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ALMA, the Atacama Large Millimeter/submillimeter Array, situated high in the Chilean desert, is the largest ground-based telescope on Earth. This is an insiders' account of how this complex mega-project came to fruition from authors with intimate knowledge of its past and present. The separate roots of ALMA in the US, Europe, and Japan are traced to their merger into an international partnership involving more than twenty countries. The book relates the search for a suitable telescope site, challenges encountered in organization, funding, and construction, and lessons learned along the way. It closes with a review of the most significant results from ALMA, now one of the most productive telescopes in the world. Written for a broad spectrum of readers, including astronomers, engineers, project managers, science historians, government officials, and the general public; the eBook edition is available to download as an Open Access publication on Cambridge Core.
Currently there is no first-line treatment recommended for the negative symptoms of schizophrenia. Psychosocial and behavioural interventions are widely used to reduce the burden of negative symptoms. Meta-analytic studies have summarised the evidence for specific approaches but not compared evidence quality and benefit.
To review and evaluate the evidence from meta-analytic studies of psychosocial and behavioural interventions for the negative symptoms of schizophrenia.
A systematic literature search was undertaken to identify all meta-analyses evaluating psychosocial and behavioural interventions reporting on negative symptom outcomes in people with schizophrenia. Data on intervention, study characteristics, acceptability and outcome were extracted. Risk of bias was evaluated. Results were summarised descriptively, and evidence ranked on methodological quality.
In total, 31 systematic reviews met the inclusion criteria evaluating the efficacy of negative symptom interventions on 33 141 participants. Exercise interventions showed effect sizes (reduction in negative symptoms) ranging from −0.59 to −0.24 and psychological interventions ranging from −0.65 to −0.04. Attrition ranged between 12% to 32%. Across the studies considered heterogeneity varied substantially (range 0–100). Most of the reviews were of very low to low methodological quality. Methodological quality ranking suggested that the effect size for cognitive remediation and exercise therapy may be more robust compared with other approaches.
Most of the interventions considered had a small-to-moderate effect size, good acceptability levels but very few had negative symptoms as the primary intervention target. To improve the confidence of these effect sizes being replicated in clinical settings future studies should minimise risk of bias.
Rural areas tend to be inhabited by more older people and thus have a higher prevalence of dementia. Combined with lower population densities and more sparse geography, rural areas pose numerous barriers and costs relating to support and resource provision. This may leave people with dementia in rural places at a significant disadvantage, leading to a heavy reliance on informal support networks. The present study explores the personal experiences of people living with dementia and carers living in rural areas, seeking to discover both benefits and challenges, as well as recommendations within the literature for improving the lives of those affected by dementia in rural areas. A scoping review following the framework of Arksey and O'Malley identified 60 studies that describe or discuss the personal experience of dementia (either by the person with dementia or carer), in relation to living in rural or remote geographical areas. Four overarching themes were derived, namely the possible benefits of living in a rural community (supportive rural communities), sources of strength described by people affected by dementia in rural areas (managing and coping), detrimental aspects of living in a rural community (rural community challenges) and difficulties with dementia care services. Three further themes yielded recommendations for improving the experience of dementia in rural areas. This review highlights some potential opportunities related to living in rural areas for people living with dementia. These often come with parallel challenges, reflecting a delicate balance between being well-supported and being in crisis for those living in rural areas. Given the limited access to formal services, supporting people with dementia in rural areas requires input and innovation from the people, organisations and services local to those communities.
Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
In at least 400 European caves such as Lascaux, Chauvet and Altamira, Upper Palaeolithic Homo sapiens groups drew, painted and engraved non-figurative signs from at least ~42,000 bp and figurative images (notably animals) from at least 37,000 bp. Since their discovery ~150 years ago, the purpose or meaning of European Upper Palaeolithic non-figurative signs has eluded researchers. Despite this, specialists assume that they were notational in some way. Using a database of images spanning the European Upper Palaeolithic, we suggest how three of the most frequently occurring signs—the line <|>, the dot <•>, and the <Y>—functioned as units of communication. We demonstrate that when found in close association with images of animals the line <|> and dot <•> constitute numbers denoting months, and form constituent parts of a local phenological/meteorological calendar beginning in spring and recording time from this point in lunar months. We also demonstrate that the <Y> sign, one of the most frequently occurring signs in Palaeolithic non-figurative art, has the meaning <To Give Birth>. The position of the <Y> within a sequence of marks denotes month of parturition, an ordinal representation of number in contrast to the cardinal representation used in tallies. Our data indicate that the purpose of this system of associating animals with calendar information was to record and convey seasonal behavioural information about specific prey taxa in the geographical regions of concern. We suggest a specific way in which the pairing of numbers with animal subjects constituted a complete unit of meaning—a notational system combined with its subject—that provides us with a specific insight into what one set of notational marks means. It gives us our first specific reading of European Upper Palaeolithic communication, the first known writing in the history of Homo sapiens.
Many decisions in everyday life involve a choice between exploring options that are currently unknown and exploiting options that are already known to be rewarding. Previous work has suggested that humans solve such “explore-exploit” dilemmas using a mixture of two strategies: directed exploration, in which information seeking drives exploration by choice, and random exploration, in which behavioral variability drives exploration by chance. One limitation of this previous work was that, like most studies on explore-exploit decision making, it focused exclusively on the domain of gains, where the goal was to maximize reward. In many real-world decisions, however, the goal is to minimize losses and it is well known from Prospect Theory that behavior can be quite different in this domain. In this study, we compared explore-exploit behavior of human subjects under conditions of gain and loss. We found that people use both directed and random exploration regardless of whether they are exploring to maximize gains or minimize losses and that there is quantitative agreement between the exploration parameters across domains. Our results also revealed an overall bias towards the more uncertain option in the domain of losses. While this bias towards uncertainty was qualitatively consistent with the predictions of Prospect Theory, quantitatively we found that the bias was better described by a Bayesian account, in which subjects had a prior that was optimistic for losses and pessimistic for gains. Taken together, our results suggest that explore-exploit decisions are driven by three independent processes: directed and random exploration, and a baseline uncertainty seeking that is driven by a prior.
HIV and severe wasting are associated with post-discharge mortality and hospital readmission among children with complicated severe acute malnutrition (SAM); however, the reasons remain unclear. We assessed body composition at hospital discharge, stratified by HIV and oedema status, in a cohort of children with complicated SAM in three hospitals in Zambia and Zimbabwe. We measured skinfold thicknesses and bioelectrical impedance analysis (BIA) to investigate whether fat and lean mass were independent predictors of time to death or readmission. Cox proportional hazards models were used to estimate the association between death/readmission and discharge body composition. Mixed effects models were fitted to compare longitudinal changes in body composition over 1 year. At discharge, 284 and 546 children had complete BIA and skinfold measurements, respectively. Low discharge lean and peripheral fat mass were independently associated with death/hospital readmission. Each unit Z-score increase in impedance index and triceps skinfolds was associated with 48 % (adjusted hazard ratio 0·52, 95 % CI (0·30, 0·90)) and 17 % (adjusted hazard ratio 0·83, 95 % CI (0·71, 0·96)) lower hazard of death/readmission, respectively. HIV-positive v. HIV-negative children had lower gains in sum of skinfolds (mean difference −1·49, 95 % CI (−2·01, −0·97)) and impedance index Z-scores (–0·13, 95 % CI (−0·24, −0·01)) over 52 weeks. Children with non-oedematous v. oedematous SAM had lower mean changes in the sum of skinfolds (–1·47, 95 % CI (−1·97, −0·97)) and impedance index Z-scores (–0·23, 95 % CI (−0·36, −0·09)). Risk stratification to identify children at risk for mortality or readmission, and interventions to increase lean and peripheral fat mass, should be considered in the post-discharge care of these children.
The New York Bight is undergoing rapid anthropogenic change amidst an apparent increase in baleen whale sightings. Though survey efforts have increased in recent years, the lack of published knowledge on baleen whale occurrence prior to these efforts impedes effective assessments of distributional or behavioural shifts due to increasing human activities. Here we synthesize opportunistic sightings of baleen whales from 1998–2017, which represent the majority of sightings data prior to recent survey efforts, and which are largely unpublished. Humpback and fin whales were the most commonly sighted species, followed by North Atlantic right whales and North Atlantic minke whales. Important behaviours such as feeding and nursing were observed, and most species (including North Atlantic right whales) were seen during all seasons. Baleen whales overlapped with multiple anthropogenic use areas, and all species, but of particular importance North Atlantic right whales, were sighted outside the spatial and temporal bounds of the Seasonal Management Areas for North Atlantic right whales. These opportunistic data are vital for providing a baseline and context of baleen whales in the New York Bight prior to broad-scale efforts and facilitate interpretation of current and future observations and trends, which can more accurately inform effective management and mitigation efforts.
Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population.
To investigate whether omega-3 polyunsaturated fatty acid (n−3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis.
Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n−3 PUFA levels predicted change in cognitive performance.
The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months.
We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n−3 PUFAs.
Prior to the COVID-19 pandemic, our research group initiated a pediatric practice-based randomized trial for the treatment of childhood obesity in rural communities. Approximately 6 weeks into the originally planned 10-week enrollment period, the trial was forced to pause all study activity due to the COVID-19 pandemic. This pause necessitated a substantial revision in recruitment, enrollment, and other study methods in order to complete the trial using virtual procedures. This descriptive paper outlines methods used to recruit, enroll, and manage clinical trial participants with technology to obtain informed consent, obtain height and weight measurements by video, and maintain participant engagement throughout the duration of the trial.
The study team reviewed the IRB records, protocol team meeting minutes and records, and surveyed the site teams to document the impact of the COVID-19 shift to virtual procedures on the study. The IRB approved study changes allowed for flexibility between clinical sites given variations in site resources, which was key to success of the implementation.
All study sites faced a variety of logistical challenges unique to their location yet successfully recruited the required number of patients for the trial. Ultimately, virtual procedures enhanced our ability to establish relationships with participants who were previously beyond our reach, but presented several challenges and required additional resources.
Lessons learned from this study can assist other study groups in navigating challenges, especially when recruiting and implementing studies with rural and underserved populations or during challenging events like the pandemic.
A subset of patients who develop post-surgical heart block have recovery of atrioventricular node function. Factors predicting recovery are not understood. We investigated our centre’s incidence of post-surgical heart block and examine factors associated with recovery of atrioventricular node function.
We conducted a single-centre retrospective study of patients 0 – 21 years who underwent cardiac surgery between January 2010 and December 2019 and experienced post-operative heart block. Data including patient and clinical characteristics and operative variables were collected and analysed.
Of 6333 surgical hospitalisations, 128 (2%) patients developed post-operative heart block. Of the 128 patients, 90 (70%) had return of atrioventricular node function, and 38 (30%) had pacemaker placement. Of the 38 patients who underwent pacemaker placement, 6 (15.8%) had recovery of atrioventricular node function noted on long-term follow-up. Median time from onset of heart block to late atrioventricular node recovery was 13 days (Interquartile range: 5 – 117). Patients with single-ventricle physiology (p = 0.04), greater weight (p = 0.03), and shorter cardiopulmonary bypass time (p = 0.015) were more likely to have recovery. The use of post-operative steroids was similar between all groups (p = 0.445). Infectious or wound complications were similar between pacemaker groups (p = 1).
Two per cent of patients who underwent congenital cardiac surgery developed post-operative heart block, and 0.6% underwent pacemaker placement. Early recovery of atrioventricular node was associated with greater weight at the time of surgery, single-ventricle physiology, and shorter cardiopulmonary bypass time. Late recovery of atrioventricular node conduction following pacemaker placement occurred in 15.8% of patients.
The use of distance-based interventions (DBIs) to reduce suicidal ideation and behaviours are an increasingly relevant form of intervention. DBIs are more affordable, scalable and available than traditional face-to-face interventions, helping to narrow the gap between needed and provided care.
To evaluate the overall effectiveness of DBIs against suicidal ideation and behaviours.
We systematically searched Web of Science, Scopus and PubMed for all DBIs primarily aimed at reducing suicidal ideation and behaviours. Data were analysed with a robust variance estimation corrected, multi-level meta-analysis.
We found 38 studies, reporting 110 outcomes. Effectiveness in reducing suicidal ideation was low (standardised mean difference −0.174, 95% CI −0.238 to −0.110). DBIs were significantly less effective against suicidal behaviours than against suicidal ideation, although still effective (standardised mean difference −0.059, 95% CI −0.087 to −0.032). Human involvement had no significant effect on effectiveness.
Despite low effectiveness, DBIs might play a role in large-scale prevention efforts against suicidal ideation within a stepped care approach. Further, DBIs may be helpful in expanding mental health services in low- and middle-income countries with otherwise limited access to mental healthcare. Although the evidence for DBIs efficacy is well grounded, the technical and scientific evaluation of DBIs regarding their set up, functionality and components needs to be addressed in future studies.
To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up.
Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo.
Community settings and care homes in 26 UK centers.
People with probable or possible Alzheimer’s disease and agitation.
Primary outcome included incremental cost of participants’ health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants’ and unpaid carers’ gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives.
One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment.
On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.
During the nineteenth century, U.S. manufacturers shifted away from the “hand labor” mode of production, characteristic of artisan shops, to “machine labor,” which was increasingly concentrated in steam-powered factories. This transition fundamentally changed production tasks, jobs, and job requirements. This paper uses digitized data on these two production modes from an 1899 U.S. Commissioner of Labor report to estimate the frequency and impact of the use of inanimate power on production operation times. About half of production operations were mechanized; the use of inanimate power raised productivity, accounting for about one-quarter to one-third of the overall productivity advantage of machine labor. However, additional factors, such as the increased division of labor and adoption of high-volume production, also played quantitatively important roles in raising productivity in machine production versus by hand.
The impact of secondary fluorescence on the material compositions measured by X-ray analysis for layered semiconductor thin films is assessed using simulations performed by the DTSA-II and CalcZAF software tools. Three technologically important examples are investigated: AlxGa1−xN layers on either GaN or AlN substrates, InxAl1−xN on GaN, and Si-doped (SnxGa1−x)2O3 on Si. Trends in the differences caused by secondary fluorescence are explained in terms of the propensity of different elements to reabsorb either characteristic or bremsstrahlung X-rays and then to re-emit the characteristic X-rays used to determine composition of the layer under investigation. Under typical beam conditions (7–12 keV), the quantification of dopants/trace elements is found to be susceptible to secondary fluorescence and care must be taken to prevent erroneous results. The overall impact on major constituents is shown to be very small with a change of approximately 0.07 molar cation percent for Al0.3Ga0.7N/AlN layers and a maximum change of 0.08 at% in the Si content of (SnxGa1−x)2O3/Si layers. This provides confidence that previously reported wavelength-dispersive X-ray compositions are not compromised by secondary fluorescence.
East of England is considered the “bread basket” of the UK, supplying domestic and global food markets but it is under pressures from policy, economic and environmental challenges. This chapter studies with a mixed-method approach the risks affecting the arable farming sector in the East of England, describing the role of knowledge networks and learning for resilience.
Bangladesh is repeatedly threatened by tropical storms and cyclones, exposing one-third of the total population of the country. As a preparedness measure, several cyclone shelters have been constructed, yet a large proportion of the coastal population, especially women, are unwilling to use them. Existing studies have demonstrated a range of concerns that discourage women from evacuating and have explored the limitations of the shelters, but the experiences of female evacuees have not been apparent in these stories. This study explores the lived-experiences of women in the cyclone shelters of Bangladesh and discusses their health and well-being as evacuees in the shelters. Nineteen women from three extremely vulnerable districts of coastal Bangladesh were interviewed. Seven research themes were identified from the participants’ narratives using van Manen’s thematic analysis process. The most salient theme, being understood (as a woman), portrayed the quintessential image of these women, which subsequently influenced their vulnerability as evacuees. The next themes–being a woman during crisis, being in a hostile situation, being fearful, being uncertain, being faithful, and being against the odds–focused on the incidents they lived through which affected their physical and mental health and the emotions they felt as evacuees. The paper offers a deep inquiry into women’s experiences of well-being in the shelters and recognizes the significance of women’s voices to improve their experiences as evacuees.
Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.
The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.
This was a naturalistic study of community patients recommended for clozapine treatment.
Of 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).
These findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.