Dynamics of runoff quality associated with an urban park and WSUD treatment train in a tropical climate.

A combination of discrete sampling using autosamplers triggered by area-velocity metres and continuous water quality monitoring using YSI datasondes enabled us to evaluate the dynamics of both stormwater runoff and dry weather water quality associated with an urban park and WSUD treatment train in Singapore. The WSUD treatment train consisted of a raingarden and sedimentation ponds. A first flush phenomenon was observed for total suspended solids (TSS) in three of four discrete-sampled events, but there was a less pronounced first flush characteristic for nutrients. Mean TN concentrations associated with runoff from the park (upstream of the WSUD treatment train) were in the range that would be associated with eutrophic conditions, while mean TP levels were in the mesotrophic/eutrophic boundary range. The raingarden reduced nutrient and TSS levels by 7-62% and loads by 65-93%, although nitrate levels were higher in the effluent compared to the influent. The sedimentation ponds successfully reduced sediment levels by 56%, based on continuous turbidity measurements. The dissolved oxygen levels in the sedimentation ponds were lower during drought periods, which has implications for aquatic organisms. The WSUD treatment train generally improved runoff quality from the park and such features can be easily integrated into the park design.

Cardiac magnetic resonance imaging in preeclampsia complicated by pulmonary edema shows myocardial edema with normal left ventricular systolic function.

BACKGROUND: Preeclampsia complicates approximately 5% of all pregnancies. When pulmonary edema occurs, it accounts for 50% of preeclampsia-related mortality. Currently, there is no consensus on the degree to which left ventricular systolic dysfunction contributes to the development of pulmonary edema. OBJECTIVE: This study aimed to use cardiac magnetic resonance imaging to detect subtle changes in left ventricular systolic function and evidence of acute left ventricular dysfunction (through tissue characterization) in women with preeclampsia complicated by pulmonary edema compared with both preeclamptic and normotensive controls. STUDY DESIGN: Cases were postpartum women aged ≥18 years presenting with preeclampsia complicated by pulmonary edema. Of note, 2 control groups were recruited: women with preeclampsia without pulmonary edema and women with normotensive pregnancies. All women underwent echocardiography and 1.5T cardiac magnetic resonance imaging with native T1 and T2 mapping. Gadolinium contrast was administered to cases only. Because of small sample sizes, a nonparametric test (Kruskal-Wallis) with pairwise posthoc analysis using Bonferroni correction was used to compare the differences between the groups. Cardiac magnetic resonance images were interpreted by 2 independent reporters. The intraclass correlation coefficient was calculated to assess interobserver reliability. RESULTS: Here, 20 women with preeclampsia complicated by pulmonary edema, 13 women with preeclampsia (5 with severe features and 8 without severe features), and 6 normotensive controls were recruited. There was no difference in the baseline characteristics between groups apart from the expected differences in blood pressure. Left atrial sizes were similar across all groups. Women with preeclampsia complicated by pulmonary edema had increased left ventricular mass (P=.01) but had normal systolic function compared with the normotensive controls. Furthermore, they had elevated native T1 values (P=.025) and a trend toward elevated T2 values (P=.07) in the absence of late gadolinium enhancement consistent with myocardial edema. Moreover, myocardial edema was present in all women with eclampsia or hemolysis, elevated liver enzymes, and low platelet count. Women with preeclampsia without severe features had similar findings to the normotensive controls. All cardiac magnetic resonance imaging measurements showed a very high level of interobserver correlation. CONCLUSION: This study focused on cardiac magnetic resonance imaging in women with preeclampsia complicated by pulmonary edema, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count. We have demonstrated normal systolic function with myocardial edema in women with preeclampsia with these severe features. These findings implicate an acute myocardial process as part of this clinical syndrome. The pathogenesis of myocardial edema and its relationship to pulmonary edema require further elucidation. With normal left atrial sizes, any hemodynamic component must be acute.

Radiation and energy budget dynamics associated with a floating photovoltaic system.

Shortwave radiation, longwave radiation, photovoltaic (PV) panel, air and near-surface water temperature data were measured for a floating PV system installed in a shallow tropical reservoir. Similar air and water temperature measurements were conducted in open water (ambient condition) for comparison. The data indicate that shortwave radiation is reduced significantly under the PV panels while the longwave radiation increased, and in fact became higher than the shortwave radiation as compared to open water conditions. The air temperature and the water temperature under the PV panels are higher than in open water. A numerical model was developed to predict the PV panel temperature, air and water temperatures beneath the panels and to investigate the heat balance at the reservoir surface, beneath the panels. The modelled air and PV panel temperatures were in good agreement with the field data. The modelled surface water temperature also replicated field measurements showing an increase of about 0.5 °C as compared to the open water temperature. Heat budget analysis showed that the thermal dynamics under the PV panels is mainly controlled by the longwave radiation from the PV panels and reduction in latent heat flux. The altered flux conditions beneath the panels result in a higher equilibrium temperature near the water surface, compared to open water conditions.

Safety and Immune Effects of Blocking CD40 Ligand in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Costimulation by CD40 and its ligand CD40L (CD154) is important for the functional differentiation of T cells. Preclinical studies have recognized the importance of this costimulatory interaction in the pathogenesis of experimental models of multiple sclerosis (MS). To determine safety, pharmacokinetics, and immune effect of a humanized monoclonal antibody (mAb) against CD40 ligand (toralizumab/IDEC-131) in patients with relapsing-remitting MS (RRMS). METHODS: This single-institution open-label dose-escalation study (phase I) enrolled 12 patients with RRMS to receive 4 doses of 1, 5, 10, or 15 mg/kg of humanized αCD40L (toralizumab) IV infusion every other week. Patients were followed up to 18 weeks, annually, and finally at 5 years. In addition to safety and pharmacokinetics, other secondary and exploratory measurements are immune effects, clinical, MRI, laboratory, and neuropsychological evaluations. RESULTS: Fifteen adverse events, all of mild to moderate severity, were considered to be of possible or of unknown relationship to treatment. No serious adverse events, including thromboembolic events, occurred during the 18-week defined study period. Annual and long-term follow-up at 5 years revealed no delayed toxicity. Pharmacokinetics were nonlinear between the 5 and 10 mg/kg dose groups. The serum half-life of toralizumab was consistent between the dose groups with a mean of 15.3 days (SD = 1.9). Flow cytometry revealed no depletion of lymphocyte subsets. An increase in the CD25+/CD3+ and CD25+/CD4+ ratio and a shift toward an anti-inflammatory cytokine response were seen after treatment. DISCUSSION: Our study suggests that blocking CD40L is safe and well tolerated in patients with RRMS while increasing CD25 + T cells and anti-inflammatory cytokine profile. These findings support further studies to assess the efficacy of blocking CD40L as a potential treatment of RRMS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence on the safety, pharmacokinetics, and immune effects of an mAb to CD40L in patients with RRMS.

Accumulation of heavy metals in stormwater biofiltration systems augmented with zeolite and fly ash.

The discharge of high levels of heavy metals into the environment is of concern due to its toxicity to aquatic life and potential human health impacts. Biofiltration systems have been used in urban environments to address nutrient contamination, but there is also evidence that such systems can be effective in reducing heavy metals concentration in stormwater. However, the accumulation pattern of heavy metals and lifespan of such systems, which are important in engineering design, have not been thoroughly explored. This study investigated the accumulation patterns of lead (Pb), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe), which are common in urban runoff, in non-vegetated filtration columns using three different types of filter media, namely sand (S), and mixtures of sand with fly ash (sand-fly ash mix, SF), and with zeolite (sand-zeolite mix, SZ). The columns were assessed in terms of infiltration rate, the mass of heavy metals accumulation at different depths, and formation of crust layer (schmutzdecke) at the surface. The results show that most of the heavy metals accumulated at the top 5-10 cm of the filter media. However, Zn was found adsorbed to a depth of 15 cm in S and SZ columns, while Mn and Fe were present in column S throughout the entire 30 cm depth of the filter media. The presence especially of Zn, Mn, and Fe in the deeper portions of the filter media before the top 5 cm layer reached its maximum adsorption capacity, hints that transport to the deeper layers is not necessarily dependent on saturation of the upper layers for these heavy metals. SF accumulated heavy metals most at the top 5 cm of the filter media layer, and retained twice the mass of heavy metals in the crust layer, compared to S and SZ columns. SF also yielded the lowest value of infiltration rate of 31 mm/h. Considering both metals accumulation and clogging potential of the filter media, the periodic maintenance of these systems is suggested to be approximately between 1.5 and 3 years.

Exploring the Gut-Brain Axis for the Control of CNS Inflammatory Demyelination: Immunomodulation by Bacteroides fragilis' Polysaccharide A.

The symbiotic relationship between animals and their resident microorganisms has profound effects on host immunity. The human microbiota comprises bacteria that reside in the gastrointestinal tract and are involved in a range of inflammatory and autoimmune diseases. The gut microbiota's immunomodulatory effects extend to extraintestinal tissues, including the central nervous system (CNS). Specific symbiotic antigens responsible for inducing immunoregulation have been isolated from different bacterial species. Polysaccharide A (PSA) of Bacteroides fragilis is an archetypical molecule for host-microbiota interactions. Studies have shown that PSA has beneficial effects in experimental disease models, including experimental autoimmune encephalomyelitis (EAE), the most widely used animal model for multiple sclerosis (MS). Furthermore, in vitro stimulation with PSA promotes an immunomodulatory phenotype in human T cells isolated from healthy and MS donors. In this review, we discuss the current understanding of the interactions between gut microbiota and the host in the context of CNS inflammatory demyelination, the immunomodulatory roles of gut symbionts. More specifically, we also discuss the immunomodulatory effects of B. fragilis PSA in the gut-brain axis and its therapeutic potential in MS. Elucidation of the molecular mechanisms responsible for the microbiota's impact on host physiology offers tremendous promise for discovering new therapies.

A Gut Feeling: The Importance of the Intestinal Microbiota in Psychiatric Disorders.

The intestinal microbiota constitutes a complex ecosystem in constant reciprocal interactions with the immune, neuroendocrine, and neural systems of the host. Recent molecular technological advances allow for the exploration of this living organ and better facilitates our understanding of the biological importance of intestinal microbes in health and disease. Clinical and experimental studies demonstrate that intestinal microbes may be intimately involved in the progression of diseases of the central nervous system (CNS), including those of affective and psychiatric nature. Gut microbes regulate neuroinflammatory processes, play a role in balancing the concentrations of neurotransmitters and could provide beneficial effects against neurodegeneration. In this review, we explore some of these reciprocal interactions between gut microbes and the CNS during experimental disease and suggest that therapeutic approaches impacting the gut-brain axis may represent the next avenue for the treatment of psychiatric disorders.

Environmental impact of Karkheh Dam in the southern part of Iran on groundwater quality by intervention and trend analysis.

The main objective of this research was to investigate the impact of the construction of Karkheh Dam in 2001 (referred to as the intervention time), on groundwater quality. The time series of total dissolved solids (TDS) and other water quality data including potassium (K+), sodium (Na+), magnesium (Mg2+), calcium (Ca2+), bicarbonate (HCO3-), sulfate (SO42-), and chloride (Cl-) for the period between 1996 and 2012 were analyzed. The magnitude of the trend by Sen's slope estimator for HCO3-, SO42-, and TDS was 0.005, - 0.02 and - 3.04, where a decline expected for SO42- and TDS, whereas for HCO3-, an increase was expected. According to the Pettitt's test, the mean of TDS decreased from 2306.9 mg/l between 1996 and 2002 to 797.2 mg/l between 2002 and 2012. During this time, the standard deviation of TDS declined from 2187.1 to 132.0 mg/l. The results of change point detection by the Pruned Exact Linear Time (PELT) algorithm were consistent with that of Pettitt's test providing confirmation that a change point in Ca2+, Mg2+, SO42-, and TDS time series data occurred in 2002.The findings from intervention analysis using the Bayesian structural time series (BSTS) technique showed that TDS concentration during the post-intervention period had an average value of 1127 mg/l compared with 1972 mg/l, before the dam construction. The time series of TDS demonstrated a decrease of about 43% following the intervention time.

Myocardial injury in systemic lupus erythematosus according to cardiac magnetic resonance tissue characterization: clinical and echocardiographic features.

OBJECTIVES: To determine the prevalence of myocardial injury (MInj) in systemic lupus erythematosus (SLE) according to cardiac magnetic resonance (CMR) criteria. To compare clinical and echocardiographic features of patients with and without MInj and identify predictors of myocardial tissue characteristics according to CMR. METHODS: SLE inpatients underwent CMR screening for MInj based on the Lake Louise Criteria (LLC). Tissue characteristics included inflammation (increased T2-weighted signal or early gadolinium enhancement ratio (EGEr)) and necrosis or fibrosis (late gadolinium enhancement (LGE)). Echocardiographic parameters included left (left ventricular ejection fraction (LVEF)) and right ventricular function (tricuspid annular plane systolic excursion (TAPSE)), global longitudinal strain (GLS), wall motion score (WMSi) and left ventricular internal diameter index (LVIDi). Variables were compared with regards to the presence/absence of CMR criteria. Logistic regression identified variables predictive of CMR tissue characteristics. RESULTS: A hundred and six SLE patients were screened of whom 49 patients were included. Fifty-seven patients were excluded due to intolerance of or contraindication to CMR (27/57 due to renal impairment). Twenty-three patients had CMR evidence of MInj, of which 60.9% was subclinical. Inflammation occurred in 16/23 and necrosis/fibrosis in 12/23 patients. Patients with any evidence of MInj were more frequently anti-dsDNA positive (p = 0.026) and patients fulfilling LLC for myocarditis had higher SLE disease activity (p = 0.022). The LVIDi (p = 0.005), LVEF (p = 0.005) and TAPSE (p = 0.011) were more abnormal in patients with an increased EGEr, whereas WMSi (p = 0.002) and GLS (0.020) were more impaired in patients with LGE. On multivariable logistic regression analyses, TAPSE predicted inflammation (OR: 0.045, p = 0.006, CI: 0.005-0.415) and GLS predicted necrosis/fibrosis (OR: 1.329, p = 0.031, CI: 1.026-1.722). A model including lymphocyte count, TAPSE and LVIDi predicted an increased EGEr on CMR (receiver operating characteristic-curve analyses: area under the curve: 0.901, p < 0.001, sensitivity: 88.9%, specificity: 76.3%). CONCLUSIONS: CMR evidence of MInj frequently occurs in SLE and is often subclinical. The utility of CMR in SLE is limited by a high exclusion rate, mainly due to renal involvement. Models including echocardiographic parameters (TAPSE, LVIDi and GLS) are predictive of CMR myocardial injury. Echocardiography can be used as a cost-effective screening tool with a high negative predictive value, in particular when CMR is contraindicated or unavailable.

Short-term organoid culture for drug sensitivity testing of high-grade serous carcinoma.

OBJECTIVE: Cancer patient-derived organoids (PDOs) grow as three dimensional (3D) structures in the presence of extracellular matrix and have been found to represent the original tumor's genetic complexity. In addition, PDOs can be grown and subjected to drug sensitivity testing in a shorter time course and with lesser expense than patient-derived xenograft models. Many patients with recurrent ovarian cancer develop malignant effusions that become refractory to chemotherapy. Since these same patients often present for palliative aspiration of ascites or pleural effusions, there is a potential opportunity to obtain tumor specimens in the form of multicellular spheroids (MCS) present in malignant effusion fluids. Our objective was to develop a short duration culture of MCS from ovarian cancer malignant effusions in conditions selected to support organoid growth and use them as a platform for empirical drug sensitivity testing. METHODS: In this study, malignant effusion specimens were collected from patients with high-grade serous ovarian carcinoma (HGSOC). MCS were recovered and subjected to culture conditions designed to support organoid growth. In a subset of specimens, RNA-sequencing was performed at two time points during the short-term culture to determine changes in transcriptome in response to culture conditions. Organoid induction was also characterized in these specimens using Ki67 staining and histologic analysis. Drug sensitivity testing was performed on all specimens. RESULTS: Our model describes organoids formed within days of primary culture, which can recapitulate the histological features of malignant ascites fluid and can be expanded for at least 6 days. RNA-seq analysis of four patient specimens showed that within 6 days of culture, there was significant up-regulation of genes related to cellular proliferation, epithelial-mesenchymal transition, and KRAS signaling pathways. Drug sensitivity testing identified several agents with therapeutic potential. CONCLUSIONS: Short duration organoid culture of MCS from HGSOC malignant effusions can be used as a platform for empiric drug sensitivity testing. These ex vivo models may be helpful in screening new or existing therapeutic agents prior to individualized treatment options.

Hydrological modeling and field validation of a bioretention basin.

An emerging green infrastructure, the bioretention basin, has been deployed world-wide to reduce peak flows, encourage infiltration, and treat pollutants. However, inadequate design of a basin impairs its treatment potential and necessitates the development and validation of a suitable hydrological model for design and analysis of bioretention basins. In this study, an existing numerical model, RECHARGE, has been adopted to simulate hydrological performance of a basin in the tropical climate of Singapore over a half year that included 80 storm events. Comparison of the model predictions with field observations shows that RECHARGE successfully simulates the basin hydrology of 80 events of varying rainfall characteristics with mass balance error of 5.1 ±â€¯7.5% per event and 0.3% overall. Using the verified model, we develop new design curves that predict bioretention basin performance as a function of three basin design parameters: detention depth; ratio of drainage basin area to bioretention area; and saturated hydraulic conductivity of the basin soil media. We evaluate basin performance in terms of the percentage of water that infiltrates and is treated in the subsurface portion of the basin and define an infiltration index to measure the change in infiltrated percentage caused by unit change in the basin design parameters. The marginal improvement in basin performance drops significantly when the basin depth (hd) is increased above 40 cm, when the ratio of drainage area to bioretention area (R) is decreased below 20, or when the saturated hydraulic conductivity (Ks) is increased above 10 cm/h.

MAP4K4 Inhibition Promotes Survival of Human Stem Cell-Derived Cardiomyocytes and Reduces Infarct Size In Vivo.

Heart disease is a paramount cause of global death and disability. Although cardiomyocyte death plays a causal role and its suppression would be logical, no clinical counter-measures target the responsible intracellular pathways. Therapeutic progress has been hampered by lack of preclinical human validation. Mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K4) is activated in failing human hearts and relevant rodent models. Using human induced-pluripotent-stem-cell-derived cardiomyocytes (hiPSC-CMs) and MAP4K4 gene silencing, we demonstrate that death induced by oxidative stress requires MAP4K4. Consequently, we devised a small-molecule inhibitor, DMX-5804, that rescues cell survival, mitochondrial function, and calcium cycling in hiPSC-CMs. As proof of principle that drug discovery in hiPSC-CMs may predict efficacy in vivo, DMX-5804 reduces ischemia-reperfusion injury in mice by more than 50%. We implicate MAP4K4 as a well-posed target toward suppressing human cardiac cell death and highlight the utility of hiPSC-CMs in drug discovery to enhance cardiomyocyte survival.

The Gut Microbiome and Multiple Sclerosis.

The microbiome can be defined as the sum of the microbial and host's genome. Recent information regarding this complex organ suggests that in animal models of multiple sclerosis (MS), the composition of the gut microbiome can be altered, giving rise to both the effector and regulatory phases of central nervous system (CNS) demyelination. Experimental findings during the past decade in animal models of MS have provided clear evidence for the significant role of gut microbes in both the effector and regulatory phase of this condition. There is mounting evidence in preliminary human studies suggesting that a dysbiotic MS gut microbiome could affect disease progression. We propose considering the gut microbiome as a key organ for the regulation of tolerance mechanisms and speculate that the gut microbiome is the major environmental risk factor for CNS demyelinating disease. Accordingly, we hypothesize that intervention of the gut microbiome could result in safer novel therapeutic strategies to treat MS.

Reduced 30-day gastrostomy placement mortality following the introduction of a multidisciplinary nutrition support team: a cohort study.

BACKGROUND: Percutaneous endoscopic gastrostomy feeding allows patients with dysphagia to receive adequate nutritional support, although gastrostomy insertion is associated with mortality. A nutrition support team (NST) may improve a gastrostomy service. The present study aimed to evaluate the introduction of a NST for assessment and follow-up of patients referred for gastrostomy. METHODS: We included adult inpatients referred for gastrostomy insertion consecutively between 1 October 2010 and 31 March 2013. During the first 6 months, a multidisciplinary NST assessment service was implemented. Patient characteristics, clinical condition, referral appropriateness and follow-up were documented prospectively. We compared the frequencies of appropriate referrals, 30-day mortality and mental capacity/consent assessment time spent between the 6 months implementation phase and 2 years following establishment of the assessment service ('established phase'). RESULTS: In total, 309 patients were referred for gastrostomy insertion and 199 (64%) gastrostomies placed. The percentage of appropriate referrals rose from 72% (61/85) during the implementation phase to 87% (194/224) during the established phase (P = 0.002). Thirty-day mortality reduced from 10% (5/52) to 2% (3/147) (P = 0.01), whereas time allocated to assessment of mental capacity and attainment of informed consent rose from mean 3 days (limits of normal variation 0-7) to mean 6 (0-13) days. CONCLUSIONS: The introduction of a NST to assess and select patients referred for gastrostomy placement was associated with a rise in the frequency of appropriate referrals and a decrease in 30-day mortality following gastrostomy insertion. Concomitantly, time spent on patient assessment and attainment of informed consent increased.

Using patients as educators for communication skills: Exploring dental students' and patients' views.

TITLE: A qualitative study to explore the issues for patients and students when giving feedback on the communication of dental students. OBJECTIVES: The Department of Health and National Institute for Health Research are committed to involving patients in improving clinical education, research and service delivery. Yet, there is a limited body of evidence on the perceptions of patients when asked to be involved in this way, and specifically when asked to provide feedback on the communication skills of dental students. This study seeks to address this gap and heighten the understanding of the issues faced by patients when asked to be involved in clinical education. METHODS: Data were collected using focus groups with dental students (n=10) and patients (n=8) being treated by these students. Both groups were asked about their thoughts, feelings and beliefs about patients being asked to provide feedback on the communication skills of dental students. Data analysis involved inductive thematic analysis of transcribed audio recordings. RESULTS: Four themes emerged from the data: "legitimacy," "co-educators," "maintaining the equilibrium of the patient-student relationship" and the "timing of patient feedback." Support for involving patients in giving feedback on students' communication skills was established, with patients considering they were best placed to comment on the communication skills of dental students. Patients and students do not want to provide feedback alone and want support to assist them, especially if feedback was negative. Issues of anonymity, confidentiality and ownership of the feedback process were worrisome, and the positioning of patient feedback in the programme was seen as critical. CONCLUSIONS: Patients and students are willing to engage in patient feedback on students' communication skills, and with support and training, the concerns around this are not insurmountable and the benefits could potentially profit both groups. These findings have resonance with other healthcare educators when using patients as educators in the development of communication skills.

CD4+ T cells from multiple sclerosis patients respond to a commensal-derived antigen.

Multiple sclerosis, an immune-mediated disease of the central nervous system, is characterized by the impaired function of regulatory cells that fail to suppress self-reactive effector cells. We have previously found that polysaccharide A, a capsular antigen derived from the human gut commensal Bacteroides fragilis, can induce a population of regulatory T cells. Herein, we demonstrate that naïve T cells isolated from patients with multiple sclerosis have the capacity to acquire regulatory characteristics when stimulated in vitro with polysaccharide A. This study demonstrates the amplification of a regulatory T cell response by a gut-derived commensal antigen in those with multiple sclerosis.