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Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP.
This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses.
Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength.
Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.
Although researchers have described numerous risk factors for salmonellosis and for infection with specific common serotypes, the drivers of Salmonella serotype diversity among human populations remain poorly understood. In this retrospective observational study, we partition records of serotyped non-typhoidal Salmonella isolates from human clinical specimens reported to CDC national surveillance by demographic, geographic and seasonal characteristics and adapt sample-based rarefaction methods from the field of community ecology to study how Salmonella serotype diversity varied within and among these populations in the USA during 1996–2016. We observed substantially higher serotype richness in children <2 years old than in older children and adults and steadily increasing richness with age among older adults. Whereas seasonal and regional variation in serotype diversity was highest among infants and young children, variation by specimen source was highest in adults. Our findings suggest that the risk for infection from uncommon serotypes is associated with host and environmental factors, particularly among infants, young children and older adults. These populations may have a higher proportion of illness acquired through environmental transmission pathways than published source attribution models estimate.
Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.
To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.
Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.
Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.
Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.
The synchrotron x-ray source provides a unique opportunity to observe many “in-situ” processes. The formation of the “short-lived” intermediate species, Ta2C, during the combustion synthesis of TaC, has been observed and reported by monitoring the Bragg diffraction peaks of the reactants and products, Similarly, the synthesis of the ferroelectric material, BaTiO3, and subsequent phase transfonnation from cubic to tetragonal have also been investigated. These experiments would not have been possible without the high incident x-ray flux available at a synchrotron source.
Thermal analysts have exploited the sensitivity of carbonate mineral decomposition to furnace atmosphere as a diagnostic tool for identifying and quantifying these minerals in mixtures and solid solutions (1-3). However, thermal analysis techniques alone cannot reveal information about the reaction products after each thermal event. In-situ high temperature x-ray diffraction is one technique that can identify these products. Using this technique, Kissinger et al. (4) identified the reaction products of the thermal decomposition of reagent grade FeCO3 (siderite) and MgCO3 (magnesite). However, the thermal behavior of analytical reagent grade carbonates differs from natural minerals (1). Milodowski and Morgan (5) used in-situ XRD to investigate the thermal behavior of the dolomite-ankerite series.
Chronic maxillary atelectasis is a rare and underdiagnosed condition in which there is a persistent and progressive decrease in maxillary sinus volume secondary to inward bowing of the antral walls. Chronic maxillary atelectasis is typically unilateral. Simultaneous bilateral chronic maxillary atelectasis is extremely uncommon.
A retrospective review was performed of patient data collected by the senior clinician over a three-year period (2015–2018). A comprehensive literature search was conducted to locate all documented cases of chronic maxillary atelectasis in English-language literature. Abstracts and full-text articles were reviewed.
Three patients presented with sinonasal symptoms. Imaging findings were consistent with bilateral chronic maxillary atelectasis. The literature review revealed at least nine other cases of bilateral chronic maxillary atelectasis. Management is typically via endoscopic middle meatus antrostomy.
Chronic maxillary atelectasis was initially defined as a unilateral disorder, but this description has been challenged by reports of bilateral cases. Further investigation is required to determine the aetiology and pathophysiology of the disease.
To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient–clinician shared decision-making about care and RCT enrollment, based on “mathematical equipoise.”
As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis.
With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making.
The KOMET predictive regression model for knee pain had four patient-specific variables, and an r2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received.
Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.
Misplacing objects is often reported as a clinically important symptom in dementia. Here we explored misplacing objects in relation to dementia type and stage in an online sample of individuals with dementia and their caregivers.
Participants were recruited from www.dementiaguide.com, a web-based tracker for common dementia symptoms. Users provided information about symptoms that they selected as important for monitoring. We analysed cross-sectional data from respondents who tracked at least three symptoms, which allowed for staging dementia severity.
Of 2,775 users with three-plus symptoms, 787 (28%) identified misplacing objects for symptom tracking. Misplacing objects was monitored by users across all stages of dementia, but was more prevalent in mild and severe dementia. Three common clinical subtypes of misplacing were investigated: lost & found (forgetting the location of items), hidden away (hiding items so others would not find them), and odd places (putting items in usual spots). Of the 787, 96% targeted lost & found, the most frequent type. Odd places (targeted in 56%) significantly increased with dementia severity (p < 0.001). Misplacing objects was most strongly associated with the symptoms of interaction with strangers (OR 4.60, 95% CI: 3.20-6.62), reading (3.68: 2.86-4.73), shopping (3.55: 2.73-4.61) and travel/vacationing (3.31: 2.54-4.31).
Misplacing objects was most often selected for tracking in mild and severe stages of dementia. As disease advances, misplacing more often reflects odd placement of objects rather than their simple loss. Misplacing objects may be a clinically important therapeutic target for improving patients’ quality of life and lessening caregiver burden.
Mules and other equine species have been used in warfare for thousands of years to transport goods and supplies. Mules are known for ‘braying’, which is disadvantageous in warfare operations. This article explores the fascinating development of surgical techniques to stop military mules from braying, with particular emphasis on the key role played by the otolaryngologist Arthur James Moffett in devoicing the mules of the second Chindit expedition of World War II.
The PubMed database (1900–2017) and Google search engine were used to identify articles related to devoicing mules in the medical and veterinary literature, along with information and images on the Chindit expedition.
This paper reviews the surgical techniques aimed at treating braying in mules, ranging from ventriculectomy and arytenoidectomy to Moffett's approach of vocal cordectomy.
Moffett's technique of vocal cordectomy provided a quick, reproducible and safe solution for devoicing mules. It proved to be advantageous on the battlefield and demonstrated his achievements outside the field of medicine.
Functional circuits of the human brain emerge and change dramatically over the second half of gestation. It is possible that variation in neural functional system connectivity in utero predicts individual differences in infant behavioral development, but this possibility has yet to be examined. The current study examines the association between fetal sensorimotor brain system functional connectivity and infant postnatal motor ability. Resting-state functional connectivity data was obtained in 96 healthy human fetuses during the second and third trimesters of pregnancy. Infant motor ability was measured 7 months after birth using the Bayley Scales of Infant Development. Increased connectivity between the emerging motor network and regions of the prefrontal cortex, temporal lobes, posterior cingulate, and supplementary motor regions was observed in infants that showed more mature motor functions. In addition, females demonstrated stronger fetal-brain to infant-behavior associations. These observations extend prior longitudinal research back into prenatal brain development and raise exciting new ideas about the advent of risk and the ontogeny of early sex differences.
Brain tumor behavior is driven by aberrations in the genome and epigenome. Many of these changes, such as IDH mutations in diffuse low-grade glioma (DLGG), are common amongst the same class of tumour and can be incorporated into the diagnostic criteria. However, any given tumor may have other, less common genomic aberrations that are essential for its biological behavior and may inform on underlying aberrant cellular pathways, and potential therapeutic agents. Precision oncology is a genomics-based approach which profiles these alterations to better manage cancer patients and has established itself within the practice of oncology and is slowly making its way into neuro-oncology. The BC Cancer’s Personalized OncoGenomics (POG) program has profiled 16 adult tumours originating from the central nervous system using whole genome and transcriptome analysis (WGTA), for the first time, within a meaningful clinical timeframe/setting. As expected, primary genomic drivers were consistent with their respective diagnoses, though secondary drivers were found to be unique to each tumour. Although these analyses did not result in altered clinical management for these patients, primarily due to availability of drug or clinical trials, they highlight the heterogeneity of secondary drivers in cancers and provide clinicians with meaningful biological information. Lastly, the data generated by POG has highlighted the frequency and complexity of novel driver fusions which are predicted to behave similarly to canonical driver events in their respective tumours. The information available to clinicians through POG has provided paramount knowledge into the biology of each unique tumour.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
While previous work showed that the Centers for Disease Control and Prevention toolkit for carbapenem-resistant Enterobacteriaceae (CRE) can reduce spread regionally, these interventions are costly, and decisions makers want to know whether and when economic benefits occur.
Orange County, California
Using our Regional Healthcare Ecosystem Analyst (RHEA)-generated agent-based model of all inpatient healthcare facilities, we simulated the implementation of the CRE toolkit (active screening of interfacility transfers) in different ways and estimated their economic impacts under various circumstances.
Compared to routine control measures, screening generated cost savings by year 1 when hospitals implemented screening after identifying ≤20 CRE cases (saving $2,000–$9,000) and by year 7 if all hospitals implemented in a regional coordinated manner after 1 hospital identified a CRE case (hospital perspective). Cost savings was achieved only if hospitals independently screened after identifying 10 cases (year 1, third-party payer perspective). Cost savings was achieved by year 1 if hospitals independently screened after identifying 1 CRE case and by year 3 if all hospitals coordinated and screened after 1 hospital identified 1 case (societal perspective). After a few years, all strategies cost less and have positive health effects compared to routine control measures; most strategies generate a positive cost-benefit each year.
Active screening of interfacility transfers garnered cost savings in year 1 of implementation when hospitals acted independently and by year 3 if all hospitals collectively implemented the toolkit in a coordinated manner. Despite taking longer to manifest, coordinated regional control resulted in greater savings over time.
Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined.
To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive.
Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy.
Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four.
A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery.
In this paper we propose a new approach to study the Parisian ruin problem for spectrally negative Lévy processes. Since our approach is based on a hybrid observation scheme switching between discrete and continuous observations, we call it a temporal approach as opposed to the spatial approximation approach in the literature. Our approach leads to a unified proof for the underlying processes with bounded or unbounded variation paths, and our result generalizes Loeffen et al. (2013).