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Innovation is needed for the growing number of patients with chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) is effective in improving exercise tolerance and quality of life, but these benefits do not appear to be sustained. This highlights the need for cost effective methods to maintain benefits on completion of therapy. The findings of a large trial from the UK are reported.
Methods
A two-center randomized controlled trial of patients discharged from PR compared the costs and benefits of PR maintenance with standard care. National Health Service (NHS) resource use, personal expenditure, and societal costs were recorded over one year, and bottom-up costing was undertaken for the PR maintenance program. Changes in health-related quality of life were recorded using the EQ-5D-5L, and differences were compared with the level identified as significant for COPD. A cost utility analysis was undertaken from an NHS perspective; uncertainties in cost and outcome data were incorporated into a sensitivity analysis. Cost-effectiveness ratios and cost-effectiveness acceptability curves (CEACs) were computed.
Results
The study included 116 patients who had finished PR within the last four weeks. The economic analysis showed that mean healthcare costs per patient for PR maintenance were approximately GBP139.72 (EUR165.57) lower than for usual care. The observed 0.118 advantage in mean quality-adjusted life-years (QALYs) (p<0.05) was above the threshold (0.051) for COPD significance. CEACs indicated there was a 97 percent chance of achieving GBP20,000 (EUR23,699.80) per QALY (NICE acceptance level ≤GBP30,000 (EUR35,549.70). Patient and societal costs increased this percentage. It was estimated that if patients with COPD completed a maintenance program following PR, the NHS could save up to GBP28.6 million (EUR33.89 million).
Conclusions
Our findings confirm that a structured PR maintenance program is highly cost effective in extending the benefits of short-term PR. The trial, undertaken during COVID, also signals the potential for emerging digital innovations to provide future transformative change in delivering self-management programs to sustain health and reduce NHS costs for people living with chronic conditions.
There is emerging evidence of heterogeneity within treatment-resistance schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and a smaller group becoming treatment-resistant after an initial response period. It has been suggested that these groups have different aetiologies. Few studies have investigated socio-demographic and clinical differences between early and late onset of TRS.
Objectives
This study aims to investigate socio-demographic and clinical correlates of late-onset of TRS.
Methods
Using data from the electronic health records of the South London and Maudsley, we identified a cohort of people with TRS. Regression analyses were conducted to identify correlates of the length of treatment to TRS. Analysed predictors include gender, age, ethnicity, positive symptoms severity, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics.
Results
We observed a continuum of the length of treatment until TRS presentation. Having severe hallucinations and delusions at treatment start was associated shorter duration of treatment until the presentation of TRS.
Conclusions
Our findings do not support a clear cut categorisation between early and late TRS, based on length of treatment until treatment resistance onset. More severe positive symptoms predict earlier onset of treatment resistance.
Disclosure
DFdF, GKS, EF and IR have received research funding from Janssen and H. Lundbeck A/S. RDH and HS have received research funding from Roche, Pfizer, Janssen and Lundbeck. SES is employed on a grant held by Cardiff University from Takeda Pharmaceutical Comp
Understanding the distribution and geometry of faults and fractures is critical for predicting both subsurface permeability architecture and the integrity of geological fluid barriers, particularly in rocks with low primary porosity and permeability. While fracture patterns in relatively competent, weathering-resistant (therefore often well-exposed) rocks are generally well studied in outcrop, the role of mechanically weak layers in defining fracture patterns is frequently overlooked or under-represented. Here we show that rock composition, specifically clay and silicate minerals versus carbonate content, exerts a strong control on fault and fracture propagation and bed-containment within a mechanically layered, Cretaceous carbonate sequence at Canyon Lake Gorge, Texas. We find that relatively incompetent, clay-rich layers limit fault and fracture propagation, and cause bed-containment of fractures in more competent beds. In our results, no clear relationships exist between mechanical layer thickness and fracture abundance. These results are important for understanding the relative importance of composition versus bed thickness on fracture abundance in the subsurface, and for predicting fracture-controlled fluid flow pathways, seals and fracture connectivity across beds with variable compositions, thicknesses and competences.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (${\sim}60\%$), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
Electrochemical capacitors featuring a modified acetonitrile (AN) electrolyte and a binder-free, activated carbon fabric electrode material were assembled and tested at <−40 °C. The melting point of the electrolyte was depressed relative to the standard pure AN solvent through the use of a methyl formate cosolvent, to enable operation at temperatures lower than the rated limit of typical commercial cells (−40 °C). Based on earlier electrolyte formulation studies, a 1:1 ratio of methyl formate to AN (by volume) was selected, to maximize freezing point depression while maintaining a sufficient salt solubility. The salt spiro-(1,1′)-bipyrrolidinium tetrafluoroborate was used, based on its improved conductivity at low temperatures, relative to linear alkyl ammonium salts. The carbon fabric electrode supported a relatively high rate capability at temperatures as low as −65 °C with a modest increase in cell resistance at this reduced temperature. The capacitance was only weakly dependent on temperature, with a specific capacitance of ∼110 F/g.
Treatment-resistant schizophrenia, affecting approximately 20–30% of patients with schizophrenia, has a high burden both for patients and healthcare services. There is a need to identify treatment resistance earlier in the course of the illness, in order that effective treatment, such as clozapine, can be offered promptly. We conducted a systemic literature review of prospective longitudinal studies with the aim of identifying predictors of treatment-resistant schizophrenia from the first episode. From the 545 results screened, we identified 12 published studies where data at the first episode was used to predict treatment resistance. Younger age of onset was the most consistent predictor of treatment resistance. We discuss the gaps in the literature and how future prediction models can identify predictors of treatment response more robustly.
In the UK, most intermediate level radioactive waste is packaged in stainless steel containers. It is important that containers should maintain their integrity for extended periods of storage prior to final disposal. A prototype 4 metre box fabricated from 304S11 stainless steel was monitored at an inland rural building for over twelve years to gain experience in monitoring environmental conditions and corrosion during storage. A wide range of different types of aerosol particles were observed on the surfaces and in the air. They contained corrosive ions such as chloride, as well as other anions such as sulfate and nitrate. The chloride deposition rate was between 0.1 and 4 μg cm−2 yr−1 depending on the orientation and location of the surface, with a chloride/sulfate ratio ranging from ∼0.3–2. The temperature and relative humidity typically ranged from 0–30°C and 40–90%, respectively. The greatest degree of corrosion developed on the base of the box, which had elevated chloride concentrations (10–140 μg cm−2). However, there was little evidence of corrosion propagation on the surface of the box and no evidence of stress corrosion cracking. The average pit propagation rates on a 316L coupon mounted next to the 4 m box were <1 μm yr−1.
Intermediate-level radioactive waste is normally encapsulated in cementitious grout. However, for some wastes, grout may not be suitable and polymeric encapsulants are being considered as an alternative. One concern with such encapsulants is their long-term chemical stability and the possibility that release of aggressive degradation products could cause corrosion.
This paper evaluates the potential for three polymeric encapsulants: two epoxy resins (the APS polymer system, (APS) and Alchemix 4760 (ALC)) and a vinyl-ester styrene (VES); to cause internal corrosion of stainless steel waste containers. The corrosion behaviour of stainless steel 316L in contact with each encapsulant was studied in saturated Ca(OH)2 solutions and deionized (DI) water, at 80°C, under non-irradiated and γ-irradiated conditions.
In aerated, alkaline conditions, 316L was resistant to corrosion in all the conditions tested. However, in DI water, the pH fell to values as low as three due to release of acidic species from the polymers. The two epoxy materials (particularly APS) also released significant levels of chloride; VES did not. Chloride release appeared to be increased by γ-irradiation. As a result of the low pH chloride-containing environment created by the APS encapsulant, 316L experienced localized corrosion, whereas coupons in Alchemix 4760 and VES did not. Weight loss measurements correlated with visual observations. γ-irradiation appeared to increase the degree of corrosion.
Objectives: We sought to clarify the nature of self-reported cognitive function among healthy older adults by considering the short-term, within-person association (coupling) of subjective cognitive function with objective cognitive performance. We expected this within-person coupling to differ between persons as a function of self-perceived global cognitive decline and depression, anxiety, or neuroticism. Methods: This was an intensive measurement (short-term longitudinal) study of 29 older adult volunteers between the ages of 65 and 80 years without an existing diagnosis of dementia or mild cognitive impairment. Baseline assessment included neuropsychological testing and self-reported depression, anxiety, and neuroticism, as well as self- and informant-reported cognitive decline (relative to 10 years previously). Intensive within-person measurement occasions included subjective ratings of cognitive function paired with performance on a computerized working memory (n-back) task; each participant attended four or five assessments separated by intervals of at least one day. Statistical analysis was comprised of multilevel linear regression. Results: Comparison of models suggested that both neuroticism and self-rated cognitive decline explained unique variance in the within-person, across-occasion coupling of subjective cognitive function with objective working memory performance. Conclusions: Self-ratings of cognition may accurately reflect day-to-day variations in objective cognitive performance among older adults, especially for individuals lower in neuroticism and higher in self-reported cognitive decline. Clinicians should consider these individual differences when determining the validity of complaints about perceived cognitive declines in the context of otherwise healthy aging. (JINS, 2018, 24, 57–66)
Late-summer subglacial water pressures have been measured in a dense array of boreholes in the ablation area of Haut Glacier d’Arolla, Switzerland. Interpolated surfaces of minimum diurnal water pressure and diurnal water-pressure variation suggest the presence of a subglacial channel within a more widespread, distributed drainage system. The channel flows along the centre of a variable pressure axis (VPA), some tens of metres wide, that is characterized by low minimum diurnal water pressures (frequently atmospheric) and high diurnal water-pressure variations. These characteristics are transitional over a lateral distance of c. 70 m to higher and more stable subglacial water pressures in the adjacent distributed system. Water-pressure variations recorded in boreholes located close to the centre of the VPA reflect the delivery of surface-derived meltwater to the glacier bed and result in a diurnally reversing, transverse hydraulic gradient that drives water out from the channel into the distributed system during the afternoon and back to the channel overnight. Subglacial observations suggest that such flow occurs through a vertically confined sediment layer. Borehole turbidity records indicate that the resulting diurnal water flows are responsible for the mobilization and transport of fine debris in suspension. Analysis of the propagation velocity and amplitude attenuation cf the diurnal pressure waves suggests that the hydraulic conductivity of the sediment layer decreases exponentially with distance from the channel, falling from c. 10−4 m s−1 at the channel boundary to c. 10−7 m s−1 70 m away. These apparent hydraulic conductivities are consistent with Darcian flow through clean sand and typical glacial till, respectively.
We suggest that fine material is systematically flushed from basal sediments located adjacent to large, melt-season drainage channels beneath warm-based glaciers. This process may have important implications for patterns of glacier erosion, hydro-chemistry and dynamics.
Fire is often used in northern grasslands to control invasive grass species but has unknown effects on Tamarix spp., more recent invaders. Temperature (using an oven as a fire surrogate) and duration combinations that would be most lethal to Tamarix seeds and seedlings were determined. Tamarix seeds were sown in soil-lined dishes, water added to saturation, and seedlings grown for 1 to 5 d. Seeds were also placed in water-saturated or dry soil just before temperature exposure (79 to 204 C [175 to 400 F]) by duration (1 to 5 min) treatments. After treatment, soil water loss was measured by weight difference, and surviving seedlings were counted for 6 d. Tamarix seedling establishment and survival decreased with increasing temperature and duration. The 5-d-old seedlings were the most affected. No 5-d-old seedlings survived 1- and 2-min exposures to 204 C, whereas 1-d-old seedlings had greater than 25% survival. If soils were saturated, two to four times more seedlings established following seed exposure to 177 and 204 C. Longer durations at lower temperatures were required to reduce Tamarix survival. Increasing duration from 2 to 5 min at 121 C decreased 5-d-old seedling survival from more than 80% to less than 10% and eliminated those seedlings at 149 C. Five minutes at 149 C decreased dry-soil seed viability to about 15%, whereas germination on saturated soils remained high (∼75%). No seeds survived the exposure to 177 and 204 C. Soil moisture loss values associated with 90% mortality of 5- and 1-d-old seedlings were 1.7 and 2.2%, respectively. On saturated soils, 90% of seeds died with 2.5% water loss. Under suitable conditions, fire can decrease Tamarix seedling survival. Fire may be useful for controlling Tamarix seedlings in northern grasslands and should be considered for management of new invasions.
Controlled burns and grazing are being tested to manage invasive grasses in the Prairie Pothole region of the Northern Great Plains. These practices, however, may inadvertently promote saltcedar infestations from seed by opening the vegetative canopy. Saltcedar seedling establishment was investigated in greenhouse experiments using intact soil cores from one summit and three footslope sites in eastern South Dakota. Establishment tests were conducted in soil cores collected from treatment and control plots immediately after spring fire treatment (postburn) and in cores that contained peak cool- or peak warm-season vegetation, with or without clipping (simulated grazing treatment), to simulate vegetation conditions typical of saltcedar seed-shed in northern regions. Cores were seeded with 100 saltcedar seeds and subirrigated to maintain high soil water conditions, characteristic of the environment near potholes during late spring/early summer. Seedlings were counted during the first 3 wk to estimate establishment and the height of five seedlings core−1 were measured weekly to estimate growth rates. Opening the canopy with fire or clipping increased saltcedar establishment. Cores taken immediately after fire treatment had two times more seedlings establish (38% vs. 19%) and greater average seedling growth rate (1.5 mm d−1 vs. 0.9 mm d−1) when compared with no-fire controls. Fire after seeding reduced seedling establishment to 5%, but did not affect growth rate. Saltcedar establishment in peak cool-season vegetation cores was 6% regardless of earlier fire treatment, whereas in peak warm-season vegetation, establishment ranged from 8% (no spring fire) to 17% (spring fire). If soils remain wet, invasion risk following spring fire may be greatest when warm-season grasses are flowering because this time coincides with northern saltcedar seed production. Areas adjacent to viable saltcedar seed sources should be managed to maximize canopy cover when seeds are released to limit further establishment. Fire after saltcedar seed deposition may control propagules and young seedlings.
We present the longest-duration directly dated terrestrial palaeoclimate record from the western Mediterranean region: a flowstone speleothem from Gitana Cave, southeast Spain. The main phase of growth was 274 to 58 ka, dated by multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS) U-series methods. Effective precipitation, which we consider primarily responsible for flowstone calcite δ13C variations, measured at 300 μm resolution, was higher during interglacials associated with marine oxygen isotope stages (MIS) 7 and 5, and lower during glacial MIS 6. There is a close correspondence between speleothem δ13C and sea surface temperature (SST) estimates from adjacent Atlantic Ocean cores during MIS 6, which implies that oceanic conditions are critical in controlling the western Mediterranean terrestrial moisture balance during glacial periods. Other features of our record, such as the sequence of termination II warming/moistening between approximately 133 and 127 ka, including a "pause" around 130–128 ka, and the lagged termination of MIS 5 warm intervals (5e, 5c and 5a) are similar to other terrestrial records within the Mediterranean basin, indicating climate synchroneity along the northern Mediterranean coast. The Gitana cave region also may have been a refugium for temperate species during short-lived cold/arid periods during MIS 5.
The glancing interaction of a Prandtl-Meyer expansion fan with a supersonic wake is examined. The particular supersonic wakes of interest are the combustion wake generated by a vertical strut injected scramjet, and the side wall boundary layer of a supersonic wind tunnel. A physical structure for the interaction is defined, and an approximate analysis of the downstream behaviour of the wake is presented. The phenomenon of wake over-turning by the glancing expansion fan is introduced, based on this analysis. This over-turning produces a high pressure zone on the expansion generating surface, which for the vertical strut injected scramjet, is part of the thrust nozzle. Combustion wake over-turning is suggested to be a major thrust producing mechanism in this form of scramjet.
Pressure measurements were taken on the expansion generating surface of a glancing interaction involving the side wall boundary layer of a small supersonic wind tunnel. Results from the analysis presented were found to be consistent with these measurements.
The objective of design is the production of manufacturing drawings which are right. This objective will rarely be achieved without first making mistakes which require experiment to rectify so that design is the work of a team which includes designers who draw, development engineers and experimental manufacturing operatives.
Design must have an output which can be valued and the value of the output must exceed its costs. In the aircraft industry, the cost of design is a considerable part of the cost of the product and must be recovered directly from the customer. Because underestimating the cost of design is endemic and because some work done to obtain orders will not be successful, not all cost of design can be recovered from the customer and so some costs must be written off.
Increasingly stringent attitude stabilisation requirements are the current trend in both experimental and commercial satellites as is seen in the current Intelsat, ESRO and UK communication studies. These craft must be lightweight, compact and rugged during the launch phase but after mission capture such requirements no longer apply. The increasingly high power requirements of such craft are met by the use of large flexible solar arrays which are packed away during launch and unfurl when the craft becomes operational. For the three-axis stabilised craft being studied reaction jets are used to achieve the high pointing accuracy required. Such actuators may be hot or cold gas systems or in the future may be electric engines’. The broad spectral content of these actuators will inevitably excite modes of vibration in a wide range of frequencies. The influence of these highly resonant modes on the performance of on-board controllers, needing a relatively high bandwidth of 0-10 Hz, to achieve high pointing accuracy of up to a few seconds of arc may lead to design difficulties.
Utilitarianism is the view that the rightness of an action depends entirely on expected utility, that is on the sum of the utilities of its consequences weighted by their various probabilities. I shall distinguish two forms of utilitarianism: hedonistic utilitarianism and preference utilitarianism. In hedonistic utilitarianism it is just a matter of pleasure and its opposite, unpleasure. Often utilitarians have used ‘pain’ instead of ‘unpleasure’, but this has the disadvantage that ‘pain’ can suggest ‘a pain’, and ‘a pain’ is not the opposite of ‘a pleasure’. If I annoy you I give you the opposite of pleasure but I do not necessarily give you a pain. In preference utilitarianism we take value to be satisfaction of desires or preferences. It is a difficult theory to work out in so far as we have to take ‘preference’ here to be intrinsic preference, and so need a clear distinction between intrinsic and extrinsic preferences.