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It remains poorly understood how negative symptoms are experienced in the daily lives of individuals in the early stages of psychosis. We aimed to investigate whether altered affective experience, anhedonia, social anhedonia, and asociality were more pronounced in individuals with an at-risk mental state for psychosis (ARMS) and individuals with first-episode psychosis (FEP) than in controls.
We used the experience sampling methodology (ESM) to assess negative symptoms, as they occurred in the daily life of 51 individuals with FEP and 46 ARMS, compared with 53 controls.
Multilevel linear regression analyses showed no overall evidence for a blunting of affective experience. There was some evidence for anhedonia in FEP but not in ARMS, as shown by a smaller increase of positive affect (BΔat−risk v. FEP = 0.08, p = 0.006) as the pleasantness of activities increased. Against our expectations, no evidence was found for greater social anhedonia in any group. FEP were more often alone (57%) than ARMS (38%) and controls (35%) but appraisals of the social situation did not point to asociality.
Overall, altered affective experience, anhedonia, social anhedonia and asociality seem to play less of a role in the daily life of individuals in the early stages of psychosis than previously assumed. With the experience of affect and pleasure in daily life being largely intact, changing social situations and appraisals thereof should be further investigated to prevent development or deterioration of negative symptoms.
During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.
As referrals to specialist palliative care (PC) grow in volume and diversity, an evidence-based triage method is needed to enable services to manage waiting lists in a transparent, efficient, and equitable manner. Discrete choice experiments (DCEs) have not to date been used among PC clinicians, but may serve as a rigorous and efficient method to explore and inform the complex decision-making involved in PC triage. This article presents the protocol for a novel application of an international DCE as part of a mixed-method research program, ultimately aiming to develop a clinical decision-making tool for PC triage.
Five stages of protocol development were undertaken: (1) identification of attributes of interest; (2) creation and (3) execution of a pilot DCE; and (4) refinement and (5) planned execution of the final DCE.
Six attributes of interest to PC triage were identified and included in a DCE that was piloted with 10 palliative care practitioners. The pilot was found to be feasible, with an acceptable cognitive burden, but refinements were made, including the creation of an additional attribute to allow independent analysis of concepts involved. Strategies for recruitment, data collection, analysis, and modeling were confirmed for the final planned DCE.
Significance of results
This DCE protocol serves as an example of how the sophisticated DCE methodology can be applied to health services research in PC. Discussion of key elements that improved the utility, integrity, and feasibility of the DCE provide valuable insights.
Contemporary ice stream flow is directly linked to conditions at the ice/bed interface, yet this environment is logistically difficult to access. Instead, we investigate subglacial processes important for ice stream flow by studying tills on the deglaciated Antarctic continental shelf. We test currently-accepted hypotheses surrounding subglacial processes and till properties with a Ross Sea dataset. Till shear strengths indicate a continuum of simultaneous processes acting at the bed, rather than discrete ‘deformation’ and ‘lodgement’ end-members. We identify a threshold water content representing saturated pore spaces, leading to basal sliding and meltwater channelization. Based on observations of till properties relative to glacial landforms, we challenge the assumption that low shear strength is linked to intense deformation. Spatial variability in landform morphology reflects variability in deforming processes at the sub-ice stream scale and suggests a maximum deforming bed thickness of 2 m at the grounding line. Regional till properties generally correlate with seafloor geology and deglacial history; the western Ross Sea is characterized by higher and more variable shear strengths and water contents, while lower-shear strength till was preserved in the Eastern Basin. These observations inform till interpretation and provide context for deforming beds beneath the modern ice sheet and on glaciated continental shelves.
A framework was examined to assist school psychologists and counsellors in recommending quality apps for supporting diabetes self-management. A content analysis was undertaken to assess behaviour change strategies in Apple and Android smartphone apps for the self-management of type 2 diabetes. The Behaviour Change Technique Taxonomy was used to assess the presence of behaviour change strategies, while the Mobile App Rating Scale was used to assess overall app quality. Raters found, on average, 7.13 behaviour change techniques out of a possible 93, indicating few behaviour change techniques in apps for the self-management of Type 2 diabetes. Analysis indicated that apps of a higher overall quality tended to incorporate more behaviour change strategies. It was concluded that mental-health professionals are advantaged if they are able to assess and refine selection tools for matching apps with the needs of students with diabetes.
Thalénite-(Y), ideally Y3Si3O10F, is a heavy-rare-earth-rich silicate phase occurring in granite pegmatites that may help to illustrate rare-earth element (REE) chemistry and behaviour in natural systems. The crystal structure and mineral chemistry of thalénite-(Y) were analysed by electron microprobe analysis, X-ray diffraction and micro-Raman spectroscopy from a new locality in the peralkaline granite of the Golden Horn batholith, Okanogan County, Washington State, USA, in comparison with new analyses from the White Cloud pegmatite in the Pikes Peak batholith, Colorado, USA. The Golden Horn thalénite-(Y) occurs as late-stage sub-millimetre euhedral bladed transparent crystals in small miarolitic cavities in an arfvedsonite-bearing biotite granite. It exhibits growth zoning with distinct heavy-rare-earth element (HREE) vs. light-rare-earth element (LREE) enriched zones. The White Cloud thalénite-(Y) occurs in two distinct anhedral and botryoidal crystal habits of mostly homogenous composition. In addition, minor secondary thalénite-(Y) is recognized by its distinct Yb-rich composition (up to 0.8 atoms per formula unit (apfu) Yb). Single-crystal X-ray diffraction analysis and structure refinement reveals Y-site ordering with preferential HREE occupation of Y2 vs. Y1 and Y3 REE sites. Chondrite normalization shows continuous enrichment of HREE in White Cloud thalénite-(Y), in contrast to Golden Horn thalénite-(Y) with a slight depletion of the heaviest REE (Tm, Yb and Lu). The results suggest a hydrothermal origin of the Golden Horn miarolitic thalénite-(Y), compared to a combination of both primary magmatic followed by hydrothermal processes responsible for the multiple generations over a range of spatial scales in White Cloud thalénite-(Y).
The biguanides do not strain an already tired pancreas but allow better utilization of insulin reserves in the body.
Jean Sterne (1969)
Clinical trials of new drugs may overstate efficacy and not identify adverse effects. It is therefore unusual for the passage of time to reveal that a drug is less toxic, has greater efficacy and a wider range of uses than first claimed. For decades metformin was misunderstood, vilified and banned in many countries, but it is now one of the most prescribed drugs in the world. In 2010 there were more than 100 million prescriptions worldwide for metformin, alone, and in combination tablets.
Gillian Shenfield (2013)
Despite a checkered history peppered with delays, uncertainties, and dead ends, as well as fortuitous accidents, metformin has come to assume prominence. It is a drug, with folklore origins, whose clinical benefits are reasonably well defined but one whose mechanism of action continues to resist precise definition. That is not to say that it is prescribed only to a select few or that it is a compound of such structural sophistication that it is intrinsically challenging as an object of research because that is not the case. Metformin is the current standard of care for the treatment of one of the most common chronic conditions in the modern world – type 2 diabetes – and its structure is remarkably simple by comparison with that of most other drugs. It is a modest methylated biguanide (dimethylbiguanide, alias N,N-dimethylimidodicarbonimidic diamide; Figure 9.1) with a molecular weight (165.6 daltons) and structural complexity no greater than that of sugar (glucose; molecular weight 180.3 daltons). Two of the many baffling aspects of the metformin story are the haphazard way in which it first got noticed and the fact that it came to assume the standing it now has at very different times – measured in decades – in different parts of the developed world. Unforeseen too is the extent to which its applications have since expanded from the treatment of type 2 diabetes to the treatment of prediabetes and polycystic ovary syndrome (PCOS), and even cancer.
The Neotoma Paleoecology Database is a community-curated data resource that supports interdisciplinary global change research by enabling broad-scale studies of taxon and community diversity, distributions, and dynamics during the large environmental changes of the past. By consolidating many kinds of data into a common repository, Neotoma lowers costs of paleodata management, makes paleoecological data openly available, and offers a high-quality, curated resource. Neotoma’s distributed scientific governance model is flexible and scalable, with many open pathways for participation by new members, data contributors, stewards, and research communities. The Neotoma data model supports, or can be extended to support, any kind of paleoecological or paleoenvironmental data from sedimentary archives. Data additions to Neotoma are growing and now include >3.8 million observations, >17,000 datasets, and >9200 sites. Dataset types currently include fossil pollen, vertebrates, diatoms, ostracodes, macroinvertebrates, plant macrofossils, insects, testate amoebae, geochronological data, and the recently added organic biomarkers, stable isotopes, and specimen-level data. Multiple avenues exist to obtain Neotoma data, including the Explorer map-based interface, an application programming interface, the neotoma R package, and digital object identifiers. As the volume and variety of scientific data grow, community-curated data resources such as Neotoma have become foundational infrastructure for big data science.
Morphological responses of nonmammalian herbivores to external ecological drivers have not been quantified over extended timescales. Herbivorous nonavian dinosaurs are an ideal group to test for such responses, because they dominated terrestrial ecosystems for more than 155 Myr and included the largest herbivores that ever existed. The radiation of dinosaurs was punctuated by several ecologically important events, including extinctions at the Triassic/Jurassic (Tr/J) and Jurassic/Cretaceous (J/K) boundaries, the decline of cycadophytes, and the origin of angiosperms, all of which may have had profound consequences for herbivore communities. Here we present the first analysis of morphological and biomechanical disparity for sauropodomorph and ornithischian dinosaurs in order to investigate patterns of jaw shape and function through time. We find that morphological and biomechanical mandibular disparity are decoupled: mandibular shape disparity follows taxonomic diversity, with a steady increase through the Mesozoic. By contrast, biomechanical disparity builds to a peak in the Late Jurassic that corresponds to increased functional variation among sauropods. The reduction in biomechanical disparity following this peak coincides with the J/K extinction, the associated loss of sauropod and stegosaur diversity, and the decline of cycadophytes. We find no specific correspondence between biomechanical disparity and the proliferation of angiosperms. Continual ecological and functional replacement of pre-existing taxa accounts for disparity patterns through much of the Cretaceous, with the exception of several unique groups, such as psittacosaurids that are never replaced in their biomechanical or morphological profiles.
Persistent major depression that does not respond to adequate first- or
second-line treatment is a common problem in psychiatry. This article
updates evidence on recommended treatment strategies and reviews the
prospects of more experimental approaches. The main pharmacological
development in recent years has been the demonstration that several atypical
antipsychotic drugs are effective adjunctive agents in improving symptoms in
depression unresponsive to selective serotonin reuptake inhibitors, although
their adverse effect burden is high. There is optimism about novel
pharmacological strategies based on glutamatergic and anti-inflammatory
mechanisms. It is important to combine drug and psychological treatments
whenever possible. With persistent therapeutic engagement, the majority of
patients remit eventually, but subsequent relapse remains a problem.
Clinicians should pursue an active and collaborative treatment plan that
makes use of all effective therapeutic modalities and continues into the
Emergency departments around the world may differ, but many of the problems they face are the same. Written by an international panel of experienced emergency department leaders Emergency Department Leadership and Management provides the latest knowledge and advice to improve your personal leadership skills. The book will assist emergency department leaders in overcoming common management and operational problems including overcrowding, risk management, implementing the right triage system, electronic and IT solutions, improving clinical teamwork, education of emergency department staff, improving patient flow, care pathways and leading during times of change. Example cases are included to allow leaders to compare common cases to the problems which they face in their own departments. Information on designing emergency medicine specialty residency programs is also provided. It is the official text of the International Emergency Department Leadership Institute (IEDLI) and has been endorsed by the International Federation for Emergency Medicine (IFEM).