Intelligence Primer

This primer explores the exciting subject of intelligence. Intelligence is a fundamental component of all living things, as well as Artificial Intelligence(AI). Artificial Intelligence has the potential to affect all of our lives and a new era for modern humans. This paper is an attempt to explore the ideas associated with intelligence, and by doing so understand the implications, constraints, and potentially the capabilities of future Artificial Intelligence. As an exploration, we journey into different parts of intelligence that appear essential. We hope that people find this useful in determining where Artificial Intelligence may be headed. Also, during the exploration, we hope to create new thought-provoking questions. Intelligence is not a single weighable quantity but a subject that spans Biology, Physics, Philosophy, Cognitive Science, Neuroscience, Psychology, and Computer Science. Historian Yuval Noah Harari pointed out that engineers and scientists in the future will have to broaden their understandings to include disciplines such as Psychology, Philosophy, and Ethics. Fiction writers have long portrayed engineers and scientists as deficient in these areas. Today, modern society, the emergence of Artificial Intelligence, and legal requirements all act as forcing functions to push these broader subjects into the foreground. We start with an introduction to intelligence and move quickly onto more profound thoughts and ideas. We call this a Life, the Universe and Everything primer, after the famous science fiction book by Douglas Adams. Forty-two may very well be the right answer, but what are the questions?Comment: 34 pages, 12 Figure

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Inflammatory bowel disease masquerading as traveller's diarrhoea

Diarrhoea that occurs during or after recent travel is predominantly infectious in nature; however, in atypical or prolonged cases a broader range of aetiologies for diarrhoea must be considered, and a careful history and examination may reveal clues to more sinister causes of diarrhoea. We report two cases in which a recent travel history and a positive stool culture or polymerase chain reaction testing for bacterial pathogens delayed the diagnosis of ulcerative colitis. As a result of severe inflammatory bowel disease, colectomy was the final result in both cases. Early consideration of causes other than infection for traveller's diarrhoea may prevent unnecessary morbidity in young patients

Facilitating treatment of HCV in primary care in regional Australia: Closing the access gap

Background: Australia has unrestricted access to direct-acting antivirals (DAA) for hepatitis C virus (HCV) treatment. In order to increase access to treatment, primary care providers are able to prescribe DAA after fibrosis assessment and specialist consultation. Transient elastography (TE) is recommended prior to commencement of HCV treatment; however, TE is rarely available outside secondary care centres in Australia and therefore a requirement for TE could represent a barrier to access to HCV treatment in primary care. Objectives: In order to bridge this access gap, we developed a community-based TE service across the Sunshine Coast and Wide Bay areas of Queensland. Design: Retrospective analysis of a prospectively recorded HCV treatment database. Interventions: A nurse-led service equipped with two mobile Fibroscan units assesses patients in eight locations across regional Queensland. Patients are referred into the service via primary care and undergo nurse-led TE at a location convenient to the patient. Patients are discussed at a weekly multidisciplinary team meeting and a treatment recommendation made to the referring GP. Treatment is initiated and monitored in primary care. Patients with cirrhosis are offered follow-up in secondary care. Results: 327 patients have undergone assessment and commenced treatment in primary care. Median age 48 years (IQR 38-56), 66% male. 57% genotype 1, 40% genotype 3; 82% treatment naïve; 10% had cirrhosis (liver stiffness >12.5 kPa). The majority were treated with sofosbuvir-based regimens. 26% treated with 8-week regimens. All patients had treatment prescribed and monitored in primary care. Telephone follow-up to confirm sustained virological response (SVR) was performed by clinic nurses. 147 patients remain on treatment. 180 patients have completed treatment. SVR data were not available for 19 patients (lost to follow-up). Intention-to-treat SVR rate was 85.5%. In patients with complete data SVR rate was 95.6%. Conclusion: Community-based TE assessment facilitates access to HCV treatment in primary care with excellent SVR rates

Distribution of interferon lambda-3 gene polymorphisms in Australian patients with previously untreated genotype 1 chronic hepatitis C: analysis from the PREDICT and CHARIOT studies

Background and Aims: The aim of this study was to examine the distribution of interferon lambda-3 (IFN-λ3) gene polymorphisms in previously untreated Australian patients with genotype 1 (Gt1) chronic hepatitis C (CHC) and to compare the IFN-λ3 genotype frequency among the different ethnic populations. Methods: This was a prospective, multicenter, observational study undertaken by the Australian Liver Association Clinical Research Network. Eligible subjects had Gt1 CHC and were being considered for and/or undergoing treatment. IFN-λ3 single nucleotide polymorphisms were genotyped by the Applied Biosystems's Taqman single nucleotide polymorphism genotyping assay. Results: Between May 2012 and June 2012, 1132 patients were recruited from 38 treatment clinics across Australia. Also, 561 subjects from the CHARIOT (collaborative group hepatitis C study using high dose Pegasys RBV Induction dose in genotype one) study of high-dose interferon who had baseline serum available were retrospectively tested. The overall frequency of IFN-λ3 rs12979860 CC/CT/TT genotypes was 36%, 52%, and 12%, and that of rs8099917 TT/TG/GG genotypes was 54%, 41%, and 5%, respectively. The prevalence of the favorable IFN-λ3 rs12979860 CC and rs8099917 TT genotypes in Causcasians, Asians, Aboriginals, Maori/Pacific Islanders, and Mediterraneans was 32% and 52%, 80% and 86%, 33% and 63%, 77% and 88%, and 19% and 29%, respectively. Compared with Caucasians, the frequency of IFN-λ3 CC was significantly higher among Asians (P < 0.0001) and Maori/Pacific Islander subjects (P < 0.0001). Conclusions: The distribution of IFN-λ3 polymorphisms among untreated patients with Gt1 CHC in Australia appears similar to that reported from North America. The frequency of the favorable response alleles varies considerably according to ethnicity, being more common in self-reported Asians and Maori/Pacific Islanders than Caucasians, Aboriginals, and Mediterraneans

A Study of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate, for Patients with Frontline and Relapsed/Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

International audienc