3Es for AI: Economics, Explanation, Epistemology

This article locates its roots/routes in multiple disciplinary formations and it seeks to advance critical thinking about an aspect of our contemporary socio-technical challenges by bracketing three knowledge formations—artificial intelligence (AI), economics, and epistemology—that have not often been considered together. In doing so, it responds to the growing calls for the necessity of further transdisciplinary engagements that have emanated from work in AI and also from other disciplines. The structure of the argument here is as follows. First, I begin by demonstrating how and why explanation is a problem in AI (“XAI problem”) and what directions are being taken by recent research that draws upon social sciences to address this, noting how there is a conspicuous lack of reference in this literature to economics. Second, I identify and analyze a problem of explanation that has long plagued economics too as a discipline. I show how only a few economists have ever attempted to grapple with this problem and provide their perspectives. Third, I provide an original genealogy of explanation in economics, demonstrating the changing nature of what was meant by an explanation. These systematic changes in consensual understanding of what occurs when something is said to have been “explained”, have reflected the methodological compromises that were rendered necessary to serve different epistemological tensions over time. Lastly, I identify the various relevant historical and conceptual overlaps between economics and AI. I conclude by suggesting that we must pay greater attention to the epistemologies underpinning socio-technical knowledges about the human. The problem of explanation in AI, like the problem of explanation in economics, is perhaps not only, or really, a problem of satisfactory explanation provision alone, but interwoven with questions of competing epistemological and ethical choices and related to the ways in which we choose sociotechnical arrangements and offer consent to be governed by them

DOES POST MENOPAUSAL BLEEDING ALMOST ALWAYS POINT TOWARDS A SINISTER CAUSE: CLINICAL SCENARIO IN THE “CANCER BELT OF NORTH INDIA” – A PROSPECTIVE HOSPITAL-BASED STUDY.

Background: Bleeding after menopause can be an early sign of malignancy in the cervix and the inner layer of the uterus. Detecting the malignancy earlier can make such malignancy manageable. The aim of this study is to determine the occurrence of bleeding after menopause in North Indian women. Methods: This was a survey-based prospective study carried out over a span of two years (January 2017 to December 2018) in the Department of Obstetrics & Gynaecology at Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, a government hospital of tertiary care. The remaining 262 women were considered as the subjects for this study. Results: Abnormal mass was detected in the abdomen and the pelvic region of 21 women. When a speculum was inserted a mass was observed in the cervical region in 116 women, most of these masses were due to malignancy. Erosion in the cervix was observed in 42 women. A relatively small number of women had growth in their vagina and vulva region. 43.5 % of the women had heavy cervical mass, 2.3% of the women had abnormal growth in the myometrium of the uterus, 6.9% of women had malignancy in the inner layer of the uterus, 5.3% of the women had abnormal growth in the endometrium and 0.4% had cancer in the ovary. Endometrium was thicker than 10mm in 3.4% of the women. Conclusion: The bleeding after menopause is generally ignored as it seems harmless. However, it can indicate malignancy of the endometrial and cervical tissues. Recommendation: Diagnosis and evaluation of the cause can reduce the mortality and morbidity rates

Immunity to HIV-1 Is Influenced by Continued Natural Exposure to Exogenous Virus

Unprotected sexual intercourse between individuals who are both infected with HIV-1 can lead to exposure to their partner's virus, and potentially to super-infection. However, the immunological consequences of continued exposure to HIV-1 by individuals already infected, has to our knowledge never been reported. We measured T cell responses in 49 HIV-1 infected individuals who were on antiretroviral therapy with suppressed viral loads. All the individuals were in a long-term sexual partnership with another HIV-1 infected individual, who was either also on HAART and suppressing their viral loads, or viremic (>9000 copies/ml). T cell responses to HIV-1 epitopes were measured directly ex-vivo by the IFN-γ enzyme linked immuno-spot assay and by cytokine flow cytometry. Sexual exposure data was generated from questionnaires given to both individuals within each partnership. Individuals who continued to have regular sexual contact with a HIV-1 infected viremic partner had significantly higher frequencies of HIV-1-specific T cell responses, compared to individuals with aviremic partners. Strikingly, the magnitude of the HIV-1-specific T cell response correlated strongly with the level and route of exposure. Responses consisted of both CD4+ and CD8+ T cell subsets. Longitudinally, decreases in exposure were mirrored by a lower T cell response. However, no evidence for systemic super-infection was found in any of the individuals. Continued sexual exposure to exogenous HIV-1 was associated with increased HIV-1-specific T cell responses, in the absence of systemic super-infection, and correlated with the level and type of exposure

High-Performance Capillary Electrophoresis for Determining HIV-1 Tat Protein in Neurons

The HIV-1 protein, Tat has been implicated in AIDS pathogenesis however, the amount of circulating Tat is believed to be very low and its quantification has been difficult. We performed the quantification of Tat released from infected cells and taken up by neurons using high performance capillary electrophoresis. This is the first report to successfully measure the amount of Tat in neurons and places Tat as a key player involved in HIV-associated neurocognitive disorders

Idiopathic pulmonary fibrosis associated with pulmonary vein thrombosis: a case report

BACKGROUND: Pulmonary vein thrombosis represents a potentially fatal disease. This syndrome may clinically mimic pulmonary embolism but has a different investigation strategy and prognosis. Pulmonary vein thrombosis is difficult to diagnose clinically and usually requires a combination of conventionally used diagnostic modalities. CASE PRESENTATION: The authors report a case of a 78-year-old previously healthy female presenting with collapse and shortness of breath. Serum biochemistry revealed acute kidney injury, positive D-dimmer's and increased C reactive protein. Chest radiography demonstrated volume loss in the right lung. The patient was started on antibiotics and also therapeutic doses of low molecular weight heparin. The working diagnosis included community acquired pneumonia & pulmonary embolism. A computed tomography pulmonary angiogram was performed to confirm the clinical suspicions of pulmonary embolism. This demonstrated a thrombus in the pulmonary vein, with associated fibrosis and volume loss of the right lower lobe. A subsequent thrombophilia screen revealed a positive lupus anticoagulant antibody and rheumatoid factor and also decreased anti thrombin III and protein C levels. The urine protein/creatinine ratio was found to be 553 mg/mmol. CONCLUSION: The diagnosis of this patient was therefore of idiopathic pulmonary fibrosis associated with pulmonary vein thrombosis. Whether or not the pulmonary vein thrombosis was a primary cause of the fibrosis or a consequence of it was unclear. There are few data on the management of pulmonary vein thrombosis, but anticoagulation, antibiotics, and, in cases of large pulmonary vein thrombosis, thrombectomy or pulmonary resection have been used

Potential therapeutic implications of new insights into respiratory syncytial virus disease

Viral bronchiolitis is the most common cause of hospitalization in infants under 6 months of age, and 70% of all cases of bronchiolitis are caused by respiratory syncytial virus (RSV). Early RSV infection is associated with respiratory problems such as asthma and wheezing later in life. RSV infection is usually spread by contaminated secretions and infects the upper then lower respiratory tracts. Infected cells release proinflammatory cytokines and chemokines, including IL-1, tumor necrosis factor-α, IL-6, and IL-8. These activate other cells and recruit inflammatory cells, including macrophages, neutrophils, eosinophils, and T lymphocytes, into the airway wall and surrounding tissues. The pattern of cytokine production by T lymphocytes can be biased toward 'T-helper-1' or 'T-helper-2' cytokines, depending on the local immunologic environment, infection history, and host genetics. T-helper-1 responses are generally efficient in antiviral defense, but young infants have an inherent bias toward T-helper-2 responses. The ideal intervention for RSV infection would be preventive, but the options are currently limited. Vaccines based on protein subunits, live attenuated strains of RSV, DNA vaccines, and synthetic peptides are being developed; passive antibody therapy is at present impractical in otherwise healthy children. Effective vaccines for use in neonates continue to be elusive but simply delaying infection beyond the first 6 months of life might reduce the delayed morbidity associated with infantile disease

A new two-phase dimeticone pediculicide shows high efficacy in a comparative bioassay

Background: \ud Dimeticones kill head lice by physical means. Here we assessed in a comparative bioassay the ex vivo efficacy of "NYDA® sensitiv", a new two-phase dimeticone-based pediculicide similar to a product established on the market, but without fragrances.\ud \ud Methods:\ud We compared efficacy of the new product to a positive dimeticone control group, a sample of four other insecticidal and natural head lice products marketed in Germany, and an untreated control. In a bioassay, lice were exposed ex vivo to products and examined for activity for up to 24 hours, following a standard protocol.\ud \ud Results:\ud After 6 and 24 hours, 13.7 and 88.5% of untreated control lice did not show major vital signs. In contrast, no lice showed major vital signs 5 minutes after treatment with the new product or the control dimeticone group (NYDA®). This effect persisted at all observation points (100% efficacy). Efficacy of 0.5% permethrin (Infectopedicul®) ranged between 76 and 96% in evaluations between 5 min and 6 hours. All lice treated with a coconut-based compound (mosquito® Läuseshampoo) did not show major vital signs after 5 min, but mortality was only 58% after one hour. Pyrethrum extract (Goldgeist® forte) showed an efficacy of 22 - 52% between 5 min and 3 hours after treatment; after 6 hours, 76% of lice were judged dead. An oxyphthirine®-based compound (Liberalice DUO LP-PRO®) killed 22 - 54% of lice in the first 6 hours.\ud \ud Conclusions:\ud The two-phase dimeticone compound NYDA® sensitiv is highly efficacious. The removal of fragrances as compared to an established dimeticone product did not affect in vitro efficacy

Adherence to Highly Active Antiretroviral Treatment in HIV-Infected Rwandan Women

Scale-up of highly active antiretroviral treatment therapy (HAART) programs in Rwanda has been highly successful but data on adherence is limited. We examined HAART adherence in a large cohort of HIV+ Rwandan women.The Rwanda Women's Interassociation Study Assessment (RWISA) was a prospective cohort study that assessed effectiveness and toxicity of ART. We analyzed patient data 12±3 months after HAART initiation to determine adherence rates in HIV+ women who had initiated HAART.Of the 710 HIV+ women at baseline, 490 (87.2%) initiated HAART. Of these, 6 (1.2%) died within 12 months, 15 others (3.0%) discontinued the study and 80 others (19.0%) remained in RWISA but did not have a post-HAART initiation visit that fell within the 12±3 month time points leaving 389 subjects for analysis. Of these 389, 15 women stopped their medications without being advised to do so by their doctors. Of the remaining 374 persons who reported current HAART use 354 completed the adherence assessment. All women, 354/354, reported 100% adherence to HAART at the post-HAART visit. The high self-reported level of adherence is supported by changes in laboratory measures that are influenced by HAART. The median (interquartile range) CD4 cell count measured within 6 months prior to HAART initiation was 185 (128, 253) compared to 264 (182, 380) cells/mm(3) at the post-HAART visit. Similarly, the median (interquartile range) MCV within 6 months prior to HAART initiation was 88 (83, 93) fL compared to 104 (98, 110) fL at the 12±3 month visit.Self-reported adherence to antiretroviral treatment 12±3 months after initiating therapy was 100% in this cohort of HIV-infected Rwandan women. Future studies should explore country-specific factors that may be contributing to high levels of adherence to HAART in this population

CXCL12 inhibits expression of the NMDA receptor's NR2B subunit through a histone deacetylase-dependent pathway contributing to neuronal survival

Homeostatic chemokines, such as CXCL12, can affect neuronal activity by the regulation of inhibitory and excitatory neurotransmission, but the mechanisms involved are still undefined. Our previous studies have shown that CXCL12 protects cortical neurons from excitotoxicity by promoting the function of the gene-repressor protein Rb, which is involved in the recruitment of chromatin modifiers (such as histone deacetylases (HDACs)) to gene promoters. In neurons, Rb controls activity-dependent genes essential to neuronal plasticity and survival, such as the N-methyl--aspartic acid (NMDA) receptor's subunit NR2B, the expression of which in the tetrameric ion channel largely affects calcium signaling by glutamate. In this study, we report that CXCL12 differentially modulates intracellular responses after stimulation of synaptic and extrasynaptic NMDA receptors, by a specific regulation of the NR2B gene that involves HDACs. Our results show that CXCL12 selectively inhibits NR2B expression in vitro and in vivo altering NMDA-induced calcium responses associated with neuronal death, while promoting prosurvival pathways that depend on stimulation of synaptic receptors. Along with previous studies, these findings underline the role of CXCL12/CXCR4 in the regulation of crucial components of glutamatergic transmission. These novel effects of CXCL12 may be involved in the physiological function of the chemokine in both developing and mature brains

A Monoclonal Antibody against p53 Cross-Reacts with Processing Bodies

The p53 tumor suppressor protein is an important regulator of cell proliferation and apoptosis. p53 can be found in the nucleus and in the cytosol, and the subcellular location is key to control p53 function. In this work, we found that a widely used monoclonal antibody against p53, termed Pab 1801 (Pan antibody 1801) yields a remarkable punctate signal in the cytoplasm of several cell lines of human origin. Surprisingly, these puncta were also observed in two independent p53-null cell lines. Moreover, the foci stained with the Pab 1801 were present in rat cells, although Pab 1801 recognizes an epitope that is not conserved in rodent p53. In contrast, the Pab 1801 nuclear staining corresponded to genuine p53, as it was upregulated by p53-stimulating drugs and absent in p53-null cells. We identified the Pab 1801 cytoplasmic puncta as P Bodies (PBs), which are involved in mRNA regulation. We found that, in several cell lines, including U2OS, WI38, SK-N-SH and HCT116, the Pab 1801 puncta strictly colocalize with PBs identified with specific antibodies against the PB components Hedls, Dcp1a, Xrn1 or Rck/p54. PBs are highly dynamic and accordingly, the Pab 1801 puncta vanished when PBs dissolved upon treatment with cycloheximide, a drug that causes polysome stabilization and PB disruption. In addition, the knockdown of specific PB components that affect PB integrity simultaneously caused PB dissolution and the disappearance of the Pab 1801 puncta. Our results reveal a strong cross-reactivity of the Pab 1801 with unknown PB component(s). This was observed upon distinct immunostaining protocols, thus meaning a major limitation on the use of this antibody for p53 imaging in the cytoplasm of most cell types of human or rodent origin