and validity of the Job Content Questionnaire (JCQ) in Vietnamese among hospital nursing staff. METHODS: The 22-items version of the JCQ was used. This includes four scales: (a) psychological demands (5 items); (b) job control (9 items); (c) supervisor support (4 items); and (d) coworker support (4 items). All 1258 nurses in a general hospital in Vietnam, excluding 11 who were due to retire, were invited to complete the cross-sectional survey. The internal consistency reliability was estimated using Cronbach's α. Construct validity was examined using exploratory factor analysis (EFA). Convergent validity was evaluated by calculating correlations between the JCQ scores and DASS 21 and overtime work. RESULTS: In total, 949 (75%) of the 1258 eligible nurses completed the survey. Cronbach's α values demonstrated acceptable internal consistency in two scales (supervisor support α = .87; coworker support α = .86), while Cronbach's α was below the acceptable threshold of 0.70 for job control (α = .45) and job demand (α = .50). EFA assuming a four-factor structure showed a factor structure that was almost identical to the original JCQ, with two items loading on other scales. The subscales of depression, anxiety, and stress response of DASS 21 and the subscales of JCQ were significantly correlated, as expected. CONCLUSION: The results suggest that the JCQ in Vietnamese can be used with some reliability and validity for examining psychosocial work environment among nurses. Further studies should be done to confirm and expand our findings in a variety of occupational groups and in other Asian low- and middle-income countries.

NTRK-1 fusion in endocervical fibroblastic malignant peripheral nerve sheath tumor marking eligibility for larotrectinib therapy: A case report.

•<1% of cervical cancers are sarcomas.•Data on neurofibrosarcoma management is scarce.•Larotrectinib is approved for NTRK1 gene fusion tumors without acquired resistance.•Targeted therapy of tumor genes may expand treatment for a rare cervical sarcoma.

Visualize the quality of frozen fish using fluorescence imaging aided with excitation-emission matrix.

The quality monitoring of frozen marine products has become essential in the fishery industry, where efficient and effective quality assurance is becoming increasingly important. In this study, we proposed a novel method of evaluating fish quality by combining the fluorescence excitation-emission matrix (EEM) with imaging techniques to visualize the spatial-temporal changes of freshness indices such as K-value and taste component IMP content. The result showed that the distribution of K-value and IMP content could be visualized with accuracy of R2 = 0.78 and R2 = 0.83, respectively. Furthermore, this innovative approach was applied to differentiate burnt meat, which is a type of abnormal meat found in many types of fish, and it was found that burnt meat could be detected even when in a frozen condition.

Determination of environmental flows in rivers using an integrated hydrological-hydrodynamic-habitat modelling approach.

We propose the novel integrated modelling procedure 3H-EMC for the determination of the environmental flow in rivers and streams; 3H-EMC combines Hydrological, Hydrodynamic and Habitat modelling with the use of the Environmental Management Classes (EMCs) that are defined by the Global Environmental Flow Calculator. We apply 3H-EMC in the Sperchios River in Central Greece, in which water abstractions for irrigation cause significant environmental impacts. Calculations of the hydrodynamic-habitat model, in which the large and the small chub are the main fish species, suggest discharge values that range from 1.0 m3/s to 4.0 m3/s. However, hydrological modelling indicates that it is practically difficult to achieve discharges that are higher than approximately 1.0-1.5 m3/s. Furthermore, legislation suggests significantly lower values (0.4-0.5 m3/s) that are unacceptable from the ecological point of view. This behaviour shows that a non-integrated approach, which is based only on hydrodynamic-habitat modelling does not necessarily result in realistic environmental flows, and thus an integrated approach is required. We propose the value of 1.0 m3/s as the "optimum" environmental flow for Sperchios River, because (a) it satisfies the habitat requirements, as expressed by the values of weighted useable area that are equal to 2180 and 1964 m2 for the large and small chub, respectively, and correspond to 82 and 95% of their respective maximum values, (b) it is consistent with the requirements of Environmental Classes A and B, whose percentiles are higher than 75% for discharge (77.2%) and for habitat availability (>83.5% for the large chub and >85.0% for the small chub), (c) it is practically achievable from the hydrological point of view, and (d) it is higher than the value proposed by the Greek legislation. The proposed modelling approach can be applied to any river or stream using the same or similar modelling tools, which should be linked via suitable coupling algorithms.

Predictors and consequences of health anxiety symptoms: a novel twin modeling study.

OBJECTIVE: The question of how to best conceptualize health anxiety (HA) from a diagnostic and etiological perspective remains debated. The aim was to examine the relationship between HA and the symptoms of anxiety and obsessive-compulsive-related disorders in a normative twin population. METHOD: Four hundred and ninety-six monozygotic adult twin pairs from the Australian Twin Registry participated in the study (age, 34.4 ± 7.72 years; 59% females). Validated scales were used to assess each domain. We applied a twin regression methodology-ICE FALCON-to determine whether there was evidence consistent with 'causal' relationships between HA and other symptoms by fitting and comparing model estimates. RESULTS: Estimates were consistent with higher levels of obsessing ('unwanted thoughts') (P = 0.008), social anxiety (P = 0.03), and body dysmorphic symptoms (P = 0.008) causing higher levels of HA symptoms, and with higher levels of HA symptoms causing higher levels of physical/somatic anxiety symptoms (P = 0.001). CONCLUSION: Obsessional thoughts, body dysmorphic concerns, and social anxiety symptoms may have a causal influence on HA. To report physical/somatic anxiety appears to be a consequence of the underlying presence of HA-related fears. Should our results be confirmed by longitudinal studies, the evaluation and treatment of HA may benefit from the consideration of these identified risk factors.

What are the differences among occupational groups related to their palliative care-specific educational needs and intensity of interprofessional collaboration in long-term care homes?

BACKGROUND: The purpose of this study was to compare the differences across occupational groups related to their end-of-life care-specific educational needs and reported intensity of interprofessional collaboration in long-term care (LTC) homes. METHODS: A cross-sectional survey, based on two questionnaires, was administered at four LTC homes in Ontario, Canada using a modified Dilman's approach. The first questionnaire, End of Life Professional Caregiver Survey, included three domains: patients and family-centered communication, cultural and ethical values, effective care delivery. The Intensity of Interprofessional Collaboration Scale included two subscales: care sharing activities, and interprofessional coordination. In total, 697 LTC staff were given surveys, including personal support workers, support staff (housekeeping, kitchen, recreation, laundry, dietician aids, office staff), and registered staff (licensed nurses, physiotherapists, social workers, pharmacists, physicians). RESULTS: A total of 317 participants completed the survey (126 personal support workers, 109 support staff, 82 registered staff) for a response rate of 45%. Significant differences emerged among occupational groups across all scales and subscales. Specifically, support staff rated their comfort of working with dying patients significantly lower than both nurses and PSWs. Support staff also reported significantly lower ratings of care sharing activities and interprofessional coordination compared to both registered staff and personal support workers. CONCLUSIONS: These study findings suggest there are differing educational needs and sense of interprofessional collaboration among LTC staff, specific to discipline group. Both the personal support workers and support staff groups appeared to have higher needs for education; support staff also reported higher needs related to integration on the interdisciplinary team. Efforts to build capacity within support staff related to working with dying residents and their families are needed. Optimal palliative care may require resources to increase the availability of support for all staff involved in the care of patients.

Mass Spectrometry-Based Methodology for Identification of Native Histone Variant Modifications From Mammalian Tissues and Solid Tumors.

Histone posttranslational modifications (PTMs) are key epigenetic marks involved in gene silencing or activation. Histone modifications impact chromatin organization and transcriptional processes through the changes in charge density between histones and DNA. They also serve as recognition and binding sites for specific binding proteins. Histone tails and globular cores contain many basic amino acid residues, which are subject to various dynamic modifications, making the modification repertoire extremely diverse. Consequently, determination of histone PTM identity and quantity has been a challenging task. In recent years, mass spectrometry-based methods have proven useful in histone PTM characterization. This chapter provides a brief overview of these methods and describes the approach to analyze the PTMs of the histone variant CENP-A, essential for the cell cycle progression, when present in minute amounts from tumor and mammalian tissues. Because this method does not rely on antibody-based immunopurification, we anticipate that these tools could be readily adaptable to the investigation to other histone variants in a range of mammalian tissues and solid tumors.

Long term renal survival in patients undergoing T-Cell depleted versus conventional hematopoietic stem cell transplants.

Calcineurin inhibitor (CNI)-sparing T-cell depleted (TCD) hematopoietic stem cell transplants (HSCTs) are presumed to be less nephrotoxic than conventional HSCTs. We evaluated incidence and risk factors for kidney failure and chronic kidney disease (CKD) in 231 TCD and 212 conventional HSCT recipients. Kidney failure required a median glomerular filtration rate (GFR) <60 ml/min/1.73 m2 for ⩾100 days anytime after 180-days post-HSCT. Two-year cumulative incidence (CI) of kidney failure was 42% in the conventional versus 31% in the TCD group (P=0.005). TCD, age, acute kidney injury and number of toxic CNI levels all impacted on kidney failure, which was associated with increased all-cause mortality (hazard ratio 2.86 (95% CI: 1.88-4.36), P<0.001). Renal recovery occurred in 28% of kidney failure patients whereas the remaining patients were defined to have CKD. In those with baseline GFR>60 ml/min/1.73 m2, only exposure to nephrotoxic medications was associated with CKD (P=0.033). In the myeloablative-conditioning subgroup only total body irradiation was associated with CKD (P=0.013). Of all patients, five (1.13%) required dialysis. These results confirm an impact of TCD on kidney failure but not CKD for which other risk factors such as radiation or nephrotoxic drug exposure may have a role.

Micronutrient status and intake in omnivores, vegetarians and vegans in Switzerland.

PURPOSE: Vegetarian and vegan diets have gained popularity in Switzerland. The nutritional status of individuals who have adopted such diets, however, has not been investigated. The aim of this study was to assess the intake and status of selected vitamins and minerals among vegetarian and vegan adults living in Switzerland. METHODS: Healthy adults [omnivores (OVs), n OV = 100; vegetarians (VGs), n VG = 53; vegans (VNs), n VN = 53] aged 18-50 years were recruited, and their weight and height were measured. Plasma concentrations of the vitamins A, C, E, B1, B2, B6, B12, folic acid, pantothenic acid, niacin, biotin and ß-carotene and of the minerals Fe, Mg and Zn and urinary iodine concentration were determined. Dietary intake was assessed using a three-day weighed food record, and questionnaires were issued in order to assess the physical activity and lifestyle of the subjects. RESULTS: Omnivores had the lowest intake of Mg, vitamin C, vitamin E, niacin and folic acid. Vegans reported low intakes of Ca and a marginal consumption of the vitamins D and B12. The highest prevalence for vitamin and mineral deficiencies in each group was as follows: in the omnivorous group, for folic acid (58 %); in the vegetarian group, for vitamin B6 and niacin (58 and 34 %, respectively); and in the vegan group, for Zn (47 %). Despite negligible dietary vitamin B12 intake in the vegan group, deficiency of this particular vitamin was low in all groups thanks to widespread use of supplements. Prevalence of Fe deficiency was comparable across all diet groups. CONCLUSIONS: Despite substantial differences in intake and deficiency between groups, our results indicate that by consuming a well-balanced diet including supplements or fortified products, all three types of diet can potentially fulfill requirements for vitamin and mineral consumption.

The effects of stress-tension on depression and anxiety symptoms: evidence from a novel twin modelling analysis.

BACKGROUND: Negative mood states are composed of symptoms of depression and anxiety, and by a third factor related to stress, tension and irritability. We sought to clarify the nature of the relationships between the factors by studying twin pairs. METHOD: A total of 503 monozygotic twin pairs completed the Depression Anxiety Stress Scales (DASS), an instrument that assesses symptoms of depression, anxiety and stress-tension. We applied a recently developed twin regression methodology - Inference about Causation from Examination of FAmiliaL CONfounding (ICE FALCON) - to test for evidence consistent with the existence of 'causal' influences between the DASS factors. RESULTS: There was evidence consistent with the stress-tension factor having a causal influence on both the depression (p < 0.0001) and anxiety factors (p = 0.001), and for the depression factor having a causal influence on the anxiety factor (p < 0.001). CONCLUSIONS: Our findings suggest a critical role for stress-tension in the structure of negative mood states, and that interventions that target it may be particularly effective in reducing depression and anxiety symptoms.

Chronic effects of stroke on hip bone density and tibial morphology: a longitudinal study.

UNLABELLED: The study aimed to quantify the long-term effects of stroke on tibial bone morphology and hip bone density. Only the trabecular bone mineral density and bone strength index in the hemiparetic tibial distal epiphysis showed a significant decline among individuals who had sustained a stroke 12-24 months ago. INTRODUCTION: This study aims to determine the changes in bone density and morphology in lower limb long bones during a 1-year follow-up period and their relationship to muscle function in chronic stroke patients. METHODS: Twenty-eight chronic stroke patients (12-166 months after the acute stroke event at initial assessment) and 27 controls underwent bilateral scanning of the hip and tibia using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, respectively. Each subject was re-assessed 1 year after the initial assessment. RESULTS: Twenty stroke cases and 23 controls completed all assessments. At the end of the follow-up, the paretic tibial distal epiphysis suffered significant decline in trabecular bone density (-1.8 ± 0.6 %, p = 0.006) and bone strength index (-2.7 ± 0.6 %, p < 0.001). More severe decline in the former was associated with poorer leg muscle strength (ρ = 0.447, p = 0.048) and motor recovery (ρ = 0.489, p = 0.029) measured at initial assessment. The loss in trabecular bone density remained significant among those whose stroke onset was 12-24 months ago (p < 0.001), but not among those whose stroke onset was beyond 24 months ago (p > 0.05) at the time of initial assessment. The changes of outcomes in the tibial diaphysis, except for cortical bone mineral content on the non-paretic side (-1.3 ± 0.3 %, p = 0.003), and hip bone density were well within the margin of error for precision. CONCLUSIONS: There is evidence of continuous trabecular bone loss in the paretic tibial distal epiphysis among chronic stroke patients, but it tends to plateau after 2 years of stroke onset. The steady state may have been reached earlier in the hip and tibial diaphysis.

Diagnostic assessment of osteosarcoma chemoresistance based on Virtual Clinical Trials.

Osteosarcoma is the most common primary bone tumor in pediatric and young adult patients. Successful treatment of osteosarcomas requires a combination of surgical resection and systemic chemotherapy, both neoadjuvant (prior to surgery) and adjuvant (after surgery). The degree of necrosis following neoadjuvant chemotherapy correlates with the subsequent probability of disease-free survival. Tumors with less than 10% of viable cells after treatment represent patients with a more favorable prognosis. However, being able to predict early, such as at the time of the pre-treatment tumor biopsy, how the patient will respond to the standard chemotherapy would provide an opportunity for more personalized patient care. Patients with unfavorable predictions could be studied in a protocol, rather than a standard setting, towards improving therapeutic success. The onset of necrotic cells in osteosarcomas treated with chemotherapeutic agents is a measure of tumor sensitivity to the drugs. We hypothesize that the remaining viable cells, i.e., cells that have not responded to the treatment, are chemoresistant, and that the pathological characteristics of these chemoresistant tumor cells within the osteosarcoma pre-treatment biopsy can predict tumor response to the standard-of-care chemotherapeutic treatment. This hypothesis can be tested by comparing patient histopathology samples before, as well as after treatment to identify both morphological and immunochemical cellular features that are characteristic of chemoresistant cells, i.e., cells that survived treatment. Consequently, using computational simulations of dynamic changes in tumor pathology under the simulated standard of care chemotherapeutic treatment, one can couple the pre- and post-treatment morphological and spatial patterns of chemoresistant cells, and correlate them with patient clinical diagnoses. This procedure, that we named 'Virtual Clinical Trials', can serve as a potential predictive biomarker providing a novel value-added decision support tool for oncologists.