Response Surface Methodology and Artificial Neural Network Modelling of Membrane Rotating Biological Contactors for Wastewater Treatment

Membrane fouling is a major hindrance to widespread wastewater treatment applications. This study optimizes operating parameters in membrane rotating biological contactors (MRBC) for maximized membrane fouling through Response Surface Methodology (RSM) and an Artificial Neural Network (ANN). MRBC is an integrated system, embracing membrane filtration and conventional rotating biological contactor in one individual bioreactor. The filtration performance was optimized by exploiting the three parameters of disk rotational speed, membrane-to-disk gap, and organic loading rate. The results showed that both the RSM and ANN models were in good agreement with the experimental data and the modelled equation. The overall R² value was 0.9982 for the proposed network using ANN, higher than the RSM value (0.9762). The RSM model demonstrated the optimum operating parameter values of a 44 rpm disk rotational speed, a 1.07 membrane-to-disk gap, and a 10.2 g COD/m² d organic loading rate. The optimization of process parameters can eliminate unnecessary steps and automate steps in the process to save time, reduce errors and avoid duplicate work. This work demonstrates the effective use of statistical modeling to enhance MRBC system performance to obtain a sustainable and energy-efficient treatment process to prevent human health and the environment.     

Silicone pneumonitis,diffuse alveolar hemorrhage and acute respiratory distress syndrome from gluteal silicone injections

Fatal complications from illegal cosmetic injection of nonmedical-grade liquid silicone (polydimethylsiloxane) by unlicensed providers are becoming more common. Silicone embolization syndrome (SES) can rapidly progress to pneumonitis and diffuse alveolar hemorrhage. Prompt and aggressive management with high-dose steroids and lung-protective ventilation strategies to minimize acute respiratory distress syndrome (ARDS) can be lifesaving. We present the case of a patient presenting with abdominal pain and shortness of breath who quickly developed respiratory failure. The patient recently had received bilateral gluteal silicone injections from an unlicensed provider.     

Linkage mapping of a nonspecific form of X‐linked mental retardation (MRX53) in a large Pakistani family

Nonspecific X‐linked mental retardation is a nonprogressive, genetically heterogeneous condition that affects cognitive function in the absence of other distinctive clinical manifestations. We report here linkage data on a large Pakistani family affected by a form of X‐linked nonspecific mental retardation. X chromosome genotyping of family members and linkage analysis allowed the identification of a new disease locus, MRX53. The defined critical region spans approximately 15 cM between DXS1210 and DXS1047 in Xq22.2–26. A LOD score value of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081. © 2001 Wiley‐Liss, Inc.     

Multilocus Sequence Types of Carbapenem-Resistant Pseudomonas aeruginosa in Singapore Carrying Metallo-β-Lactamase Genes,Including the Novel blaIMP-26 Gene

Nine imipenem-resistant Pseudomonas aeruginosa isolates were found to contain a variety of metallo-β-lactamase genes, including bla_IMP-1, bla_IMP-7, bla_VIM-2, bla_VIM-6, and the novel bla_IMP-26. Multilocus sequence typing showed a diversity of sequence types. Comparison with isolates from an earlier study showed that the epidemic clones from 2000 have not become established.Carbapenem-resistant Pseudomonas aeruginosa is an increasing problem worldwide. While many underlying mechanisms may account for carbapenem resistance in this species, the possession of metallo-β-lactamase (MBL) genes is of particular concern because these enzymes are able to hydrolyze all β-lactam antimicrobials with the exception of aztreonam. In addition, these genes may be mobilized and transferred between different species of bacteria. We conducted a study in 2008 to investigate if there were any changes in the epidemiology of P. aeruginosa isolates containing MBL genes in our hospital compared to results from an earlier survey carried out in 2000 (3).Of 2,552 nonduplicate P. aeruginosa organisms isolated in 2008, 123 isolates were imipenem resistant. Of these, 11 were positive for MBL production by imipenem-EDTA disk diffusion (5). Nine of these yielded a product by multiplex PCR for MBL genes (2). The individual MBL genes were then amplified and sequenced. The clonal relationship between isolates with MBL genes was determined by pulsed-field gel electrophoresis (PFGE) of chromosomal DNA restricted with SpeI (3). The PFGE band patterns were analyzed with Bionumerics (Applied Maths NV, Sint-Martens-Latem, Belgium), and all strains with more than 85% similarity were considered to belong to the same clone. All strains were further subjected to multilocus sequence typing (MLST) (1). Because it is a nucleic acid sequence-based method, MLST is able to characterize bacterial types in an unambiguous fashion and establish evolutionary relationships between strains better than band-based methods like PFGE. Representative MBL-producing P. aeruginosa isolates from the 2000 survey were also subjected to PFGE and MLST. MLST profiles were submitted to eBURST V3 (http://eburst.mlst.net/) on 10 March 2010. Isolates sharing six out of seven alleles were assigned to the same BURST group and can be considered to belong to the same clonal complex descended from a common founder genotype. The PFGE, MBL gene sequence, and MLST results are summarized in Fig. ​Fig.11.Open in a separate windowFIG. 1.Dendrogram of PFGE patterns of P. aeruginosa isolates with metallo-β-lactamase genes, showing the year of isolation, MLST sequence type, and BURST group.In our previous study, 21 of 2,094 (1.0%) of all nonduplicate P. aeruginosa isolates in our hospital had MBL genes (3). With the exception of one isolate with bla_IMP-7, all other isolates had bla_IMP-1 and belonged to one of two PFGE clones. Isolates belonging to clone A had sequences identical to that of the original bla_IMP-1 first reported in Japan. Four representatives of clone A isolated from our hospital in 2000 had sequence type 964 (ST964) by MLST. Isolates belonging to clone B isolated in 2000 had sequences for variant bla_IMP-1 (bla_IMP-1v) with four silent mutations. Three representatives of this clone from 2000 had ST233 and one had ST742 based on MLST. All four representatives of clone B belong to the same BURST group, which was different from that of clone A.In contrast, in the 2008 survey, 9 of 2,552 (0.35%) nonduplicate P. aeruginosa isolates had MBL genes. Unlike the earlier study, there were no large clonal outbreaks. Two isolates with bla_IMP-1v had similar PFGE patterns and belonged to the same BURST group as representative isolates from clone B in 2000.Two isolates from 2008 with bla_IMP-7 had similar PFGE patterns and shared the same BURST group. The rest of the isolates from 2008 had distinct PFGE patterns.There was a greater diversity of MBL genes compared to the 2000 survey results. In particular, this is the first time that bla_VIM-2 and bla_VIM-6 have been found in P. aeruginosa in Singapore. bla_IMP-26 is a novel MBL gene that differs from bla_IMP-4 at position 145 (G-to-T change). The translated amino acid sequence differs from IMP-4 at residue 49 (phenylalanine for valine). This sequence has been previously deposited in the GenBank database as IMP-4 from an Acinetobacter calcoaceticus isolate from Malaysia (accession number {"type":"entrez-protein","attrs":{"text":"ABC24668.1","term_id":"83583501"}}ABC24668.1).Three of the isolates in this study (separately containing bla_VIM-2, bla_IMP-1, and bla_IMP-7) belonged to ST235. This sequence type has been described in a VIM-producing P. aeruginosa isolate in Belgrade and is the founder of an international clonal complex of isolates bearing MBL genes found in several countries in Europe (6). Recently, an increasing prevalence of IMP-1-producing P. aeruginosa has been found in Hiroshima, Japan. This was due entirely to the clonal expansion of only two lineages, ST235 (BURST group 3) and ST357 (BURST group 108) (4). This is similar to the situation that existed in Singapore in 2000, where only two lineages (BURST groups 29 and 44) accounted for the majority of MBL-producing P. aeruginosa (3).It is noteworthy that the original fear that a clone of MBL-producing P. aeruginosa would become established in Singapore has not been realized. The BURST group 29 and 44 lineages from 2000 were represented by only one to two isolates in 2008. The two P. aeruginosa isolates with bla_IMP-7 in 2008 are unrelated to the solitary isolate with bla_IMP-7 from 2000. It has been suggested that P. aeruginosa displays an epidemic population structure, with a limited number of clones emerging from a large number of unrelated genotypes (7). Although we did not correlate our study with hospital infection control measures, the Japanese data and our own seem to suggest that controlling the prevalence of MBL-producing P. aeruginosa may be achieved by preventing the transmission of specific epidemic clones.While it is reassuring to note that the prevalence of MBL producers in carbapenem-resistant P. aeruginosa has not increased, the increased diversity of MBL genes represents a new cause for concern. We were unable to characterize the gene responsible for the MBL phenotype in two isolates in this study, and these may represent novel resistance determinants. Although clones of MBL-producing P. aeruginosa have not become established, it seems likely, given the variation of MBL genes and MLST types in this study, that MBL-producing P. aeruginosa continues to be introduced to our hospital from diverse sources.     

Identification of a respiratory-type nitrate reductase and its role for survival of Mycobacterium smegmatis in Wayne model

Nitrate reductase (NR) is found to be expressed in certain mycobacterium sp. whose link with the development of persistence is yet to be resolved. The present study demonstrates the action of selective inhibitors on NR as well as in the survival of Mycobacterium smegmatis using Wayne's model. During gradual shift down to anaerobic stage in Wayne's model, conversion of nitrate to nitrite became apparent in M. smegmatis. More than 97 percent inhibition was observed for the conversion of nitrate to nitrite by azide (0.05 mM) and thiocyanate (20 mM) in both whole-cell as well as its cell-free lysate, respectively. Under identical condition, chlorate (20 mM) inhibited nitrate reduction by 67 and 10 percent, respectively. At these concentrations, neither of azide, thiocyanate nor chlorate had any significant effect on cell growth under aerobic condition. In Wayne's culture model, thiocyanate and chlorate inhibited the growth of M. smegmatis by almost 2 logs at the same concentrations whereas azide inhibited by almost 1.75 log when added at the time of inoculation. Exposure of same culture at 96 h after inoculation in Wayne's model to these inhibitors showed 1.74, 1.95 and 2.37 log inhibition of viable cells with respect to azide, thiocyanate and chlorate. These findings further indicated that NR inhibitors kill the bacilli at anaerobic stage under the experimental condition mentioned. Metronidazole (MTZ) (2 mM) and Nitrofurantoin (NIT) (0.3 mM) reduced the cell number at both stages by <0.7 log. They did not have any effect on NR. Altogether, the results clearly indicate that NR-specific inhibitors could become more promising in killing the bacilli at anaerobic stage than the available conventional drugs.     

Utility of Autopsy among Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: One Last Chance to Learn?

Autopsy may confirm clinical diagnoses or identify conditions that were not suspected prior to a patient's death. Previous studies evaluating the utility of autopsy in hematopoietic stem cell transplant (HSCT) recipients yielded conflicting results.We conducted a retrospective cohort study of children (<18 years of age) undergoing allogeneic HSCT at Duke University who died of any cause between January 1, 1995, and December 31, 2016. We evaluated associations between patient characteristics and autopsy performance using chi-square or Fisher exact tests. We reviewed autopsy reports to determine the concordance between preautopsy causes of death and pathological diagnoses identified on autopsy. We classified unexpected diagnoses on autopsy using criteria developed by Goldman et al. We evaluated for temporal changes in the autopsy consent rate and the frequency of unexpected diagnoses on autopsy using Cochran-Armitage tests.During the 22-year study period, 475 patients died and had data available on autopsy performance, and 130 (27%) of these patients underwent autopsy. The autopsy consent rate declined over time (P < .0001), with autopsies being performed for 40% of deaths in 1995 to 1999 and 17% of deaths in 2009 to 2016. White patients were more likely to undergo autopsy than nonwhite patients (P?=?.03). There were no associations between autopsy performance and patient age, sex, HSCT indication, or HSCT donor. Unexpected diagnoses were identified in 31 (24%) autopsies. The proportion of autopsies with an unexpected diagnosis did not change during the study period (P?=?.45). However, infectious diagnoses that would have led to a change in management were more frequently identified on autopsies in 1995 to 2003 than in 2004 to 2016 (20% versus 0%; P?=?.001).The autopsy consent rate for pediatric HSCT recipients at our institution has declined substantially over the past several decades. The utility of autopsy in this patient population remains high despite a reduction in the identification of unexpected infections.     

Relationship between childhood atopy and wheeze: what mediates wheezing in atopic phenotypes?

BACKGROUND: The nature of the relationship between childhood wheeze and atopy remains uncertain. OBJECTIVE: To characterize childhood wheeze among atopic phenotypes in a longitudinal birth cohort study. METHODS: A whole population birth cohort (N = 1,456) was recruited in 1989. Children were seen at birth and at 1, 2, 4, and 10 years of age to obtain information on asthma and allergic disease development and relevant risk factors for these states. Skin prick testing at ages 4 (n = 980) and 10 (n = 1,036) years was used to define atopic phenotypes. Wheezing in these states was characterized, and logistic regression was used to identify independent risk factors for wheeze onset in different atopic phenotypes. RESULTS: Wheeze ever occurred in 37% of never atopics, 38% of early childhood atopics, 65% of chronic childhood atopics, and 52% of delayed childhood atopics. Chronic childhood atopics had significant wheezing morbidity and bronchial hyperresponsiveness. Their wheezing was associated with male sex, early eczema, family history of eczema, and early tobacco exposure. Never atopic wheeze was related to maternal asthma, parental smoking, and respiratory tract infections. Exclusive breastfeeding protected against early childhood atopic wheeze. Maternal asthma, family history of urticaria, and dog ownership increased delayed childhood atopic wheeze. CONCLUSIONS: In many respects, chronic childhood atopy is the atopic phenotype associated with the most significant forms of childhood wheezing. In such children, heritable drive, allergens, and synergy with other environmental triggers seem to be crucial determinants of wheeze onset. Where such sensitization is absent, numerous environmental factors plus genetic predisposition may assume importance for wheezing.     

Simplified risk stratification criteria for identification of patients with MRSA bacteremia at low risk of infective endocarditis: implications for avoiding routine transesophageal echocardiography in MRSA bacteremia

The aim of this study was to identify patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with low risk of infective endocarditis (IE) who might not require routine trans-esophageal echocardiography (TEE). We retrospectively evaluated 398 patients presenting with MRSA bacteremia for the presence of the following clinical criteria: intravenous drug abuse (IVDA), long-term catheter, prolonged bacteremia, intra-cardiac device, prosthetic valve, hemodialysis dependency, vertebral/nonvertebral osteomyelitis, cardio-structural abnormality. IE was diagnosed using the modified Duke criteria. Of 398 patients with MRSA bacteremia, 26.4 % of cases were community-acquired, 56.3 % were health-care-associated, and 17.3 % were hospital-acquired. Of the group, 44 patients had definite IE, 119 had possible IE, and 235 had a rejected diagnosis. Out of 398 patients, 231 were evaluated with transthoracic echocardiography (TTE) or TEE. All 44 patients with definite IE fulfilled at least one criterion (sensitivity 100 %). Finally, a receiver operator characteristic (ROC) curve was obtained to evaluate the total risk score of our proposed criteria as a predictor of the presence of IE, and this was compared to the ROC curve of a previously proposed criteria. The area under the ROC curve for our criteria was 0.710, while the area under the ROC curve for the criteria previously proposed was 0.537 (p?<?0.001). The p-value for comparing those 2 areas was less than 0.001, indicating statistical significance. Patients with MRSA bacteremia without any of our proposed clinical criteria have very low risk of developing IE and may not require routine TEE.