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On January 29th, 2020, 195 U.S. citizens were evacuated from the COVID-19 epidemic in Wuhan, China to March Air Reserve Base in Riverside, California, and entered the first federally mandated quarantine in over 50 years. With less than one day notice, a multi-disciplinary team from Riverside County and Riverside University Health System in conjunction with local and federal agencies established on-site 24-hour medical care and behavioral health support. This report details the coordinated efforts by multiple teams that took place to provide care for the passengers and to support the surrounding community.
Cognitive deficits at the first episode of schizophrenia are predictive of functional outcome. Interventions that improve cognitive functioning early in schizophrenia are critical if we hope to prevent or limit long-term disability in this disorder.
We completed a 12-month randomized controlled trial of cognitive remediation and of long-acting injectable (LAI) risperidone with 60 patients with a recent first episode of schizophrenia. Cognitive remediation involved programs focused on basic cognitive processes as well as more complex, life-like situations. Healthy behavior training of equal treatment time was the comparison group for cognitive remediation, while oral risperidone was the comparator for LAI risperidone in a 2 × 2 design. All patients were provided supported employment/education to encourage return to work or school.
Both antipsychotic medication adherence and cognitive remediation contributed to cognitive improvement. Cognitive remediation was superior to healthy behavior training in the LAI medication condition but not the oral medication condition. Cognitive remediation was also superior when medication adherence and protocol completion were covaried. Both LAI antipsychotic medication and cognitive remediation led to significantly greater improvement in work/school functioning. Effect sizes were larger than in most prior studies of first-episode patients. In addition, cognitive improvement was significantly correlated with work/school functional improvement.
These results indicate that consistent antipsychotic medication adherence and cognitive remediation can significantly improve core cognitive deficits in the initial period of schizophrenia. When combined with supported employment/education, cognitive remediation and LAI antipsychotic medication show separate significant impact on improving work/school functioning.
This chapter will provide an overview of the various ways in which addictive disorders can be studied using human participants in laboratory settings. Human laboratory research provides an important piece of the translational research chain by enabling researchers to examine addictive behaviors in controlled settings using validated experimental methodologies. This chapter will cover three common laboratory techniques: cue exposure protocols, stress induction protocols, and addictive object self-administration protocols. The primary goal is to provide a methodological guide to conducting research using these approaches, but not extensively review previous research. Therefore, for each technique, we discuss the background and rationale, ethical considerations, strengths and limitations, and representative examples and promising future directions in the use of the technique to study substance and behavioral addictions.
Antibiotics are commonly used in intensive care units (ICUs), yet differences in antibiotic use across ICUs are unknown. Herein, we studied antibiotic use across ICUs and examined factors that contributed to variation.
We conducted a retrospective cohort study using data from Ontario’s Critical Care Information System (CCIS), which included 201 adult ICUs and 2,013,397 patient days from January 2012 to June 2016. Antibiotic use was measured in days of therapy (DOT) per 1,000 patient days. ICU factors included ability to provide ventilator support (level 3) or not (level 2), ICU type (medical-surgical or other), and academic status. Patient factors included severity of illness using multiple-organ dysfunction score (MODS), ventilatory support, and central venous catheter (CVC) use. We analyzed the effect of these factors on variation in antibiotic use.
Overall, 269,351 patients (56%) received antibiotics during their ICU stay. The mean antibiotic use was 624 (range 3–1460) DOT per 1,000 patient days. Antibiotic use was significantly higher in medical-surgical ICUs compared to other ICUs (697 vs 410 DOT per 1,000 patient days; P < .0001) and in level 3 ICUs compared to level 2 ICUs (751 vs 513 DOT per 1,000 patient days; P < .0001). Higher antibiotic use was associated with higher severity of illness and intensity of treatment. ICU and patient factors explained 47% of the variation in antibiotic use across ICUs.
Antibiotic use varies widely across ICUs, which is partially associated with ICUs and patient characteristics. These differences highlight the importance of antimicrobial stewardship to ensure appropriate use of antibiotics in ICU patients.
Nutritional ketosis, induced via either the classical ketogenic diet or the use of emulsified medium-chain triglycerides, is an established treatment for pharmaceutical resistant epilepsy in children and more recently in adults. In addition, the use of oral ketogenic compounds, fractionated coconut oil, very low carbohydrate intake, or ketone monoester supplementation has been reported to be potentially helpful in mild cognitive impairment, Parkinson’s disease, schizophrenia, bipolar disorder, and autistic spectrum disorder. In these and other neurodegenerative and neuroprogressive disorders, there are detrimental effects of oxidative stress, mitochondrial dysfunction, and neuroinflammation on neuronal function. However, they also adversely impact on neurone–glia interactions, disrupting the role of microglia and astrocytes in central nervous system (CNS) homeostasis. Astrocytes are the main site of CNS fatty acid oxidation; the resulting ketone bodies constitute an important source of oxidative fuel for neurones in an environment of glucose restriction. Importantly, the lactate shuttle between astrocytes and neurones is dependent on glycogenolysis and glycolysis, resulting from the fact that the astrocytic filopodia responsible for lactate release are too narrow to accommodate mitochondria. The entry into the CNS of ketone bodies and fatty acids, as a result of nutritional ketosis, has effects on the astrocytic glutamate–glutamine cycle, glutamate synthase activity, and on the function of vesicular glutamate transporters, EAAT, Na+, K+-ATPase, Kir4.1, aquaporin-4, Cx34 and KATP channels, as well as on astrogliosis. These mechanisms are detailed and it is suggested that they would tend to mitigate the changes seen in many neurodegenerative and neuroprogressive disorders. Hence, it is hypothesized that nutritional ketosis may have therapeutic applications in such disorders.
Copy number variants (CNVs) play a significant role in disease pathogenesis in a small subset of individuals with schizophrenia (~2.5%). Chromosomal microarray testing is a first-tier genetic test for many neurodevelopmental disorders. Similar testing could be useful in schizophrenia.
To determine whether clinically identifiable phenotypic features could be used to successfully model schizophrenia-associated (SCZ-associated) CNV carrier status in a large schizophrenia cohort.
Logistic regression and receiver operating characteristic (ROC) curves tested the accuracy of readily identifiable phenotypic features in modelling SCZ-associated CNV status in a discovery data-set of 1215 individuals with psychosis. A replication analysis was undertaken in a second psychosis data-set (n = 479).
In the discovery cohort, specific learning disorder (OR = 8.12; 95% CI 1.16–34.88, P = 0.012), developmental delay (OR = 5.19; 95% CI 1.58–14.76, P = 0.003) and comorbid neurodevelopmental disorder (OR = 5.87; 95% CI 1.28–19.69, P = 0.009) were significant independent variables in modelling positive carrier status for a SCZ-associated CNV, with an area under the ROC (AUROC) of 74.2% (95% CI 61.9–86.4%). A model constructed from the discovery cohort including developmental delay and comorbid neurodevelopmental disorder variables resulted in an AUROC of 83% (95% CI 52.0–100.0%) for the replication cohort.
These findings suggest that careful clinical history taking to document specific neurodevelopmental features may be informative in screening for individuals with schizophrenia who are at higher risk of carrying known SCZ-associated CNVs. Identification of genomic disorders in these individuals is likely to have clinical benefits similar to those demonstrated for other neurodevelopmental disorders.
The impact of hurricanes on emergency services is well-known. Recent history demonstrates the need for prehospital and emergency department coordination to serve communities during evacuation, storm duration, and cleanup. The use of telehealth applications may enhance this coordination while lessening the impact on health-care systems. These applications can address triage, stabilization, and diversion and may be provided in collaboration with state and local emergency management operations through various shelters, as well as during other emergency medical responses.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
The Bulge Asymmetries and Dynamical Evolution (BAaDE) survey aims to explore the complex structure of the inner Galaxy and Galactic Bulge, by using the 43 GHz receivers at the Karl G. Jansky Very Large Array (VLA) and the 86 GHz receivers at the Atacama Large Millimeter/submillimeter Array (ALMA) to observe SiO maser lines in red giant stars. The goal is to construct a sample of stellar point-mass probes that can be used to test models of the gravitational potential, and the final sample is expected to provide at least 20,000 line-of-sight velocities and positions. A possible bias between the VLA and the ALMA SiO maser lines is explored, and the 86 GHz SiO line-peak velocities agree using either of the four sampled lines. Additionally, the SiO maser velocities agree with the OH maser derived velocities.
The Bulge Asymmetries and Dynamical Evolution (BAaDE) survey aims to use circumstellar SiO maser line-of-sight velocities as probes for the Galactic gravitational potential and dynamical structure. The SiO masers are detected at a high rate in specific color-selected MSX infrared sources. Furthermore, the SiO maser properties and line ratios, in combination with infrared spectral energy distributions and location in the Galaxy, will statistically yield detailed information on population and evolution of low- to intermediate-mass evolved stars in the Galaxy.
Obesity is a major challenge for people with schizophrenia.
We assessed whether STEPWISE, a theory-based, group structured lifestyle education programme could support weight reduction in people with schizophrenia.
In this randomised controlled trial (study registration: ISRCTN19447796), we recruited adults with schizophrenia, schizoaffective disorder or first-episode psychosis from ten mental health organisations in England. Participants were randomly allocated to the STEPWISE intervention or treatment as usual. The 12-month intervention comprised four 2.5 h weekly group sessions, followed by 2-weekly maintenance contact and group sessions at 4, 7 and 10 months. The primary outcome was weight change after 12 months. Key secondary outcomes included diet, physical activity, biomedical measures and patient-related outcome measures. Cost-effectiveness was assessed and a mixed-methods process evaluation was included.
Between 10 March 2015 and 31 March 2016, we recruited 414 people (intervention 208, usual care 206) with 341 (84.4%) participants completing the trial. At 12 months, weight reduction did not differ between groups (mean difference 0.0 kg, 95% CI −1.6 to 1.7, P = 0.963); physical activity, dietary intake and biochemical measures were unchanged. STEPWISE was well-received by participants and facilitators. The healthcare perspective incremental cost-effectiveness ratio was £246 921 per quality-adjusted life-year gained.
Participants were successfully recruited and retained, indicating a strong interest in weight interventions; however, the STEPWISE intervention was neither clinically nor cost-effective. Further research is needed to determine how to manage overweight and obesity in people with schizophrenia.
Declaration of interest
R.I.G.H. received fees for lecturing, consultancy work and attendance at conferences from the following: Boehringer Ingelheim, Eli Lilly, Janssen, Lundbeck, Novo Nordisk, Novartis, Otsuka, Sanofi, Sunovion, Takeda, MSD. M.J.D. reports personal fees from Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Janssen, Servier, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceuticals International Inc.; and, grants from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Janssen. K.K. has received fees for consultancy and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Servier and Merck Sharp & Dohme. He has received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim and Merck Sharp & Dohme. K.K. has received funds for research, honoraria for speaking at meetings and has served on advisory boards for Lilly, Sanofi-Aventis, Merck Sharp & Dohme and Novo Nordisk. D.Sh. is expert advisor to the NICE Centre for guidelines; board member of the National Collaborating Centre for Mental Health (NCCMH); clinical advisor (paid consultancy basis) to National Clinical Audit of Psychosis (NCAP); views are personal and not those of NICE, NCCMH or NCAP. J.P. received personal fees for involvement in the study from a National Institute for Health Research (NIHR) grant. M.E.C. and Y.D. report grants from NIHR Health Technology Assessment, during the conduct of the study; and The Leicester Diabetes Centre, an organisation (employer) jointly hosted by an NHS Hospital Trust and the University of Leicester and who is holder (through the University of Leicester) of the copyright of the STEPWISE programme and of the DESMOND suite of programmes, training and intervention fidelity framework that were used in this study. S.R. has received honorarium from Lundbeck for lecturing. F.G. reports personal fees from Otsuka and Lundbeck, personal fees and non-financial support from Sunovion, outside the submitted work; and has a family member with professional links to Lilly and GSK, including shares. F.G. is in part funded by the National Institute for Health Research Collaboration for Leadership in Applied Health Research & Care Funding scheme, by the Maudsley Charity and by the Stanley Medical Research Institute and is supported by the by the Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.
We report on the Bulge Asymmetries and Dynamic Evolution (BAaDE) survey which has observed 19 000 MSX color selected red giant stars for SiO maser emission at 43 GHz with the VLA and is in the process of observing 9 000 of these stars with ALMA at 86 GHz in the Southern sky. Our setup covers the main maser transitions, as well as those of isotopologues and selected lines of carbon-bearing species. Observations of this set of lines allow a far-reaching catalog of line-of-sight velocities in the dust-obscured regions where optical surveys cannot reach. Our preliminary detection rate is close to 70%, predicting a wealth of new information on the distribution of metal rich stars, their kinematics as function of location in the Galaxy, as well as the occurrence of lines and line ratios between the different transitions in combination with the spectral energy distribution from about 1 to 100 μm. Similar to the OH/IR stars, a clear kinematic signature between disk and bulge stars can be seen. Furthermore, the SiO J = →10 (v=3) line plays a prominent role in the derived maser properties.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
This is a special issue in honor of Kwok Leung, whose path-breaking career in social psychology, cross-cultural psychology, organizational behavior, and international management was cut short by his untimely death in 2015. Newton said, ‘If I have seen further it is by standing on the shoulders of giants’. In cultural research, it's Kwok's shoulders that enable us to see further.
Carbapenem-resistant Enterobacteriaceae (CRE) are a significant clinical and public health concern. Understanding the distribution of CRE colonization and developing a coordinated approach are key components of control efforts. The prevalence of CRE in the District of Columbia is unknown. We sought to determine the CRE colonization prevalence within healthcare facilities (HCFs) in the District of Columbia using a collaborative, regional approach.
This study included 16 HCFs in the District of Columbia: all 8 acute-care hospitals (ACHs), 5 of 19 skilled nursing facilities, 2 (both) long-term acute-care facilities, and 1 (the sole) inpatient rehabilitation facility.
Inpatients on all units excluding psychiatry and obstetrics-gynecology.
CRE identification was performed on perianal swab samples using real-time polymerase chain reaction, culture, and antimicrobial susceptibility testing (AST). Prevalence was calculated by facility and unit type as the number of patients with a positive result divided by the total number tested. Prevalence ratios were compared using the Poisson distribution.
Of 1,022 completed tests, 53 samples tested positive for CRE, yielding a prevalence of 5.2% (95% CI, 3.9%–6.8%). Of 726 tests from ACHs, 36 (5.0%; 95% CI, 3.5%–6.9%) were positive. Of 244 tests from long-term-care facilities, 17 (7.0%; 95% CI, 4.1%–11.2%) were positive. The relative prevalence ratios by facility type were 0.9 (95% CI, 0.5–1.5) and 1.5 (95% CI, 0.9–2.6), respectively. No CRE were identified from the inpatient rehabilitation facility.
A baseline CRE prevalence was established, revealing endemicity across healthcare settings in the District of Columbia. Our study establishes a framework for interfacility collaboration to reduce CRE transmission and infection.
Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
Late Medieval Castles is a companion to Anglo-Norman Castles (2003), a volume that brought together a series of historiographically significant articles on castles and castle-building in the period from the Norman Conquest to the early thirteenth century. The format and themes of the present collection are broadly comparable with the earlier book, but with the focus on those castles dating to the period c.1250–1500.
In the course of bringing Anglo-Norman Castles to publication the somewhat arbitrary cut-off date of c.1225 seemed unsatisfactory for a number of reasons. On a practical level, there were highly relevant articles that could not be included because the subject matter fell outside the chronological range of the volume. A more scholarly concern was the fact that a number of issues pertinent to castle-building in the eleventh and twelfth centuries could not be satisfactorily addressed without reference to subsequent developments in the thirteenth and fourteenth. Allied to this, a focus on Anglo-Norman building (no matter how justifiable in historical terms) does perhaps contribute, albeit unwittingly, to the erroneous idea that the eleventh and twelfth centuries are the most important centuries for castle-building, a time when the ‘true’ castle is to be found, and that the period that follows, particularly after 1300, is something of an anti-climax. The present volume should therefore be seen as a continuation of the broad themes discussed in the introduction to Anglo-Norman Castles, with the aim of pursuing them in a late medieval context.
In the years since 2003 there have been a number of important publications in the field of castle studies, and castles continue to be a source of controversy and to provoke debate. Despite the fact that the availability of some secondary material has been made easier through electronic access, I have been consistently reminded by academic colleagues that a compilation such as this is worthwhile, both for the student reader and those seeking a path into the specialist secondary literature. This author at least also believes that there is value in bringing together in one place a series of important contributions that have defined the subject and which also illustrate a diversity of approaches.