Flow and particle deposition using an integrated CFD model of the respiratory system

This paper was presented at the 3rd Micro and Nano Flows Conference (MNF2011), which was held at the Makedonia Palace Hotel, Thessaloniki in Greece. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, Aristotle University of Thessaloniki, University of Thessaly, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute.In the present study a theoretical investigation on flow, particle motion, and deposition in the respiratory system is reported. An integrated computational model of the respiratory system is developed comprised of nine sequential computational blocks corresponding to the nasal cavity, the pharyngo-trachea, and a series of branches of the pulmonary system. Airflow during steady-state inhalation inside the human respiratory system was determined using computational fluid dynamics (CFD) for inlet velocities, vin = 1-20 m/s, corresponding to inhalation flow rates of 9 to 180 L/min, and particle deposition was examined in detail for particle sizes, D=1-20μm. Local deposition efficiencies as well as spatial distribution of deposited particles were found to be strongly dependent on the particle size and volumetric flow rate

Home or hospital as the place of end-of-life care and death: A grounded theory study of parents' decision-making

BACKGROUND: While several studies have examined 'what' families want with regard to the place of a child's end-of-life care and death, few have explored 'how' parents reach a decision. AIMS: (1) to develop a model explaining how parents of a child with a life-threatening illness in Greece decide about the place of end-of-life care and death; (2) to identify the factors affecting decision-making; (3) to consider the implications for clinical practice. DESIGN: Grounded theory study of bereaved parents using semi-structured open-ended interviews following Strauss and Corbin's principles of data collection and analysis. SETTING/PARTICIPANTS: Semi-structured interviews with 36 bereaved parents of 22 children who died at home (n = 9) or in a paediatric hospital (n = 13) in Athens, Greece. RESULTS: (1) Decisions regarding place of care and death were reached in one of four ways: consensus, accommodation, imposition of professional decisions on parents or imposition of parents' decisions without including professionals. (2) Six factors were identified as affecting decisions: awareness of dying, perceived parental caregiving competence, perceived professional competence, parents' view of symptom management, timing of decision-making, and being a 'good parent'. (3) Decisions were clear-cut or shifting. Few parents did not engage in decisions. CONCLUSION: Parents' decisions about place of end-of-life care and death are affected by personal, interpersonal, timing and disease-related factors. Parents are best supported in decision-making when information is presented clearly and honestly with recognition of what acting as 'good parents' means to them, and opportunities to enhance their caregiving competence to care for their child at home, if they choose so

Molecular alterations that drive breast cancer metastasis to bone.

Epithelial cancers including breast and prostate commonly progress to form incurable bone metastases. For this to occur, cancer cells must adapt their phenotype and behaviour to enable detachment from the primary tumour, invasion into the vasculature, and homing to and subsequent colonisation of bone. It is widely accepted that the metastatic process is driven by the transformation of cancer cells from a sessile epithelial to a motile mesenchymal phenotype through epithelial-mesenchymal transition (EMT). Dissemination of these motile cells into the circulation provides the conduit for cells to metastasise to distant organs. However, accumulating evidence suggests that EMT is not sufficient for metastasis to occur and that specific tissue-homing factors are required for tumour cells to lodge and grow in bone. Once tumour cells are disseminated in the bone environment, they can revert into an epithelial phenotype through the reverse process of mesenchymal-epithelial transition (MET) and form secondary tumours. In this review, we describe the molecular alterations undertaken by breast cancer cells at each stage of the metastatic cascade and discuss how these changes facilitate bone metastasis

Identifying characteristic features of the retinal and choroidal vasculature in choroideremia using optical coherence tomography angiography

PURPOSE: Using optical coherence tomography angiography (OCTA) to investigate the area with flow in the superficial retinal vessel network (SVRN) and choriocapillaris (CC) layer among male subjects with choroideremia (CHM), female carriers, and normal controls to identify vascular changes. PATIENTS AND METHODS: Images of SRVN and CC layer were acquired in 9 affected males, 5 female carriers, and 14 age- and gender-matched controls using the Angiovue software of the RTVue XR Avanti. RESULTS: The mean age was 33 years for affected male CHM patients (median 30 years), 46 years for female carriers (median 53 years), and 39 years for controls (median 38.5). Mean SRVN area±SD in subjects with CHM was 12.93±2.06 mm², in carrier subjects 15.36±0.60 mm², and in controls 15.30±1.35 mm² (P<0.01). The mean CC area±SD with flow was 6.97±5.26 mm² in CHM subjects, 21.65±0.17 mm² in carriers and 21.36±0.76 mm² in controls (P<0.01). SRVN and CC area with flow showed a negative correlation in CHM subjects with the age (r=−0.86; P<0.003 and r=−0.77; P<0.01, respectively). CC area with flow had a positive correlation with SRVN (r=0.83, P<0.001). Overall, visual acuity had a negative correlation with SRVN and CC area with flow (r=−0.67, P<0.001 and r=−0.57, P<0.002, respectively). CONCLUSIONS: This is the first study to highlight changes in the SRVN in CHM subjects. OCTA detected a reduced area with flow in both retinal and choroidal circulations, and may be a useful tool for monitoring natural history and disease progression in forthcoming clinical trials

Biomonitoring of bisphenol A concentrations in maternal and umbilical cord blood in regard to birth outcomes and adipokine expression: a birth cohort study in Taiwan

<p>Abstract</p> <p>Background</p> <p>Bisphenol A (BPA) is a sealant and flux of plastic materials and has been determined to be an endocrine-disrupting chemical. Prenatal exposure to BPA can lead to substantial adverse effects on fetal growth and development. This study was conducted to assess BPA concentration in pregnant women and umbilical cord blood, and to investigate whether maternal BPA exposure affected fetal outcomes including lower birth weight (LBW), smaller size for gestational age (SGA), and high leptin (HLP) and low adiponectin (LAD) secretion.</p> <p>Methods</p> <p>We measured the BPA levels of maternal blood (n = 97) and umbilical cord blood (n = 97) with a high-performance liquid chromatography/UV detector. The protein secretion of leptin and adiponectin were separately determined using enzyme-linked immunosorbent assay. A logistic regression was performed to estimate the effects of maternal exposure to BPA on LBW, SGA, and adverse action of adipokines in newborns.</p> <p>Results</p> <p>The geometric means of BPA concentration in maternal blood and fetal cord blood were 2.5 ng/ml and 0.5 ng/ml, respectively. Elevated risks of LBW (OR 2.42, 95% confidence interval (CI) 1.72-3.36), SGA (OR 2.01, 95% CI 1.39-3.01), and adverse action of leptin (OR 1.67, 95% CI 1.12-2.25) and adiponectin (OR 1.25, 95% CI 1.52-3.97) were observed in male neonates in the highest quartile of maternal BPA exposure.</p> <p>Conclusions</p> <p>Elevated prenatal BPA exposure increased the risk of LBW, SGA, and adverse actions of adipokines in neonates, especially in male infants. These results provide further evidence that maternal exposure is correlated with adverse birth outcomes.</p

Preclinical evaluation of a TEX101 protein ELISA test for the differential diagnosis of male infertility

BACKGROUND: TEX101 is a cell membrane protein exclusively expressed by testicular germ cells and shed into seminal plasma. We previously verified human TEX101 as a biomarker for the differential diagnosis of azoospermia, and developed a first-of-its-kind TEX101 ELISA. To demonstrate the clinical utility of TEX101, in this work we aimed at evaluating ELISA performance in a large population of fertile, subfertile, and infertile men. METHODS: Mass spectrometry, size-exclusion chromatography, ultracentrifugation, and immunohistochemistry were used to characterize TEX101 protein as an analyte in seminal plasma. Using the optimized protocol for seminal plasma pretreatment, TEX101 was measured by ELISA in 805 seminal plasma samples. RESULTS: We demonstrated that TEX101 was present in seminal plasma mostly in a free soluble form and that its small fraction was associated with seminal microvesicles. TEX101 median values were estimated in healthy, fertile pre-vasectomy men (5436 ng/mL, N = 64) and in patients with unexplained infertility (4967 ng/mL, N = 277), oligospermia (450 ng/mL, N = 270), and azoospermia (0.5 ng/mL, N = 137). Fertile post-vasectomy men (N = 57) and patients with Sertoli cell-only syndrome (N = 13) and obstructive azoospermia (N = 36) had undetectable levels of TEX101 (≤0.5 ng/mL). A cut-off value of 0.9 ng/mL provided 100% sensitivity at 100% specificity for distinguishing pre- and post-vasectomy men. The combination of a concentration of TEX101 > 0.9 ng/mL and epididymis-specific protein ECM1 > 2.3 μg/mL provided 81% sensitivity at 100% specificity for differentiating between non-obstructive and obstructive azoospermia, thus eliminating the majority of diagnostic testicular biopsies. In addition, a cut-off value of ≥0.6 ng/mL provided 73% sensitivity at 64% specificity for predicting sperm or spermatid retrieval in patients with non-obstructive azoospermia. CONCLUSIONS: We demonstrated the clinical utility of TEX101 ELISA as a test to evaluate vasectomy success, to stratify azoospermia forms, and to better select patients for sperm retrieval. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-017-0817-5) contains supplementary material, which is available to authorized users

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income&nbsp;countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of&nbsp;countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified