•Literature as well as professional guidelines on telehealth were reviewed.•There is limited attention to health care provider issues in delivering telehealth.•Key recommendations for optimising ...supportive cancer care telehealth are made.
To investigate what factors need consideration for telehealth services for cancer supportive care, given the rapid transition to telehealth as a result of COVID-19.
A scoping review and a review of current guidance and guidelines provided by professional bodies, representing relevant discipline groups for cancer supportive care, were conducted.
We identified 19 papers and 23 telehealth guidance documents. The results highlight how the characteristics of patient group and healthcare provider influence the acceptability and utility of the service and establish a minimum set of preconditions. The reviews primarily examined patient-focused difficulties or issues with acceptability and efficacy, with only a minority highlighting how provider issues might also be implicated. By contrast, the guidance and guidelines described a need to address skills gaps in providing and receiving support through telehealth.
The capacity and willingness of services to adapt, in the context of COVID-19, is reassuring. It is important that the impact of the move to telehealth on service quality is assessed and systems put in place to ensure sustainability, acceptability, and adaptability.
Key recommendations can be made to assist service telehealth optimisation, many of which apply irrespective of the specific service focus.
Selection of the InSight Landing Site Golombek, M.; Kipp, D.; Warner, N. ...
Space science reviews,
10/2017, Volume:
211, Issue:
1-4
Journal Article
Peer reviewed
Open access
The selection of the Discovery Program InSight landing site took over four years from initial identification of possible areas that met engineering constraints, to downselection via targeted data ...from orbiters (especially Mars Reconnaissance Orbiter (MRO) Context Camera (CTX) and High-Resolution Imaging Science Experiment (HiRISE) images), to selection and certification via sophisticated entry, descent and landing (EDL) simulations. Constraints on elevation (
≤
−
2.5
km
for sufficient atmosphere to slow the lander), latitude (initially 15°S–5°N and later 3°N–5°N for solar power and thermal management of the spacecraft), ellipse size (130 km by 27 km from ballistic entry and descent), and a load bearing surface without thick deposits of dust, severely limited acceptable areas to western Elysium Planitia. Within this area, 16 prospective ellipses were identified, which lie ∼600 km north of the Mars Science Laboratory (MSL) rover. Mapping of terrains in rapidly acquired CTX images identified especially benign smooth terrain and led to the downselection to four northern ellipses. Acquisition of nearly continuous HiRISE, additional Thermal Emission Imaging System (THEMIS), and High Resolution Stereo Camera (HRSC) images, along with radar data confirmed that ellipse E9 met all landing site constraints: with slopes <15° at 84 m and 2 m length scales for radar tracking and touchdown stability, low rock abundance (<10 %) to avoid impact and spacecraft tip over, instrument deployment constraints, which included identical slope and rock abundance constraints, a radar reflective and load bearing surface, and a fragmented regolith ∼5 m thick for full penetration of the heat flow probe. Unlike other Mars landers, science objectives did not directly influence landing site selection.
The global community has adopted ambitious goals to eliminate schistosomiasis as a public health problem, and new tools are needed to achieve them. Mass drug administration programs, for example, ...have reduced the burden of schistosomiasis, but the identification of hotspots of persistent and reemergent transmission threaten progress toward elimination and underscore the need to couple treatment with interventions that reduce transmission. Recent advances in DNA sequencing technologies make whole-genome sequencing a valuable and increasingly feasible option for population-based studies of complex parasites such as schistosomes. Here, we focus on leveraging genomic data to tailor interventions to distinct social and ecological circumstances. We consider two priority questions that can be addressed by integrating epidemiological, ecological, and genomic information: (1) how often do non-human host species contribute to human schistosome infection? and (2) what is the importance of locally acquired versus imported infections in driving transmission at different stages of elimination? These questions address processes that can undermine control programs, especially those that rely heavily on treatment with praziquantel. Until recently, these questions were difficult to answer with sufficient precision to inform public health decision-making. We review the literature related to these questions and discuss how whole-genome approaches can identify the geographic and taxonomic sources of infection, and how such information can inform context-specific efforts that advance schistosomiasis control efforts and minimize the risk of reemergence.
TWIK-related acid-sensitive potassium (TASK) channels-members of the two pore domain potassium (K
) channel family-are found in neurons
, cardiomyocytes
and vascular smooth muscle cells
, where they ...are involved in the regulation of heart rate
, pulmonary artery tone
, sleep/wake cycles
and responses to volatile anaesthetics
. K
channels regulate the resting membrane potential, providing background K
currents controlled by numerous physiological stimuli
. Unlike other K
channels, TASK channels are able to bind inhibitors with high affinity, exceptional selectivity and very slow compound washout rates. As such, these channels are attractive drug targets, and TASK-1 inhibitors are currently in clinical trials for obstructive sleep apnoea and atrial fibrillation
. In general, potassium channels have an intramembrane vestibule with a selectivity filter situated above and a gate with four parallel helices located below; however, the K
channels studied so far all lack a lower gate. Here we present the X-ray crystal structure of TASK-1, and show that it contains a lower gate-which we designate as an 'X-gate'-created by interaction of the two crossed C-terminal M4 transmembrane helices at the vestibule entrance. This structure is formed by six residues (
VLRFMT
) that are essential for responses to volatile anaesthetics
, neurotransmitters
and G-protein-coupled receptors
. Mutations within the X-gate and the surrounding regions markedly affect both the channel-open probability and the activation of the channel by anaesthetics. Structures of TASK-1 bound to two high-affinity inhibitors show that both compounds bind below the selectivity filter and are trapped in the vestibule by the X-gate, which explains their exceptionally low washout rates. The presence of the X-gate in TASK channels explains many aspects of their physiological and pharmacological behaviour, which will be beneficial for the future development and optimization of TASK modulators for the treatment of heart, lung and sleep disorders.
Up to 50% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), yet the study of BM genomics has been limited by tissue access, incomplete clinical data, and a lack of ...comparison with paired extracranial specimens. Here we report a cohort of 233 patients with resected and sequenced (MSK-IMPACT) NSCLC BM and comprehensive clinical data. With matched samples (47 primary tumor, 42 extracranial metastatic), we show CDKN2A/B deletions and cell cycle pathway alterations to be enriched in the BM samples. Meaningful clinico-genomic correlations are noted, namely EGFR alterations in leptomeningeal disease (LMD) and MYC amplifications in multifocal regional brain progression. Patients who developed early LMD frequently have had uncommon, multiple, and persistently detectable EGFR driver mutations. The distinct mutational patterns identified in BM specimens compared to other tissue sites suggest specific biologic underpinnings of intracranial progression.
With the first direct detection of merging black holes in 2015, the era of gravitational wave (GW) astrophysics began. A complete picture of compact object mergers, however, requires the detection of ...an electromagnetic (EM) counterpart. We report ultraviolet (UV) and x-ray observations by Swift and the Nuclear Spectroscopic Telescope Array of the EM counter part of the binary neutron star merger GW170817. The bright, rapidly fading UV emission indicates a high mass (≈0.03 solar masses) wind-driven outflow with moderate electron fraction (Yₑ ≈ 0.27). Combined with the x-ray limits, we favor an observer viewing angle of ≈30° away from the orbital rotation axis, which avoids both obscuration fromthe heaviest elements in the orbital plane and a direct view of any ultrarelativistic, highly collimated ejecta (a γ-ray burst afterglow).
A primary goal of the recent investment in sequencing is to detect novel genetic associations in health and disease improving the development of treatments and playing a critical role in precision ...medicine. While this investment has resulted in an enormous total number of sequenced genomes, individual studies of complex traits and diseases are often smaller and underpowered to detect rare variant genetic associations. Existing genetic resources such as the Exome Aggregation Consortium (>60,000 exomes) and the Genome Aggregation Database (~140,000 sequenced samples) have the potential to be used as controls in these studies. Fully utilizing these and other existing sequencing resources may increase power and could be especially useful in studies where resources to sequence additional samples are limited. However, to date, these large, publicly available genetic resources remain underutilized, or even misused, in large part due to the lack of statistical methods that can appropriately use this summary level data. Here, we present a new method to incorporate external controls in case-control analysis called ProxECAT (Proxy External Controls Association Test). ProxECAT estimates enrichment of rare variants within a gene region using internally sequenced cases and external controls. We evaluated ProxECAT in simulations and empirical analyses of obesity cases using both low-depth of coverage (7x) whole-genome sequenced controls and ExAC as controls. We find that ProxECAT maintains the expected type I error rate with increased power as the number of external controls increases. With an accompanying R package, ProxECAT enables the use of publicly available allele frequencies as external controls in case-control analysis.
ABCB10 is one of the three ATP-binding cassette (ABC) transporters found in the inner membrane of mitochondria. In mammals ABCB10 is essential for erythropoiesis, and for protection of mitochondria ...against oxidative stress. ABCB10 is therefore a potential therapeutic target for diseases in which increased mitochondrial reactive oxygen species production and oxidative stress play a major role. The crystal structure of apo-ABCB10 shows a classic exporter fold ABC transporter structure, in an open-inwards conformation, ready to bind the substrate or nucleotide from the inner mitochondrial matrix or membrane. Unexpectedly, however, ABCB10 adopts an open-inwards conformation when complexed with nonhydrolysable ATP analogs, in contrast to other transporter structures which adopt an open-outwards conformation in complex with ATP. The three complexes of ABCB10/ATP analogs reported here showed varying degrees of opening of the transport substrate binding site, indicating that in this conformation there is some flexibility between the two halves of the protein. These structures suggest that the observed plasticity, together with a portal between two helices in the transmembrane region of ABCB10, assist transport substrate entry into the substrate binding cavity. These structures indicate that ABC transporters may exist in an open-inwards conformation when nucleotide is bound. We discuss ways in which this observation can be aligned with the current views on mechanisms of ABC transporters.
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