Controlled, parametric, individualized, 2D and 3D imaging measurements of aerosol deposition in the respiratory tract of healthy human volunteers: in vivo data analysis

Background: To provide a validation dataset for aerosol deposition modeling, a clinical trial was performed in which the inhalation parameters and the inhaled aerosol were controlled or characterized.Methods: Eleven, healthy, never-smokers, male participants completed the study. Each participant performed two inhalations of 99mTc-labeled aerosol from a vibrating mesh nebulizer, which differed by a single controlled parameter (aerosol particle size: “small” or “large”; inhalation: “deep” or “shallow”; carrier gas: air or a helium–oxygen mix). The deposition measurements were made by planar imaging, and single photon emission computed tomography–computed tomography (SPECT-CT).Results: The difference between the mean activity measured by two-dimensional imaging and that delivered from the nebulizer was 2.7%, which was not statistically significant. The total activity deposited was significantly lower in the left lung than in the right lung (p&lt;0.0001) with a mean ratio (left/right) of 0.87±0.1 standard deviation (SD). However, when normalized to lung air volume, the left lung deposition was significantly higher (p=0.0085) with a mean ratio of 1.08±0.12 SD. A comparison of the three-dimensional central-to-peripheral (nC/P3D) ratio showed that it was significantly higher for the left lung (p&lt;0.0001) with a mean ratio (left/right) of 1.36±0.20 SD. The effect of particle size was statistically significant on the nC/P3D ratio (p=0.0014), extrathoracic deposition (p=0.0037), and 24-hr clearance (p&lt;0.0001), contrary to the inhalation parameters, which showed no effect.Conclusions: This article presents the results of an analysis of the in vivo deposition data, obtained in a clinical study designed to provide data for model validation. This study has demonstrated the value of SPECT imaging over planar, the influence of particle size on regional distribution within the lung, and differences in deposition between the left and right lungs.<br/

The Cosmic Background Imager

Design and performance details are given for the Cosmic Background Imager (CBI), an interferometer array that is measuring the power spectrum of fluctuations in the cosmic microwave background radiation (CMBR) for multipoles in the range 400 < l < 3500. The CBI is located at an altitude of 5000 m in the Atacama Desert in northern Chile. It is a planar synthesis array with 13 0.9-m diameter antennas on a 6-m diameter tracking platform. Each antenna has a cooled, low-noise receiver operating in the 26-36 GHz band. Signals are cross-correlated in an analog filterbank correlator with ten 1 GHz bands. This allows spectral index measurements which can be used to distinguish CMBR signals from diffuse galactic foregrounds. A 1.2 kHz 180-deg phase switching scheme is used to reject cross-talk and low-frequency pick-up in the signal processing system. The CBI has a 3-axis mount which allows the tracking platform to be rotated about the optical axis, providing improved (u,v) coverage and a powerful discriminant against false signals generated in the receiving electronics. Rotating the tracking platform also permits polarization measurements when some of the antennas are configured for the orthogonal polarization.Comment: 14 pages. Accepted for publication in PASP. See also http://www.astro.caltech.edu/~tjp/CBI

Brief of Amici Curiae Intellectual Property Law Professors

Untethered to a sufficient public policy interest, right of publicity claims have exploded nationwide. Plaintiffs have asserted claims against inspirational plaques featuring civil rights icons, Rosa and Raymond Parks Inst. for Self Dev. v. Target Corp., 812 F.3d 824 (11th Cir. 2016),artwork commemorating significant events, Moore v. Weinstein Co., LLC, 545 Fed. App’x. 405 , 407 (6th Cir. 2013); ETW Corp. v. Jireh Publ’g, Inc., 332 F.3d 915 (6th Cir. 2003), Wikipedia edits that truthfully connected an astronaut with the watch he wore on his Moon walk, Scott v. Citizen Watch Co. of Am., Inc., 17-CV-00436-NC, 2018 WL 1626773 (N.D. Cal. Apr. 4, 2018), docudramas, de Havilland v. FX Networks, LLC, 21 Cal. App. 5th 845 (2018), and depictions of a company named for its founder, Virag, S.R.L. v. Sony Computer Entm’t Am. LLC, 699 Fed. App’x. 667 (9th Cir. 2017), among many other uses. This Court has the opportunity to keep Indiana’s right of publicity law within more appropriate bounds by focusing on protection of performers against unauthorized recordings (similar to common-law copyright, as recognized in Zacchini v. Scripps-Howard Broadcasting Co., 433 U.S. 562 (1977)) and unauthorized use of identities in advertising (protecting against false endorsements). The Court should take that opportunity, because a free-floating right of publicity operates as an unconstitutional, content-based regulation of otherwise truthful, protected speech. Given the First Amendment value of truthful, nondefamatory speech, courts should not lightly give the subjects of such speech control over it. Thus, the right of publicity must be carefully limited to avoid becoming a right to control public discourse. Cf. Hustler Magazine, Inc. v. Falwell, 485 U.S. 46, 50 (1988) (refusing to allow the tort of intentional infliction of emotional distress to evade the strict requirements of defamation as applied to editorial speech). Although the doctrine of constitutional avoidance might justify finding that these defendants’ activities do not fall within the scope of the Indiana statute, the statute is unconstitutional to the extent that it goes beyond advertising and unauthorized recordings of performances

The barriers and facilitators that indigenous health workers experience in their workplace and communities in providing self-management support: a multiple case study

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background The inequality in health outcomes between Indigenous (Throughout the paper, the term Indigenous will be used to represent both Aboriginal Australians and Torres Strait Islander Australians.) and non-Indigenous Australians continues to be a major public health issue. Chronic conditions are responsible for the majority of the gap in life expectancy for this population. Evidence suggests that chronic condition management models focusing on self-management have led to improved health outcomes in Indigenous populations. The Flinders Closing the Gap Program (FCTGP) is a chronic condition care planning tool which aims to engage Indigenous people in self-managing their chronic conditions. Indigenous health workers (IHWs) can provide culturally appropriate self-management support; however there is paucity in current literature describing specific barriers and facilitators that they may experience when attempting to deliver this support. This study aimed to explore IHWs’ perceptions of the effectiveness and appropriateness of the FCTGP, as an evidence-based example of self-management support, and to explore the barriers and facilitators that IHWs experience in their workplace and communities in providing self-management support. Methods In-depth interviews were undertaken with five IHWs, drawn from five different states in Australia. Their selection was aided by key informants from the FCTGP training unit. Interviews were recorded and transcribed verbatim, and were analysed using thematic analysis. Results The following themes were identified. IHWs reported that the FCTGP was appropriate, flexible and acceptable in their communities. Facilitators included factors improving client and worker empowerment, and activities around sharing knowledge. Barriers included competing priorities that clients experience relating to social determinants of health, and negative experiences within mainstream health services. IHW burnout from time pressures, lack of support, and high staff turnover were also considered important barriers. Conclusions This study contributes an insight into the experiences of IHWs who are considered important stakeholders in implementation and sustainability of chronic condition management programs, including the FCTGP. Recommendations focus on supporting and supplementing the role of IHWs and identify the FCTGP as a facilitator in providing self-management support to a population with complex needs

Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma

Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model

Indigenous patient experiences of returning to country: a qualitative evaluation on the Country Health SA Dialysis bus

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background Rates of End-Stage Kidney Disease among Aboriginal and Torres Strait Islander (Indigenous) Australians in remote areas are disproportionately high; however, haemodialysis is not currently offered in most remote areas. People must therefore leave their ‘Country’ (with its traditions and supports) and relocate to metropolitan or regional centres, disrupting their kinship and the cultural ties that are important for their wellbeing. The South Australian Mobile Dialysis Truck is a service which visits remote communities for one to two week periods; allowing patients to have dialysis on ‘Country’, reuniting them with their friends and family, and providing a chance to take part in cultural activities. The aims of the study were to qualitatively evaluate the South Australian Mobile Dialysis Truck program, its impact on the health and wellbeing of Indigenous dialysis patients, and the facilitators and barriers to using the service. Methods Face to face semi-structured interviews were conducted with 15 Indigenous dialysis patients and 10 nurses who had attended trips across nine dialysis units. Realist evaluation methodology and thematic analysis established patient and nursing experiences with the Mobile Dialysis Truck. Results The consequences of leaving Country included grief and loss. Barriers to trip attendance included lower trip frequencies, ineffective trip advertisement, lack of appropriate or unavailable accommodation for staff and patients and poor patient health. Benefits of the service included the ability to fulfil cultural commitments, minimisation of medical retrievals from patients missing dialysis to return to remote areas, improved trust and relationships between patients and staff, and improved patient quality of life. The bus also provided a valuable cultural learning opportunity for staff. Facilitators to successful trips included support staff, clinical back-up and a co-ordinator role. Conclusions The Mobile Dialysis Truck was found to improve the social and emotional wellbeing of Indigenous patients who have had to relocate for dialysis, and build positive relationships and trust between metropolitan nurses and remote patients. The trust fostered improved engagement with associated health services. It also provided valuable cultural learning opportunities for nursing staff. This format of health service may improve cultural competencies with nursing staff who provide regular care for Indigenous patients

Pulmonary tele-rehabilitation in the COVID-19 era

[Commentary] For patients with chronic obstructive pulmonary disease, pulmonary rehabilitation (PR) has demonstrated improvements in physiological measures(1), patient-reported outcomes(2), and health economic indices(3). There is also a growing body of evidence around improvements in frailty(4) sedentary behaviour(5) and social-connectedness(6). The clinical need for alternative delivery modes of programmes, such as pulmonary tele-rehabilitation (PTR) has been clearly established in the COVID-19 pandemic, whereby conventional face-to-face programme provision seems an unlikely reality for the foreseeable future. The rapid remodelling of health services as a result of COVID-19 provides an exciting opportunity to reflect about the traditional aims, structure, outcomes and components of conventional PR programmes.Hansen et al(7) in a recent issue of Thorax provide an excellent, concise literature review, in combination with outcomes from their study, which suggest that PTR is certainly no worse than conventional PR for commonly reported patient outcomes and could indeed offer some benefits in terms of programme completion. However, there are limitations which we believe should be highlighted further

Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2) : a randomised controlled trial and process evaluation

Background Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1β and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1β and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia. Methods VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1β and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 104 colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov, NCT01972425. Findings Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine use of antibiotics (n=106). One patient in the biomarker-guided recommendation group was withdrawn by the clinical team before bronchoscopy and so was excluded from the intention-to-treat analysis. We found no significant difference in the primary outcome of the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage in the intention-to-treat analysis (p=0·58). Bronchoalveolar lavage was associated with a small and transient increase in oxygen requirements. Established prescribing practices, reluctance for bronchoalveolar lavage, and dependence on a chain of trial-related procedures emerged as factors that impaired trial processes

Validated respiratory drug deposition predictions from 2D and 3D medical images with statistical shape models and convolutional neural networks

For the one billion sufferers of respiratory disease, managing their disease with inhalers crucially influences their quality of life. Generic treatment plans could be improved with the aid of computational models that account for patient-specific features such as breathing pattern, lung pathology and morphology. Therefore, we aim to develop and validate an automated computational framework for patient-specific deposition modelling. To that end, an image processing approach is proposed that could produce 3D patient respiratory geometries from 2D chest X-rays and 3D CT images. We evaluated the airway and lung morphology produced by our image processing framework, and assessed deposition compared to in vivo data. The 2D-to-3D image processing reproduces airway diameter to 9% median error compared to ground truth segmentations, but is sensitive to outliers of up to 33% due to lung outline noise. Predicted regional deposition gave 5% median error compared to in vivo measurements. The proposed framework is capable of providing patient-specific deposition measurements for varying treatments, to determine which treatment would best satisfy the needs imposed by each patient (such as disease and lung/airway morphology). Integration of patient-specific modelling into clinical practice as an additional decision-making tool could optimise treatment plans and lower the burden of respiratory diseases.</p