We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Wind tunnel measurements of the incident turbulent velocity fields and axial forces on a horizontal axis turbine and porous disc analogues are reported. The models were tested in both a simulated atmospheric boundary layer (ABL) and in grid turbulence, allowing for a range of turbulence length scale to rotor diameter ratios to be considered. A theoretical framework to account for the combined effect of distortion and potential flow blocking in the induction zone is presented. In the case of very large length-scale turbulence to diameter ratios, where distortion effects are minimal, a quasi-steady approach is adopted for the effect of blocking. For the small length-scale ratio limit, the method is developed from the classical analyses for rapid distortion of turbulence and blockage from flow through a porous sheet of resistance. For general length-scale ratios, an efficient prediction method based on interpolation between the two length-scale ratio extremes is established. For very large length-scale ratios, a quasi-steady theory without distortion is appropriate for a rotor or disc in a simulated ABL. The small length-scale theory is applicable for tests conducted in grid turbulence. The results of the study can inform the prediction and interpretation of typical measurements of turbulence within the induction zone and the fluctuating loads on a rotor, at both prototype and full scale. This is of particular importance to fatigue load assessments.
The Devonian Hera metaturbidite-hosted polymetallic Au–Zn–Pb–Ag deposit of central NSW, Australia, contained a total undepleted resource of 3.6 Mt @ 3.3 g/t Au, 25 g/t Ag, 2.6% Pb and 3.8% Zn. The deposit comprises a number of distinctive lodes with each containing a distinctive ore and alteration/gangue mineralogy, though generally the sulfide ore comprises various mixtures of sphalerite, galena, chalcopyrite, pyrrhotite and relatively common visible gold–electrum. The North Pod and Far West lodes are distinctly Sb rich and contain a more diverse ore mineralogy with arsenopyrite, native silver, native antimony, gudmundite, tetrahedrite-(Fe), argentotetrahedrite-(Fe), acanthite, dyscrasite, nisbite and breithauptite. From analysis of 52,760 assays from across the deposit it was found that there was a very poor correlation between gold and each of Fe, Zn, S, Pb, Cu, As and Ag, whereas Ag correlated reasonably well with both Pb and Zn. Results from EPMA shows that gold varies widely in composition from host-rock associated gold (96 wt.% Au) through more intermediate compositions (88–73 wt.% Au) to electrum (46–27 wt.% Au), commonly associated with Sb-phases and containing significant Sb within the gold itself (1.05–2.58 wt.% Sb). From the Far West lense, aurostibite occurs as distinctive rims around gold. Although aurostibite associated with gold contains no silver, the gold itself contains constant moderate amounts (10.87–12.27 wt.% Ag). We suggest that the aurostibite and other Sb phases formed from a late-stage Sb-rich hydrothermal during low-temperature retrograde skarn alteration. There is abundant evidence for both chemical and physical remobilisation at Hera and this remobilisation is largely responsible for the spectrum of gold compositions observed. The source for these fluids may be an underlying magmatic body, evidence for which occurs as granite pegmatite dykes in various locations throughout the deposit. Furthermore, gold with a moderate to high Sb content may be indicative of a low temperature of formation.
The critical period for weed control (CPWC) adds value to integrated weed management by identifying the period during which weeds need to be controlled to avoid yield losses exceeding a defined threshold. However, the traditional application of the CPWC does not identify the timing of control needed for weeds that emerge late in the critical period. In this study, CPWC models were developed from field data in high-yielding cotton crops during three summer seasons from 2005 to 2008, using the mimic weed, common sunflower, at densities of two to 20 plants per square meter. Common sunflower plants were introduced at up to 450 growing degree days (GDD) after crop planting and removed at successive 200 GDD intervals after introduction. The CPWC models were described using extended Gompertz and logistic functions that included weed density, time of weed introduction, and time of weed removal (logistic function only) in the relationships. The resulting models defined the CPWC for late-emerging weeds, identifying a period after weed emergence before weed control was required to prevent yield loss exceeding the yield-loss threshold. When weeds emerged in sufficient numbers toward the end of the critical period, the model predicted that crop yield loss resulting from competition by these weeds would not exceed the yield-loss threshold until well after the end of the CPWC. These findings support the traditional practice of ensuring weeds are controlled before crop canopy closure, with later weed control inputs used as required.
The upsurge in the number of people affected by the COVID-19 is likely to lead to increased rates of emotional trauma and mental illnesses. This article systematically reviewed the available data on the benefits of interventions to reduce adverse mental health sequelae of infectious disease outbreaks, and to offer guidance for mental health service responses to infectious disease pandemic. PubMed, Web of Science, Embase, PsycINFO, WHO Global Research Database on infectious disease, and the preprint server medRxiv were searched. Of 4278 reports identified, 32 were included in this review. Most articles of psychological interventions were implemented to address the impact of COVID-19 pandemic, followed by Ebola, SARS, and MERS for multiple vulnerable populations. Increasing mental health literacy of the public is vital to prevent the mental health crisis under the COVID-19 pandemic. Group-based cognitive behavioral therapy, psychological first aid, community-based psychosocial arts program, and other culturally adapted interventions were reported as being effective against the mental health impacts of COVID-19, Ebola, and SARS. Culturally-adapted, cost-effective, and accessible strategies integrated into the public health emergency response and established medical systems at the local and national levels are likely to be an effective option to enhance mental health response capacity for the current and for future infectious disease outbreaks. Tele-mental healthcare services were key central components of stepped care for both infectious disease outbreak management and routine support; however, the usefulness and limitations of remote health delivery should also be recognized.
A longstanding issue in the field of nutrition is the potential inaccuracy of methods traditionally used for dietary assessment (i.e. food diaries and food frequency questionnaires). It is possible to overcome the limitations and biases of these techniques by combining them with analytical measurements in human biofluids. Metabolomic technologies are gaining popularity as nutritional tools due to their capacity to measure metabolic responses to external stimuli, such as the ingestion of certain foods. This project performed both LC-MS and 1H-NMR metabolomic profiling on serum samples collected as part of the NICOLA study (Northern Irish Cohort for the Longitudinal Study of Aging) in order to discover novel dietary biomarkers. A dietary validation cohort (NIDAS) was incorporated within NICOLA, involving 45 males and 50 females, aged 50 years and over. Participants provided detailed dietary data (4-day food diary) and blood samples at two time-points, six months apart. Serum samples were processed on two analytical platforms. 1H-NMR spectra were acquired using a Bruker 600 MHz Ascent coupled to a TCI cryoprobe and processed using Bayesil (University of Alberta, Canada). A Waters TQ-S coupled with an Acquity I-class UPLC was used in combination with a targeted commercially available kit (AbsoluteIDQ p180 kit, Biocrates). Mass spectra obtained were processed with MetIDQ and verified using MassLynx (v4.1). Data were tested for normality, and metabolite concentrations were correlated with recorded dietary intake of each food type using SPSS. Additional tests (PCA, PLS-DA, ROC Curves) were performed on MetaboAnalyst 4.0 (University of Alberta, Canada). More than 50 statistically significant (P < 0.05) food-metabolite correlations were detected, 15 of which remained significant after eliminating potential confounding from sex, age and BMI. The strongest correlations were between fruit consumption and acetic acid, and between dairy consumption and certain glycerophospholipids (e.g. LysoPC aa C20:3). Stratifying the cohort by gender yielded further correlations, including PC ae C38:2 (dairy; males), PC aa C34:4 (dairy; females), PC aa C36:4 (dairy; females) and trans-4-Hydroxyproline (meat; males). A number of potential blood-based food biomarkers were detected, many of which are gender-specific, and some are corroborated by previously published studies. However, further validation work is required. For example, biological plausibility needs to be established, and the findings need to be reproduced in other cohorts to demonstrate their applicability in larger and more diverse populations. These results contribute greatly to the ongoing efforts to discover and validate reliable nutritional biomarkers as an objective and unbiased measurement of food intake.
New δ13Ccarb and microfacies data from Hereford–Worcestershire and the West Midlands allow for a detailed examination of variations in the Homerian carbon isotope excursion (Silurian) and depositional environment within the Much Wenlock Limestone Formation of the Midland Platform (Avalonia), UK. These comparisons have been aided by a detailed sequence-stratigraphic and bentonite correlation framework. Microfacies analysis has identified regional differences in relative sea-level change and indicates an overall shallowing of the carbonate platform interior from Hereford–Worcestershire to the West Midlands. Based upon the maximum δ13Ccarb values for the lower and upper peaks of the Homerian carbon isotope excursion (CIE), the shallower depositional setting of the West Midlands is associated with values that are 0.7 ‰ and 0.8 ‰ higher than in Hereford–Worcestershire. At the scale of parasequences the effect of depositional environment upon δ13Ccarb values can also be observed, with a conspicuous offset in the position of the trough in δ13Ccarb values between the peaks of the Homerian CIE. This offset can be accounted for by differences in relative sea-level change and carbonate production rates. While such differences complicate the use of CIEs as a means of high-resolution correlation, and caution against correlations based purely upon the isotopic signature, it is clear that a careful analysis of the depositional environment can account for such differences and thereby improve the use of carbon isotopic curves as a means of correlation.
Psychosocial interventions that mitigate psychosocial distress in cancer patients are important. The primary aim of this study was to examine the feasibility and acceptability of an adaptation of the Mindful Self-Compassion (MSC) program among adult cancer patients. A secondary aim was to examine pre–post-program changes in psychosocial wellbeing.
Method
The research design was a feasibility and acceptability study, with an examination of pre- to post-intervention changes in psychosocial measures. A study information pack was posted to 173 adult cancer patients 6 months–5 years post-diagnosis, with an invitation to attend an eight-week group-based adaptation of the MSC program.
Results
Thirty-two (19%) consented to the program, with 30 commencing. Twenty-seven completed the program (mean age: 62.93 years, SD 14.04; 17 [63%] female), attending a mean 6.93 (SD 1.11) group sessions. There were no significant differences in medico-demographic factors between program-completers and those who did not consent. However, there was a trend toward shorter time since diagnosis in the program-completers group. Program-completers rated the program highly regarding content, relevance to the concerns of cancer patients, and the likelihood of recommending the program to other cancer patients. Sixty-three percent perceived that their mental wellbeing had improved from pre- to post-program; none perceived a deterioration in mental wellbeing. Small-to-medium effects were observed for depressive symptoms, fear of cancer recurrence, stress, loneliness, body image satisfaction, mindfulness, and self-compassion.
Significance of results
The MSC program appears feasible and acceptable to adults diagnosed with non-advanced cancer. The preliminary estimates of effect sizes in this sample suggest that participation in the program was associated with improvements in psychosocial wellbeing. Collectively, these findings suggest that there may be value in conducting an adequately powered randomized controlled trial to determine the efficacy of the MSC program in enhancing the psychosocial wellbeing of cancer patients.
Guidelines for palliative and spiritual care emphasize the importance of screening patients for spiritual suffering. The aim of this review was to synthesize the research evidence of the accuracy of measures used to screen adults for spiritual suffering.
Methods
A systematic review of the literature. We searched five scientific databases to identify relevant articles. Two independent reviewers screened, extracted data, and assessed study methodological quality.
Results
We identified five articles that yielded information on 24 spiritual screening measures. Among all identified measures, the two-item Meaning/Joy & Self-Described Struggle has the highest sensitivity (82–87%), and the revised Rush protocol had the highest specificity (81–90%). The methodological quality of all included studies was low.
Significance of Results
While most of the identified spiritual screening measures are brief (comprised 1 to 12 items), few had sufficient accuracy to effectively screen patients for spiritual suffering. We advise clinicians to use their critical appraisal skills and clinical judgment when selecting and using any of the identified measures to screen for spiritual suffering.
In Arabidopsis, seed germination is a biphasic process involving rupture of the seed coat followed by emergence of the radicle through the micropylar endosperm. Embryo expansion results in seed coat rupture and removal of seed coat imposed dormancy with DELLA proteins blocking embryo expansion in the absence of gibberellins. Exogenous abscisic acid (ABA) treatment does not block seed coat rupture but does block radicle emergence. We used this limited effect of exogenous ABA to further investigate the mechanism by which it blocks the onset of germination marked by seed coat rupture. We show that physical nicking of the seed coat results in exogenous ABA treatment blocking both seed coat and endosperm rupture and this block requires the transcription factors ABI3 and ABI5, but not ABI4. Furthermore, we show that the repression of expression of several EXPANSIN genes (EXPA1, EXPA2, EXPA3, EXPA9 and EXPA20) by exogenous ABA requires ABI5. We conclude that ABI5 plays an important role in the ABA-mediated repression of germination through prevention of seed coat rupture and propose that this involves EXPANSIN related control of cell wall loosening.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Gut microbes have a substantial influence on systemic immune function and allergic sensitisation. Manipulation of the gut microbiome through prebiotics may provide a potential strategy to influence the immunopathology of asthma. This study investigated the effects of prebiotic Bimuno-galactooligosaccharide (B-GOS) supplementation on hyperpnoea-induced bronchoconstriction (HIB), a surrogate for exercise-induced bronchoconstriction, and airway inflammation. A total of ten adults with asthma and HIB and eight controls without asthma were randomised to receive 5·5 g/d of either B-GOS or placebo for 3 weeks separated by a 2-week washout period. The peak fall in forced expiratory volume in 1 s (FEV1) following eucapnic voluntary hyperpnoea (EVH) defined HIB severity. Markers of airway inflammation were measured at baseline and after EVH. Pulmonary function remained unchanged in the control group. In the HIB group, the peak post-EVH fall in FEV1 at day 0 (−880 (sd 480) ml) was unchanged after placebo, but was attenuated by 40 % (−940 (sd 460) v. −570 (sd 310) ml, P=0·004) after B-GOS. In the HIB group, B-GOS reduced baseline chemokine CC ligand 17 (399 (sd 140) v. 323 (sd 144) pg/ml, P=0·005) and TNF-α (2·68 (sd 0·98) v. 2·18 (sd 0·59) pg/ml, P=0·040) and abolished the EVH-induced 29 % increase in TNF-α. Baseline C-reactive protein was reduced following B-GOS in HIB (2·46 (sd 1·14) v. 1·44 (sd 0·41) mg/l, P=0·015) and control (2·16 (sd 1·02) v. 1·47 (sd 0·33) mg/l, P=0·050) groups. Chemokine CC ligand 11 and fraction of exhaled nitric oxide remained unchanged. B-GOS supplementation attenuated airway hyper-responsiveness with concomitant reductions in markers of airway inflammation associated with HIB.
To identify the behavioral determinants—both barriers and enablers—that may impact physician hand hygiene compliance.
Design.
A qualitative study involving semistructured key informant interviews with staff physicians and residents.
Setting.
An urban, 1,100-bed multisite tertiary care Canadian hospital.
Participants.
A total of 42 staff physicians and residents in internal medicine and surgery.
Methods.
Semistructured interviews were conducted using an interview guide that was based on the theoretical domains framework (TDF), a behavior change framework comprised of 14 theoretical domains that explain health-related behavior change. Interview transcripts were analyzed using thematic content analysis involving a systematic 3-step approach: coding, generation of specific beliefs, and identification of relevant TDF domains.
Results.
Similar determinants were reported by staff physicians and residents and between medicine and surgery. A total of 53 specific beliefs from 9 theoretical domains were identified as relevant to physician hand hygiene compliance. The 9 relevant domains were knowledge; skills; beliefs about capabilities; beliefs about consequences; goals; memory, attention, and decision processes; environmental context and resources; social professional role and identity; and social influences.
Conclusions.
We identified several key determinants that physicians believe influence whether and when they practice hand hygiene at work. These beliefs identify potential individual, team, and organization targets for behavior change interventions to improve physician hand hygiene compliance.
Infect Control Hosp Epidemiol 2014;35(12):1511–1520
During the past decade there has been a major advance in clinical management of schizophrenic disorders (Falloon & Shanahan, 1990; Lam, 1991; Schooler & Hogarty, 1987). This has resulted from application of strategies based upon a vulnerability-stress model of mental disorders. This considers mental disorders to result from interactions between specific biological vulnerability and non-specific environmental stresses (Falloon & Fadden, 1993).
Therapeutic interventions derived from this model combine biomedical strategies, predominantly optimal pharmacotherapy, with psychosocial strategies that aim to enhance the capacity of the index patient and his/her social network to cope with the impact of environmental stresses on the course of the disorder. Ten controlled studies have been published since 1980 that meet minimal standards of research design, with follow-up for at least 1 year (Bellack, Turner, Hersen, & Luber, 1985; Falloon, 1985; Gunderson et al., 1984; Hogarty et al., 1986; Leff, Kuipers, Berkowitz, Eberlein-Fries, & Sturgeon, 1982; Leff et al., 1989; Malm, 1982; McFarlane, 1990; Tarrier et al., 1988; Wallace & Liberman, 1985). Nine also provided 2-year results. Overall, these studies show that the addition of psychosocial strategies to optimal case management and long-term drug prophylaxis halves the rate of major clinical exacerbations in people suffering from schizophrenia. This benefit is most notable during the first year after a major schizophrenic episode, particularly when the psychosocial interventions encompass patients' immediate social support systems, usually the family or marital household (Falloon, 1985; Hogarty et al., 1986; Leff et al., 1982; Leff et al., 1989; McFarlane, 1990; Tarrier et al., 1988).
This chapter argues for an understanding of connectivity through mobility by elders living in rural areas that goes beyond the traditional transport planning focus on the supply of and demand for transport services. This involves consideration of not just physical movement, but also all the other ways in which older people can be ‘mobile’ for connectivity and the wider benefits and meanings mobility brings, for example, video-calling grandchildren using computer software, finding out about shopping delivery services for use in bad weather or compiling a scrapbook about a past alpine holiday. Following a brief review of methods, a conceptual framework for mobility that can be applied across the life course is presented. The following section applies this framework as a context to understanding some of the key mobility policy and practice challenges for the promotion of the connectivity of rural elders, which relate to the availability of mobility options – cars in particular – and the associated issues of accessibility and mobility-linked social exclusion. It is concluded that the more holistic appraisal of mobility for older citizens brings important conceptual benefits. A picture emerges of rural areas being ‘car-intensive’, but less car-dependent than identified in previous studies, with accessibility for connectivity also relatively unproblematic for the majority, although with minorities representing important exceptions. Practical relevance is drawn out for planning and urban design, as well as for health and social care professionals.
Methods
The analysis draws on the quantitative survey described in Chapter One and two qualitative data-collection activities conducted specifically for the mobility and transport study that was part of the Grey and Pleasant Land (GaPL) project: 45 semi-structured interviews, for which the participants were selected to represent a range of mobility lifestyles; and 10 phenomenological interviews, with participants selected according to varying health and mobility statuses.
The GaPL survey contained a series of mobility-related questions that addressed travel patterns and behaviours, mode choice (including over time), and whether mobility played a role in either exclusion from, or engagement with, the local community. Participants in the semi-structured interviews were mostly recruited from volunteers identified through the quantitative survey, but due to the low representation in the quantitative survey sample of a particular group of interest (people who had recently given up car-driving), seven further participants were recruited from outside of the quantitative survey sample.
Agents of opportunity (AO) in academic medical centers (AMC) are defined as unregulated or lightly regulated substances used for medical research or patient care that can be used as “dual purpose” substances by terrorists to inflict damage upon populations. Most of these agents are used routinely throughout AMC either during research or for general clinical practice. To date, the lack of careful regulations for AOs creates uncertain security conditions and increased malicious potential. Using a consensus-based approach, we collected information and opinions from staff working in an AMC and 4 AMC-affiliated hospitals concerning identification of AO, AO attributes, and AMC risk and preparedness, focusing on AO security and dissemination mechanisms and likely hospital response. The goal was to develop a risk profile and framework for AO in the institution. Agents of opportunity in 4 classes were identified and an AO profile was developed, comprising 16 attributes denoting information critical to preparedness for AO misuse. Agents of opportunity found in AMC present a unique and vital gap in public health preparedness. Findings of this project may provide a foundation for a discussion and consensus efforts to determine a nationally accepted risk profile framework for AO. This foundation may further lead to the implementation of appropriate regulatory policies to improve public health preparedness. Agents of opportunity modeling of dissemination properties should be developed to better predict AO risk.
(Disaster Med Public Health Preparedness. 2010;4:318-325)
Background: Agents of opportunity (AO) are potentially harmful biological, chemical, radiological, and pharmaceutical substances commonly used for health care delivery and research. AOs are present in all academic medical centers (AMC), creating vulnerability in the health care sector; AO attributes and dissemination methods likely predict risk; and AMCs are inadequately secured against a purposeful AO dissemination, with limited budgets and competing priorities. We explored health care workers' perceptions of AMC security and the impact of those perceptions on AO risk.
Methods: Qualitative methods (survey, interviews, and workshops) were used to collect opinions from staff working in a medical school and 4 AMC-affiliated hospitals concerning AOs and the risk to hospital infrastructure associated with their uncontrolled presence. Secondary to this goal, staff perception concerning security, or opinions about security behaviors of others, were extracted, analyzed, and grouped into themes.
Results: We provide a framework for depicting the interaction of staff behavior and access control engineering, including the tendency of staff to “defeat” inconvenient access controls. In addition, 8 security themes emerged: staff security behavior is a significant source of AO risk; the wide range of opinions about “open” front-door policies among AMC staff illustrates a disparity of perceptions about the need for security; interviewees expressed profound skepticism concerning the effectiveness of front-door access controls; an AO risk assessment requires reconsideration of the security levels historically assigned to areas such as the loading dock and central distribution sites, where many AOs are delivered and may remain unattended for substantial periods of time; researchers' view of AMC security is influenced by the ongoing debate within the scientific community about the wisdom of engaging in bioterrorism research; there was no agreement about which areas of the AMC should be subject to stronger access controls; security personnel play dual roles of security and customer service, creating the negative perception that neither role is done well; and budget was described as an important factor in explaining the state of security controls.
Conclusions: We determined that AMCs seeking to reduce AO risk should assess their institutionally unique AO risks, understand staff security perceptions, and install access controls that are responsive to the staff's tendency to defeat them. The development of AO attribute fact sheets is desirable for AO risk assessment; new funding and administrative or legislative tools to improve AMC security are required; and security practices and methods that are convenient and effective should be engineered.
(Disaster Med Public Health Preparedness. 2010;4:291-299)