Genus Erica: An identification aid version 4.00.

Species identification is fundamental to all aspects of biology and conservation. The process can be challenging, particularly in groups including many closely related or similar species. The problem is confounded by the absence of an up-to-date taxonomic revision, but even with such a resource all but professional botanists may struggle to recognise key species, presenting a substantial barrier to vital work such as surveys, threat assessments, and seed collection for ex situ conservation. Genus Erica: An Identification Aid is a tool to help both amateurs and professionals identify (using a limited number of accessible characteristics) and find information about the 851 species and many subspecific taxa of the genus Erica. We present an updated version 4.00, with new features including integrating distribution data from GBIF and iNaturalist, links to taxonomic resources through World Flora Online, and a probability function for identifications, that is freely available for PCs. It remains a work in progress: We discuss routes forward for collaboratively improving this resource.

Detecting flood-type-specific flood-rich and flood-poor periods in peaks-over-threshold series with application to Bavaria (Germany).

Previous studies suggest that flood-rich and flood-poor periods are present in many flood peak discharge series around the globe. Understanding the occurrence of these periods and their driving mechanisms is important for reliably estimating future flood probabilities. We propose a method for detecting flood-rich and flood-poor periods in peak-over-threshold series based on scan-statistics and combine it with a flood typology in order to attribute the periods to their flood-generating mechanisms. The method is applied to 164 observed flood series in southern Germany from 1930 to 2018. The results reveal significant flood-rich periods of heavy-rainfall floods, especially in the Danube river basin in the most recent decades. These are consistent with trend analyses from the literature. Additionally, significant flood-poor periods of snowmelt-floods in the immediate past were detected, especially for low-elevation catchments in the alpine foreland and the uplands. The occurrence of flood-rich and flood-poor periods is interpreted in terms of increases in the frequency of heavy rainfall in the alpine foreland and decreases of both soil moisture and snow cover in the midlands.

Citrin deficiency mimicking mitochondrial depletion syndrome.

BACKGROUND: Neonatal intrahepatic cholestasis caused by citrin deficiency (CD) is a rare inborn error of metabolism due to variants in the SLC25A13 gene encoding the calcium-binding protein citrin. Citrin is an aspartate-glutamate carrier located within the inner mitochondrial membrane. CASE PRESENTATION: We report on two siblings of Romanian-Vietnamese ancestry with citrin deficiency. Patient 1 is a female who presented at age 8 weeks with cholestasis, elevated lactate levels and recurrent severe hypoglycemia. Diagnosis was made by whole exome sequencing and revealed compound heterozygosity for the frameshift variant c.852_855del, p.Met285Profs*2 and a novel deletion c.(69 + 1_70-1)_(212 + 1_231-1)del in SLC25A13. The girl responded well to dietary treatment with a lactose-free, MCT-enriched formula. Her younger brother (Patient 2) was born 1 year later and also found to be carrying the same gene variants. Dietary treatment from birth was able to completely prevent clinical manifestation until his current age of 4.5 months. CONCLUSIONS: As CD is a well-treatable disorder it should be ruled out early in the differential diagnosis of neonatal cholestasis. Due to the combination of hepatopathy, lactic acidosis and recurrent hypoglycemia the clinical presentation of CD may resemble hepatic mitochondrial depletion syndrome.

[Right-sided or left-sided donor nephrectomy-is this really relevant?] / Rechts- oder linksseitige Donornephrektomie ­ ist das wirklich relevant?

BACKGROUND: In the context of living donation, the protection of the donor and the outcome are very important aspects. However, the side selection of the donor nephrectomy is also decisive. In this work, the basics of side selection and the question of whether there are differences regarding the left-sided or right-sided donor nephrectomy are considered. MATERIALS AND METHODS: Living kidney donation data of our center between December 2004 and July 2019 were evaluated in terms of withdrawal side, complications and outcome, as well as the current literature in PubMed. Finally, the results from our center are compared with the current literature. RESULTS: During the investigation period, 152 live donations were carried out in our center. In these cases 66 patients had a left-sided and in 86 cases a right-sided donor nephrectomy. One transplant vein thrombosis occurred in each group. Complications and outcome were similar for the recipient in both groups. It was noticed in the current literature that generally more left-sided donor nephrectomies are performed, most likely due to the preference of the surgeon. Although a low significantly increased risk of transplant vein thrombosis after right-sided donor nephrectomy is described, all authors agree that right-sided donor nephrectomy is a safe procedure with good outcome. CONCLUSIONS: Our own results and the current literature show that the right-sided donor nephrectomy is a safe procedure with only a slightly increased risk of complications compared to the left side and therefore can be recommended. It is clearly safe for the donor and organ, with an equivalent outcome for the recipient. The results are also dependent on the experience of the surgeon.

CFTR is a tumor suppressor gene in murine and human intestinal cancer.

This corrects the article DOI: 10.1038/onc.2015.483.

Requirements for a Compton camera for in vivo range verification of proton therapy.

To ensure the optimal outcome of proton therapy, in vivo range verification is highly desired. Prompt γ-ray imaging (PGI) is a possible approach for in vivo range monitoring. For PGI, dedicated detection systems, e.g. Compton cameras, are currently under investigation. The presented paper deals with substantial requirements regarding hardware and software that a Compton camera used in clinical routine has to meet. By means of GEANT4 simulations, we investigate the load on the detectors and the percentage of background expected in a realistic irradiation and we simulate γ-ray detections subsequently used as input data for the reconstruction. By reconstructing events from simulated sources of well-defined geometry, we show that large-area detectors are favourable. We investigate reconstruction results in dependence of the number of events. Finally, an end-to-end test for a realistic patient scenario is presented: starting with a treatment plan, the γ-ray emissions are calculated, the detector response is modelled, and the image reconstruction is performed. By this, the complexity of the system is shown, and requirements and limitations regarding precision and costs are determined.

[Radiation cystitis : Pathophysiology and treatment]. / Radiogen bedingte Zystitis : Pathophysiologie und Therapie.

Radiation cystitis (RC) is a common side-effect of radiation to the pelvis. Their clinical appearance as well as their degree of expression is manifold, as are the therapeutic options. However, in the absence of randomized examinations, recommendations are difficult. We differentiate between oral, systemic therapies, intravesical instillations and interventions as well as interventional, radiological and, as an ultima ratio, surgical treatments. This article provides an overview of the different treatment options with particular emphasis on the conservative-interventional therapy options.

[Improvement in Phoneme Discrimination in Noise in Normal Hearing Adults]. / Trainierbarkeit der Diskrimination von Phonemen im Störgeräusch bei normalhörenden Erwachsenen.

Objective: The study's aim was to examine the possibility to train phoneme-discrimination in noise with normal hearing adults, and its effectivity on speech recognition in noise. A specific computerised training program was used, consisting of special nonsense-syllables with background noise, to train participants' discrimination ability. Material and Methods: 46 normal hearing subjects took part in this study, 28 as training group participants, 18 as control group participants. Only the training group subjects were asked to train over a period of 3 weeks, twice a week for an hour with a computer-based training program. Speech recognition in noise were measured pre- to posttraining for the training group subjects with the Freiburger Einsilber Test. The control group subjects obtained test and restest measures within a 2-3 week break. For the training group follow-up speech recognition was measured 2-3 months after the end of the training. Results: The majority of training group subjects improved their phoneme discrimination significantly. Besides, their speech recognition in noise improved significantly during the training compared to the control group, and remained stable for a period of time. Conclusions: Phonem-Discrimination in noise can be trained by normal hearing adults. The improvements have got a positiv effect on speech recognition in noise, also for a longer period of time.

From prompt gamma distribution to dose: a novel approach combining an evolutionary algorithm and filtering based on Gaussian-powerlaw convolutions.

Range verification and dose monitoring in proton therapy is considered as highly desirable. Different methods have been developed worldwide, like particle therapy positron emission tomography (PT-PET) and prompt gamma imaging (PGI). In general, these methods allow for a verification of the proton range. However, quantification of the dose from these measurements remains challenging. For the first time, we present an approach for estimating the dose from prompt γ-ray emission profiles. It combines a filtering procedure based on Gaussian-powerlaw convolution with an evolutionary algorithm. By means of convolving depth dose profiles with an appropriate filter kernel, prompt γ-ray depth profiles are obtained. In order to reverse this step, the evolutionary algorithm is applied. The feasibility of this approach is demonstrated for a spread-out Bragg-peak in a water target.

[Phoneme discrimination training with experienced cochlear implant listeners]. / Training der Phonemdiskrimination mit erfahrenen Cochleaimplantatträgern.

BACKGROUND: Computer-based auditory training programmes seem to be a useful tool in the process of auditory rehabilitation after cochlear implantation (CI). Currently, little is known about the learning mechanism and efficiency of such programs. The aim of the study was to evaluate a specific auditory training programme for phoneme discrimination in experienced CI listeners. MATERIALS AND METHODS: A total of 15 CI adult listeners with more than 2 years' CI experience participated in the auditory training. Over a period of 3 weeks they were instructed to train their phoneme discrimination via computer twice a week. Training material consisted of special syllables for consonants (vCv) and vowels (cVc) discrimination. RESULTS: The discrimination abilities for consonants and vowels improved significantly over the training period for training group participants, whereas the changes for the consonants were higher. In addition, the improvement for voiced and unvoiced consonants was significant. CONCLUSION: Computerised auditory training with phonemes improves CI listeners' discrimination abilities for consonants and vowels.

CFTR is a tumor suppressor gene in murine and human intestinal cancer.

CFTR, the cystic fibrosis (CF) gene, encodes for the CFTR protein that plays an essential role in anion regulation and tissue homeostasis of various epithelia. In the gastrointestinal (GI) tract CFTR promotes chloride and bicarbonate secretion, playing an essential role in ion and acid-base homeostasis. Cftr has been identified as a candidate driver gene for colorectal cancer (CRC) in several Sleeping Beauty DNA transposon-based forward genetic screens in mice. Further, recent epidemiological and clinical studies indicate that CF patients are at high risk for developing tumors in the colon. To investigate the effects of CFTR dysregulation on GI cancer, we generated Apc(Min) mice that carried an intestinal-specific knockout of Cftr. Our results indicate that Cftr is a tumor suppressor gene in the intestinal tract as Cftr mutant mice developed significantly more tumors in the colon and the entire small intestine. In Apc(+/+) mice aged to ~1 year, Cftr deficiency alone caused the development of intestinal tumors in >60% of mice. Colon organoid formation was significantly increased in organoids created from Cftr mutant mice compared with wild-type controls, suggesting a potential role of Cftr in regulating the intestinal stem cell compartment. Microarray data from the Cftr-deficient colon and the small intestine identified dysregulated genes that belong to groups of immune response, ion channel, intestinal stem cell and other growth signaling regulators. These associated clusters of genes were confirmed by pathway analysis using Ingenuity Pathway Analysis and gene set enrichment analysis (GSEA). We also conducted RNA Seq analysis of tumors from Apc(+/+) Cftr knockout mice and identified sets of genes dysregulated in tumors including altered Wnt ß-catenin target genes. Finally we analyzed expression of CFTR in early stage human CRC patients stratified by risk of recurrence and found that loss of expression of CFTR was significantly associated with poor disease-free survival.

Molecular and biochemical alterations in tubular epithelial cells of patients with isolated methylmalonic aciduria.

Methylmalonic acidurias (MMAurias) are a group of inherited disorders in the catabolism of branched-chain amino acids, odd-chain fatty acids and cholesterol caused by complete or partial deficiency of methylmalonyl-CoA mutase (mut(0) and mut(-) subtype respectively) and by defects in the metabolism of its cofactor 5'-deoxyadenosylcobalamin (cblA, cblB or cblD variant 2 type). A long-term complication found in patients with mut(0) and cblB variant is chronic tubulointerstitial nephritis. The underlying pathomechanism has remained unknown. We established an in vitro model of tubular epithelial cells from patient urine (hTEC; 9 controls, 5 mut(0), 1 cblB). In all human tubular epithelial cell (hTEC) lines we found specific tubular markers (AQP1, UMOD, AQP2). Patient cells showed disturbance of energy metabolism in glycolysis, mitochondrial respiratory chain and Krebs cycle in concert with increased reactive oxygen species (ROS) formation. Electron micrographs indicated increased autophagosome production and endoplasmic reticulum stress, which was supported by positive acridine orange staining and elevated levels of LC3 II, P62 and pIRE1. Screening mTOR signaling revealed a release of inhibition of autophagy. Patient hTEC produced and secreted elevated amounts of the pro-inflammatory cytokine IL8, which was highly correlated with the acridine orange staining. Summarizing, hTEC of MMAuria patients are characterized by disturbed energy metabolism and ROS production that lead to increased autophagy and IL8 secretion.

Simulation and experimental verification of prompt gamma-ray emissions during proton irradiation.

Irradiation with protons and light ions offers new possibilities for tumor therapy but has a strong need for novel imaging modalities for treatment verification. The development of new detector systems, which can provide an in vivo range assessment or dosimetry, requires an accurate knowledge of the secondary radiation field and reliable Monte Carlo simulations. This paper presents multiple measurements to characterize the prompt γ-ray emissions during proton irradiation and benchmarks the latest Geant4 code against the experimental findings. Within the scope of this work, the total photon yield for different target materials, the energy spectra as well as the γ-ray depth profile were assessed. Experiments were performed at the superconducting AGOR cyclotron at KVI-CART, University of Groningen. Properties of the γ-ray emissions were experimentally determined. The prompt γ-ray emissions were measured utilizing a conventional HPGe detector system (Clover) and quantitatively compared to simulations. With the selected physics list QGSP_BIC_HP, Geant4 strongly overestimates the photon yield in most cases, sometimes up to 50%. The shape of the spectrum and qualitative occurrence of discrete γ lines is reproduced accurately. A sliced phantom was designed to determine the depth profile of the photons. The position of the distal fall-off in the simulations agrees with the measurements, albeit the peak height is also overestimated. Hence, Geant4 simulations of prompt γ-ray emissions from irradiation with protons are currently far less reliable as compared to simulations of the electromagnetic processes. Deviations from experimental findings were observed and quantified. Although there has been a constant improvement of Geant4 in the hadronic sector, there is still a gap to close.

Viscum album [L.] extract therapy in patients with locally advanced or metastatic pancreatic cancer: a randomised clinical trial on overall survival.

BACKGROUND: The unfavourable side-effects of late-stage pancreatic cancer treatments call for non-toxic and effective therapeutic approaches. We compared the overall survival (OS) of patients receiving an extract of Viscum album [L.] (VaL) or no antineoplastic therapy. METHODS: This is a prospective, parallel, open label, monocentre, group-sequential, randomised phase III study. Patients with locally advanced or metastatic cancer of the pancreas were stratified according to a binary prognosis index, composed of tumour stage, age and performance status; and were evenly randomised to subcutaneous injections of VaL extracts or no antineoplastic therapy (control). VaL was applied in a dose-escalating manner from 0.01 mg up to 10mg three times per week. Patients in both groups received best supportive care. The primary end-point was 12-month OS, assessed in a group-sequential analysis. FINDINGS: We present the first interim analysis, including data from 220 patients. Baseline characteristics were well balanced between the study arms. Median OS was 4.8 for VaL and 2.7 months for control patients (prognosis-adjusted hazard ratio, HR=0.49; p<0.0001). Within the 'good' prognosis subgroup, median OS was 6.6 versus 3.2 months (HR=0.43; p<0.0001), within the 'poor' prognosis subgroup, it was 3.4 versus 2.0 months respectively (HR=0.55; p=0.0031). No VaL-related adverse events were observed. CONCLUSION: VaL therapy showed a significant and clinically relevant prolongation of OS. The study findings suggest VaL to be a non-toxic and effective second-line therapy that offers a prolongation of OS as well as less disease-related symptoms for patients with locally advanced or metastatic pancreatic cancer.

[Treatment of stress urinary incontinence after radical prostatectomy: adjustable transobturator male system - results of a multicenter prospective observational study]. / Behandlung der Belastungsinkontinenz nach radikaler Prostatektomie : Adjustierbares transobturatorisches System - prospektive multizentrische Anwendungsbeobachtung.

BACKGROUND: The adjustable transobturator male system (ATOMS®) is a new method for the treatment of male stress urinary incontinence. This article presents the results of a prospective multicenter observational study with this system. PATIENTS AND METHODS: Between March 2009 and March 2011 a total of 124 patients with persistent stress urinary incontinence after radical prostatectomy received the ATOMS system. Postoperative adjustments via the implanted port chamber were performed after 6 weeks and thereafter when necessary. Postoperative evaluation consisted of medical history, mictionary protocol, 24-h pad tests, 24-h pad counts and sonography. RESULTS: The mean age of the patients was 71.2 ± 5.5 years (range 58-85 years). Previous incontinence surgery had been carried out in 36.3% of patients while 34.5% of patients had a previous history of radiation treatment. The mean operation time was 48.3 ± 11.2 min (range 36-116 min) and the mean hospital stay was 3.8 ± 1.2 days (range 2-6 days). No intraoperative urethral or bladder injuries occurred. After removal of the transurethral catheter on the first postoperative day, temporary urinary retention occurred in 3 patients who were conservatively treated. Transient perineal/scrotal pain or dysesthesia was observed in 75 patients (60.5%) and resolved after 3-4 weeks of non-opioid analgesics. There were no perineal infections; however, infections at the port site occurred in 3 patients (2.4%) leading to explantation of the system in all cases. The average number of adjustments to achieve the desired result was 4.3 ± 1.8 (range 2-7). After a mean follow-up of 19.1 ± 2.2 months (range 12-36 months), there was a significant reduction in the mean number of pads/24 h from 8.8 to 1.8 (p<0.001). The overall success rate was 93.8% with 61.6% of the patients being dry and 32.2% of the patients showing improvement. CONCLUSIONS: The results of the study demonstrate the safety and efficacy to date of the ATOMS system for treatment of stress urinary incontinence after radical prostatectomy.

[Malignant neoplasms and kidney transplantation]. / Maligne Neoplasien und Nierentransplantation.

Together with cardiovascular disorders and metabolic changes, malignant diseases are considered as great challenges in clinical transplantation. As far as long-term function of transplanted organs is concerned, an impact of malignancies is obvious. However, it is important to distinguish between neoplastic disease originating from preexisting lesions in the transplanted organs and de novo graft tumors. Further, there is also a high risk of developing malignant disease during the dialysis, likely due to potential harmful metabolic changes associated with this procedure. After curative management of tumors in such patients, an interval of 2 years for surveillance should be adhered to before patients are put back on the waiting list. The overall risk of transmission of a malignant disease with the transplanted graft has been considered to be as low as <0.2%. In this context, and considering the continual shortage of donated organs, there is an international consensus about the use of kidney grafts with a history of small tumors (<2 cm in diameter und low-grade, i.e., G1). However, the lesions should have been removed with subsequent histopathologic characterization before the acceptance of the organ for transplantation. Early diagnosis and management of de novo malignant disease in transplant patients is crucial for the prognosis of graft function and patient survival. Genitourinary malignancies are frequent among de novo malignancies in transplanted patients. Thus, there is a need for clearly structured concepts for screening of transplant patients in order to detect early malignancies. The incidence of malignant disease correlates directly with the extent of immunosuppression in patients with end-stage renal disease (ESRD) on dialysis, as well as after transplantation with life-long immunosuppressant therapy. In addition, also geographic factors seem to play a role in the differential incidence of tumors among different populations. For instance, the highest incidence of malignancies among immunosuppressed patients has been observed in Australia followed by the USA and Europe. This might be due to the high incidence of de novo skin cancer, which has been linked to the extent of UV exposure.

Intention to quit smoking: is the partner's smoking status associated with the smoker's intention to quit?

BACKGROUND: Smoking behavior among couples is often similar. PURPOSE: The aim of the study was to examine the relationship between the partner's smoking status and the intention to stop smoking of the index person. METHOD: Cross-sectional data of 1,044 patients in a random sample of 34 general medical practices in northeastern Germany were analyzed. RESULTS: Among smokers with a non-smoking partner (SNP), more intended to quit smoking in the next six months (37.0% vs. 31.4%), compared to smokers with a smoking partner (SSP). Also, more SNP intended to quit in the next four weeks (4.7% vs. 2.7%) compared to SSP. SNP were more active in the use of self-change strategies than SSP. CONCLUSION: The data confirm that the partner's smoking status is related to the intention to quit smoking. Interventions should address the different needs of both smokers with a smoking partner and those with a non-smoking partner.