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Understanding the effects of ketamine on depressive symptoms could help identify which patients might benefit and clarify its mechanism of action in both the early (≤1 day post-infusion) and late (e.g. 2–30 days post-infusion) post-infusion periods. Symptom network analyses could provide complementary information regarding relationships between symptoms.
Aims
To identify the effects of ketamine on symptom-level changes in depression across both the early and late post-infusion periods and on depressive symptom network changes.
Methods
In this secondary analysis of 152 adults with treatment-resistant depression (with 38.8% reporting suicidal ideation at baseline), we compared symptom changes in the early and late post-infusion periods between individuals randomised to a single 40 min infusion of intravenous ketamine 0.5 mg/kg (n = 103) or saline (n = 49) and identified changes in symptom networks between pre- and post-ketamine treatment using network analyses.
Results
In the early post-infusion period, the greatest improvement (comparing ketamine with saline) was in depressive symptoms related to sadness. In network analyses, symptom network connectivity increased following ketamine infusion. Symptoms of sadness and lassitude showed persistent improvement in the first week post-infusion, whereas improvements in suicidal thoughts first emerged 3–4 weeks post-infusion.
Conclusion
Ketamine improved all symptoms but showed the greatest effect on symptoms of sadness, both immediately and in the initial week after treatment. Ketamine also rapidly altered the topology of symptom networks, strengthening interrelationships between residual symptoms. The efficacy of ketamine (compared with saline) regarding suicidal symptoms emerged later. Our findings suggest potentially divergent efficacy, time courses and mechanisms for different symptoms of depression.
Skeptical theism attempts to address the problem of evil by appealing to human cognitive limitations. The causal structure of the world is opaque to us. We cannot tell, and should not expect to be able to tell, if there is gratuitous evil, that is, evil which isn’t necessary for achieving some greater good or for precluding some greater evil. At first, it seems tempting to think that the rapid development of artificial intelligence (AI) technologies might change this fact. Our cognitive limitations may no longer be a fixed point in responding to the problem of evil. But I argue that this won’t ultimately matter. The workings of any AI capable of rendering the problem of evil tractable will likely be just as opaque to us as the causal structure of the world God created. Interestingly, then, both God and a sufficiently advanced AI are alien intelligences to us. This reveals what is truly difficult, and perhaps intractable, about the problem of evil. For the evils to be defeated, we would need a relational understanding of why God permitted them. Yet such an understanding of an inscrutable God seems forever beyond our, and even our post-human descendants, ken.
In a well-known apocryphal story, Theresa of Avila falls off the donkey she was riding, straight into mud, and injures herself. In response, she seems to blame God for her fall. A playful if indignant back and forth ensues. But this is puzzling. Theresa should never think that God is blameworthy. Why? Apparently, one cannot blame what one worships. For to worship something is to show it a kind of reverence, respect, or adoration. To worship is, at least in part, to praise. You cannot praise and blame simultaneously. Indeed, Paul counsels against “back-talk” against God, suggesting we lack the standing to blame our creator (Romans 9:20). Drawing on Strawsonian theorizing about praise and blame, this chapter argues that, surprisingly, a person can both blame and worship God. Although blameful worship is possibly epistemically akratic, it may sometimes be acceptable given our nature as finite, emotional beings. In fact, blaming God might on occasion be the only way we have to stand with God’s goodness despite apparent evidence of evil in the world. This suggestion, I’ll argue, should change the way we think about the problem of evil. The problem has interpersonal and moral psychological dimensions that merit serious attention.
An individual’s birthweight, a marker of in utero exposures, was recently associated with certain psychiatric conditions. However, studies investigating the relationship between an individual’s preterm birth status and/or birthweight and risk for depression during adulthood are sparse; we used data from the Women’s Health Initiative (WHI) to investigate these potential associations. At study entry, 86,925 postmenopausal women reported their birthweight by category (<6 lbs., 6–7 lbs. 15 oz., 8–9 lbs. 15 oz., or ≥10 lbs.) and their preterm birth status (full-term or ≥4 weeks premature). Women also completed the Burnham screen for depression and were asked to self-report if: (a) they had ever been diagnosed with depression, or (b) if they were taking antidepressant medications. Linear and logistic regression models were used to estimate unadjusted and adjusted effect estimates. Compared to those born weighing between 6 and 7 lbs. 15 oz., individuals born weighing <6 lbs. (βadj = 0.007, P < 0.0001) and ≥10 lbs. (βadj = 0.006, P = 0.02) had significantly higher Burnam scores. Individuals born weighing <6 lbs. were also more likely to have depression (adjOR 1.21, 95% CI 1.11–1.31). Individuals born preterm were also more likely to have depression (adjOR 1.18, 95% CI 1.02–1.35); while attenuated, this association remained in analyses limited to only those reportedly born weighing <6 lbs. Our research supports the role of early life exposures on health risks across the life course. Individuals born at low or high birthweights and those born preterm may benefit from early evaluation and long-term follow-up for the prevention and treatment of mental health outcomes.
Modern psychometric methods make it possible to eliminate nonperforming items and reduce measurement error. Application of these methods to existing outcome measures can reduce variability in scores, and may increase treatment effect sizes in depression treatment trials.
Aims
We aim to determine whether using confirmatory factor analysis techniques can provide better estimates of the true effects of treatments, by conducting secondary analyses of individual patient data from randomised trials of antidepressant therapies.
Method
We will access individual patient data from antidepressant treatment trials through Clinicalstudydatarequest.com and Vivli.org, specifically targeting studies that used the Hamilton Rating Scale for Depression (HRSD) as the outcome measure. Exploratory and confirmatory factor analytic approaches will be used to determine pre-treatment (baseline) and post-treatment models of depression, in terms of the number of factors and weighted scores of each item. Differences in the derived factor scores between baseline and outcome measurements will yield an effect size for factor-informed depression change. The difference between the factor-informed effect size and each original trial effect size, calculated with total HRSD-17 scores, will be determined, and the differences modelled with meta-analytic approaches. Risk differences for proportions of patients who achieved remission will also be evaluated. Furthermore, measurement invariance methods will be used to assess potential gender differences.
Conclusions
Our approach will determine whether adopting advanced psychometric analyses can improve precision and better estimate effect sizes in antidepressant treatment trials. The proposed methods could have implications for future trials and other types of studies that use patient-reported outcome measures.
Stratigraphic records extending to Marine Oxygen Isotope Stage (MIS) 3 (57,000–29,000 cal yr BP) or older in Beringia are extremely rare. Three stratigraphic sections in interior western Alaska show near continuous sedimentological and environmental progressions extending from at least MIS 3, if not older, through MIS 1 (14,000 cal yr BP–present). The Kolmakof, Sue Creek, and VABM (vertical angle bench mark) Kuskokwim sections along the central Kuskokwim River, once a highland landscape at the fringe of central and eastern Beringia, contain aeolian deposition and soil sequences dating beyond 50,000 14C yr BP. Thick peaty soil, shallow lacustrine, and tephra deposits represent the MIS 3 interstade (or older). Sand sheet and loess deposits, wedge cast development, and very thin soil development mark the later MIS 3 period and the transition into the MIS 2 stade (29,000–14,000 cal yr BP). Loess accumulation with thicker soil development occurred between ~16,000–13,500 cal yr BP at the MIS 2 and MIS 1 transition. After ~13,500 cal yr BP, loess accumulation waned and peat development increased throughout MIS 1. These stratigraphic sequences represent transitions between a warm and moist period during MIS 3, to a cooler and more arid period during MIS 2, then a return to warmer and moister climates in MIS 1.
This paper presents the findings of a preliminary study comparing implementation of design changes using various computer-aided design (CAD) working styles. Our study compares individuals’ and pairs’ completion of a series of changes to a toy car CAD model. We discuss the results in terms of productivity and value added ratio, derived from time-based quantitative data. We also discuss qualitative findings acquired through post-study surveys. Overall, our findings suggest that pairs were less efficient than individual designers due to overheads like communication, history dependency and complex couplings within the CAD model tree. However, it is also noteworthy that within each pair the lead participant's performance was at par with individual participants. Lastly, we also discuss behaviors and patterns that emerge as unique to the synchronous collaborative environment, motivating future work.
This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling.
Methods
Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication.
Results
The IPS–WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS–WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS–WFM intervention (45 v. 26 weeks, p < 0.004).
Conclusions
The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.
In large, impersonal moral orders many of us wish to maintain good will toward our fellow citizens only if we are reasonably sure they will maintain good will toward us. The mutual maintaining of good will, then, requires that we somehow communicate our intentions to one another. But how do we actually do this? The current paper argues that when we engage in moral responsibility practices—that is, when we express our reactive attitudes by blaming, praising, and resenting—we communicate a desire to maintain good will to those in the community we are imbedded in. Participating in such practices alone will not get the job done, though, for expressions of our reactive attitudes are often what economists call cheap talk. But when we praise and blame in cases of moral diversity, expressions of our reactive attitudes act as costly signals capable of solving our social dilemma.
Limbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28). We examined five limbic tracts of interest: two components of the cingulum (cingulum, cingulate gyrus, and cingulum hippocampus [CGH]), the uncinate fasciculus, the fornix/stria terminalis, and the anterior limb of the internal capsule. Using effect sizes, clinically meaningful moderator effects were found only within the CGH. Greater combat exposure was associated with decreased CGH fractional anisotropy (overall structural integrity) and increased CGH radial diffusivity (perpendicular water diffusivity) among individuals with more severe childhood maltreatment. Our findings provide preliminary evidence of the moderating effect of childhood maltreatment on the relationship between combat exposure and CGH structural integrity. These differences in CGH structural integrity could have maladaptive implications for emotion and memory, as well as provide a potential mechanism by which childhood maltreatment induces vulnerability to later life trauma exposure.
In preliminary greenhouse evaluations and then in field studies, common cocklebur (Xanthium pensylvanicum Wallr.) and wild common sunflower (Helianthus annuus L.) were controlled by early postemergence applications of 3,5-dibromo-4-hydroxybenzonitrile (bromoxynil). Bromoxynil on young soybeans [Glycine max (L.) Merr.] caused temporary necrosis, retarded growth, and delayed maturity but did not reduce the stand of soybeans. Subsequent recovery and final yields of treated soybeans were such that selective control of common cocklebur and wild common sunflower appeared feasible. Treatments were applied as aqueous sprays over the tops of both the weeds and the crop. Rates of 140 or 196 g/ha were sufficient to control common cocklebur or wild common sunflower that was in the six true-leaf stage or smaller. In terms of soybean development, the optimum time for treatment appeared to be about the first trifoliolate stage.
In field studies, bentazon [3-isopropyl-1H-2,1,3-benzothiadiazin-(4)3H-one 2,2-dioxide] was applied as postemergence sprays over the top of weeds and soybeans [Glycine max (L.) Merr.]. Bentazon at 0.84 to 1.68 kg/ha applied as an early postemergence treatment controlled wild mustard [Brassica kaber (DC.) L.C. Wheeler var. pinnatifida (Stokes) L.C. Wheeler], common ragweed (Ambrosia artemisiifolia L.), velvetleaf (Abutilon theophrasti Medic.), Pennsylvania smartweed, (Polygonum pensylvanicum L.), common cocklebur (Xanthium pensylvanicum Wallr.), and wild common sunflower (Helianthus annuus L.). Pigweeds (Amaranthus sp.) were controlled by applications in the three true-leaf stage but became more resistant at later stages. Control of common lambsquarters (Chenopodium album L.) was erratic. The optimum time for controlling weeds with bentazon was around the first trifoliolate stage of soybeans. Rainfall within several hours after treatment reduced weed control. Eight yield studies, two of which included eight cultivars, were conducted on weed-free soybeans. In none were yields reduced significantly by bentazon at 3.36 kg/ha (the highest rate studied). Eight yield studies were conducted on soybeans infested with common cocklebur or velvetleaf. Weed control was generally excellent with 0.84 kg/ha of bentazon. Where infestations were sufficient to reduce yields, bentazon treatments increased the yields to levels generally comparable with those of the handweeded checks. One exception was an application of bentazon to soybeans growing in a low area that was periodically flooded by heavy rains. In that experiment the benefit of controlling common cocklebur was offset by bentazon injury to the soybeans, and yields from the treated plots were about the same as those of the weedy check.
Unilateral audiovestibular symptoms are commonly seen in clinical practice and are rarely caused by retrocochlear pathology. However, clinicians are often required to rule out potentially serious causes of these unilateral symptoms. Gadolinium enhanced magnetic resonance imaging (GdMRI) is the most accurate test for detecting small cerebellopontine angle lesions and also screens the adjacent CNS structures. Its main disadvantage is the cost of the procedure.
Methods:
We studied 100 consecutive patients with both GdMRI and a newer MRI screening study utilizing unenhanced T2-weighted fast spin echo (fse) MRI. Acquired images were randomly assessed by a panel of three neuro-radiologists.
Results:
We found that the screening (fse) MRI was as sensitive and specific when detecting cerebellopontine angle tumors.
Conclusions:
We conclude that T2-weighted fse MRI is a safe and cost-effective alternative to GdMRI and offers better diagnostic utility when compared to auditory brain stem response (ABR) and CT scans.
The continental margin of southern South Africa exhibits an array of emergent marginal marine sediments permitting the reconstruction of long-term eustatic sea-level changes. We report a suite of optical luminescence ages and supplementary amino acid racemization data, which provide paleosea-level index points for three sites on this coastline. Deposits in the Swartvlei and Groot Brak estuaries display tidal inlet facies overlain by shoreface or eolian facies. Contemporary facies relations suggest a probable high stand 6.0-8.5 m above modern sea level (amsl). At Cape Agulhas, evidence of a past sea-level high stand comprises a gravel beach (ca. 3.8 m amsl) and an overlying sandy shoreface facies (up to 7.5 m amsl). OSL ages between 138±7 ka and 118±7 ka confirm a last interglacial age for all marginal marine facies. The high stand was followed by a sea-level regression that was associated with the accumulation of eolian dunes dating to between 122±7 ka and 113±6 ka. These data provide the first rigorous numerical age constraints for last interglacial sea-level fluctuations in this region, revealing the timing and elevation of the last interglacial high stand to broadly mirror a number of other far-field locations.
U-Th isochron ages of tufas formed on shorelines suggest that the last pluvial event in Lake Lahontan and Searles Lake was synchronous at about 16,500 cal yr B.P. (equivalent to a radiocarbon age of between 14,000 and 13,500 yr B.P.), whereas the timing of this pluvial event determined by radiocarbon dating is on the order of 1000 yr younger. The timing of seven distinct periods of near desiccation in Searles Lake during late-glacial time has been reinvestigated for U-Th age determination by mass spectrometry. U-Th dating of evaporite layers in the interbedded mud and salt unit called the Lower Salt in Searles Lake was hampered by the uncertainty in assessing the initial 230Th/232Th of the samples. The resulting ages, corrected by a conservative range of initial 230Th/232Th ratios, suggest close correlation of the abrupt changes recorded in Greenland ice cores (Dansgaard-Oeschger events) and wet–dry conditions in Searles Lake between 35,000 and 24,000 cal yr B.P.
People have natural affinities with the sea and coastlines, using them for work, recreation and aesthetic enjoyment. Interest in coastal areas has increased with growing awareness of environmental sustainability, issues such as natural coastal vulnerability and potential climatic changes, as well as the development of a greater appreciation of impacts on coasts due to urban and industrial development.
In order to make a contribution towards an understanding of the evolution of the South Australian coast and its current changes, and thereby contribute towards its better management, the authors are sharing their coastal knowledge and research. Collectively the contributors, who have been friends and academic collaborators over several decades, have accumulated a vast amount of experience related to the evolution of coastal features of South Australia. From this unique position they have synthesised this information in a manner to make it accessible to students, planners and the general public.
Geologically, the South Australian coast is very young, having evolved only over 1% of geological time, during the past 43 million years since the separation of Australia and Antarctica. It is also very dynamic, with the current shoreline position having been established from only 7000 years ago. There is a remarkable diversity of coastal landscapes in South Australia, ranging through rocky cliffed coasts, submarine canyons, high wave energy sandy beaches and estuarine environments to tidally dominated coasts with sandflats and mangrove woodlands. This diversity of coastal landforms has resulted from the interaction of tides, winds and wave-generated processes operating on a range of rock types impacted by relative movements of the land and sea. Highlighting past changes at the coastline such as erosion, siltation, land movements and fluctuations in sea level provides a sound basis for understanding future changes and instigating appropriate planning strategies. Some features of the South Australian coast have national and global research significance for understanding sea level changes, coastal evolution and management by providing present analogues of past landforms.
The main aim of this book is educational. By explaining the variable character of the coast and its long-term evolution, it is hoped that this book will provide people with background information and awaken curiosity about the coast, enabling them to understand and interpret coastal landscapes, or ‘to read the coastal landscape’.