Machine Learning is the study of methods for programming computers to learn. Computers are applied to a wide range of tasks, and for most of these it is relatively easy for programmers to design and implement the necessary software. However, there are many tasks for which this is difficult or impossible. These can be divided into four general categories. First, there are problems for which there exist no human experts. For example, in modern automated manufacturing facilities, there is a need to predict machine failures before they occur by analyzing sensor readings. Because the machines are new, there are no human experts who can be interviewed by a programmer to provide the knowledge necessary to build a computer system. A machine learning system can study recorded data and subsequent machine failures and learn prediction rules. Second, there are problems where human experts exist, but where they are unable to explain their expertise. This is the case in many perceptual tasks, such as speech recognition, hand-writing recognition, and natural language understanding. Virtually all humans exhibit expert-level abilities on these tasks, but none of them can describe the detailed steps that they follow as they perform them. Fortunately, humans can provide machines with examples of the inputs and correct outputs for these tasks, so machine learning algorithms can learn to map the inputs to the outputs. Third, there are problems where phenomena are changing rapidly. In finance, for example, people would like to predict the future behavior of the stock market, of consumer purchases, or of exchange rates. These behaviors change frequently, so that even if a programmer could construct a good predictive computer program, it would need to be rewritten frequently. A learning program can relieve the programmer of this burden by constantly modifying and tuning a set of learned prediction rules. Fourth, there are applications that need to be customized for each computer user separately. Consider, for example, a program to filter unwanted electronic mail messages. Different users will need different filters. It is unreasonable to expect each user to program his or her own rules, and it is infeasible to provide every user with a software engineer to keep the rules up-to-date. A machine learning system can learn which mail messages the user rejects and maintain the filtering rules automatically. Machine learning addresses many of the same research questions as the fields of statistics, data mining, and psychology, but with differences of emphasis. Statistics focuses on understanding the phenomena that have generated the data, often with the goal of testing different hypotheses about those phenomena. Data mining seeks to find patterns in the data that are understandable by people. Psychological studies of human learning aspire to understand the mechanisms underlying the various learning behaviors exhibited by people (concept learning, skill acquisition, strategy change, etc.).

Machine learning

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

http://www.healthcare.uiowa.edu/corefacilities/esr/publications/buettnerpubs/pdf/FRBM-2001-30-1191-FQS-Redox.pdf

Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple.

Pathology and genetics of tumors of soft tissue and bone

In this paper we extend the “network theory of aging,” and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as “inflamm-aging,” is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age-related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ-specific age-related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.

Inflamm‐aging: An Evolutionary Perspective on Immunosenescence

Severe sepsis remains a clinical challenge today, even indeveloped countries, because of the increased age of thepatients and the high burden of antibiotic resistance [1]. Inaddition, in recent years, we have become increasinglyaware that, even in the early stages of sepsis, a high pro-portion of patients experience a severe dysfunction ofnative and adaptive immunity, which is closely related topatients’ outcome [2]. In this context, understanding thefunctionality of receptors able to modulate the immuneresponse, and in particular to downregulate inﬂammation,has great importance for designing new therapeutic strat-egies. Among these molecules, a main role is occupied bythe TAM family of receptor tyrosine kinases, which isformed by three members, i.e., Tyro3, AxI, and Mer, thathave two vitamin K-dependent ligands, i.e., the growtharrest-speciﬁc protein (Gas)6 and Protein S [3]. In theSeptember 2013 issue of Intensive Care Medicine, Gui-gnant et al. [4] explored by an elegant experimental studythe expression of TAM receptors in circulating immunecells in patients with septic shock and after trauma, and inhealthy volunteers. A signiﬁcant early alteration of MerTKexpression on monocytes and neutrophils was observed inpatients with septic shock, and a persistent MerTK over-expression after septic shock was associated with adverseoutcome. The ex vivo analysis showed also a differentMerTK surface expression of healthy monocytes after48 h incubation with plasma from septic or traumapatients, supporting the difference in TAM expressionbetween infection-induced inﬂammation and sterileinﬂammation (i.e., trauma). The study provides newimportant data on the mechanisms of immune response insepsis, but the true reasons for the observed alterations inMerKT expression and their role in the complex patho-physiological context of sepsis remain to be clariﬁed.TAM receptors are under the control of Toll-likereceptors (TLR), and are widely expressed by cells of theinnateimmunesystem[5].ActivationofTAMreceptorsbytheir ligands triggers a cascade of intracellular events thatculminate in the inhibition of nuclear factor-kappaB (NF-jB), a crucial proinﬂammatory molecule, and results indownregulation of inﬂammation [6]. When expressed bymonocytes and granulocytes, these receptors (and in par-ticular MerTK) can also mediate the phagocytosis ofapoptoticcells[7],whichisfundamentalinordertoremovedead cells without triggering inﬂammation. Several datanow exist that underline the importance of MerTK activa-tion in the elimination of potential autoantigens derived byapoptotic cells, in the inhibition of the production of pro-inﬂammatory cytokines, and in the prevention of theexpansion of autoreactive lymphocytes [8–10]. The func-tional impairment of MerTK promotes not onlyautoimmunity but also atherosclerosis, while its overex-pression is linked to poor prognosis in cancer [11].The strong relationships existing between TAMreceptors and a proinﬂammatory molecule such as tumornecrosis factor-alpha (TNF-a) are reinforced by theobservation that they can interact with a common protein,the matrix metalloproteinase TNF-a converting enzyme,also known as ‘‘a disintegrin and a metalloproteinase 17’’(ADAM17). In order to provide the mature, soluble,secretable form of TNF-a, ADAM17 cleaves the mem-brane form of this important proinﬂammatory cytokine[12]. Interestingly, ADAM17 is also able to cleave the

/pdf/a-janus-role-for-mertk-in-the-outcome-of-septic-shock-3r0weesxey.pdf

A Janus role for MerTK in the outcome of septic shock.

The aim of our study was to evaluate whether the introduction of SDD in a structured protocol for VAP prevention was effective in reducing the occurrence of ventilator-associated pneumonia (VAP) in COVID-19 patients without changes in the microbiological pattern of antibiotic resistance. This observational pre-post study included adult patients requiring invasive mechanical ventilation (IMV) for severe respiratory failure related to SARS-CoV-2 admitted in three COVID-19 intensive care units (ICUs) in an Italian hospital from 22 February 2020 to 8 March 2022. Selective digestive decontamination (SDD) was introduced from the end of April 2021 in the structured protocol for VAP prevention. The SDD consisted of a tobramycin sulfate, colistin sulfate, and amphotericin B suspension applied in the patient’s oropharynx and the stomach via a nasogastric tube. Three-hundred-and-forty-eight patients were included in the study. In the 86 patients (32.9%) who received SDD, the occurrence of VAP decreased by 7.7% (p = 0.192) compared to the patients who did not receive SDD. The onset time of VAP, the occurrence of multidrug-resistant microorganisms AP, the length of invasive mechanical ventilation, and hospital mortality were similar in the patients who received and who did not receive SDD. The multivariate analysis adjusted for confounders showed that the use of SDD reduces the occurrence of VAP (HR 0.536, CI 0.338–0.851; p = 0.017). Our pre-post observational study indicates that the use of SDD in a structured protocol for VAP prevention seems to reduce the occurrence of VAP without changes in the incidence of multidrug-resistant bacteria in COVID-19 patients.

/pdf/role-of-selective-digestive-decontamination-in-the-sba0bivh.pdf

Role of Selective Digestive Decontamination in the Prevention of Ventilator-Associated Pneumonia in COVID-19 Patients: A Pre-Post Observational Study

According to the Joint United Nations Program of HIV/AIDS (UNAIDS) and the World Health Organization (WHO) (Joint United Nations Program of HIV/AIDS, 2001), as of the end of 2001, there were about 40 million adults and children living with human immunod-eficiency virus (HIV) infection. This total does not include the 20 million people around the world who already died of AIDS. Of the 40 million currently alive, 37.2 are adults, 17.6 are women, and more than 2.7 are children. In 2001, there were 5 million new cases of HIV infection in the world, and 3 million AIDS related deaths. The large majority (almost three quarters) live in Sub-Saharan Africa where the prevalence rate of the infection among adults is 8.4%; more than 55% of infected individuals are women. The second major pocket of HIV infection is in South and Southeast Asia, with more than 6 million people infected. In North America where the epidemic was first described, there are 940,000 individuals who are HIV- , and in Western Europe, 540,000. Furthermore, South America, China, and East-ern Europe are characterized by a rapid increase in infection rates. These dramatic numbers clearly indicate that the fight against HIV/AIDS is an absolute health, social, economical and political priority in all parts of the world.

Complementary and Alternative Medicine During HIV Infection

A randomized, controlled trial to evaluate change in cardiometabolic and endothelial function in HIV-infected patients with optimal viral suppression on Darunavir/ritonavir monotherapy vs. triple-therapy.

 Abstract— The infection with HIV, the virus that causes AIDS, triggers a number of immune responses that have the aim to control the production and propagation of the virus, mainly by blocking its binding to CD4+ T cells by neutralizing antibodies, or killing infected cells by cytotoxic T lymphocytes. However, in most cases the immune system is not able to control this retrovirus, that uses sophisticated evolutionary mechanisms to survive and propagate its progeny. In this review some immune mechanisms that try to contrast HIV are discussed, putting an accent on the variety of problems that immunologists have had, and actually have in designing and producing an effective vaccine.

Andrea Cossarizza

Papers

A Janus role for MerTK in the outcome of septic shock.

Role of Selective Digestive Decontamination in the Prevention of Ventilator-Associated Pneumonia in COVID-19 Patients: A Pre-Post Observational Study

Complementary and Alternative Medicine During HIV Infection

A randomized, controlled trial to evaluate change in cardiometabolic and endothelial function in HIV-infected patients with optimal viral suppression on Darunavir/ritonavir monotherapy vs. triple-therapy.

Immune Response and HIV Infection: Old Problems for New Challenges