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Raffinose family oligosaccharides (RFOs) fulfil multiple functions in plants. In seeds, they possibly protect cellular structures during desiccation and constitute carbon reserves for early germination. Their biosynthesis proceeds by the transfer of galactose units from galactinol to sucrose. Galactinol synthase (GolS), which mediates the synthesis of galactinol from myo-inositol and UDP-galactose, has been proposed to be the key enzyme of the pathway. However, no significant relationship was detected between the extractable GolS activity and the amount of RFOs in seeds from seven pea (Pisum sativum L.) genotypes selected for high variation in RFO content. Instead, a highly significant correlation was found between the levels of myo-inositol and RFOs. Moderately strong relationships were also found between sucrose and RFO content as well as between myo-inositol and galactinol. Further evidence for a key role of myo-inositol for the synthesis of galactinol was obtained by feeding exogenous myo-inositol to intact pea seeds and by the analysis of four barley (Hordeum vulgare L.) low phytic acid mutants. In seeds of three of these mutants, the reduced demand for myo-inositol for the synthesis of phytic acid (myo-inositol 1,2,3,4,5,6-hexakisphosphate) was associated with an increased level in myo-inositol. The mutants seeds also contained more galactinol than wild-type seeds. The results suggest that the extent of RFO accumulation is controlled by the levels of the initial substrates, myo-inositol and sucrose, rather than by GolS activity alone. [ABSTRACT FROM PUBLISHER]

Objective: Lung transplantation is limited by scarcity of donor organs. Lung retrieval from non-heart-beating donors (NHBD) might have the potential to extend the donor pool and has been reported recently. However, no studies in NHBD exist using the novel approach of retrograde preservation with Perfadex solution. Methods: Asystolic heparinized pigs (n=5/group) were continuously ventilated for 90, 180 or 300 min of warm ischemia. Lungs were then retrogradely preserved with Perfadex and stored at 4 °C in inflation. After 3 h of additional cold ischemia, left lung transplantation was performed. Hemodynamics, pO2/FiO2 and dynamic compliance were monitored for 5 h. Intrapulmonary lung water was determined by both global wet-to-dry lung weight ratio (W/D ratio) and standard stereological examination of relative volume fractions of intraalveolar edema. All results were compared to sham-operated controls and to lungs obtained from standard heart-beating donors after retrograde preservation with Perfadex and 27 h of cold ischemia. Statistics comprised ANOVA analysis with repeated measures and Mann–Whitney tests. Results: No mortality was observed. During flush preservation of NHBD lungs, continuous elimination of blood clots via the pulmonary artery was observed. Oxygenation, compliance, intraalveolar edema fraction and W/D ratio were comparable between groups, whereas PVR was significantly lower in sham-controls. Conclusions: Use of NHBD lungs is feasible and results in similar postischemic outcome when compared to sham-controls and standard preservation procedures even after 5 h of pre-harvest warm ischemia. Especially, the NHBD with high-risk constellations for intravascular coagulation might benefit from retrograde preservation by elimination of thrombi from the pulmonary circulation. This innovative technique might also be considered in situations, where brain-dead organ donors become hemodynamically unstable prior to onset of organ harvest. Further trials with longer warm and cold ischemic periods are initiated to further elucidate this promising approach of donor pool expansion. [Copyright &y& Elsevier]

Approximately one-fourth of all cigarettes sold in the United States are mentholated. An understanding of the consequences, patterns, and correlates of menthol cigarette use can guide the development and implementation of strategies to reduce smoking prevalence and smoking-attributable morbidity and mortality. This paper summarizes the literature on the health effects of mentholated cigarettes and describes various patterns of use as indicated by consumption and survey data from the United States and other nations. The epidemiological literature on menthol cigarettes and cancer risk is inconclusive regarding whether these cigarettes confer a risk for cancer above that of nonmentholated varieties. Available data indicate that mentholated cigarettes are at least as dangerous as their nonmentholated counterparts. In addition, because mentholation improves the taste of cigarettes for a substantial segment of the smoking population and appears to mask disease symptoms, this additive may facilitate initiation or inhibit quitting. Menthol market share is high in the Philippines (60%), Cameroon (35%-40%), Hong Kong (26%), the United States (26%), and Singapore (22%). Newport has become the leading menthol brand in the United States. Surveys from four nations indicate that menthol use among adult smokers is more common among females than males. Among U.S. smokers, 68.9% of Blacks, 29.2% of Hispanics, and 22.4% of Whites reported smoking a mentholated variety. Research is needed to better explain factors that may influence menthol preference, such as marketing, risk perceptions, brand formulation, and taste preferences. Such research would guide the development of potentially more effective programs and policies. [ABSTRACT FROM AUTHOR]

Background: Studies carried out over the past 10 years have suggested that hydrosalpinges reduce the pregnancy rate in IVF. Here we report our observations of spontaneous pregnancies in patients who underwent salpingectomy (n = 18) or proximal tubal occlusion (n = 7) following diagnoses of unilateral hydrosalpinges and patent contralateral tubes.Methods: This multi-centre, retrospective study included 25 infertility patients with known unilateral hydrosalpinges with a patent contralateral Fallopian tube. Laparoscopic treatment of unilateral hydrosalpinges by either salpingectomy or tubal occlusion was performed in each patient. Rates of subsequently observed spontaneous pregnancy, and time to pregnancy, are reported.Results: The average duration of infertility in these patients was 3 years with a range of 1-10 years. Following laparoscopic surgical treatment, a total of 22 patients (88%) achieved intrauterine pregnancies, all without IVF treatment. Pregnancies occurred in an average of 5.6 months with a range of 1-21 months. There were no ectopic pregnancies in the study population.Conclusions: Selected patients with unilateral hydrosalpinges and a patent contralateral Fallopian tube may exhibit increased cycle fecundity after salpingectomy or proximal tubal occlusion of the affected tube and conceive without the need for IVF. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies carried out over the past 10 years have suggested that hydrosalpinges reduce the pregnancy rate in IVF. Here we report our observations of spontaneous pregnancies in patients who underwent salpingectomy (n = 18) or proximal tubal occlusion (n = 7) following diagnoses of unilateral hydrosalpinges and patent contralateral tubes. METHODS: This multi-centre, retrospective study included 25 infertility patients with known unilateral hydrosalpinges with a patent contralateral Fallopian tube. Laparoscopic treatment of unilateral hydrosalpinges by either salpingectomy or tubal occlusion was performed in each patient. Rates of subsequently observed spontaneous pregnancy, and time to pregnancy, are reported. RESULTS: The average duration of infertility in these patients was 3 years with a range of 1-10 years. Following laparoscopic surgical treatment, a total of 22 patients (88%) achieved intrauterine pregnancies, all without IVF treatment. Pregnancies occurred in an average of 5.6 months with a range of 1-21 months. There were no ectopic pregnancies in the study population. CONCLUSIONS: Selected patients with unilateral hydrosalpinges and a patent contralateral Fallopian tube may exhibit increased cycle fecundity after salpingectomy or proximal tubal occlusion of the affected tube and conceive without the need for IVF. [ABSTRACT FROM AUTHOR]

Background: Despite considerable improvement in the treatment of advanced ovarian cancer, the optimization of efficacy and tolerability remains an important issue. Therefore, we performed a randomized, phase III non-inferiority trial comparing paclitaxel plus cisplatin (PT) with paclitaxel plus carboplatin (TC) in patients with advanced ovarian cancer.Methods: A total of 798 patients with International Federation of Gynecology and Obstetrics stage IIB-IV were randomly assigned to receive six courses of either PT or TC at 3-week intervals. The primary endpoint was the proportion of patients without progression at 2 years. Secondary endpoints included toxicity, response to treatment, quality of life, and overall and progression-free survival time. Quality of life was evaluated using the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30, version 2.0. Survival curves were calculated using the Kaplan-Meier method, and hazard ratios were estimated using the Cox proportional hazards model.Results: The proportion of patients without progression at 2 years was not statistically significantly different between the two treatment arms (40.0% for PT versus 37.5% for TC, difference = 2.5%, one-sided 95% confidence interval [CI] = - infinity to 8.2%). Median progression-free survival time in the TC arm (17.2 months, 95% CI = 15.2 to 19.3 months) and the PT arm (19.1 months, 95% CI = 16.7 to 21.5 months) were also not statistically significantly different; the same was true of median overall survival time (43.3 months, 95% CI = 37.2 to 47.8 months versus 44.1 months, 95% CI = 40.2 to 49.4 months, for the TC and PT arms, respectively). The TC regimen was associated with a higher frequency of hematologic toxicity, but a lower frequency of gastrointestinal and neurologic toxicity, than the PT regimen. Mean global quality-of-life scores at the end of treatment were statistically significantly better in the TC arm than in the PT arm (65.25 versus 51.97, respectively; difference = -13.28, 95% CI = -18.88 to -7.68).Conclusion: The TC regimen achieved comparable efficacy to the PT regimen but was associated with better tolerability and quality of life, and should, therefore, be considered as an important alternative for standard first-line chemotherapy in patients with advanced ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Human embryonic stem (hES) cell lines were first cultured using fetal mouse fibroblasts as feeder cells. To avoid feeders and to reduce the amount of xeno-components, Matrigel- and laminin-coated dishes, and conditioned mouse feeder cell medium have been used, and hES cells have also been cultured on human fetal muscle and skin, and adult Fallopian tube epithelial cells.Methods: We used post-natal, commercially available human foreskin fibroblasts as feeder cells. Inner cell masses (ICM) were isolated from five supernumerary blastocysts, obtained as donations from couples undergoing IVF treatment.Results: Two ICM showed continuous growth. One line, HS181, has been in culture for 41 weeks with a doubling time of 24-36 h. It continues to express stem cell markers alkaline phosphatase, Oct-4, stage-specific embryonic antigen (SSEA)-4 and tumour-related antigen (TRA)-1-60. The karyotype is 46,XX. Pluripotency was demonstrated by teratoma formation in immunodeficient mice. In high-density cultures, spontaneous differentiation to beating cells and neuron-like cells was seen. The second line, HS207, was cultured for 9 weeks and cryopreserved, as were samples of line HS181. Both lines began to grow after thawing.Conclusions: We used successfully human foreskin fibroblasts as feeder cells for derivation and continued undifferentiated growth of hES cells. These feeder cells are convenient for IVF units, because no fetal human tissues or tissue from operations are needed. [ABSTRACT FROM AUTHOR]

Tobacco-specific nitrosamines (TSNAs) are one of the major classes of carcinogens found in tobacco products. As part of collaborative efforts to reduce tobacco use and resulting disease, the U.S. Centers for Disease Control and Prevention (CDC) carried out a two-phase investigation into the worldwide variation of the levels of TSNAs in cigarette tobacco. In the first phase, representatives of the World Health Organization (WHO) purchased cigarettes; scientists from the CDC subsequently measured the levels of TSNAs in tobacco from 21 different countries. Although the data collected from this initial survey suggested that globally marketed U.S.-brand cigarettes typically had higher TSNA levels than locally popular non-U.S. cigarettes in many countries, the number of samples limited the statistical power of the study. To improve statistical power and to ensure adequate sampling, the CDC conducted a second survey of 14 countries. In addition to the United States, the CDC selected the world's 10 most populous countries and three additional countries, so that at least two countries from each of the six WHO regions were represented. For each country, the CDC compared 15 packs of Marlboro cigarettes, which is the world's most popular brand of cigarettes, with 15 packs of a locally popular non-U.S. brand in the study country. Marlboro cigarettes purchased in 11/13 foreign countries had significantly higher tobacco TSNA levels than the locally popular non-U.S. brands purchased in the same country. The findings suggest that TSNA levels in tobacco can be substantially reduced in some cigarettes. [ABSTRACT FROM AUTHOR]

Little is known about the interactions between Helicobacter pylori, which specializes in colonizing the mucin layer that covers the gastric mucosa, and primary gastric epithelial cells. The expression pattern of Toll-like receptors (TLRs) in primary gastric epithelial cells and cell lines was compared. Primary cells did not express TLR4, whereas all cell lines expressed a nonsignaling form of TLR4. Because other cells within the mucosa expressed TLR4, it was next investigated whether H. pylori can be recognized by TLR4—they cannot. Moreover, H. pylori infection of primary cells induced a regulated production of interleukin (IL)-6, IL-8, and tumor necrosis factor-α, whereas infection of cell lines only resulted in IL-8 production. The cytokine production in all cell types was strictly cag dependent. These findings indicate that, although the epithelium is important in directing the immune response against H. pylori infections, the response is independent of TLR4. [ABSTRACT FROM AUTHOR]

Describes the events that occurred before, during, and after the trichinellosis outbreak in Canada and documents how the prevention program contributed to successful resolution of the outbreak. Trichinellosis prevention programs for residents of Nunavik, Canada initiated in 1992; Characteristics of consumers of infected meat identified during an outbreak of trichinellosis in northern Quebec in September 1997; Detection of Trichinella larvae.

Research into the short‐term fluctuations of oxygen concentrations in tree stems has been hampered by the difficulty of measuring oxygen inside tissues. A new method, which is based on fluorescence quenching of a ruthenium complex in the presence of oxygen, has been applied to measure changes of oxygen concentration in the sapwood of trees. During a field day‐course oxygen increased with the radiation load and fell during the night (in Fagus orientalis from 20.3% in the afternoon to 17.5% in the morning next day). In a greenhouse experiment the sapwood oxygen concentration of Laurus nobilis could be influenced by flooding the root system. The very fast response, high resolution (better than 0.1%), easy calibration, and dependence only on oxygen and temperature make the technique well suited for measurements of oxygen concentrations in the sapwood. [ABSTRACT FROM PUBLISHER]

A phage displayed dodecapeptide library and synthetic octapeptides spanning the complete sequence of α- and γ-type gliadin and overlapping in six amino acids (pepscan) were screened for binding to human gliadin antibodies (AGA). Phage display experiments led to four sequences recognized with significantly higher frequency by sera with raised IgA-AGA titres than by control sera. All these peptides contained the core sequence PEQ. Pepscan experiments revealed binding of AGA to five prominent regions: (i) QXQPFP (binding to IgG and IgA, X representing P, Q, and L); (ii) IPEQ (IgG) and WQIPEQ (IgA); (iii) FFQP (IgG) and QGXFQP (IgA, X representing F and S); (iv) PQQLPQ (IgG and IgA), all in α-type gliadin; and (v) QPQQPF (IgG and IgA) in γ-type gliadin. In two of the sequences (QPQQPF and QQQPFP), substitution of Q by E resulting in QPEQPF and QEQPFP, respectively, increased significantly binding of AGA from sera of patients with biopsy-proven or suspected coeliac disease (CoD), all positive for endomysium antibodies (EmA). In contrast, binding of sera with high AGA titre from EmA-negative patients (CoD and dermatitis herpetiformis excluded) was not enhanced by this substitution. Thus, AGA directed against these modified epitopes can be regarded as specific for CoD. This is the first study demonstrating that deamidation of gliadin improves reactivity of AGA of CoD patients. [ABSTRACT FROM AUTHOR]

Summary: LigDig is a web server designed to answer questions that previously required several independent queries to diverse data sources. It also performs basic manipulations and analyses of the structures of protein–ligand complexes. The LigDig webserver is modular in design and consists of seven tools, which can be used separately, or via linking the output from one tool to the next, in order to answer more complex questions. Currently, the tools allow a user to: (i) perform a free-text compound search, (ii) search for suitable ligands, particularly inhibitors, of a protein and query their interaction network, (iii) search for the likely function of a ligand, (iv) perform a batch search for compound identifiers, (v) find structures of protein–ligand complexes, (vi) compare three-dimensional structures of ligand binding sites and (vii) prepare coordinate files of protein– ligand complexes for further calculations. [ABSTRACT FROM AUTHOR]

Background: Today, patient self-determination has become an issue in many western countries due to the widespread availability and use of technology, which makes it possible to prolong life often in spite of severe disability and poor quality of life. Many people fear an overzealous use of modern life-saving procedures which merely serve to prolong the dying process. As a first step towards autonomy and increasing self-determination, advance directives (living wills) have been introduced in some countries. Methods: To survey a general population's attitudes towards advance directives and self-determination a questionnaire was mailed to a representative sample of 600 citizens in northern Sweden. Issues regarding importance of control, concerns about own health care, treatment preferences and support for and use of advance directives were addressed. Results: There was a response rate of 80% and the great majority of respondents reported that it was extremely or very important to have a say in decisions about their health care (79.5%). A significant number of subjects were concerned about either being treated too aggressively or not aggressively enough. There was a variability in treatment preferences, depending on the reversibility of the condition. Conclusions: The results demonstrate a vital interest among the Swedish general public for greater self-determination in health care, which is also reflected by their support of advance directives. [ABSTRACT FROM AUTHOR]

Presents a study that evaluated general population's attitudes towards self-determination in health care in Northern Sweden. Fears regarding the use of life-saving procedures; Use of questionnaire on health care, treatment preferences and others; General support of advance directives.

One of the proteins encoded by the riboflavin operon of Bacillus subtilis, RibA, was identified as the rate limiting enzyme in an industrial riboflavin producing strain. An additional single copy of the ribA gene was introduced into the sacB locus of the riboflavin production strain and was expressed constitutively from the medium strength vegI promoter. This led to improved riboflavin titers and yields of riboflavin on glucose of up to 25%. Both enzymatic activities of RibA, the 3,4-dihydroxy-2-butanone 4-phosphate synthase activity located in the N-terminal half of the protein and the GTP cyclohydrolase II activity of the C-terminal domain, are necessary for the improved riboflavin productivity. [ABSTRACT FROM AUTHOR]

Presents a study concerning the population-based information, relating to trends and outpatient mastectomy among elderly women, while focusing on the numerous legislative proposals to mandate a minimum hospital stay following mastectomy. Examination of the medicare data for elderly women with fee-for-service coverage; How logistic regression was used; How the outpatient mastectomies were more likely performed.

Rheumatoid arthritis is characterized by chronic inflammation and proliferation of a number of important elements within the joint including the synovial fibroblasts. Elevated levels of a number of cytokines such as IL-1, IL-2, IL-6, interferon-gamma (IFN-γ), transforming growth factor-β and tumour necrosis factor-alpha (TNF-α) have been detected in the synovial fluid of patients with rheumatoid arthritis and other inflammatory arthritides. It seems likely that local release of such mediators may be responsible for the proliferation and overgrowth of connective tissue elements in these disorders. In order to ascertain whether there was evidence to suggest local production or release of fibroblast growth factors in the joint in inflammatory arthritis, and to determine their identity, cells were obtained from the synovial fluid of 15 patients with chronic inflammatory arthritides. All subjects' synovial fluid cells spontaneously released growth factor activity for fibroblasts. This was present in large amounts, being detectable in culture supernatants diluted to a titre of at least 1/625. By a series of depletion experiments using solid-phase bound antibodies to cytokines, it was possible to demonstrate that this activity was due to TNF-α and platelet-derived growth factor (PDGF). Thus, this study showed for the first time that functionally active PDGF was released front synovial fluid cells. Both PDGF and TNF-α appeared to contribute in approximately equal amounts to this fibroblast growth factor activity, and were synergistic in effect. Thus this study provides evidence for the local production and release of these two cytokines and suggests that together they arc the dominant factors in fibroblast proliferation within the synovial cavity. [ABSTRACT FROM AUTHOR]

We report the expression of a cDNA clone encoding 695 carboxyl-terminal amino acids of human DNA topoisomerase I (topoI) in Escherichia coli. More than 96% of the anti-HeLa topoI-positive sera from patients with a connective tissue disease displayed also an immunoreactivity with this recombinant protein (the HTopoA protein). Sera from patients with a definite diagnosis systemic sclerosis and reacting with HeLa topoI, all reacted with the HTopoA protein as well. Sera from patients with systemic sclerosis that did not contain anti-topoI antibodies (about 30% of the systemic sclerosis sera), as concluded from HeLa immunoblot, displayed also no immunoreactivity with our recombinant antigen. By expressing different fragments of HTopoA, we were able to assign at least three different autoimmune epitope regions on the HTopoA protein and we show that over a period of 5 years the amount of anti-topoI antibodies against these regions may fluctutate. [ABSTRACT FROM AUTHOR]

Classical robust optimization (cRO) in intensity-modulated proton therapy (IMPT) considers isocenter position and particle range uncertainties; anatomical robust optimization (aRO) aims to consider additional non-rigid positioning variations. This work compares the influence of different uncertainty sources on the robustness of cRO and aRO IMPT plans for head and neck squamous cell carcinoma (HNSCC). Two IMPT plans were optimized for 20 HNSCC patients who received weekly control CTs (cCT): cRO, using solely the planning CT, and aRO, including 2 additional cCTs. The robustness of the plans in terms of clinical target volume (CTV) coverage and organ at risk (OAR) sparing was analyzed considering stepwise the influence of (1) non-rigid anatomical variations given by the weekly cCT, (2) with fraction-wise added rigid random setup errors and (3) additional systematic proton range uncertainties. cRO plans presented significantly higher nominal CTV coverage but are outperformed by aRO plans when considering non-rigid anatomical variations only, as cRO and aRO plans presented a median target coverage (D98%) decrease for the low-risk/high-risk CTV of 1.8/1.1 percentage points (pp) and −0.2 pp/−0.3 pp, respectively. Setup and range uncertainties had larger influence on cRO CTV coverage, but led to similar OAR dose changes in both plans. Considering all error sources, 10/2 cRO/aRO patients missed the CTV coverage and a limited number exceeded some OAR constraints in both plans. Non-rigid anatomical variations are mainly responsible for critical target coverage loss of cRO plans, whereas the aRO approach was robust against such variations. Both plans provide similar robustness of OAR parameters. The influence of different uncertainty sources was quantified for robust IMPT HNSCC plans. [ABSTRACT FROM AUTHOR]

Background In September 2018, pharmacy antimicrobial stewardship services were expanded to include weekends at Cleveland Clinic. Activities performed by antimicrobial stewardship (AMS) pharmacists on the weekend include blood culture rapid diagnostic (RDT) review, antiretroviral therapy (ART) review, prospective audit and feedback (PAF) utilizing clinical decision support, vancomycin dosing, and operational support. The purpose of this study was to assess the operational and clinical impact of these expanded AMS services. Methods This single-center, the quasi-experimental study included data from 13 weekends before (9/2017 – November 2017) and after (9/2018 – November 2018) implementation of weekend services. The primary outcome was the number of reviews relating to each stewardship activity. Secondary outcomes were time to AMS opportunity resolution, time to escalation or de-escalation following PAF or RDT alert, time to resolution of other AMS-related opportunities, length of stay (LOS), and antimicrobial use outcomes. Patients were included in time to resolution outcomes if they had an RDT, ART, or select PAF review requiring intervention. Time to opportunity resolution was defined as the time from AMS alert to implementation of the recommendation in the electronic health record. Results During the post-intervention period 1261 reviews were conducted, averaging 97/weekend. This included 187 RDT, 432 PAF, 124 ART, 331 vancomycin dosing notes and 187 other. Inclusion criteria for time to resolution outcomes were met by 72 patients pre-intervention compared with 59 patients post. No significant differences were seen in baseline characteristics between groups with 43% of patients requiring ID consultation and 58% requiring ICU admission. The median time to opportunity resolution improved significantly overall (P < 0.01), with de-escalation (P = 0.03), and with time to other AMS opportunity (P = 0.01) (Figure 1). A numerical reduction was seen with time to escalation (P = 0.1). LOS was a median of 13 and 14 days pre- and post-intervention, respectively (P = 0.4). No differences were seen in antimicrobial use outcomes. Conclusion Presence of pharmacist-driven weekend AMS services significantly reduced time to resolution of AMS interventions. These data support the value of weekend AMS services. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background CR Ab is a major cause of healthcare-associated infections and is associated with high mortality due to the lack of reliable treatment options. We aimed to elucidate the contemporary population structure of CR Ab isolates circulating in US hospitals using whole-genome sequencing (WGS). Methods A total of 131 CR Ab isolates were identified at four tertiary care medical centers located in Ohio, Pennsylvania, Texas and North Carolina between 2017 and 2018. The genomes were sequenced with Illumina NextSeq and de novo assembled. Sequence types (STs) were identified using the Pasteur Institute MLST scheme. β-Lactamase genes were identified by ResFinder and manually curated. Results The 131 isolates belonged to 10 different ST types, including 8 known and 2 novel ones. In this collection, 101 isolates (77.1%) belonged to ST2, the dominant drug-resistant clone in the United States and Europe; 20 isolates belonged to ST499, a less common, but also globally distributed clone. Two isolates each belonged to ST46 and ST79, both common in South America. For the chromosomally encoded bla OXA-51-group genes, 11 variants were identified with bla OXA-66, bla OXA-82, and bla OXA-95 being predominant. For the chromosomally encoded bla ADC-group genes, 26 variants were identified, with bla ADC-161, bla ADC-181, and bla ADC-30 being the most common. The most frequent acquired carbapenemase gene was bla OXA-23, which was present in 89 isolates (67.9%). Other acquired bla OXA carbapenemase genes were identified much less frequently and included bla OXA-24, bla OXA-72, bla OXA-207, and bla OXA-237. 17 isolates (13.0%) did not contain any known acquired carbapenemase genes despite resistance to carbapenems. Conclusion ST2 is the most prevalent ST type among contemporary CR Ab isolates identified in US hospitals, however, new STs are emerging, most notably ST499. Significant diversity was seen among chromosomal bla OXA-51-group carbapenemase, intrinsic bla ADC-group cephalosporinase and plasmid-mediated bla OXA-group carbapenemase genes, which likely represented diversification within the STs. Correlations between clinical presentation and outcomes and the genomic features of the infecting isolates are being investigated Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Urinary tract infection (UTI) is the most common clinical manifestation of carbapenem-resistant Klebsiella pneumoniae (CR Kp). Persistent CR Kp bacteriuria is associated with the spread of CR Kp and antibiotic overuse. Risk factors for persistent CR Kp bacteriuria are uncertain. Methods CRACKLE-1 was a multicenter, prospective study that included 960 patients with at least one carbapenem-resistant Enterobacteriaceae (CRE)-positive culture from December 2011 to June 2016 collected from 18 hospitals encompassing 8 healthcare systems in the Midwestern US and North Carolina. Patients with CR Kp bacteriuria who were discharged alive from index hospitalization were included in the current study, and sporadic (single positive CR Kp urine culture) and persistent (≥2 CR Kp urine cultures during independent hospital admissions occurring at least 2 days apart) cases were compared. Antibiotic susceptibility testing was performed by local laboratories. Amikacin, gentamicin (GENT), and trimethoprim/sulfamethoxazole were included in the analysis based on variance and frequency of testing. The CDC/National Healthcare Safety Network criteria for UTI were used. Results CR Kp was the most common CRE isolate (n = 869, prevalence 91%). In patients with CR Kp , 527 had CR Kp isolated from the urine (prevalence 61%, 95% CI 0.57, 0.64). Of these, 486 patients, of whom 129 (27%) were diagnosed with a UTI, were discharged alive. Notably, 135/486 (28%) patients with CR Kp bacteriuria were readmitted and yielded a second urine culture of CR Kp. Most patients with persistent bacteriuria, 99/135 (73%), were asymptomatic at initial admission. Of these patients, 20/99 (20%) were diagnosed with a UTI at second admission. In multivariable analysis, only GENT non-susceptibility was associated with an increased risk (adjusted OR 1.66, 95% CI 1.10–2.49) of persistent bacteriuria. Persistent bacteriuria was independent of GENT treatment during index hospitalization (GENT was used in 15% of patients). Conclusion Bacteriuria with GENT non-susceptible CR Kp strains was associated with persistent bacteriuria. As this was independent of GENT treatment, GENT resistance determinants may be co-transmitted along with traits that promote bacterial persistence in CR Kp. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

We report on the association of Mayer–von Rokitansky–Küster–Hauser syndrome (MRKHS) with a unique form of Holt–Oram syndrome (HOS) with an aorto‐pulmonary window. A 24‐year‐old Turkish woman was referred to our hospital because of primary amenorrhoea. Both her vagina and uterus were absent, and the diagnosis of MRKHS was established. Laparoscopic creation of a neovagina by the modified Vecchietti technique was performed. A rare congenital malformation of the heart, namely an aorto‐pulmonary window, had required cardiac surgery when the patient was a 6‐month‐old infant. This cardiac malformation plus associated upper limb anomalies led to the clinical diagnosis of HOS. To the best of our knowledge, this is only the second report in the scientific literature on the concurrence of MRKHS and HOS, and the first published case of HOS with an aorto‐pulmonary window as the cardiac malformation. [ABSTRACT FROM AUTHOR]

We describe the first Mycobacterium haemophilum infection that occurred in a patient with human immunodeficiency virus in Germany and report 7 newly diagnosed cases of M. haemophilum infection. In the former case, a local M. haemophilum skin infection resolved as a result of successful antiretroviral therapy only; however, that clinical outcome may not be possible for more invasive forms of the disease. [ABSTRACT FROM AUTHOR]

Presents correspondence on the successful topical immunotherapy treatment of bowenoid papulosis with imiquimod. Case example of a 38-year-old woman; Presenting signs and symptoms; Drug background of imiquimod.

Background The corn leaf aphid (Rhopalosiphum maidis Fitch) is the most economically damaging aphid pest on maize (Zea mays), one of the world's most important grain crops. In addition to causing direct damage by removing photoassimilates, R. maidis transmits several destructive maize viruses, including maize yellow dwarf virus, barley yellow dwarf virus, sugarcane mosaic virus, and cucumber mosaic virus. Findings The genome of a parthenogenetically reproducing R. maidis clone was assembled with a combination of Pacific Biosciences (207-fold coverage) and Illumina (83-fold coverage) sequencing. The 689 assembled contigs, which have an N50 size of 9.0 megabases (Mb) and a low level of heterozygosity, were clustered using Phase Genomics Hi-C interaction maps. Consistent with the commonly observed 2n = 8 karyotype of R. maidis, most of the contigs (473 spanning 321 Mb) were successfully oriented into 4 scaffolds. The genome assembly captured the full length of 95.8% of the core eukaryotic genes, indicating that it is highly complete. Repetitive sequences accounted for 21.2% of the assembly, and a total of 17,629 protein-coding genes were predicted with integrated evidence from ab initio and homology-based gene predictions and transcriptome sequences generated with both Pacific Biosciences and Illumina. An analysis of likely horizontally transferred genes identified 2 from bacteria, 7 from fungi, 2 from protozoa, and 9 from algae. Repeat elements, transposons, and genes encoding likely detoxification enzymes (cytochrome P450s, glutathione S-transferases, carboxylesterases, uridine diphosphate–glucosyltransferases, and ABC transporters) were identified in the genome sequence. Other than Buchnera aphidicola (642,929 base pairs, 602 genes), no endosymbiont bacteria were found in R. maidis. Conclusions A high-quality R. maidis genome was assembled at the chromosome level. This genome sequence will enable further research related to ecological interactions, virus transmission, pesticide resistance, and other aspects of R. maidis biology. It also serves as a valuable resource for comparative investigation of other aphid species. [ABSTRACT FROM AUTHOR]

An editorial is presented on the epidemiological studies on the risk and clinical manifestations of diseases encountered by travelers. It expresses the view that clinical observations obtained from case reports improve researchers' knowledge on the full spectrum of clinical manifestations, often also describing unusual clinical presentations.

In the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), trimethoprim-sulfamethoxazole (TMP-SMX) had a limited role in the treatment of less severe carbapenem-resistant Enterobacteriaceae (CRE) infections, especially urinary tract infections. Of tested CRE, only 29% were susceptible to TMP-SMX. Development of resistance further limits the use of TMP-SMX in CRE infections. [ABSTRACT FROM AUTHOR]

Bacterial infection of the kidney leads to a rapid cascade of host protective responses, many of which are still poorly understood. We have previously shown that following kidney infection with uropathogenic Escherichia coli (UPEC), vascular coagulation is quickly initiated in local perivascular capillaries that protects the host from progressing from a local infection to systemic sepsis. The signaling mechanisms behind this response have not however been described. In this study, we use a number of in vitro and in vivo techniques, including intravital microscopy, to identify two previously unrecognized components influencing this protective coagulation response. The acylation state of the Lipid A of UPEC lipopolysaccharide (LPS) is shown to alter the kinetics of local coagulation onset in vivo. We also identify epithelial CD147 as a potential host factor influencing infection-mediated coagulation. CD147 is expressed by renal proximal epithelial cells infected with UPEC, contingent to bacterial expression of the α-hemolysin toxin. The epithelial CD147 subsequently can activate tissue factor on endothelial cells, a primary step in the coagulation cascade. This study emphasizes the rapid, multifaceted response of the kidney tissue to bacterial infection and the interplay between host and pathogen during the early hours of renal infection. [ABSTRACT FROM AUTHOR]

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease. [ABSTRACT FROM AUTHOR]

Summary: Peripheral vascular malformations (VMs) are birthmarks or swellings caused by the faulty development of blood vessels in the embryo. Different types are classified according to whether the components are mainly lymph vessels (LMs), veins (VMs) or combined arteries and veins (AVMs). It is hard to assess the various medical and surgical treatments available because there are no agreed methods for measuring the outcome. This international group carried out an on‐line survey of health professionals and patients to decide which factors would be important to record in future clinical trials. First they listed aspects of the condition and its treatment in 36 domains covering 97 specific items. Then they asked 167 doctors and 134 patients and parents of patients to score the domains from 0 (not important) to 4 (crucial). The options were progressively narrowed down over 3 rounds of the survey and a consensus conference. The finally agreed “core outcome set” covered: scan results, doctors’ assessment of problems caused by pressure from the VM, patient or parent's assessments of symptoms, pain and quality of life, and their satisfaction with the treatment, outcome and any adverse effects. Additional specific factors for LMs were infections and lymphatic fluid leakage, for VMs thrombosis and for AVMs heart function and bleeding. Recurrence after treatment and appearance were also recommended for inclusion. This international consensus establishes what factors should be assessed in future trials of treatments for vascular malformations, but further work is required to decide exactly how they should be measured and reported. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 42-year-old German traveller presented with a 2-day history of a transient creeping eruption on the left palpebral region. It mentions that the patient had a slowly migrating, thread-shaped subcutaneous swelling, and was under immunosuppressive therapy with methotrexate for rheumatoid arthritis. It mentions that Dirofilaria are nematode parasites of dogs and other carnivores, transmitted by various mosquito species.

Summary: Modern biological experiments create vast amounts of data which are geographically distributed. These datasets consist of petabytes of raw data and billions of documents. Yet to the best of our knowledge, a search engine technology that searches and cross-links all different data types in life sciences does not exist.We have developed a prototype distributed scientific search engine technology, ‘Sciencenet’, which facilitates rapid searching over this large data space. By ‘bringing the search engine to the data’, we do not require server farms. This platform also allows users to contribute to the search index and publish their large-scale data to support e-Science. Furthermore, a community-driven method guarantees that only scientific content is crawled and presented. Our peer-to-peer approach is sufficiently scalable for the science web without performance or capacity tradeoff.Availability and Implementation: The free to use search portal web page and the downloadable client are accessible at: http://sciencenet.kit.edu. The web portal for index administration is implemented in ASP.NET, the ‘AskMe’ experiment publisher is written in Python 2.7, and the backend ‘YaCy’ search engine is based on Java 1.6.Contact: urban.liebel@kit.eduSupplementary Material: Detailed instructions and descriptions can be found on the project homepage: http://sciencenet.kit.edu. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 50-year-old homeless man who was found by the police officers in a park with a bleeding lump on his face and was taken to the emergency department. The man underwent biopsy and haemostasis and was diagnosed with paranoid schizophrenia. Meanwhile, the patient takes olanzapine daily for psychological treatment however his computerized tomography (CT) results show massive growth of tumour and increase cutaneous malignancies.

Low-input winter feeding programs and early weaning of calves can reduce annual feed costs and maintain cow performance; however, few reports in the literature examine long-term response or the interaction of these management strategies on the cow herd. The objective of this study was to evaluate the effects of early versus normal weaning (WEAN) in conjunction with two winter feeding strategies (WINTER) on cow BW, body condition score (BCS), reproductive performance, and calf performance. Mixed-age Angus x Simmental cows (n = 239) were used in a 6-yr study conducted at the SDSU Antelope Livestock and Range Research Station. Cows were randomly assigned to one of two weaning treatments (early wean [EW] in August or normal wean [NW] in November). Following normal weaning and through calving, cows were randomly assigned to one of two feeding treatments: wintered on native range with access to a distillers-grains-based supplement (low-input winter feeding [LOW]) or fed mixed alfalfa-grass hay with the option of grazing native range (high-input winter feeding [HIGH]). After initial treatment assignment, cows remained in original treatments throughout the project. Cow BW and BCS were recorded before calving, at initiation of breeding, at early weaning, and at normal weaning. Reproductive response, calf performance, and culling rates were recorded. Cow B W and BCS were greater (P < 0.05) for EW vs. NW cows at normal weaning every year. Cows on the EW treatment lost more B W from calving to breeding compared to the NW treatment (mean loss 28.5 vs. 7.0 ± 3.9 kg; P = 0.0001). There was a WEAN x WINTER interaction (P = 0.05) for pregnancy rate (98% for NW HIGH vs. 94% NW LOW cows, with EW treatment intermediate). Mean calving date was 3 d later (P < 0.05) by cows on EW HIGH than EW LOW or NW HIGH. Calving and weaning rates did not differ (P > 0.70) among WEAN or WINTER treatments. Calf ADG from birth to EW tended (P = 0.06) to be greater for EW vs. NW calves (1.09 vs. 1.06 ± 0.015 kg/d, respectively). Cows on LOW had greater (P < 0.05) cull rates and were on study a shorter amount of time compared to cows on HIGH. Early vs. normal weaning maintained cow BW and BCS at greater levels throughout the study. WEAN and WINTER treatments rarely interacted in their influence on performance. [ABSTRACT FROM AUTHOR]

Disruption of the Krebs cycle is a hallmark of cancer. IDH1 and IDH2 mutations are found in many neoplasms, and germline alterations in SDH genes and FH predispose to pheochromocytoma/paraganglioma and other cancers. We describe a paraganglioma family carrying a germline mutation in MDH2, which encodes a Krebs cycle enzyme. Whole-exome sequencing was applied to tumor DNA obtained from a man age 55 years diagnosed with multiple malignant paragangliomas. Data were analyzed with the two-sided Student's t and Mann-Whitney U tests with Bonferroni correction for multiple comparisons. Between six- and 14-fold lower levels of MDH2 expression were observed in MDH2-mutated tumors compared with control patients. Knockdown (KD) of MDH2 in HeLa cells by shRNA triggered the accumulation of both malate (mean ± SD: wild-type [WT] = 1±0.18; KD = 2.24±0.17, P = .043) and fumarate (WT = 1±0.06; KD = 2.6±0.25, P = .033), which was reversed by transient introduction of WT MDH2 cDNA. Segregation of the mutation with disease and absence of MDH2 in mutated tumors revealed MDH2 as a novel pheochromocytoma/paraganglioma susceptibility gene. [ABSTRACT FROM AUTHOR]

Short-term inducible gene inactivation for the first three enzymatic steps in the Mg branch towards chlorophyll synthesis does not modify retrograde signaling-mediated nuclear gene expression. Long-term gene silencing of the same genes involved in tetrapyrrole biosynthesis causes either a pale-green or a necrotic leaf phenotype and feedback-regulated ALA synthesis or 1O2-induced signaling affect nuclear gene expression.In photosynthetic organisms, tetrapyrrole-mediated retrograde signals are proposed to contribute to a balanced nuclear gene expression (NGE) in response to metabolic activity in chloroplasts. We followed an experimental short-term approach that allowed the assessment of modified NGE during the first hours of specifically modified enzymatic steps of the Mg branch of tetrapyrrole biosynthesis, when pleiotropic effects of other signals can be avoided. In response to 24-h-induced silencing of CHLH, CHLM, and CHL27 encoding the CHLH subunit of Mg chelatase, the Mg protoporphyrin methyltransferase and Mg protoporphyrin monomethylester cyclase, respectively, deactivated gene expression rapidly led to reduced activity of the corresponding enzymes and altered Mg porphyrin levels. But NGE was not substantially altered. When these three genes were continuously inactivated for up to 4 d, changes of transcript levels of nuclear genes were determined. CHL27 silencing for more than 24h results in necrotic leaf lesions and modulated transcript levels of oxidative stress-responsive and photosynthesis-associated nuclear genes (PhANGs). The prolonged deactivation of CHLH and CHLM results in slightly elevated transcript levels of PhANGs and tetrapyrrole-associated genes. These time-resolved studies indicate a complex scenario for the contribution of tetrapyrrole biosynthesis on NGE mediated by 1O2-induced signaling and feedback-regulated ALA synthesis. [ABSTRACT FROM PUBLISHER]

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients. [ABSTRACT FROM PUBLISHER]

During the spring of 2009, pandemic influenza A (H1N1) virus (pH1N1) was recognized and rapidly spread worldwide. To describe the geographic distribution and patient characteristics of pH1N1-associated deaths in the United States, the Centers for Disease Control and Prevention requested information from health departments on all laboratory-confirmed pH1N1 deaths reported from 17 April through 23 July 2009. Data were collected using medical charts, medical examiner reports, and death certificates. A total of 377 pH1N1-associated deaths were identified, for a mortality rate of .12 deaths per 100 000 population. Activity was geographically localized, with the highest mortality rates in Hawaii, New York, and Utah. Seventy-six percent of deaths occurred in persons aged 18–65 years, and 9% occurred in persons aged ≥65 years. Underlying medical conditions were reported for 78% of deaths: chronic lung disease among adults (39%) and neurologic disease among children (54%). Overall mortality associated with pH1N1 was low; however, the majority of deaths occurred in persons aged <65 years with underlying medical conditions. [ABSTRACT FROM PUBLISHER]

Abundance, distribution, population structure, lipid content, lipid composition and reproductive and feeding activity of Rhincalanus nasutus were studied in the Gulf of Aqaba and in the northern Red Sea during RV “Meteor”-cruise M 44-2 in February/March 1999. Rhincalanus nasutus occurred in higher numbers in the Gulf of Aqaba (585 ind m−2) than in the northern Red Sea (254 ind m−2). Young developmental stages (nauplii, copepodite stages CI and CII) were absent. In the southern Gulf of Aqaba, the bulk of the population developed from stage CV to adult in the course of the 3-week study period. In contrast, immature CV stages dominated at the adjacent stations in the northern Gulf of Aqaba and in the northern Red Sea. Development was associated with the seasonal vertical migration from wintering mid-water layers and initiation of feeding starting as early as beginning of March in the southern Gulf of Aqaba. No upward migration was observed in the northern parts of the Gulf and in the northern Red Sea, where more than 90% of the females remained immature during our study. Lipids were dominated by wax esters in females and CV. The fatty acid and fatty alcohol compositions of females were very similar throughout the study region and period. Major fatty acids were 18:1(n−9), 16:1(n−7), 16:2(n−4) and 20:5(n−3). Our results support the previous reports of a seasonal dormancy of R. nasutus in the Gulf of Aqaba and suggest that the timing of vertical migration, feeding and maturation is closely coupled to the development of the spring bloom in oligotrophic subtropical waters. [ABSTRACT FROM AUTHOR]

We analysed the influence of mesial temporal lobe epilepsy on the thickness of the corpus callosum (CC) in a large sample of well-characterized patients (n = 96) and healthy controls (n = 28). In particular, we investigated whether callosal structures are differentially affected depending on the affected hemisphere and age of epilepsy onset. Overall, we observed that epilepsy is associated with a decreased thickness in posterior callosal regions. Patients with an early onset, especially patients with left onset, additionally exhibited a smaller callosal thickness in more anterior and midbody regions. These findings may reflect non-specific as well as specific effects of temporal lobe epilepsy on CC development and interhemispheric connectivity. [ABSTRACT FROM AUTHOR]

: BACKGROUND In Germany, preimplantation genetic diagnosis (PGD) is currently not legal, but there is still a controversial debate about legalization. Studies about the attitudes of infertile couples towards PGD are rare. : METHODS A survey was conducted with 265 German infertile couples about knowledge, attitudes and prospective use of PGD. The influence of independent variables associated with approval of PGD is analysed by binary logistic regression. : RESULTS Sixty percent of respondents have heard about PGD. Eighty-seven percent support a general legalization of PGD in Germany for severe, early-onset genetic diseases. Seventy-four percent consider PGD morally acceptable. Sixty percent supported legalizing PGD for HLA-matching. But only a minority approved PGD to test for non-health-related traits. Respondents with a higher education level were the least supportive to all uses of PGD. : CONCLUSIONS Our results suggest that German infertile couples are as liberal towards PGD for health-related uses as in other western countries. They would legalize and use PGD to raise the rates to get pregnant and to avoid severe diseases of the offspring. Taking the opinions of German infertile couples into consideration could help redefine and reframe the public debate towards legalization of PGD and the moral status of the embryo in Germany. [ABSTRACT FROM AUTHOR]

Background and Aims Increased levels of nitrogen (N) deposition lead to enhanced N contents and reduced productivity of many bryophyte species. This study aimed at elucidating the mechanisms by which enhanced N uptake may cause growth reduction of bryophytes, focusing on the effects of N addition on carbon (C) metabolism of bryophytes. Methods Plantlets of Thuidium tamariscinum and Hylocomium splendens were fertilized with NH4NO3 (N load equalling 30 kg ha−1 year−1) for 80 d, including a pulse labelling experiment with 13CO2 to dissect the partitioning of carbon in response to N addition. Key Results Growth of T. tamariscinum was not affected by N addition, while H. splendens showed a trend towards growth reduction. Total N concentration was significantly increased by N addition in H. splendens, a significant increase in amino acid-N was found in T. tamariscinum only. In both bryophyte species, a reduction in concentration of lipids, the greatest C storage pool, as well as markedly enhanced turnover rates of C storage pools in fertilized plants were observed. Conclusions The results suggest that growth reduction of H. splendens under high levels of N deposition may be caused by enhanced synthesis of N-containing organic compounds, most probably of cell wall proteins. Disturbance of cellular C metabolism, as indicated by enhanced C pool turnover, may further contribute to the decline in productivity of H. splendens. [ABSTRACT FROM AUTHOR]

To interpret H[sub 2] quasar absorption-line observations in damped Lyα clouds (DLAs), we model the H[sub 2] spatial distribution within a DLA. Based on numerical simulations of disc structures with parameters similar to those derived for such absorbers, we calculate the H[sub 2] distribution as a function of ultraviolet background (UVB) intensity and dust-to-gas ratio. For typical values of these two quantities we find that the area in which the H[sub 2] fraction exceeds 10[sup -6] (typical observational detection limit) only covers ...10 per cent of the disc surface, i.e. H[sub 2] has a very inhomogeneous, clumpy distribution even at these low abundance levels. This explains the relative paucity of H[sub 2] detections in DLAs. We also show the dependence of the covering fraction of H[sub 2] on dust-to-gas ratio and UVB intensity, and we comment on the physics governing the H[sub 2] chemical network at high redshift. [ABSTRACT FROM AUTHOR]