Integrating modelling and phenotyping approaches to identify and screen complex traits: transpiration efficiency in cereals.

Following advances in genetics, genomics, and phenotyping, trait selection in breeding is limited by our ability to understand interactions within the plant and with the environment, and to identify traits of most relevance to the target population of environments. We propose an integrated approach that combines insights from crop modelling, physiology, genetics, and breeding to characterize traits valuable for yield gain in the target population of environments, develop relevant high-throughput phenotyping platforms, and identify genetic controls and their value in production environments. This paper uses transpiration efficiency (biomass produced per unit of water used) as an example of a complex trait of interest to illustrate how the approach can guide modelling, phenotyping, and selection in a breeding programme. We believe that this approach, by integrating insights from diverse disciplines, can increase the resource use efficiency of breeding programmes for improving yield gains in target populations of environments.

Radiographic Characteristics of Adrenal Masses Preceding the Diagnosis of Adrenocortical Cancer.

Incidentally discovered adrenal masses are common and the clinical evaluation and surveillance aims to diagnose hormone excess and malignancy. Adrenocortical cancer (ACC) is a very rare malignancy. This study aims to define the imaging characteristics of adrenal tumors preceding the diagnosis of ACC. Patients with prior (>5 months) adrenal tumors (<6 cm) subsequently diagnosed with ACC were identified in a large registry at a tertiary referral center. Retrospective chart and image review for patient characteristics and initial, interval, and diagnostic imaging characteristics (size, homogeneity, borders, density, growth rate, etc.) was conducted. Twenty patients with a diagnosis of ACC and a prior adrenal tumor were identified among 422 patients with ACC. Of these, 17 patients were initially imaged with CT and 3 with MR. Only 2 of the 20 patients had initial imaging characteristics suggestive of a benign lesion. Of initial tumors, 25% were <2 cm in size. Surveillance led to the diagnosis of ACC within 24 months in 50% of patients. The growth pattern was variable with some lesions showing long-term stability (up to 8 years) in size. In conclusion, antecedent lesions in patients with a diagnosis of ACC are often indeterminate by imaging criteria and can be small. Surveillance over 2 years detected only 50% of ACCs. Current practice and guidelines are insufficient in diagnosing ACCs. Given the rarity of ACC, the increased risk and health care costs of additional evaluation may not be warranted.

QTL analysis in multiple sorghum populations facilitates the dissection of the genetic and physiological control of tillering.

KEY MESSAGE: A QTL model for the genetic control of tillering in sorghum is proposed, presenting new opportunities for sorghum breeders to select germplasm with tillering characteristics appropriate for their target environments. Tillering in sorghum can be associated with either the carbon supply-demand (S/D) balance of the plant or an intrinsic propensity to tiller (PTT). Knowledge of the genetic control of tillering could assist breeders in selecting germplasm with tillering characteristics appropriate for their target environments. The aims of this study were to identify QTL for tillering and component traits associated with the S/D balance or PTT, to develop a framework model for the genetic control of tillering in sorghum. Four mapping populations were grown in a number of experiments in south east Queensland, Australia. The QTL analysis suggested that the contribution of traits associated with either the S/D balance or PTT to the genotypic differences in tillering differed among populations. Thirty-four tillering QTL were identified across the populations, of which 15 were novel to this study. Additionally, half of the tillering QTL co-located with QTL for component traits. A comparison of tillering QTL and candidate gene locations identified numerous coincident QTL and gene locations across populations, including the identification of common non-synonymous SNPs in the parental genotypes of two mapping populations in a sorghum homologue of MAX1, a gene involved in the control of tiller bud outgrowth through the production of strigolactones. Combined with a framework for crop physiological processes that underpin genotypic differences in tillering, the co-location of QTL for tillering and component traits and candidate genes allowed the development of a framework QTL model for the genetic control of tillering in sorghum.

[Incidence of colorectal carcinoma and patient survival in the Grand-Duchy of Luxembourg]. / Inzidenz des kolorektalen Karzinoms und Uberleben der patienten im Grossherzogtum Luxemburg.

As in many other Western countries, colorectal cancer is one of the most common malignant tumours in Luxembourg. It is thus an important target for prevention measures. In light of the discussions on the introduction of organized screening programmes in Luxembourg a description of the current cancer incidence and relative survival rates, as well as a comparison with neighbouring countries are important. The tumour incidence is comparable to that in other countries with similar socio-economic development. The standardized incidence rate (world population) in 2010 was 26.4 and 44.4 per 100,000 for women and men, respectively. In some, but not all, Western European countries, a decreasing trend of the standardized incidence is emerging. No such trend is currently observed in Luxembourg. The mortality and relative survival rates are comparable to those in other European countries. The proportion of colorectal carcinomas of stages T1 + T2, 18.7% in the years 2000 to 2011, is markedly lower in Luxembourg than for example in Rhineland -Palatinate (29.4%), while the proportion of carcinomas of stage T4 is higher (17.4% versus 13.9%). This suggests that further successes in prevention are possible and illustrates the benefits of an organized screening colonoscopy program compared with opportunistic screening.

Feasibility of balloon sinuplasty in patients with chronic rhinosinusitis: the Graz experience.

BACKGROUND: Balloon sinuplasty (BSP) is a catheter-based technique to dilate sinus ostia and drainage pathways to create ventilation and drainage. The aim of this study was to evaluate the feasibility of BSP in routine treatment of patients suffering from chronic rhinosinusitis (CRS). METHODOLOGY: Patients with CRS refractory to medical therapy who had been scheduled for endoscopic sinus surgery between 2009 and 2011 were included in this study. RESULTS: Forty-five consecutive patients were included in this study, in whom 112 sinuses were approached by BSP. Of the 112 sinuses, 68 (60%) were planned as a "Balloon-Only" procedure and 44 (40%) were planned as a "Hybrid" procedure. Of the 68 sinuses in the "Balloon-Only" group, in 44 sinuses BSP failed, equating to a failure rate of 65%. Forty-four sinuses were planned for "Hybrid" procedures. In 29 of these sinuses BSP failed, giving a failure rate of 66%. CONCLUSION: According to literature, BSP can be a useful adjunct technique to standard FESS. In our experience, however, a failure rate of 65% for "Balloon-Only" and of 66% for "Hybrid" procedures occurred, which was regarded as unacceptable by the study group. Therefore, the study initially scheduled for 200 consecutive patients, was abandoned.

Experience of 11 years use of cidofovir in recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a viral induced disease, associated with exophytic epithelial lesions affecting the upper airways. Problem of treatment is the high recurrence of papilloma growth after surgical removal; therefore adjuvant therapy schemes have been established. Cidofovir was one of the agents used off-label in adjuvant therapy in the last years. However, there is ongoing discussion about the effectiveness and possible side effects. Aim of our study was to share our experience in treatment of RRP with cidofovir during the last 11 years. We analyzed all the data of patients treated for RRP at the Department for Phoniatrics of the Medical University of Graz between 1999 and 2011. 25 out of the 34 treated patients are at the moment under complete remission, in six patients partial remission could be achieved and two patients showed poor response to therapy, therefore the treatment with cidofovir was stopped. 21 patients received one cycle of monthly cidofovir, 11 patients received two and one patient three cycles of therapy. Number of procedures reached from one to six during each cycle. Average cumulative dose of one cycle was 79.7 mg (15-277.5 mg), in one patient 435 mg were used. One patient developed temporary, borderline neutropenia without symptoms. Despite the retrospective approach of this study with the limitation of several incomplete records, our results show promising long-term effects of adjuvant use of cidofovir. During this period, we did not observe any relevant side effects.

Cholesterol granulomas of the petrous apex; endonasal endoscopic approach.

OBJECTIVE: Cholesterol granulomas are benign lesions that sometimes occur on the petrous apex (PA). We report our experience using an endoscopic endonasal approach to remove PA cholesterol granulomas. MATERIAL AND METHODS: A retrospective patient chart analysis was conducted at a tertiary care university hospital. RESULTS: Four patients (3 females, 1 male) were included in this study. Patients' ages ranged from 27 to 78 years. Computed tomography (CT) and magnetic resonance imaging (MRI) for diagnosis and computer-assisted navigation were performed. The most common symptom was abducens nerve palsy. The largest granuloma measured 5 x 2 cm and was located on the left side. An endoscopic endonasal approach was chosen and navigation was applied (3/4 patients) to identify the optimal area for opening the granuloma. No complications occurred, and patients were free from recurrence during the follow-up period. CONCLUSION: The endoscopic endonasal approach to PA cholesterol granulomas is feasible and safe. Intra-operative navigation is recommended to identify the position of the internal carotid artery and determine the safest area for opening the granuloma without damaging the artery. Another advantage of this approach is an easier follow-up through diagnostic nasal endoscopy.

Syphilis is back: presentation of three cases at the ENT department.

PROBLEM: Syphilis is a sexually-transmitted disease caused by the spirochete Treponema pallidum, and is transmitted either through sexual contact or vertically across the placenta. Rates of infection were at a low point in the early 1990s. Since then, increasing numbers of new cases of infections have been observed in all Western countries. AIM: Presentation of three patients with syphilis who presented within a short period of time in an ENT outpatient clinic. CONCLUSIONS: One must be aware of the increasing incidence of syphilis, even in head and neck disciplines. Typical symptoms of an early infection are an ulcerous lesion in the mouth, with or without cervical lymphadenopathy. The main therapy is high doses of penicillin G administered intramuscularly. Other simultaneous sexually-transmitted diseases, especially HIV infection, must be excluded. Unnoticed and untreated patients may develop late and life-threatening complications.

[Organ procurement in Germany: a regional survey among students]. / Organspendebereitschaft in Deutschland.

BACKGROUND AND OBJECTIVE: In Germany the extent of organ donation is still low and not sufficent to duly address all patients on the waiting lists. It is likely that a lack of information and a consecutive uncertainty in the adult population relate to this imbalance. Virtually no data exist about teenagers' knowledge of the facts of organ donation. METHODS: 4000 questionnaires were distributed in secondary schools in the state capital city Mainz, Germany. The students were asked to respond to 12 questions. The survey was voluntary and performed in class, without the students using any information sources. RESULTS: Data from 1155 questionnaires were analysed. Overall 11.3 % of the teenagers carried an organ donor card. 48.9 % of the students had spoken about organ donation and brain death in their families. 37.0 % of the students declined organ donation. Of these, 72.4 % named a lack of education and informations as the primary reason for this statement. More non-German than German pupils declined organ donation (43.4 % vs. 36.2 %). CONCLUSIONS: More than half of the pupils between 14 years and 20 years of age support the concept of organ transplantation as therapeutic option. Nevertheless the proportion of organ card holders is small among these students. These regional results identify an information deficit in young people in Germany as one of the main causes for inadequate acceptance of organ donation. Therefore, information and structured education should be intensified in German schools as possible measure to increase the number of future organ donor card holders in Germany.

QTL for nodal root angle in sorghum (Sorghum bicolor L. Moench) co-locate with QTL for traits associated with drought adaptation.

Nodal root angle in sorghum influences vertical and horizontal root distribution in the soil profile and is thus relevant to drought adaptation. In this study, we report for the first time on the mapping of four QTL for nodal root angle (qRA) in sorghum, in addition to three QTL for root dry weight, two for shoot dry weight, and three for plant leaf area. Phenotyping was done at the six leaf stage for a mapping population (n = 141) developed by crossing two inbred sorghum lines with contrasting root angle. Nodal root angle QTL explained 58.2% of the phenotypic variance and were validated across a range of diverse inbred lines. Three of the four nodal root angle QTL showed homology to previously identified root angle QTL in rice and maize, whereas all four QTL co-located with previously identified QTL for stay-green in sorghum. A putative association between nodal root angle QTL and grain yield was identified through single marker analysis on field testing data from a subset of the mapping population grown in hybrid combination with three different tester lines. Furthermore, a putative association between nodal root angle QTL and stay-green was identified using data sets from selected sorghum nested association mapping populations segregating for root angle. The identification of nodal root angle QTL presents new opportunities for improving drought adaptation mechanisms via molecular breeding to manipulate a trait for which selection has previously been very difficult.

Pathways in the diagnosis of prevertebral tendinitis.

INTRODUCTION: The prevertebral tendinitis is an inflammatory process, which affects the cervicothoracic prevertebral muscles. This extremely rare entity was first described by Hartley and Fahlgren in 1964 and until now there are just some case reports dealing with this process. Unfortunately it is quite easy to misdiagnose or mistake the prevertebral tendinitis as an abscess, because of the imaging features. The aim of this case series is to offer guidelines in the diagnosis of this rare disease to prevent unnecessary surgery. MATERIAL AND METHODS: Six patients with already by imaging or retrospectively after surgery by pathologic report diagnosed prevertebral tendinitis were included in this study. None of these patients suffered from a chronically inflammatory disease. Three patients just received contrast enhanced computed tomography (CT) and another group of three patients received magnetic resonance imaging (MRI). In two out of three MRI examinations, we additionally performed diffusion weighted images and calculated the apparent diffusion coefficient (ADC) map. The laboratory reports obtained on the day of the computed tomography (CT) or magnetic resonance imaging (MRI) examinations were reviewed for C-reactive protein (CRP) and white blood cell count (WBCC). RESULTS: All patients revealed a prevertebral cervical effusion. Five out of six patients showed amorphous calcifications in the tendon of the prevertebral muscles. In one case calcifications could not be identified at all because of very strong beam hardening artefacts caused by dental prothesis. The CRP values were increased in all patients (mean value 44.9 mg/l; SD ± 28.3). However, WBCC remained normal (mean value 8.4G/l; SD ± 2.7). Only for the two patients who received DWI it was possible to assess the quality of the prevertebral fluid accumulation and to detect the benign prevertebral effusion, which is typical for the retropharyngeal tendinitis. CONCLUSION: According to the experience with our patients the best imaging feature is MRI with DWI and ADC map to reveal the benign prevertebral effusion and confirm the diagnosis of prevertebral tendinitis. In some cases MRI might not be available. Here we recommend CT scans to detect typical prevertebral calcifications. Especially a slight elevation of CRP and normal WBCC make the prevertebral tendinitis more likely.

Environment characterization as an aid to wheat improvement: interpreting genotype-environment interactions by modelling water-deficit patterns in North-Eastern Australia.

Genotype-environment interactions (GEI) limit genetic gain for complex traits such as tolerance to drought. Characterization of the crop environment is an important step in understanding GEI. A modelling approach is proposed here to characterize broadly (large geographic area, long-term period) and locally (field experiment) drought-related environmental stresses, which enables breeders to analyse their experimental trials with regard to the broad population of environments that they target. Water-deficit patterns experienced by wheat crops were determined for drought-prone north-eastern Australia, using the APSIM crop model to account for the interactions of crops with their environment (e.g. feedback of plant growth on water depletion). Simulations based on more than 100 years of historical climate data were conducted for representative locations, soils, and management systems, for a check cultivar, Hartog. The three main environment types identified differed in their patterns of simulated water stress around flowering and during grain-filling. Over the entire region, the terminal drought-stress pattern was most common (50% of production environments) followed by a flowering stress (24%), although the frequencies of occurrence of the three types varied greatly across regions, years, and management. This environment classification was applied to 16 trials relevant to late stages testing of a breeding programme. The incorporation of the independently-determined environment types in a statistical analysis assisted interpretation of the GEI for yield among the 18 representative genotypes by reducing the relative effect of GEI compared with genotypic variance, and helped to identify opportunities to improve breeding and germplasm-testing strategies for this region.

Laparoscopic resection is inappropriate in patients with known or suspected adrenocortical carcinoma.

BACKGROUND: Complete surgical resection is the mainstay of treatment for patients with adrenocortical cancer (ACC). Use of laparoscopy has been questioned in patients with ACC. This study compares the outcomes of patients undergoing laparoscopic versus open resection (OR) for ACC. METHODS: A retrospective review (2003-2008) of patients with ACC was performed. Data were collected for demographics, operative and pathologic data, adjuvant therapy, and outcome. Chi-square analysis was performed. RESULTS: Eighty-eight patients (66% women; median age, 47 (range, 18-81) years) were identified. Seventeen patients underwent laparoscopic adrenalectomy (LA). Median tumor size of those who underwent LA was 7.0 (range, 4-14) cm versus 12.3 (range, 5-27) cm for OR. Recurrent disease in the laparoscopic group occurred in 63% versus 65% in the open group. Mean time to first recurrence for those who underwent LA was 9.6 months (+/-14) versus 19.2 months (+/-37.5) in the open group (p < 0.005). Fifty percent of patients who underwent LA had positive margins or notation of intraoperative tumor spill versus 18% of those who underwent OR (p = 0.01). Local recurrence occurred in 25% of the laparoscopic group versus 20% in the open group (p = 0.23). Mean follow-up was 36.5 months (+/-43.6). CONCLUSIONS: ACC continues to be a deadly disease, and little to no progress has been made from a treatment standpoint in the past 20 years. Careful and complete surgical resection is of the utmost importance. Although feasible in many cases and tempting, laparoscopic resection should not be attempted in patients with tumors suspicious for or known to be adrenocortical carcinoma.

Is cancer risk of radiation workers larger than expected?

Occupational exposures to ionising radiation mainly occur at low-dose rates and may accumulate effective doses of up to several hundred milligray. The objective of the present study is to evaluate the evidence of cancer risks from such low-dose-rate, moderate-dose (LDRMD) exposures. Our literature search for primary epidemiological studies on cancer incidence and mortality risks from LDRMD exposures included publications from 2002 to 2007, and an update of the UK National Registry for Radiation Workers study. For each (LDRMD) study we calculated the risk for the same types of cancer among the atomic bomb survivors with the same gender proportion and matched quantities for dose, mean age attained and mean age at exposure. A combined estimator of the ratio of the excess relative risk per dose from the LDRMD study to the corresponding value for the atomic bomb survivors was 1.21 (90% CI 0.51 to 1.90). The present analysis does not confirm that the cancer risk per dose for LDRMD exposures is lower than for the atomic bomb survivors. This result challenges the cancer risk values currently assumed for occupational exposures.

[Quantification of pulmonary emphysema in multislice-CT using different software tools]. / Quantifizierung des Lungenemphysems in der Mehrschicht-CT mittels verschiedener Softwareverfahren.

PURPOSE: The data records of thin-section MSCT of the lung with approx. 300 images are difficult to use in manual evaluation. A computer-assisted pre-diagnosis can help with reporting. Furthermore, post-processing techniques, for instance, for quantification of emphysema on the basis of three-dimensional anatomical information might be improved and the workflow might be further automated. MATERIALS AND METHODS: The results of 4 programs (Pulmo, Volume, YACTA and PulmoFUNC) for the quantitative analysis of emphysema (lung and emphysema volume, mean lung density and emphysema index) of 30 consecutive thin-section MSCT datasets with different emphysema severity levels were compared. The classification result of the YACTA program for different types of emphysema was also analyzed. RESULTS: Pulmo and Volume have a median operating time of 105 and 59 minutes respectively due to the necessity for extensive manual correction of the lung segmentation. The programs PulmoFUNC and YACTA, which are automated to a large extent, have a median runtime of 26 and 16 minutes, respectively. The evaluation with Pulmo and Volume using 2 different datasets resulted in implausible values. PulmoFUNC crashed with 2 other datasets in a reproducible manner. Only with YACTA could all graphic datasets be evaluated. The lung volume, emphysema volume, emphysema index and mean lung density determined by YACTA and PulmoFUNC are significantly larger than the corresponding values of Volume and Pulmo (differences: Volume: 119 cm(3)/65 cm(3)/1 %/17 HU, Pulmo: 60 cm(3)/96 cm(3)/1 %/37 HU). Classification of the emphysema type was in agreement with that of the radiologist in 26 panlobular cases, in 22 paraseptalen cases and in 15 centrilobular emphysema cases. CONCLUSION: The substantial expenditure of time obstructs the employment of quantitative emphysema analysis in the clinical routine. The results of YACTA and PulmoFUNC are affected by the dedicated exclusion of the tracheobronchial system. These fully automatic tools enable not only fast quantification without manual interaction, but also a reproducible measurement without user dependence.

Management of patients with adrenal cancer: recommendations of an international consensus conference.

Adrenocortical carcinomas are rare, highly malignant tumors that account for only 0.2% of deaths due to cancer. Given the limited number of patients seen in most medical centers with this diagnosis, series usually reported are small and clinical trials not randomized or blinded. In an attempt to answer important questions concerning the management of patients with adrenal cancer, a consensus conference was organized and held at the University of Michigan in Ann Arbor, MI, 11-13 September 2003, with the participation of an international group of physicians who had reported on the largest series of patients with this disease and who had recognized basic and clinical research expertise in adrenal cortical cancer. Totally 43 questions were addressed by the presenters and recommendations discussed in plenary and breakout sessions. Evidence for the recommendations of this conference was at the 2-4+ level and based on available literature and participants' experience. In addition to setting up guidelines in specific areas of the diagnosis and treatment of adrenal cancer, the conference recommended and initiated the planning of an international prospective trial for treatment of patients with adrenal cancer in stages III and IV. In terms of new therapies, first trials of dendritic cell therapy in human subjects with adrenal cancer have been started, but it is too early to comment on efficacy. Different strategies of immunotherapy, including DNA vaccination are currently being tried in animal models. There are no clinical gene therapy trials for human adrenal cortical cancer. The adrenals are a preferred target for adenovirus and the results of gene therapy in preclinical studies are promising. In addition, there is evidence that histone deacetylase inhibitors can further enhance the rate of adenoviral infectivity in human adrenal cancer cells. Testing of retroviral vectors, non-viral vectors, small interfering RNA technology, and combined approaches could be performed in various laboratories. Anti-angiogenic substances have only been applied in preclinical studies. The use of these and other agents in the treatment of adrenal cancer should be hypothesis-driven and based on a thorough analysis of tumor biology.

Role of the inhibin/activin system and luteinizing hormone in adrenocortical tumorigenesis.

Adrenal masses are one of the most common endocrine tumors diagnosed. Although most adrenal tumors are inactive adenomas, a considerable proportion is associated with hormonal hyperfunction and/or malignancy. The adrenocortical carcinoma (ACC) is a rare but highly malignant tumor. Most ACCs in adults are diagnosed in an advanced tumor stage limiting therapeutic options. Accordingly, despite some progress in diagnostic and therapeutic approaches, the overall survival rate of patients with ACC remains poor. However, the prerequisite for the development of new diagnostic tools and therapeutic options in the management of patients with ACC is the elucidation of the molecular pathogenesis of adrenal tumorigenesis. Although our understanding of adrenal tumor biology has increased substantially over the last decades, the regulation of many molecular pathways involved in adrenocortical growth and differentiation awaits further elucidation. Luteinizing hormone (LH) and activin have only recently emerged as hormones likely to play opposite roles in adrenocortical hormone secretion and cellular proliferation. Recent evidence from studies on human surgical tumor sample expression and detailed characterization of murine adrenal tumor models suggests stimulatory effects of LH on adrenocortical growth and function. On the contrary, activin, which plays a critical role as a paracrine and autocrine factor regulating cellular growth and differentiation, has been demonstrated to induce apoptosis and suppress proliferation in the human and murine adrenal cortex. In this review, we will summarize molecular and functional aspects of adrenal tumorigenesis and highlight some prospects for future clinical applications.