Modeling of an Air Conditioning System with Geothermal Heat Pump for a Residential Building

The need to address climate change caused by greenhouse gas emissions attaches great importance to research aimed at using renewable energy. Geothermal energy is an interesting alternative concerning the production of energy for air conditioning of buildings (heating and cooling), through the use of geothermal heat pumps. In this work a model has been developed in order to simulate an air conditioning system with geothermal heat pump. A ground source heat pump (GSHP) uses the shallow ground as a source of heat, thus taking advantage of its seasonally moderate temperatures. GSHP must be coupled with geothermal exchangers. The model leads to design optimization of geothermal heat exchangers and to verify the operation of the geothermal plant

The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

Obesity is a global epidemic associated with significant morbidity and mortality in adults and ill health in children. A proven successful approach in weight management has been the disruption of nutrient digestion, with orlistat having been used to treat obesity for the last 10 years. Although orlistat-induced weight loss remains modest, it produces meaningful reductions in risk factors for obesity-related conditions such as diabetes and cardiovascular disease. Moreover, this lipase inhibitor is free of the serious side effects that have dogged appetite-suppressing drugs. This success had driven investigation into new generation nutraceuticals, supplements and pharmaceutical agents that inhibit the breakdown of complex carbohydrates and fats within the gut. This review focuses on agents purported to inhibit intestinal enzymes responsible for macronutrient digestion. Except for some synthetic products, the majority of agents reviewed are either botanical extracts or bacterial products. Currently, carbohydrate digestion inhibitors are under development to improve glycemic control and these may also induce some weight loss. However, colonic fermentation induced side effects, such as excess gas production, remain an issue for these compounds. The α-glucosidase inhibitor acarbose, and the α-amylase inhibitor phaseolamine, have been used in humans with some promising results relating to weight loss. Nonetheless, few of these agents have made it into clinical studies and without any clinical proof of concept or proven efficacy it is unlikely any will enter the market soon

Justice and law in the thought of Arthur Schopenhauer (1788–1860)

The German philosopher Arthur Schopenhauer (1788–1860) stated that the world has two coexisting dimensions: the Will-side, which is the metaphysical, ideal, and ultimate reality where isolated creatures do not exist; and the Representational side, which Will-powered, self-centered individual phenomenon inhabits. Schopenhauer asserted that in human societies under the imperative of the Will, temporal justice may only aspire to prevent ill-natured actions towards humans and animals. Absolute freedom happens at the metaphysical level of the primeval Will, and an eternal justice exists, because victims and perpetrators belong to the same essence, and their deeds are therefore balanced. In Schopenhauerian terms, the only bridge between temporal and eternal justice is Will-denial, which leads to compassion and asceticism, and occurs after the awareness of the unity of all living beings. However, Will-denial, by being a strictly individual and unpredictable issue, led to Schopenhauer's pessimism about an enduring collective well-being. Approaching eternal and temporal justices is thus, a worthy quest, which is visible in the current worldwide concern and interest in altruism, cooperation, and compassion. Nevertheless, if this progress is devoid of compassion and asceticism (cooperation and healthy austerity in modern terms) it could lead to increased malicious social control and manipulation. Schopenhauer's thought may thus be part of the philosophical foundations of contemporary forensic psychiatry. This paper discusses these aspects of the philosopher's work, with reference to current ideas and literature in forensic psychiatry, psychology, law, and issues in contemporary physics which are pertinent to this debate

Grotta Romanelli (Southern Italy, Apulia): legacies and issues in excavating a key site for the Pleistocene of the Mediterranean

Grotta Romanelli, located on the adriatic coast of southern apulia (Italy), is considered a key site for the Mediterranean Pleistocene for its archaeological and palaeontological contents. The research team had to deal with the consequences of more than 40 years of inactivity in the eld and the combined effect of erosion and legal, as well as illegal, excavations. In this paper, we provide a database of all the information published during the rst 70 years of excavations and highlight the outstanding problems and contradictions between the chronological and geomorphological evidence, the features of the faunal assemblages and the limestone artefacts

Functional genomics provide key insights to improve the diagnostic yield of hereditary ataxia

Improvements in functional genomic annotation have led to a critical mass of neurogenetic discoveries. This is exemplified in hereditary ataxia, a heterogeneous group of disorders characterised by incoordination from cerebellar dysfunction. Associated pathogenic variants in more than 300 genes have been described, leading to a detailed genetic classification partitioned by age-of-onset. Despite these advances, up to 75% of patients with ataxia remain molecularly undiagnosed even following whole genome sequencing, as exemplified in the 100,000 Genomes Project. This study aimed to understand whether we can improve our knowledge of the genetic architecture of hereditary ataxia by leveraging functional genomic annotations, and as a result, generate insights and strategies that raise the diagnostic yield. To achieve these aims, we used publicly-available multi-omics data to generate 294 genic features, capturing information relating to a gene's structure, genetic variation, tissue-specific, cell-type-specific and temporal expression, as well as protein products of a gene. We studied these features across genes typically causing childhood-onset, adult-onset or both types of disease first individually, then collectively. This led to the generation of testable hypotheses which we investigated using whole genome sequencing data from up to 2,182 individuals presenting with ataxia and 6,658 non-neurological probands recruited in the 100,000 Genomes Project. Using this approach, we demonstrated a high short tandem repeat (STR) density within childhood-onset genes suggesting that we may be missing pathogenic repeat expansions within this cohort. This was verified in both childhood- and adult-onset ataxia patients from the 100,000 Genomes Project who were unexpectedly found to have a trend for higher repeat sizes even at naturally-occurring STRs within known ataxia genes, implying a role for STRs in pathogenesis. Using unsupervised analysis, we found significant similarities in genomic annotation across the gene panels, which suggested adult- and childhood-onset patients should be screened using a common diagnostic gene set. We tested this within the 100,000 Genomes Project by assessing the burden of pathogenic variants among childhood-onset genes in adult-onset patients and vice versa. This demonstrated a significantly higher burden of rare, potentially pathogenic variants in conventional childhood-onset genes among individuals with adult-onset ataxia. Our analysis has implications for the current clinical practice in genetic testing for hereditary ataxia. We suggest that the diagnostic rate for hereditary ataxia could be increased by removing the age-of-onset partition, and through a modified screening for repeat expansions in naturally-occurring STRs within known ataxia-associated genes, in effect treating these regions as candidate pathogenic loci

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

Preneoplastic somatic mutations including MYD88(L265P) in lymphoplasmacytic lymphoma

Normal cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B lymphocytes before lymphoma remains uncertain. We sequenced multiple stages of the B lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of the high prevalence of mutated MYD88. We observed similar accumulation of random mutations in B lineages from both cohorts and unexpectedly found MYD88(L265P) in normal precursor and mature B lymphocytes from patients with lymphoma. We uncovered genetic and transcriptional pathways driving malignant transformation and leveraged these to model lymphoplasmacytic lymphoma in mice, based on mutated MYD88 in B cell precursors and BCL2 overexpression. Thus, MYD88(L265P) is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

Neurochemical mechanisms involved in nicotine's effects on anxiety and modulation of these effects by physiological factors

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Phytochemicals in the Control of Human Appetite and Body Weight

Since obesity has grown to epidemic proportions, its effective management is a very important clinical issue. Despite the great amount of scientific effort that has been put into understanding the mechanisms that lead to overconsumption and overweight, at the moment very few approaches to weight management are effective in the long term. On the other hand, modern society is also affected by the growing incidence of eating disorders on the other side of the spectrum such as anorexia and bulimia nervosa which are equally difficult to treat. This review will try to summarise the main findings available in the literature regarding the effect of plants or plant extracts (phytochemicals) on human appetite and body weight. The majority of plant extracts are not single compounds but rather a mixture of different molecules, therefore their mechanism of action usually targets several systems. In addition, since some cellular receptors tend to be widely distributed, sometimes a single molecule can have a widespread effect. This review will attempt to describe the main phytochemicals that have been suggested to affect the homeostatic mechanisms that influence intake and body weight. Clinical data will be summarised and scientific evidence will be reviewed