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People with schizophrenia die almost 20 years earlier than the general population, most commonly from avertable cardiometabolic disease. Existing pharmacological weight-loss agents including metformin have limited efficacy. Recently available glucagon-like peptide (GLP-1) receptor agonists such as semaglutide have shown promise for weight loss but have yet to be trialled in this population.
To examine the efficacy of semaglutide to ameliorate antipsychotic-induced obesity in people with schizophrenia who have been treated with clozapine for more than 18 weeks.
This is a 36-week, double-blinded, randomised placebo-controlled trial. We will recruit 80 clozapine-treated patients with schizophrenia or schizoaffective disorder, aged 18–64 years, with a baseline body mass index ≥26 kg/m2, who will be randomised to subcutaneous semaglutide of 2.0 mg once a week or placebo for 36 weeks. The primary endpoint will be percentage change in body weight from baseline.
This trial will assess the efficacy and side-effects of the GLP-1 receptor agonist semaglutide on body weight and provide evidence on the possible clinical utility of semaglutide in patients with inadequate response to metformin. The study is registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) with clinical trial registration number ACTRN12621001539820.
This research could benefit individuals with schizophrenia who experience significant health issues, leading to premature mortality, owing to antipsychotic-induced weight gain. Study findings will be disseminated through peer-reviewed publications and conference presentations.
Cognitive behavioural therapy (CBT) is an effective treatment for depression but a significant minority of clients do not complete therapy, do not respond to it, or subsequently relapse. Non-responders, and those at risk of relapse, are more likely to have adverse childhood experiences, early-onset depression, co-morbidities, interpersonal problems and heightened risk. This is a heterogeneous group of clients who are currently difficult to treat.
The aim was to develop a CBT model of depression that will be effective for difficult-to-treat clients who have not responded to standard CBT.
The method was to unify theory, evidence and clinical strategies within the field of CBT to develop an integrated CBT model. Single case methods were used to develop the treatment components.
A self-regulation model of depression has been developed. It proposes that depression is maintained by repeated interactions of self-identity disruption, impaired motivation, disengagement, rumination, intrusive memories and passive life goals. Depression is more difficult to treat when these processes become interlocked. Treatment based on the model builds self-regulation skills and restructures self-identity, rather than target negative beliefs. A bespoke therapy plan is formed out of ten treatment components, based on an individual case formulation.
A self-regulation model of depression is proposed that integrates theory, evidence and practice within the field of CBT. It has been developed with difficult-to-treat cases as its primary purpose. A case example is described in a concurrent article (Barton et al., 2022) and further empirical tests are on-going.
Luke 14:26 has commonly been viewed as an example of hyperbole. This article applies modern studies on hyperbole that hold as its principle criteria both a scalar property and an evaluative/expressive function. We apply these criteria, analyzing Luke 14:26 in terms of encoded language, co-text, and context. We argue that hyperbole arises from the choice to use “hate” rather than “love more than” but also that the hyperbolic usage relies on a cause for effect (emotion for emotional response) metonym.1 In terms of language, we show that “hate” has variant meanings that may be different in their degrees of encoding. In terms of co-text, we argue that Luke’s use of “hate” and Matthew’s use of “love more than” are relevantly chosen; in other words, they are suited to and to be interpreted against their co-texts.
Provision of critical care and resuscitation was not practical during early missions into space. Given likely advancements in commercial spaceflight and increased human presence in low Earth orbit (LEO) in the coming decades, development of these capabilities should be considered as the likelihood of emergent medical evacuation increases.
PubMed, Web of Science, Google Scholar, National Aeronautics and Space Administration (NASA) Technical Server, and Defense Technical Information Center were searched from inception to December 2018. Articles specifically addressing critical care and resuscitation during emergency medical evacuation from LEO were selected. Evidence was graded using Oxford Centre for Evidence-Based Medicine guidelines.
The search resulted in 109 articles included in the review with a total of 2,177 subjects. There were two Level I systematic reviews, 33 Level II prospective studies with 647 subjects, seven Level III retrospective studies with 1,455 subjects, and two Level IV case series with four subjects. There were two Level V case reports and 63 pertinent review articles.
The development of a medical evacuation capability is an important consideration for future missions. This review revealed potential hurdles in the design of a dedicated LEO evacuation spacecraft. The ability to provide critical care and resuscitation during transport is likely to be limited by mass, volume, cost, and re-entry forces. Stabilization and treatment of the patient should be performed prior to departure, if possible, and emphasis should be on a rapid and safe return to Earth for definitive care.
Objectives: Autobiographical memory dysfunction is a marker of vulnerability to depression. Patients with obstructive sleep apnea (OSA) experience high rates of depression and memory impairment, and autobiographical memory impairments have been observed compared to healthy controls; however, these groups were not age-matched. This study aimed to determine whether individuals with untreated OSA have impaired autobiographical memory when compared to age-matched controls, and to assess the quality of autobiographical memories from three broad time points. Methods: A total of 44 participants with OSA (M age=49.4±13.0) and 44 age-matched controls (M age=50.0±13.1) completed the Autobiographical Memory Interview (AMI) to assess semantic and episodic memories from three different life stages, and 44 OSA participants and 37 controls completed the Autobiographical Memory Test (AMT) to assess overgeneral memory recall (an inability to retrieve specific memories). Results: OSA participants had significantly poorer semantic recall of early adult life on the AMI (p<.001), and more overgeneral autobiographical memories recalled on the AMT (=.001), than controls. Poor semantic recall from early adult life was significantly correlated with more depressive symptoms (p=0.006) and lower education (p<0.02), while higher overgeneral memory recall was significantly associated with older age (p=.001). Conclusions: A specific deficit in semantic autobiographical recall was observed in individuals with OSA. OSA patients recalled more overgeneral memories, suggesting that aspects of the sleep disorder affect their ability to recollect specific details of events from their life. These cognitive features of OSA may contribute to the high incidence of depression in this population. (JINS 2019, 25, 266–274)
Schizophrenia affects 1% of the population. Clozapine is the only medication licensed for treatment-resistant schizophrenia and is intensively monitored to prevent harm from neutropenia. Clozapine is also associated with increased risk of pneumonia although the mechanism is poorly understood.
To investigate the potential association between clozapine and antibody deficiency.
Patients taking clozapine and patients who were clozapine-naive and receiving alternative antipsychotics were recruited and completed a lifestyle, medication and infection-burden questionnaire. Serum total immunoglobulins (immunoglobulin (Ig)G, IgA, IgM) and specific IgG antibodies to haemophilus influenzae type B, tetanus and IgG, IgA and IgM to pneumococcus were measured.
Immunoglobulins were all significantly reduced in the clozapine-treated group (n = 123) compared with the clozapine-naive group (n = 111). Odds ratios (ORs) for a reduction in clozapine:control immunoglobulin values below the fifth percentile were IgG, OR = 6.00 (95% CI 1.31–27.44); IgA, OR = 16.75 (95% CI 2.18–128.60); and IgM, OR = 3.26 (95% CI 1.75–6.08). These findings remained significant despite exclusion of other potential causes of hypogammaglobulinaemia. In addition, duration on clozapine was associated with decline in IgG. A higher proportion of the clozapine-treated group reported taking more than five courses of antibiotics in the preceding year (5.3% (n = 5) versus 1% (n = 1).
Clozapine use was associated with significantly reduced immunoglobulin levels and an increased proportion of patients using more than five antibiotic courses in a year. Antibody testing is not included in existing clozapine monitoring programmes but may represent a mechanistic explanation and modifiable risk factor for the increased rates of pneumonia and sepsis-related mortality previously reported in this vulnerable cohort.
Declaration of interest
S.J. has received support from CSL Behring, Shire, LFB, Biotest, Binding Site, Sanofi, GSK, UCB Pharma, Grifols, BPL SOBI, Weatherden, Zarodex and Octapharma for projects, advisory boards, meetings, studies, speaker and clinical trials.
The present paper offers a new interpretation of the three-clause reading of Jude 22–23 and demonstrates how Jude carries on the Jesus tradition by inverting the norms of invective. It is demonstrated that this interpretation is especially surprising given that the epistle follows many conventions of Greco-Roman invective. Given the character of invective, one would expect the writer to instruct the beloved to expel the ungodly from the community. Instead, Jude commands the beloved to ‘show mercy’ to the very ones with whom they contend (Jude 22), a profound reflection of Jude's understanding of mercy and faith.
In order to obtain a better knowledge of past oceanographic variability offshore southern Chile, this study reappraises the changes in the sources of nutrients over the last 25 ka based on a detailed comparison of previously published nitrogen isotope and microfossil records (dinoflagellate cysts, coccoliths and diatoms) from ODP Site 1233 (41°S). Our findings support the main conclusions of Martinez et al. (2006) in the sense that both the Subantarctic Surface Water and the Gunther Undercurrent are potential sources for the recorded late Quaternary sedimentary δ15N signatures at Site 1233, with variable contributions of both sources during different time periods. This study indicates that Subantarctic Surface Water forms the main source for nutrients during the last glacial maximum (25–18.6 cal ka BP), the first part of the deglaciation (18.6–15.7 cal ka BP) and the Holocene (9.8 cal ka BP until present). An increased contribution of Equatorial Subsurface Water as a source of nutrients to the photic zone offshore southern Chile is observed between 14.4 and 9.8 cal ka BP, which is indicative for upwelling conditions at least after 13.2 cal ka BP as indicated by the microfossil data.
Previous work on surface (modern) sediments has defined diatom species which appear to be good indicators of various oceanographic/ecologic conditions in the North Pacific Ocean and marginal seas. Three long cores from the eastern and northern sides of the Aleutian Basin show changes in species assemblage which can be interpreted in terms of changes in the ocean environment during the last glaciation (Wisconsin) and the Holocene. The early and late Wisconsin maxima were times of prolonged annual sea-ice cover and a short cool period of phytoplankton productivity during the ice-free season. The middle Wisconsin interstade, at least in the southern Bering Sea, had greater seasonal contrast than today, with some winter sea-ice cover, an intensified temperature minimum, and high spring productivity. Variations in clastic and reworked fossil material imply varying degrees of transport to the basin by Alaskan rivers. The results of Jousé from the central Bering Sea generally correspond with those presented here, although there are problems with direct comparison.
Limited information exists on the tolerance of processing tomato to postemergence (POST) application of thifensulfuron-methyl. The tolerance of 13 processing tomato varieties, ‘CC337’, ‘H9144’, ‘H9314’, ‘H9478’, ‘H9492’, ‘H9553’, ‘H9909’, ‘N1069’, ‘N1082’, ‘N1480E’, ‘N1480L’, ‘N1522’, and ‘PETO696’, to POST applications of thifensulfuron-methyl at the maximum use rate (6 g ai/ha) and twice the maximum use rate (12 g/ha) for soybean was evaluated at two Ontario locations in 2001 and 2002. At 7 days after treatment (DAT), thifensulfuron applied POST caused 0.2 to 1% visible injury to CC337, H9144, N1082, N1522, and PETO696 at the high rate. H9553, H9909, N1069, and N1480E were the most sensitive to POST thifensulfuron-methyl, with visible injury ranging from 1 to 6% at the high rate. There was no visible injury to H9314, H9478, H9492, or N1480L at either application rate of thifensulfuron-methyl. By 28 DAT, no visible injury was noted to any variety, except for H9909, N1069, and N1480L, which showed minimal (<2%) visible injury. There were no adverse effects on shoot dry weight and marketable yield for any variety at either rate. Although thifensulfuron-methyl applied POST caused minimal and transient injury to the varieties tested, more tolerance trials with other fresh and processing tomato varieties are required to confirm these initial results.
Eleven radiocarbon age determinations clearly show that a lens of Holocene fluvial organic debris on the Alaskan Arctic Coastal Plain contains mostly pre-Holocene organic material. Radio-carbon ages of identified plant macrofossils indicate the material was deposited about 9000 to 9500 yr B.P. Radiocarbon analyses of bulk samples from this deposit, however, range from 13,300 to 30,300 yr B.P. Most of the old organic matter seems to be in the smaller size fractions in the deposit, particularly in the fraction between 0.25 and 0.5 mm, but all size fractions are contaminated. Particular caution must be exercised in submitting bulk samples for radiocarbon dating from areas where conditions favor redeposition of isotopically “dead” carbon.
The Neogene species Petaloconchus sculpturatus presents a contradiction in terms, for it grows whorl “packages” of nearly perfect regularity, but ranks within the most geometrically irregular family of uncoiled gastropods, the Vermetidae. We perform a first biometric study of vermetids (only possible because sufficient regularity of growth permits us to number and identify whorls) to specify and characterize the factors on both sides of this “exquisite tension” between promotion and prevention of recoiling. Promoting factors include the older phyletic heritage of preserved dextral coiling, and the more immediate vermetid (or specifically petaloconchid) features of growth toward open spaces (where regular coiling might proceed in an unimpeded fashion); radular excision of discordant feeding tubes with shaping of the resulting scar so that growth may proceed in conformity with previous whorls; and locking of subsequent whorls upon a keel formed by longitudinal bead-rows of the previous whorl. Preventing factors include prominent phyletic heritage of all vermetids—maximal early irregularity enjoined by discordance between larval and subsequent growth (with teleoconch wrapping itself around the protoconch), thus precluding an ordered substrate to act as a foundation for regular whorl “packages” of intermediary growth—and a set of features specific to this lineage and acting as geometric constraints. In this category, we particularly document the exceedingly low rate of whorl expansion and the consequently wide umbilical space that produces a shell akin to winding a cylindrical coil of narrow-diameter rope around the periphery of a wide circular platform. This complex combination of promoting and preventing factors produces a shell that is tantalizingly close to fully regular, but cannot truly reattain this previous phyletic state—thus providing a fine example of Dollo's Law at the centenary of his formation of irreversibility.
Cryptosporidium parvum is the major cause of livestock and zoonotically-acquired human cryptosporidiosis. The ability to track sources of contamination and routes of transmission by further differentiation of isolates would assist risk assessment and outbreak investigations. Multiple-locus variable-number of tandem-repeats (VNTR) analysis provides a means for rapid characterization by fragment sizing and estimation of copy numbers, but structured, harmonized development has been lacking for Cryptosporidium spp. To investigate potential for application in C. parvum surveillance and outbreak investigations, we studied nine commonly used VNTR loci (MSA, MSD, MSF, MM5, MM18, MM19, MS9-Mallon, GP60 and TP14) for chromosome distribution, repeat unit length and heterogeneity, and flanking region proximity and conservation. To investigate performance in vitro, we compared these loci in 14 C. parvum samples by capillary electrophoresis in three laboratories. We found that many loci did not contain simple repeat units but were more complex, hindering calculations of repeat unit copy number for standardized reporting nomenclature. However, sequenced reference DNA enabled reproducible fragment sizing and inter-laboratory allele assignation based on size normalized to that of the sequenced fragments by both single round and nested polymerase chain reactions. Additional Cryptosporidium loci need to be identified and validated for robust inter-laboratory surveillance and outbreak investigations.
CZT is a semiconductor material that promises to be a good candidate for uncooled gamma radiation detectors. However, to date, technological difficulties in production of large size defect-free CZT crystals are yet to be overcome. The most common problem is accumulation of tellurium precipitates as microscopic inclusions. These inclusions influence the charge collection through charge trapping and electric field distortion. The common work-around solutions are to fabricate pixelated detectors by either grouping together many small volume CZT crystals to act as individual detectors, or to deposit a pixelated grid of electrical contacts on a larger, but defective, crystal, and selectively collect charge. These solutions are satisfactory in an R&D environment, but are unsuitable for mass production and commercial development. Our modeling effort is aimed at quantifying the various contributions of tellurium inclusions in CZT crystals to the charge generation, transport, and collection, as a function of inclusions size, position, and concentration. We model the energy deposition of gamma photons in the sensitive volume of the detector using LANL’s MCNP code. The electron-hole pairs produced at the energy deposition sites are then transported through the defective crystal and collected as integral charge at the electrical contact sites using CERN’s Garfield software package. The size and position distribution of tellurium inclusions is modeled by sampling experimentally measured distributions of such inclusions on a variety of commercially-grown CZT crystals using IR microscopy and image processing software packages.
We report an intracerebral abscess caused by a recently identified nocardial species, in an immunocompetent individual without extraneural involvement.
A 63-year-old non-smoking Caucasian male with an unremarkable history of hypertension, presented with a 2-week history of personality changes including apathy, some difficulty walking, a tendency to veer to the left and a possible seizure. Preliminary assessment, including laboratory investigations were unremarkable. Computed tomography (CT) of his brain revealed a right frontal lobe multi-loculated, ring-enhancing lesion with vasogenic edema and associated mass effect (Figure 1). He was then referred to our institution.