Validation of Fourier Transform Infrared Spectroscopy for Serotyping of Streptococcus pneumoniae.

Fourier transform infrared (FT-IR) spectroscopy (IR Biotyper; Bruker) allows highly discriminatory fingerprinting of closely related bacterial strains. In this study, FT-IR spectroscopy-based capsular typing of Streptococcus pneumoniae was validated as a rapid, cost-effective, and medium-throughput alternative to the classical phenotypic techniques. A training set of 233 strains was defined, comprising 34 different serotypes and including all 24 vaccine types (VTs) and 10 non-vaccine types (NVTs). The acquired spectra were used to (i) create a dendrogram where strains clustered together according to their serotypes and (ii) train an artificial neural network (ANN) model to predict unknown pneumococcal serotypes. During validation using 153 additional strains, we reached 98.0% accuracy for determining serotypes represented in the training set. Next, the performance of the IR Biotyper was assessed using 124 strains representing 59 non-training set serotypes. In this setting, 42 of 59 serotypes (71.1%) could be accurately categorized as being non-training set serotypes. Furthermore, it was observed that comparability of spectra was affected by the source of the Columbia medium used to grow the pneumococci and that this complicated the robustness and standardization potential of FT-IR spectroscopy. A rigorous laboratory workflow in combination with specific ANN models that account for environmental noise parameters can be applied to overcome this issue in the near future. The IR Biotyper has the potential to be used as a fast, cost-effective, and accurate phenotypic serotyping tool for S. pneumoniae.

Human health risks associated with consumption of fish contaminated with trace elements from intensive mining activities in a peri-urban region.

Worldwide, numerous rural communities and low-income groups depend on fish harvested by subsistence fishers from local rivers and its impoundments as a source of protein. The aim of the present study was to determine the trace element bioaccumulation (As, Cd, Cr, Cu, Ni, Pb, Pt, Zn) in three edible fish species (Cyprinus carpio, Clarias gariepinus, Oreochromis mossambicus) from two impoundments in the Hex River system, South Africa, as well as the chronic health risk these trace elements pose to regular fish consumers. Trace element concentrations in the Hex River are naturally high (geogenic source), however, increased anthropogenic activities, such as intensive platinum mining activities, elevate the already high background concentrations. Concentrations of As, Cr, and Pt in C. carpio and C. gariepinus, as well as Ni and Zn in O. mossambicus were significantly higher in the impacted impoundment as compared to the reference impoundment. Concentrations of Cr and Cu were at both sampling sites the highest in O. mossambicus. From the human health risk assessment, As poses non-carcinogenic (HQ = 2-7) and carcinogenic risks (33-93 out of 10,000 people), while Cr (3-10 out of 10,000 people) and Ni (2-6 out of 10,000 people) pose only carcinogenic risks for the regular consumption of all three fish species from both impoundments, indicating a high probability of adverse human health effects. For As, Cr and Ni, also the sediment concentrations exceeded the levels of concern within the consensus based sediment quality guideline (CBSQG), while Cd, Cu, Ni and Zn exceeded the water quality guideline values. Thus, the CBSQG approach could be a promising tool for predicting human health risk associated with fish consumption. Since the present study only focused on the individual trace element risks, mixed toxicity of these trace elements and possible other pollutants within these fish species may pose an even greater risk to people who consume these fish regularly.

Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN).

BACKGROUND: Schizophrenia is a severe and often difficult to treat psychiatric illness. In many patients, negative symptoms dominate the clinical picture. Meta-analysis has suggested moderate, but significant effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on these symptoms. For treatment of depression a much shorter protocol - intermittent theta burst stimulation (iTBS) - has shown to be non-inferior to conventional high-frequency rTMS. This randomized, sham-controlled, rater-blinded clinical trial assesses the effects of conventional HF-rTMS as well as of iTBS of the left dorsolateral prefrontal cortex in comparison with sham. METHODS: The study will be conducted at two psychiatric university hospitals in Germany and at two in the Czech Republic. Assuming an effect size of 0.64 to be detected with a power of 80%, the calculated sample size is 90 patients. Primary outcome will be the difference in the Scale for the Assessment of Negative Symptoms (SANS) score between each active arm and the sham arm at end of treatment.In addition, the trial investigates effects on depressive symptoms, cognitive performance and cigarette smoking. Recording magnetic resonance imaging (MRI) and electroencephalography (EEG) data will serve to assess whether treatment success can be predicted by neural markers and is related to specific neurobiological changes. DISCUSSION: This is a clinical trial directly comparing 10 Hz-rTMS and iTBS in a sham-controlled manner in treating negative symptoms of schizophrenia. If successful, this would present an interesting treatment option for a chronic and severe condition that can be applied at most psychiatric hospitals and only takes up a few minutes per day. TRIAL REGISTRATION NUMBER: This trial has been registered at clinicaltrials.gov, Identifier: NCT04318977. DATA DISSEMINATION: Results from the trial shall be published in peer-reviewed journals and presented at meetings and conferences.

Electrospray ionization ion mobility spectrometer with new tristate ion gating for improved sensitivity for compounds with lower ion mobility.

An electrospray is a dispersed nebula of charged droplets produced under the influence of a strong electric field. The charged droplets subsequently result in ions in the gas phase. Therefore, electrospray is a commonly used method for transferring liquids to the gas phase while ionizing its constituents at the same time. In this work, we investigate the performance of an electrospray ionization ion mobility spectrometer by varying the electric field strength in the desolvation region. In particular, we investigate a new tristate ion shutter with increased sensitivity for ions with higher molecular mass and lower ion mobility that are usually suppressed by classical Bradbury-Nielsen or Tyndall-Powell ion shutters when using short gating times as required for high resolving power. The electric field in the tristate ion shutter affects the optimal ratio of the electric field strengths in the drift and desolvation region. Furthermore, the solvent flow rate needs to be considered when setting the field strengths in the desolvation region. However, a higher electric field strength in the desolvation region affects the field at the emitter tip. For this reason, a smaller ratio of the drift field strength and the desolvation field strength is beneficial, especially since higher solvent flow rates require higher fields to initiate an electrospray. In this work, we use tetraoctylammonium bromide as an instrument standard and the fungicide metalaxyl, the herbicide isoproturon and the antibiotic cefuroxime as model compounds.

[Contact endoscopy with narrow-band imaging for detection of perpendicular vascular changes in benign, dysplastic, and malignant lesions of the vocal folds]. / Kontaktendoskopie mit Narrow Band Imaging zur Erkennung perpendikulärer Gefäßveränderungen bei benignen Läsionen, Dysplasien und Karzinomen der Stimmlippen.

BACKGROUND: Perpendicular vascular changes (PVC) are markers of tumor-induced neoangiogenesis at the vocal folds. Contact endoscopy with narrow-band imaging (CE-NBI) allows a detailed analysis of such vascular changes. OBJECTIVE: This work intends to evaluate the potential of CE-NBI for diagnosis of benign, dysplastic, and malignant lesions of the vocal folds. In addition, it should be determined whether CE-NBI offers an additional benefit in detecting PVC compared to white-light endoscopy (WLE) and NBI alone. MATERIALS AND METHODS: Three examiners evaluated histologically verified cases of benign, dysplastic, and malignant lesions of the larynx in WLE, NBI, and CE-NBI (n = 60). In each mode, they examined the lesion for PVC and assessed the lesion's dignity. The proportion of lesions with detected PVC, the statistical measures of performance in detecting high-grade dysplasia and carcinoma, and the interrater variability for each mode were calculated. RESULTS: CE-NBI proved superior to the other investigated diagnostic methods in terms of detecting PVC and in terms of sensitivity and accuracy in the diagnosis of high-grade dysplasia and carcinoma. A clear association of such pathologies with PVC was seen. CONCLUSION: CE-NBI detects PVC more frequently and reliably than the other methods investigated. The association of these vascular patterns to high-grade dysplasia and vocal fold carcinomas could be confirmed. Compared to WLE and NBI endoscopy, the diagnostic quality for detecting high-grade dysplasia and carcinoma is increased. Thus, CE-NBI can improve endoscopic differentiation between benign and malignant lesions of the vocal folds by enhancing the detection of PVC.

Dose constraints for whole breast radiation therapy based on the quality assessment of treatment plans in the randomised Danish breast cancer group (DBCG) HYPO trial.

PURPOSE: Quality assessment of the treatment plans in the Danish Breast Cancer Group (DBCG) HYPO trial was carried out based on prospectively reported dosimetric parameters and evidence-based dose constraints for whole breast radiation therapy were derived. MATERIALS AND METHODS: From 2009 to 2014, 1882 patients (pts) were randomised between 50 Gy/25fractions (fr) versus 40 Gy/15fr. Doses to CTVp_breast (V95%, V107%-V110%, Dmax, and in addition for 40 Gy plans V105%-V107%), ipsilateral lung (V20Gy/V17Gy), heart (V20Gy/V17Gy, V40Gy/V35Gy), and left anterior descending coronary artery (LADCA) (Dmax) and use of respiratory gated technique were prospectively reported to the DBCG database. After end of accrual, these dosimetric parameters from all plans in the trial were compared to the pre-specified treatment constraints. RESULTS: In total, 1854 pts from eight radiation therapy (RT) centres in three countries were treated. No statistically significant differences were found between the results for 40 Gy and 50 Gy plans, except for CTVp_breast hot-spot volume (V107%-V110%). Of the 40 Gy pts, 90% with CTVp_breast > 600 mL and 95% with CTVp_breast ≤ 600 mL had a CTVp_breast hot-spot volume (V105%-V107%) <2%. In 95% of the 50 Gy plans, the CTVp_breast absolute hot-spot volume (V107%-V110%) was <0.5 mL and 1.7 mL for CTVp_breast ≤ 600 mL and > 600 mL, respectively. Compliance was >99% for both heart and lung constraints. Largest deviation from protocol constraints was found for the volume of CTVp_breast covered with 95% of the prescription dose or more (V95%). The CTV dose coverage (V95%) was >94.3% in 95% of the right-sided pts, whereas the figures for 95% of the left-sided pts treated with and without respiratory gating were 93.2% and 88.8%, respectively. CONCLUSION: A high degree of compliance with protocol dose constraints was found for treatment plans in the DBCG HYPO trial. New constraints for dose to organs at risk and high-dose volumes in the breast are suggested for breast-only RT planning.

Late-onset and long-lasting immune-related adverse events from immune checkpoint-inhibitors: An overlooked aspect in immunotherapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy but frequently cause immune-related adverse events (irAEs). Description of late-onset and duration of irAEs in the literature is often incomplete. METHODS: To investigate reporting and incidence of late-onset and long-lasting irAEs, we reviewed all registration trials leading to ICI's approval by the US FDA and/or EMA up to December 2019. We analysed real-world data from all lung cancer (LC) and melanoma (Mel) patients treated with approved ICIs at the University Hospital of Lausanne (CHUV) from 2011 to 2019. To account for the immortal time bias, we used a time-dependent analysis to assess the potential association between irAEs and overall survival (OS). RESULTS: Duration of irAEs and proportion of patients with ongoing toxicities at data cut-off were not specified in 56/62 (90%) publications of ICIs registration trials. In our real-world analysis, including 437 patients (217 LC, 220 Mel), 229 (52.4%) experienced at least one grade ≥2 toxicity, for a total of 318 reported irAEs, of which 112 (35.2%) were long-lasting (≥6 months) and about 40% were ongoing at a median follow-up of 369 days [194-695] or patient death. The cumulative probability of irAE onset from treatment initiation was 42.8%, 51.0% and 57.3% at 6, 12 and 24 months, respectively. The rate of ongoing toxicity from the time of first toxicity onset was 42.8%, 38.4% and 35.7% at 6, 12 and 24 months. Time-dependent analysis showed no significant association between the incidence of irAEs and OS in both cohorts (log Rank p = 0.67 and 0.19 for LC and Mel, respectively). CONCLUSIONS: Late-onset and long-lasting irAEs are underreported but common events during ICIs therapy. Time-dependent survival analysis is advocated to assess their impact on OS. Real-world evidence is warranted to fully capture and characterise late-onset and long-lasting irAEs in order to implement appropriate strategies for patient surveillance and follow-up.

Machine-assisted interpretation of auramine stains substantially increases through-put and sensitivity of microscopic tuberculosis diagnosis.

Of all bacterial infectious diseases, infection by Mycobacterium tuberculosis poses one of the highest morbidity and mortality burdens on humans throughout the world. Due to its speed and cost-efficiency, manual microscopy of auramine-stained sputum smears remains a crucial first-line detection method. However, it puts considerable workload on laboratory staff and suffers from a limited sensitivity. Here we validate a scanning and analysis system that combines fully-automated microscopy with deep-learning based image analysis. After automated scanning, the system summarizes diagnosis-relevant image information and presents it to the microbiologist in order to assist diagnosis. We tested the benefit of the automated scanning and analysis system using 531 slides from routine workflow, of which 56 were from culture positive specimen. Assistance by the scanning and analysis system allowed for a higher sensitivity (40/56 positive slides detected) than manual microscopy (34/56 positive slides detected), while greatly reducing manual slide-analysis time from a recommended 5-15 min to around 10 s per slide on average.

[Surgical reconstruction in laryngeal carcinoma]. / Chirurgische Rekonstruktionen beim Larynxkarzinom.

Tumors of the larynx can substantially impair vocal function, breathing and also swallowing. The primary goal of reconstructive surgical treatment of laryngeal tumors is to sufficiently resect the tumor while minimizing the effects of the treatment on the voice, breathing and swallowing. In general, primary reconstructions in primary laryngeal surgery have many advantages. The tissue at this point in time is soft because the scarring process has not yet been initiated. A better prerequisite for a sufficient glottic closure can also be expected through the immediate adjustment of the volume of the vocal folds; however, reconstructive treatment can also be carried out secondarily. Different methods of reconstructive surgery for laryngeal carcinoma are presented and discussed.

Does vancomycin resistance increase mortality in Enterococcus faecium bacteraemia after orthotopic liver transplantation? A retrospective study.

BACKGROUND: The relevance of vancomycin resistance in enterococcal blood stream infections (BSI) is still controversial. Aim of this study was to outline the effect of vancomycin resistance of Enterococcus faecium on the outcome of patients with BSI after orthotopic liver transplantation (OLT). METHODS: The outcome of OLT recipients developing BSI with vancomycin-resistant (VRE) versus vancomycin-susceptible Enterococcus faecium (VSE) was compared based on data extraction from medical records. Multivariate regression analyses identified risk factors for mortality and unfavourable outcomes (defined as death or prolonged intensive care stay) after 30 and 90 days. RESULTS: Mortality was similar between VRE- (n = 39) and VSE- (n = 138) group after 30 (p = 0.44) or 90 days (p = 0.39). Comparable results occurred regarding unfavourable outcomes. Mean SOFANon-GCS score during the 7-day-period before BSI onset was the independent predictor for mortality at both timepoints (HR 1.32; CI 1.14-1.53; and HR 1.18; CI 1.08-1.28). Timely appropriate antibiotic therapy, recent ICU stay and vancomycin resistance did not affect outcome after adjusting for confounders. CONCLUSION: Vancomycin resistance did not influence outcome among patients with Enterococcus faecium bacteraemia after OLT. Only underlying severity of disease predicted poor outcome among this homogenous patient population. TRIAL REGISTRATION: This study was registered at the German clinical trials register (DRKS-ID: DRKS00013285).

Metal accumulation in riverine macroinvertebrates from a platinum mining region.

South Africa is the world's main supplier of Pt. The Bushveld Igneous Complex in South Africa contains 75% of the world's Pt resources. Mining of this precious metal requires large volumes of water for production and removal of waste products. Most of this wastewater is discharged into river systems. Although the source of contamination with Pt in aquatic systems due to mining activities is known, little to no information is available about the impact of Pt on aquatic organisms. Additionally, other metals are released as byproducts of Pt mining, which might also be discharged into the environment. Therefore, concentrations of Cr, Ni, Cu, Zn, Cd, Pt and Pb were determined in water, sediment and macroinvertebrate samples from a reference site (Site 1), a highly impacted site (Site 2) and a moderately impacted site (Site 3) along the Hex River, South Africa. Aquatic invertebrate families representing different functional feeding groups i.e. scraper-grazers (Lymnaeidae), collector-gatherers (Potamonautidae, Hydropsychidae, Tubificidae and Chironomidae), shredders (Baetidae) and predators (Coenagrionidae and Libellulidae) were studied. In the sediments, the concentrations of Cr and Pt were significantly higher at Site 2 than at Sites 1 and 3, respectively, whereas concentrations of Ni, Cu, Cd, and Pb showed no significant differences between the sites. Depending on the metal, the aquatic invertebrate families showed different grades of bioaccumulation. The results from especially Lymnaeidae, Baetidae, Tubificidae and Chironomidae showed great promise for the use of these taxa for biomonitoring of metal contaminations. The macroinvertebrates accumulated metals associated with Pt mining, with epi-benthic dwelling taxa (Tubificidae) accumulating higher concentrations of Pt and Cr than other families (e.g. Potamonautidae, Coenagrionidae and Lymnaeidae). These results provide valuable information on the behavior of metals related to Pt mining in aquatic ecosystems and therefore can contribute to the risk assessment of these intensive mining activities.

Soil net nitrogen mineralisation across global grasslands.

Soil nitrogen mineralisation (Nmin), the conversion of organic into inorganic N, is important for productivity and nutrient cycling. The balance between mineralisation and immobilisation (net Nmin) varies with soil properties and climate. However, because most global-scale assessments of net Nmin are laboratory-based, its regulation under field-conditions and implications for real-world soil functioning remain uncertain. Here, we explore the drivers of realised (field) and potential (laboratory) soil net Nmin across 30 grasslands worldwide. We find that realised Nmin is largely explained by temperature of the wettest quarter, microbial biomass, clay content and bulk density. Potential Nmin only weakly correlates with realised Nmin, but contributes to explain realised net Nmin when combined with soil and climatic variables. We provide novel insights of global realised soil net Nmin and show that potential soil net Nmin data available in the literature could be parameterised with soil and climate data to better predict realised Nmin.

Efficacy of adoptive therapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 in advanced cutaneous melanoma: a systematic review and meta-analysis.

Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) has been tested in advanced melanoma patients at various centers. We conducted a systematic review and meta-analysis to assess its efficacy on previously treated advanced metastatic cutaneous melanoma. The PubMed electronic database was searched from inception to 17 December 2018 to identify studies administering TIL-ACT and recombinant interleukin-2 (IL-2) following non-myeloablative chemotherapy in previously treated metastatic melanoma patients. Objective response rate (ORR) was the primary end point. Secondary end points were complete response rate (CRR), overall survival (OS), duration of response (DOR) and toxicity. Pooled estimates were derived from fixed or random effect models, depending on the amount of heterogeneity detected. Analysis was carried out separately for high dose (HD) and low dose (LD) IL-2. Sensitivity analyses were carried out. Among 1211 records screened, 13 studies (published 1988 - 2016) were eligible for meta-analysis. Among 410 heavily pretreated patients (some with brain metastasis), 332 received HD-IL-2 and 78 LD-IL-2. The pooled overall ORR estimate was 41% [95% confidence interval (CI) 35% to 48%], and the overall CRR was 12% (95% CI 7% to 16%). For the HD-IL-2 group, the ORR was 43% (95% CI 36% to 50%), while for the LD-IL-2 it was 35% (95% CI 25% to 45%). Corresponding pooled estimates for CRR were 14% (95% CI 7% to 20%) and 7% (95% CI 1% to 12%). The majority of HD-IL-2 complete responders (27/28) remained in remission during the extent of follow-up after CR (median 40 months). Sensitivity analyses yielded similar results. Higher number of infused cells was associated with a favorable response. The ORR for HD-IL-2 compared favorably with the nivolumab/ipilimumab combination following anti-PD-1 failure. TIL-ACT therapy, especially when combined with HD-IL-2, achieves durable clinical benefit and warrants further investigation. We discuss the current position of TIL-ACT in the therapy of advanced melanoma, particularly in the era of immune checkpoint blockade therapy, and review future opportunities for improvement of this approach.

Temperature and moisture are minor drivers of regional-scale soil organic carbon dynamics.

Storing large amounts of organic carbon, soils are a key but uncertain component of the global carbon cycle, and accordingly, of Earth System Models (ESMs). Soil organic carbon (SOC) dynamics are regulated by a complex interplay of drivers. Climate, generally represented by temperature and moisture, is regarded as one of the fundamental controls. Here, we use 54 forest sites in Switzerland, systematically selected to span near-independent gradients in temperature and moisture, to disentangle the effects of climate, soil properties, and landform on SOC dynamics. We estimated two SOC turnover times, based on bulk soil 14C measurements (τ14C) and on a 6-month laboratory soil incubation (τi). In addition, upon incubation, we measured the 14C signature of the CO2 evolved and quantified the cumulated production of dissolved organic carbon (DOC). Our results demonstrate that τi and τ14C capture the dynamics of contrasting fractions of the SOC continuum. The 14C-based τ14C primarily reflects the dynamics of an older, stabilised pool, whereas the incubation-based τi mainly captures fresh readily available SOC. Mean site temperature did not raise as a critical driver of SOC dynamics, and site moisture was only significant for τi. However, soil pH emerged as a key control of both turnover times. The production of DOC was independent of τi and not driven by climate, but primarily by the content of clay and, secondarily by the slope of the site. At the regional scale, soil physicochemical properties and landform appear to override the effect of climate on SOC dynamics.

Bacterial sepsis : Diagnostics and calculated antibiotic therapy.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of ß­lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).

Analysis of the Beaufort Gyre Freshwater Content in 2003-2018.

Hydrographic data collected from research cruises, bottom-anchored moorings, drifting Ice-Tethered Profilers, and satellite altimetry in the Beaufort Gyre region of the Arctic Ocean document an increase of more than 6,400 km3 of liquid freshwater content from 2003 to 2018: a 40% growth relative to the climatology of the 1970s. This fresh water accumulation is shown to result from persistent anticyclonic atmospheric wind forcing (1997-2018) accompanied by sea ice melt, a wind-forced redirection of Mackenzie River discharge from predominantly eastward to westward flow, and a contribution of low salinity waters of Pacific Ocean origin via Bering Strait. Despite significant uncertainties in the different observations, this study has demonstrated the synergistic value of having multiple diverse datasets to obtain a more comprehensive understanding of Beaufort Gyre freshwater content variability. For example, Beaufort Gyre Observational System (BGOS) surveys clearly show the interannual increase in freshwater content, but without satellite or Ice-Tethered Profiler measurements, it is not possible to resolve the seasonal cycle of freshwater content, which in fact is larger than the year-to-year variability, or the more subtle interannual variations.

Size-dependent loss of aboveground animals differentially affects grassland ecosystem coupling and functions.

Increasing evidence suggests that community-level responses to human-induced biodiversity loss start with a decrease of interactions among communities and between them and their abiotic environment. The structural and functional consequences of such interaction losses are poorly understood and have rarely been tested in real-world systems. Here, we analysed how 5 years of progressive, size-selective exclusion of large, medium, and small vertebrates and invertebrates-a realistic scenario of human-induced defaunation-impacts the strength of relationships between above- and belowground communities and their abiotic environment (hereafter ecosystem coupling) and how this relates to ecosystem functionality in grasslands. Exclusion of all vertebrates results in the greatest level of ecosystem coupling, while the additional loss of invertebrates leads to poorly coupled ecosystems. Consumer-driven changes in ecosystem functionality are positively related to changes in ecosystem coupling. Our results highlight the importance of invertebrate communities for maintaining ecological coupling and functioning in an increasingly defaunated world.

HcTOK1 participates in the maintenance of K+ homeostasis in the ectomycorrhizal fungus Hebeloma cylindrosporum, which is essential for the symbiotic K+ nutrition of Pinus pinaster.

Most land plants rely on root symbioses to complement or improve their mineral nutrition. Recent researches have put forward that mycorrhizal fungi efficiently absorb and transfer potassium (K+) from the soil to host plant roots, but the molecular mechanisms involved are not completely elucidated yet. We have recently revealed that K+ is likely released from the fungal Hartig net to the plant by TOK channels in the ectomycorrhizal model Hebeloma cylindrosporum - Pinus pinaster. H. cylindrosporum harbours three TOK members. Herein, we report that one of them, HcTOK1, has similar features than the yeast ScTOK1. Moreover, we propose a role for this channel in the transport of K+ from the medium to ectomycorrhizal roots under K+ starvation.

Treatment outcomes of recurrent respiratory papillomatosis : Retrospective analysis of juvenile and adult cases.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare, chronic disease of viral etiology which is characterized by multiple, recurrent growth of papillomas in the aerodigestive tract. MATERIALS AND METHODS: The surgical outcomes and the recurrence rates of 106 patients with RRP of the larynx were analyzed. The patients were treated at the University of Magdeburg between 1983 and 2014. The surgical outcomes of conventional and laser surgery regarding time to relapse and complications were compared. In addition, the influence of the quadrivalent vaccine Gardasil® on the disease was analyzed in 10 patients. RESULTS: Children with RRP had a statistically significant greater number of surgeries throughout their lifetimes compared to adult patients. There were no differences between the adult (n = 79) and juvenile (n = 27) groups in the time to relapse and the number of surgeries/year. The time to relapse and number of procedures/year were not influenced by the various surgical methods. Complications after conventional and laser surgery were not statistically different between the two groups. Serious complications and the need for a tracheotomy were only reported after conventional surgery. In the 10 patients who were immunized with Gardasil®, a statistically significant lower number of surgeries/year after vaccination was achieved. CONCLUSION: RRP is a rare disease. Treatment requires experience and may be very difficult. The analysis of the course of the disease has shown that the treatment of choice is surgical excision with the CO2 laser combined with the quadrivalent or polyvalent vaccine. Consequent vaccination of both boys and girls has the potential to reduce the occurrence of RRP.

[Bacterial sepsis : Diagnostics and calculated antibiotic therapy]. / Bakterielle Sepsis : Diagnostik und kalkulierte Antibiotikatherapie.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).