A Mobile Health App to Support Home-Based Aerobic Exercise in Neuromuscular Diseases: Usability Study.

BACKGROUND: Home-based aerobic exercise in people with neuromuscular diseases (NMDs) has benefits compared to exercise in the hospital or a rehabilitation center because traveling is often cumbersome due to mobility limitations, and societal costs are lower. Barriers to home-based aerobic exercise include reduced possibilities for monitoring and lack of motivation. To overcome these and other barriers, we developed a mobile health app: Keep on training with ReVi (hereafter referred to as ReVi). OBJECTIVE: We aimed to determine the usability of the ReVi app. METHODS: Patients followed a 4-month, polarized, home-based aerobic exercise program on a cycle or rowing ergometer, with 2 low-intensity sessions and 1 high-intensity session per week supported by the ReVi app. The app collected training data, including heart rate and ratings of perceived exertion, provided real-time feedback on reaching target intensity zones, and enabled monitoring via an online dashboard. Physiotherapists instructed patients on how to use the ReVi app and supervised them during their training program. Patients and physiotherapists separately evaluated usability with self-developed questionnaires, including 9 questions on a 5-point Likert scale, covering the usability elements efficiency, effectiveness, and satisfaction. RESULTS: Twenty-nine ambulatory adult patients (n=19 women; mean age 50.4, SD 14.2 years) with 11 different slowly progressive NMDs participated. Both patients and physiotherapists (n=10) reported that the app, in terms of its efficiency, was easy to use and had a rapid learning curve. Sixteen patients (55%) experienced 1 or more technical issue(s) during the course of the exercise program. In the context of effectiveness, 23 patients (81%) indicated that the app motivated them to complete the program and that it helped them to exercise within the target intensity zones. Most patients (n=19, 70%) and physiotherapists (n=6, 60%) were satisfied with the use of the app. The median attendance rate was 88% (IQR 63%-98%), with 76% (IQR 69%-82%) of time spent within the target intensity zones. Four adverse events were reported, 3 of which were resolved without discontinuation of the exercise program. CONCLUSIONS: The usability of the ReVi app was high, despite the technical issues that occurred. Further development of the app to resolve these issues is warranted before broader implementation into clinical practice.

In situ calibration of charged particle spectrometers on the OMEGA Laser Facility using 241Am and 226Ra sources.

Charged particle spectrometry is a critical diagnostic to study inertial-confinement-fusion plasmas and high energy density plasmas. The OMEGA Laser Facility has two fixed magnetic charged particle spectrometers (CPSs) to measure MeV-ions. In situ calibration of these spectrometers was carried out using 241Am and 226Ra alpha emitters. The alpha emission spectrum from the sources was measured independently using surface-barrier detectors (SBDs). The energy dispersion and broadening of the CPS systems were determined by comparing the CPS measured alpha spectrum to that of the SBD. The calibration method significantly constrains the energy dispersion, which was previously obtained through the measurement of charged particle fusion products. Overall, a small shift of 100 keV was observed between previous and the calibration done in this work.

EXHANCE-3: a cohort study of the exhalation delivery system with fluticasone for chronic sinusitis with or without nasal polyps.

BACKGROUND: Inhaled nasal corticosteroid sprays (INS) are often inadequate to treat chronic rhinosinusitis (CRS). The exhalation delivery system with fluticasone (EDS-FLU; XHANCE®) may improve outcomes in CRS by increasing medication delivery to target superior/posterior anatomic sites. This study assessed safety and efficacy of EDS-FLU in a large population with moderate-to-severe CRS with or without nasal polyps (CRSwNP, CRSsNP). METHODS: Prospective, multicenter, 12-week, single-arm study of EDS-FLU 372 Â#181;g twice daily (BID) at 38 U.S. sites. Safety was assessed by adverse-event evaluations, nasal endoscopy, and ocular examinations. Efficacy was serially assessed by outcomes including nasal endoscopy (Lund-Kennedy Score, polyp grade), patient- and physician-reported outcomes (22-item Sinonasal Outcome Test [SNOT-22]), study-defined surgical indicator assessment, and Patient Global Impression of Change (PGIC). RESULTS: 705 comparatively refractory subjects were enrolled, 603 CRSsNP and 102 CRSwNP [moderate-to-severely symptomatic; baseline SNOT-22 ~43, high rates of prior INS use (92.3%) and/or prior surgery (27.5%)]. More than 90% reported improvement on treatment by PGIC. SNOT-22 scores improved substantially and similarly in patients with NP (-23.7) and without NP (-24.4). Among patients with baseline Lund-Kennedy edema scores >0, 33.3% (CRSwNP) and 54.8% (CRSsNP) had complete resolution of edema. In CRSwNP patients, 48% had polyp elimination in ?1 nostril, 63% had ?1-point improvement in polyp grade, mean bilateral polyp grade decreased from 2.9 to 1.6, and study-defined surgical eligibility decreased. EDS-FLU was generally well tolerated, with a safety profile similar to conventional INS sprays when used to treat CRS CONCLUSION: EDS-FLU 372 #181;g BID in the treatment of CRS with or without polyps was safe, well-tolerated, and produced substantial improvement across a broad range of both objective and subjective measures.

Developing a patient portal for haematology patients requires involvement of all stakeholders and a customised design, tailored to the individual needs.

BACKGROUND: Electronic patient portals are increasingly being implemented, also in (haemato) oncology. However, portal usage is low and depends on user and provider engagement. We explored wishes, expectations and thoughts of patients with a haematologic malignancy and their physicians with regard to the electronic patient portal. METHODS: Based on insights from literature and a focus group discussion we built a 44-item questionnaire. This questionnaire was spread amongst patients with a haematologic malignancy at the outpatient clinic that was not yet exposed to patient portal facilities. Haematologists completed a questionnaire based on literature. RESULTS: Patients were interested in many different types of access to information and portal functionalities. However, their opinions varied about the provision of access to the portal to other people, the role of the physician, possibilities for communication via the portal and timing of access. The physicians acknowledged the relevance of the electronic patient portal, but had some worries about the patients' autonomous information handling, organizational and technical issues. Patients frequently expressed to be open about the potential of the patient portal to orchestrate their care. Nevertheless, most physicians appreciated their supporting role towards the patient. CONCLUSIONS: Patients and physicians appreciated the electronic patient portal. Both groups need to be involved in further portal development to improve engagement by meeting patients' wishes, taking into account organizational and professional issues and managing expectations for both parties. To fit various patient profiles, portal design should be flexible and individualized. Further research should focus on the perceived added value and the impact on patient related outcome measures of portals.

Hormone variations associated with quantitative fat measures in the menopausal transition.

OBJECTIVE: Reproductive hormone levels are associated with body size, and the association between estradiol and body size varies over the menopausal transition. This study aims to delineate these relationships using quantitative measures of visceral and subcutaneous fat. METHODS: Early follicular hormones (follicle stimulating hormone (FSH), estradiol, luteinizing hormone, dehydroepiandrosterone sulfate, testosterone) and T-1 weighted abdominal MRI images were obtained in a cross-sectional assessment of 77 women in the Penn Ovarian Aging Study. Fat volume (cm(3)) was quantified using validated software (Amira) and divided into tertiles of visceral and subcutaneous fat volume for analysis. Multivariable linear regression models compared hormone values between tertiles adjusting for race, age, and menopausal status. RESULTS: In adjusted models, estradiol was positively associated with visceral fat tertiles (geometric mean (GM) estradiol (pg/ml): Low 13.0, Mid 17.5, High 26.7, p = 0.006) while FSH was inversely associated with visceral fat tertiles (GM FSH (mIU/ml): Low 42.8, Mid 43.2, High 30.8, p = 0.03). The association of estradiol with visceral and subcutaneous fat tertiles varied by menopausal status (p < 0.001). In the early transition, estradiol was similar across tertiles of fat; postmenopause, estradiol was positively associated with visceral fat. Other hormones were not associated with fat measures. CONCLUSIONS: Estradiol was associated with quantitative measures of visceral fat and varies by menopausal status. This finding suggests that visceral fat may be an important mediator in hormone changes over the menopausal transition.

Vulnerability of CMOS image sensors in Megajoule Class Laser harsh environment.

CMOS image sensors (CIS) are promising candidates as part of optical imagers for the plasma diagnostics devoted to the study of fusion by inertial confinement. However, the harsh radiative environment of Megajoule Class Lasers threatens the performances of these optical sensors. In this paper, the vulnerability of CIS to the transient and mixed pulsed radiation environment associated with such facilities is investigated during an experiment at the OMEGA facility at the Laboratory for Laser Energetics (LLE), Rochester, NY, USA. The transient and permanent effects of the 14 MeV neutron pulse on CIS are presented. The behavior of the tested CIS shows that active pixel sensors (APS) exhibit a better hardness to this harsh environment than a CCD. A first order extrapolation of the reported results to the higher level of radiation expected for Megajoule Class Laser facilities (Laser Megajoule in France or National Ignition Facility in the USA) shows that temporarily saturated pixels due to transient neutron-induced single event effects will be the major issue for the development of radiation-tolerant plasma diagnostic instruments whereas the permanent degradation of the CIS related to displacement damage or total ionizing dose effects could be reduced by applying well known mitigation techniques.

A versatile high-resolution x-ray imager (HRXI) for laser-plasma experiments on OMEGA.

A high-resolution x-ray imager (HRXI) devoted to laser-plasma experiments combines two state-of-the-art technologies developed in France: a high-resolution x-ray microscope and a high-speed x-ray streak camera. The resulting streaked imager achieves spatial and temporal resolutions of approximately 5 microm and approximately 10 ps, respectively. The HXRI has recorded enhanced spatial and temporal resolution radiographs of indirectly driven targets on OMEGA. This paper describes the main features of the instrument and details the activation process on OMEGA (particularly the alignment). Recent results obtained on joint CEA/LLE radiographic OMEGA experiments will also be presented.

Diagnostics hardening for harsh environment in Laser Megajoule (invited).

The diagnostic designs for the Laser Megajoule (LMJ) will require components to operate in environments far more severe than those encountered in present facilities. This harsh environment will be induced by fluxes of neutrons, gamma rays, energetic ions, electromagnetic radiations, and, in some cases, debris and shrapnel, at levels several orders of magnitude higher than those experienced today on existing facilities. The lessons learned about the vulnerabilities of present diagnostic parts fielded mainly on OMEGA for many years, have been very useful guide for the design of future LMJ diagnostics. The present and future LMJ diagnostic designs including this vulnerability approach and their main mitigation techniques will be presented together with the main characteristics of the LMJ facility that provide for diagnostic protection.

Diagnostic components in harsh radiation environments: possible overlap in R&D requirements of inertial confinement and magnetic fusion systems.

The next generation of large scale fusion devices--ITER/LMJ/NIF--will require diagnostic components to operate in environments far more severe than those encountered in present facilities. This harsh environment is the result of high fluxes of neutrons, gamma rays, energetic ions, electromagnetic radiation, and in some cases, debris and shrapnel, at levels several orders of magnitude higher than those experienced in today's devices. The similarities and dissimilarities between environmental effects on diagnostic components for the inertial confinement and magnetic confinement fusion fields have been assessed. Areas in which considerable overlap have been identified are optical transmission materials and optical fibers in particular, neutron detection systems and electronics needs. Although both fields extensively use cables in the hostile environment, there is little overlap because the environments and requirements are very different.

Innate immune responses to LCMV infections: natural killer cells and cytokines.

Although much remains to be learned, the study of early responses to LCMV infections of mice has contributed to the basic understanding of the regulation of a variety of important innate immune responses. Major discoveries have included the appreciation of the levels of type 1 IFNs induced during endogenous responses to viral infections, the importance of IFN-alpha/beta for induction of NK cell cytotoxicity, and the roles for IFN-alpha/beta in regulating the expression of other innate cytokines, i.e., IL-12 and IFN-gamma produced by NK cells (Fig. 11). Taken together with the characterization of adaptive responses to LCMV, a paradigm is emerging for a possible initial to innate to adaptive response cascade during infections with viruses eliciting endogenous expression of high levels of IFN-alpha/beta. The results not only advance the understanding of endogenous responses to viral infections and how they are balanced to achieve the best possible outcome for the host, but also give insights into possible consequences of therapeutic intervention with type 1 IFNs.

Radiation safety at the University of Rochester's Laser Fusion Research Facility.

The fusion research conducted at the Laboratory for Laser Energetics requires large amounts of tritium and generates brief but very high, neutron fluxes. This raises a number of radiological concerns that have been satisfactorily addressed via a combination of engineering controls, training, and administrative controls. These problems encountered and our solutions to them are described in this paper.

Use of an implantable pleural catheter for trapped lung syndrome in patients with malignant pleural effusion.

STUDY OBJECTIVES: We describe a series of patients with symptomatic, refractory malignant pleural effusion (MPE) and underlying trapped lung syndrome who underwent placement of a small-bore, flexible indwelling pleural catheter for home drainage of recurrent MPE. DESIGN: The medical records of 11 consecutive patients who underwent pleural catheter placement for MPE with trapped lung syndrome were reviewed retrospectively. SETTING: Patients were evaluated and followed up in the Pulmonary Outpatient Practice at the Hospital of the University of Pennsylvania. PATIENTS: Nine men and two women with underlying malignancies including lung cancer, lymphoma, and mesothelioma underwent pleural catheter placement. INTERVENTIONS: Thirteen pleural catheters were placed in 11 patients, all under local anesthesia. Patients received detailed instructions for drainage and catheter care. They were reevaluated weekly for the first 2 weeks, and then as clinically indicated. Patients typically performed pleural drainage at home up to 1,000 mL two or three times weekly. MEASUREMENTS AND RESULTS: All patients reported symptomatic benefit, defined as improved dyspnea and exercise tolerance, except for one patient. In 10 patients, the pleural catheters remained in place until death, for 15 to 234 days. The mean length of placement was 115 days. One patient required revision after catheter occlusion. Other complications included catheter infection, localized skin breakdown, and possible cellulitis. CONCLUSION: We have described a series of patients with MPE and trapped lung syndrome for whom placement of a permanent pleural catheter provided a convenient, effective alternative to the procedures currently in use. Our patients reported good symptomatic relief following catheter placement with few major complications.

SAP controls T cell responses to virus and terminal differentiation of TH2 cells.

SH2D1A, which encodes signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), is altered in patients with X-linked lymphoproliferative disease (XLP), a primary immunodeficiency. SAP-deficient mice infected with lymphocytic choriomeningitis virus had greatly increased numbers of CD8+ and CD4+ interferon-gamma-producing spleen and liver cells compared to wild-type mice. The immune responses of SAP-deficient mice to infection with Leishmania major together with in vitro studies showed that activated SAP-deficient T cells had an impaired ability to differentiate into T helper 2 cells. The aberrant immune responses in SAP-deficient mice show that SAP controls several distinct key T cell signal transduction pathways, which explains in part the complexity of the XLP phenotypes.

Cutting edge: selective IL-18 requirements for induction of compartmental IFN-gamma responses during viral infection.

Optimal protective effects for defense against infection require orchestration of immune responses spanning multiple host compartments and divergent local regulation at particular sites. During murine cytomegalovirus infections known to target spleen and liver, IL-12-induced IFN-gamma from NK cells is crucial for resistance. However, the roles for IL-18 and/or IL-12 in regulating hepatic IFN-gamma responses, as compared with systemic or splenic responses, have not been defined. In this report, mice genetically deficient in either IL-18 or IL-12p35 exhibited up to 95% reductions in systemic and splenic IFN-gamma responses. Surprisingly, IFN-gamma responses were preserved in the livers of IL-18-deficient, but not IL-12p35-deficient, mice. Cytokine requirements for host survival also differed. Under conditions where mice lacking IL-12p35 exhibited 100% mortality, those lacking IL-18 survived. Taken together, our results delineate contrasting compartmental requirements for IL-18 and suggest that preservation of local, hepatic IFN-gamma production is critical for host defense during murine cytomegalovirus challenge.

Compartmental differences in NK cell responsiveness to IL-12 during lymphocytic choriomeningitis virus infection.

Some, but not all, viral infections induce endogenous IL-12 to drive NK cell IFN-gamma production and downstream antiviral defenses during innate immune responses. Even though lymphocytic choriomeningitis virus (LCMV) can be sensitive to IFN-gamma-mediated antiviral effects, infections with this agent do not elicit IL-12 or early IFN-gamma in immunocompetent hosts. Studies presented here demonstrate that LCMV infections of mice not only fail to induce IL-12, but also modify responsiveness to exogenous IL-12 for IFN-gamma production. IFN-gamma responses induced by IL-12 administration were greatly diminished in splenic populations, but significantly increased in serum and hepatic leukocytes, during the early course of LCMV infections. The IFN-gamma production was NK cell dependent, and the compartmental dichotomy between spleen and liver was also demonstrated in response to in vitro IL-12 stimulation. Although infections did increase proportions and numbers of liver NK cells, changes in responsiveness for IFN-gamma expression could not be explained by cell redistribution. Corroborating changes in proportions of NK cells induced to express intracellular IFN-gamma protein within the compartments were observed. The reduction in ability of splenic populations to produce IL-12-induced IFN-gamma after infection by LCMV was associated with decreased efficacy of administered IL-12 for promoting IFN-gamma-dependent antiviral effects in the spleen. Concomitantly, the maintenance of hepatic population IFN-gamma production was associated with preserved efficacy of administered IL-12 to elicit IFN-gamma-dependent antiviral effects in the liver. Taken together, these results demonstrate modifications of compartmental responses to IL-12 by viral infections and the consequences of these changes for efficacy of cytokine therapy.

Interferon alpha/beta-mediated inhibition and promotion of interferon gamma: STAT1 resolves a paradox.

Induction of high systemic levels of type 1 interferons (IFNs) IFN-alpha and IFN-beta is a hallmark of many viral infections. In addition to their potent antiviral effects, these cytokines mediate a number of immunoregulatory functions and can promote IFN-gamma expression in T cells. However, during viral infections of mice IFN-gamma production is not always observed at the same time as systemic IFN-alpha/beta production and when, elicited at these times, is IFN-alpha/beta-independent. We demonstrate that type 1 interferons not only fail to induce, but also act to inhibit, IFN-gamma expression by both NK and T cells. The mechanism of inhibition is dependent upon the IFN-alpha/beta receptor and the signal transducer and activator of transcription 1 (STAT1). In the absence of STAT1, not only are the IFN-alpha/beta-mediated inhibitory effects completely abrogated, but the cytokines themselves can induce IFN-gamma expression. These results indicate that endogenous biochemical pathways are in place to negatively regulate NK and T cell IFN-gamma expression elicited by IFN-alpha/beta or other stimuli, at times of innate responses to viral infections. They also show that type 1 interferon signaling can occur through STAT1-dependent and independent mechanisms and suggest that efficient induction of IFN-gamma expression by IFN-alpha/beta requires STAT1 regulation. Such immunoregulatory pathways may be critical for shaping the endogenous innate and virus-specific adaptive immune responses to viral infections.

Natural killer cells in antiviral defense: function and regulation by innate cytokines.

Natural killer (NK) cells are populations of lymphocytes that can be activated to mediate significant levels of cytotoxic activity and produce high levels of certain cytokines and chemokines. NK cells respond to and are important in defense against a number of different infectious agents. The first indications for this function came from the observations that virus-induced interferons alpha/beta (IFN-alpha and -beta) are potent inducers of NK cell-mediated cytotoxicity, and that NK cells are important contributors to innate defense against viral infections. In addition to IFN-alpha/beta, a wide range of other innate cytokines can mediate biological functions regulating the NK cell responses of cytotoxicity, proliferation, and gamma interferon (IFN-gamma) production. Certain, but not all, viral infections induce interleukin 12 (IL-12) to elicit NK cell IFN-gamma production and antiviral mechanisms. However, high levels of IFN-alpha/beta appear to be unique and/or uniquely dominant in the context of viral infections and act to regulate other innate responses, including induction of NK cell proliferation in vivo and overall negative regulation of IL-12 production. A detailed picture is developing of particular innate cytokines activating NK cell responses and their consorted effects in providing unique endogenous milieus promoting downstream adaptive responses, most beneficial in defense against viral infections.

Uniformity of the Soft-X-Ray Emissions from Gold Foils Irradiated by OMEGA Laser Beams Determined by a Two-Mirror Normal-Incidence Microscope with Multilayer Coatings.

A two-mirror normal-incidence microscope with multilayer coatings was used to image the soft-x-ray emissions from planar foils irradiated by OMEGA laser beams. The bandpass of the multilayer coatings was centered at a wavelength of 48.3 ? (257-eV energy) and was 0.5 ? wide. Five overlapping OMEGA beams, without beam smoothing, were typically incident on the gold foils. The total energy was 1500 J, and the focused intensity was 6 x 10(13) W cm(-2). The 5.8x magnified images were recorded by a gated framing camera at various times during the 3-ns laser pulse. A pinhole camera imaged the x-ray emission in the energy range of >2 keV. On a spatial scale of 10 mum, it was found that the soft-x-ray images at 257 eV were quite uniform and featureless. In contrast, the hard-x-ray images in the energy range of >2 keV were highly nonuniform with numerous features of size 150 mum.