General purpose architecture for intelligent computer-aided training

An intelligent computer-aided training system having a general modular architecture is provided for use in a wide variety of training tasks and environments. It is comprised of a user interface which permits the trainee to access the same information available in the task environment and serves as a means for the trainee to assert actions to the system; a domain expert which is sufficiently intelligent to use the same information available to the trainee and carry out the task assigned to the trainee; a training session manager for examining the assertions made by the domain expert and by the trainee for evaluating such trainee assertions and providing guidance to the trainee which are appropriate to his acquired skill level; a trainee model which contains a history of the trainee interactions with the system together with summary evaluative data; an intelligent training scenario generator for designing increasingly complex training exercises based on the current skill level contained in the trainee model and on any weaknesses or deficiencies that the trainee has exhibited in previous interactions; and a blackboard that provides a common fact base for communication between the other components of the system. Preferably, the domain expert contains a list of 'mal-rules' which typifies errors that are usually made by novice trainees. Also preferably, the training session manager comprises an intelligent error detection means and an intelligent error handling means. The present invention utilizes a rule-based language having a control structure whereby a specific message passing protocol is utilized with respect to tasks which are procedural or step-by-step in structure. The rules can be activated by the trainee in any order to reach the solution by any valid or correct path

Fecal Viral Concentration and Diarrhea in Norovirus Gastroenteritis

Fecal viral concentrations of 40 patients infected with norovirus genogroup GII.4 correlated with diarrhea duration and frequency of vomiting. Higher viral concentration and older age were independently associated with prolonged diarrhea (>4 days). These findings provide information on the pathogenesis and transmission of norovirus infections

A second polymorph of β-arteether

The crystal structure of the title compound, C17H28O5, reported here is a polymorph of the structure first reported by El-Feraly, Al-Yahya, Orabi, McPhail & McPhail [J. Nat. Prod. (1992). 55, 878–883]. It is a derivative of the anti­malaria compound artemisinin and consists primarily of three substituted ring systems fused together. A cyclo­hexane ring (distorted chair conformation) fused to a tetra­hydro­pyran group (distorted chair) is adjacent to an oxacyclo­heptane unit containing an endo-peroxide bridge, giving the mol­ecule its particular three-dimensional arrangement. The crystal packing is stabilized by inter­molecular C—H⋯O inter­actions between an O atom from the endo-peroxide bridge and H atoms from both the cyclo­hexane and seven-membered oxacyclo­heptane fused rings, as well as between an O atom and H atom from adjacent tetra­hydro­pyran rings. The two polymorphs have the same space group and similar cell parameters for the a and b axes, but significantly different values for the c axis

Managing and preventing vascular catheter infections : a position paper of the international society for infectious diseases

CITATION: Lutwick, L., et al. 2019. Managing and preventing vascular catheter infections : a position paper of the international society for infectious diseases. International Journal of Infectious Diseases, 84:22-29, doi:10.1016/j.ijid.2019.04.014.The original publication is available at https://www.clinicalkey.com/ENGLISH ABSTRACT: A panel of experts was convened by the International Society for Infectious Diseases (ISID) to overview recommendations on managing and preventing vascular catheter infections, specifically for the prevention and management of central line-associated bloodstream infections. These recommendations are intended to provide insight for healthcare professionals regarding the prevention of infection in the placement and maintenance of the catheter and diagnosis as well as treatment of catheter infection. Aspects of this area in pediatrics and in limited-resource situations and a discussion regarding the selection of empiric or targeted antimicrobial therapy are particular strengths of this position paper.https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S1201971219301845?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1201971219301845%3Fshowall%3Dtrue&referrer=https:%2F%2Fpubmed.ncbi.nlm.nih.gov%2FPublisher's versio

Cytokine Response Patterns in Severe Pandemic 2009 H1N1 and Seasonal Influenza among Hospitalized Adults

BACKGROUND: Studying cytokine/chemokine responses in severe influenza infections caused by different virus subtypes may improve understanding on pathogenesis. METHODS: Adults hospitalized for laboratory-confirmed seasonal and pandemic 2009 A/H1N1 (pH1N1) influenza were studied. Plasma concentrations of 13 cytokines/chemokines were measured at presentation and then serially, using cytometric-bead-array with flow-cytometry and ELISA. PBMCs from influenza patients were studied for cytokine/chemokine expression using ex-vivo culture (Whole Blood Assay,±PHA/LPS stimulation). Clinical variables were prospectively recorded and analyzed. RESULTS: 63 pH1N1 and 53 seasonal influenza patients were studied. pH1N1 patients were younger (mean±S.D. 42.8±19.2 vs 70.5±16.7 years), and fewer had comorbidities. Respiratory/cardiovascular complications were common in both groups (71.4% vs 81.1%), although severe pneumonia with hypoxemia (54.0% vs 28.3%) and ICU admissions (25.4% vs 1.9%) were more frequent with pH1N1. Hyperactivation of the proinflammatory cytokines IL-6, CXCL8/IL-8, CCL2/MCP-1 and sTNFR-1 was found in pH1N1 pneumonia (2-15 times normal) and in complicated seasonal influenza, but not in milder pH1N1 infections. The adaptive-immunity (Th1/Th17)-related CXCL10/IP-10, CXCL9/MIG and IL-17A however, were markedly suppressed in severe pH1N1 pneumonia (2-27 times lower than seasonal influenza; P-values<0.01). This pattern was further confirmed with serial measurements. Hypercytokinemia tended to be sustained in pH1N1 pneumonia, associated with a slower viral clearance [PCR-negativity: day 3-4, 55% vs 85%; day 6-7, 67% vs 100%]. Elevated proinflammatory cytokines, particularly IL-6, predicted ICU admission (adjusted OR 12.6, 95%CI 2.6-61.5, per log(10)unit increase; P = 0.002), and correlated with fever, tachypnoea, deoxygenation, and length-of-stay (Spearman's rho, P-values<0.01) in influenza infections. PBMCs in seasonal influenza patients were activated and expressed cytokines ex vivo (e.g. IL-6, CXCL8/IL-8, CCL2/MCP-1, CXCL10/IP-10, CXCL9/MIG); their 'responsiveness' to stimuli was shown to change dynamically during the illness course. CONCLUSIONS: A hyperactivated proinflammatory, but suppressed adaptive-immunity (Th1/Th17)-related cytokine response pattern was found in severe pH1N1 pneumonia, different from seasonal influenza. Cytokine/immune-dysregulation may be important in its pathogenesis

Impending Regeneration Failure of the IUCN Vulnerable Borneo Ironwood (Eusideroxylon zwageri)

The regeneration of many climax species in tropical forest critically depends on adequate seed dispersal and seedling establishment. Here, we report the decreased abundance and increased spatial aggregation of younger trees of the Borneo ironwood (Eusideroxylon zwageri) in a protected forest in Sabah Malaysia. We observed a high level of seedling herbivory with strong density dependence, likely exacerbated by local aggregation and contributing to the progressively shrinking size distribution. We also note the largely undocumented selective herbivory by sambar deer on E. zwageri seedlings. This study highlights the combined impact of altered megafauna community on a tree population through interlinked ecological processes and the need for targeted conservation intervention for this iconic tropical tree species

Early intervention for incipient insanity: early notions from the 19th century English literature.

AIM: Early intervention programmes in mental illnesses started to bloom in the 1990s, and many programmes have been established worldwide during the past twenty years. However, the concept of early intervention has emerged during the 19th century but it did not make much impact on practice. The aim of this review is to identify the difficulties appeared during that period of time which could provide insight into the modern development of early intervention initiatives. METHODS: A narrative review which focused on English literature about early intervention for insanity during the 19th century was undertaken. RESULTS: Clinicians during the 19th century recognized that treatment would be the most effective at the early stage of the mental illness and they had emphasized the importance of early intervention. However, because of a number of factors, such as the limited roles of asylums, lack of knowledge about mental disorder and the lack of effective treatment, the idea of early intervention did not make impact in clinical service during that period of time. CONCLUSION: During the past two hundred years, understanding towards mental illness has advanced and more effective treatments, such as the use of anti-psychotic medications, have been developed. Reflecting on the past experience and difficulties might shed light on the development of today early intervention in mental disorder.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Wiley

A clinicopathological study of non-functioning pituitary neuroendocrine tumours using the World Health Organization 2022 classification

BackgroundThe 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET).MethodsA total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses.ResultsBased on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p&lt;0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease.ConclusionThe 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570