Microsensor measurements of hydrogen gas dynamics in cyanobacterial microbial mats

© 2015 Nielsen, Revsbech and Kühl. We used a novel amperometric microsensor for measuring hydrogen gas production and consumption at high spatio-temporal resolution in cyanobacterial biofilms and mats dominated by non-heterocystous filamentous cyanobacteria (Microcoleus chtonoplastes and Oscillatoria sp.). The new microsensor is based on the use of an organic electrolyte and a stable internal reference system and can be equipped with a chemical sulfide trap in the measuring tip; it exhibits very stable and sulfide-insensitive measuring signals and a high sensitivity (1.5-5 pA per μmol L-1 H2). Hydrogen gas measurements were done in combination with microsensor measurements of scalar irradiance, O2, pH, and H2S and showed a pronounced H2 accumulation (of up to 8-10% H2 saturation) within the upper mm of cyanobacterial mats after onset of darkness and O2 depletion. The peak concentration of H2 increased with the irradiance level prior to darkening. After an initial build-up over the first 1-2 h in darkness, H2 was depleted over several hours due to efflux to the overlaying water, and due to biogeochemical processes in the uppermost oxic layers and the anoxic layers of the mats. Depletion could be prevented by addition of molybdate pointing to sulfate reduction as a major sink for H2. Immediately after onset of illumination, a short burst of presumably photo-produced H2 due to direct biophotolysis was observed in the illuminated but anoxic mat layers. As soon as O2 from photosynthesis started to accumulate, the H2 was consumed rapidly and production ceased. Our data give detailed insights into the microscale distribution and dynamics of H2 in cyanobacterial biofilms and mats, and further support that cyanobacterial H2 production can play a significant role in fueling anaerobic processes like e.g., sulfate reduction or anoxygenic photosynthesis in microbial mats

Consistent quantum mechanics admits no mereotopology

It is standardly assumed in discussions of quantum theory that physical systems can be regarded as having well-defined Hilbert spaces. It is shown here that a Hilbert space can be consistently partitioned only if its components are assumed not to interact. The assumption that physical systems have well-defined Hilbert spaces is, therefore, physically unwarranted.Comment: 10 pages; to appear in Axiomathe

Preoperative systemic inflammation predicts postoperative infectious complications in patients undergoing curative resection for colorectal cancer

The presence of systemic inflammation before surgery, as evidenced by the glasgow prognostic score (mGPS), predicts poor long-term survival in colorectal cancer. The aim was to examine the relationship between the preoperative mGPS and the development of postoperative complications in patients undergoing potentially curative resection for colorectal cancer. Patients (n=455) who underwent potentially curative resections between 2003 and 2007 were assessed consecutively, and details were recorded in a database. The majority of patients presented for elective surgery (85%) were over the age of 65 years (70%), were male (58%), were deprived (53%), and had TNM stage I/II disease (61%), had preoperative haemoglobin (56%), white cell count (87%) and mGPS 0 (58%) in the normal range. After surgery, 86 (19%) patients developed a postoperative complication; 70 (81%) of which were infectious complications. On multivariate analysis, peritoneal soiling (P<0.01), elevated preoperative white cell count (P<0.05) and mGPS (P<0.01) were independently associated with increased risk of developing a postoperative infection. In elective patients, only the mGPS (OR=1.75, 95% CI=1.17-2.63, P=0.007) was significantly associated with increased risk of developing a postoperative infection. Preoperative elevated mGPS predicts increased postoperative infectious complications in patients undergoing potentially curative resection for colorectal cancer

Changing indications and socio-demographic determinants of (adeno)tonsillectomy among children in England--are they linked? A retrospective analysis of hospital data.

OBJECTIVE: To assess whether increased awareness and diagnosis of obstructive sleep apnoea syndrome (OSAS) and national guidance on tonsillectomy for recurrent tonsillitis have influenced the socio-demographic profile of children who underwent tonsillectomy over the last decade. METHOD: Retrospective time-trends study of Hospital Episodes Statistics data. We examined the age, sex and deprivation level, alongside OSAS diagnoses, among children aged <16 years who underwent (adeno)tonsillectomy in England between 2001/2 and 2011/12. RESULTS: Among children aged <16 years, there were 29,697 and 27,732 (adeno)tonsillectomies performed in 2001/2 and 2011/12, respectively. The median age at (adeno)tonsillectomy decreased from 7 (IQR: 5-11) to 5 (IQR: 4-9) years over the decade. (Adeno)tonsillectomy rates among children aged 4-15 years decreased by 14% from 350 (95%CI: 346-354) in 2001/2 to 300 (95%CI: 296-303) per 100,000 children in 2011/12. However, (adeno)tonsillectomy rates among children aged <4 years increased by 58% from 135 (95%CI: 131-140) to 213 (95%CI 208-219) per 100,000 children in 2001/2 and 2011/2, respectively. OSAS diagnoses among children aged <4 years who underwent surgery increased from 18% to 39% between these study years and the proportion of children aged <4 years with OSAS from the most deprived areas increased from 5% to 12%, respectively. CONCLUSIONS: (Adeno)tonsillectomy rates declined among children aged 4-15 years, which reflects national guidelines recommending the restriction of the operation to children with more severe recurrent throat infections. However, (adeno)tonsillectomy rates among pre-school children substantially increased over the past decade and one in five children undergoing the operation was aged <4 years in 2011/12.The increase in surgery rates in younger children is likely to have been driven by increased awareness and detection of OSAS, particularly among children from the most deprived areas

Effects of protein–carbohydrate supplementation on immunity and resistance training outcomes: a double-blind, randomized, controlled clinical trial

Purpose: To examine the impact of ingesting hydrolyzed beef protein, whey protein, and carbohydrate on resistance training outcomes, body composition, muscle thickness, blood indices of health and salivary human neutrophil peptides (HNP1-3), as reference of humoral immunity followed an 8-week resistance training program in college athletes. Methods: Twenty-seven recreationally physically active males and females (n = 9 per treatment) were randomly assigned to one of the three groups: hydrolyzed beef protein, whey protein, or non-protein isoenergetic carbohydrate. Treatment consisted of ingesting 20 g of supplement, mixed with orange juice, once a day immediately post-workout or before breakfast on non-training days. Measurements were performed pre- and post-intervention on total load (kg) lifted at the first and last workout, body composition (via plethysmography) vastus medialis thickness (mm) (via ultrasonography), and blood indices of health. Salivary HNP1-3 were determined before and after performing the first and last workout. Results: Salivary concentration and secretion rates of the HNP1-3 decreased in the beef condition only from pre-first-workout (1.90 ± 0.83 μg/mL; 2.95 ± 2.83 μg/min, respectively) to pre-last-workout (0.92 ± 0.63 μg/mL, p = 0.025, d = 1.03; 0.76 ± 0.74 μg/min, p = 0.049, d = 0.95), and post-last-workout (0.95 ± 0.60 μg/mL, p = 0.032, d = 1.00; 0.59 ± 0.52 μg/min, p = 0.027, d = 1.02). No other significant differences between groups were observed. Conclusions: Supplementation with a carbohydrate–protein beverage may support resistance training outcomes in a comparable way as the ingestion of only carbohydrate. Furthermore, the ingestion of 20 g of hydrolyzed beef protein resulted in a decreased level and secretion rates of the HNP1-3 from baseline with no negative effect on blood indices of health

Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive transfer with tumor-infiltrating lymphocytes in melanoma

BACKGROUND: Neoantigen-driven recognition and T cell-mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with Tumor-Infiltrating Lymphocytes (TILs). Yet, how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS: Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic mela-noma patients who received ACT. RESULTS: We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with in-creased survival, and that detection of engrafted CD8+ T cells in post-treatment (i.e. originating from the TIL infusion product) were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS: These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma, and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells. FUNDING: NEYE Foundation; European Research Council; Lundbeck Foundation Fellowship; Carlsberg Foundation

Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

The Risk of West Nile Virus Infection Is Associated with Combined Sewer Overflow Streams in Urban Atlanta, Georgia, USA

BACKGROUND: At present, the factors favoring transmission and amplification of West Nile Virus (WNV) within urban environments are poorly understood. In urban Atlanta, Georgia, the highly polluted waters of streams affected by combined sewer overflow (CSO) represent significant habitats for the WNV mosquito vector Culex quinquefasciatus. However, their contribution to the risk of WNV infection in humans and birds remains unclear.\ud \ud OBJECTIVES: Our goals were to describe and quantify the spatial distribution of WNV infection in mosquitoes, humans, and corvids, such as blue jays and American crows that are particularly susceptible to WNV infection, and to assess the relationship between WNV infection and proximity to CSO-affected streams in the city of Atlanta, Georgia.\ud \ud MATERIALS AND METHODS: We applied spatial statistics to human, corvid, and mosquito WNV surveillance data from 2001 through 2007. Multimodel analysis was used to estimate associations of WNV infection in Cx. quinquefasciatus, humans, and dead corvids with selected risk factors including distance to CSO streams and catch basins, land cover, median household income, and housing characteristics.\ud \ud RESULTS: We found that WNV infection in mosquitoes, corvids, and humans was spatially clustered and statistically associated with CSO-affected streams. WNV infection in Cx. quinquefasciatus was significantly higher in CSO compared with non-CSO streams, and WNV infection rates among humans and corvids were significantly associated with proximity to CSO-affected streams, the extent of tree cover, and median household income.\ud \ud CONCLUSIONS: Our study strongly suggests that CSO-affected streams are significant sources of Cx. quinquefasciatus mosquitoes that may facilitate WNV transmission to humans within urban environments. Our findings may have direct implications for the surveillance and control of WNV in other urban centers that continue to use CSO systems as a waste management practice

Multiple S-isotopic evidence for episodic shoaling of anoxic water during Late Permian mass extinction

Global fossil data show that profound biodiversity loss preceded the final catastrophe that killed nearly 90% marine species on a global scale at the end of the Permian. Many hypotheses have been proposed to explain this extinction and yet still remain greatly debated. Here, we report analyses of all four sulphur isotopes (32S, 33S, 34S and 36S) for pyrites in sedimentary rocks from the Meishan section in South China. We observe a sulphur isotope signal (negative δ34S with negative Δ33S) that may have resulted from limitation of sulphate supply, which may be linked to a near shutdown of bioturbation during shoaling of anoxic water. These results indicate that episodic shoaling of anoxic water may have contributed to the profound biodiversity crisis before the final catastrophe. Our data suggest a prolonged deterioration of oceanic environments during the Late Permian mass extinction