Thirty silicate glasses were synthesized as realistic analogs to those expected to exist on Mars, the Moon, and Mercury. Samples were measured using visible/near‐infrared and Mössbauer spectroscopy ...to determine the effects of varying bulk chemistry, oxygen fugacity, and temperature on spectral properties. For Martian glasses, the fO2 during fusion strongly affects absorption band intensities in the spectra, while bulk chemistry has noticeable secondary effects on absorption band positions. Titanium and iron content drive spectral changes in lunar glasses, where Fe3+ is effectively absent. Iron‐free Mercury analog glasses have much higher albedos than all other samples, and their spectral shape is a close match to some pyroclastic deposits on Mercury. Synthetic glass spectra were used as inputs into a spectral unmixing model applied to remote orbital datasets to test for the presence of glass. The model is validated against physical laboratory mixture spectra, as well as previous detections of glass‐rich pyroclastic deposits on the Moon. Remote data were then used from suspected impact deposits and possible pyroclastic deposits on Mars as a new application of the model: the results reveal spatially coherent glass‐rich material, and the strong spectral match of the synthetic glasses to these remotely sensed data gives new insights into the presence and character of glasses on the Martian surface. The large library of glass spectra generated here, acquired from consistently synthesized and measured samples, can serve as a resource for further studies of volcanic and impact processes on planetary bodies.
Key Points
Visible/near‐infrared spectral properties are examined for a wide range of synthetic planetary glasses
A spectral mixing model is described to detect the presence of glass in mixed pixels
Using the spectral mixing model, glasses are identified in both impact and volcanic settings on Mars
One-third of stroke patients are dependent on others to get outside their homes. This can cause people to become housebound, leading to increased immobility, poor health, isolation and misery. There ...is some evidence that outdoor mobility rehabilitation can reduce these limitations.
To test the clinical effectiveness and cost-effectiveness of an outdoor mobility rehabilitation intervention for stroke patients.
Multicentre, parallel-group randomised controlled trial, with two groups allocated at a 1 : 1 ratio plus qualitative participant interviews.
Fifteen UK NHS stroke services throughout England, Scotland and Wales.
A total of 568 stroke patients who wished to get out of the house more often, mean age of 71 years: 508 reached the 6-month follow-up and 10 were interviewed.
Control was delivered prior to randomisation to all participants, and consisted of verbal advice and transport and outdoor mobility leaflets. Intervention was a targeted outdoor mobility rehabilitation programme delivered by 29 NHS therapists to 287 randomly chosen participants for up to 12 sessions over 4 months.
Primary outcome was participant health-related quality of life, measured by the Short Form questionnaire-36 items, version 2 (Social Function domain), 6 months after baseline. Secondary outcomes were functional ability, mobility, number of journeys (from monthly travel diaries), satisfaction with outdoor mobility (SWOM), psychological well-being and resource use health care and Personal Social Services (PSS) 6 months after baseline. Carer well-being was recorded. All outcome measures were collected by post and repeated 12 months after baseline. Outcomes for the groups were compared using statistical significance testing and adjusted for multiple membership to account for the effect of multiple therapists at different sites. Interviews were analysed using interpretive phenomenology to explore confidence.
A median of seven intervention sessions interquartile range (IQR) 3-7 sessions, median duration of 369 minutes (IQR 170-691.5 minutes) per participant was delivered. There was no significant difference between the groups on health-related quality of life (social function). There were no significant differences between groups in functional ability, psychological well-being or SWOM at 6- or 12-month follow-ups. There was a significant difference observed for travel journeys with the intervention group being 42% more likely to make a journey compared with the control group rate ratio 1.42, 95% confidence interval (95% CI) 1.14 to 1.67 at 6 months and 76% more likely (rate ratio 1.76, 95% CI 1.36 to 1.95) at 12 months. The number of journeys was affected by the therapist effect. The mean incremental cost (total NHS and PSS cost) of the intervention was £3413.75 (95% CI -£448.43 to £7121.00), with an incremental quality-adjusted life-year gain of -0.027 (95% CI -0.060 to 0.007) according to the European Quality of Life-5 Dimensions and -0.003 (95% CI -0.016 to 0.006) according to the Short Form questionnaire-6 Dimensions. At baseline, 259 out of 281 (92.2%) participants in the control group were dissatisfied with outdoor mobility but at the 6-month assessment this had reduced to 77.7% (181/233), a 15% reduction. The corresponding reduction in the intervention group was slightly greater (21%) than 268 out of 287 (93.4%) participants dissatisfied with outdoor mobility at baseline to 189 out of 261 (72.4%) at 6 months. Participants described losing confidence after stroke as being detrimental to outdoor mobility. Recruitment and retention rates were high. The intervention was deliverable by the NHS but had a neutral effect in all areas apart from potentially increasing the number of journeys. This was dependent on the therapist effect, meaning that some therapists were more successful than others. The control appeared to affect change.
The outdoor mobility intervention provided in this study to these stroke patients was not clinically effective or cost-effective. However, the provision of personalised information and monthly diaries should be considered for all people who wish to get out more.
Current Controlled Trials ISRCTN58683841.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 29. See the NIHR Journals Library website for further project information.
... expansion of the proteomic analysis to compare a wider range of tumour and normal cell types may reveal why some malignant cells are more sensitive to drug inhibition than others. ... perhaps the ...most exciting potential use of this new approach is in personalized medicine, to predict whether a patient would respond to treatment with Hsp90 inhibitors. ... it is conceivable that determining the proportion of the Hsp90 population in a patient's cancer cells that is available for binding to a tagged inhibitor could predict drug sensitivity in the clinic.
To determine the clinical and cost effectiveness of a multifactorial fall prevention programme compared with usual care in long term care homes.
Multicentre, parallel, cluster randomised controlled ...trial.
Long term care homes in the UK, registered to care for older people or those with dementia.
1657 consenting residents and 84 care homes. 39 were randomised to the intervention group and 45 were randomised to usual care.
Guide to Action for Care Homes (GtACH): a multifactorial fall prevention programme or usual care.
Primary outcome measure was fall rate at 91-180 days after randomisation. The economic evaluation measured health related quality of life using quality adjusted life years (QALYs) derived from the five domain five level version of the EuroQoL index (EQ-5D-5L) or proxy version (EQ-5D-5L-P) and the Dementia Quality of Life utility measure (DEMQOL-U), which were self-completed by competent residents and by a care home staff member proxy (DEMQOL-P-U) for all residents (in case the ability to complete changed during the study) until 12 months after randomisation. Secondary outcome measures were falls at 1-90, 181-270, and 271-360 days after randomisation, Barthel index score, and the Physical Activity Measure-Residential Care Homes (PAM-RC) score at 91, 180, 270, and 360 days after randomisation.
Mean age of residents was 85 years. 32% were men. GtACH training was delivered to 1051/1480 staff (71%). Primary outcome data were available for 630 participants in the GtACH group and 712 in the usual care group. The unadjusted incidence rate ratio for falls between 91 and 180 days was 0.57 (95% confidence interval 0.45 to 0.71, P<0.001) in favour of the GtACH programme (GtACH: six falls/1000 residents
usual care: 10 falls/1000). Barthel activities of daily living indices and PAM-RC scores were similar between groups at all time points. The incremental cost was £108 (95% confidence interval -£271.06 to 487.58), incremental QALYs gained for EQ-5D-5L-P was 0.024 (95% confidence interval 0.004 to 0.044) and for DEMQOL-P-U was 0.005 (-0.019 to 0.03). The incremental costs per EQ-5D-5L-P and DEMQOL-P-U based QALY were £4544 and £20 889, respectively.
The GtACH programme was associated with a reduction in fall rate and cost effectiveness, without a decrease in activity or increase in dependency.
ISRCTN34353836.
Molecular hydrogen produced through iron oxidation during formation of serpentine and magnetite can sustain terrestrial subsurface ecosystems. The Fe3+ in serpentine partitions into octahedral and ...tetrahedral sites differently as serpentinization proceeds, and tetrahedral Fe3+ is present toward the end of serpentinization. We map Fe oxidation states in a serpentinite to determine the degree to which serpentinization progressed and where hydrogen production has been maximized to assess habitability at an abandoned chrysotile mine in Norbestos, Quebec, in association with the Canadian Space Agency's Mars Methane Analogue Mission. We also analyzed stable isotopes of carbon and oxygen in carbonates to constrain the conditions of water–rock interaction during serpentinization. Iron oxidation and coordination was determined through field imaging of rock walls with a visible hyperspectral imager (420–720 nm), and samples collected from imaged rocks and elsewhere in the mine were imaged in the laboratory (420–1100 nm). Sample chemistry, mineralogy, and oxidation state were determined with laboratory measurements of visible through mid-infrared reflectance spectra, major element chemistry, mineralogy, and Mössbauer spectroscopy. Mapping with hyperspectral imaging of outcrops and hand samples shows that tetrahedral Fe3+ is common in serpentinites at this site, and results are confirmed through other measurements. Major element chemistry and mineralogy are consistent with serpentine plus minor carbonate. Carbonate samples show an exceptional range in δ13C (−13.14 to +16.12‰ VPDB) and δ18O (−15.48 to −3.20‰ VPDB) that vary with location in the mine. Carbonates south of a shear zone (δ13C more positive) likely formed during periods of serpentinization in a carbon-limited reservoir closed to carbon addition but open to methane escape. Carbonates in a shear zone (δ13C more negative) probably formed later at low temperatures through CO2-metasomatism or atmospheric weathering, and isotopic trends are consistent with kinetic fractionation. The extensive presence of tetrahedral Fe3+ in serpentine shows the system liberally produced H2 while the isotope systematics have implications for preservation of indicators of the aqueous conditions that formed serpentinites on Mars and their habitability.
•Hyperspectral imaging maps iron oxidation state and coordination in serpentine.•Spectrally-determined iron oxidation state relates to hydrogen production.•Stable isotopes show that serpentinization occurred in a carbon-limited environment.•Isotopic signatures of serpentinization events are preserved in an ancient deposit.•This is a habitable subsurface environment relevant to Mars.
Falls in care home residents are common, unpleasant, costly and difficult to prevent.
The objectives were to evaluate the clinical effectiveness and cost-effectiveness of the Guide to Action for ...falls prevention in Care Homes (GtACH) programme.
A multicentre, cluster, parallel, 1 : 1 randomised controlled trial with embedded process evaluation and economic evaluation. Care homes were randomised on a 1 : 1 basis to the GtACH programme or usual care using a secure web-based randomisation service. Research assistants, participating residents and staff informants were blind to allocation at recruitment; research assistants were blind to allocation at follow-up. NHS Digital data were extracted blindly.
Older people's care homes from 10 UK sites.
Older care home residents.
The GtACH programme, which includes care home staff training, systematic use of a multidomain decision support tool and implementation of falls prevention actions, compared to usual falls prevention care.
The primary trial outcome was the rate of falls per participating resident occurring during the 90-day period between 91 and 180 days post randomisation. The primary outcome for the cost-effectiveness analysis was the cost per fall averted, and the primary outcome for the cost-utility analysis was the incremental cost per quality adjusted life-year. Secondary outcomes included the rate of falls over days 0-90 and 181-360 post randomisation, activity levels, dependency and fractures. The number of falls per resident was compared between arms using a negative binomial regression model (generalised estimating equation).
A total of 84 care homes were randomised: 39 to the GtACH arm and 45 to the control arm. A total of 1657 residents consented and provided baseline measures (mean age 85 years, 32% men). GtACH programme training was delivered to 1051 staff (71% of eligible staff) over 146 group sessions. Primary outcome data were available for 630 GtACH participants and 712 control participants. The primary outcome result showed an unadjusted incidence rate ratio of 0.57 (95% CI 0.45 to 0.71;
< 0.01) in favour of the GtACH programme. Falls rates were lower in the GtACH arm in the period 0-90 days. There were no other differences between arms in the secondary outcomes. Care home staff valued the training, systematic strategies and specialist peer support, but the incorporation of the GtACH programme documentation into routine care home practice was limited. No adverse events were recorded. The incremental cost was £20,889.42 per Dementia Specific Quality of Life-based quality-adjusted life-year and £4543.69 per quality-adjusted life-year based on the EuroQol-5 dimensions, five-level version. The mean number of falls was 1.889 (standard deviation 3.662) in the GtACH arm and 2.747 (standard deviation 7.414) in the control arm. Therefore, 0.858 falls were averted. The base-case incremental cost per fall averted was £190.62.
The GtACH programme significantly reduced the falls rate in the study care homes without restricting residents' activity levels or increasing their dependency, and was cost-effective at current thresholds in the NHS.
Future work should include a broad implementation programme, focusing on scale and sustainability of the GtACH programme.
A key limitation was the fact that care home staff were not blinded, although risk was small because of the UK statutory requirement to record falls in care homes.
This trial is registered as ISRCTN34353836.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 26, No. 9. See the NIHR Journals Library website for further project information.
International Arctic Systems for Observing the Atmosphere (IASOA) activities and partnerships were initiated as a part of the 2007–09 International Polar Year (IPY) and are expected to continue for ...many decades as a legacy program. The IASOA focus is on coordinating intensive measurements of the Arctic atmosphere collected in the United States, Canada, Russia, Norway, Finland, and Greenland to create synthesis science that leads to an understanding of why and not just how the Arctic atmosphere is evolving. The IASOA premise is that there are limitations with Arctic modeling and satellite observations that can only be addressed with boots-on-the-ground, in situ observations and that the potential of combining individual station and network measurements into an integrated observing system is tremendous. The IASOA vision is that by further integrating with other network observing programs focusing on hydrology, glaciology, oceanography, terrestrial, and biological systems it will be possible to understand the mechanisms of the entire Arctic system, perhaps well enough for humans to mitigate undesirable variations and adapt to inevitable change.
Fragment‐based approaches are used routinely to discover enzyme inhibitors as cellular tools and potential therapeutic agents. There have been few reports, however, of the discovery of small‐molecule ...enzyme activators. Herein, we describe the discovery and characterization of small‐molecule activators of a glycoside hydrolase (a bacterial O‐GlcNAc hydrolase). A ligand‐observed NMR screen of a library of commercially available fragments identified an enzyme activator which yielded an approximate 90 % increase in kcat/KM values (kcat=catalytic rate constant; KM=Michaelis constant). This compound binds to the enzyme in close proximity to the catalytic center. Evolution of the initial hits led to improved compounds that behave as nonessential activators effecting both KM and Vmax values (Vmax=maximum rate of reaction). The compounds appear to stabilize an active “closed” form of the enzyme. Such activators could offer an orthogonal alternative to enzyme inhibitors for perturbation of enzyme activity in vivo, and could also be used for glycoside hydrolase activation in many industrial processes.
Glykosidase‐Aktivatoren: Ein biophysikalischer fragmentbasierter Screening‐Ansatz identifiziert niedermolekulare Aktivatoren für eine Glykosidhydrolase. Kristallstrukturen zeigen, dass die Aktivatoren (gelbes Molekül im Bild) in der Nähe des katalytische Enzymzentrum binden und als nichtessenzielle Aktivatoren wirken. Die Aktivierung könnte auf der Stabilisierung einer katalytisch aktiven Enzymkonformation beruhen.
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