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Supplemental Digital Content is available in the text., Precis: Multiple questionnaires exist to measure glaucoma’s impact on quality of life (QoL). Selecting the right questionnaire for the research question is essential, as is patients’ acceptability of the questionnaire to enable collection of relevant patient-reported outcomes. Purpose: QoL relating to a disease and its treatment is an important dimension to capture. This scoping review sought to identify the questionnaires most appropriate for capturing the impact of glaucoma on QoL. Methods: A literature search of QoL questionnaires used in glaucoma, including patient-reported outcomes measures, was conducted and the identified questionnaires were analyzed using a developed quality criteria assessment. Results: Forty-one QoL questionnaires were found which were analyzed with the detailed quality criteria assessment leading to a summary score. This identified the top 10 scoring QoL questionnaires rated by a synthesis of the quality criteria grid, considering aspects such as reliability and reproducibility, and the authors’ expert clinical opinion. The results were ratified in consultation with an international panel of ophthalmologists (N=49) from the Educational Club of Ocular Surface and Glaucoma representing 23 countries. Conclusions: Wide variability among questionnaires used to determine vision related QoL in glaucoma and in the responses elicited was identified. In conclusion, no single existing QoL questionnaire design is suitable for all purposes in glaucoma research, rather we have identified the top 10 from which the questionnaire most appropriate to the study objective may be selected. Development of a new questionnaire that could better distinguish between treatments in terms of vision and treatment-related QoL would be useful that includes the patient perspective of treatment effects as well as meeting requirements of regulatory and health authorities. Future work could involve development of a formal weighting system with which to comprehensively assess the quality of QoL questionnaires used in glaucoma.

Objective To examine whether children with brain tumors treated with resection benefit from inpatient rehabilitation and to explore what factors present at admission may predict better functional outcomes. Design Retrospective cohort design. Setting Pediatric inpatient rehabilitation unit. Participants Forty patients (N=40; ages 3-21y; 42.5% female) admitted to the rehabilitation unit between 2003 and 2015 after brain tumor resection. Interventions Patients received multidisciplinary rehabilitation therapies as part of their admission to inpatient rehabilitation, including occupational, physical, and speech-language therapy. Main Outcome Measures Functional outcomes included the FIM for Children (WeeFIM) at discharge and 3-month follow-up as well as WeeFIM efficiency. Results A repeated-measures analysis of variance using patient WeeFIM Developmental Functional Quotients (DFQs) at admission, discharge, and 3-month follow-up showed significant gains in total WeeFIM DFQ scores across time. Admission WeeFIM DFQ, time from surgery to admission, and age at admission provided the strongest model for predicting discharge and 3-month follow-up WeeFIM DFQ scores. Admission WeeFIM DFQ and time from surgery to admission provided the strongest model for predicting WeeFIM efficiency. Total Neurological Predictor Scale (NPS) at admission did not add predictive power to any of the 3 models over and above patient characteristics (admission WeeFIM DFQ, age at admission, time from surgery to admission). Conclusions Patients admitted to inpatient rehabilitation after brain tumor resection made significant functional gains (as measured by the WeeFIM) during inpatient rehabilitation and continued to make significant gains 3 months after discharge. Age and timing of admission provided the strongest models for predicting patient outcomes. The NPS did not predict functional outcomes after rehabilitation when controlling for other variables known to influence rehabilitation outcomes.

Background There have been limited studies evaluating capsule endoscopy (CE) in equivocal celiac disease (CD). Objective To determine the role CE may have in equivocal CD cases, compared with patients with biopsy-proven and serology-proven CD who have persisting symptoms. Design Prospective cohort study. Setting University hospital. Patients A total of 62 patients with equivocal CD and 69 patients with nonresponsive CD. Intervention CE. Main Outcome Measurements Diagnostic yield of CE in equivocal cases and accuracy of mucosal abnormality detection in patients with nonresponsive CD. Results Equivocal cases (n = 62) were divided into two subgroups: group A (antibody-negative villous atrophy, n=32) and group B (Marsh 1-2 changes, n=30). In group A, CE secured a diagnosis of CD or Crohn's disease in 28% (9/32), significantly higher than the diagnostic yield in group B (7%; P = .044). In patients with CD with persisting symptoms, significant CE findings were identified in 12% (8/69), including 2 cases of enteropathy-associated lymphoma, 4 type 1 refractory disease cases, 1 polypoidal mass histologically confirmed to be a fibroepithelial polyp, and 1 case of ulcerative jejunitis. This outcome was significantly lower than the diagnostic yield of CE in antibody-negative villous atrophy ( P = .048). Limitations Single center. Conclusion There have been no previous reports systematically evaluating equivocal CD by using CE. The diagnostic yield of CE in patients with antibody-negative villous atrophy is better than that of CE in patients with CD with persisting symptoms. We advocate the use of CE in equivocal cases, particularly in patients with antibody-negative villous atrophy.

We have determined the effect of combining the chemotherapy agent doxorubicin and the anti-resorptive drug zoledronic acid on the early stages of spontaneous mammary tumour development using the immunocompetent PyMT mouse model that closely mimics human breast cancer development. 6-week-old PyMT mice were treated weekly for 6 weeks with PBS, 2 mg/kg doxorubicin, 100 μg/kg zoledronic acid or doxorubicin followed 24 h later by zoledronic acid (n = 15/group). Untreated, 6-week-old animals were used for comparison of tumour development. Tumour volume, apoptosis and angiogenesis were analysed on H&E, caspase 3, CD31 and CD34 stained histological sections. Proliferation was measured by BrdU incorporation and Ki67 staining and tumour macrophage infiltration assessed by F4/80 immunohistochemistry. Animals treated with doxorubicin followed by zoledronic acid did not develop palpable mammary tumours, whereas in all other treatment groups tumours progressed to late stage adenocarcinomas. Tumours from the combination treatment group were of comparable size to those in 6-week-old untreated animals, remaining pre-malignant with well-differentiated acinar arrangements and with tumour volume only reaching on average 26% of that in the PBS control group. Tumour cell apoptosis and proliferation was significantly reduced compared to control, single agent or untreated 6-week-old mice. Significantly fewer circulating tumour cells were present in animals following sequential treatment compared to all other groups. Combination treatment with doxorubicin followed by zoledronic acid inhibits development and progression of spontaneously occurring mammary tumours.

Equine recurrent airway obstruction (RAO) has been used as a naturally occurring model of human asthma. However, it is unknown whether there is an early-phase response in RAO. The aim of this study was to determine whether exposure to organic dust induces immediate changes in lung function in RAO-affected horses, which could be mediated by airway mast cells. Six RAO-affected horses in remission and six control horses were challenged with hay-straw dust suspension by nebulization. Total respiratory resistance at 1 Hz, measured by forced oscillation, was increased from 0.62 ± 0.09 cmH2O·l−1·s (mean ± SE) to 1.23 ± 0.20 cmH2O·l−1·s 15 min after nebulization in control horses ( P = 0.023) but did not change significantly in the RAO group. Total respiratory reactance at 1 Hz ( P = 0.005) was significantly lower in the control horses (−0.77 ± 0.07 cmH2O·l−1·s) than in the RAO group (−0.49 ± 0.04 cmH2O·l−1·s) 15 min after nebulization. Bronchoalveolar lavage fluid (BALF) histamine concentration was significantly elevated 10 and 20 min postnebulization in control horses but not in RAO horses. Minimum reactance at 1 Hz in the early postnebulization period significantly correlated with both prechallenge BALF mast cell numbers ( r = −0.65, P = 0.02) and peak BALF histamine concentration postnebulization ( r = −0.61, P = 0.04). In conclusion, RAO horses, unlike human asthmatic patients, do not exhibit an early-phase response. However, healthy control horses do demonstrate a mild but significant early (

SmartView™ Lower Minimums (SVLM) is a Synthetic Vision Guidance System (SVGS) that has been developed as a Flight Path Vector (FPV) Primary Flight Display (PFD) with additional pilot in the loop control display elements and system integrity monitors. SVLM is based upon previously certified Primus Epic® avionics architecture with a software update to an existing Primus Epic SmartView certified display. The flight instrument design enables any typically trained pilot to fly a more tightly controlled approach easily and routinely, achieving a sustained level of performance for the entire instrument approach procedure. SVLM is intended to enable lower than standard approach minimums at Category (CAT) I and CAT II airfields with a CAT I trained crew.

Summary Reasons for performing study: Heart rate is one of the most commonly measured variables in equine exercise physiology and relative exercise intensity commonly expressed as % of maximal heart rate. A number of influences affect maximal heart rate (HRmax), including age of the horse but other factors have not been described. Objectives: To determine if fitness, health status, gender, breed, athletic use, body mass, in addition to age, are predictive of HRmax in the horse. Methods: Maximal heart rate data from 328 horses which underwent treadmill exercise tests at 5 different laboratories were obtained retrospectively. Univariable linear regression analyses were performed on individual variables. Multiple linear regression analysis using a backward elimination modelling procedure was then used to relate the observed HRmax values simultaneously with different predictive variables. Variables were retained in the final regression model if they or any of their categories were significantly predictive of HRmax at P

Summary Reason for performing study: Limited information exists about the physiological changes and clinical problems that occur in elite horses competing in high-speed 160 km endurance races. Objectives: To provide initial data describing changes in physiological and laboratory measurements in horses competing in a high-speed, 160 km endurance race under temperate conditions and to compare data between horses that successfully completed the race and those that failed to finish. Methods: Body mass (BM) was measured, blood samples were collected, and veterinary examinations performed on horses before, during, and at the finish of a CEI*** 160 km endurance race. Results: Of 36 horses participating in the study, 22 (61%) completed the race. Twelve horses were eliminated for lameness and 2 for persistent heart rate elevation. Mean speed of finishers was 15.2 km/h. Mean ± s.d. BM loss of finishers at the end of the race (5.7 ± 2.6%) was not different (P = 0.58) from BM loss of nonfinishers at elimination (6.7 ± 3.4%). Similarly, there were no significant differences in heart rate or veterinary assessment of hydration at the race end for finishers as compared to the elimination point for nonfinishers. PCV increased while sodium, chloride and potassium concentrations decreased with exercise but differences between finishers and nonfinishers were not detected. In contrast, both total and ionised calcium concentrations decreased in successful horses but remained unchanged in nonfinishers. Conclusions: Elite endurance horses are more likely to be eliminated from competition for lameness than metabolic problems; however, it remains unclear whether these conditions are entirely distinct. The magnitude of the decrease in sodium concentration in both finishers and nonfinishers was greater than in previous reports of 160 km rides. Potential relevance: These data should be of use for both organisers and participants in elite 160 km endurance races. The tendency toward hyponatraemia as well as the difference in calcium concentrations between finishers and nonfinishers warrant further study.

Improving the quality of life of individuals with severe mental illness has been the focus of considerable research. With advances in treatments for severe mental illness, particularly in psychiatric rehabilitation, evaluating outcomes has become increasingly important. Given the complex and multidimensional nature of severe mental illness, outcome evaluation of psychiatric rehabilitation is particularly difficult. This article addresses issues in evaluating psychiatric rehabilitation outcomes, including key outcome domains, selection of methods and measures, and meaningful use of results. Continuing conceptual and methodological issues are discussed. Also, future directions are explored, including evaluating multidimensional treatment effects and interactions and building an integrated understanding of all of the outcomes involved in psychiatric rehabilitation. More than 8% of individuals 18 years of age or older in the United States, or approximately 17.5 million people, have a severe mental illness resulting in significant functional impairment in their daily lives (Substance Abuse & Mental Health Services Administration, 2003). The social and economic costs of these illnesses are high. Needless to say, the suffering of affected individuals and their families is immeasurable. The Global Burden of Disease Study (Murray & Lopez, 1996) identified mental illness as one of the leading burdens, second only to cardiovascular conditions, in market economies such as the United States. Although individuals with severe mental illness represent a small proportion of all individuals having a mental illness, they account for a significant proportion of the economic burden. Reducing the costs of and improving the quality of life of individuals with severe mental illness have thus been the foci of considerable research during the past three decades. Severe mental illness (also labeled severe and persistent, serious, disabling, or chronic mental illness) encompasses a group of

Objectives: Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the perspective of the healthcare payer in The Netherlands. Methods: A previously constructed Markov state-transition model was adapted and updated with costs and utilities relevant to the Dutch setting. The cost-effectiveness of RDN was compared with standard of care (SoC) for patients with resistant hypertension. The efficacy of RDN treatment was modeled as a reduction in the risk of cardiovascular events associated with a lower systolic blood pressure (SBP). Results: Treatment with RDN compared to SoC gave an incremental quality-adjusted life year (QALY) gain of 0.89 at an additional cost of €1315 over a patient’s lifetime, resulting in a base case incremental cost-effectiveness ratio (ICER) of €1474. Deterministic and probabilistic sensitivity analyses (PSA) showed that treatment with RDN therapy was cost-effective at conventional willingness-to-pay thresholds (€10,000–80,000/QALY). Conclusion: RDN is a cost-effective intervention for patients with resistant hypertension in The Netherlands.

This paper describes some practical cockpit aural annunciation and visual display concepts that have been developed to help reduce the risk of Loss of Control (LOC) and / or Lack of Control (LAC) by bringing awareness of the possible development of unusual attitude or stall conditions to the pilots. An additional objective was to provide sufficient information to aid in the recovery from the loss of control. The approach taken by the team in developing any solution was to minimize the impact on the cockpit both from the pilot understanding and training as well as the overall cost to implement into the avionics suite. Using this approach, our team developed several potential solutions. One of our solutions was to add a corrective roll arrow to the attitude indicator when an excessive bank angle is detected. A proposed preventative measure is integration of Synthetic Vision System into the head down primary flight display. Additional solutions utilized aural annunciations to alert the pilot to inappropriate flap settings and low airspeed conditions.

Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use. Bisphosphonates (BPs), such as zoledronic acid, are anti-resorptive agents approved for treatment of skeletal complication associated with metastatic breast cancer and prostate cancer. These agents act on osteoclasts, key cells in the bone microenvironment, to inhibit bone resorption. Over the past 30 years this has led to a great reduction in skeletal-related events (SRE's) in patients with advanced cancer and improved the morbidity associated with cancer-induced bone disease. However, there is now a growing body of evidence, both from in vitro and in vivo models, showing that zoledronic acid can also target tumour cells to increase apoptotic cell death and decrease proliferation, migration and invasion, and that this effect is significantly enhanced in combination with chemotherapy agents. Whether macrophages in the peripheral tumour microenvironment are exposed to sufficient levels of bisphosphonate to be affected is currently unknown. Macrophages belong to the same cell lineage as osteoclasts, the major target of BPs, and are highly phagocytic cells shown to be sensitive to bisphosphonates in model studies; In vitro, zoledronic acid causes increased apoptotic cell death; in vivo the drug has been shown to inhibit the production of pro-angiogenic factor MMP-9, as well as most recent evidence showing it can trigger the reversal of the TAMs phenotype from pro-tumoral M2 to tumoricidal M1. There is thus accumulating evidence supporting the hypothesis that effects on TAMs may contribute to the anti-tumour effect of bisphosphonates. This review will focus in detail on the role of tumour associated macrophages in breast cancer progression, the actions of bisphosphonates on macrophages in vitro and in tumour models in vivo and summarise the evidence supporting the potential for the targeting of tumour macrophages with bisphosphonates.

This paper describes a field study of the procedures and weather information sources used by a major airline's dispatchers in the pre-flight route selection process in the presence of significant weather. Additionally, this paper will describe how the AWIN decision-support tool, an aide for selecting optimal four-dimensional routes that avoid weather hazards, could be incorporated into the flight dispatch process to produce safer, more fuel-efficient routes that avoid hazardous weather. The challenges lie in effectively integrating route and weather information in the same application to facilitate decision-making, and to standardize the definitions of what weather is to be avoided and the thresholds of severity across an airline's dispatchers. The current work processes of a major airline's dispatchers were studied via a combination of observational field studies, interviews, written questionnaires, and surveys. With such a system in place, airlines can expect gains in safety, in fuel efficiency of planned routes, and in time efficiency in the preflight dispatch process.